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  Table of Contents    
CASE REPORT  
Year : 2021  |  Volume : 64  |  Issue : 4  |  Page : 799-801
Eosinophilic solid and cystic renal cell carcinoma: A rare under-recognized indolent entity


1 Department of Pathology, Rajiv Gandhi Cancer Institute and Research Centre, Rohini, New Delhi, India
2 Department of GenitoUro-Oncology, Rajiv Gandhi Cancer Institute and Research Centre, Rohini, New Delhi, India

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Date of Submission06-Aug-2020
Date of Decision16-Aug-2020
Date of Acceptance09-Dec-2020
Date of Web Publication20-Oct-2021
 

   Abstract 


Eosinophilic solid and cystic renal cell carcinoma (ESCRCC) is an under-recognized, emerging new entity of sporadic renal neoplasms, with an approximate incidence of 0.2% of renal tumors. A total of 60 cases have been reported in the literature till date. ESCRCC are usually seen in adult females, with a low stage and indolent behavior, and rare incidence of recurrence or metastasis. They are solid and cystic tumors with variably sized cysts resembling eosinophilic RCC, showing a characteristic positive immune-expression for PAX-8, CK20 (in ~80% cases) and/or Melan–A (in ~6.7%), with negative CK7 and CA-IX expression. They consistently harbor TSC1 or TSC2 mutations in all tumors, which is a proposed molecular marker for this entity. We here present the first reported case of this rare tumor from India. The tumor was positive for PAX-8, and showed diffuse strong positivity for Melan-A, while was negative for CK7 and CK20. It was an early-stage tumor (T1), managed with partial nephrectomy, with no evidence of any recurrence/metastasis after 1 year of follow-up.

Keywords: CK20, eosinophilic solid and cystic renal cell carcinoma, low stage, Melan-A, renal cell carcinoma

How to cite this article:
Kamboj M, Gupta G, Pasricha S, Rawal S, Sharma A, Durga G, Mehta A. Eosinophilic solid and cystic renal cell carcinoma: A rare under-recognized indolent entity. Indian J Pathol Microbiol 2021;64:799-801

How to cite this URL:
Kamboj M, Gupta G, Pasricha S, Rawal S, Sharma A, Durga G, Mehta A. Eosinophilic solid and cystic renal cell carcinoma: A rare under-recognized indolent entity. Indian J Pathol Microbiol [serial online] 2021 [cited 2021 Nov 28];64:799-801. Available from: https://www.ijpmonline.org/text.asp?2021/64/4/799/328585





   Introduction Top


Eosinophilic solid cystic renal cell carcinoma (ESCRCC) is an under-recognized renal neoplasms, with morphologic features first described in 2010 in patients with tuberous sclerosis complex (TSC),[1] and later described as a subtype of renal cell carcinoma (RCC) in 2016.[2] The morphologic large cells with abundant eosinophilic cytoplasm, makes it difficult to separate this specific entity among the list of other eosinophilic renal tumors. The characteristic immunophenotype of positive PAX-8 and CK20 with negative CK7 leads to a conclusive diagnosis of ESCRCC.

ESCRCC has been associated with distinct diagnostic and prognostic profile. It is an indolent tumor, with rare case reports of metastasis and recurrence.


   Case Report Top


A 55-year-old female was incidentally detected with a right renal mass. The positron enhancing tomographic (PET) scan showed a non-FDG avid enhancing lesion in superior pole of kidney, with no other lesion in rest of body. A clinico-radiological diagnosis of oncocytoma was made.

The patient underwent robotic nephron-sparing surgery. The cut surface of tumor on gross examination showed a pale-brown solid and cystic well-circumscribed tumor measuring 2.7 × 2 × 1.5 cm with few hemorrhagic areas, and variable-sized cysts (0.3 to 0.5 cm diameter) [Figure 1].
Figure 1: Cut surface of the renal mass showing a pale-brown solid and cystic tumor, with few tiny black areas of hemorrhage. {Capsular and perinephric surface marked by green ink (black arrow) and parenchymal cut surface by black ink (white arrow)}

