The term "rhabdoid" is being applied to describe a histological pattern of a poorly-differentiated neoplasm composed of loosely cohesive polygonal cells with eccentric vesicular nuclei, prominent nucleoli, and eosinophilic cytoplasm that displaces the nucleus. These cells are characterized by aggregates of intermediate filaments found on electron microscopy and by a specific immunohistochemical staining pattern revealing combined positivity for vimentin and cytokeratins, together with an absent reactivity to muscle, vascular or melanocytic markers. Weeks et al. [
8] outlined strict criteria for the definition of MRTK and proposed a hypothesis claiming that extrarenal rhabdoid tumors (ERRTs) represent a heterogeneous group of malignancies with a common phenotype, but no histogenic specificity. In ERRTs, the rhabdoid component may represent the sole histological pattern in so-called "pure" rhabdoid neoplasm or may comprise areas within epithelial, mesenchymal or other malignancies in what are defined as "composite" or "mixed" tumors [
9,
10]. In composite lesions, the original component of the carcinoma or other malignancy defines the diagnostic category, with rhabdoid differentiation emphasized in the final report, as it signifies an aggressive biological behavior. Much controversy still exists as to whether ERRTs constitute a distinct nosological entity or whether they represent similarly appearing variants of de-differentiation within a primary malignancy at various localizations. There has been a focus on molecular genetics investigating changes in the tumor suppressor gene
INI1 [
11,
12] and the chromosome 22q [
13] in rhabdoid lesions. INI1 (BAF 47) antibody serves as a surrogate marker for an intact
INI1 gene and could easily be assessed immunophenotypically [
12]. Investigators discovered very poor association of genetic alterations with ERRTs; intact INI1 expression was noted in the vast majority of lesions analyzed. Follow-up data in these cases, however, revealed an aggressive biological behavior, implying that the rhabdoid morphology by itself, even without
INI1 gene abnormalities, signifies worse prognosis, poor response to conventional therapeutic modalities, and rapid disease progression [
13].
INI1 gene mutations have been described in a number of different malignant neoplasms, including renal medullary carcinomas, epithelioid sarcomas, malignant peripheral nerve sheath tumors, etc. - a proof, that alterations of the
INI1 gene are neither sensitive nor specific to rhabdoid tumors.
Published data on rhabdoid neoplasms arising in the lower gastrointestinal tract describe these malignancies as sharing many similarities in pathological appearance and clinical behavior to those from other locations. Of note, three investigators have searched for microsatellite instability, CpG island methylation, and
KRAS and
BRAF gene mutations in colonic rhabdoid tumors. Two of them reported that their published tumors harbored BRAF V600E mutation, wild-type KRAS and high methylation status [
10,
14]; one case was reported to carry a wild-type
KRAS gene and to have no evidence of microsatellite instability (
BRAF gene and CpG island methylation status was not investigated) [
15]. Similarly, our case demonstrated BRAF V600E mutation, wild-type KRAS and no evidence of microsatellite instability on immunohistochemical workup. However, we did not assess our case for CpG island methylation status. From the therapeutic standpoint, wild-type KRAS status would imply tumor responsiveness to novel biological molecules such as Bevacizumab or anti-epidermal growth factor receptor (EGFR) compounds; however, a BRAF mutation and rhabdoid morphology would signify the opposite: a poor response to conventional and novel chemotherapy regimens and a likely refractory disease with relapses. In line with the latter proposition was an observation reported by Pancione et al. [
14], where despite multiple cycles of Bevacizumab and Cetuximab-based therapies, no significant benefit was noted, with rapid disease progression and short survival in their patient diagnosed with a rhabdoid tumor. Our patient shared a very similar fate: rapid tumor progression irrespective of intensive standard chemotherapy regimens (FOLFIRI and FOLFOX4); biological and anti-EGFR therapies were not attempted due to clinical contraindications.
This case illustrates the importance of correct classification and identification of particular rare components within neoplastic lesions: histological identification of rhabdoid morphology was an early and accurate predictor of poor outcome despite available therapies. Future studies, especially on the biology and the genetics of these tumors, are important to search for specific therapeutic agents and more effective treatment regimens.