Chromophobe renal cell carcinoma with concomitant sarcomatoid transformation and osseous metaplasia: a case report

To the best of our knowledge, this is the first reported case of CRCC with concomitant osseous metaplasia and sarcomatoid transformation.

A number of recent studies concerning the prognosis of patients with CRCC have reported relatively good survival rates for this disease [1, 6], and cancer-related death occurred in 22%, 16%, and 8.6% of clear, papillary, and CRCC cases, respectively [7]. The good survival outcomes in these cases were probably because more than 70% of patients had organ-confined disease and more than 60% of tumors were low grade [7].

The incidence of sarcomatoid transformation is approximately 5% in RCC [8], increasing to 8% in the CRCC subtype [2, 9]. Heterologous sarcomatoid components, such as chondrosarcomatous, osteosarcomatous or rhabdomyosarcomatous component have also been reported [10]. Akhtar et al. suggested that sarcomatoid development in CRCC might be associated with its peculiar genetic profile, which makes cells prone to hyperploidization [11]. Bruneli et al. demonstrated that both the epithelial and sarcomatoid elements in a CRCC have different genetic abnormalities and that the latter show multiple gains of chromosomes 1, 2, 6, 10, and 17 [12]. The coexistence of both CRCC and sarcomatoid carcinoma may be due to either the dedifferentiation of the more highly differentiated chromophobe cell tumor or the coincidental development of two synchronous tumors [13]. The former model is more widely accepted as it is based on the evolution of renal carcinoma into a spindle cell population. This sarcomatoid change may be the result of extensive chromosomal rearrangement, leading to identical spindle morphology [12].

Sarcomatoid CRCC is a more aggressive neoplasm and has a very poor prognosis compared with classic chromophobe carcinoma [4]. The presence of a sarcomatoid component has been reported to be associated with an increased risk of metastasis and an unfavorable prognosis [2, 9, 14]. Previously reported cases of CRCC with sarcomatoid differentiation have shown distant organ metastases to sites including the bone, liver, lung, and lymph nodes [14].

RCCs exhibit a number of changes such as hemorrhage, necrosis, fibrosis, and hyalinization. However, although calcification is a well-recognized feature of renal tumors, they are rarely ossified. Daniel reported that 10.3% of RCCs had calcified foci, based on a review of 2,709 renal masses at the Mayo Clinic [15]. Moreover, reports of histopathologically confirmed osseous metaplasia or bone formation within RCC are rare [16]. The presence of ossification in CRCC, however, was noted in four previously reported cases [4].

The mechanism of ossification is unclear, although it might involve a metaplastic or reparative response either in the tumor or in the surrounding tissue, the production of bone by tumor cells, or the ossification of a preexisting mucin or calcium deposit [4]. Osseous metaplasia may occur secondary to ischemia, necrosis, or inflammation in the tumor or surrounding tissues [4].

The prognostic significance of ossification in CRCC remains unclear because of the limited number of cases reported to date. However, several studies demonstrated that ossification is a significant prognostic marker for patients with RCC [4, 17] and is usually representative of an early stage without invasion or metastasis [17]. Therefore, RCC with osseous metaplasia implies a more favorable prognosis, although this is contradicted by some reports, suggesting that ossification is actually associated with high-grade tumors and a poor prognosis [18].

Written informed consent was obtained from the patient for publication of this case report and the accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.