Eosinophilic Solid and Cystic Renal Cell Carcinoma: From Unclassified to Classified, A Case Report
Rashim SHARMA1, Balamurugan THIRUNAVUKKARASU1, Poonam ELHENCE1, Mahaveer Singh RODHA2, Binit SUREKA3
1Departments of Pathology and Lab Medicine, All India Institute of Medical Sciences, RAJASTHAN, INDIA
2Departments of Trauma and Emergency, All India Institute of Medical Sciences, RAJASTHAN, INDIA
3Departments of Diagnostic and Interventional Radiology, All India Institute of Medical Sciences, RAJASTHAN, INDIA
Keywords: Eosinophilic solid and cystic renal cell carcinoma, Unclassified renal cell carcinoma, Emerging entity, Oncocytic renal tumour
Eosinophilic solid and cystic renal cell carcinoma (ESC RCC) is a novel tumour with unique morphological and immunohistochemical features.
It is a recently described entity after the 2016 World Health Organization Classification of Tumours of the Urinary System and Male Genital
Organs and is characterised by a solid cystic tumour composed of polygonal cells with voluminous eosinophilic cytoplasm and CK20 positivity.
This tumour has uncertain malignant potential and also has an association with tuberous sclerosis complex (TSC). Sarcomatoid differentiation
has not been reported in ESC RCC till now. ESC RCC poses a diagnostic challenge as many eosinophilic/oncocytic renal tumours are included
in the differentials. We present a case of ESC RCC with sarcomatoid differentiation in an elderly female without any clinical features of TSC and
discuss the differential diagnosis of oncocytic renal tumours.
Our understanding of renal tumours has significantly
improved in the past years. This is due to advancements
in the field of molecular pathology. Several new entities
have been described and there is reclassification of the
existing tumours after consideration of clinical features,
morphology, immunohistochemistry and genetic
alterations. Oncocytic renal tumours, that were once in
the unclassified category, have gained a separate diagnostic
category owing to their prognostic implication and
clinical relevance. Attention to the histomorphology and a
methodical immunohistochemical approach can lead to an
accurate diagnosis in many such tumours.
A 67-year-old female presented with a gradually increasing
abdominal lump for 7 months. On clinical examination,
a palpable lump was noted in the right lumbar region.
Urine testing for malignant cytology was negative on
three consecutive samples. Computed Tomography
urography revealed a large, heterogeneously enhancing
mass measuring 18x16x15 cm in the inferior pole of right
kidney and causing superior displacement of the remaining
kidney with splaying of the pelvicalyceal system (Figure
). There was heterogeneous moderate enhancement
in the corticomedullary phase and the same pattern of moderate enhancement in the nephrographic phase with
no washout in the delayed phase (Figure 1B
). A large central
non-enhancing region was also noted suggesting necrosis
along with multiple enhancing septations. The lesion was
displacing the infrahepatic inferior vena cava, pancreas and
second part of duodenum to the left side with no evidence
of metastasis. The patient subsequently underwent radical
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|Figure 1: A) Coronal CT image in corticomedullary phase shows large malignant mass in the right kidney (arrows) with heterogeneous
moderate enhancement and a large area of necrosis. B) Nephrographic phase scan showing same pattern of moderate enhancement with
no washout (arrows). C) Growth is solid cystic, predominantly yellowish and necrotic in the inferior and middle poles and fleshy tan
brown in the upper pole.
On gross examination, the kidney measured 21x16x12cm.
