relevant financial relationship(s) none off label usage...

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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