Renal Tumors with Eosinophilic Cytoplasm: 2013 Classification. Jesse K. McKenney, MD Associate Head, Surgical Pathology
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1 Renal Tumors with Eosinophilic Cytoplasm: 2013 Classification Jesse K. McKenney, MD Associate Head, Surgical Pathology
2 Renal Epithelial Neoplasia History 1981: WHO Classification of Renal Neoplasms 1. Adenoma 2. Carcinoma (RCC or other)
3 Renal Cell Carcinoma: Classification 1997
4 Renal Cell Carcinoma: Classification 1997
5 AFIP, Third Series, Fascicle 11 (1994)
6 Renal Neoplasms with Eosinophilic Cytoplasm 1997 Renal cell carcinoma Clear cell, eosinophilic Chromophobe Papillary, eosinophilic Collecting duct Medullary Unclassified Misc Oncocytoma AML
7 Renal Neoplasms with Eosinophilic Cytoplasm 2012 Renal cell carcinoma subtypes Clear cell, eosinophilic Xp11/TFE3 Papillary, eosinophilic TFEB Chromophobe ACKD associated Collecting duct Birt-Hogg-Dubé Medullary Unclassified HLRCC Tubulocystic SDHB
8 Renal Neoplasms with Eosinophilic Cytoplasm 1. Chromophobe vs. Oncocytoma 2. Tumors Resembling Onco/Chromo 3. Eosinophilic, but not Onco/Chromo
9 1. Chromophobe RCC vs. Oncocytoma
10 Chromophobe RCC: Prototypical Features
11 Chromophobe RCC (Eosinophilic): Nuclear Features Tickoo et al. Am J Clin Pathol 1998;110(6):
12 Chromophobe RCC (Classic-Plant Cell Type)
13 Chromophobe RCC: (Classic-Plant Cell Type)
14 Chromophobe RCC: Morphologic Heterogeneity
15 Chromophobe RCC: Clear Broad Cell RCC alveolar architecture
16 Chromophobe RCC: Broad alveolar architecture
17 Chromophobe RCC: Small nested pattern
18 Chromophobe RCC: Mixed eosinophilic/classic
19 Chromophobe RCC: Oncocytoma-like Foci
20 Chromophobe RCC: Adenomatous
21 Chromophobe RCC: Adenomatous
22 Chromophobe RCC: Microcystic/Cribriform
23 Chromophobe RCC: Halos are Sufficient
24 Metastatic Chromophobe
25 Oncocytoma
26 Oncocytoma
27 Oncocytoma
28 Oncocytoma
29 Oncocytoma
30 Oncocytoma
31 Oncocytoma with Atypical Features Davis CJ et al. J Urogenital Pathol 1991; 1:41-52 Amin MB et al. Am J Surg Pathol 1997; 21:1-12 Perez-Ordonez et al. Am J Surg Pathol 1997; 21:871-83
32 Oncocytoma with Extrarenal Invasion
33 Oncocytoma with Extrarenal Invasion
34 Oncocytoma with Extrarenal Invasion
35 Oncocytoma with Intravascular Tumor
36 Oncocytoma
37 Oncocytoma with Degenerative Atypia
38 Prototypical Chromophobe RCC vs. Prototypical Oncocytoma
39 Oncocytic Gray Zone Tumors
40 Gray Zone Oncocytoma Chromophobe
41 RCC, Unclassified Chromophobe Oncocytoma
42 General classification strategies Managerial/Therapeutic Prognostic Follow-up Response to therapy Adjuvant therapy (in the future?) Biologic gold standard Cytogenetic abnormality Molecular abnormality Antigen expression
43
44 Adjunctive Studies in the Classification of Renal Neoplasia Immunohistochemistry Electron Microscopy Conventional cytogenetics FISH Gene expression array SNP array Sequencing mirna
45 Oncocytoma?
46 How Much Nuclear Variation is Allowable?
47 How Much Nuclear Variation is Allowable?
48 How Much Nuclear Variation is Allowable?
49 The Median Assumption Specific genetic Cytokeratin alteration 7 by? Oncocytoma Chromophobe Clinical Outcome Response to Therapy
50 Gray Zone Cases Kidney, left, radical nephrectomy: Oncocytic renal neoplasm of low malignant potential Low grade oncocytic renal neoplasm Renal cell carcinoma, low grade oncocytic type