The attached adrenal gland was unremarkable. On serial
sectioning, an ill-circumscribed solid cystic tan brown,
yellowish tumour was noted in the middle and inferior
pole, abutting the capsule and measuring 19.5x14x9.5 cm
(Figure 1C). Two coalescing nodules were noted. The larger
nodule was predominantly yellowish cystic whereas the
smaller nodule showed solid-grey brown area. The cystic
spaces ranged from 0.3 to 1.6 cm. The renal sinus was
pushed to upper pole and appeared free. Areas of necrosis
were noted. On microscopy, the macrocysts were lined by
round to polygonal tumour cells with eosinophilic granular
cytoplasm, round nuclei, coarse to hyperchromatic nuclei
and conspicuous nucleoli (Figure 2A,B). Lymphocytes and
foamy histiocytes were interspersed with the tumour cells
(Figure 2C). The solid area showed tumour arranged in
nests/insular/archipelagenous, trabecular and solid pattern
(Figure 2D,E). Cells with voluminous cytoplasm, nuclear pleomorphism and hobnailing were noted predominantly
in the cystic areas, while the cytoplasm was dense, bright
eosinophilic in the organoid areas. Focally, intracytoplasmic
amphophilic to basophilic leishmania-like inclusions with
halo were also seen (Figure 2F). However, papillary pattern,
abundant clear cytoplasm, perinuclear halo, psammoma
bodies, raisinoid nuclei, and biphasic cellular population
were absent. Sarcomatoid differentiation in the form of
spindling (10%) and areas of necrosis (40%) were seen
(Figure 3A,B). The renal sinus, pelvis, adrenal gland and
renal vessels were free of tumour.
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|Figure 2: A) Cystic area (H&E; x4). B) Polygonal tumour cells with hobnailing (H&E; x20). C) Tumour cells admixed with foamy
macrophages and scattered lymphocytes (H&E; x20). D) Solid arrangement of tumour cells with vacuolated eosinophilic cytoplasm
(H&E; x40). E) Nested/archipelagenous pattern with dense cytoplasm (H&E; x40). F) Intracytoplasmic amphophilic leishmania-like
inclusions in the tumour cells (yellow arrow) (H&E; x60)
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|Figure 3: A) Sarcomatoid areas
noted in the tumour (H&E;
x40). B) Large area of tumour
necrosis (H&E; x20). C) Strong
and diffuse membranous
CD117 positivity in the nested
area (IHC; x40). D) Weak
membranous CD117 positivity
in the solid area (IHC; x40).
The differentials considered were oncocytic renal tumours
such as eosinophilic solid and cystic renal cell carcinoma,
eosinophilic variant of chromophobe renal cell carcinoma,
hybrid oncocytic/chromophobe tumour (HOCT), low
grade oncocytic tumour (LOT), high grade oncocytic
tumour (HOT), ALK rearranged renal cell carcinoma, MiT
family translocation renal cell carcinoma, and epithelioid angiomyolipoma (AML). Immunohistochemistry (IHC)
was done (Figure 4). The tumour cells were diffusely and
strongly positive for PAX8 (MRQ-50, Cell Marque, RTU),
Pan cytokeratin (AE1/AE3, Thermofisher, RTU). Tumour
cells showed focal strong positivity for CK20 (Ks20.8,
Thermofisher, RTU) predominantly in the cystic areas.
There was variable expression of CD117 (A4502, Dako,
1:200 dilution) in the nested areas (intense) vs. solid area
(weak positive) (Figure 3C,D). Tumour cells were also
positive for CD10 (GM003, PathnSitu, RTU), and Melan
A (A103, Thermofisher, RTU). They were negative for
CK7 (OV-TL12/30, Thermofisher, RTU), AMACR (13H4,
Thermofisher, RTU), S100P (4C4.9, Thermofisher, RTU),
TFE3 (MRQ-37, Cell Marque, RTU), and ALK (CD246,
Dako, RTU). Based on the histomorphology and IHC,
a diagnosis of eosinophilic solid and cystic renal cell
carcinoma, pT2bN0 was rendered. There were no postoperative
complications and currently the patient is on
routine post-operative care.
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|Figure 4: A,B) CK20 focal strong membranous positivity in cystic area (IHC; x10 and x40). C) CK7 is negative in the tumour area
(positive internal control - distal convoluted tubules) (IHC; x10). D) PAX-8 positivity (IHC; x20). E) Melan-A positivity (IHC; x20).
