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Year : 2023  |  Volume : 66  |  Issue : 2  |  Page : 363-365
Chromophobe renal cell carcinoma with rare distant metastasis

1 Department of Pathology, Sri Manakula Vinayagar Medical College and Hospital, Puducherry, India
2 Department of Pathology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
3 Department of Neurosurgery, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India

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Date of Submission11-Jun-2021
Date of Decision27-Jun-2021
Date of Acceptance07-Jul-2021
Date of Web Publication27-Apr-2022


Metastasis accounts for the most common tumor of the central nervous system (CNS) in adults. Renal cell carcinoma (RCC) is one of the common carcinoma showing brain metastasis, with a predilection for clear cell variant. Chromophobe RCC (ChRCC) in contrast to clear cell RCC shows far less common distant metastasis. When they metastasize, commonly involve the liver, lungs, and lymph nodes. ChRCC metastasizing to the brain is extremely rare. Isolated brain metastasis from RCCs is also uncommon. We report an unusual case of a 54-year-old woman with ChRCC with isolated metastasis to the brain, 2 years after radical nephrectomy for renal mass.

Keywords: Brain metastasis, chromophobe, grading, prognosis

How to cite this article:
Keloth T, Srinivas BH, Ganesh RN, Ramesh AS. Chromophobe renal cell carcinoma with rare distant metastasis. Indian J Pathol Microbiol 2023;66:363-5

How to cite this URL:
Keloth T, Srinivas BH, Ganesh RN, Ramesh AS. Chromophobe renal cell carcinoma with rare distant metastasis. Indian J Pathol Microbiol [serial online] 2023 [cited 2023 Jun 3];66:363-5. Available from:

   Introduction Top

Renal cell carcinoma (RCC) represents 2%–3% of all malignancies in adults and constitutes about 85% of malignant renal tumors. Among the various histological subtypes of RCC, clear cell carcinoma is the commonest followed by papillary and chromophobe variants. Chromophobe renal cell carcinoma (ChRCC) constitutes about 5% of adult RCCs.[1],[2] ChRCC rarely metastasize, liver, lungs, lymph nodes, and bones being the sites for metastasis. Metastasis to the brain is extremely rare in the case of ChRCC.[1],[2],[3],[4] Isolated metastasis to the brain is uncommon in RCCs. Hereby we report a rare case of ChRCC with isolated metastasis to the brain.

   Case Report Top

A 54-year-old woman who was a known and treated case of ChRCC 2 years ago, presented with headache and few episodes of vomiting for a period of 3–4 weeks. On examination, she was conscious, but disoriented. She did not have neurological deficits. Routine hematological and biochemical investigations were within normal limits. Contrast-enhanced computed topography (CECT) showed a 5 cm × 4 cm × 4 cm, non-enhancing, hyperdense mass lesion in the right parieto-occipital region [Figure 1]a with a probable diagnosis of a metastatic tumor or a primary high-grade glioma.
Figure 1: (a) CECT image showing a tumor in the right parieto-occipital region. Photomicrographs showing (b) tumor with adjacent normal brain tissue (H and EX100), (c and d) tumor fragments composed of polygonal cells with distinct cytological border, perinuclear halo and vesicular nuclei (H and EX400)

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She had undergone radical nephrectomy with splenectomy and subtotal pancreatectomy 2 years before for a mass lesion in the kidney, morphology, and immunohistochemistry (IHC) of which favored a ChRCC. Hale's colloidal iron, CK7, and CD117 were positive in the tumor cells and CD10 was negative. There was no nuclear crowding or sarcomatoid areas present. The tumor was abutting the spleen and the pancreas, but no infiltration was present. Coagulative necrosis amounting to less than 50% of the tumor and areas of osseous metaplasia were present. Also, there was lymphovascular invasion (LVI). Capsular invasion was absent and the resected margins and lymph nodes were free of tumor. She was on follow-up; however, adjuvant immunotherapy was not initiated after the initial surgery which is the routinely followed management for localized ChRCC.

She underwent right temporo-parietal craniotomy with decompression of the lesion. The histopathological examination of the brain lesion showed normal parenchyma admixed with tumor fragments composed of sheets of polygonal cells with distinct cytological border, perinuclear halo, vesicular nuclei, and few showing prominent nucleolus [Figure 1]b, [Figure 1]c, [Figure 1]d. Differential diagnoses included granular cell astrocytoma, Glioblastoma, and metastatic ChRCC. Glioblastoma was excluded as features like necrosis, microvascular proliferation or pleomorphism were not present. Keeping in mind the previous history of primary ChRCC and the classical histopathological features, we went ahead with IHC which showed tumor cells positive for CD117 and CK7 [Figure 2] and negative for CD10 and vimentin. Based on the histomorphological features and IHC, a diagnosis of metastatic ChRCC was confirmed.
Figure 2: Immunohistochemistry images: (a and b) tumor cells showing positivity for CD117 and CK7 (DAB 400), (c and d) tumor cells negative for CD10 and Vimentin (endothelial cells as control positive) (DAB ×400 and DABX200)

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She was started on oral tyrosine kinase inhibitor (sunitinib) based on the final diagnosis. But she had residual tumor and succumbed to her disease one year after the surgery.