51 Diagnosis?
52 Diagnosis?
53 Diagnosis?
54 Diagnosis?
55 CK7 Diagnosis?
56 Diagnosis Kidney, left, radical nephrectomy: Low grade oncocytic renal neoplasm (see comment)
57 Follow-up Liver Biopsy
58 Unclassified RCC
59 Unclassified RCC
60 Unclassified RCC
61 2. Other Renal Tumors That Resemble Oncocytoma and Chromophobe
62 Clear cell RCC
63 Clear Cell RCC
64 Clear RCC with cytoplasmic eosinophilia CAIX +, CD10+, CK7-
65 Clear Cell RCC: Rhabdoid
66 Birt-Hogg-Dubé Associated RCC
67 Birt-Hogg-Dubé Syndrome Autosomal dominant with incomplete penetrance (BHD gene 17p12-q11.2) Renal tumors Cutaneous lesions Fibrofolliculoma Trichodiscoma Spontaneous pneumothorax Colorectal neoplasia Medullary thyroid carcinoma Lipomas
68 RCC Associated with Birt-Hogg-Dubé
69 RCC Associated with Birt-Hogg-Dubé HOT
70 RCC Associated with Birt-Hogg-Dubé
71 Birt-Hogg-Dubé Associated Oncocytosis
72 Birt-Hogg-Dubé Associated Oncocytosis
73 Birt-Hogg-Dubé Associated Renal Neoplasm
74 Birt-Hogg-Dubé Associated Renal Neoplasm
75 Birt-Hogg-Dubé Syndrome: Recognition Multiple oncocytic renal tumors Hybrid forms Scattered clear cells or nodules within tumors Oncocytosis History of multiple chromophobe RCC Associated skin lesions Present earlier- 30 s
76 Tubulocystic RCC
77
78 Tubulocystic ********** Carcinoma
79 Tubulocystic ********** Carcinoma
80 Tubulocystic Carcinoma
81 Tubulocystic ********** Carcinoma
82 Epithelioid Angiomyolipoma
83 Angiomyolipoma
84 Angiomyolipoma: Classic
85 Epithelioid Angiomyolipoma Actin +, HMB-45 +, CK - PAX8 -, CD117 -
86 Atypical Epithelioid Angiomyolipoma
87 Atypical Epithelioid Angiomyolipoma
88 Atypical Epithelioid Angiomyolipoma
89 Atypical Epithelioid Angiomyolipoma
90 Atypical Epithelioid Angiomyolipoma
91 SDHB Mutant RCC
92 SDH Mutant RCC Families with hereditary paraganglioma syndrome occasionally have members with RCC Type 4: Germline SDHB mutations (PGL4)
93 Kreb Cycle
94
95 SDH Mutant RCC: Solid
96 SDH Mutant RCC: Cystic
97 SDH Mutant RCC: Inclusions
98 SDH Mutant RCC: Inclusions
99 SDH Mutant RCC: Inclusions Courtesy of: Dr. Anthony Gill, Royal North Shore, Sydney
100 Housley et al. Histopathol 2010;56:401 1) Inclusions are abnormal mitochondria 2) Contain degenerating cristae and ground substance, but retain the mitochondrial double membrane. 3) Mitochondria are as large as the adjacent nucleus.
101 SDH Mutant RCC Courtesy of: Dr. Anthony Gill, Royal North Shore, Sydney SDHB
102 Immunohistochemistry for SDH Courtesy of: Dr. Anthony Gill, Royal North Shore, Sydney SDHB lost SDHB normal
103 SDH Mutant RCC: Recognition Oncocytic renal neoplasm with eosinophilic cytoplasmic inclusions Verification of SDHB loss by IHC Associated neoplasms Family history of familial paraganglioma syndrome SDHB mutant GISTs
104 3. Eosinophilic, But Not Oncocytoma or Chromophobe
105 Translocation TFE3/Xp11.2
106 Xp11.2 Renal Translocation Carcinomas Characterized by translocation creating TFE3 gene fusion Heterogeneous morphology and immunophenotype Of RCC in children, common subtype Some associated with past chemotherapy Can be indolent, even with nodal mets Deaths reported Occurs in adults Aggressive compared to other types? More rapid course?