F) Pancytokeratin positivity (IHC; x20).
The term “Eosinophilic solid and cystic renal cell carcinoma
(ESC RCC)” was coined by Trpkov et al in 2016
. Once described under unclassified RCC/eosinophilic/
oncocytic tumours, the characteristic features of ESC RCC
were later described in a series illustrating the various RCC
in patients with tuberous sclerosis (TSC associated RCC)
. Subsequently, tumours with identical morphology
were also described in sporadic cases, exclusively in
. As the name states, ESC RCC are characterised
by solid and cystic areas. Both micro and macrocysts
lined by tumour cells with or without hobnailing can be
seen. Though predominantly described in adult females,
cases have been described in teenagers and in males 1,4
Grossly, size of most of the tumours are less than 5 cm
(Range: 0.5 cm to 13.5 cm). Size of tumour in the present
case was 19.5 cm which is the largest documented till date
. The classically described features such as nested and
solid architecture, hobnailing, voluminous granular cytoplasm with amphophilic to basophilic “leishmania-like”
inclusions were also identified in the present case 1,2,5
The signature IHC profile in ESC RCC is CK20 positivity
(patchy or diffuse) with CK7 absent to weak positivity.
CK20 can be negative in up to 12% of cases but it should
never be diffuse CK7 positive with CK20 negative in ESC
RCC. Our case showed strong CK 20 positivity, albeit focal.
CD117 is usually negative. Focal positivity was described
in 1 out of 16 patients in a series 1
. In the present case,
CD117 expression was limited to nested “Oncocytoma-like
region” and weak to absent in the solid areas.
ESC RCC has a wide range of differentials to be considered.
The eosinophilic renal neoplasms include oncocytoma,
eosinophilic variant of chromophobe RCC, hybrid
oncocytic/chromophobe tumour (HOCT), MiT family
translocation carcinoma, clear cell RCC, epithelioid
angiomyolipoma, low grade oncocytic tumour (LOT)
and high grade oncocytic tumour (HOT)/ eosinophilic
vacuolated tumour (EVT), Succinate dehydrogenase (SDH) deficient RCC, ALK rearranged RCC, and
epithelioid angiomyolipoma. Other tumours less relevant
to this case include tubulocystic RCC, acquired cystic
disease associated RCC, Fumarate hydratase deficient RCC,
papillary RCC, and thyroid-like follicular carcinoma of the
kidney 5-7. Oncocytoma is a benign tumour characterised
by monomorphic population of tumour cells. Though there
were focal compact areas resembling oncocytoma in this
case, there were other areas with variable architectural
pattern with voluminous eosinophilic granular cytoplasm
and cystic areas. This case lacked the perinuclear halo and the
irregular hyperchromatic raisinoid nuclei of chromophobe
renal cell carcinoma. CK7 was negative giving credence
to exclusion of both these differentials and HOCT. ESC
RCC can express Melan A, HMB45 or Cathepsin K. PAX-
8 positivity rules out an epithelioid angiomyolipoma,
in addition to absence of other morphological features
of AML 2,6,8. There was absence of the characteristic
“intracytoplasmic vacuoles/ flocculent cytoplasm” seen in
SDH deficient RCC. In addition, diffuse pan cytokeratin
positivity noted in this case negates the diagnosis. MiT
family translocation carcinoma presents in a younger age
group and can either be Xp11.2 or t6,11 type. Few features
shared by these tumours and ESC RCC are the polygonal
cells with abundant vacuolated cytoplasm and positivity for
Melan A. However, the macrocystic areas, lack of papillary
pattern, CK20 positivity and negative TFE3 favours ESC
RCC. ALK rearranged RCC shows variable architectural
pattern, and mucinous myxoid stroma with or without
signet ring cells with ALK positivity.
Other recently described oncocytic tumours are LOT
and HOT/EVT. LOT is grossly predominantly solid, and
tan yellow. Microscopy resembles that of oncocytoma.
