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Case Presentation

A 43 year old male, with partial nephrectomy for a right kidney mass


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


Immunohistochemistry

CK7 CK903

RCMS


DIAGNOSISClear cell (tubulo)papillary renal cell carcinoma


New (and refined) entities in the ISUP Vancouver and WHO 2016 Classification of Renal Neoplasia

Rafael E. Jiménez

[email protected]


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


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


• 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.


Tubulocystic RCC

• Dx should be restricted to pure cases

• >90% indolent behavior

• Distant metastasis and death described in 4 cases.


• 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



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


CCTP-RCC CC-RCC


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.


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


Translocation Xp11 RCCASPL-TFE3 PRCC-TFE3


Translocation Xp11RCC

IHC Profile

• Focal or negative expression of keratins and EMA

• RCC, CD10, PAX2 positive

• Strong nuclear TFE3 immunoreactivity

Keratin - Negative

TFE3 +


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)


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


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


Acquired Cystic Disease-Associated RCC

Calcium oxalate crystals


Precursor multicystic lesions End-stage kidney background


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


Papillae (previously

papillary RCC or CDC)Tubulocystic


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.


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


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


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


Oncocytosis

• Oncocytic tumors and other oncocytic changes in the renal parenchyma:

• Oncocytomas

• Chromophobecarcinomas

• Hybrid tumors

• Oncocytic change in medullary tubules


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.


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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