The subject matter of volume 1 of the 2-volumes-handbook focusses on leiomyosarcoma, low-grade and high-grade endometrial sarcoma and undifferentiated uterine sarcoma of the whole female genitalia. The book aims to identify and provide diagnostic and therapeutic guidance. The listed tumor entities also constitute a particular diagnostic challenge for pathologists that contains numerous pitfalls and difficulties.
Günter Köhler, Katja Evert, Marek Zygmunt and Matthias Evert Endometrial stromal tumors – endometrial stromal nodule, endometrial stromal tumor with sex cord-like elements (ESTSCLE), uterine tumor resembling ovarian sex-cord tumor (UTROSCT) and similar tumors Introduction The current WHO Classification (36) divides EST and similar neoplasms into ESN, LGESS, HG-ESS and UUS UTROSCT also belong to the EST family of tumors ESN are benign stromal tumors There are special forms of EST with different types of differentiation, like the endometrial stromal tumor with endometrioid glands, mixed endometrial stromal tumors and smooth muscle tumors as well as endometrial stromal tumors with sex cord-like elements (ESTSCLE), and uterine tumors resembling ovarian sex-cord tumor (UTROSCT) Uterine stromal sarcomas (LG-ESS, HG-ESS, UUS) belong to the family of pure homologous sarcomas and are discussed in separate chapters (Chapters and 5) 3.1 Endometrial stromal nodule 3.1.1 Uterine endometrial stromal nodule General, pathogenesis, pathological-anatomical features ESN is a benign EST with histological features unambiguously reminiscent of endometrial stroma in the proliferation phase Overall, ESN are only very rarely diagnosed, accounting for only % of all EST in the DKSM database (25) ESN have been observed to arise in women aged 23–86 The majority of patients are premenopausal, with a median and mean age of 47 resp 53 years It can already be deduced from this age distribution that ESN share an epidemiologic relationship with LG-ESS, which, according to the DKSM data, arise in patients aged 18 to 80 years Median age of patients with LG-ESS is 46 years, suggesting that, like ESN, the majority of such tumors arise in premenopausal women (25) These two types of neoplasm in fact share clear pathogenetic commonalities On the one hand, the differences between the two in terms of their microscopic features are more gradual than abrupt Both LG-ESS and ESN exhibit t(7;17) translocations and consecutive fusions of the JAZF1 and SUZ12 (previously: JJAZ1) genes as well as t(6;7) translocations (JAZF1/SUZ12 gene fusion) (26) The t(7;17) (p15;q21) translocation is regarded as an early genetic aberration in the development 232 | Endometrial stromal tumors of ESN and LG-ESS Interestingly, this translocation can also be observed in ESN that exhibit focal smooth muscle differentiation, which allows the conclusion that such tumors originate from a progenitor cell (35), and could also serve to explain why ESN and LG-ESS so frequently arise within the myometrium LG-ESS, ESN and CLM express common immunohistochemical markers (CD10, SMA, WT-1), another factor that supports the notion that stromal and myogenic tumors might derive from the same precursor cells (48) What is rather conspicuous from an epidemiologic perspective is that ESN account for only a very small proportion of all EST Subtle analyses have revealed that, when ESN and LG-ESS are summed together, the latter account for a substantially larger share (84 %) than the former (16 %) (45) Given the fact that microscopically differentiating between LG-ESS and ESN is very difficult, this can essentially only be explained by the fact that a non-negligible number of ESN (for example such with limited infiltration or myogenic differentiation) are probably classified or diagnosed as LG-ESS just to be “on the safe side” That could also help to explain why there is so much variation in terms of the propensity of such tumors to recur The situation might actually be very similar to that of STUMP and LMS Endometrial stromal nodules are rare benign endometrial stromal tumors that predominantly arise in premenopausal women They are regarded as a precursor of low-grade endometrial stromal sarcoma Similar to LM, ESN are usually situated intramurally Their intramural growth serves to visibly compress the surrounding myometrium, and potentially the endometrium as well The tumor is thus well-circumscribed ESN have a yellowish, tan, occasionally almost white color on the predominantly smooth, fleshy cut surface Sometimes cystic structures, necrosis and focal hemorrhages can be visible in the cut-open specimen Nodular or polypoid growth into the cavum uteri is not uncommon ESN are usually considerably softer than LM Their size can range from only a few mm to 22 cm, with a mean diameter of 5–7 cm Multiple ESN can develop simultaneously Microscopy also very frequently reveals that ESN are situated entirely within the myometrium Myometrial compression caused by the tumor’s strong displacing growth is usually easy to see, and can appear to resemble an actual capsule in some cases The densely packed, diffusely growing small oval to spindle cells strongly resemble the endometrial stromal cells of the proliferative endometrium The cells contain scant cytoplasm and usually have unclear margins The oval to spindle, relatively uniform nuclei are practically void of pleomorphism, have unsuspicious nucleoli and exhibit a prominent coloration that often makes them appear deep blue in histological specimens The cells often focally whorl around the vessels (1) Virtually all ESN contain ample uniform vessels (15) reminiscent of endometrial spiral arterioles The vessels can occasionally be thick-walled and hyalinized, but are usually situated within areas of smooth muscle differentiation in such cases 3.1 Endometrial stromal nodule | 233 Densely cellular tumors are predominant (roughly 80 %), while 20 % are hypocellular with fibrous, hyalinized, myxoid or edematous sections (15) ESN with an abundance of epithelioid cells have also been described in the literature (33) Occasional areas consisting of foam cells within the tumor are another noticeable feature (31) There are no entirely cytologic criteria that can be drawn on to differentiate ESN from LG-ESS Hyalinized areas, cystic degeneration and necroses occur in both of these types of tumors, and are thus not suitable specific DD criteria (1) In microscopy, the tumor is usually sharply