December 2022 – Genitourinary

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.

Figure 1. 42M NR-22-10655 20X
Figure 2. 42M NR-22-10655 40X
Figure 3. 42M NR-22-10655 60X CA-IX cup shaped
Figure 4. 42M NR-22-10655 60X CK AE1-AE3
Figure 5. 42M NR-22-10655 60X CK7
Figure 6. 42M NR-22-10655 60X GATA3
Figure 7. 42M NR-22-10655 60X PAX8

Based on the histomorphology and immunohistochemical studies, what is the correct diagnosis?

  • Clear cell renal cell carcinoma.
  • Clear cell papillary renal cell tumor.
  • TFE3-rearranged renal cell carcinoma.
  • Papillary renal cell carcinoma.

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.

References

  1. Griffin BB, Lin X. Cytomorphologic analysis of clear cell papillary renal cell carcinoma: Distinguishing diagnostic features. Cancer Cytopathol. 2021 Mar;129(3):192-203. doi:10.1002/cncy.22355. Epub 2020 Oct 9. PMID: 33036062.
  2. Jianping Zhao, Eduardo Eyzaguirre; Clear Cell Papillary Renal Cell Carcinoma. Arch Pathol Lab Med 1 September 2019; 143 (9): 1154–1158. doi:https://doi.org/10.5858/arpa.2018-0121-RS
  3. Sayeed S, Lindsey KG, Baras AS, Jackson C, Powers CN, Uram-Tuculescu C, Smith SC. Cytopathologic features of clear cell papillary renal cell carcinoma: A recently described variant to be considered in the differential diagnosis of clear cell renal epithelial neoplasms. Cancer Cytopathol. 2016 Aug;124(8):565-72. doi:10.1002/cncy.21721. Epub 2016 Apr 7. PMID: 27062008. https://pubmed.ncbi.nlm.nih.gov/27062008/
  4. Kuroda N, Ohe C, Kawakami F, Mikami S, Furuya M, Matsuura K, Moriyama M, Nagashima Y, Zhou M, Petersson F, López JI, Hes O, Michal M, Amin MB. Clear cell papillary renal cell carcinoma: a review. Int J Clin Exp Pathol. 2014 Oct 15;7(11):7312-8. PMID: 25550767; PMCID: PMC4270541.

Anu Abraham, M.B.B.S.

Fellow, Surgical Pathology
Mayo Clinic
@Dr_AnuAbrahamMD

Charles Sturgis, M.D.

Consultant, Anatomic Pathology
Mayo Clinic
Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science

MCL Education (@mmledu)

MCL Education

This post was developed by our Education and Technical Publications Team.