Seattle. Case Presentations. Case year old female with a history of breast cancer 12 years ago. Now presents with a pleural effusion.

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1 Seattle Montreal IAP September 2006 Case Presentations Allen M. Gown, M.D. Medical Director and Chief Pathologist PhenoPath Laboratories Clinical Professor of Pathology University of British Columbia Case 1 76 year old female with a history of breast cancer 12 years ago. Now presents with a pleural effusion.

2 Case 1 DIFFERENTIAL DIAGNOSES Carcinoma (lung primary or metastatic) Mesothelioma Other (malignant vascular tumor) Calretinin WT-1 WT-1 MOC-31

3 Bg8 Bg8 Case 1 IHC Results Antibodies to: Results: Lewis Y Ag [Bg8] Tx Glycoprotein [MOC31] Calretinin WT-1 *Cytoplasmic signal Positive* Positive* Red Flag or Red Herring? Lewis Y Antigen Tonga Blood group antigen Expressed on both epithelial, endothelial and red blood cells

4 WT-1 Antibody clone from DAKOCytomation cross reacts with endothelial antigen (cytoplasmic) The Art of Immunohistochemistry Like people, all antibodies have individual personalities Like people, all antibodies need to be handled individually to cater to these unique properties CK (OSCAR) OSCAR OSCAR Vimentin

5 CD34 CD31 Case 1 IHC Results Antibodies to: Results: vwf Cytokeratins [OSCAR] CD34 CD31 vwf Vimentin Positive Positive Positive Case 1 ANGIOSARCOMA, METASTATIC FROM BREAST Histologic Mimics of Mesothelioma Lung adenocarcinoma Angiosarcoma of pleura Ovarian surface epithelial carcinoma

6 Am J Surg Pathol: 20:1431-9, 1996 Pseusomesotheliomatous Vascular Tumors of Pleura 14 cases Lin T-Y, et al., Am J Surg Pathol 20:1431-9, 1996) Diffuse involvement of pleural, peritoneal, or pericardial surfaces Age range: (mean, 52) Growth patterns: diffuse, sheet-like, tubulopapillary, spindle Differential diagnosis: mesothelioma, leiomyosarcoma Case 2 Intracranial tumor in a 40 year old male. No known tumor elsewhere.

7 Case 2 DIFFERENTIAL DIAGNOSES Metastatic carcinoma Malignant glioma Paraganglioma Rhabdomyosarcoma Epithelioid angiosarcoma?other OSCAR GFAP S100

8 Desmin CD34 CD31 Vimentin Case 2 IHC Results Antibodies to: Results: Cytokeratin GFAP CD31, CD34 Desmin Vimentin S100 Chromogranin A Case 2 DIFFERENTIAL DIAGNOSES Metastatic carcinoma Malignant glioma Paraganglioma Rhabdomyosarcoma Epithelioid angiosarcoma?other

9 Tumors for Everything Lymphomas, especially plasmablastic variants Seminoma Alveolar soft part sarcoma Alveolar Soft Part Sarcoma Rare tumor occurring principally in young adults and adolescents Most commonly arises in fascial planes of lower extremities, but can be extraskeletal First described (Christopherson, et al) in 1952 Recent review by Ordonez (Adv Anat Pathol 6:125-39,1999) Suggestions of Histogenesis Paraganglioma Schwann Cell Secretory (?epithelial) cell Skeletal muscle Myogenous Differentiation? Wang, NP. Mod Pathol 9: , cases of ASPS No cases showed nuclear signal with antibodies to myogenin, myod1 ASPS not related to skeletal muscle or rhabdomyosarcoma Genogenic Immunohistochemistry The application of protein-based immunohistochemistry to identify changes at the gene level Common Genetic Alterations in Cancer Gene deletion Gene Loss of point protein mutation expression Gene silencing (e.g., by methylation) Chromosomal Novel fusion gene translocation product Gene Protein amplification overexpression

10 Common Genetic Alterations in Cancer Oncogene 20:48-57, 2001 Chromosomal Novel fusion gene translocation product t(2;5) ALCL ALK PNET/ES t(11;22) FLI1 t(x;17) ASPS TFE3 Am J Surg Pathol 27: (June 2003) Argani P et al., Am J Surg Pathol 27:750-61, 2003 Alveolar soft part sarcoma characterized by der(17)t(x;17)(p11.2;q25) translocation Results in novel fusion gene product of ASPL-TFE3 Subset of renal cell carcinomas in children and young adults have t(x;1) (p11.2;q21) also involving TFE3 (PRCC- TFE3) Subset of renal cell carcinomas also have t(x;17)(p11.2;q25) resulting in ASPL-TFE3 Argani P et al., Am J Surg Pathol 27:750-61, 2003 Argani P et al., Am J Surg Pathol 27:750-61, 2003 TFE3 not expressed in normal tissues Translocation results in C terminal portion of TFE3 overexpressed Antibodies to (C terminal portion of) TFE3 act as surrogate for translocation involving Xp11.2

11 Argani P et al., Am J Surg Pathol 27:750-61, 2003 Nuclear expression of TFE3 a highly sensitive and specific assay for neoplasms bearing TFE3 gene fusions Immunohistochemistry for TFE3 can identify alveolar soft part sarcoma as well as a subset of renal cell carcinomas TFE3 Immunohistochemistry ASPS RCC with t(x;17)(p11.2;q25). from Argani P et al., Am J Surg Pathol 27:750-61, 2003 And now back to the case... TFE3 TFE3 Case 2 Final Diagnosis METASTATIC ALVEOLAR SOFT PART SARCOMA

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