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

28.01.2021 4

28.01.2021 5

28.01.2021 6

28.01.2021 7

28.01.2021 8

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 %

28.01.2021 11

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

28.01.202112

SMARCB1 deficient tumors

Arnaud et al. Cancer letters 2018

28.01.2021 14

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 !!

00.00.2019Verfasser | Dokumenten-Name | 16

28.01.2021 17

Biopsy: papillary pattern

28.01.2021 18

Biopsy Pleural effusion

28.01.2021 19

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

28.01.202123

AcknowledgementsDr. Francesca SaroPD Dr. Sylvia HöllerDr. Jan Rüschoff

00.00.2019Verfasser | Dokumenten-Name |24

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