Case of the month. Dr Charles Bénière, Institut universitaire de pathologie, Lausanne
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1 Case of the month Dr Charles Bénière, Institut universitaire de pathologie, Lausanne
2 Clinical history 39 years old male, smoker (19 pack-year) without any prior medical record nor professional exposure. Presenting with a left flank pain and dyspnea for two weeks
3 Imaging A chest X-ray and a thoracic CT-scan (not available) show a severe left pleural effusion, left lung atelectasia and enlarged mediastinal lymphnodes Clinical suspicion for lymphoma, lung neoplasm
4 Pleural effusion cytology A chest drain was installed with a removal of 6 liters of liquid. Cytologic examination performed with presence of atypical cells. Multinucleated cells with enlarged nuclei, prominent nucleoli, isolated or grouped
5 Immunocytochemistry Cells are positive for synaptophysin and EMA, negative for lymphoid markers, keratins and melanocytic markers. Synaptophysin
6 Cytologic diagnosis Poorly differentiated malignant tumor possibly : sarcomatoid carcinoma large cell neuroendocrine carcinoma
7 Pleural biopsy Patient was then adressed to our institution and a left pleural biopsy was performed with frozen section analysis. Touch-prep of the frozen section Multinucleated atypical cells Large nucleus and nucleoli Mitosis Apoptosis
8 Touch-prep of the frozen section Rhabdoid cell
9 Poorly cohesive sheets Large atypical cells, with enlarged nuclei and vesicular chromatin, paranuclear eosinophilic cytoplasmic inclusion, Numerous mitosis and apoptosis.
10 Immunohistochemistry on biopsy Synaptophysin and CD34 positivity Partial SALL4 expression with rare cells expressing EMA, calretinin, Keratin. TTF1 negative INI1 expression retained. CD34 SYN SALL4
11 Definitive diagnosis A diagnosis of SMARCA4 deficient thoracic sarcoma (SMARCA4-DTS) was suggested Confirmed by immunohistochemistry (loss of SMARCA4 and SMARCA2 expression and preservation of SOX2 expression). (Institut Bergonié, Bordeaux, France)
12 SMARCA4-deficient thoracic sarcoma Rare and recently described disease (Le Loarer, 2015) poorly differentiated malignant tumor with rhabdoid features. Clinical presentation young male smoking patients with rapidly growing bulky thoracic mass (pleural, lung and/or mediastinal)
13 Median overall survival is 7 months and death is secondary to local progression (mediastinal compression).
14 SMARCA4 (Brg1) part of the SWI/SNF complex involved in chromatin remodeling. Expression also lost in small cell carcinoma of the ovary, hypercalcemic type. Other members of the family include SMARCB1 (INI1), involved in malignant rhabdoid tumors and epithelioid sarcoma.
15 Immunophenotype Positive for CD34, SALL4, SOX2. INI1 expression is retained SMARCA4 and SMARCA2 expression are lost.
16 Differential diagnosis Some differential diagnosis include : Proximal epithelioid sarcoma, but INI1 expression is lost and SMARCA2 expression retained SMARCA4 deficient lung carcinoma but SOX2 expression is lost and CD34 expression uncommon. Malignant rhabdoid tumors are confined to infants and show germline mutations.
17 In our case, diffuse synaptophysin expression with focal chromogranin A possible pitfall with diagnosis of neuroendocrine carcinoma. Focal calretinin, keratin and GATA3 possible pitfall with diagnosis of mesothelioma
18 Take-home message Knowledge of this rare and new entity is key in rendering the correct diagnosis CD34 is readily available in most pathology laboratories and should be performed in the occurrence of a thoracic mass in a young patient. Secondary consultation with testing for SMARCA4, SMARCA2 and SOX2 will confirm the diagnosis
19 References Le Loarer F, Watson S, Pierron G, de Montpreville VT, Ballet S, Firmin N, et al. SMARCA4 inactivation defines a group of undifferentiated thoracic malignancies transcriptionally related to BAF-deficient sarcomas. Nat Genet Oct;47(10): Yoshida A, Kobayashi E, Kubo T, Kodaira M, Motoi T, Motoi N, et al. Clinicopathological and molecular characterization of SMARCA4- deficient thoracic sarcomas with comparison to potentially related entities. Mod Pathol Off J U S Can Acad Pathol Inc Jun;30(6): Sauter JL, Graham RP, Larsen BT, Jenkins SM, Roden AC, Boland JM. SMARCA4-deficient thoracic sarcoma: a distinctive clinicopathological entity with undifferentiated rhabdoid morphology and aggressive behavior. Mod Pathol Off J U S Can Acad Pathol Inc Jun 23;
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