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On microscopic examination, the tumor showed predominantly solid areas comprising of large polygonal cells having abundant eosinophilic-granular cytoplasm with nuclear features of World Health Organization (WHO)/International Society of Urological Pathology (ISUP) Grade 2. Many cystic areas were seen lined by hobnailed cells [Figure 2]. Mitotic activity was sparse. There was no evidence of any high-grade atypia, sarcomatoid or rhabdoid features, tumor necrosis, or lymphovascular invasion. No infiltrative pattern was seen, and the capsule was intact. The morphologic differentials included frank malignant entity like chromophobe RCC, eosinophilic clear cell renal cell carcinoma (CCRCC), and benign tumor-like oncocytoma, ESCRCC, and epithelioid angiomyolipoma (AML).
Figure 2: Microphotograph of the tumor: (a) Solid areas of tumor with cells arranged in acinar and tubular pattern (H&E, 200×); (b) Cystic areas lined by hobnail cells (H&E, 100×).(c and d) Higher magnification showing large polygonal tumor cells with abundant eosinophilic-granular cytoplasm, and WHO/ISUP grade 2 nuclear features (H&E, 400×)

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On immunohistochemistry (IHC) the tumor cells showed diffuse positivity for Pan-cytokeratin (CK), PAX-8, Vimentin, AMACR, and Melan-A, with focal CD10 expression, while were negative for CK7, EMA, carbonic anhydrase-IX (CA-IX), TFE-3, CD-117, CK20, and HMB45. IHC for succinate dehydrogenase (SDH)-B and fumarate hydratase (FH) was retained in the tumor cells [Figure 3].
Figure 3: Immunohistochemistry images showing focal and patchy CD10 (DAB, 200×) expression (a), with diffuse strong AMACR (DAB, 200×) (b), Melan-A (DAB, 200×) (c) and Vimentin (DAB, 200×) (d) in the tumor cells

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Hence, with the above morphological and IHC profile, a final diagnosis of ESCRCC was rendered, with pathologic stage of T1aNx. We could not establish the molecular profile of tumor. On follow-up for 1 year, there is no evidence of recurrence or metastasis.


   Discussion Top


Eosinophilic solid cystic renal cell carcinoma (ESCRCC) is a recently described emerging entity of sporadic renal neoplasms, currently not included in the WHO classification of renal tumors (4th edition).

Precise incidence of ESCRCC is unknown, as most of them were previously labeled as unclassified RCC with oncocytic or eosinophilic morphology. A total of 60 cases have been reported in literature till date, as per our knowledge, with an incidence of ~0.2%.[3]

ESCRCC shows a female preponderance, being uncommon in males, with a median age of 55 years.[4] They are usually unilateral, with rare multifocal and bilateral tumors.[5] Most of these tumors are detected in early stage (T1a or T1b), and show indolent behavior, with no recurrence or metastasis in the great majority of the cases/series. A single study has reported metastatic disease in ESCRCC in less than <10% cases.[4]

The unique morphology of this tumor was first described in patients with TSC in 2010,[1] and was first described as a novel subtype of RCC by Trpkov et al. in 2016.[2]

Grossly, ESCRCC tumors show a tan colored area with a median size of 31 mm. Solid and cystic areas are seen with variably sized macrocysts and microcysts. Microscopically, they show diffuse acinar or nested growth, with cysts lined by hobnailed cells. Cells have voluminous eosinophilic cytoplasm, with granular stippling, and round to oval nuclei (WHO/ISUP grade 2-3). Some cells may also show leishmania body like dense eosinophilic cytoplasmic globules. Intracytoplasmic vacuolization (micro or macro), insular, tubular or clear cell areas may also be identified. Multinucleation, calcification, psammoma bodies have been described rarely.[6]

Predominant morphologic differentials of ESCRCC include eosinophilic clear cell RCC (CCRCC), chromophobe RCC, oncocytomas, succinyl dehydrogenase (SDH)-deficient RCC, hybrid oncocytic RCC, and epithelioid angiomyolipoma (eAML).[6] Use of IHC panel helps distinguish all these entities.

On immunophenotyping the tumor cells uniformly express PAX-8, and Pan-cytokeratin (AE1/AE3 and CK8/18). CK20 is characteristically seen in 74% to 80% cases, while CK7 is usually negative (focal expression seen in 31% cases). CA-IX is mostly negative (positive in CCRCC), and focal expression of CD10 and CD117 has been reported.[4],[6] Although AMACR is usually negative, focal positivity in 85% cases has been seen,[4] (diffuse expression in our case). Expression of vimentin and cathepsin-K (not done in our case) has also been reported.[6]

Tretiakova et al. compared cases of ESCRCC resembling eAML, with PAX-8 as the distinguishing marker for ESCRCC, and expression of SMA and HMB45 in eAML. Expression of Melan-A (focal patchy to diffuse strong, similar to our case) and CK20 (focal to diffuse) was seen in all 4 cases of ESCRCC series (~6.7% of all reported ESCRCC).[6]

