(BQ) Part 2 book Cytology diagnostic principles and clinical correlates presents the following contents: Breast, thyroid, salivary gland, lymph nodes, liver, pancreas and biliary tree, kidney and adrenal gland, ovary, soft tissue, laboratory management.
c h a pt er BREAST Barbara S Ducatman | Helen H Wang Specimen Types Fine-Needle Aspiration Nipple Discharge Cytology Reporting Terminology Evaluation of the Specimen The Normal Breast Benign Conditions Cysts Fibrocystic Changes Fibroadenoma Pregnancy-Related and Lactational Changes Fat Necrosis Radiation Change Mastitis Subareolar Abscess Gynecomastia Papillary Neoplasms Phyllodes Tumor Breast Cancer Invasive Ductal Carcinoma Invasive Lobular Carcinoma Specimen Types Breast cytology includes the nipple discharge and fine needle aspiration (FNA) The more common specimen by far is the FNA sample Fine-Needle Aspiration FNA is used to evaluate palpable breast masses and cysts as well as nonpalpable mammographic abnormalities FNA is highly accurate for palpable lesions,1,2 although its accuracy is limited with lesions smaller than cm Despite competition from the automated core needle biopsy (CNB) under stereotactic guidance, FNA delivers good results, especially in a multidisciplinary setting with on-site radiologists and pathologists.3-7 Complications of FNA are rare, the most common being bleeding Occasionally, FNA causes partial infarction of the lesion, particularly fibroadenomas, which can hinder histologic confirmation of the diagnosis.8 For nonpalpable lesions, FNA is a useful technique for sampling cystic lesions with ultrasound guidance, whereas the CNB is more often used for mammographically identified calcifications.9 In pregnant or postpartum patients, FNA is preferred in order to avoid a draining, nonhealing wound that can result after a core or incisional biopsy FNA is also useful for assessment of recurrent lesions The accuracy of FNA of the breast, as with most things, is operator-dependent: Sensitivity for malignancy ranges from 65% to 98%, and specificity from 34% to Medullary Carcinoma Mucinous (Colloid) Carcinoma Tubular Carcinoma Metaplastic Carcinoma Uncommon Breast Tumors Apocrine Carcinoma Adenoid Cystic Carcinoma Non-Hodgkin Lymphoma Sarcoma Metastatic Tumors 100%.1,10-16 False-positive results occur in to 2% of cases.17 False-suspicious result rates are higher, ranging from 1% to 13% In general, the sensitivity of FNA for palpable and nonpalpable malignant lesions (i.e., those sampled with mammographic or ultrasound guidance) is comparable.18-34 False-negative results occur because of errors in sampling, interpretation, or both.14,35 Some studies show that satisfactory specimens are more likely when pathologists rather than clinicians perform the aspiration.14,36-41 Whether clinician or pathologist, however, practice makes perfect, and the physician with more FNA experience obtains the more accurate result.42-44 The use of p63 and CK5/6 immunostaining increases the accuracy of FNA by helping distinguish well-differentiated carcinomas from benign lesions.45-48 A major advantage of FNA is the ease with which the sample can be assessed for adequacy.49,50 Although a touch imprint or wash of a CNB specimen can be done for rapid diagnosis, their utility is debatable.51-56 The use of FNA and/or CNB significantly decreases health care costs by decreasing the number of open surgical biopsies per breast cancer identified, without sacrificing early detection.57 When the diagnosis is benign, such as a lactating adenoma in a pregnant patient, FNA spares a patient with a solid and palpable lesion an open biopsy A diagnosis of malignancy allows preoperative evaluation of available therapeutic options (lumpectomy with irradiation versus mastectomy), or it might persuade a reluctant patient to undergo surgical biopsy 233 234 BREAST FNA of the breast has its limitations Although sensitive in detecting ductal carcinomas, it cannot distinguish between an in situ and an invasive ductal carcinoma It cannot identify the presence of lymphatic or vascular invasion It is less sensitive in tumors with low-grade cancer histology (e.g., tubular and lobular), papillary proliferations, and mucinous lesions.58-60 The diagnosis of lobular carcinoma and tubular carcinoma requires considerable experience in FNA interpretation25,59 even so, equivocal findings are common because of the benign cytologic appearance of such tumors.60 As with FNA of other sites, considerable discrepancy in performance exists among laboratories.61 In comparison with CNB, the nondiagnostic rate for FNA is higher, and FNA has a lower negative predictive value.55,58,62 Nevertheless, some authors have reported excellent results with breast FNA, and the combination of FNA and CNB may be superior to either alone.3,5,16,63-66 Although atypical ductal proliferative lesions are more amenable to classification by CNB than by FNA, false-negative diagnoses and underestimates of malignancy have been reported in a considerable percentage of cases even with CNB.67-70 Prognostic markers can be assessed with either technique.2,71 Many practitioners favor CNB over FNA62,72,73 because of the superior negative predictive value and wider acceptance of histopathology The resulting increased use of CNB, particularly with stereotactic or ultrasound guidance, has led to diminished use of FNA,16,74 although some practitioners continue to use FNA for patients with radiologically and clinically negative lesions.75,76 The cost-effectiveness of FNA versus CNB is still debated.77-79 The increasing use of neoadjuvant chemotherapy in higher-stage cancers has further limited the use of FNA Because an open biopsy is not performed, CNB, usually under ultrasonographic guidance, is superior because of its more robust sensitivity and ability to distinguish between ductal carcinoma in situ and invasive carcinoma Furthermore, a CNB sample usually contains more abundant material for the determination of estrogen receptor (ER), progesterone receptor (PR), and HER2 status Although a cell block prepared from an FNA sample permits multiple immunohistochemical stains, staining for PR in cell blocks may be discordant with tissue results, and staining for HER2 may be unreliable.80 Breast tumors are now classified in part on their molecular expression profile (luminal A, luminal B, HER2-positive, basal-like),81 and molecular-based risk stratification and prognostic testing by commercial products like Oncotype DX (Genomic Health) and MammaPrint (Agendia) is playing an increasing role in the management of patients.81 Entrance into many current neoadjuvant clinical trials stipulates core biopsy material for molecular testing As new molecular tests are validated, the use of FNA may decline further unless studies incorporate FNA specimens in their design FNA of axillary lymph nodes remains indispensable in the evaluation of lymph node status prior to neoadjuvant treatment or for preoperative staging,82-92 although some institutions are using CNB instead of FNA Nipple Discharge Cytology A spontaneous nipple discharge not related to lactation or pregnancy is an abnormal finding It may result from a breast lesion like a papilloma or a carcinoma or from a hormonal abnormality like that produced by a prolactin-secreting pituitary adenoma Cytologic examination of a nipple discharge is generally used when the patient has no palpable or mammographic abnormality and is helpful in identifying small breast cancers and papillomatosis.93,94 If a palpable or mammographic abnormality is present, either FNA, CNB, or excisional biopsy is usually performed.95 The sensitivity of nipple discharge cytology ranges from 41% to 60%.96-98 Nipple discharge cytology is not useful as a screening test for breast cancer because a discharge can be obtained in only 7% to 14% of asymptomatic, nonpregnant, nonlactating women.96,98,99 In the future, biomarker analysis of nipple discharge fluid might help increase the sensitivity of cytology.100 Nipple discharge specimens are prepared by gently massaging the breast in the direction of the nipple A glass slide is then touched to the secreted drops; the discharge need not be smeared unless it is abundant The slides are fixed by spray fixation or by immersion in 95% ethyl alcohol and stained with the Papanicolaou stain An alternative method is to air-dry the slide and stain it with a Romanowsky-type stain A nipple discharge can be unilateral or bilateral; unilateral discharges are more likely to be malignant.96 The secretion can be milky, serous, purulent, or bloody Cancer is most prevalent when the discharge is macroscopically bloody (4%) and less prevalent when it is purulent (0.8%), serous (0.2%), or milky (0.1%).96 Because bloody discharges are more likely than nonbloody discharges to contain malignant cells,94,101 some authors recommend cytologic examination of bloody secretions only, which represent 11% of all secretions.96 Others recommend examination of all discharges.98 Most patients with an intraductal papilloma have a discharge,98 which may or may not be bloody Although most patients with breast cancer not have a discharge from the nipple, about 2% of breast cancers are detected by this method and by no other.98 Cytomorphology of benign nipple secretions • • • • • usually sparsely cellular ductal cells foam cells inflammatory cells red blood cells REPORTING TERMINOLOGY Benign ductal cells are arranged in tight clusters that are small and spherical or large and branching; isolated benign ductal cells are very uncommon Usually, the cells are small and have scant cytoplasm, but occasionally they are larger and have abundant cytoplasm It is common for benign ductal cells to mold themselves around one another, giving the cluster a scalloped appearance Foam cells are large histiocytes that are usually dispersed as isolated cells They contain abundant vacuolated cytoplasm and a round or oval nucleus that is sometimes degenerated (Fig 9.1A) When a secretion contains numerous groups of benign ductal cells, especially large, branching clusters, it is likely that the patient has an intraductal papilloma or a florid intraductal hyperplasia, lesions that can only be distinguished histologically Cytomorphology of malignant nipple secretions (Fig 9.1B ) • • • • • • • enlarged ductal cells, isolated and in clusters variable nuclear size and shape stripped nuclei nucleoli acute inflammation blood necrotic debris Reporting Terminology To report FNA and nipple discharge results, the use of general categories with an implicit probability/risk of malignancy, followed by a specific diagnosis, is recommended.75,102-110 As might be expected, interobserver reproducibility is excellent for the positive category, poor for atypical, and fair to good for other categories.111 A 235 General categories for reporting results of breast fine-needle aspiration • negative for malignant cells (or: no malignant cells seen) • atypical • suspicious • positive for malignant cells • nondiagnostic (or: unsatisfactory, insufficient) The exact wording for each category or diagnosis is less important than having a probabilistic (risk-based) system that clearly communicates the likelihood of malignancy One pathologist might use the term “nondiagnostic” and another, “insufficient,” but the fact that this specimen is unsatisfactory is understood by clinician and pathologist alike Nondiagnostic specimens contain too few well-preserved cells to permit an adequate evaluation—fewer than six epithelial cell clusters of at least to 10 cells or less than 10 intact bipolar cells per 10 medium-power fields (×200).112,113 A negative (benign) diagnosis should be reserved for an adequate specimen with a minimum of five to six well-preserved benign ductal cell groupings A negative FNA result is more reliable when a specific diagnosis corroborates a clinical and radiologic impression (e.g., fibroadenoma, lactating adenoma).102 The clinician should always correlate the cytologic result with the clinical findings and the mammographic impression (these constitute the so-called “triple test”) to reduce the risk of an undiagnosed malignancy, and clinical follow-up is indicated.113-115 The false-negative rate is greatly reduced when the triple-negative test is implemented.116 Needless to say, a negative cytologic result is by no means a guarantee that the nodule is benign, and a mammographically or clinically suspicious lesion necessitates a biopsy despite a negative cytologic result B Figure 9.1 Nipple discharge cytology A, Benign nipple discharge Histiocytes (foam cells) have a kidney bean–shaped nucleus and abundant vacuolated cytoplasm (Papanicolaou stain) B, Suspicious nipple discharge The sample contains very atypical cells with enlarged nuclei The subsequent biopsy showed a high-grade comedocarcinoma (Papanicolaou stain) 236 BREAST The atypical category is used for a specimen with a low probability of malignancy This category is unavoidable due to the significant overlap in the cytologic features of some benign and malignant entities It generally requires biopsy assessment.117 The suspicious diagnosis is used for lesions that are probably malignant, but the atypical cells are too few, too poorly preserved, or too obscured by blood or inflammation for a definitive diagnosis, or when the findings suggest a type of breast cancer with minimal cytologic atypia, such as lobular carcinoma, tubular carcinoma,118 or papillary carcinoma A histologic specimen should be obtained with any FNA sample that is deemed suspicious Positive diagnoses are reserved for specimens with unequivocal features of malignancy Although confirmation of all positive results with frozen section before definitive surgery is wise, some surgeons proceed directly to