Chromophobe Renal Cell Carcinoma



Chromophobe Renal Cell Carcinoma


Satish K. Tickoo, MD

Victor E. Reuter, MD





Key Facts


Terminology



  • Chromophobe renal cell carcinoma (Ch-RCC)


  • Characterized by large pale and smaller eosinophilic tumor cells in variable proportions, with wrinkled nuclei and perinuclear halos


Etiology/Pathogenesis



  • Ch-RCC typically shows combined chromosomal losses usually affecting chromosomes 1, 6, 10, 13, 17, 21, and Y


Clinical Issues



  • Prognosis of Ch-CRC much better than clear cell RCC, and also than papillary RCC in some studies


  • Sarcomatoid features in tumor; most frequent association with aggressive clinical behavior


Microscopic Pathology



  • Pattern of growth is predominantly solid, separated by thin, incomplete fibrovascular septa


  • In “classic” type tumors, predominant cell type is that with a pale, somewhat clear-appearing cytoplasm


  • In “eosinophilic” variants, predominance of tumor cells with densely eosinophilic, granular cytoplasm


  • Most tumors show admixture of pale and eosinophilic cells


  • Most characteristic histological feature: Hyperchromatic nuclei with irregular, wrinkled outlines (“raisinoid” nuclei)


  • Another characteristic feature: Presence of perinuclear cytoplasmic clarity (perinuclear halos)


  • Presence of cytoplasmic microvesicles is unique and consistent ultrastructural feature of Ch-RCC







Chromophobe renal cell carcinoma is typically well circumscribed, with tan-gray, multilobulated cut surface. Hemorrhage and necrosis image are grossly identified in more than a quarter of the cases.






Typically, a chromophobe renal cell carcinoma shows solid sheets of clear and eosinophilic cells, separated by thin and incomplete image vascular septations that do not completely encircle cell nests.


TERMINOLOGY


Abbreviations



  • Chromophobe renal cell carcinoma (Ch-RCC)


Definitions



  • 3rd most common subtype of renal cell carcinoma



    • Characterized by large pale and smaller eosinophilic tumor cells in variable proportions, with wrinkled nuclei and perinuclear halos


ETIOLOGY/PATHOGENESIS


Genetic Features



  • Ch-RCC typically shows combined chromosomal losses usually affecting chromosomes 1, 6, 10, 13, 17, 21, and Y



    • Loss of multiple chromosomes leads to almost consistently present hypodiploidy


  • Abnormalities in mitochondrial DNA may be observed, but their specificity remains controversial


  • Recently, gene expression profiling has shown up-regulation of a number of genes encoding proteins integrated to membranes



    • Many of these up-regulated gene products are related to vesicle-mediated transport


Cell of Origin



  • Ch-RCC are thought to arise from intercalated cells of renal cortex, similar to renal oncocytomas


CLINICAL ISSUES


Epidemiology



  • Incidence



    • Comprise 6-11% of renal epithelial tumors


  • Age



    • Mean: 58 years (range: 26-62 years)


  • Gender



    • M:F = 1.5:1


Presentation



  • Usually present as unilateral renal mass


  • Overwhelming majority are asymptomatic, with incidentally detected tumors following investigations for unrelated symptoms


  • < 1/3 present with palpable mass



    • Hematuria is presenting symptom in rare cases


Treatment



  • Surgical approaches



    • Partial nephrectomy surgical treatment of choice, whenever feasible


  • Drugs



    • No specific chemotherapeutic agent consistently effective in metastatic cases


    • Recently, targeted therapies against vascular growth factor tyrosine kinase receptors and mTOR pathway molecules have shown some rare responses


Prognosis



  • Prognosis of Ch-CRC better than papillary RCC in some studies and consistently better than clear cell RCC


  • Overall, close to 95% survival rates at 5-year follow-ups


  • Sarcomatoid features and perinephric extension frequently associated with aggressive clinical behavior


  • Other important indicators correlating with adverse clinical outcome include



    • Pathologic tumor stage


    • Large tumor size


    • Tumor necrosis


  • Overall, patients with metastatic Ch-RCC tend to do better than patients with metastasis from other common subtypes of RCC



IMAGE FINDINGS


Radiographic Findings



  • Usually large, well-circumscribed, unicentric renal mass


  • Often with features of hypovascularity


  • May show central scar, similar to that seen in oncocytomas and large, low-grade clear cell RCC



