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Aruna Nambirajan



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    EP1.15 - Thymoma/Other Thoracic Malignancies (ID 205)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Thymoma/Other Thoracic Malignancies
    • Presentations: 2
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.15-03 - SMARCA4-Deficient Thoracic Malignancies: A Unifying Genetic Aberration Across Tumors of Divergent Differentiation (Now Available) (ID 1614)

      08:00 - 18:00  |  Author(s): Aruna Nambirajan

      • Abstract
      • Slides

      Background

      Mutations in ATPase-dependant chromatin remodelling units are one of the most common genetic alterations observed in human cancer. Germline mutations in SMARCA4 encoding for Brg-1 protein, a subunit of the SWI/SNF chromatin modifier unit, are well recognised as the causative genetic event in rhabdoid tumor predisposition syndromes that occur in infants and young children. In recent years, somatic mutations in SMARCA4 have been increasingly identified in many adult-onset malignancies ranging from well differentiated carcinomas to poorly differentiated high grade sarcomas in a variety of anatomical sites, including thorax. Documentation of such tumors is essential to our understanding of the pathogenesis and possible mechanisms of therapeutic targetting.

      Method

      Case 1: A 60-year-old male smoker presented with chronic emphyema thoracis of non-tubercular etiology which was treated by intercostal drainage. He had repeated episodes of blockade of chest drain over the next 6 months and eventually a thoracic window was surgically created. Five months following thoracotomy, patient presented with a mass growing at the site of the thoracic window . No other masses in the lung parenchyma or mediastinal lymphadenopathy was seen. Patient underwent an excision of the granulation tissue-like mass. Formalin fixed paraffin embedded sections were subject to microscopy and immunohistochemistry for vimentin, CD34, MIC2, p53, SALL4, pan-cytokeratin (AE1/AE3), EMA, p40, TTF-1, cytokeratin-7, Hepar-1, desmin, myogenin, CD31, S100, Melan-A, HMB-45, GATA-3, calretinin, WT1, INI-1, brg-1 and hematolymphoid markers.

      Case 2: A 58-year old male smoker presented with hemoptysis and cough. On evaluation, an endobronchial mass was identified and was excised. Formalin fixed paraffin embedded sections from excised tumor mass was subject to microscopy and immunohistochemistry for cytokeratin 7, cytokeratin 19, epithelial membrane antigen, chromogranin, synaptophysin, cytokeratin 20, CD117, TTF-1, NUT1, Her2neu, GATA3, p40, S100, INI-1 and brg-1.

      Result

      Case 1: Microscopy revealed a tumor centred in the soft tissue of the chest wall ulcerating the overlying skin. No lung parenchymal involvement was seen. The tumor was arranged in sheets composed of monomorphic large tumor cells with abundant eosinophilic cytoplasm and prominent nucleoli showing frequent mitoses and foci of necrosis. No squamous or glandular differentiation was seen. Tumor cells were only immunopositive for vimentin, CD34, MIC2, p53, and SALL4, very focally immunopositive for CK (AE1/AE3) and showed retained INI-1 protein expression. Brg-1 expression was lost in tumor cells leading to a diagnosis of SMARCA4-deficient thoracic sarcoma.

      Case 2: Microscopy revealed a high grade tumor arising from the main bronchi with parenchymal and tracheal extension ulcerating the overlying squamous epithelium. Tumor cells were arranged in lobules with peripheral palisading and central necrosis. The tumor cells were large with frequent cytoplasmic clearing and frequent mitoses. Tumor cells were immunopositive for CK-7, CK-19, EMA, CG while were negative for others. INI-1 was retained while brg-1 was lost leading to a diagnosis of SMARCA4-deficient carcinoma.

      Conclusion

      Two independant studies have delineated SMARCA4-deficient thoracic sarcomas and SMARCA4-deficient lung carcinomas as distinct clinicopathological entities. Despite a unifying genetic alteration, these tumors appear to show varied histomorphology and immunoprofiles. Long term follow-up and molecular analysis of such tumors is necessary.

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      EP1.15-19 - Primary Endobronchial Hyalinising Clear Cell Carcinoma Presenting in Association with Active Pulmonary Tuberculosis (Now Available) (ID 1619)

      08:00 - 18:00  |  Author(s): Aruna Nambirajan

      • Abstract
      • Slides

      Background

      Hyalinising clear cell carcinoma (HCCC) is a rare tumor of putative salivary gland origin that most commonly presents as an oral submucosal lesion in middle aged to elderly adults. With a characteristic histomorphology of infiltrating cords and nests of clear tumor cells set in a hyalinised stroma, these tumors frequently harbour EWSR1:ATF1 fusions, the latter serving as a useful diagnostic marker in differentiation from other clear cell-rich tumors. Only four cases with primary pulmonary origin have been previously reported, all of which were incidentally detected small (<3 cm) intrabronchial masses in non-smoking middle aged men. We report the fifth case in a 44-year-old non-smoker who presented with hemoptysis and was found to harbour a 3.5 cm intra-bronchial HCCC in association with active pulmonary and mediastinal tuberculosis.

      Method

      A 44-year-old male, non-smoker, presented with 2 episodes of hemoptysis. On imaging, a heterogeneously enhancing FDG-lobulated soft tissue mass was noted within the left lower lobe bronchus with lobar collapse. FDG avid nodular lesions were also seen in the left lower lobe parenchyma with enlarged aortopulmonary window and bilateral hilar lymphnodes. No pleural effusion was seen. There was no evidence of any metastatic lesions. He underwent an endobronchial biopsy from the left main bronchus followed by left lower lobectomy and mediastinal lymphadenectomy. Formalin fixed paraffin embedded tumor sections were subject to special stains for detection of acid fast bacilli and fungi, immunohistochemistry for p40, TTF-1, chromogranin, synaptophysin, epithelial membrane antigen, smooth muscle actin, S100 and smooth muscle myosin heavy chain, and fluorescence-in-situ hybridisation for 22q12 locus using the Vysis EWSR1 dual color, break apart rearrangement probe.

      Result

      Microscopic sections from the endobronchial biopsy revelaled a subepithelial tumor arranged in nests, cords and trabeculae within a densely hyalinised stroma. Tumor cells were monomorphic with clear to eosinophilic cytoplasm and occasional mitoses. Left lower lobectomy specimen showed a grossly circumscribed solid tumor in the wall of the left main bronchus abutting the cartilage and demarcated from adjacent lung parenchyma by a thin fibrous capsule. Tumor cells were immunopositive for p40, epithelial membrane antigen, while were negative for TTF-1, and myoepithelial markers. FISH revealed presence of EWSR1-re-arrangement in tumor cells, confirming the diagnosis of HCCC. Numerous mililary parenchymal and pleural nodules with necrotic caseous material containing acid fast bacilli were also seen, consistent with tuberculosis. Further work-up did not reveal presence of tumor elsewhere ascertaining a primary lung origin. Patient was started on anti-tubercular therapy and adjuvant radiotherapy/chemotherapy was not given. Patient is currently on follow-up

      Conclusion

      From the limited numbers reported, primary pulmonary HCCCs appear to be indolent slow growing neoplasms with an excellent outcome after surgical excision. The differential diagnoses include the commoner squamous cell carcinomas with clear cell change, clear cell adenocarcinomas, mucoepidermoid carcinomas, metastatic clear cell renal cell carcinoma, and myoepithelial neoplasms. Knowledge of its typical histomorphology aided by prudent immunohistochemistry and demonstration of EWSR1 gene rearrangement or more specifically, EWSR1:ATF1 fusion transcripts should lead one towards the correct diagnosis.

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