mastectomy or wide local excision Therefore, it is prudent to diagnose any case for which the pathologist is not comfortable with definitive surgery as “suspicious.” Evaluation of the Specimen Low-power evaluation • cellularity • cellular arrangements • background elements Cellularity is important, although there is considerable overlap between categories Hypocellular aspirates can be obtained from a fibroadenoma, fibrocystic changes (FCCs), fat necrosis, radiation changes, pregnancy/lactation, and carcinoma, both in situ and invasive (particularly scirrhous, tubular, and lobular types) Moderately cellular aspirates are seen with a fibroadenoma, phyllodes tumor, pregnancy/lactation, FCCs, and carcinoma Hypercellular aspirates are seen in some fibroadenomas, phyllodes tumors, and invasive carcinomas Cellular arrangements provide important clues to the diagnosis Cells can be arranged in sheets, tightly or loosely cohesive three-dimensional clusters, branching papillary clusters, or as isolated cells The spacing of nuclei in cell clusters varies in different breast lesions Regular nuclear spacing suggests a benign process; irregular spacing is characteristic of malignancy Lesions associated with architectural patterns Sheets: • fibrocystic changes • fibroadenoma • lobular carcinoma in situ Tightly cohesive three-dimensional aggregates: • fibroadenoma and phyllodes tumor • intraductal papilloma • lobular carcinoma in situ • ductal proliferative lesions, from intraductal hyperplasia to ductal carcinoma in situ • well-differentiated ductal carcinomas • mucinous carcinoma Loosely cohesive three-dimensional clusters: • phyllodes tumor • ductal carcinoma in situ • invasive carcinoma Branching papillary clusters: • fibroadenoma • intraductal papilloma • papillary carcinoma Numerous isolated cells: • carcinoma • pregnancy/lactation • non-Hodgkin lymphoma • intramammary lymph node Background elements include inflammatory cells, amorphous debris, fresh and old blood, and mucin Acute inflammatory cells are seen with mastitis and necrotic carcinomas Lymphocytes are noted with intramammary lymph nodes, medullary carcinoma, and lymphoproliferative disorders Although amorphous granular debris suggests malignancy, it does not provide sufficient grounds for making a positive diagnosis, as it may also be observed with pregnancy/lactation and apocrine metaplasia Presence of blood is a clue to an intraductal papilloma, papillary or another carcinoma, and angiosarcoma Mucin and myxoid material are seen with fibroadenoma, mucinous carcinoma, and mucocele High-power examination • types of isolated cells • nuclear characteristics • cytoplasmic characteristics Isolated cells are epithelial or mesenchymal in origin and may be intact or stripped of cytoplasm (naked nuclei) Isolated epithelial cells are seen during pregnancy and lactation and with carcinoma Mesenchymal cells are noted in fibroadenoma, phyllodes tumor, invasive carcinoma, and sarcoma Naked nuclei are common in pregnancy, lactation, and fibroadenoma Inflammatory cells are commonly seen in fat necrosis, FCCs, mastitis, lymphoma, and intramammary lymph nodes Histiocytes are seen in fat necrosis, radiation, FCCs, granulomas, and status post silicone injection or a ruptured silicone implant Nuclear atypia is assessed on the basis of nuclear location, size, and shape; the chromatin pattern; and the quality of nucleoli Although the standard cytologic criteria for malignancy (eccentrically placed, large, angulated, pleomorphic nuclei with irregular and large BENIGN CONDITIONS nucleoli) apply with moderately and poorly differentiated ductal carcinomas, some malignant tumors, including tubular, lobular, and mucinous carcinoma, show little nuclear atypia The recognition of other features, like the architectural arrangement or the presence of abundant extracellular mucin, is important in the diagnosis of these tumors Cytoplasmic characteristics are useful in classifying some breast lesions Distinctive features include apocrine change and cytoplasmic vacuolization Apocrine cytoplasm is seen in apocrine metaplasia and apocrine carcinoma Vacuolated cytoplasm is observed with pregnancy and lactation, fat necrosis, radiation effect, mucinous carcinoma, lobular carcinoma, lipid-rich carcinoma, secretory carcinoma, and status post silicone injection or ruptured silicone implant The Normal Breast The breast contains 15 to 25 lactiferous ducts, which begin at the nipple, then branch into smaller ducts, and end in the terminal duct lobular unit (or lobule) The lobule is composed of a terminal duct and many small ductules (or acini) An inner layer of cuboidal or columnar epithelial cells and an outer layer of myoepithelial cells line all ducts and ductules The connective tissue within the lobule is a hormonally responsive mixture of fibroblasts, occasional lymphocytes, and histiocytes, in a background of collagen and acid mucin The interlobular stroma is hypocellular and contains fibroadipose tissue During pregnancy there is a marked proliferation of ductules, which results in very large lobules, and the epithelial cells have abundant cytoplasm filled with secretory vacuoles These secretory changes usually disappear after lactation; in some instances, however, they persist for years after pregnancy and are sometimes seen even in patients who have not been pregnant The cause in such cases has been ascribed to pharmaceutical agents 237 Fibrocystic Changes FCCs are the most common breast disorder Findings may include any combination of small or large cysts, apocrine metaplasia, focal fibrosis, adenosis, and ductal hyperplasia These changes can result in palpable, sometimes painful, masses Cysts arise from the terminal duct lobular units by an unfolding and simplification of adjacent ductules Moderate and florid ductal hyperplasia, which is seen in some but not all cases, is a marker for increased cancer risk For this reason, FCC is usually categorized as nonproliferative or proliferative, depending on whether ductal hyperplasia is present Nonproliferative Fibrocystic Changes Cytomorphology of nonproliferative fibrocystic changes • apocrine cells • foam cells • small ductal cells Nonproliferative lesions yield a scant specimen when the lesion is predominantly fibrous When a cyst is present, the specimen is a fluid that may be thin and yellow or thick and darker in color Apocrine cells line many but not all benign cysts Apocrine cells have abundant granular cytoplasm that stains pink or green with the Papanicolaou stain and gray with a Romanowsky stain (Fig 9.2) The nucleus is centrally located and round, with a prominent nucleolus, and moderate anisonucleosis is present in some cases Benign apocrine cells are arranged as flat sheets; isolated cells are rare Foam cells have abundant cytoplasm that is vacuolated rather than granular (see Fig 9.1) Ductal epithelial cells are arranged in sheets and three-dimensional clusters (Fig 9.3) Benign Conditions Cysts The aspiration of breast cysts and the need for cytologic analysis is controversial Aspiration collapses a cyst and is thereby therapeutic The great majority of cyst fluids are benign; only about 2% prove to be carcinoma.119 Even complex cystic lesions are virtually always benign; in one study, only 0.3% were malignant.120 Furthermore, atypical cells can be seen in a cyst fluid, resulting in overdiagnosis and overtreatment when conservative follow-up would have been adequate.120,121 On the other hand, a small number of carcinomas are cystic and yield fluid that looks grossly much like that from benign cysts.122 If the fluid is not submitted for cytologic evaluation, these carcinomas will remain undiagnosed and untreated It has been suggested that symptomatic complicated cysts, cystic lesions with thick indistinct walls and/or thick septations, intracystic masses, and predominantly solid masses with cystic degeneration are more likely to be malignant and thus merit cytologic or histopathologic examination.123 Differential diagnosis of nonproliferative fibrocystic changes • granular cell tumor • apocrine carcinoma Granular cell tumors of the breast are rare The cells of this tumor, thought to be of Schwann cell origin, have a very low nuclear-to-cytoplasmic ratio, a small nucleus, and a coarsely granular cytoplasm.124 The background is usually clean (Fig 9.4) An apocrine carcinoma should be suspected when there is hypercellularity, marked nuclear atypia, and pronounced cell dyshesion, but a cautious diagnostic approach is advisable, because marked variation in nuclear size is also seen in apocrine metaplasia Apocrine adenosis, although rare, can also manifest with nuclear atypia, but there is less nuclear hyperchromasia than with carcinoma, and there are many naked nuclei.125 238 BREAST A B Figure 9.2 Apocrine metaplasia Large, flat sheets of apocrine cells have distinct cytoplasmic borders, a centrally located nucleus, and a prominent nucleolus The abundant granular cytoplasm is gray-purple with a Romanowsky-type stain (A) and green with the Papanicolaou stain (B) Figure 9.3 Benign ductal epithelium (nonproliferative fibrocystic changes) A tightly cohesive cluster of ductal epithelial cells without atypia is noted adjacent to apocrine metaplastic cells (Papanicolaou stain) Proliferative Fibrocystic Changes Ductal proliferative lesions (i.e., proliferative FCC) comprise a group of lesions that vary in severity and degree of atypia The spectrum includes proliferative lesions without atypia (“usual ductal hyperplasia”), atypical ductal hyperplasia, and atypical lobular hyperplasia The criteria that define these entities and distinguish them from carcinoma in situ are histologic, not cytologic.126,127 Nevertheless, the degree of crowding and nuclear atypia allows for separation of the higher end of this spectrum from the lower In one study, lesions reported cytologically as “proliferative lesion with atypia” were associated with a significantly higher frequency of histologically confirmed malignancywthan those reported as “proliferative lesion without atypia” (36.5% versus 1.7%).128 A lesion diagnosed as atypical by FNA should be considered for excision, because the morphologic features of well-differentiated invasive and in situ carcinomas overlap with those of benign entities.117 Cytomorphology of ductal proliferative lesion without atypia (Fig 9.5) • sheets and tight clusters of cells without significant nuclear overlap • regular cellular spacing • finely granular chromatin pattern • inconspicuous to small nucleolus Cytomorphology of ductal proliferative lesion with atypia (Fig 9.6) Figure 9.4 Granular cell tumor Tumor cells have a low nuclearto-cytoplasmic ratio because of an abundance of granular cytoplasm (hematoxylin and eosin [H & E] stain) • sheets and tight clusters of cells with significant nuclear overlap • regular to irregular cellular spacing • finely to coarsely granular chromatin • prominent and/or multiple nucleoli BENIGN CONDITIONS 239 Figure 9.5 Ductal proliferative lesion without atypia Note the interspersed myoepithelial cells, which stand out like sesame seeds on a bun (Papanicolaou stain) Figure 9.7 Suspicious for malignancy The cells are loosely cohesive, with marked nuclear pleomorphism, prominent nucleoli, and a dirty background Such specimens cannot be distinguished from invasive carcinoma by FNA Histologic examination revealed comedo-type ductal carcinoma in situ (Papanicolaou stain) Figure 9.6 Ductal proliferative lesion with atypia In contrast with Figure 9.5, there is less regular nuclear spacing, more overlapping, and more prominent nuclear atypia, with a suggestion of cribriform spaces Such proliferative lesions cannot be categorized precisely by FNA Histologic examination revealed atypical ductal hyperplasia bordering on non comedo ductal carcinoma in situ (Papanicolaou stain) Differential diagnosis of ductal proliferative lesion without atypia • intraductal papilloma • fibroadenoma • carcinoma in situ An intraductal papilloma is cytologically indistinguishable from proliferative FCC Unlike proliferative FCC, however, many patients with an intraductal papilloma present with a nipple discharge or a discrete subareolar mass Proliferative FCC may be impossible to distinguish from a fibroadenoma or phyllodes tumor,129 except that stromal fragments are fairly common in the latter two, and rarely seen in proliferative FCC Pleomorphic carcinoma cells, calcium, necrosis, large nucleoli, and macrophages are indicative of comedotype ductal carcinoma in situ and are usually diagnosed as either “suspicious” or “positive” (Fig 9.7).130,131 Ductal carcinomas in situ of low and intermediate grade are usually interpreted as “atypical.”102 Some but not all welldifferentiated ductal carcinomas in situ show more dyshesion than proliferative FCC Still, distinguishing between ductal hyperplasia, atypical ductal hyperplasia, and welldifferentiated ductal carcinoma in situ by cytology is difficult,19,104,117,131-135 even with the aid of image cytometry136,137 Although ductal carcinomas in situ are more likely than papillomas and other benign ductal lesions to have numerical chromosomal aberrations as detected by fluorescence in situ hybridization (FISH),138 it is unlikely that ductal proliferative lesions will be easily categorized by FNA in the near future This limitation is not surprising, because primarily architectural, not nuclear or cellular, features define these lesions The use of cell blocks may help in the cytologic classification of these entities.139 Fibroadenoma Fibroadenoma is the most common benign tumor of the female breast Although more common in young women, it is seen in women of any age, including those who are postmenopausal Fibroadenomas are well-circumscribed, freely