Kidney tumor

Adult renal cell carcinoma - rare

Eosinophilic, solid and cystic

Editorial Board Member: Maria Tretiakova, M.D., Ph.D.
Editor-in-Chief: Debra L. Zynger, M.D.
Doreen Palsgrove, M.D.
Pedram Argani, M.D.

Last author update: 25 May 2021
Last staff update: 22 June 2022

Copyright: 2019-2022,, Inc.

PubMed Search: Eosinophilic, solid and cystic renal cell carcinoma

Doreen Palsgrove, M.D.
Pedram Argani, M.D.
Page views in 2021: 5,091
Page views in 2022 to date: 5,722
Cite this page: Palsgrove D, Argani P. Eosinophilic, solid and cystic. website. Accessed December 9th, 2022.
Definition / general
  • Emerging subtype of renal cell carcinoma (RCC) with abundant eosinophilic cytoplasm and solid / cystic growth, not yet recognized in the 2013 International Society of Urological Pathology (ISUP) Vancouver Classification of Renal Neoplasia or the updated 2016 World Health Organization (WHO) renal tumor classification (Am J Surg Pathol 2013;37:1469, Eur Urol 2016;70:93)
Essential features
  • Solid and cystic components
  • Voluminous eosinophilic cytoplasm which frequently displays basophilic intracytoplasmic stippling / inclusions
  • No clinical history or features of tuberous sclerosis complex
  • CK20+ / CK7- / c-kit- / PAX8+ immunoprofile
  • Frequently harbors somatic loss of function mutations in TSC1 or TSC2
ICD coding
  • ICD-10: C64.1 - malignant neoplasm of right kidney, except renal pelvis
  • ICD-10: C64.2 - malignant neoplasm of left kidney, except renal pelvis
  • ICD-10: C64.1 - malignant neoplasm of unspecified kidney, except renal pelvis
  • ICD-O: 8312 / 3 - renal cell carcinoma, NOS
  • F > M
  • Broad age range (14 - 75 years)
  • No documented clinical features, family history or germline genetic testing suggestive of tuberous sclerosis complex; see differential diagnosis below for more information
  • Left = right (no reported predilection)
  • Sporadic tumors believed to fall within a spectrum of renal neoplasms that harbor TSC1 / 2 genetic alterations (including the granular eosinophilic macrocystic subtype of tuberous sclerosis associated RCC and possibly the oncocytoid subtype of RCC postneuroblastoma, Am J Surg Pathol 2018;42:1166)
    • TSC1 (hamartin) and TSC2 (tuberin) form a functional heterodimer in the cytoplasm involved in cell signaling and proliferation through the kinase mTOR
    • Negative regulators of the AKT / mTOR signaling pathway
    • Loss of function mutations in TSC1 or TSC2 lead to constitutive mTORC1 activation that is uncoupled from upstream signaling inputs
Diagrams / tables

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mTOR mediated pathways

Radiology description
  • Heterogeneous, well defined nodule(s) with small cystic areas (Urology 2018;114:e9)
  • Cysts may display thickened irregular walls and septa
Radiology images

Contributed by Doreen Palsgrove, M.D.

CT abdomen and pelvis

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CT and MRI with gross specimen

Prognostic factors
Case reports

Case series:
  • 4 cases (3 women, 1 man; ages 27 - 50) including 1 with bone metastases and 1 with locally aggressive disease (Hum Pathol 2018;80:65)
  • 6 cases (all women; ages 42 - 66), all with deleterious mutations in either TSC1 or TSC2 (biallelic alterations in 2 cases) (Am J Surg Pathol 2018;42:1166)
  • 10 cases (all women; ages 32 - 85) including 1 case with multifocal disease (Am J Surg Pathol 2017;41:1299)
  • 10 cases (6 women, 4 men; ages 14 - 35) including 4 cases with multifocal lesions (1 bilateral), 1 case with metastatic disease to the liver and lung and 1 case with history of sickle cell trait (Histopathology 2018;72:588)
  • 16 cases, all solitary sporadic neoplasms with indolent behavior occurring in women (ages 31 - 75) (Am J Surg Pathol 2016;40:60)
  • Surgery is typically curative without progression of disease (solitary, renal confined lesions)
  • Possible role for mTOR inhibition in metastatic cases
    • Complete clinical response in a case of metastatic TSC2 mutated tumor using first generation rapamycin analog everolimus (Am J Surg Pathol 2018;42:1166)
Gross description
  • Frequently solitary lesions (occasionally multifocal, rarely bilateral) (Histopathology 2018;72:588)
  • Well delineated with a circumscribed pushing border
  • Yellow-tan solid nodules typically interspersed with macrocystic spaces
  • Occasional cases may be exclusively solid (Am J Surg Pathol 2017;41:1299)
  • < 1.0 - 20.5 cm in greatest diameter (Hum Pathol 2018;80:65)
  • Variable hemorrhage with associated necrosis
Gross images

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Microscopic (histologic) description
  • Unencapsulated
  • Solid or compact nested growth of eosinophilic cells admixed with macroscopic cysts or microscopic tubules / cysts (cysts may be focal to absent) (Am J Surg Pathol 2016;40:60)
  • Cysts typically lined by a single hobnail layer of neoplastic cells that are often multinucleated
  • May display papillary architecture
  • Voluminous granular eosinophilic cytoplasm, sometimes condensed centrally with a surrounding rim or more clear or flocculent cytoplasm (solid foci may have less voluminous cytoplasm)
  • Finely granular to coarse basophilic intracytoplasmic stippling / inclusions (most cases)
  • Densely eosinophilic to purple cytoplasmic globules surrounded by a delicate clear rim, reminiscent of leishmaniasis
  • Round to oval nuclei with mild pleomorphism and variably prominent nucleoli
  • Scattered binucleation / multinucleation
  • Cytoplasmic vacuolization (either macrovesicular or microvesicular) may give areas a clear cell appearance
  • Foamy macrophages (common)
  • Calcifications or osseous metaplasia (rare) (Hum Pathol 2018;80:65)
Microscopic (histologic) images

Contributed by Doreen Palsgrove, M.D.

Solid growth

Abundant cytoplasm

Basophilic cytoplasmic inclusions


Positive stains
Negative stains
Electron microscopy description
Molecular / cytogenetics description
Molecular / cytogenetics images

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Copy number alterations

Differential diagnosis
Board review style question #1

Which of the following immunoprofiles would support the diagnosis of this kidney lesion an eosinophilic, solid and cystic RCC and distinguish it from an epithelioid angiomyolipoma?

  1. Diffusely CD117+ / diffusely CK7+ / CK20-
  2. PAX8+ / CK20+ / CD117-
  3. SDHB- / PAX8+ / vimentin-
  4. TFE3+ / TFEB- / HMB45+
Board review style answer #1
B. PAX8+ / CK20+ / CD117-. This is an eosinophilic, solid and cystic (ESC) renal cell carcinoma. ESC RCCs are consistently immunoreactive for PAX8, frequently CK20+ (74% of cases, may be focal) and usually CK7- / CD117- (may be focal but never diffuse). Epithelioid angiomyolipomas, on the other hand, are typically negative for PAX8 and CK20 and positive for CD117. Both entities would be negative for strong nuclear TFE3 and show intact SDHB expression.

Comment Here

Reference: Eosinophilic, solid and cystic renal cell carcinoma
Board review style question #2
Eosinophilic, solid and cystic (ESC) renal cell carcinoma is most frequently associated with genetic alterations in which gene(s)?

  1. FLCN
  2. SDHB
  3. TSC1 / 2
  4. VHL
Board review style answer #2
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