Rectal adenocarcinoma with oncocytic features: possible relationship with preoperative chemoradiotherapy

Abstract

Background: The introduction of preoperative chemoradiation into the treatment protocol of rectal adenocarcinomas has affected the microscopical morphology in subsequent resection specimens. The constellation of histopathological changes is varied and well documented. Aim: To describe oncocytic change in rectal cancers that have been treated with chemoradiation before surgery. Methods: 7 of 54 patients with rectal cancer were identified with a history of chemoradiation, specifically directed to the rectal tumours in fractions of 4500-5000 cGy of radiation and 5-fluorouracil. The rectal tumours in five of these seven patients were composed of oncocytes that constituted 30-80% of the cancers. The patients were three men and two women aged 65-73 years, all with T3 N0 tumours. The intervals between chemoradiation and resection varied from 3 to 12 weeks. Results: The tumour cells conformed to oncocytes morphologically (large size with abundant, granular eosinophilic cytoplasm, vesicular nuclei and prominent acidophilic nucleoli), immunohistochemically (positive for carcinoembryonic antigen, cytokeratin 20 and caudal type homeo box transcription factor 2, but negative for both chromogranin and synaptophysin) and ultrastructurally (large cells showing tight junctions, cytoplasmic engorgement by mitochondria and absence of neurosecretory granules). Conclusions: The changes in these cells differ from those described previously in endocrine cells encountered in pretreated rectal cancers. Oncocytic change in this particular clinical context occurs as a reflection of cytotoxic damage or cellular hypoxia induced by chemoradiation resulting in degeneration of the cell and the oncocytic phenotype. Oncocytic change may be an under-recognised histopathological change in rectal cancers receiving preoperative chemoradiation.

Mucosal endocrine cell micronests and single endocrine cells following neo-adjuvant therapy for adenocarcinoma of the distal oesophagus and oesophagogastric junction

“…Characteristic treatment induced changes within the residual tumour include attenuation of glands, increased cytological atypia, degenerative nuclear changes and decreased mitotic activity 8. Cytoplasmic vacuolation and eosinophilia have been described in rectal adenocarcinomas after therapy, and the latter appearances may reflect an endocrine or oncocytic phenotype 9 10. Stromal changes that commonly follow treatment include fibrosis, dystrophic calcification, atypical fibroblasts and vascular obliteration.…”

Oncocytic rectal adenocarcinomas

“…Twenty-four of 28 cases reported by Ambrosini-Spaltro et al [18] and 5 of 7 cases described by Rouzbahman et al [19] showed rectal adenocarcinomas with oncocytes being the dominant cell type. Most pretreatment biopsies in the former study contained variable numbers of oncocytes [18], and we noted that oncocytes are present in most rectal cancers we examined [19]. It is reasonable to postulate that oncocytes are resistant to and survive chemoradiation, remaining as the dominant tumor cells in residual rectal cancers.…”

“…Oncocytic rectal adenocarcinomas have thus far been documented in 2 clinical contexts: 2 series describing oncocytic rectal carcinomas in resection specimens with the patients having received preoperative chemoradiation [18,19] and 2 separate case reports documenting the occurrence of oncocytes in patients without preoperative chemoradiation [20,21].…”

“…This highlights the non-specificity of the antibody as it stains mitochondrion-containing cells indiscriminately and thus lacks utility in detecting true oncocytes and separating them from other mitochondrion-rich cells. Rouzbahman and colleagues [19] evaluated the pretreatment diagnostic biopsies in 5 of 7 cases with post-chemoradiation oncocytic rectal adenocarcinomas. None of the 5 biopsies examined contained oncocytes; however, these were small superficial biopsies and may not have been entirely representative.…”

“…There have been 2 series describing oncocytic change in rectal adenocarcinomas after preoperative chemoradiation [18,19]. In addition, there have been 2 case reports of oncocytic rectal adenocarcinomas occurring without antecedent chemoradiation [20,21].…”