2020-1 / JANUARY 6

A 56 yo man presented with a complaint of hoarseness. Imaging studies revealed multiple nodules in his right lung and an 11 cm mass in his left kidney. Clinically, he was thought to have a kidney cancer with lung metastases. He underwent a radical nephrectomy. PAX8 (image 4) and TTF1 (image 5) immunostains are shown.


1. What is the correct diagnosis?

a. Clear cell renal cell carcinoma, grade 4

b. Clear cell renal cell with extramedullary hematopoiesis

c. Lung adenocarcinoma metastatic to clear cell renal cell carcinoma

d. Metastatic lung adenocarcinoma

1. Lung adenocarcinoma metastatic to clear cell renal cell carcinoma

The histologic sections show nests of tumor cells with clear cytoplasm, low grade nuclei and “chicken-wire” vasculature, characteristic of a low grade clear cell renal cell carcinoma (RCC). Within the tumor, there is a distinct 2nd population of tumor cells with basophilic cytoplasm and high grade nuclei forming vague glands. Immunohistochemical studies show the clear cell RCC is positive for PAX8 and is negative for TTF-1 and CK7, while the high grade tumor cells forming glands show the opposite staining pattern (negative for PAX8, positive for TTF-1 and CK7). The results support the diagnosis of metastatic lung adenocarcinoma to a clear cell renal cell carcinoma.
A high grade component can be seen in a clear cell RCC that is largely low grade due to intratumoral heterogeneity. Both components have similar architectural features and immunohistochemical staining patterns.
Nests of megakaryocytes are rarely seen in clear cell RCC due to extramedullary hematopoiesis as the result of erythropoietin production by tumor cells. Other hematopoietic cells including nucleated erythrocytes are often present.
Metastasis of an extrarenal tumor to a RCC (tumor to tumor metastasis) should be considered for any renal tumor with two morphologically distinct populations of tumor cells. When suspected, immunohistochemical stains can be used to confirm the diagnosis. Metastases of non-renal tumors to renal neoplasms are exceedingly rare and have been previously reported in case reports [1-3]. Lung cancer is the most common cancer type that metastasizes to renal tumors [4]. The most common recipient renal tumor is clear cell RCC, although metastases to oncocytomas and angiomyolipoma have also been reported. It is critical to recognize metastasis of non-renal tumors to renal neoplasms for proper patient management. A metastasis to renal tumors represents “M1” stage for the non-renal tumor. As reported in the literature, these non-renal tumors with metastasis to renal tumors are often aggressive and have widespread metastasis to other body sites in addition to RCCs. Therapies in these cases, therefore, should target the non-renal tumors.

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Sanhong Yu, Elizabeth M Genega, Ming Zhou
Tufts Medical Center


Metastatic, clear cell renal cell carcinoma, lung adenocarcinoma