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2017 CM08 Mcken 0801 Post.Pdf 3/23/2017 The Longer I Practice Pathology, Disclosure of Relevant The Less I Like Immunohistochemistry: Financial Relationships Genitourinary Pitfalls USCAP requires that all planners (Education Committee) in a position to influence or control the content of CME disclose any relevant financial Arthur Purdy Stout Society relationship WITH COMMERCIAL INTERESTS which they or their Annual Meeting 2017 spouse/partner have, or have had, within the past 12 months, which relates to the content of this educational activity and creates a conflict of interest. Jesse K . McKenney, MD Dr. Jesse K McKenney, MD declares he has no conflict(s) of interest to disclose. Immunohistochemistry Pitfalls in GU General Rules • Morphology driven IHC • Adjunct • No immunostain is infallible • When you need IHC most… it helps the least Immunohistochemistry Pitfalls in GU Immunohistochemistry Pitfalls in GU Antibody Specificity Over Time Immunohistochemical “Pitfalls” in GU Pathology 100% • Diagnosis • Tissue of Origin Specificity • Prostate Cancer Diagnosis • Prostate vs Urothelial • Renal Neoplasia Classification • Urothelial vs Renal • Germ Cell Tumor Classification • Metastatic RCC • Metastatic Germ Cell 0% Time Immunohistochemistry Pitfalls in GU Immunohistochemistry Pitfalls in GU 1 3/23/2017 Diagnosis of Minimal Prostate Cancer •Blind IHC pre-staining of prostate core biopsies is at best inadvisable • Difficult to interpret • Stains are neither 100% sensitive, nor 100% specific • More pitfalls… increases atypical diagnosis rate • Overutilization of resources • In violation of Palmetto Local Coverage Determination (LCD) Immunohistochemistry Pitfalls in GU Immunohistochemistry Pitfalls in GU Benign Prostate: p63 + AMACR Prostate Bx HMWCK + AMACR Immunohistochemistry Pitfalls in GU Immunohistochemistry Pitfalls in GU Prostate Bx Prostate Bx p63 + HMWCK + AMACR Immunohistochemistry Pitfalls in GU Immunohistochemistry Pitfalls in GU 2 3/23/2017 Diagnosis of Minimal Prostate Cancer Partial Atrophy P63+HMWCK+AMACR •Antibodies • Cancer “specific” •AMACR Specificity? •ERG Sensitivity? • Basal cell markers •P63 •HMWCK Interpretation? •CK5/6 Immunohistochemistry Pitfalls in GU Immunohistochemistry Pitfalls in GU AMACR Immunoreactivity Nephrogenic Adenoma Adenosis Partial Atrophy HGPIN Immunohistochemistry Pitfalls in GU Immunohistochemistry Pitfalls in GU Nephrogenic Adenoma AMACR is NOT a AMACR + p63 Prostatic Epithelial Marker •Papillary RCC •Colorectal AdenoCA HMWCK •Ovarian AdenoCA •Breast AdenoCA •Urothelial CA •Etc….. Immunohistochemistry Pitfalls in GU Immunohistochemistry Pitfalls in GU 3 3/23/2017 p63 positive PCA Basal Cell Markers p63+HMWCK+AMACR •Pattern of reactivity? •“Aberrant” nuclear p63 in carcinoma •Non-specific cytoplasmic HMWCK Immunohistochemistry Pitfalls in GU Immunohistochemistry Pitfalls in GU Prostatic Adenocarcinoma with p63 Expression HMWCK and Prostate CA Cytoplasmic blush with some clones Immunohistochemistry Pitfalls in GU Immunohistochemistry Pitfalls in GU Prostatic vs. Urothelial Carcinoma • PSA • p63 • PSAP •HMWCK • CK7/CK20 • PSMA •GATA3 • NKX3.1 • Uroplakin antibodies •ERG • Thrombomodulin • CK7+/CK20+ Immunohistochemistry Pitfalls in GU Immunohistochemistry Pitfalls in GU 4 3/23/2017 CK 7 and CK 20 Profiling: Probability, Not Absolute Immunophenotypic overlap CK7 and CK20 expression increases with increasing grade Immunohistochemistry Pitfalls in GU Immunohistochemistry Pitfalls in GU Poorly Differentiated Prostatic Adenocarcinoma Optimal Panel? NKX3.1 GATA3 1. NKX3.1 and GATA-3 2. PSA and p63 Immunohistochemistry Pitfalls in GU Immunohistochemistry Pitfalls in GU Breast Carcinoma Paraganglioma GATA-3 Immunoreactivity • Urothelial carcinoma • Mesothelium • Lung CA • Breast carcinoma • Skin squamous cell • Gastric CA • Paraganglioma carcinoma • Colorectal CA Lymphocytes or • Subset of T lymphocytes • Chromophobe • Endometrial CA Tumor Cells? RCC • Trophoblasts • Ovarian CA • Skin adnexal tumors • Squamous cell CA: cervix, larynx, lung • Parathyroid • Renal oncocytoma • Other RCC • Synovial sarcoma Immunohistochemistry Pitfalls in GU Immunohistochemistry Pitfalls in GU 5 3/23/2017 Urinary Bladder Bx: Secondary Involvement of Cervical Squamous Cell Carcinoma GATA3 HPV CISH p16 Immunohistochemistry Pitfalls in GU Immunohistochemistry Pitfalls in GU GATA3 Reactivity in Renal Neoplasia RCC vs. Urothelial Carcinoma (renal pelvis) Abstract # 975 GATA-3 in CC-P RCC • PAX-8 • p63 •HMWCK • CK7/CK20 •GATA3 • Uroplakin antibodies • Thrombomodulin Immunohistochemistry Pitfalls in GU Immunohistochemistry Pitfalls in GU Poorly Differentiated Carcinoma with Destructive, Permeative Growth PAX8 in Upper Tract Urothelial Carcinoma Diff Dx is key!! Urothelial •15-30% express PAX-8!! Urothelial •May be strong and diffuse Urothelial Metastasis HLRCC CDC Immunohistochemistry Pitfalls in GU Immunohistochemistry Pitfalls in GU 6 3/23/2017 Urothelial Carcinoma: Renal Pelvis Immunophenotypic Possibilities IHC Favored: Additional Phenotype Renal vs Urothelial inspection and PAX8+/GATA3-/p63- Renal more sections of PAX8+/GATA3+/p63- ? the renal pelvis PAX8+/GATA3+/p63+ Urothelial may be more PAX8-/GATA3-/p63- ? helpful than PAX8-/GATA3+/p63- Urothelial IHC!! PAX8-/GATA3-/p63+ Urothelial Immunohistochemistry Pitfalls in GU Immunohistochemistry Pitfalls in GU Urothelial Carcinoma of Renal Pelvis PAX-8 CD10 p63 CD10 Immunohistochemistry Pitfalls in GU Immunohistochemistry Pitfalls in GU IHC! IHC? Diagnosis of Angiomyolipoma/PEComa •Differential Diagnosis: • Renal Cell Carcinoma • Melanoma • Liposarcoma Immunohistochemistry Pitfalls in GU Immunohistochemistry Pitfalls in GU 7 3/23/2017 Angiomyolipoma IHC in Angiomyolipoma: Negative or Focal? Sclerosing Epithelioid Lipid-rich HMB45 SMA PAX-8 Negative HMB45 MART-1 Cathepsin-K Immunohistochemistry Pitfalls in GU Immunohistochemistry Pitfalls in GU Lipid-Predominant Angiomyolipoma Angiomyolipoma/PEComa • Melanocytic Markers • Epithelial markers •HMB45 • Cytokeratins • S-100 protein •PAX-8 • Melan-A NOT amplified • Cathepsin-K • Smooth Muscle Markers What is positive? • Smooth muscle actin Immunohistochemistry Pitfalls in GU Immunohistochemistry Pitfalls in GU Diagnosis of Metastatic RCC •Markers of purported renal specificity • PAX-8 • PAX-2 • CD10 • RCCma Immunohistochemistry Pitfalls in GU Immunohistochemistry Pitfalls in GU 8 3/23/2017 Diagnosis of Metastatic RCC Diagnosis of Metastatic RCC •PAX-8 Expression Expected (Antibody Specific) PAX-8 • Gynecologic •PAX-8 Sensitivity •Thyroid • Clear Cell 95% • Upper Tract Urothelial (15-30%)!!!! • Papillary 95% • Pancreatic Neuroendocrine (polyclonal Ab) • Chromophobe 85% • Seminal Vesicle • Other??? 