delineated from the myometrium due to the absence of infiltration (Fig 3.1.1 (A)) (A) (B) Fig 3.1.1: Histological findings of an endometrial stromal nodule and diagnostic differentiation from cellular leiomyoma; (A) a clear, sharp margin between the stromal nodule (top left) and the myometrium (bottom right) constitutes an important characteristic feature, the stromal cells with scant cytoplasm morphologically correspond to those of low-grade endometrial stromal sarcoma; (B) cellular leiomyoma can have a very similar appearance and needs to be ruled out via immunohistochemical testing The tumor margins can also be slightly irregular or poorly defined as a result of tongueor finger-like protrusions of the main tumor up to mm deep into the bordering myometrium Even the presence of small individual nodules located no further than mm away from the tumor does not serve to exclude such cases from being diagnosed as ESN Tumors in such cases are referred to as ESN or EST with limited infiltration (15, 49, 51) or LG-ESS with limited infiltration (1) VI and LVI are absent by definition Tumors in which the infiltrations or satellite masses extend beyond mm or in which there is VI will be LG-ESS In some cases, tumors with focal margin irregularities that extend up to mm beyond the main border of the tumor still not have to be classified as LG-ESS (15) Such infiltrations usually only occur focally and should be limited to three localizations in order to fulfill the ESN criteria (1) These criteria must indeed appear vague even to non-pathologists, and constitute a substantial reason why ESN and LG-ESS share such overlap in a diagnostic “gray area” 234 | Endometrial stromal tumors Smooth muscle differentiations are far from the exception in ESN, and are present in up to 50 % of cases (15) At times, the smooth muscle cells can also appear to resemble epithelioid cells Tumors in such cases are referred to as ESN with smooth muscle differentiation, regardless of the extent of the smooth muscle component (32) In the past, tumors in which the smooth muscle tissue accounted for > 30 % were termed stromal myoma Today, these tumors constitute a special subgroup of EST called mixed endometrial stromal smooth muscle tumors (see below) Larger sections of smooth muscle differentiation can be “interlocked” with stromal cells in a cog- or phalanx-like fashion, a situation that can be misinterpreted as myometrial infiltration by stromal cells and thus result in a misdiagnosis as LG-ESS Larger areas of smooth muscle differentiation can thus cause differential diagnostic problems, especially in curettage specimens (see below) Besides fibrous elements, 24 % of tumors also contain focal visible degrees of sex cord-like differentiation arranged in cords/bundles in a glandular epithelioid structure (15) These tumors are further subdivided into two subtypes along the lines of the extent of sex cord-like differentiation in the tumor – ESTSCLE and UTROSCT (in which sex cord-like differentiation is predominant) (see below) The majority of ESN exhibit no mitotic activity or MI < M/10 HPF MI of up to 15 M/10 HPF have been described in the literature (49), but only 10 % of ESN have > M/10 HPF (15) MI is not relevant for the diagnostic context and has no impact on prognosis Cysts resulting from cystic degeneration as well as infarct-type necroses are observed in 24 and 68 % of ESN, respectively (15, 17) Regarding IHC, ESN virtually always express ER and PGR, vimentin and CD10 Pure ESN without further differentiation are usually negative for desmin and hcaldesmon (34) The corresponding lead markers can be found in cases in which tumors exhibit additional morphologic differentiations, for instance: desmin and hcaldesmon when there is smooth muscle differentiation; inhibin, calretinin, CD99 and O-13 when there is sex cord-like differentiation; myogenin when there is skeletal muscle differentiation CD10 constitutes the most reliable and most characteristic marker for endometrial stromal cells, and thus for ESN and LG-ESS CD10 is typically diffusely expressed and strongly positive in both ESN and LG-ESS (see also the table on p XXVI) In ESN, areas with smooth muscle differentiation also stain with CD10 ESN usually show strong and diffuse positive immunoreactive staining for the WT-1 antibody (48) Endometrial stromal nodules can barely be macroscopically discerned from leiomyoma or lowgrade endometrial stromal sarcoma, also in terms of their localization Endometrial stromal nodules are noticeably soft and of a conspicuously yellow color The only real histological difference between endometrial stromal nodules and low-grade endometrial stromal sarcomas is the absence of infiltration in cases of the former It consists of very densely packed small cells with low levels of pleomorphism that are reminiscent of proliferative endometrial stroma Endometrial stromal nodules typically express CD10 Smooth muscle and sex cord-like differentiations with corresponding immunophenomena are possible 3.1 Endometrial stromal nodule | 235 Clinical presentation, diagnostics, imaging, differential diagnostics, screening Like LG-ESS, ESN are often incidental findings made on the basis of specimens obtained via HE Uterus enlargement, menorrhagia and possibly AUB in the form of additional bleeding are the central clinical symptoms Patients occasionally also complain of abdominal pains when there is uterine enlargement The noticeable softness of such tumors often becomes apparent either during gynecologic examination or intraoperatively Overall, at the latest during surgery, ESN or LG-ESS should be considered as possible diagnoses when a tumor is soft and appears very smooth and yellowish on the cut surface In principle, symptoms largely correspond to those of LM and can thus also be entirely absent Accordingly, and analogous to LG-ESS, they are usually operated on under the diagnosis LM Diagnostics primarily involve sonography, and also include HSC in combination with targeted biopsy or curettage when there is AUB The problems pertaining to curettage are discussed at greater length in the chapter on LG-ESS (Chapter 4) The aforementioned diagnostic steps are often not taken when LM is assumed Similar to smooth muscle tumors and LG-ESS, the hysteroscopic picture usually only reveals a smooth bulge in the endometrium caused by a displacing tumor (Fig 3.1.2) Fig 3.1.2: Hysteroscopic findings of an endometrial stromal