Microscopic description:

Granular eosinophilic cytoplasm

No distinct cell borders

Finely granular intracytoplasmic stippling/inclusions

Occasional binucleations/multinucleations

Cytoplasmic vacuolization

Positive: FH, SDHB, CD10, CAM 5.2, Vimentin, PAX8, CAIX (granular, non-membranous staining), CK20, AMACR, RCC, patchy AE1/E3

Negative: Melan A, CK7, Inhibin, HMB45

Discussion:

Renal cell carcinoma accounts for ~90% of all kidney cancers. The most common subtypes of RCC are clear cell, papillary and chromophobe which account for 75%, 10%, and 5% of RCC cases, respectively. WHO 2016 classification has also described any tumor that does not suit a well-defined subtype as unclassified RCC, which also accounts for 2%-6% of all RCCs. Under the unclassified classification, Eosinophilic solid and cystic (ESC) RCC is a unique indolent emerging entity that has been seen to mostly affect females.

RCC generally presents in a person's sixth to seventh decade of life with a predominance of cases being male. Although most presentations are incidental, local signs and symptoms can occur including hematuria, flank pain, and palpation of abdominal mass. Systemic symptoms can be related to metastases and/or paraneoplastic events related to protein secretion.

Gross examination of ESC RCC tumors generally reveal both solid and cystic characteristics, which could also reveal variable hemorrhage with associated necrosis. Upon microscopic examination, eosinophilic cytoplasm and prominent granular cytoplasmic stippling/inclusions within cells are generally seen. Nuclei are viewed having round to oval, with mild pleomorphism and variably prominent nucleoli. Positivity is generally seen on IHC stains such as PAX-8, CK20, AMACR, FDHB, FH, Vimentin and show general negativity in CK7, CAIX, and CD117. ESC RCC has been shown to harbor TSC mutations as well.

There are viable treatment options in both surgical approach, such as partial/radical nephrectomy and thermal ablation, and systemic therapy, such as chemotherapy and immunotherapy.

References:

Kryvenko, O. N., Jorda, M., Argani, P., & Epstein, J. I. (2014). Diagnostic approach to eosinophilic renal neoplasms. Archives of Pathology & Laboratory Medicine, 138(11), 1531–1541. https://doi.org/10.5858/arpa.2013-0653-ra 

Monzon, F. A., Shen, S. S., Kemp, B., Alvarez, K., & Ayala, A. G. (2010). Oncocytic renal NEOPLASMS. Pathology Case Reviews, 15(1), 20–24. https://doi.org/10.1097/pcr.0b013e3181d2d808

Muglia, V. F., & Prando, A. (2015). Renal cell carcinoma: Histological classification and correlation with imaging findings. Radiologia Brasileira, 48(3), 166–174. https://doi.org/10.1590/0100-3984.2013.1927

Rini, B. I., Campbell, S. C., & Escudier, B. (2009). Renal cell carcinoma. The Lancet, 373(9669), 1119–1132. https://doi.org/10.1016/s0140-6736(09)60229-4 

Sirohi, D., Smith, S. C., Agarwal, N., & Maughan, B. L. (2018). Unclassified renal cell carcinoma: Diagnostic difficulties and treatment modalities. Research and Reports in Urology, Volume 10, 205–217. https://doi.org/10.2147/rru.s154932 

Trpkov, K., Abou-Ouf, H., Hes, O., Lopez, J. I., Nesi, G., Comperat, E., Sibony, M., Osunkoya, A. O., Zhou, M., Gokden, N., Leroy, X., Berney, D. M., Werneck Cunha, I., Musto, M. L., Athanazio, D. A., Yilmaz, A., Donnelly, B., Hyndman, E., Gill, A. J., … Bismar, T. A. (2017). Eosinophilic solid and cystic renal cell carcinoma (esc rcc). American Journal of Surgical Pathology, 41(10), 1299–1308. https://doi.org/10.1097/pas.0000000000000838

CASE IMAGES