Case Report: Unclassified Renal Cell Carcinoma With Medullary Phenotype and SMARCB1/INI1 Deficiency, Broadening the Spectrum of Medullary Carcinoma

Abstract

Renal medullary carcinoma (RMC) is a rare entity with poor prognosis bearing inactivating genomic alterations in SMARCB1/INI1 resulting in the loss of expression of INI1 and occurring in young patients with sickle cell trait or sickle cell disease. Recently, rare examples with histological characteristics of RMC have been described in older patients without hemoglobinopathies and provisionally termed “Renal cell carcinoma unclassified with medullary phenotype” (RCCU-MP). Fluorescence in situ Hybridization (FISH) can detect alterations in SMARCB1/INI1 consisting mostly in inactivating translocation of one allele and deletion of the second. To date, only seven further cases of RCCU-MP have been described in the literature. Here we report the second Italian case of RCCU-MP, a 62-year-old man presenting with persistent dull back pain and incidentally discovering a 13 cm mass in the right kidney. The nomenclature of this entity is still debated and might be updated as a variant of medullary carcinoma in the upcoming WHO classification. In the meantime, we encourage awareness of these extraordinarily rare neoplasms with poor outcomes.

A pediatric and young adult case of unclassified renal cell carcinoma with medullary phenotype (RCCU-MP): Clinical course and treatment

“…10,[30][31][32] Loss of INI1 in these tumors eliminates potential differential diagnoses such as upper tract urothelial carcinoma and anaplastic lymphoma kinase (ALK)-rearranged-or other RCC subtypes. 5,16 Immunohistochemically, our findings largely concur with those of Sirohi et al, 14 Lai et al, 15 and Sarkar et al, 17 showing immunostaining for PAX8 and pancytokeratin. In contrast to the previous adult reports, our pediatric case showed OCT4 negativity, in line with the pediatric case by Sarkar et al 17 This has also been observed in fumarate-hydratase deficient RCC, collecting duct carcinoma and upper tract urothelial carcinoma.…”

“…5,22,23 Despite the fact that the diagnostic terminology of RCCU-MP is still debated, our cases seem to meet the currently proposed definition of RMCs without sickle cell disease and -trait. 5,11,12,16 Nevertheless, reports of pediatric RCCU-MP are rare (Table 2). Sarkar et al 17 recently reported a case of RCCU-MP with pulmonary metastases in a 15-year old female with neurofibromatosis type 2.…”

“…25 Previously described cases of RCCU-MP seem to appear aggressive on imaging, with a bulky and ill-defined appearance, often invading the kidney and surrounding tissue. 14,16,17,24 In contrast, the more frequently occurring Wilms tumor in children is a large, round lesion with a tumor pseudo-capsule. 26 The MRI-findings of our reported pediatric case raised the suspicion for RCC because of the relatively small size, bulky lymphadenopathy and the lack of pseudo-capsule.…”

“…5,[11][12][13] At the moment of presentation of the two patients described here, only nine patients diagnosed with RCCU-MP had been des cribed. 10,[14][15][16][17] The majority of these cases are adult white males, aged between 24 and 71 years. RMC in adults appears less sensitive to the targeted therapies for other RCCs, resulting in very low survival rates.…”

“…RMC in adults appears less sensitive to the targeted therapies for other RCCs, resulting in very low survival rates. 16 Knowledge of the clinical course and treatment approach of this recently identified subtype remains limited, posing a question for clinicians as to how to treat these patients. 6,7 Here, we describe the clinical characteristics, treatment and course of a child and a young adult with RCCU-MP, and summarize literature-based insights of this rare and yet fairly unexplored renal malignancy, especially in these age categories.…”