nodule, differentiation from leiomyoma is barely possible on gross observation An irregular surface or polypoid structures are also possible features The cut surface usually has a conspicuous yellowish color The tumor appears softer than LM in biopsy The diagnostic flowchart can be drawn on in ambiguous or uncertain cases (cf Chapter 6) Symptoms, findings and clinical diagnostics all largely correspond to those of leiomyoma or lowgrade endometrial stromal sarcoma Hysteroscopy and curettage are indicated when there is abnormal uterine bleeding Given the rarity of ESN, only very few data are available that can give insight into their imaging characteristics Sonography does not yield findings that are specific to 236 | Endometrial stromal tumors ESN, but typically reveals a well-circumscribed heterogeneous tumor that is largely hypoechoic (38) While the presence of anechoic structures (cysts or necroses) is not a finding that is specific to ESN, they can nonetheless be suggestive of ESN when the tumor in which they are situated is hypoechoic Large ESN also appear as wellcircumscribed heterogeneous hypoechoic masses with cystic/necrotic and solid parts (17) (Fig 3.1.3 (A), (B)) (A) (B) Fig 3.1.3: (A) endometrial stromal nodules with predominantly cystic structures in sonography; (B) the tumor also appeared to be cystic in uterus-sparing surgery, the findings were later pathologico-anatomically characterized as pseudocysts within the tumor Since the only microscopic and macroscopic difference between ESN and LG-ESS is the absence of myometrial and VI in the former, it cannot be realistically expected that these two types of neoplasm will exhibit greatly differing imaging-related features Assessing the margins of the tumor with a view to identifying infiltrations can, however, be helpful Cases of ESN that are isoechoic to the myometrium or to LM have been reported (8) Accordingly, as is also the case with LG-ESS, the majority of ESN are classified as LM in sonography Findings similar to those for ESN and LG-ESS have also been described for LMS and DLM Overall, the sonographic picture merely serves to suggestively indicate the presence of an unusual mesenchymal mass CT reveals unspecific tumor enlargement with occasionally discernible cysts The tumor shows heterogeneous enhancement in CECT that is absent in the cystic sections CT is not an appropriate tool for reaching a specific diagnosis (41) T1W-MRI usually reveals a tumor with SI that is isointense to the myometrium (38) Administration of gadolinium shows homogeneous to inhomogeneous enhancement that can be lower than or identical to that of normal myometrium Cystic structures remain hypointense (41) In one case (38), only the areas on the margins of the tumor showed enhancement, while the rest of the tumor did not The non-enhancing areas apparently corresponded to hemorrhagic degeneration T2W reveals a heterogeneous tumor that is intermediately intense to hyperintense SI is slightly higher than that of 3.1 Endometrial stromal nodule | 237 the myometrium and skeletal musculature (18) Hypointense bands within the tumor, a typical feature of LG-ESS (cf Chapter 4), are absent in T2W (38) These features serve to distinguish ESN from LM rather well Cystic structures that appear hypointense in T1W are hyperintense in T2W Analogous to LG-ESS that exhibit worm- or tongue-like invasion, T2W should also reveal hypointense bands in ESN with more pronounced smooth muscle differentiation LG-ESS with little or no certain myometrial invasion are typically separated from the myometrium by a narrow hypointense rim (cf Chapter 4) This rim might well serve as a criterion for differentiation from DLM and LG-ESS with diffuse infiltration (18) It is generally assumed that ESN cannot be reliably differentiated from LG-ESS with limited or little infiltration in MRI (18) Endometrial stromal nodules have no specific sonographic criteria or features They typically present as well-circumscribed masses with heterogeneous hypoechoicity, sometimes with cystic structures In T2W-MRI endometrial stromal nodules are heterogeneously intermediate to hyperintense Signal intensity is slightly higher than that of normal myometrium, and tumors are usually surrounded by a hypointense rim These characteristics and features are well suited for differentiating endometrial stromal nodules from leiomyoma Differentiation from low-grade endometrial stromal sarcoma is often not possible From a clinical perspective, ESN and LG-ESS are often mistaken for LM, both preoperatively and intraoperatively In fact, the majority of both of these types of neoplasm are subjected to surgery under the indication LM, and such tumors are thus often incidental findings (cf Chapter 4) Intramurally localized ESN are only exceptionally accessible to curettage, as is also the case with other intramural mesenchymal tumors ESN are, however, usually softer than LM on palpation and are usually solitary Cut-open ESN have a yellowish-brown color, a smooth cut surface and lack a clear pseudo-capsule, making them relatively easy to discern macroscopically from LM with their more whitish color and whorled structures DD from CLM, which are also rather soft (Fig 3.1.1 (A), (B)), is particularly challenging from a clinical and pathologicalanatomical perspective Discerning between CLM and ESN is practically impossible using purely clinical methods CLM and STUMP can be similar to ESN in terms of color and consistency, and can also contain cystic structures and necroses Polypoid protrusion or “bulging” into the cavum militates against a diagnosis of LM, CLM or STUMP LG-ESS constitutes the most important DD in terms of microscopic and macroscopic features ESN cannot be discerned from LG-ESS solely on the basis of cytology A tumor can only be definitively and reliably diagnosed as ESN when the entirety of the tumor’s margins is observable/assessable A reliable diagnosis of ESN cannot be reached when the tumor borders are incomplete following curettage, morcellation or enucleation, but the clinician might nonetheless have to settle for that diagnosis, even though LG-ESS cannot be ruled out Differentiating ESN with limited infiltration from LG-ESS is very difficult even when the margins of the tumor are all clearly assessable, 238 | Endometrial stromal tumors but also has prognostic consequences The same applies for intraoperative frozen sections, whose value is already