p63 Immunohistochemistry Differentiates Salivary Gland Oncocytoma and Oncocytic Carcinoma from Metastatic Renal Cell Carcinoma

Abstract

Metastatic renal cell carcinoma (RCC) can pose diagnostic challenges in the head and neck often resembling benign and malignant oncocytic lesions. Immunohistochemical panels have been reported to help with this differential but are not entirely specific or sensitive. We have noticed that p63 routinely stains salivary gland oncocytomas but not metastatic RCC. Nineteen oncocytomas, 9 cases of oncocytosis, 9 oncocytic carcinomas and 16 head and neck metastatic RCC were studied. Morphologic features evaluated were cytoplasmic character (clear versus oncocytic), Fuhrman nuclear grade, mitotic rate, growth pattern, presence of lumens/blood lakes and stromal characteristics. Tumors were stained with antibodies to p63, renal cell carcinoma marker (RCCm), CD10, and vimentin. Eight benign oncocytic tumors (29%) had clear cell features while 6 metastatic RCC (37%) had oncocytic features. Median Fuhrman nuclear grade was 2 in oncocytoma and oncocytosis and 3 both oncocytic carcinoma and metastatic RCC. Mitotic rates were only significantly different between benign oncocytic tumors and metastatic RCC. All oncocytomas had lumina compared to half of metastatic RCC, all of which also demonstrated blood lakes. Seven benign oncocytic tumors (25%) and 5 oncocytic carcinomas (56%) had RCC-like vascular stroma. All primary salivary gland tumors were positive for p63, predominately in basal cell-type distribution. None of the metastatic RCC was positive. RCCm was entirely specific but lacked sensitivity for metastatic RCC while CD10 and vimentin showed variable sensitivity and specificity. While clinical history and morphology usually are adequate, demonstration of p63 staining can definitively exclude metastatic RCC from the differential diagnosis of similar appearing tumors in salivary glands, namely oncocytoma and oncocytic carcinoma, with 100% specificity and sensitivity. While RCCm, CD10, and vimentin performed adequately, they were significantly less reliable than p63 with both false positives and false negatives.

Hyalinizing Clear Cell Carcinoma of Salivary Gland: A Review and Update

“…The nuclei are larger and more atypical than HCCC, there is never squamous differentiation, and the dual stroma of HCCC is lacking. In addition, RCC never expresses p63 [17], which is almost always expressed in HCCC [9].…”

Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: Tumors of the Salivary Gland

“…In contrast to oncocytoma, there is no 1 3 dominant encapsulated lesion. Clear cell predominance may mimic the appearance of metastatic renal cell carcinoma, though nodular oncocytic hyperplasia does not show the hemorrhage or vascularity typically seen in renal cell carcinoma [19]. Lymphoepithelial lesions are pathognomonic for lymphoepithelial sialadenitis that is seen in Sjögren syndrome [20].…”

My Journey into the World of Salivary Gland Sebaceous Neoplasms

“…It also stains the germinative cells of the secretory portion of sebaceous glands [54]. In a recent paper, p63 stained all sebaceous and NSLs, 11 and 7, respectfully [21], while a separate study found that all 16 metastatic renal cell carcinomas were negative for this antibody [55]. In addition, three primary sebaceous carcinomas of the skin in several recent studies also stained with p63 [54,56,57].…”