movable, rubbery masses that result from both stromal and glandular proliferation Cytomorphology of fibroadenoma • hypercellular • large sheets (see Fig 9.8) • three-dimensional clusters with an antlerlike configuration (Fig 9.9) • bipolar cells and spindled/oval naked nuclei (Fig 9.10) • fibrillar stromal fragments • bluish-gray with the Papanicolaou stain • intensely red-purple with a Romanowsky-type stain Continued 240 • • • • • BREAST nuclear atypia (Fig 9.11) some loss of epithelial cohesion regular nuclear spacing finely granular chromatin pattern small, round nucleolus Differential diagnosis of fibroadenoma • ductal proliferation with or without atypia • phyllodes tumor • ductal carcinoma Although no single criterion distinguishes a fibroadenoma from the ductal proliferations, a combination of features permits a distinction in most cases.140 In general, fibroadenomas are more cellular Naked nuclei, although more abundant in fibroadenomas, are seen in both conditions Stromal fragments and papillary antlerlike configurations, seen in many (but not all) fibroadenomas, are very uncommon in FCCs.140,141 The distinction between fibroadenoma and phyllodes tumor is difficult Numerous individual, long, plump, spindle-shaped nuclei are characteristic of a phyllodes tumor.142,143 Also characteristic of phyllodes tumors are fibromyxoid stromal fragments with Figure 9.8 Fibroadenoma, low magnification The specimen is hypercellular, with many folded sheets and antler-horn clusters (Papanicolaou stain) A B Figure 9.9 Fibroadenoma A, Branching antler-horn clusters are the predominant arrangement of cells There are rare stripped naked nuclei and bipolar cells in the background, but they are not prominent in this case, making it difficult to distinguish from a ductal proliferative process (Romanowsky stain) B, Clusters of tightly cohesive cells with minimal nuclear atypia are characteristic of fibroadenomas (Romanowsky stain) BENIGN CONDITIONS spindle-shaped nuclei and “fibroblastic pavements”: small fragments of cohesive fibroblasts forming a flat “pavement.”144 Hypercellular stromal fragments are more common in phyllodes tumor,143 but can be seen in fibroadenoma as well The distinction between fibroadenoma and ductal carcinoma is usually straightforward; the most helpful diagnostic features are stromal fragments, antlerlike epithelial configurations, and honeycomb sheets of ductal cells, all of which are uncommon in ductal carcinomas Some features can be misleading, however Cytologic atypia is prominent in some fibroadenomas,140,145-147 and isolated cells with intact cytoplasm, a highly characteristic feature of ductal 241 carcinoma, are seen in about 20% of fibroadenomas.8,140,147-149 Conversely, some ductal carcinomas masquerade as fibroadenomas The greatest mimics are well-differentiated invasive ductal carcinoma and ductal carcinoma in situ Naked nuclei, characteristic of fibroadenomas, are seen in some ductal carcinomas,148 although usually in fewer numbers than in a fibroadenoma Nuclear hyperchromasia favors a diagnosis of malignancy, whereas nuclei with small, uniform nucleoli suggest fibroadenoma.148 The distinction is not discernible in all cases, and the differential diagnosis may be difficult, especially in older women.140,148,149 Another mimic of fibroadenoma is papillary carcinoma.150 Most of the isolated epithelial cells from carcinomas are round to oval with eccentrically placed nuclei, whereas those from fibroadenomas are elongated or columnar, with cytoplasm on both sides of the nucleus Papillary carcinomas, however, can have isolated spindle-shaped or columnar epithelial cells on FNA Smears with equivocal findings should be reported as atypical or suspicious Pregnancy-Related and Lactational Changes Figure 9.10 Fibroadenoma Clusters of epithelial cells in a background of numerous stripped, elongated naked nuclei are characteristic of fibroadenomas When stromal cells are absent, the diagnosis is more difficult (Papanicolaou stain) Figure 9.11 Fibroadenoma Note the presence of nuclear atypia and prominent nucleoli The tightness of the cluster is an important clue for avoiding an over-diagnosis of malignancy (Papanicolaou stain) During pregnancy and lactation, the ductules of the terminal duct lobular unit become hyperplastic and manifest cytoplasmic vacuolization and luminal secretion Occasionally, this change results in a discrete nodule, called a lactating adenoma, which is difficult to distinguish clinically from a malignancy Because carcinoma is occasionally diagnosed in the setting of pregnancy, this diagnosis must be excluded in a pregnant or lactating woman FNA in this setting may be especially useful, because a diagnosis of pregnancy-related or lactational changes could at least postpone and even spare the woman an excisional biopsy 242 BREAST Cytomorphology of pregnancy and lactational changes (Fig 9.12) • moderately cellular specimen • numerous isolated epithelial cells and/or stripped nuclei • nuclear enlargement without variation in size/ shape • prominent nucleolus • mitoses • abundant delicate and wispy granular or finely vacuolated cytoplasm • cytoplasm easily stripped away, revealing: • foamy proteinaceous background • many naked nuclei • occasional small ductal cell clusters and portions of lobules the nucleoli less prominent, and the cytoplasm less wispy than in lactating adenoma Non-Hodgkin lymphoma can resemble the changes of pregnancy and lactation Both can have many isolated cells with prominent nucleoli, but the cytoplasmic features, proteinaceous background, and intact benign breast tissue typical of lactating adenomas are helpful The isolated cells of lymphoma vary more in size and shape than those of a lactating adenoma.152 Fat Necrosis Fat necrosis can mimic carcinoma both clinically and mammographically and is commonly seen in patients who have had a previous surgical biopsy or other trauma to the breast Fat necrosis is also encountered in male patients.153 Cytomorphology of fat necrosis (Fig 9.13) • hypocellular • predominantly histiocytes with fine to coarse cytoplasmic vacuoles • round to kidney bean–shaped nucleus • low nuclear-to-cytoplasmic ratio • multinucleated and atypical cells • background of neutrophils, lymphocytes, and plasma cells Differential diagnosis of pregnancy and lactational changes • carcinoma, lobular or ductal • non-Hodgkin lymphoma The cells of invasive lobular carcinoma are similar in size to those of a lactating adenoma, but the foamy background, intact acini and lobules of benign breast tissue, and the prominent nucleoli of a lactating adenoma are absent in invasive lobular cancer The nuclear size and shape of lactating adenoma cells can also resemble those of some well-differentiated ductal cancers, and the cytoplasmic features can overlap with secretory carcinoma.151 In general, ductal cancers not have the foamy background characteristic of a lactating adenoma, and the cohesive groups of malignant cells in ductal cancers are not arranged in normal acinar structures Also, the nuclei in ductal cancers are more hyperchromatic, A Differential diagnosis of fat necrosis • • • • silicone granuloma infection ductal carcinoma lipid-rich carcinoma The histiocytes seen in reactions to silicone injection or a ruptured silicone implant contain vacuoles B Figure 9.12 Pregnancy/lactational changes A, Numerous stripped (“naked”) nuclei are seen B, Cells in loose clusters can also be seen Nuclei are round or oval, with prominent nucleoli (ThinPrep, Papanicolaou stain) 548 INDEX Alveolar soft part sarcoma (ASPS), 507–508, 508f cytomorphology of, 507b differential diagnosis of, 508b Amebiasis, 23 Amebic abscess, 377 cytomorphology of, 377b Amebic meningoencephalitis, primary, 180 American Cancer Society (ACS), 2–3 American College of Obstetricians and Gynecologists (ACOG), 2–3 American Medical Association (AMA), 520 American Society for Clinical Pathology (ASCP), 2–3 American Society for Colposcopy and Cervical Pathology (ASCCP), 2–3 American Society for Cytotechnology (ASCT), 521 American Society of Clinical Pathology (ASCP), 522 Ammonium biurate crystals, 112 Amorphous protein, 68 Ampullary adenoma, 214f Amylase, 400t Amylase crystalloids, 301, 302f Amyloid with medullary thyroid carcinoma, 278 with pancreatic endocrine neoplasms, 408 Amyloid goiter, 278, 278f Amyloidoma, 513 cytomorphology of, 513b Amyloidosis pulmonary, 76 salivary gland, 308 Anal cancer, screening for, 215 Anal Pap test, 215–216 Anaplastic astrocytoma, cytomorphology of, 190b Anaplastic carcinoma, 279, 287–289, 288f, 405, 407f cytomorphology of, 288b differential diagnosis of, 289b Anaplastic ependymomas, 191 Anaplastic large cell lymphoma (ALCL), 140, 360–361, 362f, 364b cytomorphology of, 361b Anaplastic lymphoma kinase (ALK), 65, 337t Anaplastic lymphoma kinase (ALK) protein, 360–361 Anesthesia, local, 222 Angiomatoid fibrous histiocytoma (AFH), 500–501, 501f cytomorphology of, 500b differential diagnosis of, 501b Angiomyolipoma (AML), 381–383, 428, 429f atypical spindle cells, 428 cytomorphology of, 428b diagnosed by FNA, 428 hepatic, 381, 382f Angiosarcoma, 258, 390 cytomorphology of, 258b, 390b differential diagnosis of, 258b, 390b epithelioid, 150f post-radiation, 258f Angiostrongyliasis, 180 Angiostrongylus cantonensis, 177, 180 Anisonucleosis, 167–168 Annual statistics, 536, 536b Anti-thyroid peroxidase (anti-TPO), 275 Antigen, microsomal, 275 Antineutrophil cytoplasmic antibody (ANCA) test, 75 Apocrine adenosis, 237 Apocrine carcinoma, 255, 256f cytomorphology of, 255b differential diagnosis of, 255b Apocrine metaplasia, 238f, 255 Architectural atypia, 271 Arginase (ARG)-1, 380, 386, 388f Arias-Stella reaction, 24, 48 Artifacts, and contaminants of specimen, 18, 19f Asbestos bodies, 68 Asbestos fibers, 68 ASC See Atypical squamous cells (ASC) ASC/SIL ratio, 38 ASC-US (atypical squamous cells of undetermined significance), 38–40, 39f associated with atrophy, 39f with atypical parakeratosis, 40f atypical repair reaction, 40f cytomorphologic patterns of, 38b with parakeratosis, 40f Ascites, 151f ASCUS/LSIL Triage Study (ALTS), 29 Aseptic meningitis, 178–179, 178f–179f cytomorphology of, 178b differential diagnosis of, 179b list of causes of, 178t Aspergillosis, 73–74 fruiting body, 73f Astrocytic neoplasm, high grade, 181f Atlas of Exfoliative Cytology, 28 Atrophy, squamous, of cervix, 11 Atypia of undetermined significance (AUS), 270, 292–293, 293f cytomorphologic patterns of, 292t Atypical adenomatous hyperplasia (AAH), 79, 80f, 84–86 Atypical carcinoid tumor, 91, 91f cytomorphology of, 91b Atypical endocervical cells, 48 differential diagnosis of, 48b Atypical endometrial cells, 48, 49f Atypical glandular cells, 48 Atypical intradermal smooth muscle neoplasm, 488 Atypical lipomatous tumor, 477–478 cytomorphology of, 477b differential diagnosis of, 477b Atypical mycobacteria, 207, 208f Atypical parakeratosis, 12, 38 Atypical squamous cells (ASC), 4, 38–40 associated with atrophy, 38 cannot exclude HSIL (ASC-H), 38, 40, 40f–41f with squamous intraepithelial lesion ratio, 540 of undetermined significance, high-risk human papillomavirus-positivity rates for, 540 Atypical squamous metaplasia, 23–24, 40, 82f Atypical teratoid/rhabdoid tumor (ATRT), 191, 192f Atypical urine specimens, patterns of, 120b Auer rod, 186 AutoCyte Prep, 4–5 Autoimmune pancreatitis, 403, 404f AutoPap 300 QC System, AutoPap System, AutoPap System-Primary Screener, Ayre, Ernest J., B B-cell lymphoma clinical features of, 350t clonality in, 335 B-cell lymphoma (Continued) differential immunophenotype and genetics of, 351t diffuse, 187f, 326, 326b marginal zone, 292f World Health Organization (WHO) classification of, 350t Bacterial abscesses, cytomorphology of, 377b Bacterial lymphadenitis, aspirates of acute, 341 Bacterial meningitis, acute, 177–178 Bacterial pneumonias, 70–71 Bacterial vaginosis cytomorphology of, 18b shift in flora suggestive of, 18–22, 19f “Bags of polys,” 46–47 Barrett's esophagus/epithelium, 202–203 adenocarcinomas in, 203, 203b cytomorphology of, 202b dysplasia in, 203–204, 203b with goblet cells, 202f high-grade dysplasia in, 204f low-grade dysplasia in, 203f Basal cell adenocarcinoma, 322–323 Basal cell adenoma, 311–314 cytomorphology of, 311b membranous type, 314f Basal cells, 11, 60 parabasal cells and, 11f Basal urothelial cells, 110f Basaloid carcinoma, 87 Basaloid neoplasms, 301, 313f differential diagnosis of, 312b reporting, 314b Baylisascaris procyonis, 180 Bcl-2 in follicular lymphoma, 350 in solitary fibrous tumor, 495f in synovial sarcoma, 491–492 Bcl-6, 337t BD FocalPoint Guided Screening Imaging System, BD TriPath Imaging, Behỗet disease, 37 Bellini tumor, 438 Benign adrenal cortical adenoma, cytomorphology of, 443b, 444f Benign atypia, 38 Benign bronchial cells, 66 Benign ductal cells, cytomorphology of, 401b Benign ductal epithelium, in nonproliferative FCC, 238f Benign effusion, 128 mesothelial cells in, 129 Benign follicular nodules, 271–275, 272f–273f cytomorphology of, 273b differential diagnosis of, 274b Benign lymphadenopathies, 339–340, 339b Benign lymphoepithelial lesion, 305 Benign mucinous tumors, 459 Benign ovarian cyst, ultrasound features of, 453b Benign pancreatic acinar cells, cytomorphology of, 401b Benign peritoneal washings, cytomorphology of, 156b Benign serous tumors, 458–459 cytomorphology of, 458b Benign squamous cell changes, 23–24, 23f Benign stone atypia, 113f Benign thyroid nodules, 271 Beta-catenin, 411, 412f, 495, 496f Bethesda System for cervical and vaginal cytology, 8–10 for cervicovaginal specimen adequacy, 9t INDEX Bethesda System (Continued) general categorization, 10, 10b interpretation and results of, 10, 10t for reporting thyroid cytopathology, 269, 269t Web Atlas, Bevacizumab, 65 