limited as it is (see below) In histological tissue specimens, the uniformity of the cells, dense cellularity, strong staining in the nucleoli and the fact that they are typically well-delineated from the myometrium are all factors collectively suggestive of CLM The latter, however, are characterized by relatively large, thick-walled vessels and narrow clefts in the tumor The clefts possibly correspond to compressed vessels (34) Thick-walled arterioles are occasionally also found in ESN, but are usually situated at the periphery/near the margins of the tumor in such cases (15) Performing frozen sections without IHC analysis (Fig 3.1.1 (B)) is thus greatly prone to error for this group of neoplasms, and must be regarded critically by clinicians In contrast to CLM, ESN exhibit strong and diffuse CD10 expression With the exception of ESN with smooth muscle differentiation, and in contrast to CLM, ESN not stain positively for desmin H-caldesmon appears to be the most important differential diagnostic marker as it virtually never shows staining in ESN (48) Since CD10 can also be traceable in 20–55 % of CLM, the latter can best be discerned from ESN by drawing on a combination of desmin, h-caldesmon and CD10 (cf Tab 4.1.1) (10, 34) However, it should be noted that LMS can also be CD10 positive and h-caldesmon negative (4, 42) Assessing CD10 is generally not enough for safely and reliably distinguishing between ESN and smooth muscle neoplasms Extensive smooth muscle differentiations with interposed stromal elements can serve to mimic invasion and subsequently result in overdiagnosis as LG-ESS Related problems tend to arise in cases in which extensive morcellation has been performed leaving many small pieces of tissue ESN with epithelioid cells with ample eosinophilic cytoplasm (33) can be confused with PEComa in microscopy Effort must be devoted to differentiating ESN from ESTSCLE (see below) and UTROSCT (see below) when sex cord-like elements are found to be present Stromal endometriosis constitutes a further differential diagnostic challenge, a nomenclature used to describe endometriosis with sparse or no glandular differentiation, sometimes also referred to as stromatosis Stromal endometriosis is sometimes observed to arise after long-lasting or highly-dosed progestin therapy (29) Stromal endometriosis usually arises on the surface of the peritoneum in the vicinity of other areas of endometriosis and does not develop actual tumors as such (7) Cyclic changes or older hemorrhages with hemosiderin can be recognizable in the stromal endometriosis Stromal endometriosis occasionally arises in the cervix (12), where it can also be confused with ESN or LG-ESS An AS can be overlooked in specimens obtained via biopsy or curettage when no glands are visible in the small amount of tissue available ESN with focal endometrioid glandular differentiation are usually endometrial stromal tumors with endometrioid glands There is also an LG-ESS equivalent to such neoplasms AS must also be considered from a DD perspective whenever glands are present However, cuff-like accumulations of stromal cells around the vessels make AS generally easy to recognize as such (cf Chapter 6, Vol 2) 3.1 Endometrial stromal nodule | 239 There is no particular screening that we are aware of Nor is such a screening necessary due to the rarity of such tumors and the fact that they are benign The low rate of cellular atypia also serves to rule out incidental detection of ESN in the context of cytological screenings for cervical carcinoma Low-grade endometrial stromal sarcoma and common leiomyoma are the most important clinical differential diagnoses Microscopically differentiating endometrial stromal nodules from cellular leiomyoma can be very difficult without applying additional immunohistochemical methods, especially in frozen sections The same applies for rarer differential diagnoses, like PEComa, ESTSCLE and UTROSCT There is no specific screening for endometrial stromal nodules, nor is such screening necessary given the rarity and benignity of such tumors Course, prognosis, primary surgery, adjuvant and additive radio-, chemoand hormone therapy ESN are benign tumors that not recur or metastasize (49) Accordingly, prognosis is good so long as the tumor margins are well-circumscribed and open to assessment Such assessment is largely based on tumors that have been removed via THE No reliable prognostic assessments can be made concerning the application of conservative surgery to ESN since case numbers are so low Among the few cases that have been recounted in the literature, none have recurred (15, 43, 49) From a pathologicalanatomical perspective, it is assumed that limited myometrial invasion of up to mm depth is unlikely to impact unfavorably on prognosis This notwithstanding, a case is recounted in the literature in which a uterine ESN with limited invasion exhibited extrauterine dissemination, though the lesion in question was probably in fact very early LG-ESS (24) A case has been reported in which an ESN with more than three permeations not exceeding mm metastasized (47) Due to a lack of data, the prognostic impact of the presence of tumor margin irregularities of to 10 mm depth remains uncertain (15, 52) For practical purposes, it is therefore recommended that such tumors also be classified as LG-ESS, and that it is pointed out independently that the degree of infiltration at hand is far lower than is usually observed in LG-ESS (1) In cases in which tumors are subjected to morcellation or RX resection, or in which the tumor borders cannot be assessed in their entirety, pathologists must unequivocally point out that the tumor in question may also be LG-ESS Endometrial stromal nodules are benign tumors that neither recur nor metastasize This statement only applies when all tumor margins are reliably observable or assessable There is currently no alternative to adopting a primarily surgical approach to therapy, not least because ESN need to be regarded as a precursor for LG-ESS Since LG-ESS generally cannot be ruled out whenever an ESN is suspected – neither clinically, nor in 240 | Endometrial stromal tumors imaging or via HSC or curettage – the tumor should be approached as though it were LG-ESS THE is therefore the therapeutic method of choice, because the tumor margins can only really be reliably assessed when the uterus remains intact For the same reasons, morcellation, SLH