Post on 31-Jan-2021
PD Dr. med. Peter Karl Bode
Case 8
Slide Seminar of the Swiss Society of Pathology and the IAP Swiss SectionCyto-histo correlation in daily practice / 30. January 2021
Clinical Data
56 yo maleUnclear pleural effusion. Malignant cells? Inflammation?
Macroscopy: 1000 ml red, turbid liquid
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Cell Block
Top Differential Diagnosis (submitted diagnosis)
Malignant 95 %
1. (Adeno-) Carcinoma 29 % EPCAM, TTF1, CDX2, Cytokeratins negative2. Mesothelioma 22 % Calretinin, Cytokeratins negative3. Melanoma 17 % S100, SOX10 negative4. Lymphoma 10 % CD45, CD5, CD20, HHV8
Differential Diagnosis
1. (Adeno-) Carcinoma2. Mesothelioma3. Melanoma4. Lymphoma5. Other neoplasms (with epithelioid morphology)
3 %
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Loss of INI1
Alterations of BAF (SWI/SNF) complex in cancer
Terminology: SWItch/Sucrose Non-Fermenting (SWI/SNF) complexBRG1-Associated Factor (BAF) complexFunction:ATP-dependent remodeler of nucleosomes(up to 10 000 binding sites over the entire genome)Affects many genes and pathwaysRelevance:Mutations of SWI/SNF subunits > non-functional proteinFew tumors with pathognomonic alterationsBUT: also present at low frequencies in other tumors
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SMARCB1 deficient tumors
Arnaud et al. Cancer letters 2018
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INI1
Presented case 27 yo male with metastasized epithelioid sarcoma
mSWI/SNF subunit genes are mutated in various human cancers
Shain et al. PLOS ONE 2013Kadoch et al. Nature Genetics 2013
Back to the patient
56 yo maleUnclear pleural effusion
Additional informationProgressive dyspnea40 packyearsCar painterHighly suspicious for pleural mesothelioma !!
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Biopsy: papillary pattern
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Biopsy Pleural effusion
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INI1: Biopsy INI1: Pleural effusion
Bott et al Nature Genetics 2011
SMARCB1 mutations in malignant mesothelioma
Verfasser | Dokumenten-Name |
Kimura et al.Autopsy Case
Our Case
WT1BUT other markers negative:
CalretininCytokeratins (incl CK5/6, CK7)D2-40BAP1 expression retained
CD34 negativeERG negative
Molecular Analysis?
SMARCB1 mutation subtypeCDKN2A deletion?P16 FISH?
Patient died 1 month after diagnosisAutopsy refused
Conclusion
Final Diagnosis:INI1 deficient neoplasm with pleural manifestation
Take Home Messages- INI1 pathognomonic for epithelioid sarcoma and malignant rhabdoid tumor- mSWI/SNF subunit gene mutation may occur in various human cancers
(e.g. INI1 deficient pleural mesothelioma)- Never forget the clinical and cyto-/histological correlation
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AcknowledgementsDr. Francesca SaroPD Dr. Sylvia HöllerDr. Jan Rüschoff
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Thank you for yourattention!
Case 8Clinical DataFoliennummer 3Foliennummer 4Foliennummer 5Foliennummer 6Foliennummer 7Foliennummer 8Top Differential Diagnosis (submitted diagnosis)Differential DiagnosisFoliennummer 11Alterations of BAF (SWI/SNF) complex in cancerSMARCB1 deficient tumors Foliennummer 14mSWI/SNF subunit genes are mutated in various human cancers Back to the patientFoliennummer 17Foliennummer 18Foliennummer 19Foliennummer 20Foliennummer 21Foliennummer 22ConclusionFoliennummer 24