Bilateral ureteral washings, 118f Bile duct, 401–403 Bile duct cystadenomas, 378 Bile duct epithelium, cytomorphology of, 376b Bile duct hamartoma and adenoma, 381–383 cytomorphology of, 381b Bile pigment, 376, 377f, 386f Biliary ductal cells, cytomorphology of, 381b Biohazard warning label, 543f Birt-Hogg-Dube syndrome, 427–428 BK viruses, human polyomaviruses, 111–112 Black thyroid, 278–279, 278f Bladder, viral infections of, 111 Bladder cancers, superficial, 114 Bladder washings, 106 accuracy of sample, 108 Blast crisis, 186 Blastoma, pulmonary, 89 Blastomyces dermatitidis, 71–72 Blastomycosis, 71–72 Bleeding, as complication of FNA, 231 Blind biopsy, cytology and, 128 Blood, common contaminant, 172 Blue blobs, 11, 12f Boerhaave's syndrome, 130 Bone marrow, 176f Bosniak system, 431 BRAF gene, 65, 270 Brain tissue, 175f BRD4-NUT fusion oncogene, 98 Breast, 233–266 benign conditions, 237–245 cancer, 248 cytomorphology of ductal, 183b cytomorphology of lobular, 183b metastatic, 142f carcinoma of, 183 cysts of, 237 ductal carcinoma of, 142f, 145f, 183f evaluation of specimen, 236–237, 236b lobular carcinoma of, 143, 144f, 183f metastatic tumors, 258, 441f normal, 237 papillary neoplasms, 245–246 phyllodes tumor, 246–255 reporting terminology, 235–236 specimen types, 233–235 tumors, 255–258 Breast fine-needle aspiration, categories for, 235b Brenner tumors, 459 benign, 459 Bronchial brushing, 60f Bronchial cells normal ciliated, 60f reactive, 66, 66f–67f Bronchial gland tumors, adenoid cystic carcinoma and, 93 Bronchial specimens, 61–62 bronchial aspirations, 61 bronchial brushings, 61–62 bronchoalveolar lavage, 62 washings, 61 Bronchiolitis obliterans organizing pneumonia (BOOP), 77 Bronchoalveolar lavage (BAL), 62 on AIDS patients, 62 on HIV patients, 62 Bronchoscopy, fiberoptic, 61 Brushing cytology, sensitivity and specificity of, 199 Brushings, for diagnosing cholangiocarcinomas, 400 “bubble gum” colloid, 284 Burkitt lymphoma, 358–359, 359f cytomorphology of, 358b C C-kit, 211 C-myc, proto-oncogene on chromosome, 359 Calcitonin, 289 Calcium oxalate crystals, 112 Call-Exner bodies, 466 Calretinin, 138 Calymmatobacterium granulomatis, 23 Canalicular adenoma, 311 Cancer, lung, 79–92 Cancer antigen 125 (CA125), 454 Candida albicans, 20 Candida glabrata, 20 Candida infection of bladder, 111 of cervix and vagina, 20–21, 20f cytomorphology of, 21b of esophagus, 200, 200b, 200f pseudohyphae, 20–21, 20f Candida pneumonia, 74 Candidiasis, 74 Carcinoembryonic antigen (CEA), 128, 380, 400t, 454 Carcinoid tumor GI tract, 210f lung, 90–91, 91f cytomorphology of, 90b differential diagnosis of, 90b metastatic, 392f ovary, 463–465 Carcinoma, 367–369 anaplastic, 279, 287–289 basaloid, 87 clear cell, 87, 463 differentiated, 286–287 epithelial-myoepithelial, 323–324 giant cell, 88 hepatocellular, 383–387 high-grade, 323f large cell, 87–88 lipid-rich, 243f low grade, 114 PUNLMP and, 114 metastatic, 292 metastatic small cell, 393f papillary, 282 pleomorphic, 88 salivary duct, 322, 323f sarcomatoid, 88–89 small cell, 91–92 spindle cell, 88 undifferentiated, 287–289 Carcinoma in situ, cytomorphology of, 116b differential diagnosis of, 117b high-grade urothelial carcinoma and, 116–118 Carcinosarcoma, 89 of uterus, 164–165 Carotid artery disease, ultrasound for, 267 Carpet beetle parts, 19f Castleman disease (CD), 339–340 549 Casts, in urine specimens, 112 Cat scratch disease, 342, 342f cytomorphology of, 342b differential diagnosis of, 342b Catheterized urine, 106 CD3, 337t CD5, 337t, 351t CD10, 337t, 351t CD15, 337t CD19, 337t CD20, 337t, 351t CD23, 337t, 351t CD30, 337t, 360 CD34 in dermatofibrosarcoma protuberans, 497–498 in epithelioid angiosarcoma, 509b in epithelioid hemangioendothelioma, 508 in hepatocellular carcinoma, 385, 387 for Kaposi sarcoma, 370 in solitary fibrous tumor, 495f for spindle cell and pleomorphic lipomas, 477 CD43, 351t CD45, 337t CD56, 411 CD68, 130, 283–284 CD99, 491–492 CD117, 150–151, 211 CD138, 149f CD163, 130 CEA See Carcinoembryonic antigen (CEA) Cell blocks for effusions, 127–128, 134f, 145f for kidney FNAs, 424 for peritoneal washings, 155, 161 for urine and bladder cytology, 106 Cellient, preparation method for effusions, 127–128 Cells acinar, 302 atypical endocervical, 48 endometrial, 48 glandular, 48 basal, 11, 60 urothelial, 110f benign bronchial, 66 squamous, 66 cercariform, 439 ciliated columnar, 60, 271 Clara, 60 clue, 19f, 20 comet, 248b cyst lining, 274 decidual, 17 degenerated, 107 ductal, 302 endocervical, 12–13, 14f exfoliated endometrial, 13–15 glomeruli and tubular, 425–426 goblet, 60 inflammatory, 17–18 intermediate, 11 Kulchitsky, 60 luteinized granulosa, 456 mesothelial, 64f, 156f–157f neuroendocrine, 60 parabasal, 11 physaliphorous, 487 reserve, 60 seminal vesicle epithelial, 110f superficial, 11 trophoblastic, 17 550 INDEX Cells (Continued) tubular, 426f umbrella, 109, 109f vegetable, 69f Cellular follicle cysts, 456 Cellularity, 236 Centers for Medicare and Medicaid Services, 519–520 Central nervous system lymphoma, primary, 188 tumors of, 187–193 clinical features of, 188t Centroblasts, 338 Centrocytes, 338 Cercariform cells, 439 Cerebrospinal fluid (CSF), 171–196 abnormal inflammatory cells, 174–177 accuracy, 172–173 anatomy and physiology of, 171 benign cells in, 173b cytomorphology of lymphoma in, 186b differential diagnosis of eosinophils in, 177b of neutrophils in, 175b flow cytometric analysis of, 188f macrophages in, 174b malignant cells in, 171 neoplasms, 180–193 non-neoplastic disorders, 177–180 normal, 174f normal elements, 173–174 obtaining and preparing specimen, 171–172 plasma cells in, 175b primaries in patient with positive, and no history of cancer, 181b reporting terminology, 172 tumor involvement of, 173f Cerebrospinal fluid cytology role of, 172 sensitivity of, 173b specificity of, 173 Cervarix, Cervical and vaginal cytology, 1–58 accuracy and reproducibility, 7–8 automated screening, 5–7 benign and reactive changes, 23–27 Bethesda system, 8–10 diagnostic terminology and reporting systems, organisms and infections, 18–23 sampling and preparation methods, 3–4, 3b Cervical cancer, 166 false-positive diagnoses of, screening guidelines, 2t Cervical intraepithelial neoplasia (CIN), 8, 31f Cervical smears, numerical system for reporting, Cervix, squamous cell carcinoma, 145f Charcot-Leyden crystals, 68, 68f, 131 Chemotherapy, effects of, 112–113 “Chicken wire” artifact, 273–274, 274f Chlamydia trachomatis, 22, 458 “Chocolate cyst,” 457 Cholangiocarcinoma, 388–390, 389f brushings for diagnosing, 400 cytomorphology of, 388b differential diagnosis of, 388b Chondrocyte, 176f Chondromyxoid matrix, 301 Chondrosarcoma cytomorphology of, 505b extraskeletal myxoid, 480 Chordoma, 487, 487f cytomorphology of, 487b differential diagnosis of, 487b Choroid plexus, 171, 174f Choroid plexus carcinoma, 192 cytomorphology of, 192b Choroid plexus papilloma, 192f cytomorphology of, 192b Choroid plexus tumors, 191–192 Chromatin, 279 Chromogranin, 210 Chromophobe renal cell carcinoma, 435–438 classic variant of, 435 cytomorphology of, 437b differential diagnosis of, 437b eosinophilic variant of, 435 mixed variant of, 435 versus oncocytoma, 437–438 typical variant of, 437f Chronic leukemias, 149 Chronic lymphocytic leukemia (CLL), 186 Chronic lymphocytic thyroiditis, 275–277, 276f Chronic mastitis, 244 Chronic pancreatitis, 403 cytomorphology of, 403b and reactive ductal atypia, 403 Chronic sclerosing sialadenitis, 303–304 Chronic sialadenitis, 304f, 306 aspirates of, 303–304 cytomorphology of, 303b differential diagnosis of, 304b FNA of, 302 Churg-Strauss syndrome, 130–131 Ciliary tufts, detached, 157 Ciliocytophthoria, 70 Cirrhosis, 127, 378–379 cytomorphology of, 379b differential diagnosis of, 379b CK7, 95, 438–439, 460 CK20, 460 Clara cells, 60 Clear cell carcinoma, 87, 119, 324, 463 cytomorphology of, 119b differential diagnosis of, 324b of kidney, 142f Clear cell renal cell carcinoma, 432–434, 434f cytomorphology of, 433b differential diagnosis of, 433b Clear cell sarcoma cytomorphology of, 507b of soft tissue, 507, 507f Clear cell tumor, 93 CLIA 88 See Clinical Laboratory Improvement Amendments of 1988 (CLIA 88) Client service manual, 523b Clinical and Laboratory Standards Institute (CLSI), 523 Clinical Laboratories Improvement Advisory Committee (CLIAC), 521 Clinical Laboratory Improvement Amendments of 1988 (CLIA 88), 519–521, 521b Clonality, in B-cell lymphomas, 335 Clonorchis sinensis, 388 “Clue cells,” 19f, 20 CMV See Cytomegalovirus (CMV) Coagulation disorder, 334 Coaxial needle technique, 399 Coccidioides immitis, 72, 73f, 341 Coccidioidomycosis, 72 Cockleburrs, 19f Collagen balls, 157, 157f Collecting duct carcinoma, 438 College of American Pathologists (CAP), 520 Colloid, 270–271, 273f and amyloid, 269 “bubble gum,” 270–271, 284 “folded tissue paper,” 273–274, 274f Colloid nodules, 271–272 Colon, cytology of, 215 Colon adenoma, 215f Colon cancer, metastatic, to bladder neck, 120f Colonic carcinoma, 119–120, 120f metastatic, 391f Colorectal cancer, 391–392 Columnar cell ciliated, 60 variant, 282 Commission on Accreditation of Allied Health Education Programs, 520 Competency assessment, 536–537 minimal requirements for, 537b Computed tomography (CT), 267, 399 Congenital cysts, 306 Congestive heart failure (CHF), 127 Consultation cases, coding, 533–534, 533b Contaminants, artifacts and, of specimen, 18, 19f Conventional smears, 3–4 Core needle biopsy (CNB), automated, of breast, 233 Cornflaking, 19f Corpora amylacea, 68, 69f Corpus luteum cyst, 456, 457f cytomorphology of, 456b Coy cells, 120–121, 122f CPT See Current procedural terminology (CPT) CPT modifier, 525 Creola bodies, 66, 67f, 84 Cribriform carcinoma, 282 Cross-contamination, 523–524 Cryptococcal meningitis, 179, 180f cytomorphology of, 179b Cryptococcosis, 71 of breast, 242–243, 243f Cryptococcus, 62 Cryptococcus neoformans, 71, 179, 341 Cryptosporidia, 213, 214f Crystalloids amylase, 301 tyrosine, 301 Crystals in urine specimens, 110, 112 Culdocentesis, 127 Current procedural terminology (CPT), 521, 524 Curschmann spirals, 68, 68f Cushing syndrome, 443 Cyclin D1, 351t Cyst fluid only (CFO), 269–270 Cyst lining cells, 274–275, 275f, 286 Cystadenocarcinomas, 378 Cystadenofibroma, 458 Cystic degeneration, 284 Cystic follicle, and follicle cyst, 455–456 Cystic nephroma, 430 Cystic teratoma, 464f Cysticercosis, 180 cytomorphology of, 180b Cysts acquired, of salivary gland, 306–307 breast, 237 classified as per Bosniak system, 431 corpus luteum, 456 cytomorphology of simple, 457b INDEX Cysts (Continued) dermoid, 464f echinococcal, 377–378, 378f endometriotic, 457b epithelial, 454 follicular/lutein, 454 functional, 455 lymphoepithelial, simple, 306 mucin-containing, 306–308 non-neoplastic, 306–308, 455–458 paratubal, 457–458 parovarian, 457–458 renal, 431–432, 431f retention, 306–307 serous, 457 solitary, 378 squamous-lined, 306 Cytocentrifugation, to prepare specimen, 172 Cytogenetics and molecular cytogenetics, 473 Cytologic-histologic correlation, 535–536 Cytology/biopsy correlation, 540–541 Cytology laboratories federal retention requirement for, 524t steps in the flow of work of, 523b Cytology screening devices, automated, 6f Cytology slides, 524 re-examination requirements, 534b Cytolysis, 18 CytoLyt®, 198, 229 Cytomegalovirus (CMV), 21–22, 22f, 69, 133 cytomorphology of, cytopathic changes, 22b cytomorphology of cells infected with, 200b Cytopathologists, scoring grid for, 537t Cytoplasmic inclusions, 109f CytoRich Red®, 198, 229 CytoSpin®, 172, 400 Cytotechnologists, 522–523 performance measures for, 538–541, 538b qualifications of, 522b responsibilities of, 522b scoring grid for, 537t Cytyc, D Decidual cells as isolated cells, 17 trophoblastic cells and, 17 “Decoy cells,” 111–112, 117 Dedifferentiated sarcomas, 512 Dendritic cells, 338 Dendritic-lymphocytic aggregates, 276–277, 337–338 Dendritic neoplasms, 366t de Quervain thyroiditis, 277 Dermal analogue tumor, 312 Dermatofibrosarcoma protuberans (DFSP), 497–498 cytomorphology of, 497b differential diagnosis of, 498b Dermatopathic lymphadenitis, 346, 346f Dermoid cysts, 464f “DES daughters,” vaginal specimens in, 28 Desmin, muscle marker, 289 Desmoid fibromatosis, 496f Desmoplastic small round cell tumor (DSRCT), 503–504 cytomorphology of, 503b, 504f Detached ciliary tufts, 157, 458f Diethylstilbestrol (DES), 2–3 Diffuse large B-cell lymphoma (DLBL), 139, 146–147, 147f, 210, 211f, 326b, 327, 327f, 356–357, 357f characterization of, 356–357 cytomorphology of, 356b differential features of, 358t variants of, 357–358 Diffuse sclerosing variant, 282 Dirofilariasis, 75 Distal tubular cells, 426 cytomorphology of, 425b differential diagnosis of, 425b Dithiothreitol (DTT), for homogenization, 61 DLBL See Diffuse large B-cell lymphoma (DLBL) DNA probes, 337 DOG1, 211, 394, 489 Dog heartworm infection, 75 Donovan body, 23 “drunken honeycomb,” 405 Ductal adenocarcinomas, 404–405, 406f–407f cytomorphology of, 405b differential diagnosis of, 405b variants of, 405, 407f Ductal atypia, reactive, 404, 404f cytomorphology of, 403b Ductal breast cancer, cytomorphology of, 183b Ductal carcinoma, 142f, 249f–250f of breast, 96f, 142f Ductal cells benign, 235 of salivary glands, 302 Ductal epithelium, benign, 238f Ductal proliferative lesions, 238 cytomorphology of with atypia, 239f without atypia, 238b, 239f differential diagnosis of, without atypia, 239b Duodenal adenoma, cytomorphology of, 213b Duodenal epithelial cells, 403f Duodenal mucosa, cytomorphology of, 402b Duodenum brush cytology of, 212 common lesions of, 213 Dysgerminomas, 150–151, 465, 466f aspirates from, 465 of ovary, 163f Dysplasia, in Barrett's esophagus, 203–204 of bladder, 116 cytomorphology of high-grade, 203, 203b low-grade, 203b and gastric adenomas, 