or clamping the tumor with sharp instruments should be avoided, not least because injuring the tumor or the uterus has a negative impact on prognosis for LG-ESS LAVH or TLH can be opted for so long as the integrity of the uterus and the tumor is not endangered Given the difficulty associated with successfully differentiating from LG-ESS, indications for SAH and SLH should be subject to strict criteria when a diagnosis of EST is known prior to or during surgery BSO is not necessary in premenopausal patients The regular expression of ER and PGR notwithstanding, there are no data which suggest that sparing the ovaries facilitates or promotes recurrence As a precaution, an approach analogous to that which would be adopted for an LG-ESS should be opted for in cases in which the resection margins cannot be reliably assessed following morcellation or other tumor injuries Uterus-sparing TE can be considered for young women who urgently wish to preserve their fertility (15, 43, 49) The removed specimen should have a wide margin of myometrial tissue so as not to miss any infiltrations In light of the fact that ESN constitutes a precursor of LG-ESS, a certain risk of recurrence needs to be reckoned with, especially when there is limited infiltration, and indications for organ-sparing surgery need to be subject to very strict criteria or be made analogous to STUMP The central problem, however, lies in the fact that the diagnosis “ESN” is usually not known prior to surgery, and that most ESN are subjected to surgery under the diagnosis “LM” Against this backdrop, subjecting LM to laparoscopic intracapsular ME (as is recommended by some) (50) constitutes a real prognostic risk In the case presented in Fig 3.1.3 (A), (B), the patient delivered a mature and healthy child via cesarean section within one year of laparoscopic surgery, and there was no evidence of any recurrence of disease Further detail is presented in Chapter 8, Vol ESN that have been resected leaving unclear margin status should be subjected to reresection so as to be able to reach a definitive diagnosis Postoperative HT should be considered in cases in which reresection is not possible for whatever reason Regarding the surgical treatment of primarily advanced tumors that are confined to the pelvis and the abdominal cavity, only one case has been reported of synchronous spread of an ESN with limited infiltration into structures of the lesser pelvis (24) Complete tumor resection constitutes the therapeutic measure of choice in any case HT can be 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References | 409 (118) Zhao Z, Yoshida Y, Kurokawa T, Kiyono Y, Mori T, Okazawa H 18F-FES and 18F-FDG PET for differential diagnosis and quantitative evaluation of mesenchymal uterine tumors: correlation with immunohistochemical analysis J Nucl Med 2013; 54: 499–506 Image references Bauer B, Berner U Radiologie Sachsenhausen GmbH Frankfurt/Main Fig 6.5.2 (C), (D); 6.7.1 (B) Böhm D Rheinclinic, Gyn Chirurgie, Mainz/Bodenheim Fig 6.2.1 (C) Dennis K, Kuhfus S Krankenhaus Sachsenhausen, operative Gynäkologie, Frankfurt/Main Fig 6.7.1 (A) Köhler G, Zygmunt M Universitätsmedizin Greifswald, Klinik Frauenheilkunde und Geburtshilfe, Greifswald Fig 6.6.1; 6.7.2 Mertiny E Krankenhaus der Barmherzigen Brüder, Zentrale interdisziplinäre Sonographie, Trier Fig 6.8.1 (A), (B) Mustea, A Universitätsmedizin Greifswald, Klinik Frauenheilkunde und Geburtshilfe, Greifswald Fig 6.2.1 (D) Riechmann C, Köller M Krankenhaus Sachsenhausen, operative Gynäkologie, Frankfurt/Main Fig 6.5.1 (A)–(D); 6.5.2 (A), (B) Rosenthal V Universitätsmedizin Greifswald, Institut für Pathologie, Greifswald Fig 6.2.1 (B) Seyboth F Gesundheitszentrum Wetterau, Hochwaldkrankenhaus Bad Nauheim, Frauenklinik, Bad Nauheim Fig 6.4.1 Willenbrock K Gemeinschaftspraxis Pathologie Wiesbaden, Wiesbaden Fig 6.2.1 (A) Index 1p-deletions 10, 13, 20, 21 A adenomyomatosis, intravenous 93, 98 adenomyosis 143, 144, 149, 159, 271, 278, 280, 281, 286 alveolar soft tissue tumor 33 angioleiomyoma – adjuvant therapy – chemotherapy – embolization – high-frequency ultrasound therapy – hormone therapy – radiotherapy – aftercare – hormone therapy – clinical presentation – course – diagnostics – curettage – hysteroscopy – differential diagnostics – adenomyoma, cystic – angiosarcoma – hemangioma – leiomyoma – leiomyoma, degenerated – PEComa – stromal sarcoma, endometrial – epidemiology – imaging – CT – MRI – sonography – macroscopic features – metastases and recurrences – microscopic features – pathogenesis – primary surgery – hysterectomy – morcellement – salpingo-oophorectomy – tumorectomy – prognosis angiolipoleiomyoma angiomyolipoma angiosarcoma atypical smooth muscle tumor 36 C calcifying fibrous tumor 75 collision tumor 259 combined stromal smooth muscle 243 E endometrial stromal nodule with limited infiltration 233, 237, 239–243 endometrial stromal nodule, extrauterine 243 endometrial stromal nodule, uterine 231 – adjuvant therapy 239, 240 – hormone therapy 241 – chemotherapy 241 – ovarectomy 241 – radiotherapy 241 – aftercare 242 – imaging 242 – laparoscopy 242 – clinical presentation 235 – course 239 – diagnostics 235 – biopsy 235 – curettage 235 – hysteroscopy 235 – sonography 235 – differential diagnostics 237 – adenosarcoma 238 – endometrial stromal sarcoma, low-grade 237, 238 – endometriosis 238 – ESTSCLE 238 – h-caldesmon 238 – leiomyoma 237 – leiomyoma, cellular 237 – PEComa 238 – STUMP 237 – UTROSCT 238 – epidemiology 231 – etiology 231 – genetics 231 – fusion gene 231 – JAZF1/SUZ12 231 412 | Index – imaging 235 – CT 236 – MRI 236 – sonography 235 – inoperability 241 – hormone therapy 241 – macroscopis features 232 – metastases and recurrences 242 – morcellement 242 – microscopic features 232 – immunohistochemistry 234 – pathogenesis 231 – prognosis 239 – screening 239 – surgery, primary 239 – debulking 240 – hysterectomy 240 – morcellement 240 – salpingo-oophorectomy 240 – tumorectomy 240 endometrial stromal tumor with endometrioid glands 243 endometrial stromal tumor with sex cord-like elements type I, uterine, ESTSCLE 244 endometriosis 10, 65, 66, 75, 82, 84, 86, 238, 243, 246, 258, 259, 306, 309, 310 F fibrothecoma 86 G gestation 28, 33, 46, 57, 60, 65–67, 70, 72, 76, 78, 80 GIST 308 H high-grade endometrial stromal sarcoma and undifferentiated uterine sarcoma, extrauterine 365 high-grade endometrial stromal sarcoma and undifferentiated