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17 February 2016 - Case of the Week #379

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Case of the Week #379

Clinical history:
A 52 year old woman with nonalcoholic steatohepatitis was found to have a right kidney mass. Imaging studies showed a 2.5 cm, non-infiltrative exophytic mass. She underwent partial nephrectomy.

Gross description:
Gross examination revealed a partial kidney with adherent adipose tissue weighing 20 g and measuring 4.0 cm x 3.0 cm x 2.5 cm. Sectioning revealed a protruding, subcortical and well circumscribed tan mass with small hemorrhagic foci measuring 1.9 x 1.8 x 1.5 cm. There was no central scar and no foci of necrosis.

Micro images:




What is your diagnosis?

Hybrid oncocytic - chromophobe tumor


Immunostains were obtained:



Hales colloidal iron

Histopathology shows a non-infiltrative, well circumscribed intrarenal tumor composed of neoplastic cells arranged in a solid, alveolar and cystic pattern. There is a dual population of eosinophilic cells. The oncocytic cells are medium sized, round and contain granular eosinophilic cytoplasm with a round concentric nucleus and a prominent nucleolus. The chromophobe cells are large and plant-like with a distinct cell membrane and flaky eosinophilic cytoplasm. A diagnostic clue is the presence of a perinuclear halo surrounding a wrinkled raisinoid nucleus. Focally, a third population of eosinophilic cells featuring both oncocytic and chromophobe morphology are seen. Mitoses are rare.

The neoplastic cells are positive for CD117, E-cadherin and focally for CK7. Hales colloidal iron stain shows both a cytoplasmic and luminal pattern.

Hybrid oncocytic-chromophobe tumor (HOCT) is rare renal neoplasm classified as a subcategory of chromophobe renal cell carcinoma (Am J Surg Pathol 2013;37:1469). HOCT can occur in three distinct clinical settings: sporadically, associated with renal oncocytomatosis and as a component of the Birt-Hogg-Dubé syndrome (Histol Histopathol 2013;28:1257). Birt-Hogg-Dubé syndrome is an autosomal dominant inherited disorder associated with a genetic abnormality on chromosome 17p11.2 leading to a mutation in the BHD gene. Clinical manifestations include spontaneous pneumothorax, multiple benign cutaneous follicular tumors (fibrofolliculoma, trichodiscoma and acrochordon), oncocytomatosis and multifocal chromophobe renal cell tumors (Pol J Pathol 2014;65:93).

HOCT is a distinct tumor with overlapping features of oncocytoma and chromophobe renal cell tumors (ChRCC), showing histopathologic and immunophenotypic features of each. Oncocytoma is negative for CK7 and shows a luminal pattern with Hales colloidal iron, and ChRCC is diffusely positive for CK7 and shows a cytoplasmic pattern with Hales colloidal iron; HOCT expresses a mixed immunophenotypic pattern (J Clin Pathol 2014;67:97).

The histopathologic differential diagnosis includes other eosinophilic renal cell neoplasms including oncocytic papillary renal cell carcinoma and eosinophilic clear cell renal cell carcinoma. Oncocytic papillary renal cell carcinoma has a papillary architecture, is negative for CD117, and is associated with a worse prognosis (Arch Pathol Lab Med 2014;138:1531). Eosinophilic clear cell renal cell carcinoma is composed of sheets of neoplastic cells separated by thin fibrous septa and containing a prominent vascular network. It expresses CD10, is negative for CD117 and is also associated with a worse prognosis (Arch Pathol Lab Med 2014;138:1531).

HOCT has a good prognosis and indolent behavior (Virchows Arch 2010;456:355). Its rarity and histologic subjectivity make it a diagnostic challenge for general pathologists. If tumors are multiple, this may be a clue to a diagnosis of BHD syndrome. Communication with the clinician in this case is essential to ensure appropriate clinical investigation and follow-up.

Discussion edited by Dr. Jennifer R. Kaley, University of Arkansas for Medical Sciences (USA).

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