MiTF translocation RCC also shows a similar expression of PAX-8 and Melan-A (along with HMB45 and Cathepsin-K), but will under-express or be negative for CK, and show strong nuclear expression of TFE-3 or TFEB on IHC, with confirmation on translocation studies. Melan-A and Cathepsin-K expression in ESCRCC suggests a similar pathogenetic pathway and differentiation in eAML and MiTF translocation RCC.[7]

ESCRCCs predominantly demonstrate an indolent behavior, with no disease progression.[4] However, they can rarely show malignant features; 5% of reported cases had malignant disease with visceral (lung and liver) or lymph node metastases.[2],[4],[5],[8] In a series comparing ESCRCC resembling epithelioid AML (eAML), 2 of 4 ESCRCC were malignant.[6]

ESCRCC shows a molecular karyotype profile of recurring copy number (CN) alterations, different from other recognized renal neoplasms.[3] ESCRCC is postulated to be the sporadic counterpart of TSC-associated RCC, as they consistently harbor TSC1 or TSC2 mutations in all tumors, suggested to be a molecular marker for this tumor. A study has reported TSC1 or TSC2 mutations in 8 of 9 pediatric and in all 6 adult cases of ESCRCC.[9] Among patients with documented TSC, with somatic biallelic loss or mutation of TSC genes, specifically TSC1 or TSC2, ESCRCC has been reported in 10% cases.[3]

The treatment of ESCRCC is surgical, with partial or radical nephrectomy depending on the size and extent of tumor (tumor stage), amenability to resection, and comorbidities. In the largest series of ESCRCC of 19 patients, with stage pT1 in 89% patients and mean follow-up of 49.6 months, 3 died of unrelated causes.[4]

In conclusion, pathologists should be aware of this new and relatively under-recognized entity. A diligent histomorphological examination and a judicious IHC panel are essential for ruling out the other benign and malignant differentials, as this entity carries a distinct prognostic and therapeutic implications.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
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.  Back to cited text no. 1
    
2.
Trpkov K, Hes O, Bonert M, Lopez JI, Bonsib SM, Nesi G, et al. Eosinophilic, solid, and cystic renal cell carcinoma clinicopathologic study of 16 unique, sporadic neoplasms occurring in women. Am J Surg Pathol 2016;40:60-71.  Back to cited text no. 2
    
3.
Trpkov K, Hes O. New and emerging renal entities: A perspective post-WHO 2016 classification. Histopathology 2019;74:31-59.  Back to cited text no. 3
    
4.
Trpkov K, Abou-Ouf H, Hes O, Lopez JI, Nesi G, Comperat E, et al. Eosinophilic solid and cystic renal cell carcinoma (ESCRCC): Further morphologic and molecular characterization of ESCRCC as a distinct entity. Am J Surg Pathol 2017;41:1299-308.  Back to cited text no. 4
    
5.
Li Y, Reuter VE, Matoso A, Netto GJ, Epstein JI, Argani P. Re-evaluation of 33 'unclassified' eosinophilic renal cell carcinomas in young patients. Histopathology 2018;72:588-600.  Back to cited text no. 5
    
6.
Tretiakova MS. Eosinophilic solid and cystic renal cell carcinoma mimicking epithelioid angiomyolipoma: Series of 4 primary tumors and 2 metastases. Human Pathol 2018;80:65-75.  Back to cited text no. 6
    
7.
Argani P, Cheville J, Ladanyi M. MiT family translocation renal cell carcinomas. In: Eble JN, Sauter G, Epstein JI, Sesterhenn IA, editors. World Health Organization Classification of Tumours: Pathology and Genetics of tumors of the Urinary system and Male Genital Organs. 4th ed. Lyon (France): International Agency for Research on Cancer (IARC); 2016. p. 33-4.  Back to cited text no. 7
    
8.
McKenney JK, Przybycin CG, Trpkov K, Magi-Galluzzi C. Eosinophilic solid and cystic renal cell carcinomas have metastatic potential. Histopathology 2017;72:1066-7.  Back to cited text no. 8
    
9.
Palsgrove DN, Li Y, Lin MT, Pallavajjalla A, Gocke C, De Marzo AM, et al. 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.  Back to cited text no. 9
    

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Correspondence Address:
Meenakshi Kamboj
Consultant, Department of Pathology, Rajiv Gandhi Cancer Institute and Research Centre, Sector 5, Rohini, New Delhi - 110 085
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/IJPM.IJPM_938_20

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