uterine sarcoma, uterine 327 – adjuvant therapy 351 – chemotherapy 352, 353 – hormontherapie 353 – radiotherapy 351, 352 – aftercare 356 – hormone replacement thrapy 357 – imaging 356 – N/L-ratio 356 – clinical presentation 335 – course 346, 347 – diagnostics 335 – abrasio, curretage 335 – hysteroscopy 335 – differential diagnostics 343 – cyclin D1 344 – adenosarcoma 343, 345 – carcinosarcoma 343, 345 – endometrial sarcoma 343 – endometrial stromal sarcoma, low-grade 344 – leiomyosarcoma 345 – epidemiology 328 – etiology 328 – genetics 328 – fusion gene 332 – JAZF1 332, 333 – JJAZ1 332, 333 – YWHAE/FAM22 332, 333 – imaging 336 – CT 340, 341 – MRI 340 – sonography 336 – inoperability 354 – chemotherapy 354 – hormone therapy 355 – hyperthermia therapy 355 – radiotherapy 354 – macroscopic features 329 – metastases and recurrences 357, 358 – chemotherapy 358, 360 – hormone therapy 361 – imaging 357 – radiotherapy 359, 360 – surgery 358 – microscopic features 330 – cyclin D1 331, 333 – immunohistochemistry 331, 333 – palliative therapy 361 – radiotherapy 361 – chemotherapy 361–363 – hormone therapy 363 – hyperthermia therapy 364 – immunotherapy 363 – pathogenesis 328 – prognosis 346, 347 – screening 335 – staging 329 Index | – surgery, primary 349 – debulking 350 – salpingo-oophorectomy 349 – hysterectomy 349 – lymphonodectomy 349 – tamoxifen exposure 328, 336, 353, 357 I inflammatory myofibroblastic tumor 75 intravenosus leiomyomatosis 280, 301 L leiomyoblastoma 30 leiomyoma, benign metastasizing 81 – adjuvant therapy – chemotherapy 89 – hormone therapy 89 – ovarectomy 89 – radiotherapy 89 – tamoxifen exposure 90 – aftercare 92 – clinical presentation 84 – course 88 – diagnostics – biopsy 84 – imaging 84 – differential diagnostics – endometriosis 86 – fibroma 86 – fibrosarcoma, ovarian 86 – fibrothecoma 86 – leiomyomatosis, primary pulmonary 86 – leiomyosarcoma 86 – lymphangioleiomyomatosis 86 – neurofibromatosis 86 – STUMP 86 – imaging – CT 85 – MRI 85 – radiographic 85 – sonography 85 – inoperability – chemotherapy 90 – hormone therapy 90 – ovarectomy 91 – radiotherapy 90 – macroscopic features 83 – metastases and recurrences 92 – microscopc features – immunohistochemistry 83 413 – pathogenesis 81 – primary surgery – biopsy 89 – hysterectomy 88 – salpingo-oophorectomy 88 – prognosis 88 leiomyoma, cellular 10 – adjuvant therapy 21 – aftercare – imaging 22 – laparoscopy 22 – clinical presentation 13 – course 19 – diagnostics – biopsy 13 – differential diagnostics – CD10 18 – leiomyosarcoma 18 – stromal nodule, endometrial 18 – stromal sarcoma, endometrial low-grade 18 – etiology – 1p-deletions 10 – genetics 10 – imaging – CT 14, 16 – MRI 14 – sonography 14 – inoperability 21 – macroscopic features 10 – metastases and recurrences 22 – microscopic features 11 – immunohistochemistry 11 – pathogenesis 10 – primary surgery – embolization 21 – hysterectomy 21 – lymphonodectomy 21 – morcellement 21 – myomectomy 21 – salpingo-oophorectomy 21 – ultrasound-thermotherapy 21 – prognosis 19 leiomyoma, clear-cell epithelioid 31 leiomyoma, cotyledonoid dissecting – adjuvant therapy 10 – clinical presentation – course – diagnostics 414 | Index – differential diagnostics – adnexal tumor – leiomyoma, parasitic – leiomyomatosis peritonealis disseminata – leiomyomatosis, intravenous – sarcoma – imaging – MRI – sonography – inoperability 10 – macroscopic features – microscopic features – pathogenesis – primary surgery – hysterectomy – tumorectomy – prognosis leiomyoma, epithelioid 30 – adjuvant therapy 33 – clinical presentation 32 – diagnostics 32 – differential diagnostics – leiomyosarcoma 33 – melanoma 33 – PEComa 33 – soft part tumors, alveolar 33 – stromal nodule, endometrial 33 – stromal sarcoma, endometrial low-grade 33 – STUMP 33 – trophoblastic tumors 33 – UTROSCT 33 – imaging 32 – inoperability 33 – macroscopic features 31 – microscopic features 32 – immunohistochemistry 32 – pathogenesis 30 – primary surgery – hysterectomy 33 – prognosis 33 leiomyoma, mitotically active 27 – adjuvant therapy 30 – clinical presentation 28 – course 30 – diagnostics 28 – differential diagnostics – leiomyosarcoma 28 – STUMP 28 – imaging 28 – MRI 28 – inoperability 30 – microscopic features 27 – tamoxifen exposure 28 – pathogenesis 27 – gestation 28 – primary surgery – hysterectomy 30 – prognosis 30 leiomyoma, myxoid 33 – adjuvant therapy 36 – clinical presentation 35 – course 35 – diagnostics – curettage 35 – differential diagnostics – leiomyomsarcoma 35 – STUMP 35 – imaging – MRI 35 – inoperability 36 – macroscopic features 33 – microscopic features 33 – pathogenesis 33 – gestation 33 – primary surgery – hysterectomy 35 – prognosis 35 leiomyoma, ovarian and tubal 59 – adjuvant therapy 61 – clinical presentation 60 – course 61 – diagnostics 60 – differential diagnostics – angiofibroma 61 – angiomyofibroblastoma 61 – fibroma 61 – leiomyoma, retroperitoneal 60 – STUMP 60 – imaging – CT 61 – MRI 60 – sonography 60 – macroscopic features 59 – microscopic features 59 – pathogenesis 59 Index | – primary surgery – oophorectomy 61 – prognosis 61 leiomyoma, pleomorphic or symplastic 23 leiomyoma, plexiform 31 leiomyoma, retroperitoneal and vaginal 62 – adjuvant therapy 65 – clinical presentation 62 – course 65 – diagnostics 62 – differential diagnostics – leiomyosarcoma 64 – liposarcoma 64 – imaging – CT 64 – MRI 64 – sonography 64 – macroscopic features 62 – microscopic features 62 – pathogenesis 62 – primary surgery 65 – prognosis 65 leiomyoma, vulvar 56 – adjuvant therapy 58 – clinical presentation 57 – course 58 – diagnostics 57 – differential diagnostics – angiomyofibroblastoma 58 – angiomyoma 58 – Bartholin´s cyst 58 – histiocytoma, myxoid malignant fibrous 58 – leiomyomatosis 58 – imaging – CT 58 – MRI 58 – sonography 58 – macroscopic features 56 – microscopic features 56 – pathogenesis 56 – primary surgery 58 – prognosis 58 leiomyoma, with bizarre nuclei 23 – adjuvant therapy 27 – clinical presentation 26 – course 26 – diagnostics 26 415 – differential diagnostics – leiomyosarcoma 26 – STUMP 26 – imaging 26 – inoperability 27 – macroscopic features 24 – microscopic features 24 – immunohistochemistry 26 – PHH3 24 – pathogeneis 23 – primary surgery – hysterectomy 27 – morcellement 27 – myomectomy 27 – prognosis 26 leiomyomatosis peritonealis disseminata and parasitic leiomyoma 65 – adjuvant therapy 77 – aftercare – hormone therapy 80 – imaging 80 – clinical presentation 