A 42-year-old man presented for management of scrotal abscess and was found to have a 3.6 cm endophytic renal mass in the mid-right kidney on imaging. Ultrasound-guided right kidney mass biopsy was performed, and the hematoxylin and eosin-stained slides were reviewed. Several immunohistochemical studies were also performed and the figures are shown below.
The correct answer is ...
Clear cell papillary renal cell tumor.
The hematoxylin-eosin stained slide sections show a mixture of tubular/acinar and papillary patterns in the background of hyalinized stroma. The tumor cells are cuboidal to low columnar cell with clear cytoplasm, and low-grade nuclei are horizontally arranged away from the basement membrane. Hemosiderin deposition, necrosis, foamy macrophages and psammoma bodies are absent.
The immunohistochemical (IHC) study slides show the neoplastic cells are diffusely positive for CK AE1/AE3, CK7, PAX8, CA-IX, and GATA3. CA-IX staining is of characteristic “cup”-like pattern with apical surface of the tumor cells devoid of staining. The combined histology along with immunohistochemistry is most consistent with clear cell papillary renal cell tumor.
Clear cell papillary renal cell tumour (CCPRCT) is a recently described entity, recognized by the World Health Organization in 2016 that shares microscopic features with both clear cell renal cell carcinoma (CCRCC) and papillary renal cell carcinoma. CCPRCT is a low-grade and indolent tumor regarding its biological behavior. A substantial majority of cases demonstrate low pathologic staging at the time of presentation or initial diagnosis, with >90% of patients having primary tumor stage I. This tumor was originally described in the setting of end-stage kidney disease; since then, multiple studies have demonstrated that CCPRCT occurs sporadically and is the fourth most common RCC subtype. Partial nephrectomy or total nephrectomy is generally the treatment provided for a solitary tumor when surgical resection is feasible. As this tumor is generally indolent, active surveillance with strict follow-up may be possible for selective cases and if the diagnosis can be reliably established preoperatively such as by a core biopsy.
Clear cell renal cell carcinoma has predominantly clear cells with sharp cell borders with fine arborizing vascularity that surround essentially every nest of tumor cells. High nuclear grade, the immunohistochemical positivity for CD10, CA-IX (box-like) and negativity of cytokeratin 7 and AMACR, and loss of chromosome 3p or VHL gene alterations can achieve the final diagnosis of clear cell RCC.
Papillary renal cell carcinoma has papillary and tubular architecture with cuboidal to columnar cells (often basophilic) with foamy macrophages and psammoma bodies. Positivity for cytokeratin 7 and AMACR and polysomy of chromosomes 7 and 17 and loss of chromosome Y can lead to the diagnosis of papillary RCC. Clear cell change in papillary RCC is usually in combination with hemosiderin deposition and/or necrosis, and this cytoplasmic clearing may reflect phagocytic activity of carcinoma cells
In TFE3-rearranged renal cell carcinoma, papillary architecture, voluminous tumor cells, psammoma bodies or hyaline nodules may be observed. Nuclear TFE3 and negativity for epithelial markers may be helpful in the distinction between CCPRCT and TFE3-rearranged RCC.
Anu Abraham, M.B.B.S.
Fellow, Surgical Pathology
Charles Sturgis, M.D.
Consultant, Anatomic Pathology
Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science