Urinary Bladder: WHO Classification and AJCC Staging Update 2017

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1 Urinary Bladder: WHO Classification and AJCC Staging Update 2017 Houston Society of Clinical Pathologists 58 th Annual Spring Symposium Houston, TX April 8, 2017 Jesse K. McKenney, MD

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4 Classification Overview Early papillary lesions Variants Plasmacytoid Nested Microcystic Micropapillary Staging scenarios pt1 Urethra Diverticula

5 Classification of Urothelial Neoplasia

6 Bladder Neoplasia: WHO 2016 Papillary Papilloma PUNLMP Low Grade CA High Grade CA Flat Lesions with Atypia Reactive Atypia Atypia UMP/Dysplasia Carcinoma in situ High Grade CA

7 Bladder Neoplasia: WHO 2016 Flat Hyperplasia? Papillary Hyperplasia (Atypia)? Early / Incipient Lesions?

8 Urothelial Proliferation of Uncertain Malignant Potential

9 Urothelial Proliferation of Uncertain Malignant Potential

10 Urothelial Proliferation of Uncertain Malignant Potential

11 Urothelial Proliferation of Uncertain Malignant Potential

12 NOT Urothelial Proliferation of Uncertain Malignant Potential

13 NOT Urothelial Proliferation of Uncertain Malignant Potential

14 Variants of Invasive Urothelial Carcinoma

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17 Plasmacytoid Carcinoma Recognition Inflammatory cells Gastric and breast cancer Prognosis Poor response to chemotherapy Unusual patterns of disease failure

18 Plasmacytoid Carcinoma

19 Plasmacytoid Carcinoma

20 Plasmacytoid Carcinoma

21 Plasmacytoid Carcinoma

22 Plasmacytoid Carcinoma Cytokeratin AE1/3

23 Plasmacytoid Rhabdoid

24 Plasmacytoid Carcinoma: Presence of Signet Ring-Like Cells

25 Plasmacytoid Carcinoma Signet-ring Adenocarcinoma

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27 Saphir O. Am J Pathol 1955; 31:223-31

28 Saphir O. Am J Pathol 1955; 31:223-31

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30 Plasmacytoid Carcinoma in Peri-Ureteral Tissue Plasmacytoid Carcinoma: Presence of Signet Ring-Like Cells

31 WHO 2016 Criteria Plasmacytoid Carcinoma NO extracellular mucin Similar to diffuse type gastric CA or lobular breast CA Mucinous AdenoCA with Signet-Ring Cells Extracellular mucin Similar to mucinous adenoca of colon

32 Saphir O. Am J Pathol 1955; 31:223-31

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34 Peritoneal spread common Bowel serosa and mesentery Ovary Peritoneal carcinomatosis Malignant effusions (pleural)

35 Plasmacytoid Carcinoma: Peritoneal Spread

36 Plasmacytoid Carcinoma in Peri-Ureteral Tissue

37 Plasmacytoid Carcinoma in Peri-Ureteral Tissue

38 Plasmacytoid Carcinoma in Peri-Prostatic Tissue

39 Plasmacytoid Carcinoma in Lymph Node Cytokeratin AE1/3

40 Plasmacytoid Carcinoma Differential Diagnosis Metastatic carcinomas to bladder? Lobular breast Diffuse type gastric Hematopoietic

41 Urothelial Carcinoma with Plasmacytoid Features GATA-3 Lobular breast CA: GATA-3

42 GATA-3 Positive Urothelial CA Breast CA T-lymphocyte subset Salivary gland CA Paraganglioma Parathyroid Subset of squamous cell CA Prostatic basal cells (patchy) GYN tract urothelial neoplasia

43 Gastric Carcinoma Met to Bladder Stomach Urinary bladder

44 Immunohistochemical Differential Mammaglobin Type GATA3 S100p CK7 CK20 ER PR CD138 P63 Urothelial Gastric Breast

45 Invasive urothelial carcinomas. Deceptively benign and Under-diagnosed

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47 Invasive Urothelial Carcinoma: Nested Variant

48 Invasive Urothelial Carcinoma: Nested Variant

49 Invasive Urothelial Carcinoma: Nested Variant

50 Invasive Urothelial Carcinoma: Nested Variant

51 Invasive Urothelial Carcinoma: Nested Variant

52 Invasive Urothelial Carcinoma: Nested Variant Cytology

53 Invasive Florid Von urothelial Brunn s carcinoma, nest proliferation nested variant?

54 Nested Variant with Lymph Node Met

55 Invasive Urothelial Carcinoma: Large Nested

56 Invasive Urothelial Carcinoma: Large Nested

57 Invasive Urothelial Carcinoma: Large Nested

58 Invasive Urothelial Carcinoma: Large Nested

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60 Invasive Urothelial Carcinoma: Microcystic Variant

