Although the great majority of papillary renal cell carcinomas are classified as type 1 or type 2, principally on the absence or presence of nuclear pseudostratification and cytoplasmic eosinophilia, a third variant, designated "oncocytic papillary renal cell carcinoma" (OPRCC) was first reported in 2006. OPRCC show unique pathological features with indolent clinical behavior and are more similar clinicopathologically to type 1 than to type 2 PRCC.
Oncocytic papillary renal cell carcinoma is characterized by the presence of a papillary architecture, with tumor cells exhibiting a voluminous and intensely eosinophilic cytoplasm.
The median age is 67 years. Grossly, tumors were well-circumscribed and small (1.2 cm +/- 0.4 cm).
Epidemiology
In series published to date, there is a strong gender association with 87% of cases occurring in male patients. Age at diagnosis is similar to that for other forms of adult renal cell carcinoma with patient ages ranging from 40 to 80 years (mean 65 years).
Macroscopy
Reflecting the current trend for renal neoplasms to be diagnosed at an early stage through imaging studies, oncocytic papillary renal cell carcinomas reported to date ranged in size from 0.8 to 27 cm at diagnosis (mean 4.9, median 3 cm).
Macroscopically the tumors are well demarcated with a cut surface of varying shades of brown. Intratumoral hemorrhage is a relatively frequent finding, even in small tumors.
Microscopy
Microscopically, the OPRCC are composed of well-developed thin papillae, lined with a single layer of cuboidal-to-columnar oncocytic cells.
The tumor cells have round-to-oval nuclei and eosinophilic granular cytoplasm, which was strongly positive for anti-mitochondrial immunostaining.
The nuclei are characteristically polarized toward the surface of the papillae and contained mostly small nucleoli.
Histologically the tumors are composed of papillae and trabeculae, with fibro-vascular cores covered by tumor cells with eosinophilic cytoplasm exhibiting a low nuclear/cytoplasmic ratio.
In the majority of cases the nuclei are round although in some tumors nuclei show varying degrees of pleomorphism. The distribution of nuclear grades from published series to date are grade 1; 17 cases, grade 2; 18 cases and grade 3; 11 cases, with grading apparently being based upon the degree of nucleolar prominence. Ultrastructure studies show the tumor cytoplasm to be packed with mitochondria with lamella cristae.
The position of the nuclei within the cytoplasm of the neoplastic cells appears to be somewhat variable in these tumors. In the majority of reported cases there was no evidence of pseudostratification, with nuclei predominantly having a luminal rather than basal distribution. In other reported cases pseudostratification of nuclei was occasionally observed.
In some cases aggregates and individual foamy macrophages were frequently seen, whereas tumor necrosis appears to be a common feature. Occasionally psammoma bodies have also been identified.
Although these tumors commonly have a papillary architecture, solid variants have been reported. In these cases the identification of the tumors as papillary renal cell carcinoma was based upon the presence of foamy tumor cells, abortive papillary structures and necrosis, and immunoexpression of neoplastic cells.
Immunochemistry
The tumors have high expression of alpha-methylacyl-coenzyme A racemase, CD15, CD117, cytokeratin (CK) 7, E-cadherin, epithelial membrane antigen, MOC 31, mucin-1, vascular endothelial growth factor and vimentin, low expression of CD10 and Ki-67, and no expression of CK20.
Immunohistochemical expression of oncocytic papillary renal cell carcinoma varied somewhat between series, with CD10 and AMACR showing strong diffuse cytoplasmic staining in virtually all cases.
Expression of cytokeratin 7 (CK7), cytokeratin 19 (CK19), e-cadherin, RCC antigen and vimentin was variable, with positive cytoplasmic staining observed in 50, 65, 50, 50 and 60% of cases respectively. EMA was either negative or only weakly positive.
Genetically, gain of chromosomes 3p, 11q, and 17q, and loss of chromosome 4q is observed.
The genetics of these tumors appears to be similar to those of typical papillary renal cell carcinoma with trisomy 7, (13 of 19 cases), trisomy 17 (14 of 19 cases) and loss of Y (5 of 14 cases) being shown on FISH.110, 111 Karyotyping to date is limited to four cases and three of these showed loss of chromosomes 1, 14 and Y, whereas in one case trisomy 3 was present. In a single case CGH showed partial loss of the long arm of chromosome 11.
Differential diagnosis
The main differential diagnosis for these tumors is oncocytoma and chromophobe renal carcinoma. Although papillary architecture is impermissible in oncocytoma, oncocytic papillary renal cell carcinoma with solid architecture can resemble oncocytoma. The presence of foamy macrophages, foamy tumor cells and extensive microscopic necrosis favors oncocytic papillary renal cell carcinoma, as does positive immunoexpression for AMACR, CD10, RCC, cytokeratin 7 and vimentin. Eosinophilic chromophobe renal carcinoma usually contains foci of classic chromophobe cells, albeit focally. Immunohistochemical staining may provide further diagnostic evidence as AMACR and vimentin are usually negative, whereas EMA is frequently positive in chromophobe renal carcinoma.
There may be some overlap between oncocytic papillary renal cell carcinoma and type 2 papillary renal cell carcinoma. In those cases where there is no evidence of pseudostratification then type 2 papillary renal cell carcionoma can be excluded. In those cases where this is present, diagnosis relies on assessment of the cytoplasmic volume of tumor cells, although in reality it may be that these two tumor types are closely related morphotypes of papillary renal cell carcinoma.
Prognosis
Assessment of outcome for oncocytic papillary renal cell carcinoma is, to date, limited. Virtually all tumors in published series were organ confined at diagnosis108, 110, 111 (pT1a, 16 cases; pT1b, 8 cases; pT2, 3 cases; pT3-2). One of the pT3 cases was staged on the basis of spread of a co-existing clear cell renal cell carcinoma. Outcome data were available for 29 cases with follow-up ranging from 3.5 to 144 months. One pT2 tumor recurred 2 years post-nephrectomy and the patient died 2 years later. For all other cases the patient was either alive without evidence of recurrence or had died of unrelated causes.
Variants
oncocytic papillary renal cell carcinoma with inverted nuclear pattern (19261090)
See also
oncocytic renal cell carcinomas
References
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