However, they are negative for CD117 and are diffusely
positive for CK7 7. High-grade oncocytic tumour was
recently relabelled as “Eosinophilic vacuolated tumour”
characterised by large vacuolated cytoplasm and higher
nuclear grade with positivity of pan CK, PAX8 and CD117
9. CK7 is negative to focal weak positive. The cells lack the
granular cytoplasm of ESC RCC and are negative for Melan
A and CK20 9.
Tubulocystic RCCs are dominantly microcystic along
with tightly cohesive tubules lined by eosinophilic cells.
Hobnailing can also be seen. They are diffusely positive
for CK7, AMACR, CD10, EMA, Vimentin and PAX8 10.
Fumarate hydratase deficient RCC characteristically has
papillary pattern and prominent nucleoli with perinuclear
halo. Acquired cystic kidney disease associated RCC is seen
mainly in end stage renal disease 11. Morphologically variable patterns are noted with solid, microcystic and
macrocystic areas. Cells have prominent nucleoli along
with numerous oxalate crystals. On IHC, these tumours
are positive for CD10, AMACR and negative for CK7 6.
In conclusion, eosinophilic solid and cystic renal cell
carcinoma (ESC RCC) is one of the tumours described
post 2016 WHO classification and is classified as a “novel
entity” by the genitourinary pathology society (GUPS)
9,12. So far, approximately 65 cases have been reported
in several case series 1-4,8,13-17. This is probably an
understatement as many oncocytic tumours in the archives
are being reviewed and recognised. Currently, WHO
nuclear grading is not recommended. The exact prognosis
and metastatic potential are yet to be determined as few
reports have documented metastases in ESC 4,8,17.
Sarcomatoid differentiation has not been described in
CONFLICT of INTEREST
The authors declare no conflict of interest.
All the authors were involved in conception and design of
the work. RS and BT were involved in design, data collection
and writing. BT and PE were involved in data analysis and
approval. MSR and BS were involved in analysis of data and
1) Trpkov K, Hes O, Bonert M, Lopez JI, Bonsib SM, Nesi G,
Comperat E, Sibony M, Berney DM, Martinek P, Bulimbasic
S, Suster S, Sangoi A, Yilmaz A, Higgins JP, Zhou M, Gill AJ,
Przybycin CG, Magi-Galluzzi C, McKenney JK. Eosinophilic,
solid, and cystic renal cell carcinoma: Clinicopathologic study of
16 unique, sporadic neoplasms occurring in women. Am J Surg
2) Schreiner A, Daneshmand S, Bayne A, Countryman G, Corless
CL, Troxell ML. Distinctive morphology of renal cell carcinomas
in tuberous sclerosis. Int J Surg Pathol. 2010;18:409-18.
3) Guo J, Tretiakova MS, Troxell ML, Osunkoya AO, Fadare
O, Sangoi AR, Shen SS, Lopez-Beltran A, Mehra R, Heider A,
Higgins JP, Harik LR, Leroy X, Gill AJ, Trpkov K, Campbell
SC, Przybycin C, Magi-Galluzzi C, McKenney JK. Tuberous
sclerosis-associated renal cell carcinoma: A clinicopathologic
study of 57 separate carcinomas in 18 patients. Am J Surg Pathol.
4) Li Y, Reuter VE, Matoso A, Netto GJ, Epstein JI, Argani P. Reevaluation
of 33 ‘unclassified’ eosinophilic renal cell carcinomas
in young patients. Histopathology. 2018;72:588-600.
5) Trpkov K, Hes O. New and emerging renal entities: A perspective
post-WHO 2016 classification. Histopathology. 2019;74:31-59.
6) Kryvenko ON, Jorda M, Argani P, Epstein JI. Diagnostic
approach to eosinophilic renal neoplasms. Arch Pathol Lab Med.
7) Siadat F, Trpkov K. ESC, ALK, HOT and LOT: Three letter
acronyms of emerging renal entities knocking on the door of the
WHO classification. Cancers (Basel). 2020;12:168.