    • Presence of radiographically detected central scar offers little diagnostic information except suggesting presence of slow-growing neoplasm


MACROSCOPIC FEATURES


General Features



  • Characteristically, well circumscribed but not encapsulated


  • Cut surface homogeneous beige or pale-tan; occasionally dark brown or mahogany



    • Gross appearance is reflection of microscopic cell types



      • More brown with increasing proportion of cells with eosinophilic cytoplasm


  • Central scar is present in approximately 15% of tumors


  • Gross hemorrhage and necrosis present in 25-30%



    • Cystic change less common


  • Multifocality in < 10%


  • Gross involvement of renal vein seen in small number of cases


  • Up to 1/3 of patients may exhibit perirenal adipose tissue invasion


Size



  • Mean: ˜ 9 cm (range: 2-23 cm)



    • Largest among common subtypes of renal cell carcinoma



      • Mean tumor size progressively decreasing now because of earlier incidental detection on radiologic investigations for unrelated causes


      • Mean size in past 10-15 years has decreased to much smaller than 9 cm


MICROSCOPIC PATHOLOGY


Key Descriptors



  • Predominant Pattern/Injury Type



    • Neoplastic


  • Predominant Cell/Compartment Type



    • Epithelial


  • Histologic Features



    • Pattern of growth is predominantly solid, separated by thin, incomplete fibrovascular septa


    • Some tumors with variable nested, broad alveolar, solid, cystic, tubular, trabecular, or even papillary/pseudopapillary patterns



      • Nested/alveolar pattern usually associated with eosinophilic variants


    • Small percentage exhibit sarcomatoid pattern of growth



      • Probably the subtype with proportionately most frequent sarcomatoid differentiation among all RCCs


    • Microscopic foci of necrosis present in 15-25% of cases


    • In classic type tumors, predominant cell type is that with pale, somewhat clear-appearing cytoplasm



      • Unlike clear cell RCC, cytoplasm is not optically entirely clear but somewhat translucent and finely reticulated


      • Cytoplasm has frothy/microvesiculated appearance


      • Some larger cells with more voluminous clear to foamy (“hydropic”) cytoplasm often present among other “clear” cells


    • In eosinophilic variants, predominance of tumor cells with densely eosinophilic, granular cytoplasm



      • Cells with eosinophilic cytoplasm predominate in 30-40% of tumors


    • Most tumors show admixture of pale and eosinophilic cells




      • Both cell types may be juxtaposed to one another without specific patterns, or


      • Both cell types may have special spatial arrangement with eosinophilic cell in center and clear cells at periphery


    • Hyperchromatic nuclei with irregular, wrinkled outlines (“raisinoid” nuclei) is most characteristic feature



      • Proportion of such nuclei variable from case to case


      • Wrinkled nuclei more prevalent in classic types than eosinophilic variants


    • Another characteristic feature is presence of perinuclear cytoplasmic clarity (perinuclear halos)



      • While usually prominent, perinuclear halos may be only focal in some eosinophilic variants, and require careful search in such cases


    • Binucleated cells present in virtually all cases


    • Cell membranes usually appear prominent



      • Most cytoplasmic organelles are displaced to periphery of cytoplasm by abundant microvesicles in these tumors


      • This leads to impression of thick cell membranes, somewhat resembling thick cell walls in plant cells


    • Foci with bizarre, hyperchromatic, degenerate atypia similar to those in renal oncocytoma are common, and may be prominent in rare cases


    • Mitotic activity is uncommon in Ch-RCC but may be prominent in sarcomatoid and some epithelial tumors


    • Because of consistent presence of hyperchromatic, wrinkled, pleomorphic nuclei, Fuhrman nuclear grading is not appropriate for Ch-RCC



      • Currently, attempts are ongoing for clinically more relevant type-specific grading system


ANCILLARY TESTS


Histochemistry



  • Colloidal iron stain



    • Variable granular or reticular and diffuse cytoplasmic staining with Hale colloidal iron in majority of cases


    • Difficult stain to perform well with consistency and is highly laboratory-dependent



      • Focal, weak, or luminal-type staining may be seen in some cases with predominance of eosinophilic cells


      • Value limited in difficult cases


Immunohistochemistry

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Jul 6, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Chromophobe Renal Cell Carcinoma

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