61 Invasive Urothelial Carcinoma: Microcystic Variant

62 Invasive Urothelial Carcinoma: Microcystic Variant

63 Invasive Urothelial Carcinoma: Microcystic Variant

64 Invasive Urothelial Carcinoma: Microcystic Variant

65 Invasive Urothelial Carcinoma: Microcystic Variant

66 Invasive Urothelial Carcinoma: Microcystic Variant

67 Invasive Urothelial Carcinoma: Microcystic Variant

68 Deceptively Bland Carcinomas: Nested and Microcystic Prognosis Stage-for-stage behaves as aggressively as a high-grade carcinoma

69 Deceptively Bland Carcinomas Differential Diagnosis Nephrogenic adenoma von Brunn nests Inverted/Endophytic Urothelial Neoplasia

70 Deceptively Bland Carcinoma Nested Benign Mimics of Carcinoma Von Brunn s nests (ureter; renal pelvis) Urothelium Lamina Propria Muscularis Propria Tubular Microcystic Nephrogenic adenoma Von Brunn s nests (bladder)

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72 Slender, delicate filiform processes or tight papillary clusters reminiscent of papillary serous carcinoma of ovary

73 Bladder Micropapillary CA Ovarian Serous Carcinoma

74 Invasive Micropapillary Carcinoma in Muscularis Propria

75 Invasive Micropapillary Carcinoma with LVI

76 Lymph Node Metastasis

77 Therapeutic Significance: On TURBT IF: pt1 (no invasion of muscularis propria) AND: micropapillary morphology THEN: suggest re-staging biopsies

78 J Urol 2006; 175:

79 Micropapillary Carcinoma: Cystectomy for pta and pt1 Disease? Pathologic assessment Extent of micropapillary component? Definition of non-invasive micropapillary? Definition of invasive micropapillary? Kamat, Gee, Dinney et al. J Urol 2006;175: Kamat, Dinney, Gee et al. Cancer 2007;110:62-67.

80 When does typical urothelial carcinoma become micropapillary?

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82 Recommended Restricted Criteria Major feature 1 Multiple small nests in same lacunar space Frequently seen features 1 Epithelial ring forms 2 Back to back lacunae 3 Peripheral nuclei 4 Cytoplasmic vacuolization

83 Features Suggesting NOT Micropapillary Major features 1 Large nests (> 5 cells across narrowest width) 2 Epithelial confluence and branching

84 Back-to-Back Lacunae Multiple Nests in Same Lacunar Space

85 Epithelial Ring Forms Back-to-Back Lacunae

86 Intracytoplasmic Vacuoles

87 NOT Classic Micropapillary

88 NOT Classic Micropapillary

89 NOT Classic Micropapillary

90 Not Classic Micropapillary, But What Is It?

91 Urothelial CA with Distinct Mixed Features: Quantitative Problem 99% 1%

92 Even small foci of micropapillary differentiation portend a poor prognosis: report %

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94 Micropapillary 96% Usual UC with Retrxn 63% MUC-1 33% 13% CA % 8% Her2/neu Sangoi et al. Mod Pathol 2009; 22:660

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96 Non-invasive Micropapillary Carcinoma (pta) Included in studies proposing immediate surgery Criteria problems Qualitative threshold Definition? Quantitative threshold Glandular (villoglandular) differentiation

97 Non-Invasive Papillary Urothelial Carcinoma, Micropapillary

98 Non-Invasive Papillary Urothelial Carcinoma Does Cribriform = Micropapillary?

99 Non-Invasive Papillary Urothelial Carcinoma Micropapillary or Villoglandular/Glandular?

100 Clinical outcome is similar to other noninvasive high-grade urothelial carcinomas

101 WHO 2016 If these processes (micropapillary) are only present in the non-invasive component, the tumor should NOT be classified as micropapillary carcinoma

102 Micropapillary Reporting Recommendation 1. Use restrictive criteria for invasive micropapillary carcinoma 2. Report presence of ANY invasive micropapillary component and give percentage 3. Per WHO: do NOT diagnosis pta carcinoma using micropapillary term

103 BLADDER STAGING

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105 Substaging in TUR pt1 Probably important! Not standardized Not recommended by consensus groups

106 Invasion of Prostatic Stroma: Which Route?

107 Invasion of Prostatic Stroma (pt4) pt2 pt3 Bladder pt4 Urethral pt2 Prostate

108 Staging in Bladder Diverticula

109 Classification Summary Early papillary lesions Variants Plasmacytoid Nested Microcystic Micropapillary Staging scenarios pt1 Urethra Diverticula

110 Urinary Bladder: WHO Classification and AJCC Staging Update 2017 Jesse K. McKenney, MD

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