208 mild, 8, 29–30, 31f E E2 levels See Estradiol levels EBER See Epstein-Barr virus (EBV)encoded RNA (EBER) EBUS (endobronchial ultrasound-guided) fine-needle aspiration, 62 Echinococcal cyst, 377–378, 378f cytomorphology of, 377b Echinococcosis, 75 Echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK), 65, 66f Ectopic spleen, 417, 418f 551 Effusions, 127 eosinophilic, 130–133, 131f immunochemistry for, 128b tips for detecting malignant cells in, 134b Elastofibroma, 513 cytomorphology of, 513b Embryonal carcinoma, of ovary, 164f, 465 tumor cells of, 465 Embryonal rhabdomyosarcoma, 504 cytomorphology of, 504b Endobronchial granular cell tumor, 79 cytomorphology of, 79b Endocervical adenocarcinoma, 43–46, 44f–45f cytomorphology of, 43b with endocervical cells, 45f Endocervical cells, 12–13, 14f atypical, 48 reactive, 24f–25f Endocervical changes, benign, 24 Endocervical polyp, 34f, 47f Endometrial adenocarcinoma, 46 compared to IUD effect, 47f cytomorphology of, 46b inflamed endocervical polyp mimicking, 47f Endometrial cancer, 163–166 clear cell type, 166f cytomorphology of, 164b endometrioid type, 164f–165f peritoneal washing cytology in women with, 166t types of, 164–165 Endometrial cells, 14f abraded, and lower uterine segment, 15–17 atypical, 48 cytomorphology of exfoliated, 13b differential diagnosis of, 15b, 52b exfoliated, 13–15 mimics of, 15f sample report, 51b sampled, 16f shedding, 14–15 in women, 50–52, 51f, 51t Endometrial glandular cells, 160 Endometrioid carcinoma, of ovary, 462–463, 464f cytomorphology of, 462b Endometriosis, 159–160, 160f of cervix, 27, 27f cytomorphology of, 159b Endometriotic cyst, 457, 457f cytomorphology of, 457b Endometrium and lower uterine segment, cytomorphology of, 17b Endosalpingiosis, 158, 159f and benign proliferations, 157–159 cytomorphology of, 158b Endoscopic retrograde cholangiopancreatography (ERCP), 375, 400 Endoscopic ultrasound-guided fine needle aspiration, 399 Endothelial cells, 387 Entamoeba gingivalis, 23 Entamoeba histolytica, 23, 180, 377 Eosinophilic effusions, 130–133 Eosinophils, 177f in cerebrospinal fluid, 177 hematoxylin and eosin staining of, 132–133 Ependyma, 171 Ependymal cells, 174f Ependymoma cells, 191, 191f cytomorphology of, 191b 552 INDEX Epidermal growth factor receptor (EGFR), 64–65, 144 Epithelial cells in ileal loop specimens, 110, 111f seminal vesicle, 110 type A, 96 Epithelial cysts, 454 Epithelial membrane antigen (EMA), 135, 197–198, 252, 347–348, 428–429 differential immunoreactivity for, 430–431 Epithelial-myoepithelial carcinoma, 323–324, 323f cytomorphology of, 324b differential diagnosis of, 324b Epithelial repair, 201–202, 201f, 208 cytomorphology of, 201b Epithelioid angiosarcoma, 86–87, 150f, 509 cytomorphology of, 509b differential diagnosis of, 509b of lung, 89f Epithelioid hemangioendothelioma (EHE), 86–87, 390, 508–509 cytomorphology of, 390b, 508b differential diagnosis of, 508b in pleural effusions, 140f Epithelioid neoplasms, 505–510 immunoprofile of, 505t Epithelioid sarcoma, 505–507, 506f cytomorphology of, 506b differential diagnosis of, 507b Epstein-Barr virus (EBV)-encoded RNA (EBER) in effusions, 139–140, 148 in nasopharyngeal carcinoma, 368f ERBB-2, 65 Esophageal adenocarcinoma cytomorphology of, 204b differential diagnosis of, 205b Esophageal balloon cytology, 198 Esophageal dysplasia cytomorphology of, 203b differential diagnosis of, 204b Esophagus adenocarcinoma of, 204–205, 205f leiomyoma of, 206, 207f small cell carcinoma of, 206f squamous cell carcinoma of, 205 uncommon tumors of, 206 Estradiol levels, 453 Estrogen receptor (ER), immunochemistry for, 143–144, 144f Ewing sarcoma, 501–503, 502f, 503b cytomorphology of, 502b differential diagnosis of, 503b Exfoliative cytology, 59 Exposure control, 542–543 contaminated sharps, 543b engineering and work practice controls, 542b methods of compliance, 542b potentially infectious human materials, 542b written, plan, 542b Extramedullary hematopoiesis (EMH), 149, 150f Extraskeletal mesenchymal chondrosarcoma, 505 cytomorphology of, 505b Extraskeletal myxoid chondrosarcoma (EMC), 480, 487–488, 488f cytomorphology of, 488b differential diagnosis of, 488b Extruded lipid, 479f Exudates, 127 F False-negative rate calculation, 539t Familial adenomatous polyposis, 282 Fat necrosis (FN), 242–243, 243f, 475f cytomorphology of, 242b differential diagnosis of, 242b “Feathering,” 41, 42f Ferruginous bodies, 68 “Fiber cells,” 36, 37f Fibroadenoma, 239–241, 240f–241f cytomorphology of, 239b–240b differential diagnosis of, 240b fibrocystic changes (FCC), 236–237 Fibrocystic changes, 237–239 nonproliferative, 237 proliferative, 238–239 Fibrohistiocytic neoplasms, 499–501 Fibrolamellar hepatocellular carcinoma, 389f cytomorphology of, 387b Fibroma, ovary, 468–469 Fibromatosis, 494–496 cytomorphology of, 495b differential diagnosis of, 496b Fibromyxoid sarcoma, low-grade, 483–484 Fibrosarcoma, hemangiopericytoma and, 498 Fibrosis, idiopathic retroperitoneal, 512–513 Fine-needle aspiration (FNA), 299, 375, 399, 423b of acute sialadenitis, 302 advantages of, for soft tissue lesions, 472b of breast, 233–234 categories for reporting results, 235b of chronic sialadenitis, 302 coding, 531–533 complications of, 231 diagnostic dilemmas in salivary gland, 301b endobronchial ultrasound-guided (EBUS), 62–63 endoscopic ultrasound (EUS) guided, 399 equipment, 222t, 223f explanation of procedure, sample, 222 management of adverse and unexpected events, 231 in pediatric patients, 441–442 percutaneous, 63–64 pneumothorax and, 231t post-procedure information for patient, 229–230 preparing sample, 224–229, 229f procedure, 399 procedure codes for, 531t procedure for, of a palpable mass, 221–224, 222b reporting results for soft tissue lesions, 473b and specimen handling, 221–232 statistical performance characteristics of, 472b transbronchial, 62 transesophageal, 63 types of sample preparations, 230t variations on biopsy technique, 230–231, 230f Fire safety placard, 544f FISH See Fluorescence in situ hybridization (FISH) Fite-Faraco stain, 71 “floret” cell, 476, 477f Flow cytometry, 336, 336b advantages of, 335b and immunocytochemistry, 335t Fluorescence in situ hybridization (FISH), 239, 405, 424 for follicular lymphoma, 350 Fluorescence in situ hybridization (Continued) for mesothelioma, 135, 137f for papillary renal cell carcinoma, 436f soft tissue FNA, 472 for synovial sarcoma, 491–492 in urinary samples, 121 Fluorochromes, 336b FNA See Fine-needle aspiration (FNA) Focal nodular hyperplasia (FNH), 375, 379–380, 379f cytomorphology of, 379b differential diagnosis of, 379b FocalPoint Slide Profiler, Follicle cyst, 455f–456f cystic follicle and, 455–456 cytomorphology of, 455b differential diagnosis of, 456b Follicular adenoma (FA), 272–273, 284f Follicular carcinoma (FC), 274–275, 279 clear cell variant, 280 oncocytic (Hürthle cell) variant of, 281 Follicular cells, in black thyroid, 278–279 Follicular center fragments, 338 Follicular cervicitis, 17–18, 17f, 52, 52f Follicular dendritic cell sarcoma, 367, 370, 370f Follicular lesion of undetermined significance (FLUS), 292 Follicular lymphoma (FL), 187f, 350–351, 352f cytomorphology of, 350b Follicular neoplasm, 279–280, 284f cytomorphology of suspicious for, 280b differential diagnosis of suspicious for, 280b Hürthle cell type, 280–282, 281f suspicious for, 280f Follicular variant, 282 Foregut cyst cytomorphology of ciliated, 378b differential diagnosis of ciliated, 378b French-American-British (FAB) classification on ALL, 184 on AML, 185 Fuhrman system, 432 Functional cysts, 455 Fungal abscesses, cytomorphology of, 377b Fungal infections, pulmonary, 71–74, 72t Fungi, invasive, 73–74 G Gardasil, Gardner syndrome, 282 Gardnerella vaginalis, 18 Gastric adenocarcinoma, 208 cytomorphology of, 208b, 209f differential diagnosis of, 208b–209b Gastric adenomas, dysplasia and, 208 Gastric dysplasia cytomorphology of, 208b differential diagnosis of, 208b Gastric epithelial cells, 403f Gastrointestinal stromal tumor (GIST), 211–212, 213f, 393f cytomorphology of, 212b differential diagnosis of, 212b Gastrointestinal tract, 197–220 accuracy of cytology for, 199 clinical indications, 197–198, 197b colon, 215 duodenum, 212–213 esophagus, 200–206 review of morphologic findings, 199–200, 199b–200b INDEX Gastrointestinal tract (Continued) sample collection and processing, 198–199 stomach, 206–212 Gastrointestinal tumors, endoscopic brushing and biopsy in detecting, 199t Gene expression profiling, 336b, 337 General supervisor (GS), 522 qualifications of, 522b Germ cell tumors, 97–98, 150–151, 193, 463–465 nonseminomatous, 151 Germinal matrix, 176f Germinoma, 193f, 369 cytomorphology of, 193b, 369b Giant cell carcinoma, 88, 89f Giant cell tumor, tenosynovial, 499–500, 499f Giant cells multinucleated, 271 osteoclast-type, 287–288 Giardia lamblia, 212 Giemsa stain, 23 Glandular cells, 16f, 17 atypical, 48 status post hysterectomy, 27, 27f Glandular lesions, comparison of, 204t Glial fibrillary acidic protein (GFAP), 181, 181f Glioblastoma, 190, 190f astrocytomas and, 190–191 cytomorphology of anaplastic, 190b Gliomatosis cerebri, 190 Glomeruli, 425f cytomorphology of, 425b differential diagnosis of, 425b and tubular cells, 425–426 Glycogen, 18 Glypican, 3, 385, 385f Gnas, molecular analysis for, 400t Gnathostoma spinigerum, 180 Goblet cells, 60 Goiter, amyloid, 278 Gouty tophi, 500 Graafian follicle, 455 Granular cell tumors, 282, 509–510, 510f of breast, 237, 238f cytomorphology of, 509b differential diagnosis of, 510b Granuloma inguinale, 23 Granuloma venereum, 23 Granulomas, 71f, 277, 278f, 378 Granulomatous inflammation, 71 Granulomatous lobular mastitis, 244 Granulosa cell tumors, 466–468, 467f adult, 151f cytomorphology, 466b differential diagnosis of adult, 466b juvenile, 468 Graves' disease, 279 Gynecomastia, 245 cytomorphology of, 245b, 246f differential diagnosis of, 245b H Hale's colloidal iron (HCI) stain, 427–428 “hallmark cell,” 140 Hamartoma, pulmonary, 78, 78f Hashimoto thyroiditis (HT), 269, 275–277, 276f cytomorphology of, 276b differential diagnosis of, 277b Hassall corpuscles, 96 HCPCS See Healthcare Common Procedure Coding System (HCPCS) HCPCS modifiers, 525 Health care facilities, National Fire Protection Association Standard for, 544–545 Health Care Financing Administration (HCFA), 519 Health Insurance Portability and Accountability Act of 1996 (HIPAA), 519, 521 Healthcare Common Procedure Coding System (HCPCS) codes, 525 Helicobacter pylori, 206–207, 207f Hemangioma liver, 381, 381f cytomorphology of, 381b salivary gland, 327 Hemangiopericytomas, 494 and fibrosarcoma, 498 Hematoma, 231 Hematoxylin bodies, 132–133, 133f, 344–345 Hematuria, 105 Hemosiderin-laden macrophages, 159–160 Hepatic abscess, 377 Hepatic adenoma, 380–381, 380f cytomorphology of, 380b differential diagnosis of, 380b Hepatic angiomyolipoma (AML), 381 cytomorphology of, 382b differential diagnosis of, 382b Hepatitis, 378 Hepatitis B vaccination, 543 Hepatoblastoma, 390 Hepatocellular carcinoma (HCC), 383–387, 383f–387f, 400 cytomorphology of, 383b, 386b differential diagnosis of, 385b–386b fibrolamellar, 387, 389f immunomarkers of, 388f Hepatocytes cytomorphology of, 375b–376b normal, 376f HER2, 65 Herpes simplex infection, of esophagus, 200b, 200f Herpes simplex virus (HSV), 21, 21b, 22f, 69 Hettich centrifuge, HHV-8, 139 Hibernoma, 475–476, 476f cytomorphology of, 475b differential diagnosis of, 475b High-grade dysplasia, in Barrett's epithelium, 204f High-grade squamous intraepithelial lesion (HSIL), 30–35, 32f–33f anal cytology for, 215f cell blocks in hyperchromatic cell clusters in, 34f cytomorphology of, 30b differential diagnosis of, 32b distinguishing from invasive carcinoma, 35 endocervical polyp atypia mimicking, 34f keratinizing type, 33f High-grade urothelial carcinoma, differential diagnosis of, 117b Highly active antiretroviral therapy (HAART), 62 Histiocytes, 18f, 130f, 157, 158f cytomorphology of, 130b Histiocytic necrotizing lymphadenitis, 344 Histiocytic neoplasms, 366t Histoplasma capsulatum, 71, 341 553 Histoplasmosis, 71 HIV-associated cystic lymphoepithelial lesions, 306 HIV-associated lymphadenopathy (HIVAL), 345–346, 346f HMB-45 for angiomyolipoma, 428 for clear cell tumor, 93 Hodgkin lymphoma (HL), 148–149, 149f, 378 classical, 347–348, 348f cytomorphology of, 348b diagnosis of, 348–349 differential diagnosis of, 349b L & H cells in, 339 primary pulmonary, 94 World Health Organization (WHO) classification of, 347t Homer-Wright rosettes, 501 Homogenization, dithiothreitol (DTT) for, 61 Honeycomb, drunken, 405 Hormone replacement therapy (HRT), 51 Horner syndrome, 80 HPV 16, HPV 18, HPV capsid protein L1, HPV test, 29 HPV vaccines, prophylactic, for cervical cancer prevention, HSIL Pap, 35 Human epidermal growth factor receptor (HER2), immunochemistry for, 143–144 Human herpesvirus (HHV-8), 139, 141f Human immunodeficiency virus (HIV) BAL on, 62 lymphoepithelial cysts and, 306 Human papillomavirus (HPV) in anal neoplasia, 215 effects on host cell, 29f examples of low-risk and high-risk, 29b genome of, 28–29, 29f testing for, 29 vaccines against, Human papillomavirus (HPV)-associated squamous cell carcinoma, 368–369 Hürthle cell carcinoma, 279 Hürthle cell metaplasia, focal, 274f Hürthle cell neoplasm, 280–282 cytomorphology of suspicious for, 281b differential diagnosis of suspicious for, 281b Hürthle cell nodules, hyperplastic, 277 Hürthle cells, 271 of HT, 277 in MNG, 274, 274f Hyaline casts, 112 Hyalinizing trabecular tumor (HTT), 286 Hydatid cyst, 377–378 Hydatid disease, 75 Hydrosalpinx, 458 Hypercellular specimens, 301 Hyperkeratosis, 12, 13f Hyperplasia, reactive, 338–339, 354 I ICD-9-CM See International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) Idiopathic recurrent