What are the microscopic architectural growth pattern findings characteristic of clear cell renal cell carcinoma (CCRCC)?

Updated: Mar 11, 2019
  • Author: Ronald J Cohen, MB, BCh, PhD, FRCPA, FFPATH; Chief Editor: Liang Cheng, MD  more...
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CCRCC may grow in various architectural patterns, with the most common types being compact-alveolar (nested), tubular (acinar), and microcystic. In the compact-alveolar or nested pattern, solid rounded nests of epithelial cells are separated by a delicate branching network of connective tissue that is highly vascularized with thin walled blood vessels, resulting in a sinusoidal appearance. See the images below.

Typical histologic appearance of clear cell renal Typical histologic appearance of clear cell renal cell carcinoma on hematoxylin and eosin stain, showing nests of epithelial cells with clear cytoplasm and a distinct cell membrane, separated by a delicate branching network of vascular tissue.
Immunohistochemistry with anti-CD31 antibody highl Immunohistochemistry with anti-CD31 antibody highlights the extensive vasculature of clear cell renal cell carcinoma.

In the tubular or acinar pattern, epithelial cells line the septa of vascularized connective tissue and form central lumens. In regions of cystic degeneration, these structures dilate to form a microcystic and/or macrocystic pattern with luminal spaces containing necrotic material, pale eosinophilic fluid, and red blood cells. [41, 55] CCRCCs often contain more than one architectural pattern, and focal regions of papillary or pseudopapillary architecture may also occur. See the images below.

Microcystic architecture in clear cell renal cell Microcystic architecture in clear cell renal cell carcinoma showing dilated luminal spaces containing necrotic material, pale eosinophilic fluid and red blood cells.
A region of clear cell renal cell carcinoma with p A region of clear cell renal cell carcinoma with pseudopapillary architecture.

When mixed patterns are seen, the possibility of an Xp11 translocation RCC must be considered. These tumors commonly show both papillary architecture and a nested pattern with vascular stroma similar to compact-alveolar (nested) CCRCC. [11]

In addition, rare tumors are described in which the malignant clear cell epithelial component is embedded within prolific metaplastic spindle cell stroma (see the image below). [56, 57]

A rare variant of clear cell renal cell carcinoma A rare variant of clear cell renal cell carcinoma with prolific metaplastic smooth muscle stroma.

The spindle cells show evidence of smooth muscle differentiation and, in some cases, merge with the walls of blood vessels, suggestive of vascular proliferation in response to angiogenic factors produced by the tumor. [56] Genetic analysis has demonstrated loss of chromosome 3 or 3p in all 3 cases analyzed, [57] supporting the authors' proposed classification as a variant of CCRCC.

When papillary areas are noted, care must be taken to exclude the more recently described entity of clear cell papillary renal carcinoma. These tumors are characterized by low-grade nuclear features, usually Fuhrman grade 1 or occasionally grade 2. The tubulopapillary areas are lined by cells with nuclei orientated away from the basement membrane. More classical clear-cell–like areas are often seen. Immunostains for CK7 and CA9 are characteristically positive, while stains for CD10 and AMACAR are negative. Cytogenetic analysis shows no 3p deletions or trisomy 7/17. [58]


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