Chromophobe

Chromophobe refers to cells or tissues that stain poorly with routine histological dyes, producing a pale or light cytoplasm on standard sections. The name derives from chroma (color) and phobe (bearing or fearing), reflecting their relatively subdued staining. In pathology, chromophobe features are most often discussed in relation to renal tumors, where chromophobe-type cells can be a key diagnostic clue.

Chromophobe renal cell carcinoma (RCC) is the principal tumor associated with the term in contemporary practice. It represents a minority of RCCs, arising most likely from intercalated cells of the cortical collecting ducts. Patients may present with hematuria, flank pain, or an incidental mass on imaging. Compared with clear cell RCC, chromophobe RCC generally has a more favorable prognosis, particularly after surgical treatment.

Histologically, chromophobe RCC is characterized by pale, reticulated cytoplasm with well-defined cell borders and a perinuclear halo. Nuclei are often raisinoid (irregular, wrinkled) and may be binucleated. Tumor cells can be arranged in solid, nested, or sheet-like patterns, sometimes with focal storiform areas. The pale cytoplasm and distinct cell outlines contribute to the characteristic appearance.

Immunohistochemistry commonly shows positivity for cytokeratin 7 (CK7) and KIT (CD117), with negativity or only focal positivity for CD10. Genetically, chromophobe RCC often exhibits multiple chromosomal losses, contributing to a hypodiploid pattern. Birt-Hogg-Dubé syndrome is a known association in a subset of cases.

Differential diagnosis includes oncocytoma and other RCC subtypes; distinguishing features rely on a combination of morphology, immunoprofile, and, when needed, genetic studies. Clinically, treatment is typically surgical, with prognosis better than several other RCC variants.