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Coughing up – Small cell carcinoma lung with gingival metastasis Journal of the Egyptian National Cancer Institute (2016) xxx, xxx–xxx Cairo University Journal of the Egyptian National Cancer Instit[.]

Journal of the Egyptian National Cancer Institute (2016) xxx, xxx–xxx Cairo University Journal of the Egyptian National Cancer Institute www.elsevier.com/locate/jnci www.sciencedirect.com Case Report Coughing up – Small cell carcinoma lung with gingival metastasis Antony George Francis Thottian a, Sushmita Pathy a,*, Ajeet Kumar Gandhi a, Prabhat Malik b, Aruna Nambirajan c a Department of Radiation Oncology, Dr BRA Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, India Department of Medical Oncology, Dr BRA Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, India c Department of Pathology, All India Institute of Medical Sciences, India b Received 30 July 2016; revised 26 August 2016; accepted 27 September 2016 KEYWORDS Small cell lung cancer; Metastasis; Gingiva; Radiation therapy Abstract Small cell lung cancer (SCLC) is known for its metastatic potential The most common sites are liver, adrenal, bone and brain We report a case of a 37 year old female patient, diagnosed with SCLC, presenting with gingival metastasis, an unusual metastatic site Radiation therapy to the metastatic lesion to a dose of 20 Gray in fractions over days was delivered which achieved haemostasis and good palliation However, the patient expired in months owing to systemic metastasis Ó 2016 National Cancer Institute, Cairo University Production and hosting by Elsevier B.V This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) Introduction Small Cell lung cancer (SCLC) is an aggressive subtype of lung cancer known for its metastatic potential [1] Around 70% of Abbreviations: SCLC, small cell lung cancer; CECT, contrast enhanced computed tomography; CT, computed tomography; PET CT, positron emission tomography – computed tomography; ECOG PS, Eastern cooperative oncology group performance status; AJCC, American Joint Committee on Cancer; Gy, Gray * Corresponding author at: Department of Radiation Oncology, Dr BRA Institute Rotary Cancer Hospital, AIIMS, New Delhi, India Fax: +91 11 26588663 E-mail addresses: antonygft@gmail.com (A.G.F Thottian), drspathy@gmail.com (S Pathy), ajeetgandhi23@gmail.com (A.K Gandhi), drprabhatsm@gmail.com (P Malik), dr.arunacastro@ gmail.com (A Nambirajan) Peer review under responsibility of The National Cancer Institute, Cairo University SCLC presents with extensive disease With combination chemotherapy, about 20% achieve a complete response with a median survival of months However, only 2% are alive at years [2] The most common sites of metastasis of SCLC are liver, adrenals, bone and brain Metastasis to gingiva and hard palate is rare Cases of lung cancer metastasizing to these sites have been reported [3–7] and in one case metastasis to gingiva was the presenting feature [8] Herein, we report a case of extensive stage SCLC treated with chemotherapy and radiation therapy presenting with metastasis to gingiva This unusual site of metastasis was a cause of bleeding, thus requiring palliation Case history A thirty-eight year old housewife presented with dry cough, progressive dyspnoea and chest pain for two months There was no fever, haemoptysis, weight loss, seizures or any medical http://dx.doi.org/10.1016/j.jnci.2016.09.003 1110-0362 Ó 2016 National Cancer Institute, Cairo University Production and hosting by Elsevier B.V This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) Please cite this article in press as: Thottian AGF et al Coughing up – Small cell carcinoma lung with gingival metastasis, J Egyptian Nat Cancer Inst (2016), http://dx doi.org/10.1016/j.jnci.2016.09.003 co-morbidity She did not have any history of smoking or alcohol intake Her performance status was good and systemic examination did not reveal any abnormalities Chest X-ray showed a mediastinal mass and contrast enhanced computed tomography (CECT) showed a 7.1  7.0  4.6 cm mass in left peri-hilar region with necrosis and calcification encasing the great vessels (Fig 1) In view of her young age and nonsmoker status, a DOTANOC scan was done suspecting bronchial carcinoid However no uptake was noted Biopsy revealed a malignant small round cell tumour with areas of necrosis