72 – course 76 – hormone therapy 76 – morcellement 76 – diagnostics 72 – biopsy 75 – differential diagnostics – CA 125 74 – calcifying fibrous tumor 75 – endometriosis 75 – inflammatory myofibroblastic tumor 75 – leiomyoma, benign metastasizing 75 – leiomyosarcoma 75 – PEComatosis 75 – peritoneal carcinosis 74 – peritoneal sarcomatosis 75 – STUMP 75 – etiology – genetics 66 – imaging – CT 72, 74 – MRI 72 – sonography 72 – inoperability 77 – chemotherapy 78 – hormone therapy 78 – radiotherapy 77 – macroscopic features 65 416 | Index – metastases and recurrences – biopsy 80 – chemotherapy 80 – hormone therapy 80 – operation 80 – ovarectomy 80 – microscopic features 65 – immunohistochemisty 66 – pathogenesis 65 – endometriosis 65 – gestation 65 – hormone exposure 65 – morcellement 66 – primary surgery – conservative LM surgery 77 – debulking 77 – hysterectomy 77 – morcellment 77 – salpingo-oophorectomy 77 – prognosis 76 leiomyomatosis, intravenous 92 – adjuvant therapy – chemotherapy 99 – hormone therapy 99 – radiotherapy 99 – aftercare – hormone therapy 101 – imaging 101 – clinical presentation 95 – course 98 – diagnostics – imaging 96 – differential diagnostics – hepatocellular carcinoma 98 – leiomyomsarcoma, intravascular 97 – lymphangioleiomyomatosis, primary retroperitoneal 98 – phleboliths 97 – phlebothrombosis 98 – renal cell carcinoma 98 – stromal sarcoma, endometrial low grade 98 – STUMP 98 – imaging – CT 96 – MRI 96 – sonography 96 – inoperability – hormone therapy 100 – macroscopic features 93 – metastases and recurrences 101 – microscopic features 95 – immunohistochemistry 95 – pathogenesis 92 – adenomyomatosis, intravenous 93 – primary surgery – hysterectomy 99 – myomectomy 99 – salpingo-oophorectomy 99 – venotomy 99 – prognosis 98 leiomyosarcoma, ovarian 192 – adjuvant therapy 195 – clinical presentation 194 – course 194 – diagnostics 194 – differential diagnostics 194 – fibrosarcoma 194 – GIST 194 – leiomyoma 194 – leiomyoma, cellular 194 – sex cord stromal tumor 194 – stromal sarcoma, endometrial low-grade 194 – STUMP 194 – imaging 194 – sonography 194 – macroscopic features 193 – microscopic features 193 – immunohistochemistry 193 – pathogenesis 193 – primary surgery 194 – debulking 195 – lymphonodectomy 194 – omentectomy 195 – ovarectomy 195 – resection 194 – prognosis 194 leiomyosarcoma, tubal 196 – clinical presentation 196 – course 196 – diagnostics 196 – differential diagnostics 196 – imaging 196 – macroscopic features 196 – pathogenesis 196 – prognosis 196 – therapy 196 Index | leiomyosarcoma, uterine 119 – adjuvant therapy 166 – chemotherapy 167, 168 – hormone therapy 169 – radiotherapy 166, 167 – aftercare 172 – chemotherapy 173 – hormone therapy 174 – imaging 172, 173 – L/M-ratio 173 – laparoscopy 173 – LDH 173 – N/L-ratio 173 – tamoxifen exposure 175 – aplliative therapy – chemotherapy 189 – clinical presentation 134–138 – course 155–158, 160 – diagnostics 136, 138 – biopsy 138 – curettage 136 – frozen section 137 – GDF-15 138 – hysteroscopy 136 – LDH 138 – morcellement 137 – N/L-ratio 138 – sonography 136 – differential diagnostics 150 – adenosarcoma 150 – carcinosarcoma 150 – endometrial carcinoma 150 – inflammatory myofibroblastic tumor 153 – leiomyoma 150 – leiomyoma, atypical 152 – leiomyoma, cellular 153 – leiomyoma, degenerated 152 – leiomyoma, epitheliod 153 – lymphoma 153 – myoma in statu nascendi, necrotized 150 – PEComa 153 – stromal nodule, endometrial 153 – stromal sarcoma, endometrial high-grade 150 – stromal sarcoma, endometrial low-grade 150 – STUMP 150 – undifferentiated uterine sarcoma 150 – epidemiology 120 – etiology 121 – hormone therapy 121 – tamoxifen exposure 121 – imaging 139 – CT 145, 149, 150 – MRI 146, 148 – sonography 139, 140, 143, 145 – inoperability 170 – chemotherapy 170, 171 – hormone therapy 172 – hyperthermia 171 – radiotherapy 170 – L/M-ratio 156, 173 – LDH 138, 145, 148, 149, 151, 154, 170, 173 – macroscopic features 124 – metastases and recurrences 175, 177 – brain metastases 183 – chemotherapy 178, 184 – debulking 178 – liver metastases 182 – pulmonary metastases 182 – radiotherapy 178, 184 – resection 177, 178 – two compartement-surgery 180 – microscopic features 126 – diagnosis 130 – epithelioid leiomyosarcoma 130 – immunohistochemistry 128 – low-grade leiomyosarcoma 131 – myxoid leiomyosarcoma 130 – microscopic featuresdiagnosis 127 – N/L-ratio 138, 145, 151, 156, 173 – palliative therapy 184 – chemotherapy 185–188 – hormone therapy 189–191 – radiotherapy 184 – targeted therapy 191 – pathogenesis 120, 121 – genetics 121 – immunohistochemistry 120, 121 – primary surgery 161 – biopsy 164 – debulking 165 – hysterectomy 161, 164, 165, 194 – laparoscopy 165 – lymphonodectomy 162 – morcellement 161, 164 – omentectomy 162 – parametrian resection 162 417 418 | Index – re-operation 164 – salpingo-oophorectomy 162 – tumorectomy 162, 164 – prognosis 155, 157 – hysterectomy 159, 160 – L/M-ratio 156 – lymphonodectomy 157 – morcellement 157, 159 – ovarectomy 156 – tumorectomy 160 – screening 138 – tamoxifen exposure 139 – staging 121 – tamoxifen exposure 121, 139, 175 leiomyosarcoma, vaginal 199 – adjuvant therapy 202 – chemotherapy 202 – radiotherapy 202 – clinical presentation 200 – course 201 – diagnostics 200 – differential diagnostics 200 – Gardner’s duct cysts 200 – leiomyoma 200 – melanoma 200 – metastases 200 – neurofibroma 200 – rhabdomyosarcoma 200 – differential diagnostics, vaginal carcinoma 200 – imaging 200 – CT 200 – MRI 200 – sonography 200 – macroscopic features 199 – microscopic features 199 – pathogenesis 199 – primary surgery 201 – debulking 202 – downstaging 202 – hysterectomy 202 – lymphonodectomy 202 – re-operation 201 – resection 201 – salpingo-oophorectomy 202 – prognosis 201 leiomyosarcoma, venous 197 – aftercare 198 – CT 198 – clinical presentation 197 – course 198 – diagnostics 197 – differential diagnostics – leiomyomatosis, intravascular 197 – stromal sarcoma, endometrial low-grade 197 – imaging 198 – CT 198 – MRI 198 – sonography 198 – macroscopic features 197 – pathgenesis 197 – primary surgery 198 – resection 198 – prognosis 198 – staging 197 leiomyosarcoma, vulvar 203 – adjuvant therapy 206 – chemotherapy 208 – hyperthermia 208 – radiotherapy 207 – re-operation 208 – aftercare 208 – classification 204 – clinical presentation 205 – course 206 – diagnostics 206 – biopsy 206 – frozen section 206 – differential diagnostics 205 – angiomyoma 206 – Bartholin´s