3rd Annual A Practical Approach to Surgical and Cytopathology Friday, April 7, 2017 Hotel Del Coronado Coronado, California Educational Symposia TABLE OF CONTENTS Friday, April 7, 2017 Diagnostic Approach to Flat and Papillary Urothelial Lesion (Ming Zhou, M.D.) ............................................................ 137 Practical Issues Related to the Endometrium Biopsy II (Marisa Rose Nucci, M.D.) .......................................................... 155 What’s New in the World Health Organization Classification of Lung Tumors (Carol Farver, M.D.) ................................ 185 Thyroid Pathology in the Molecular Era (Jennifer L. Hunt, M.D.) .................................................................................... 199 Pattern Based Approach to Diagnosis and Classification of Renal Tumors (Ming Zhou, M.D.) ...................................... 215 SAVE THE DATES - 2018 Pathology Symposia 137 138 Diagnostic Approach to Papillary and Flat Urothelial Clinical Implications of Pathological Diagnoses on TUR or Biopsy Specimens: Lesions What Diagnoses Pathologists Really Matter? Ming Zhou, MD, PhD Dr. Charles T. Ashworth Professor of Pathology Director, Anatomic Pathology The University of Texas Southwestern Medical Center Dallas, TX [email protected] What Diagnoses Pathologists May Not Need to Struggle with? 2 Pathological Parameters Important Urothelial Carcinoma Staging for Management of Patients with Ta, Tis- non- Urothelial Carcinoma invasive T1- Lamina propria invasion 1. Depth of invasion )tumor stage) T2- muscularis 2. Tumor grade propria invasion 3. Variant histology T3- Perivesical 4. Lymphovascular invasion invasion T4- Invasion into adjacent organs AJCC 2016 3 4 Grading of Papillary Urothelial Clinical Decision Based on Stage and Grade Neoplasms Muscle Radical cystectomy WHO 2016 Invasive UC LN dissection Biopsy/TUR Non-muscle 1. Papilloma Invasive UC 2. Papillary urothelial neoplasm of low malignant potential (PUNLMP) Low risk Intermediate risk High risk 3. Low grade papillary urothelial carcinoma (initial, single, low (recurrent, multifocal (High grade) 4. High grade papillary urothelial carcinoma grade, <3cm) low grade, >3cm) Single installation Multiple installation of of intravesical intravesical chemo BCG chemo 5 (European Society of Medical Oncology) 6 139 Urothelial Carcinoma Variant Histology Clinical Decision Based on Stage and Grade Squamous cell Glandular What is critical? - Invasion of muscularis propria - High grade UC What is not so critical? - Invasion of lamina propria vs Nested Micropapillary non-invasive - Low grade vs PUNLMP 7 8 Urothelial Carcinoma Variant Histology Urothelial Carcinoma Variant Histology Significance What to do? 1. Common, seen in up to ¼ cases - Squamous histology most common 1. Report any component of variant 2. In general, no impact on clinical histology outcomes 2. Diagnosis of “pure variant histology” 3. Associated with aggressive pathological reserved for cases without concomitant features urothelial carcinoma and CIS component - Invasion of muscularis propria 3. Otherwise, diagnose “urothelial - Lymph node metastasis carcinoma with a component of variant - Upstaging histology” 4. Rule out metastasis 9 10 Lymphovascular Invasion (LVI) Diagnostic Criteria for LVI LVI Retraction Significance of LVI - Predicts worse clinical outcomes - LVI in TUR associated with higher risk for upstaging in radical cystectomy (Turker et al BJUI 2012) 30% T<1 TCC with LVI in TUR was Clear endothelial lining No upstaged in radical cystectomy Single/a few Multiple Odds ratio=5.8 Tight cluster with smooth border Rough borders with single cells Fibrin, RBC Cellular debris 11 (Algaba Current Opinion Urol 2006) 12 140 Clinical Implications of Pathological Lymphovascular Invasion in TUR Diagnoses on TUR or Biopsy Specimens: Take home message What to do? Top 4 Diagnoses in TUR/Biopsy Specimens 1. Look for and report it 1. Invasion of muscularis propria 2. Use stringent criteria 2. High grade urothelial carcinoma - Minimum criterion: true endothelial lining 3. Endothelial markers in ambiguous cases 3. Variant histology 4. Lymphovascular invasion 13 14 Case 1 1. 58-year-old paraplegic female 2. Gross hematuria 3. 1.3-cm papillary lesion on cystoscopy 15 17 141 Differential Diagnosis of Papillary Your Diagnosis? Lesions of the Bladder Biopsy artifact Polypoid mucosal folds Inflammatory lesions 1. Urothelial papilloma Proliferative cystitis Polypoid cystitis 2. Low grade papillary urothelial carcinoma Nephrogenic adenoma 3. High grade papillary urothelial carcinoma Papillary urothelial hyperplasia Papillary urothelial neoplasms 4. Papillary nephrogenic adenoma Papilloma Papillary neoplasm of low malignant potential Low grade carcinoma NOT ALL High grade PAPILLARY carcinoma LESIONS ARE Non-urothelialPAPILLARY neoplasms UROTHELIAL Condyloma Villous adenomaCARCINOMA! 