Synaptophysin, chromogranin and cytokeratin were positive on immunohistochemistry (Fig 2) with MIB-1 labelling index greater than 90% Whole body Positron Emission Tomography (PET) CT revealed an additional asymptomatic brain metastasis The patient was diagnosed as small cell carcinoma lung and staged as T4N1M1b according to the seventh American Joint Committee on Cancer (AJCC) recommendations [9] In view of good performance status whole brain irradiation to a dose of 30 Gray (Gy) in 10 fractions over weeks was delivered Subsequently she received cycles of chemotherapy with cisplatin and etoposide A response assessment PET CT showed no change in the size of lung mass However the previously noted brain metastasis was non 18Fluorodeoxyglucose avid Following this she was treated with radiation therapy (RT) to a dose of 20 Gy in five fractions over five days to the lung mass After one month of RT she presented to our clinic with a single episode of bleeding (10– 15 ml) from oral cavity Detailed physical and local examination showed two ulcero – proliferative lesions – one  cm in the upper gingiva posterior to the first molar and one  cm lesion in hard palate (Fig 3) The blood counts were within normal limits A course of antibiotics and anti-fungals showed no improvement CT face and neck showed a mass in the upper gingiva, causing destruction of alveolus and extending to adjacent hard palate and buccal mucosa (Fig 4) Biopsy revealed it to be a small cell A.G.F Thottian et al Figure Sections from the lung biopsy show a small cell carcinoma composed of hyperchromatic cells with scant cytoplasm arranged in lobules with crushing artefacts (H&E, 200) Figure Ulcero-proliferative lesion is noted in left maxillary gingiva posteriorly, a separate ulcerated lesion is seen in the hard palate carcinoma The immuno-histochemical markers were similar to the one reported from the lung primary thus linking it to be metastatic from the lung (Fig 5A–E) The patient received palliative RT, 20 Gy in five fractions over five days to the metastatic site At one month follow up she had partial regression of the lesion and did not report any further episodes of bleeding from oral cavity Unfortunately, she developed jaundice at the next visit and imaging showed multiple liver metastases She was offered best supportive care as performance status was not suitable for further cancer directed therapy She expired at home two months post detection of the oral cavity ulcers Discussion Figure Computed tomography image of the lung primary – mass in left upper lobe encasing the arch of aorta Though small cell lung cancer is notorious for hematogenous dissemination, oral cavity is a rare site for metastasis If Please cite this article in press as: Thottian AGF et al Coughing up – Small cell carcinoma lung with gingival metastasis, J Egyptian Nat Cancer Inst (2016), http://dx doi.org/10.1016/j.jnci.2016.09.003 Gingival metastasis from small cell lung cancer Figure CT image of the same lesion – showing soft tissue mass in the region of left alveolus causing destruction of bone and eroding the pterygoid plates metastasis from any primary cancer is detected in oral cavity, the most common primary is lung cancer Previously reported literature describes metastasis in oral cavity from lung to mandibular bone, tongue, gingiva and tonsil [10] Metastasis to oral cavity generally signifies widespread systemic disease Median survival after discovery of oral metastasis is dismal and is often limited to few months [10] Till date around 20 cases of lung cancer metastasizing to gingiva have been reported in literature Oral metastasis can present as either rapidly growing masses or ulcero-proliferative lesions [6] A review of 17 cases of oral metastasis from lung primary by Huang et al revealed undifferentiated carcinoma to be the most common histology followed by large cell carcinoma, adenocarcinoma, small cell carcinoma and squamous cell carcinoma in that order [6] In this case, an ulcero-proliferative lesion was observed, which also caused erosion of the alveolus and the pterygoid plates Though not immediately life threatening, oral cavity lesions can be troublesome as they interfere with nutrition and thus quality of life The pathogenesis of metastasis is complicated The presence of chronic inflammation in gingiva has been postulated as a cause Fragmented basement membranes