cysts 205 – epithelioid sarcoma 206 – fibroma 206 – leiomyoma, atypical 206 – leiomyoma, cellular 206 – leiomyosarcoma, cutaneous 206 – lipoma 206 – STUMP 205 – grading 204 – imaging 205 – CT 206 – MRI 205 – sonography 205 – inoperability 208 – macroscopic features 205 – microscopic features 205 – immunohistochemistry 205 – pathogenesis 203 Index | – primary surgery 206 – resection 207 – prognosis 206 – staging 203, 204 lipoleiomyoma – adjuvant therapy – chemotherapy – hormone therapy – radiotherapy – clinical presentation – course – diagnostics – differential diagnostics – adipocytic sarcoma – imaging – CT – MRI – sonography – inoperability – chemotherapy – radiotherapy – macroscopic features – microscopic features – pathogenesis – primary surgery – hysterectomy – prognosis low-grade endometrial stromal sarcoma, extrauterine 309 low-grade endometrial stromal sarcoma, uterine 257 – adjuvant therapy 291 – chemotherapy 292 – hormone therapy 292, 294, 295 – ovarectomy 293 – radiotherapy 291 – tamoxifen exposure 295 – aftercare 298 – hormone therapy 299 – imaging 298 – laparoscopy 299 – N/L-Ratio 299 – tamoxifen-, toremifen exposure 300 – clinical presentation 267 – course 282 – diagnostics 268 – biopsy 268 – curettage 268 – hysteroscopy 268 – differential diagnostics 279 – adenomyosis 280 – adenosarcoma 279 – carcinosarcoma 279 – endometrial stromal nodule 279, 280 – endometrial stromal sarcoma, high-grade 280 – leiomyoma 279 – leiomyoma, cellular 280 – leiomyoma, degenerated 280 – leiomyomatosis, intravenosus 280 – leiomyosarcoma 279 – lymphangioleiomyomatosis 282 – PEComa 281 – epidemiology 257, 258 – etiology 258 – endometrial stromal nodule 258 – genetics 258 – fusion gene 258 – JAZF1-SUZ12 258 – imaging 270 – CT 274, 278 – MRI 274, 276, 278 – sonography 270, 271, 273 – inoperability 296 – chemotherapy 297 – hormone therapy 297 – radiotherapy 296 – macroscopic features 260, 263 – microscopic features 263 – CD10 266 – immunohistochemistry 266 – palliative therapy 304 – chemotherapy 304, 305 – hormone therapy 305–307 – immunotherapy 308 – mTOR-inhibitor 307 – ovarectomy 305 – radiotherapy 304 – tamoxifen exposure 306 – pathogenesis 258, 259 – endometriosis 258 – fusion gene 258 – hormone therapy 259 – hyperestrogenic states 258 – immunohistochemistry 258 – tamoxifen exposure 259 – toremifen exposure 259 – xenoestrogens 259 419 420 | Index – primary surgery 288 – debulking 290 – hysterectomy 288 – lymphonodectomy 288 – morcellement 288 – salpingo-oophorectomy 288 – tumorectomy 289 – prognosis 282 – immunohistochemistry 283 – N/L-Ratio 287 – recurrences and metastases 301 – chemotherapy 303 – hormone therapy 303 – radiotherapy 303 – surgical therapy 301 – screening 269 – staging 259 – tumor thrombi 263, 265, 276, 280, 300 lymphangioleiomyomatosis 75, 282 lymphovascular invasion 244, 246, 250, 251 M mixed endometrial stromal and smooth muscle tumor 243 mTOR-inhibitor 307 N N/L-Ratio 287, 299 N/L-ratio 138, 145, 151, 156, 173 neurofibromatosis 86 P p16 20, 40, 46, 47, 50, 51 p53 20, 26, 40, 46, 47, 50, 51, 88 PEComa 248 PHH 24, 40, 46 phleboliths 97 prevention, criteria suggestive of sarcoma 382 – clinical criteria 382, 384–386, 388 – imaging 382 – leiomyosarcoma 382 – stromal sarcoma, endometrial low-grade 382 prevention, diagnostic flowchart 395 – imaging 396 – OP methods 395 – risk factors 396 prevention, extended diagnostics 388 – biopsy 394 – curettage 389 – hysteroscopy 389 – imaging 388 – CT 391 – MRI 391, 392 – sonography 388, 390 – LDH 390 – N/L-ratio 390 – risk factors 389 prevention, inadequate surgical treatment 373 – adenosarcoma 373 – characteristics 374 – indications 373 – leiomyosarcoma 373 – stromal sarcoma, endometrial high-grade 373 – stromal sarcoma, endometrial low-grade 373 – STUMP 373 – undifferentiated uterine sarcoma 373 prevention, measures 400 – adjuvant therapy 401 – imaging 401 – laparoscopy 401 – re-operation 400 prevention, prevalence 380 – hysterectomy 380 – leiomyosarcoma 380 – LM-operations 380 – morcellement 381 – myomectomy 380 – stromal sarcoma, endometrial low-grade 381 – STUMP 381 – tumorectomy 381 prevention, prognosis 373 – hysterectomy, laparoscopic assisted vaginal 376 – hysterectomy, supracervical abdominal 376 – hysterectomy, supracervical laparoscopic 376 – hysterectomy, total 373 – hysterectomy, total abdominal 374 – hysterectomy, total endoscopic 376 – morcellement 374–376, 379 – myomectomy 378 – tumorectomy 376 prevention, risk assessment 398 – novel sarcoma preoperative diagnosis score 399 – risk criteria 398 S Sternberg tumor stromal endometriosis 238, 243 Index | STUMP 36 – adjuvant therapy – chemotherapy 52 – hormone therapy 52 – ovarectomy 52 – radiotherapy 52 – aftercare – hormone therapy 53 – imaging 53 – laparoscopy 53 – clinical presentation 43 – course 47 – p16 and p53 47 – diagnostics – biopsy 44 – curettage 44 – morcellement 44 – differential diagnostics – leiomyoma 43 – leiomyoma, cellular 43 – leiomyoma, degenerated 43 – leiomyosarcoma 43 – epidemiology 37 – imaging – CT 45, 46 – MRI 45 – sonography 44 – inoperability – hormone therapy 52 – macroscopic features 37 – metastases and recurrences – chemotherapy 54 421 – hormone therapy 55 – operation 54 – ovarectomy 55 – radiotherapy 54 – microscopic features 37 – epithelioid STUMP 42 – immunohistochemistry 40 – immunohistochemistry; p16 and p53 40 – myxoid STUMP 42 – pathogenesis 36 – primary surgery – embolization 52 – hysterectomy 50 – lymphonodectomy 50 – morcellement 50 – salpino-oophorectomy 50 – ultrasound-thermotherapy 52 – prognosis 47 T tamoxifen exposure 28, 65, 68, 90, 121, 139, 175, 246, 247, 259, 270, 295, 300, 306, 309 toremifen exposure 259, 300 U undifferentiated uterine sarcoma and high-grade endometrial stromal sarcoma 327 uterine tumors resembling ovarian sex-cord tumors type II, UTROSCT 247 UTROSCT 33 ... that of normal myometrium Cystic structures remain hypointense (41) In one case (38), only the areas on the margins of the tumor showed enhancement, while the rest of the tumor did not The non-enhancing... long-lasting or highly-dosed progestin therapy (29 ) Stromal endometriosis usually arises on the surface of the peritoneum in the vicinity of other areas of endometriosis and does not develop actual... dependent on the presence or absence of infiltration Accordingly, classification either as ESN or as LG-ESS is based on these criteria The IHC of the stromal cells corresponds to that of ESN (Fig 3 .2. 1