aseptic meningitis, 179 Idiopathic retroperitoneal fibrosis, 512–513 cytomorphology of, 513b differential diagnosis of, 513b Ileal conduits, urine and bladder cytology, 106 554 INDEX Ileal loop specimen, 111f Immature teratoma, 463 Immunoblasts, 338 Immunocytochemistry, 181, 336 advantages of, 336b Immunohistochemical panels, 139t Incidentalomas of adrenal, 442 of thyroid, 267 Infections, 110–112, 110b in duodenum, 212–213 esophageal, 200 polyomavirus, 112f in respiratory tract, 69–75 in stomach, 206–207 viral, 69–70 differential diagnosis of, 200b Infectious mononucleosis, 345, 345f cytomorphology of, 345b differential diagnosis of, 345b Inflammatory atypia, 38 Inflammatory cells, 17–18, 301 Inflammatory myofibroblastic tumor (IMT), 78–79, 498 cytomorphology of, 79b, 498b differential diagnosis of, 498b Inflammatory processes, common, 76–78 Inform Thyroid Panel, 270 Insular carcinoma, of thyroid, 287f Insulin-like growth factor receptor, 65 Interdigitating dendritic cell sarcoma/tumor, 367 Intermediate cells, 11, 11f International Classification of Diseases, 9th Revision, Clinical Modification (ICD9-CM), 521, 525–527 International Federation of Gynecology and Obstetrics (FIGO), 163 International Society of Urologic Pathologists (ISUP), 114 WHO and, classification system for urothelial neoplasms, 114b Intraductal papillary mucinous neoplasm (IPMN), 400, 415–416 cytomorphology of, 416b Intraductal papillomas, 235, 239, 245 Intraepithelial lesion high-grade squamous See High-grade squamous intraepithelial lesion (HSIL) low-grade squamous See Low-grade squamous intraepithelial lesion (LSIL) Intramuscular myxoma, 480–481, 480f cytomorphology of, 480b differential diagnosis of, 481b Intranuclear pseudoinclusions (“holes”), 283–284 Intrauterine devices (IUDs), 14–15 and Actinomyces, 21 cellular changes associated with, 26–27, 85f cytomorphology of effect, 26b differential diagnosis of effect, 26b effect, 27f, 47f Invasive ductal carcinoma, 248–250 cytomorphology of, 248b differential diagnosis of, 248b Invasive lobular carcinoma, 250–251 cells of, 242 cytomorphology of, 251b differential diagnosis of, 251b Invasive micropapillary carcinoma, 246f Islet cell tumor, 407 ISUP See International Society of Urologic Pathologists (ISUP) J JC viruses, human polyomaviruses, 111–112 Joint Commission, 520 Juvenile granulosa cell tumors (JGCTS), 468 Juxta-articular myxoma, 480 K K-ras, molecular analysis for, 400t Kaposi carcinoma, 370 kappa, 337t Karyorrhexis, 146–147 Keratosis, 13f Ki67, 337t, 394, 408, 410f Ki-1, 337t, 360 Kidney, 423–442 accuracy of, 424 adequacy of, 425 and adrenal gland, 442–446 benign lesions, 426–432 clear cell carcinoma of, 142f FNA of, 423 metastatic tumors, 440–441 normal elements, 425–426 specimen collection and preparation, 424 Kikuchi lymphadenitis (KL), 344–345, 344f cytomorphology of, 344b differential diagnosis of, 344b Koilocytes, 28, 112 KRAS, 65–66 Krukenberg tumors, 469 Kulchitsky cells, 60 Kupffer cells, cytomorphology of, 376b Kuttner tumor, 303–304 L Laboratory director, 521–522 qualifications of, 522b responsibilities of, 521b Laboratory management, 519–546 agencies and organizations, 519–520 billing, 524–534 competency assessment, 536–537 laboratory personnel, 521–523 performance evaluation, 538–541 policy and procedural manuals, 523, 523b proficiency testing, 537–538 quality control and quality assurance, 534–536, 534b regulations, 520–521 safety, 541–545 workflow, 523–524 Lactate dehydrogenase (LDH), 127 Lactating adenoma, 241 Lactational changes cytomorphology of, 242b, 242f differential diagnosis of, 242b pregnancy and, 241–242 Lactic acid, 18 Lactobacillus, 18, 18f lambda, 337t Langerhans cell histiocytosis, 344, 367 Large cell carcinoma (LCC), 87–88, 88f, 197–198 cytomorphology of, 87b, 368b differential diagnosis of, 87b Large cell lymphomas, differential diagnosis of, 211b, 364–367, 364b Large cell neuroendocrine carcinoma (LCNEC), 87, 88f Legionella sp., 71 Leiomyomas, of GI tract, 207f, 212 Leiomyosarcoma, 488–490, 489f cytomorphology of, 489b differential diagnosis of, 490b Leptomeningeal metastasis (LM), 171, 180–181 Leptomeninges, 171 Leptothrix, 20 LESA See Lymphoepithelial sialadenitis Lesions associated with architectural patterns, 236b Leukemias, 94–95, 184–186 acute, 149 chronic, 149 differential diagnosis of, 94b Leukocyte common antigen (LCA), 139–140, 197–198 Lipid-rich carcinoma, 243f Lipoblast, 478f Lipoblastoma, 485 cytomorphology of, 485b Lipofuscin, 375, 376f Lipogenic neoplasms, 473–480 Lipoma, 473–475, 475f cytomorphology of, 475b differential diagnosis of, 475b Lipophage, 475 Liposarcoma inflammatory, 478 pleomorphic, 478–480 well-differentiated, 477–478 Liquid-based cytology (LBC), Liquid-based preparations, 269 method for estimating adequacy of squamous, 9f Liver benign lesions, 378–383 FNA, complications of, 375 infections, 377–378 malignant tumors, 383–394 normal, 375–377 Lobular breast cancer, cytomorphology of, 183b Lobular carcinoma of breast, 143, 144f, 251f in effusions, 144, 144f Lobular carcinoma in situ (LCIS), 251, 251f Location-guided screening, 5, Low estrogen states, 11b Low-grade dysplasia, in Barrett's epithelium, 203f Low-grade cribriform cystadenocarcinoma, 322 Low-grade fibromyxoid sarcoma (LGFMS), 480, 483–484, 483f cytomorphology of, 483b differential diagnosis of, 483b Low-grade lesions architectural criteria for, 115b, 115f cytologic criteria for, 114b, 115f urothelial, 114–116 Low-grade squamous intraepithelial lesion (LSIL), 30 avoiding overdiagnosis of, 35 cytomorphology of, 30b differential diagnosis of, 30b distinguishing, from HSIL, 35 keratinizing type, 32f koilocytes, 31f management of woman with, 30 nonkoilocytic, 31f Lower dietary iodine, 271 Lower uterine segment (LUS), 3, 15–17 Lubricant, Lumbar puncture (LP), 171 Lung adenocarcinoma of, 141f, 182f carcinoma of, 182 cytomorphology tahir99-VRG vip.persianss.ir INDEX Lung (Continued) of adenocarcinoma, 182b of small cell carcinoma, 182b epithelioid hemangioendothelioma of, 140f small cell carcinoma of, 146f, 183f squamous cell carcinoma of, 145f Lung cancers, 79–92 metastatic, 95, 440f molecular testing of, 64–66 Lung injury, types of, 87 Lupus erythematosus (LE) cell, 132–133 Lupus pleuritis, 132–133 Luteinized granulosa cells, 456 Lyme disease, 177f Lymph node fine-needle aspiration advantages of, 333b comprehensive workup of, 347b indications for, 333b limitations of, 334b Lymph nodes, 333–374 ancillary studies, 335–337, 335b complications of, 334 FNA of, 335 microanatomy of, 337 neoplasms, 347–370 non-neoplastic lesions, 337–347 reporting terminology and accuracy, 334–335 technical aspects, 334 Lymphadenitis acute, 341f bacterial and fungal, 341–347 Lymphadenopathy, associated with Toxoplasma gondii, 340 Lymphoblastic leukemia, acute, 184–185 Lymphoblastic lymphoma, 147f, 363f cytomorphology of, 363b precursor T- and B-cell, 362–363 Lymphocytic effusions, 131, 131f–132f differential diagnosis of, 131b Lymphocytic interstitial pneumonia, 94f Lymphocytic thyroiditis, chronic, 275–277, 276f Lymphoepithelial carcinoma, 326 cytomorphology of, 326b Lymphoepithelial cysts, 415, 415f cytomorphology of, 415b differential diagnosis of, 415b simple, 306 Lymphoepithelial islands, 306 Lymphoepithelial sialadenitis (LESA), 305–306 cytomorphology of, 305b differential diagnosis of, 305b Lymphoepithelioma-like carcinoma, 87 Lymphoglandular bodies, 337–338 Lymphoid cells, recognition of, 197–198 Lymphoid hyperplasia, reactive, 338f Lymphoid tissues, aspirated, consistent findings in, 337b Lymphomas, 94–95 classification of, 335 differential diagnosis of, 94b, 148b FNA of, used in primary diagnosis and classification of, 347b Hodgkin, 148–149 of large cells, 356–367 mediastinal, 97 non-Hodgkin, 148f of small cells, 350–356 of thyroid, 290–292 Lymphoproliferative disorders, immunocytochemical markers for diagnosis of, 337t M Macrofollicular fragment, 273 Macrofollicular variant, 282 Macrophages, 176f, 270f in cerebrospinal fluid, 174b Magnetic resonance imaging (MRI), 267, 375 Malakoplakia, 23, 110 Malignancy, suspicious for, 239f Malignant cells in lacunae, 134f negative for, 235 positive for, 236 tips for detecting, in effusions, 134b Malignant effusions, 133–151 tumors that cause, 134t Malignant fibrous histiocytoma (MFH), 481–482 Malignant lymphomas, 49, 186–187, 326–327 cytomorphology of, 326b Malignant melanoma See Melanoma Malignant mesothelial cells, 135 Malignant mesothelioma, diffuse, 134–139, 136f–137f Malignant mixed tumor, 49, 321–322 Malignant peripheral nerve sheath tumor (MPNST), 491, 492f cytomorphology of, 491b differential diagnosis of, 491b Malignant tumors, 160–167 MALT See Mucosa-associated lymphoid tissue (MALT) Mammary analogue secretory carcinoma (MASC), 324–325, 325f cytomorphology of, 324b differential diagnosis of, 325b Mantle cell lymphoma (MCL), 353–354, 355f aspirates of, 354 cytomorphology of, 354b Marginal zone lymphoma (MZL), 351, 352f cytomorphology of, 351b Masson bodies, 77, 77f Mast cells, 314–315 Mastitis, 244 acute, 244 chronic, 244 granulomatous, 244 plasma cell, 244 Matrix absent, 309 adenoid cystic-like, 309–310 chondromyxoid, 301 sparse, 309 Mature teratoma, 463, 464f Measles virus, 69–70 cytopathic effect, 70f Mediastinal lymphoma, 97 Mediastinum anterior masses, differential diagnosis of, 95b tumors of, 95–98 Medicaid programs, 519 Medicare programs, 519 Medullary carcinoma, of the breast, 252 cytomorphology of, 252b, 252f differential diagnosis of, 252b Medullary thyroid carcinoma (MTC), 282, 289–290, 291f cytomorphology of, 289b differential diagnosis of, 290, 290b Medulloblastoma, 189–190, 189f cytomorphology of, 188b differential diagnosis of, 188b lymphocytes and monocytes mimicking, 189f 555 Megakaryocytes, 149, 150f Melamed-Wolinska bodies, 109, 109f Melanoma, 183–184, 184f cytomorphology of, 49b, 184b, 369b in effusions, 146, 146f in lymph nodes, 369, 369f malignant, 49, 50f Melanosis cerebri, 183 Membranous type of basal cell adenoma, 312, 314f Meningioma, 193 Merkel cell carcinoma, 146, 367–368, 367f Mesodermal tumors, malignant mixed, 49 Mesothelial cells, 64f, 156–157, 156f–157f with acute or chronic injury, 129 atypia, 167f in benign effusion, 128, 129f cytomorphology of, 129b differential diagnosis of reactive, 129b reactive, 129f, 158f Mesotheliomas, 134–135 versus adenocarcinoma, 135–138 cytomorphology of, 135b differential diagnosis of, 135b versus reactive mesothelial cells, 135, 137f versus squamous cell carcinoma, 139 staining patterns for, 138t versus vascular tumors, 139 MET, 65 Metanephric adenoma (MA), 428–430 cytomorphology of, 430 differential diagnosis of, 429b Metaplasia apocrine, 238f mucinous, in pleomorphic adenoma, 310 squamous, in pleomorphic adenoma, 310 squamous, of cervix, 11 transitional cell, of cervix, 11, 12f tubal, 12–13, 14f, 43f Metaplastic carcinoma, 247, 254–255, 255f cytomorphology of, 255b differential diagnosis of, 255b Metastatic adenocarcinoma, differential diagnosis of, 143b Metastatic cancers, 119–120 Metastatic carcinoma, 140, 292 Metastatic gastrointestinal stromal tumor (GIST), 393f Metastatic melanoma, 393f Metastatic papillary carcinoma, of thyroid, 142f Metastatic small cell carcinoma, of the lung, 259f Metastatic squamous cell carcinoma, 259f Metastatic tumors, 49–50, 140–151, 181–184, 258, 327, 390–394, 440–441, 446 cytomorphology of, 391b of ovary, 469 primary renal tumors as, 441b Michaelis-Gutmann bodies, 110 Microfollicles, 271 Microglandular hyperplasia, 24, 25f Micropapillomatosis, 157 Microsomal antigen, 275 Microsporidia, 212–213, 214f Midwest Institute for Medical Education (MIME), 537 Mikulicz disease, 305 Minocycline, 278–279 Mitomycin C, thiotepa and, 113 Mollaret cells, 179 Mollaret meningitis, 179 MRI See Magnetic resonance imaging (MRI) tahir99-VRG vip.persianss.ir 556 INDEX MTC See Medullary thyroid carcinoma (MTC) Mucicarmine stain, 143, 144f Mucin, 143, 301 Mucin-containing cysts, 306–308, 308f cytomorphology of, 307b differential diagnosis of, 308b sample report of, 308b Mucinous adenocarcinoma, 463f of appendix mimicking ovarian cancer, 163f aspirates from, 462 cytomorphology of, 462b Mucinous borderline tumor, and adenocarcinoma, 462 Mucinous carcinoma, of breast, 252–253, 253f cytomorphology of, 253b differential diagnosis of, 253b Mucinous cystadenoma of the ovary, 459f–460f cytomorphology of, 459b diagnosis of, 459 Mucinous cystic neoplasm (MCN), 417f cytomorphology of, 416b of pancreas, 401, 415–416 Mucinous tubular and spindle cell carcinoma, 438–439, 439f Muciphages, 308 Mucoceles, 253, 306–307 Mucoepidermoid carcinoma (MEC), 316–318 cytomorphology of, 316b high-grade, 317, 317f differential diagnosis of, 317b low-grade, 316, 317f differential diagnosis of, 316b Mucosa-associated lymphoid tissue (MALT), 197–198, 257, 306 extranodal marginal zone lymphoma of, 326–327, 326b, 327f lymphoma of, 210, 212f, 351 Mucosal neuroma syndrome, 289 Müllerian inclusion cysts, 158 Multicolor cytometry, advantages of, 336b Multilocular cyst, 430 Multinodular goiter (MNG), 271 toxic, 271 uninodular, 271–272 Multinucleated giant cells, 271 in papillary thyroid carcinoma, 283–284 in subacute thyroiditis, 276–277 Multiple endocrine neoplasia, 289 Multiple myeloma, 149, 149f Mycobacterial lymphadenitis, 342–343, 343f cytomorphology of, 342b differential diagnosis of, 342b Mycobacterium tuberculosis, 62 direct test (MTD), 71 Mycoplasma genitalium, 458 Mycosis fungoides, lymph node involvement by, 361 Myeloid sarcomas, 365–366, 366f Myelolipoma, 442–443 Myeloma, multiple, 149 Myeloproliferative neoplasms, 149, 186 Myoepithelial carcinoma, 311 Myoepithelial cell-rich neoplasm, 311f Myoepithelial sialadenitis (MESA), 305 Myoepithelial tumors, plasmacytoid, 311 Myoepithelioma, 310–311 cytomorphology of, 310b Myofibroblastic