2021-37/ September 13
Contributors: Lagnajita Datta, Sounak Gupta

A female patient in her 50s presented with a 3.9 cm renal mass and underwent partial nephrectomy. On gross examination, a well circumscribed un-encapsulated solid mass with a tan brown cut surface is noted.


1. What is the correct diagnosis?

a. Oncocytoma

b. Eosinophilic variant of chromophobe renal cell carcinoma

c. Eosinophilic vacuolated tumor/ High grade oncocytic tumor (EVT/HOT)

d. Eosinophilic solid cystic renal cell carcinoma (ESC-RCC)


2. What is the usual immunoprofile of this tumor?

a. CD117+/CK7-/CK20-/Cathepsin K+

b. CD117+/CK7+/CK20-/ Cathepsin K-

c. CD117-/CK7+/CK20-/ Cathepsin K-

d. CD117-/CK7-/CK20+/ Cathepsin K-

1. c; 2. a

1. Eosinophilic vacuolated tumor/High grade oncocytic tumor (EVT/HOT); 2. CD117+/CK7-/CK20-/Cathepsin K+

Eosinophilic vacuolated tumor/ High grade oncocytic tumor (EVT/HOT) is an emerging renal tumor with characteristic morphology, consistent immunoprofile and distinct molecular genetic features. This tumor emerged from the spectrum of “unclassified eosinophilic tumors” and does not fit into any of the currently recognized renal tumor categories.

These tumors are more common in females and are found in patients with a broad age range of 25 to 73 years (median 50, mean 49 years). The tumors are usually small, ranging from 1.5 to 7.0 cm in the greatest dimension (median 3, mean 3.4 cm) and are usually diagnosed at low stage and follow an indolent course.

Grossly, these tumors are solid with tan, or mahogany brown cut surface. Cystic areas are usually not seen. Microscopically, the tumors are unencapsulated and well-circumscribed with a solid to nested growth and focal tubulocystic areas. Tumor cells exhibit abundant eosinophilic (oncocytic) cytoplasm and prominent cell membranes, with characteristic and easily recognizable large intracytoplasmic vacuoles. Nuclei are round to oval with prominent nucleoli. However, no aggressive behavior has been reported.

The tumor cells have an immunohistochemical profile like an oncocytoma and are positive for PAX8, AE1/AE3, CD117 and CD10 with variable CK7, from negative to focally positive. However, Cathepsin K is usually positive with focal to diffuse staining. Vimentin, CK20, HMB45, Melan-A, and TFE3 are negative. SDHB and FH expressions are retained. Some tumors show germline mutations in TSC1 and MTOR and have been reported in patients with tuberous sclerosis. Somatic TSC2 inactivating mutations or MTOR activating mutation been reported in sporadic tumors. The copy number alterations seen in EVT/HOT include losses of chromosomes 1 and 19.

Although renal oncocytoma and chromophobe renal cell carcinoma share some morphological similarities, these tumors do not fit into these recognized categories. The high grade cytologic appearance and prominent large intracytoplasmic are usually not seen in oncocytomas and chromophobe RCC. EVT/HOT shares molecular similarities with ESC RCC and both tumors can be seen in TSC patients. Immunohistochemically ESC RCC are usually negative for CD117 and positive for CK20, which is different from the immunoprofile of EVT/HOT.

1. Trpkov, K., Williamson, S.R., Gill, A.J. et al. Novel, emerging and provisional renal entities: The Genitourinary Pathology Society (GUPS) update on renal neoplasia. Mod Pathol. 2021; 34, 1167–1184.

2. Chen YB, Mirsadraei L, Jayakumaran G, Al-Ahmadie HA, Fine SW, Gopalan A, Sirintrapun SJ, Tickoo SK, Reuter VE. Somatic Mutations of TSC2 or MTOR Characterize a Morphologically Distinct Subset of Sporadic Renal Cell Carcinoma With Eosinophilic and Vacuolated Cytoplasm. Am J Surg Pathol. 2019 Jan;43(1):121-131.

3. He H, Trpkov K, Martinek P, Isikci OT, Maggi-Galuzzi C, Alaghehbandan R, Gill AJ, Tretiakova M, Lopez JI, Williamson SR, Montiel DP, Sperga M, Comperat E, Brimo F, Yilmaz A, Pivovarcikova K, Michalova K, Slouka D, Prochazkova K, Hora M, Bonert M, Michal M, Hes O. “High-grade oncocytic renal tumor”: morphologic, immunohistochemical, and molecular genetic study of 14 cases. Virchows Arch. 2018 Dec;473(6):725-738.

4. Gupta S, Jimenez RE, Herrera-Hernandez L, Lohse CM, Thompson RH, Boorjian SA, Leibovich BC, Cheville JC. Renal Neoplasia in Tuberous Sclerosis: A Study of 41 Patients. Mayo Clin Proc. 2021 Jun;96(6):1470-1489.

Lagnajita Datta
Sounak Gupta
Mayo Clinic, Rochester, MN


Eosinophilic vacuolated tumor, high grade oncocytic tumor, EVT, HOT