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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).

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 t^6,11 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 literature.

CONFLICT of INTEREST
The authors declare no conflict of interest.

FUNDING
None

AUTHOR’S CONTRIBUTION
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 approval.

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