tumor, inflammatory, 78–79 Myxofibrosarcoma, 481–483, 482f cytomorphology of, 482b differential diagnosis of, 483b Myxofibrosarcoma-like dedifferentiated liposarcoma, 485, 486f cytomorphology of, 485b Myxoid liposarcoma, 484–485, 484f cytomorphology of, 484b differential diagnosis of, 484b–485b Myxoid malignant fibrous histiocytoma, 481–482 Myxoid matrix, 480f Myxoid neoplasms, 480–488 Myxoinflammatory fibroblastic sarcoma (MIFS), 486–487, 486f cytomorphology of, 486b differential diagnosis of, 486b Myxoma cellular, 480 intramuscular, 480–481 juxta-articular, 480 Myxopapillary ependymoma, 191 N Naegleria fowleri, 180 NANOG, 98, 151, 394, 465, 466f Nasopharyngeal carcinoma (NPC), 368f cytomorphology of, 368b metastatic, 350 National Cancer Institute (NCI), 79–80 National Fire Protection Association (NFPA), 520 standard for health care facilities, 544–545, 544b standard on fire protection, 544–545 Necrosis and hemorrhage, 462 and phagocytic histiocytes, 344–345 Needle hub, retrieving material from, 226–229, 228f Needle track seeding, 268–269 Negative for intraepithelial lesion or malignancy (NILM), 10–11 Neisseria gonorrhoeae, 458 Neoplasms architectural atypia, 271 epithelioid, 505–510 fibrohistiocytic, 499–501 myeloproliferative, 149 pleomorphic, 510–512 round cell, 501–505 Nephroma, cystic, 430 Nephrotic syndrome, 127 Neuroblastoma, 501, 503 cytomorphology of, 501b Neuroendocrine carcinomas (NECs), 209 Neuroendocrine cells, 60 Neuroendocrine tumors (NETs), 89–92, 209–210, 407–410 cytologic features of pulmonary, 90t cytomorphology of, 209b differential diagnosis of, 210b well-differentiated, 210f Neuron, 175f Nipple discharge, 234–235, 235f Nipple secretions cytomorphology of benign, 234b cytomorphology of malignant, 235b Nocardia, 71 Nodular fasciitis, 496–497, 497f cytomorphology of, 496b Nodular histiocytic/mesothelial hyperplasia, 130 Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL), 348, 349f Nodules adenomatous or adenomatoid, 271–272 colloid, 271–272 for papillary carcinoma, 286 Non-Hodgkin lymphoma, 133, 146–148, 148f, 188f, 210–211, 242, 257–258, 350 cytomorphology of, 210b, 258b differential diagnosis of, 258b Non-neoplastic conditions, 130, 133 cysts, 306–308, 455–458 soft tissue lesions, 512–513 Nondiagnostic (unsatisfactory) specimens, 107b Nongynecologic, non-fine-needle aspiration specimens, procedure codes for, 530t Nonhematopoietic neoplasms, 365 Nonlymphoid neoplasms, 367–370 Nonproliferative fibrocystic changes, 237, 238f benign ductal epithelium in, 238f cytomorphology of, 237b differential diagnosis of, 237b Nonseminomatous germ cell tumors, 151 Nontyrosine crystalloids, 301, 302f Normal liver cells, differential diagnosis of, 376b Nuclear atypia, 236–237 NUT midline carcinoma, 83, 92, 98 O O13, 503 Occupational Safety and Health Administration (OSHA), 520, 541–543 Laboratory Standard, 544, 544b Oct 3/4, 98, 151, 369, 394, 465, 466f Office of Civil Rights (OCR), 521 Oligodendroglioma, 191 cytomorphology of, 191b Ommaya reservoir, 171, 172f Oncocytes, 271, 314–315, 315f Oncocytic lesions, differential diagnosis of, 315b Oncocytic variant, 282 Oncocytoma, 315–316, 315f, 426–428, 427f versus chromophobe RCC, 437–438 cytomorphology of, 315b, 426b differential diagnosis of, 426b One-smear preparation method, 225, 225f Opportunistic screening, Pap test, 1–2 Organized screening, Pap test, Ovarian, parovarian, and paratubal cysts, 457–458 cytomorphology of, 457b Ovarian cancer, 160–163 Ovarian tumors, uncommon primary, 469 Ovary, 453–470 accuracy of FNA for, 454 benign surface epithelial-stromal tumors, 458–459 benign tumor-like lesions of, 455–458 dysgerminoma of, 163f embryonal carcinoma of, 164f, 465 germ cell tumors, 463–465 immunohistochemistry for, 460 indications for fine-needle aspiration of, 453b malignant surface epithelial-stromal tumors, 459–463 metastatic tumors, 469 obtaining the specimen, 454 preparing specimen and reporting results, 454 tahir99-VRG vip.persianss.ir INDEX Ovary (Continued) serous adenocarcinoma of, 160, 162f, 462f serous adenofibroma of, 159f sex cord-stromal tumors, 465–469 small cell carcinoma of, 468f stages in primary carcinoma of, 161t uncommon primary ovarian tumors, 469 P p53, 204, 404 p63, 34 for adenocarcinoma of lung, 83t for squamous cell carcinoma of lung, 83t PAL See Pyothorax-associated lymphoma (PAL) Palpation, in assessing thyroid nodularity, 267 Pancreas accuracy and limitations, 400–401 acinar cell carcinoma, 410–411 complications, 400 ductal adenocarcinoma, 404–405 variants of, 405 indications for, 399 intraductal papillary mucinous neoplasm, 415–416 normal pancreas and bile duct, 401–403 pancreatic cysts, 413–416 pancreatic intraepithelial neoplasia, 404 pancreatic neuroendocrine tumor, 407–410 pancreatitis and reactive changes, 403–404 pancreatoblastoma, 413 reporting terminology, 401 sample preparation and cyst fluid analysis, 400 sampling techniques, 399–400 secondary pancreatic neoplasms, 417 solid-pseudopapillary neoplasm, 411–413 Pancreatic acinar cells, normal, 402f Pancreatic cysts, 413–416 biochemical and molecular tests for, 400t Pancreatic ductal cells, normal, 402f Pancreatic endocrine neoplasm, 407 Pancreatic intraepithelial neoplasia (PanIN), 404 Pancreatic neuroendocrine tumor (PanNET), 407–410, 409f–410f, 410t cytomorphology of, 408b differential diagnosis of, 408b Pancreatoblastoma, 413, 413f cytomorphology of, 413b differential diagnosis of, 413b Papanicolaou, George N., 2, 105 Papanicolaou (Pap) test, coding, 527–530 commonly used ICD-9 codes for, 528t definition of a diagnostic, 529b definition of a screening (high-risk), 528b definition of a screening (routine), 527b diagnostic, 529–530 history of, and its current place, 2–3 normal, 10–18 procedure codes for, 527t screening (high-risk), 528–529 screening (routine), 527–528 Papillary carcinoma, of breast, 245 Papillary neoplasms, 245–246 cytomorphology of benign, 245b, 246f malignant, 245b, 246f differential diagnosis of, 245b Papillary renal cell carcinoma, 434–435 cytomorphology of, 435b differential diagnosis of, 435b Papillary thyroid carcinoma (PTC), 270, 282–292, 283f–284f cytomorphology of, 283b differential diagnosis of, 285b with fasciitis-like stroma, 282 follicular variant, 284f oncocytic variant, 285f tall cell variant, 285f Warthin-like, 282 Papillary urothelial neoplasm of low malignant potential (PUNLMP), 114 and low-grade urothelial carcinoma, 114–116 Papillomas bladder, 114 breast, intraductal, 235, 245 Paps and biopsies, analyses of discrepancies between, 535t Parabasal cells and basal cells, 11 postmenopausal smear, 12f postpartum smear, 11f Paracentesis, 127 Paracoccidioides brasiliensis, 72–73 Paracoccidioidomycosis, 72–73, 73f Parakeratosis, 12, 13f Paranuclear blue bodies, 92 Parathyroid adenoma, 280, 293, 293f Parathyroid carcinoma, 293 Paratubal cysts, 457–458 Parovarian cysts, 457–458 Pathognomonic, 132 Pathologic crystals, 112 PAX8, 460 PAX8-PPARγ gene fusion, 275 PAX5/BSAP, 337t PEComa, 93, 505 Pelvic inflammatory disease, 458 Pemphigus vulgaris, 37, 48 Percutaneous fine-needle aspiration, 63–64 accuracy of, 63b contaminants of, 64b contraindications to, 63b Percutaneous pancreatic fine needle aspiration, 399 Pericardiocentesis, 127 Periodic acid-Schiff (PAS), 300, 411 Periodic acid-Schiff diastase (PAS-D), 138 Peripheral T-cell lymphomas, 360, 361f Peritoneal washing cytology (PWC), 155–170 accuracy, 156 benign conditions, 157–160 indications for, 155b malignant tumors, 160–167 monitoring response to treatment, 167–168 normal, 156–157 specimen collection, preparation, and reporting terminology, 155–156 Peritoneum, serous adenocarcinoma of, 162f Permissible exposure limits (PELs), 544 Personal protective equipment (PPE), 543 PET See Positron emission tomography (PET) Pheochromocytoma, 444–446, 445f Phosphotungstic acid hematoxylin (PTAH) stain, 316 Phyllodes tumor, 246–255 cytomorphology of, 247b, 247f–248f differential diagnosis of, 247b “pick and smear” technique, 61 557 Pigmented villonodular synovitis (PVNS), 499 PIK3CA, 65 Pilocytic astrocytoma, 190 Pineal tumors, 192–193 Pineocytes, 192 Pineocytomas, 192–193 Pituitary carcinomas, 193 Pituitary tumors, 193 Plasma cell, 177f mastitis, 244 myeloma, 350t Plasmablastic lymphoma, 359–360, 359f Plasmacytoid myoepithelial cells, in pleomorphic adenoma, 312f Plasmacytoma, 350t Pleomorphic adenoma (PA), 308–310, 309f with adenoid cystic-like foci, 310f with atypia, 311f cytomorphology of, 308b pitfalls associated with, 309–310 Pleomorphic carcinoma, 88 Pleomorphic lipoma, 476–477 cytomorphology of, 476b differential diagnosis of, 476b Pleomorphic liposarcoma, 478–480, 479f cytomorphology of, 479b Pleomorphic neoplasms, 510–512 Pleomorphic rhabdomyosarcoma, 150f, 511–512, 512f cytomorphology of, 512b differential diagnosis of, 512b Pleomorphic sarcoma undifferentiated, 510–511, 511f cytomorphology of, 510b differential diagnosis of, 511b Pleural, pericardial, and peritoneal fluids, 127–154 accuracy, 128 benign elements, 128–130 eosinophilic effusions, 130–133 non-neoplastic conditions, 130 specimen collection, preparation, and reporting terminology, 127–128 PM cells, 23f, 30 Pneumocystis jirovecii (formerly carinii), 62, 74–75, 74f effusions and, 133 Pneumocytes hyperplasia, type II, 67–68, 68f causes of, 67b cytomorphology of, 67b type I, 60 type II, 60 Pneumonia, organizing, 77f cytomorphology of, 77b Pneumothorax, 63 as complication of FNA, 231, 231t Polymerase chain reaction (PCR), 336b for clonality, 336–337 to detect breakpoints in lymphomas, 337 and fluorescence in situ hybridization (FISH), 336b, 337 Polymorphous low-grade adenocarcinoma (PLGA), 322 Polyomavirus infection, 111–112, 112f Poorly differentiated thyroid carcinoma (PDTC), 286–287, 287f–288f cytomorphology of, 286b diagnosis of, 287 Positron emission tomography (PET), 267 Post-transplant lymphoproliferative disorders (PTLDs), 140, 363–364, 364f monomorphic, 363–364 polymorphic, 363–364 tahir99-VRG vip.persianss.ir 558 INDEX Pregnancy cytomorphology of, 242b, 242f differential diagnosis of, 242b and lactational changes, 241–242 PrepMate™, PrepStain™ robotic sample processer, PreservCyt, preservative solution, Primary central nervous system (CNS) lymphoma, 189f Primary effusion lymphoma (PEL), 139–140, 141f cytomorphology of, 139b differential diagnosis of, 140b Primary myelofibrosis, 149 Primary small cell carcinoma, 325 cytomorphology of, 325b Primary thyroid non-Hodgkin lymphoma, 290 Primitive neuroectodermal tumor (PNET), 365 Procedural codes, 524–525 Proficiency testing, 537–538 Progesterone receptor (PR), immunochemistry for, 143–144 Progressive transformation of germinal centers (PTGC), 340 Proliferative fasciitis, 496 Proliferative fibrocystic changes, 238–239 cytomorphology of, 238b Proliferative myositis, 496 Prostate-specific antigen (PSA), 143, 392f Prostatic acid phosphatase (PAP), 143 Prostatic carcinoma, 119, 119f metastatic, 392f Proximal tubular cells, 426, 426f cytomorphology of, 425b differential diagnosis of, 425b Psammoma bodies in cervicovaginal preparations, 50, 50f in effusions, 142 in ovarian specimens, 461f, 462 in peritoneal washings, 159f, 162f in respiratory cytology, 68 in thyroid, 283f, 284 Pseudocyst, pancreatic, 413–414, 414f cytomorphology of, 414b “Pseudogoblet” cells, 199, 201–202 Pseudomyxoma peritonei, 142–143, 143f, 462 PTLD See Post-transplant lymphoproliferative disorders (PTLDs) Pulmonary alveolar proteinosis (PAP), 76, 76f Pulmonary amyloidosis, 76 Pulmonary blastoma, 89 Pulmonary hamartoma, 78, 78f cytomorphology of, 78b Pus, 341 Pyelonephritis, xanthogranulomatous, 430–431 Pyothorax-associated lymphoma (PAL), 140 R Radiation changes, 25–26, 26f in breast, 243–244, 244f cytomorphology of, 243b, 244f differential diagnosis of, 243b, 244f cytomorphology of, 26b differential diagnosis of, 26b in esophagus, 201, 202f in thyroid, 279 cytomorphology of, 279b in urinary cytology, 112–113 Radioactive iodine effect, 279f RAS proto-oncogenes, 283 Reactive atypia, 38 Reactive changes, and pancreatitis, 403–404 Reactive lymphoid hyperplasia, 338–339, 338f–339f cytomorphology of, 338b differential diagnosis of, 339b Receiver operating characteristic (ROC) curves, 542f Receptor tyrosine kinase (RTK) signaling in cancer, 65f Recordkeeping, 543, 543b Red blood cell casts, 112 Reed-Sternberg (RS) cells, 94, 148, 149f in lymph nodes, 339, 347–348, 349f Renal abscess, 424, 430 Renal cell carcinoma (RCC), 119, 417, 432–439 chromophobe, 424, 435–438, 437f clear cell, 432–434, 434f cystic, 432f metastatic, 280, 282f papillary, 434–435, 436f sarcomatoid, 438, 438f subtypes of, 433t Xp11.2 translocation-associated, 438 Renal cortical adenoma, 428 Renal cysts, 431–432, 431b–432b, 431f Renal infarct, 431 Repair, 25, 67 cytomorphology of, 25b, 67b differential diagnosis of, 25b esophagus, differential diagnosis of, 202b typical, 25, 25f Reparative epithelium, 25, 25f in tracheobronchial brushings, 67 Requisitions, 523, 523b Reserve cell hyperplasia (RCH), 67, 67f bronchial, 67 cytomorphology of, 67b Reserve cells, 60 Respiratory epithelium, precursor lesions of, 79 Respiratory syncytial virus, 69–70 Respiratory tract anatomy and cellular components of, 60b benign cellular changes, 66–68 benign neoplasms of the lung, 78–79 lower, 59–60 and mediastinum, 59–104 metastatic cancers, 95 molecular testing of lung cancers, 64–66 non-neoplastic, noninfectious pulmonary diseases, 75–78 noncellular elements and specimen contaminants, 68 normal anatomy, histology, and cytology of, 59–60 sampling techniques, preparation methods, reporting terminology and accuracy, 60–64 uncommon pulmonary tumors, 93–95 upper, 59–60 RET/PTC, 283 Retention cysts, 306–307 Reticulin stain, 385, 385f Rhabdomyosarcoma alveolar, 504–505 embryonal, 504 pleomorphic, 150f, 512b Rheumatoid pleuritis, 