8) Tretiakova MS. Eosinophilic solid and cystic renal cell carcinoma
mimicking epithelioid angiomyolipoma: Series of 4 primary
tumors and 2 metastases. Hum Pathol. 2018;80:65-75.
9) Trpkov K, Williamson SR, Gill AJ, Adeniran AJ, Agaimy A,
Alaghehbandan R, Amin MB, Argani P, Chen YB, Cheng L,
Epstein JI, Cheville JC, Comperat E, da Cunha IW, Gordetsky
JB, Gupta S, He H, Hirsch MS, Humphrey PA, Kapur P, Kojima
F, Lopez JI, Maclean F, Magi-Galluzzi C, McKenney JK, Mehra
R, Menon S, Netto GJ, Przybycin CG, Rao P, Rao Q, Reuter VE,
Saleeb RM, Shah RB, Smith SC, Tickoo S, Tretiakova MS, True
L, Verkarre V, Wobker SE, Zhou M, Hes O. Novel, emerging and
provisional renal entities: The Genitourinary Pathology Society
(GUPS) update on renal neoplasia. Mod Pathol. 2021 Feb 1.
10) Skenderi F, Ulamec M, Vranic S, Bilalovic N, Peckova K,
Rotterova P, Kokoskova B, Trpkov K, Vesela P, Hora M,
Kalusova K, Sperga M, Perez Montiel D, Alvarado Cabrero
I, Bulimbasic S, Branzovsky J, Michal M, Hes O . Cystic renal
oncocytoma and tubulocystic renal cell carcinoma: Morphologic
and immunohistochemical comparative study. Appl
Immunohistochem Mol Morphol. 2016;24:112-9.
11) Tickoo SK, dePeralta-Venturina MN, Harik LR, Worcester
HD, Salama ME, Young AN, Moch H, Amin MB. Spectrum of
epithelial neoplasms in end-stage renal disease: An experience
from 66 tumor-bearing kidneys with emphasis on histologic
patterns distinct from those in sporadic adult renal neoplasia.
Am J Surg Pathol. 2006;30:141-53.
12) Moch H, Cubilla AL, Humphrey PA, Reuter VE, Ulbright TM.
The 2016 WHO classification of tumours of the urinary system
and male genital organs-part a: Renal, penile, and testicular
tumours. Eur Urol. 2016;70:93-105.
13) Parilla M, Kadri S, Patil SA, Ritterhouse L, Segal J, Henriksen
KJ, Antic T. Are sporadic eosinophilic solid and cystic renal cell
carcinomas characterized by somatic tuberous sclerosis gene
mutations?. Am J Surg Pathol. 2018;42:911-7.
14) Palsgrove DN, Li Y, Lin MT, Pallavajjalla A, Gocke C, De Marzo
AM, Matoso A, Netto GJ, Epstein JI, Argani P. Eosinophilic solid
and cystic (ESC) renal cell carcinomas harbor TSC mutations:
Molecular analysis supports an expanding clinicopathologic
spectrum. Am J Surg Pathol. 2018;42:1166-81.
15) Xia QY, Wang X, Wei X, Wang XT, Ma HH, Lu ZF, Rao
Q. Eosinophilic solid and cystic renal cell carcinoma:
Clinicopathological analysis and molecular characterization.
Zhonghua Bing Li Xue Za Zhi. 2019;48:840-5.
16) Yang WP, Chang KTE, Xu HY, Kuick CH, Ng EHQ, Huang H,
Xiong F, Wu Y, Zeng ST, Fan JX, Loh XY. Eosinophilic solid and
cystic renal cell carcinoma with TSC2 gene mutations in children.
Zhonghua Bing Li Xue Za Zhi. 2020;49:693-8.
17) McKenney JK, Przybycin CG, Trpkov K, Magi-Galluzzi
C. Eosinophilic solid and cystic renal cell carcinomas have
metastatic potential. Histopathology. 2018;72:1066-7.