   Discussion Top

ChRCC was first described by Thoenes et al.[5] in 1985. ChRCC accounts only for five percent of the RCCs, with recent studies showing increased incidence up to 10.4%.[6] ChRCC is a unique subtype of RCC which arises from the intercalated cells of the collecting ducts. ChRCC is histologically characterized by broadsheets of polygonal cells with granular eosinophilic cytoplasm with distinct cell borders arranged along vascular septae. Perinuclear halo is a distinct feature. Necrosis and hemorrhage are uncommon. The morphological differential diagnoses of ChRCC include renal oncocytoma, eosinophilic variant of clear cell RCC, and oncocytic variant of papillary RCC. Staining with Hale's colloidal iron is positive in ChRCC, which is a differentiating feature from other variants of RCCs and oncocytomas. Immunohistochemically, ChRCC is positive for CD117 (c-kit) and CK7, while negative for CD10 and vimentin.[2],[7],[8] Renal oncocytomas are negative for CK7. Clear cell RCCs are positive for vimentin, CD10, and RCC antigen and negative for CK7, while papillary RCCs are positive for AMACR, CD10, vimentin, and RCC antigen. CK7 is expressed more in type I than type II papillary RCC.[4],[7]

Differentiating ChRCC from other variants is important as the prognosis is different for different types of RCCs. Generally, ChRCCs have an excellent prognosis and less incidence of sarcomatoid differentiation with a 5-year progression-free survival rate approximately 90%. However, some studies have shown that patients with locally advanced or metastatic malignancies and those with sarcomatoid differentiation and coagulative necrosis have a poor prognosis.[1],[6],[9],[10] Furhman nuclear grading is used as a prognostic indicator in RCC. However, this grading system which focuses on nuclear atypia and presence of nucleoli may not be applicable for ChRCC as nuclear atypia is an inherent feature in ChRCC.[6],[9] Hence most of the ChRCC would be having a higher Furhman grade. A three-tier system, 'Chromophobe tumor grading' for grading of this variant of RCC was proposed, which includes nuclear crowding, pleomorphism, and sarcomatoid change.[7],[9] This system excludes the nuclear atypia from the grading. Recent studies propose to include coagulative necrosis also in the grading and risk stratification of ChRCCs.[9] Our case did not have sarcomatoid differentiation or nuclear crowding, but had coagulative necrosis and LVI in the primary tumor. Reviewing the previously reported cases of ChRCC with brain metastasis, complete details of the primary tumor were not mentioned. In some cases, there was no sarcomatoid differentiation, necrosis, or nuclear crowding, but few cases had lymph node involvement at the time of primary ChRCC diagnosis.[1],[2],[8]

Different variants of RCCs have different rate and sites of metastasis.[2] Usually brain metastasis is seen with concurrent metastases to other sites.[1],[3] Metastasis from ChRCC is uncommon, with a reported incidence of one to seven percent, liver, lung, lymph node, and bones being the commonest sites.[2],[4],[6] To the best of our knowledge only a handful of cases of brain metastasis from ChRCC have been reported till date.[1],[2],[3],[4],[8]

Brain imaging as a part of routine surveillance is not recommended after curative nephrectomy in asymptomatic patients. Brain metastases are generally associated with bad prognosis and a high degree of morbidity and mortality.[1],[4] A possibility of brain metastasis should be considered if a patient presents with neurological symptoms in a case of RCC including ChRCC even though metastasis to the brain is uncommon. Presence of coagulative necrosis and LVI in ChRCC should be considered as bad prognostic indicators and regular follow-up with adjuvant immunotherapy should be recommended for such cases.

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


Conflicts of interest

There are no conflicts of interest.

   References Top

Alshamsi H, Al Muhrij A, Taha M, Al Mousa R. Brain metastasis from chromophobe renal cell carcinoma. Int J Cancer Res Mol Mech 2017;3:8-10.  Back to cited text no. 1
Prayson RA. Metastatic chromophobe renal cell carcinoma to the brain. J Clin Neurosci 2016;26:152-3.  Back to cited text no. 2
Shuch B, La Rochelle JC, Klatte T, Riggs SB, Liu W, Kabbinavar FF, et al. Brain metastasis from renal cell carcinoma: Presentation, recurrence, and survival. Cancer 2008;113:1641-8.  Back to cited text no. 3
Dudani S, De Velasco G, Wells JC, Gan CL, Donskov F, Porta C, et al. Evaluation of clear cell, papillary, and chromophobe renal cell carcinoma metastasis sites and association with survival. JAMA Netw Open 2021;4:e2021869.  Back to cited text no. 4
Thoenes W, Storkel S, Rumpelt HJ. Human chromophobe cell renal carcinoma. Virchows Arch B Cell Pathol Incl Mol Pathol 1985;48:207-17.  Back to cited text no. 5
Volpe A, Novara G, Antonelli A, Bertini R, Billia M, Carmignani G, et al. Chromophobe Renal cell carcinoma (RCC): Oncological outcomes and prognostic factors in a large multicentre series. BJU Int 2012;110:76-83.  Back to cited text no. 6
Moch H, Ohashi R. Chromophobe renal cell carcinoma: Current and controversial issues. Pathology 2021;53:101-8.  Back to cited text no. 7
Gaspar BL, Gupta K, Singh AP, Salunke P. A 39-year old gentleman with headache, visual blurring and a renal mass. Brain Pathol 2018;28:301-2.  Back to cited text no. 8
Avulova S, Cheville JC, Lohse CM, Gupta S, Popretzke TA, Tsivian M, et al. Grading chromophobe renal cell carcinoma: Evidence for a four-tiered classification incorporating coagulative tumor necrosis. Eur Urol 2021;79:225-31.  Back to cited text no. 9
Ged Y, Chen Y-B, Knezevic A, Casuscelli J, Redzematovic A, DiNatale RG, et al. Metastatic chromophobe renal cell carcinoma: Presence or absence of sarcomatoid differentiation determines clinical course and treatment outcomes. Clin Genitourin Cancer 2019;17:e678-88.  Back to cited text no. 10

Correspondence Address:
Bheemanathi Hanuman Srinivas
Department of Pathology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry - 605 006
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijpm.ijpm_590_21

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