19 20 Differential Diagnosis of Papillary Urothelial Lesions Detached Papillary Structures of the Urinary Bladder Are detached papillary structures present? No Yes Morphology of the papillary structures Mucosal folds Papillary hyperplasia Broad Thin Edematous Slender Inflammatory lesion Inflamed Non-inflamed Biopsy artifact Polypoid cystitis Papillary urothelial Inflammatory neoplasm lesion 21 Papillary Urothelial Hyperplasia (Urothelial proliferation of uncertain malignant potential, WHO 2016) Undulating mucosal folds without detached papillary fronds Thicker than normal urothelium; increased vascularity at base 142 Papillary Urothelial Hyperplasia Papillary Urothelial Hyperplasia (Urothelial proliferation of uncertain malignant potential, WHO 2016) De novo diagnosis Significance unknown; suggest clinical follow-up Prior h/o papillary tumors Early recurrence Patient monitored more closely than the general population Cytology similar to normal urothelium 26 Differential Diagnosis of Papillary Urothelial Lesions of the Urinary Bladder Neoplastic Reactive Papillae Papillae Are detached papillary structures present? No Yes Morphology of the papillae Mucosal folds Papillary hyperplasia Broad Thin Edematous Slender Inflammatory lesion Inflamed Non-inflamed Biopsy artifact Inflammatory lesion Papillary urothelial Polypoid cystitis neoplasm 27 28 Fat Neoplastic Papillae Usually a focal finding Case 1: Reactive (papillary nephrogenic adenoma) Thin papillae always neoplastic 143 Correlation of Cystoscopic Impression with Histologic Diagnosis of Biopsy Specimens WHO/International Society of Urological Pathology Classification of Papillary of the Bladder Urothelial Neoplasms (WHO 2016) Cystoscopy correctly discriminates between dysplastic/malignant and benign/reactive 1. Papilloma lesions 2. Papillary neoplasm of low malignant - Sensitivity and specificity: 100% potential (PUNLMP) - Positive and negative predictive value: 100% 3. Papillary carcinoma, low grade When you are not sure if you are looking at a 4. Papillary carcinoma, high grade papillary tumor or reactive lesion, talk to your urologists! Cina et al Hum Pathol 2001 31 32 Grading of Papillary Urothelial Neoplasm Grading of Papillary Urothelial Neoplasms Papilloma PUNLMP Low grade High grade Architecture of Delicate Delicate Fused / branched / delicate 1. Architecture of papillae papillae occasionally fused 2. # of cell layers # of cell layers Normal Any thickness Organization of 3. Disorganization of cells Normal Normal Loss of polarity 4. Nuclear size cells 5. Nuclear shape Nuclear size Normal Slightly 6. Chromatin Nuclear shape Normal Uniform Variation in size and shape 7. Nucleoli Chromatin Fine Fine Hyperchromasia 8. Mitosis Nucleoli Absent Prominent Rare Occasional any Frequent Mitosis Absent basal level any level 33 34 Simplified Approach for Grading Papillary Papilloma Urothelial Tumors Normal urothelium Papilloma on a simple stalk Thick, normal appearing urothelium PUNLMP on a stalk Abnormal urothelium w/ uniformity Low grade Simple papillae covered with on a stalk normal urothelium Abnormal urothelium Not papilloma if: w/o uniformity High grade - Thickened urothelium on a stalk - Fused or branching papillae 35 36 144 PUNLMP Low grade Normal, but thicker mucosa Not PUNLMP if: Appreciable atypia at low power, - Appreciable atypia at low power but uniformity maintained High grade Grading Papillary Urothelial Tumors: Issues 1. Grading represents arbitrary division of a morphological continuum into distinct categories that correlate with clinical behavior - Borderline cases exist 2. More objective parameters are not used in the grading scheme - Mitosis - Immunohistochemistry Uniformity lost (size, shape, spacing) 40 Grading Papillary Urothelial Tumors: FAQ 1. Do you use mitosis to grade? - No - Yes in selective cases (borderline b/w low and high grade) - State the reason in Comment: This tumor is histologically low grade, but has brisk mitosis. Therefore it is graded as high grade. 41 145 Grading Papillary Urothelial Tumors: FAQ Grading Papillary Urothelial Tumors: FAQ 2. Do you use IHC to grade? 3. How do you sign out a low grade tumor with - No focal high grade component? - Too much overlap between tumors of - 5% cutoff (but no hard data on this!) different grades - < 5%: Low grade with focal high grade component - Urologists treat patient like high grade - > 5%: High grade 43 44 Denuded Papillae Denuded Papillae What happened? 1. Majority of cases (79%) associated with high grade 2. Caused by biopsy artifact - 52% with cautery artifact - 48% due to mechanical disruption in anatomically limited areas (ureter, renal pelvis,