90% • Thymic Epithelium/Thymoma • Merkel Cell Carcinoma Immunohistochemistry Pitfalls in GU Immunohistochemistry Pitfalls in GU Diagnosis of Metastatic RCC: General Rules Biopsy: soft tissue mass PAX-8 Patient also has 5 cm renal mass! • Renal mass or history of RCC? • Does it look like RCC histologically? • Known mimics in the anatomic site biopsied? • Know sensitivity and specificity of markers used Immunohistochemistry Pitfalls in GU Immunohistochemistry Pitfalls in GU GATA-3 CK20 Biopsy: Supraclavicular lymph node Patient has remote history of “Clear Cell RCC”! PAX-8 Immunohistochemistry Pitfalls in GU Immunohistochemistry Pitfalls in GU 9 3/23/2017 Original Nephrectomy Biopsy: Retroperitoneal lymph node Patient with history of “Clear Cell RCC”! PAX-5 PAX-8 CD20 Immunohistochemistry Pitfalls in GU Immunohistochemistry Pitfalls in GU RCC-like Carcinoma of Nasal Cavity Clear Cell Sarcoma of Soft Parts Notochord Neoplasm Differential Diagnosis of Clear Cell Tumors in a Given Anatomic Location? True Peripheral Chordomas Exist!! Immunohistochemistry Pitfalls in GU Immunohistochemistry Pitfalls in GU Sex Cord Stromal (Sertoli) Diagnosis of Testicular Germ Cell Tumors SF-1 Germ cell Sex Cord Stromal OCT3/4 Inhibin SALL4 Calretinin PLAP SF-1 FOXL2 Immunohistochemistry Pitfalls in GU Immunohistochemistry Pitfalls in GU 10 3/23/2017 Germ Cell Tumor (Seminoma) SF-1PLAP Subtyping of Testicular Germ Cell Tumors Seminoma: OCT3/4, PLAP, cKIT Embryonal: OCT3/4, CD30 OCT3/4 Yolk Sac: Glypican3, AFP, GATA3 ChorioCA: BhCG, GATA3 Immunohistochemistry Pitfalls in GU Immunohistochemistry Pitfalls in GU SALL4 Immunoreactivity OCT3/4 Immunoreactivity • “Pan” germ cell • Hepatocellular carcinoma • Mammary carcinoma • Seminoma • B cell lymphomas • Serous carcinoma (GYN) • Colorectal adenocarcinoma • Embryonal carcinoma • Acute myeloid leukemias • Malignant rhabdoid tumor • Prostatic adenocarcinoma • Renal medullary carcinoma • Gastric adenocarcinoma • Melanoma • Urothelial carcinoma • DSRCT • Epithelioid sarcoma • Rhabdomyosarcoma • B cell lymphoma (DLBCL) • Leukemia Immunohistochemistry Pitfalls in GU Immunohistochemistry Pitfalls in GU Seminoma vs Lymphoma? Primitive Carcinomas and SALL4: e.g., Esophageal Seminoma DLBCL Adenocarcinoma with Fetal Gut Differentiation Immunohistochemistry Pitfalls in GU Immunohistochemistry Pitfalls in GU 11 3/23/2017 Metastatic Tumor in Liver: Esophageal mass SALL4 Summary • Diagnosis • Tissue of Origin • Prostate Cancer Diagnosis • Prostate vs Urothelial • Renal Neoplasia Classification • Urothelial vs Renal • Germ Cell Tumor Classification • Metastatic RCC • Metastatic Germ Cell Immunohistochemistry Pitfalls in GU Immunohistochemistry Pitfalls in GU Immunohistochemistry Pitfalls in GU 12.
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