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©2013 MFMER | slide-1
Relevant Financial Relationship(s)None
Off Label UsageNone
Disclosure
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Case Presentation
A 43 year old male, with partial nephrectomy for a right kidney mass
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Morphologic diagnosis:
• A. Clear cell renal cell carcinoma
• B. Papillary carcinoma
• C. Mixed epithelial stromal tumor
• D. Clear cell tubulopapillary renal cell carcinoma
• E. Tubulocystic renal cell carcinoma
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Immunohistochemistry
CK7 CK903
RCMS
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DIAGNOSISClear cell (tubulo)papillary renal cell carcinoma
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New (and refined) entities in the ISUP Vancouver and WHO 2016 Classification of Renal Neoplasia
Rafael E. Jiménez
jimenez.rafael@mayo.edu
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New Renal Epithelial Tumor Categories
• Tubulocystic renal cell carcinoma
• Acquired cystic disease-associated renal cell carcinoma
• Clear cell (tubulo)papillary renal cell carcinoma
• MiT family translocation carcinomas
• Xp11 tranlocation RCC (*)
• t(6;11) RCC
• Hereditary leiomyomatosis-RCC syndrome-associated RCC
• Succinate dehydrogenase-deficient RCC
(*) already included in 2004 WHO classif
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Tubulocystic carcinoma
• Previously considered as a “low grade” variant of collecting duct carcinoma.
• >70 cases reported
• Usually present in low stages (pT1-pT2).
• Well circumscribed, encapsulated, “bubble wrap” cut surface
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• TC-RCC demonstrates variable status of chromosomes 7, 17,
and Y even in cases with typical/uniform morphology.
• The biological nature of Papillary RCC or High-grade NOS RCC-
like areas within TC-RCC remains unclear.
• Heterogeneous TC-RCCs may be associated with an adverse
clinical outcome.
• HG TC-RCC indistinguishable from HLRCC
Appl Immunohistochem Mol Morphol. 2016 Aug;24(7):521-30.
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Tubulocystic RCC
• Dx should be restricted to pure cases
• >90% indolent behavior
• Distant metastasis and death described in 4 cases.
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• Initially reported in end
stage kidneys, however
majority are sporadic.
• Variable papillary,
tubular/acinar, cystic
architecture.
• May contain dense
muscular stroma
(RAT).
• Linear arrangement of
low grade nuclei away
from base.
Clear cell tubulopapillary RCC
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Clear cell tubulopapillary RCC
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Clear cell tubulopapillary RCC
IHC Profile
• Diffuse CK7
• CD10 negative
• Diffuse CA-IX (cup shaped distribution)
• Negative racemase
• Patchy to diffuse 34BE12
Prognosis
• Indolent clinical behavior
• No metastases reported in pure tumors
• One case with sarcomatoid change, metastases, and DOD recently reported
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CCTP-RCC CC-RCC
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Am J Surg Pathol 2015;39:1502–1510
• 22 cases with morphologic overlap with CC TubPap-RCC
• Atypical features, including labeling for CD10 and AMACR,
higher nuclear grade and tumor stage, and tumor necrosis.
• The majority of such tumors demonstrated abnormalities of
chromosome 3p by FISH or karyotyping, arguing that they are
best regarded as a manifestation of clear cell renal cell
carcinoma.
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Translocation-associated carcinomas
• Translocations involving Xp11.2 (TFE3).
• ASPL-TFE3
• PRCC-TLFE3
• Translocation involving TFEB [t(6;11)]
• TFE3 and TFEB part of the MiT subfamily of transcription factors
• 50% of RCC of pediatric age.
• <5% of adult RCC
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Translocation Xp11 RCCASPL-TFE3 PRCC-TFE3
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Translocation Xp11RCC
IHC Profile
• Focal or negative expression of keratins and EMA
• RCC, CD10, PAX2 positive
• Strong nuclear TFE3 immunoreactivity
Keratin - Negative
TFE3 +
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Translocation Xp11 RCC
Prognosis
• Usually present with high stage
• Children good prognosis despite high stage
• Not enough long term survival data
• Adults 1-2 years survival
• Late recurrences (20-30 years)
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t(6;11) RCC
• Mean age 28.5 years
• Alpha-TFEB gene fusion.
• Biphasic morphology: large and small cells
• Basement membrane material
• Express melanocytic markers
• Negative for cytokeratins
• 10% metastatic and death rate in reported cases
Image from: Magers et al, Arch Pathol Lab Med. 2015;139:1224–1233
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Acquired Cystic Disease-Associated RCC
• Most common neoplasm in the end-stage kidney setting
• Arise from cyst wall or adjacent parenchyma
• Multifocality and bilaterality
• IHC Profile
• Diffusely for racemase
• Negative CK7
• Relatively good prognosis, although sarcomatoid and rhabdoid change may occur
“Sieve-like” appearance
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Acquired Cystic Disease-Associated RCC
Calcium oxalate crystals
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Precursor multicystic lesions End-stage kidney background
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Hereditary Leiomyomatosis-related RCC
• Autosomal dominant mutations in the fumaratehydratase gene
• Smooth muscle and renal neoplasms
• Highly aggressive renal neoplasms
• High-grade with inclusion-like nucleoli surrounded by halo
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Papillae (previously
papillary RCC or CDC)Tubulocystic
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Succinate-dehydrogenase-deficient RCC
• Part of spectrum of tumors developed by patients with germline mutations of SDH, which also include paragangliomas and GISTS.
• Oncocytic tumor with characteristic cytoplasmic vacuolization
• Other SDH-deficient histologies being identified, but rare.
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SDH-deficient RCC
• Typical vacuolated cytoplasm with floculentinclusions
• Absent staining in tumor cells with SDHB
• At least one case with widespread metastasis and DOD reported, although majority low grade, indolen
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Refinement of concepts on old entities
• Clear cell renal cell carcinoma:
• Multilocular cystic renal cell neoplasm of low malignant potential
• Chromophobe renal cell carcinoma:
• Hybrid oncocytic tumors
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Multilocular cystic renal cell neoplasm of low malignant potential
• Numerous cysts, the septa of which contain small groups of clear cells grade I
• Cysts lined by clear cells.
• No solid areas with expansive nodules
• Excellent prognosis
• >200 patients with f/u >5 years
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Oncocytosis
• Oncocytic tumors and other oncocytic changes in the renal parenchyma:
• Oncocytomas
• Chromophobecarcinomas
• Hybrid tumors
• Oncocytic change in medullary tubules
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Hybrid oncocytic tumors
• Oncocytomas with focal atypia
• Well-defined nests, but cellular atypia.
• Classic cytologic features of oncocytoma, but loss of the nested architecture.
• Others exhibit well-defined areas of chromophobe carcinoma, coexisting with classic areas of oncocytoma.
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Summary
• The Vancouver ISUP classification of renal neoplasia and the 2016 WHO classification define new entities readily identifiable on morphologic basis.
• Selected concepts on well-established diagnostic categories continue further refinement.
• Unresolved issues on kidney tumor categories guarantees further updates and revisions of renal neoplasia classification
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