Brain Pathology Case of the Month - November 2017

FINAL DIAGNOSIS

Metastatic chromophobe renal cell carcinoma in cerebellum.

DISCUSSION

Renal cell carcinoma (RCC) is the commonest neoplasm of the kidney. Chromophobe renal cell carcinoma (chRCC) accounts for 5-10% of all RCC [4]. Although a wide range of histomorphologic prognostic parameters have been investigated for RCC, those that really matter to the patient are very limited. Tumour morphology is one of the most important of prognostic parameters with chRCC documented to have a better prognosis than the other subtypes. Other time tested parameters include Fuhrman nuclear grade, sarcomatoid and rhabdoid differentiation. Interestingly, chRCC is an exception to the rule, as it is the only variant amongst the other subtypes, for which the International Society of Urological Pathologists (ISUP) has recently agreed upon not grading this subtype [1]. A vast majority of chRCC are indolent, present at a low stage and are associated with a more favourable outcome. Only a few behave aggressively with a higher stage. The most common metastatic sites are liver, lung and lymph nodes [1,2]. To the best of our knowledge, unequivocal brain metastasis is reported in only 2 cases of chRCC [2,3]. Our case is unique in several aspects: 1) first documented case of chRCC with a solitary cerebellar metastasis, 2) rarity of chRCC presenting with brain metastasis compared to other variants of RCC especially, clear cell RCC,3) existing controversies regarding the management and outcome of such patients.

Until date, the following issues remain unaddressed with respect to chRCC metastasis localized to the cerebellum:

  1. Why cerebellar metastasis is very uncommon in chRCC as compared to clear cell RCC?
  2. Why the common sites of metastasis such as lymph nodes, liver and lung were skipped?
  3. Unlike the primary site, should we ignore grading of chRCC in metastatic sites, especially brain?
  4. In asymptomatic solitary cerebellar chRCC metastasis, what is the role of gross total excision?
  5. Role of upcoming histopathologic prognostic parameters such as coagulative necrosis, ISUP/WHO nucleolar grading, microvessel density (MVD), microscopic vascular invasion (MVI), etc. in primary and metastatic tumors.
  6. What is the likely outcome?

Differential diagnoses of cerebellar lesions include hemangioblastoma, microcystic meningioma, clear cell RCC and rarely low grade gliomas. Neoplastic cells express immunoreactivity with inhibin in hemangioblastoma while meningiomas are diffusely positive with EMA and vimentin. Immunoreactivity with glial fibrillary acidic protein helps in distinguishing low grade gliomas from other lesions arising within cerebellum. Neoplastic cells in clear cell RCC characteristically show immunoreactivity with CD10, besides being positive for CK, EMA and PAX8.

The postoperative period of the index case was uneventful and a radical nephrectomy is anticipated provided the performance status permits.

REFERENCES

  1. Delahunt B, Cheville JC, Martignoni G, Humphrey PA, Magi-Galluzzi C, McKenney J, et al (2013) The International Society of Urological Pathology (ISUP) grading system for renal cell carcinoma and other prognostic parameters. Am J Surg Pathol 37: 1490-504.
  2. Prayson RA (2016) Metastatic chromophobe renal cell carcinoma to the brain. J Clin Neurosci 26: 152-3.
  3. Shuch B, La Rochelle JC, Klatte T, Riggs SB, Liu W, Kabbinavar FF, et al (2008) Brain metastasis from renal cell carcinoma: presentation, recurrence, and survival. Cancer 113: 1641-8.
  4. Vera-Badillo FE, Conde E, Duran I (2012) Chromophobe renal cell carcinoma: a review of an uncommon entity. Int J Urol 19: 894-900.

Contributed by Balan Louis Gaspar, MD, Kirti Gupta, MD, Apinder Preet Singh, MS, M Ch, Pravin Salunke, MS, M Ch

International Society of Neuropathology