107 Xp11/TFE3 RCC
108 Xp11/TFE3 RCC
109 Xp11/TFE3 RCC
110 Lymph Node Core Biopsy: Xp11/TFE3 RCC
111 Xp11/TFE3 RCC: Well-formed papillae
112 Xp11/TFE3 RCC: Dimorphic
113 Xp11/TFE3 RCC: Dimorphic
114 Cytokeratin PAX8
115 Conventional Cytogenetics
116
117 FISH: TFE3 Break-apart
118 When should we test retrospectively? Unusual papillary carcinoma Abundant clear or granular cytoplasm Nested architecture Granular cytoplasm Psammoma bodies!!!!! Biphasic (dimorphic) pattern Central small cells with pyknotic nulclei surrounded by rim of larger cells
119 When should we test retrospectively? Immunohistochemical Screening Cytokeratin negative RCC CK mix CK 7 Capthesin-K positive (sufficient)? TFE3 positive (sufficient)? Technically challenging
120 Papillary RCC
121 Papillary RCC, Type I
122 Papillary RCC, Type I
123 Papillary RCC, Type I CK7
124 Papillary RCC, Type I
125 Papillary RCC solid type with eosinophilic cytoplasm
126 Papillary RCC solid type with eosinophilic cytoplasm
127 Papillary RCC solid type with eosinophilic cytoplasm
128 Papillary RCC, Type II
129 Papillary RCC, Type II
130 Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome (HLRCC)
131 HLRCC Autosomal dominant syndrome Leiomyomas of skin and uterus Renal cell carcinoma Germline activating mutation in fumarate hydratase
132 HLRCC Syndrome Spectrum of neoplasia Leiomyomas of skin and uterus Most patients develop cutaneous leiomyomas Early hysterectomy for myomas Renal carcinomas Often solitary and unilateral Low penetrance (20-35%)
133 Am J Surg Pathol 2007;31(10):
134 Renal Cell Carcinoma in HLRCC
135 Renal Cell Carcinoma in HLRCC
136 Renal Cell Carcinoma in HLRCC
137 Renal Cell Carcinoma in HLRCC: Perinucleolar Halo
138 Renal Cell Carcinoma in HLRCC: Type II Papillary
139 Renal Cell Carcinoma in HLRCC: Complex Secondary Papillae
140 Renal Cell Carcinoma in HLRCC: Solid
141 Renal Cell Carcinoma in HLRCC: Cribriform
142 Renal Cell Carcinoma in HLRCC: Spindled
143 HLRCC: Recognition Unusual RCC with features of type II Papillary RCC and perinucleolar halos Multiple cutaneous or uterine leiomyomas Uterine leiomyomas <30 years of age Differential Diagnosis (solitary, unilateral) Papillary RCC, Type II Collecting Duct Carcinoma Translocation RCC
144 Acquired Cystic Kidney Disease RCC
145 1) 35% of patients on dialysis get ACKD 2) 5.8% of these patients develop RCC 1) Increasing percent of patients get ACKD with increased number of years on dialysis 2) Reports that 3-7% develop RCC
146 ACKD-RCC most common subtype in ESRD Represented dominant mass in 23%
147
148 ACKD-RCC: Papillary Architecture
149 ACKD-RCC: Sieve-like Pattern
150 ACKD-RCC: Sieve-like Pattern
151 ACKD-RCC: Sieve-like Pattern
152 ACKD-RCC: Mixed Sieve and Papillary
153 Tickoo et al. SHS #1 SHS #2 SHS #3
154 Oxalate Crystals
155
156 Background Cysts: Variation
157 Background Cysts: Variation
158 Background Cysts: Eosinophilic Cells
159 Background Cysts: Oxalate Crystals
160 Background Cysts: Tumorlet
161 Immunophentype Antibody ACKD-RCC Papillary RCC CK7 - + Racemase + +
162 CK 7: Negative
163 Clinical Behavior Frequently present at lower stage because patients are on surveillance May explain relatively indolent course Metastases and tumor related deaths do occur
164 Summary 1. Chromophobe vs. Oncocytoma 2. Tumors Resembling Onco/Chromo 3. Eosinophilic, but not Onco/Chromo
165 Summary 1. Chromophobe vs. Oncocytoma -- Gray zone cases of LMP 2. Tumors Resembling Onco/Chromo 3. Eosinophilic, but not Onco/Chromo
166 Summary 1. Chromophobe vs. Oncocytoma 2. Tumors Resembling Onco/Chromo -- Clear cell RCC -- Birt Hogg Dubé RCC -- Low grade tubulocystic RCC -- Epithelioid Angiomyolipoma -- SDHB mutant RCC 3. Eosinophilic, but not Onco/Chromo
167 Summary 1. Chromophobe vs. Oncocytoma 2. Tumors Resembling Onco/Chromo 3. Eosinophilic, but not Onco/Chromo -- Translocation RCC -- Papillary RCC -- HLRCC -- ACKD RCC
168 Renal Tumors with Eosinophilic Cytoplasm Jesse K. McKenney, M.D. Cleveland Clinic
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