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
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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
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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…..
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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
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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
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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
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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
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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
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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
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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
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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
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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
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