in the vessels and cytokines around the site of inflammation may act as a homing trigger for the metastatic clone [11] The current case was treated according to National Comprehensive Cancer Network (NCCN) guidelines, which advocate combination chemotherapy with cisplatin/carboplatin and etoposide/irinotecan and cranial irradiation Treatment of gingival metastasis is controversial Both systemic chemotherapy and radiotherapy has been used Surgical excision can also be tried to improve nutrition and hygiene or control bleeding [6] In this case, the lesion presented as an ulcer with bleeding; hence radiotherapy was delivered for haemostasis and palliation Since it is rare for lung cancer to metastasize to the oral cavity, a variety of differential diagnoses are entertained They include pyogenic granuloma, dental abscess, neutropenic ulcer and second primary malignancy in oral cavity However metastasis from the primary tumour should be always considered in a known case of lung cancer and a detailed evaluation with histopathological examination is mandatory Small cell lung cancer is very sensitive to radiation treatment and therefore is very effective in achieving haemostasis and palliation Conflict of interest The authors have no conflict of interest to report Figure A Sections from the oral cavity mass show a similar tumour as in Fig (H&E, 400) B: The tumour cells show ’dot like’ immunopositivity for pan-cytokeratin (IHC, 400) C: The Ki-67 labelling index is approximately 90% (IHC, 400) D: Tumour cells show diffuse cytoplasmic positivity for synaptophysin (IHC, 400) E: Tumour cells show nuclear immunopositivity for Thyroid Transcription factor-1 (IHC, 400) Please cite this article in press as: Thottian AGF et al Coughing up – Small cell carcinoma lung with gingival metastasis, J Egyptian Nat Cancer Inst (2016), http://dx doi.org/10.1016/j.jnci.2016.09.003 References [1] Elias AD Small cell lung cancer: state-of-the-art therapy in 1996 Chest 1997;112(4 suppl):251S–8S [2] Jackman DM, Johnson BE Small-cell lung cancer Lancet 2005;366:1385–96 [3] Staalsen N-H, Nielsen JS Bronchogenic metastasis to the gingiva Oral Surg Oral Med Oral Pathol 1992;74:561–2 [4] Jaguar GC, Prado JD, Soares F, Alves FA, Toleda Oso´rio CA Gingival metastasis from non-small cell undifferentiated carcinoma of the lung mimicking a pyogenic granuloma Oral Oncol Extra 2006;42:36–9 [5] Hentati D, Chraiet N, Kochbati L, Maalej M Gingival metastasis from the lung through a needle and a pin: a case report Cancer Radiother 2007;11(8):500–2 [6] Huang C-J, Chang Y-L, Yang M-C, Hsueh C, Yu C-T Lung cancer metastatic to the maxillary gingiva—a case report and literature review Oral Oncol Extra 2005;41:118–20 A.G.F Thottian et al [7] Moharil RB, Khandekar S, Dive A Metastatic lung malignancy to mandibular gingiva Indian J Dent Res 2010;21:449–51 [8] Rajini Kanth M, Ravi Prakash A, Raghavendra Reddy Y, Sonia Bai JK, Ravindra Babu M Metastasis of lung adenocarcinoma to the gingiva: a rare case report Iran J Med Sci 2015;40:287–91 [9] Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti III A, editors AJCC cancer staging manual New York: Springer; 2010 p 253–70 [10] Hirshberg A, Shnaiderman-Shapiro A, Kaplan I, Berger R Metastatic tumours to the oral cavity – pathogenesis and analysis of 673 cases Oral Oncol 2008;44(8):743–52 [11] Allon I, Pessing A, Kaplan I, Allon DM, Hirshberg A Metastatic tumors to the gingiva and the presence of teeth as a contributing factor: a literature analysis J Periodontol 2014;85:132–9 Please cite this article in press as: Thottian AGF et al Coughing up – Small cell carcinoma lung with gingival metastasis, J Egyptian Nat Cancer Inst (2016), http://dx doi.org/10.1016/j.jnci.2016.09.003 ... et al Coughing up – Small cell carcinoma lung with gingival metastasis, J Egyptian Nat Cancer Inst (2016), http://dx doi.org/10.1016/j.jnci.2016.09.003 Gingival metastasis from small cell lung. .. cases of oral metastasis from lung primary by Huang et al revealed undifferentiated carcinoma to be the most common histology followed by large cell carcinoma, adenocarcinoma, small cell carcinoma. .. Tumour cells show nuclear immunopositivity for Thyroid Transcription factor-1 (IHC, 400) Please cite this article in press as: Thottian AGF et al Coughing up – Small cell carcinoma lung with gingival

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