131–132, 133f cytomorphology of, 132b Riedel disease, 277–278 Romanowsky-type stain, 198, 269, 300, 321f, 424 Rosai-Dorfman disease (RDD), 343–344, 343f cytomorphology of, 343b differential diagnosis of, 343b Round cell liposarcoma, 484–485, 484f cytomorphology of, 484b differential diagnosis of, 485b Round cell neoplasms, 501–505 RPMI, 229 S S-100 protein, 343 SAA See Satellite accumulation area Saccomanno method, 61 Salivary duct carcinoma, 322 cytomorphology of, 322b Salivary gland, 299–332 benign neoplasms, 308–316 crystalloids, 302f diagnostic overview, 300–301, 301b lymphomas of, 326–327, 327f malignant neoplasms, 322–326 non-neoplastic conditions, 302–308 normal, 303f normal aspirate, 301–302 normal elements, cytomorphology of, 301b rationale, indications and technical considerations, 299–300 salivary origin, carcinomas of, 316–322 SALL4, 151, 394, 465, 466f Sample collection, for gastrointestinal tract, 198–199 Sampling error, 471–472 Sarcoidosis, 75, 340–341, 341f cytomorphology of, 75b, 340b differential diagnosis of, 340b Sarcomas, 93–94, 150, 258, 369–370, 370b cytomorphology of, 94b differential diagnosis of, 94b primary, of breast, 258 Sarcomatoid carcinoma, 88–89 SATB2, 391 Satellite accumulation area (SAA), 544 Schistosoma hematobium, and squamous cell carcinoma of the bladder, 118 Schwannoma, 490–491 cytomorphology of, 490b differential diagnosis of, 490b Screening devices, automated cytology, 6f Screening guidelines, Pap test, Screening Pap test, definition of, 527b Screening programs, Pap test opportunistic, organized, Screening skills, 538–539 'Second look' procedures, 155, 167–168 Seminal vesicle cells, 110, 110f Seminoma, 97–98, 150–151, 369, 369f cytomorphology of, 369b of mediastinum, 98f Serosa, 127 Serositis, acute, 130 Serous adenocarcinoma, 160–161, 462f aspirates from, 462 cytomorphology of, 160b, 462b Serous adenofibroma, of ovary, 158, 159f Serous borderline tumors, 161, 162f, 461f and adenocarcinoma, 460–462 aspirates from, 460 cytomorphology of, 161b, 460b differential diagnosis for, 161 tahir99-VRG vip.persianss.ir INDEX Serous cyst, 457 Serous cystadenoma, 414–415, 459f cytomorphology of, 414b differential diagnosis of, 414b Sestamibi scans, for hyperparathyroidism, 267 Sex cord stromal tumors, 151, 151f, 163, 465–469 SF1, 443, 446 Sialadenitis acute, 302 chronic, 302–304 granulomatous, 304–305 lymphoepithelial See Lymphoepithelial sialadenitis (LESA) Sialadenosis, 305 Sialolithiasis, 303–304 Signet ring cell carcinoma, 209f SIL See Squamous intraepithelial lesion Silicone injection/implant, 242–243 Silicone lymphadenitis, 346–347, 347f Simple lymphoepithelial cysts, 306 Simple ovarian cyst, 458f Sipple syndrome, 289 Sjögren syndrome, 306 Slide preparation methods, liquid-based, 5f SMAD4, 404, 407f Small blue cells, 52 Small cell carcinoma, 49, 91–92, 93f, 145–146 of bladder, 119 cytomorphology of, 49b, 92b, 146b differential diagnosis of, 92b of lung, 146f in lymph nodes, 367–368, 367f of ovary, 468, 468f of pancreas, 417 of salivary glands, 325 Small cell lymphoma algorithm for discriminating among, 354b differential diagnosis of, 211b, 354–356, 354b Small lymphocytic lymphoma (SLL), 353, 353f cytomorphology of, 353b Smears air-dried, versus alcohol-fixed, 228t conventional, 3–4 fixing of, 226 making cell blocks from, 229 multiple, splitting material for, 225–226, 227f preparation of, 224–225 Soft tissue perineurioma, 481, 481f cytomorphology of, 481b differential diagnosis of, 481b Soft tissue tumors, 471–518 adipocytic and lipogenic neoplasms, 473–480 ancillary studies, 473 associated chromosomal changes, and fluorescence in situ hybridization (FISH) probes, 474t FNA screening tool, 472 non-neoplastic soft tissue lesions, 512–513 pleomorphic neoplasms, 510–512 reporting terminology, 473 specimen collection and preparation, 472–473, 472b Solid-pseudopapillary neoplasm (SPN), 411–413, 412f cytomorphology of, 412b Solid tumors, metastatic, 182–184 Solitary cysts, 378 Solitary fibrous tumor (SFT), 494, 495f cytomorphology of, 494b differential diagnosis of, 494b SOX2, 98 Specimen adequacy, 2001 Bethesda system categories for, 9t Spinal tap, 171 Spindle cell carcinoma, 88 mucinous tubular and, 438–439, 439f Spindle cell lipoma, 476–477, 477f cytomorphology of, 476b differential diagnosis of, 476b and pleomorphic lipoma, 476–477 Spindle cell neoplasms, 477, 488–498 immunoprofile of, 489t Splenomegaly, EBV and, 345 Splenosis, 417 Sporotrichosis, 73 Spot-counting method, to evaluate LBC, Sputum, 60f, 61 adequacy of, 61 sensitivity of, 61 SQC See Squamous cell carcinoma (SQC) Squamous atrophy, 11 Squamous cell carcinoma (SQC), 15, 36–38, 80–83, 118–119, 144–145, 289, 289f, 326, 417 of cervix, 145f cytomorphology of, 36b, 119b, 144b moderately and poorly differentiated, 81b poorly differentiated, esophagus, 205, 205b, 206f well-differentiated, 80b well-differentiated, esophagus, 205b, 206f differential diagnosis of, 36b, 81b, 205b of esophagus, 205 keratinizing, 36, 37f of lung, 145f mesothelioma versus, 139 nonkeratinizing, 36, 37f, 47 poorly differentiated, 81f well-differentiated, 81f Squamous cells, 11–12, 24f abnormalities of, 28–40 atypical, 38–40 immature, 11 mature, 11 reactive changes, 66 superficial and intermediate, 11f Squamous intraepithelial lesion (SIL), 8, 28–35 cytologic pre-invasive, natural history of, 28t grade cannot be determined, 35f cytomorphologic patterns of, 35b grading, 29–30 high grade, 215f problems in the diagnosis of, 35 Squamous-lined cysts, 306 compared to squamous cell carcinoma (SQC), 307f cytomorphology of, 306b differential diagnosis of, 306b Squamous metaplasia, 11–12 atypical, 34 of endocervix, 13f Standard on Fire Protection for Laboratories, using chemicals, 520 State of Maryland, 537 Statistics, 536 Steatosis, 377f Stellate microabscesses, 342 Stem cell factor, 211 Stomach, adenocarcinoma of, 142f, 208–209 Stromal tumor, 430 Strongyloidiasis, 75, 75f 559 Subacute thyroiditis, 277, 278f cytomorphology of, 277b Subarachnoid space, 171 Subareolar abscess, 244–245 cytomorphology of, 245b Sugar tumor, 93 Superficial cells, 11, 11f SurePath Pap test, 4, 5f Syncytiotrophoblast, 17, 17f Synovial carcinoma, 370 Synovial sarcoma, 491–494, 492f–494f cytomorphology of, 492b differential diagnosis of, 493b Systemic lupus erythematosus (SLE) effusions and, 132 lymph nodes and, 343 T T-and NK-cell neoplasms, WHO classification of, 360t T-cell lymphomas, 360–363 cytomorphology of peripheral, 360b peripheral, 360, 361f T-cell-rich large B-cell lymphoma (TCRLBL), 349 “Tadpoles,” 36, 37f Tandem needle technique, 399 Targeted therapies, 144 Tart cells, 132–133 Tdt See Terminal deoxynucleotidyl transferase (Tdt) Technical supervisor, 522 qualifications of, 522b responsibilities of, 522b Tenosynovial giant cell tumor, 499–500, 499f cytomorphology of, 499b differential diagnosis of, 500b Teratoma, 463–465, 464f cystic, 464f immature, 463 mature, 463 Terminal deoxynucleotidyl transferase (Tdt), 351t immunochemistry for, in cerebrospinal fluids, 185 Test report, 524b Tetracycline antibiotics, 278–279 Thecoma, 468 Thinlayer preparation, to prepare specimen, 172, 269 ThinPrep Imaging System (TIS), 5–7 ThinPrep Pap test, 4, 5f Thiotepa, and mitomycin C, 113 Thymic carcinoma, 97 Thymoma, 95–96, 97f, 131, 132f Thyroid, 267–298 accuracy of, 270 ancillary molecular testing for, 270 aspiration technique and slide preparation, 268–269 atypia of undetermined significance, 292–293 benign conditions, 271–279 Bethesda system for reporting, 269t black, 278–279 evaluation of specimen of, 270–271 follicular neoplasm, suspicious for, 279–280 Hürthle cell neoplasm, suspicious for, 280–282 malignant conditions, 282–292 metastatic papillary carcinoma of, 142f parathyroid tumors, 293 terminology for reporting results, 269–270 tahir99-VRG vip.persianss.ir 560 INDEX Thyroid gland, radiation changes, 279 Thyroid lymphoma, 290–292 cytomorphology of, 290b extranodal marginal zone B-cell, 292f primary, 277 Thyroid nodule, 267 transverse sonogram of, 268f Thyroid peroxidase (TPO), 275 Thyroid-stimulating hormone (TSH), 267 Thyroid transcription factor-1 (TTF-1), 410 for adenocarcinoma of lung, 83t for mesothelioma, 138 for small cell carcinoma, 146 for squamous cell carcinoma of lung, 83t for thyroid tumors, 280 Thyroiditis de Quervain, 277 subacute, 277 “tigroid (tiger stripe) pattern,” 98, 98f, 369, 369f, 502 Tingible-body macrophages, 338 Touton type giant cells, 79 Toxoplasma meningoencephalitis, 180f cytomorphology of, 179b Toxoplasma tachyzoites, 179–180 Toxoplasmosis, 179–180 TPO See Thyroid peroxidase (TPO) Transitional cell carcinomas, 114 Transitional cell metaplasia, 11, 12f, 33–34 Transudates, 127 Transvaginal aspiration, 454 Traut, Herbert, Treatment effect, cytomorphology of, 167b Trichome, 19f Trichomonas vaginalis, 20, 20f cytomorphology of, 20b in urine, 111 Triple phosphate crystals, 112 TRK gene, 283 Trophoblastic cells, and decidual cells, 17 TSH See Thyroid-stimulating hormone (TSH) TTF-1 See Thyroid transcription factor-1 (TTF-1) Tubal metaplasia, 12–13, 14f Tuberculosis, 71 Tuberous sclerosis (TS), 428 Tubo-ovarian abscess, 458 Tubular carcinoma, 253–254, 254f cytomorphology of, 254b differential diagnosis of, 254b Tubular cells, 425–426, 426f cytomorphology of proximal, 425b differential diagnosis of proximal, 425b Tumor diathesis, 36, 36f–37f, 205 Tumoral amyloidosis, 513, 514f Tumors carcinoid, 463–465 clear cell, 93 as cystic, 301b dermal analogue, 312 germ cell, 97–98, 150–151, 193, 463–465 hyalinizing trabecular, 286 Kuttner, 303–304 malignant, 160–167 malignant mixed, 321–322 mesodermal, 49 metastatic, 49–50, 140–151, 327 Tumors (Continued) metastatic carcinoid, 392f parathyroid, 293f pineal, 192–193 primary, 134–140 serous borderline, 161 Two-smear preparation method, 225, 226f Tyrosine crystalloids, 301, 302f U Ultrasonography (US) for carotid artery disease, 267 in diagnosing benign cysts and RCCs, 423 Ultrasound gel, 268f Umbrella cells, 109, 109f Undifferentiated carcinoma See Anaplastic carcinoma Undifferentiated high grade pleomorphic sarcoma, 499, 511f Uninodular MNG, 271–272 Universal precautions, 542 Uric acid crystals, 112 Urinary calculi, urothelial atypia with, 113 Urinary epithelium, cytomegalovirus affecting, 111 Urinary tract primary cancers of, 118–119 upper, washings and brushings of, 106 Urinary tract infection (UTI), 424 Urine accuracy of sample, 107–108 specimen types, advantages and disadvantages of, 106t Urine and bladder cytology, 105–126 accuracy, 107–108 ancillary techniques, 121–123, 121b benign lesions, 110–113 clinical indications for, 105b cystoscopy in, 108 diagnosing difficult or borderline specimens, 120–121 indication for, 105 malignant lesions, 118–120 normal elements, 108–110, 108b processing, 107 reporting terminology and adequacy criteria, 107 sensitivity of, 108t specimen collection, 106 urothelial neoplasms, 113–118 Urothelial atypia with urinary calculi, 113 Urothelial carcinoma (UC), 105, 439, 439f cytomorphology of, 439b degenerating cells of high-grade, 122f differential diagnosis of, 439b high-grade, 116f–117f, 122f and carcinoma in situ, 116–118 cytomorphology of, 116b differential diagnosis of, 117b variants, 117f Urothelial cells clusters of, 120 nonspecific reactive, changes, 112, 112b reactive, 112f Urothelial neoplasms, 113–118 risk factors for, 113b UroVysion™ test for bladder cancer, 121–123, 122f Uterine segment endometrial cells and, 15–17 lower (LUS), V Vaccine, human papillomavirus, Vagina, malignant melanoma of, 50f Vaginal specimens, in “DES daughters,” 28 Vascular endothelial growth factor (VEGF), 65 Vascular tumors, mesothelioma versus, 139 Vasoactive intestinal polypeptide (VIP), 407–408 Vegetable cells, 69f Ventricles, 171 Verocay bodies, 310–311 Villoglandular adenocarcinoma, 44–46 Viral infections, 69–70 differential diagnosis of, 200b pulmonary, 70t Virus measles, 69–70 respiratory syncytial, 69–70 Voided urine, 106 normal, 109f von Hippel-Lindau (VHL) syndrome, 424 Von Meyenburg complex, 381 W Wang needle, 62–63 Warthin-like PTC, 282 Warthin tumor, 314–315, 314f cytomorphology of, 314b Wegener granulomatosis, 75, 76f cytomorphology of, 75b Weibel-Palade bodies, 473 Well-differentiated liposarcoma, 477–478, 478f–479f cytomorphology of, 477b differential diagnosis of, 477b Whipple disease, 510 WHO See World Health Organization (WHO) Wilms tumor, 428–429, 442f cytomorphology of, 442b Wilms tumor protein (WT1) for mesothelioma, 135, 138 Workload records, 536, 536b World Health Organization (WHO), 114 classification of hematologic malignancies, 347 classification of leukemias, 184 classification system for urothelial neoplasms, 114b X Xanthogranulomatous pyelonephritis, 430–431 Z Ziehl-Neelsen stain, 71 Zygomycosis, 74 tahir99-VRG vip.persianss.ir tahir99-VRG vip.persianss.ir Instructions for online access Thank you for your purchase Please note that your purchase of this Elsevier eBook also includes access to an online version Please click here (or go to ebooks.elsevier.com) to request an activation code and registration instructions in order to gain access to the web version tahir99-VRG vip.persianss.ir ... Breast Cancer 20 05; 12( 4) :27 2 -27 8 174 Pathmanathan N, Albertini AF, Provan PJ, et al Diagnostic evaluation of papillary lesions of the breast on core biopsy Mod Pathol 20 10 ;23 (7):1 021 -1 028 175 Nayar... 19 92; 36 (2) :20 3 -20 7 180 Jayaram G, Sthaneshwar P Fine-needle aspiration cytology of phyllodes tumors Diagn Cytopathol 20 02; 26(4) :22 2 -22 7 181 Florentine BD, Cobb CJ, Frankel K, Greaves T, Martin SE Core... 1997; 122 (4): 824 - 828 16 Lieske B, Ravichandran D, Wright D Role of fine-needle aspiration cytology and core biopsy in the preoperative diagnosis of screen-detected breast carcinoma Br J Cancer 20 06;95(1): 62- 66