Telomere dysfunction and loss of p53 cooperate in defective mitotic segregation of chromosomes in cancer cells.

Aneuploidy is a fundamental principle of many cancer cells and is mostly related to defects in mitotic segregation of chromosomes. Many solid tumors as well as some preneoplastic lesions have been shown to contain polyploid chromosome numbers. The exact mechanisms behind whole-genome duplications are not known but have been linked to compromised mitotic checkpoint genes. We now report that the telomere checkpoint plays a key role for polyploidy in colon cancer cells. Telomerase suppression by a dominant-negative mutant of hTERT and consecutive telomere dysfunction in wild-type HCT116 colon cancer cells resulted in only minor stable chromosomal alterations. However, higher ploidy levels with up to 350 chromosomes were found when the cell-cycle checkpoint proteins p53 or p21 were absent. These findings indicate that telomere dysfunction in the absence of cell-cycle control may explain the high frequency of alterations in chromosome numbers found in many solid tumors.

A rare entity of an unusual site: adenomatoid tumour of the adrenal gland: a case report and review of the literature.

This is a case report of a 51 year old male who was found to have an incidental left sided non-functioning adrenal mass on routine medical examination and which was confirmed by CT and MRI scans. A laparoscopic left adrenalectomy was done. On gross examination the tumour was a solitary well circumscribed solid-cystic mass with a homogenous pinkish white cut surface. On microscopic examination, the tumour was composed of variably sized tubules and fenestrated channels lined by bland cuboidal cells to epithelioid cells. There was focal extension to capsule and peri-adrenal fat. Immunohistochemically the tumour cells stained with calretinin, Cam5.2, CK7, vimentin and focally with EMA. Ki-67 fraction was <1%. They were negative for ER, CD31, CD34, Factor 8, chromogranin, synaptophysin S100 and inhibin. A diagnosis of an adenomatoid tumour as made. Adenomatoid tumours are rare benign tumours of mesothelial derivation. The adrenal gland is devoid of a mesothelial lining and the most accepted hypothesis for an adenomatoid tumour originating in the adrenal gland is derivation from mesothelial rests. As the adrenal gland is an extremely rare site of occurrence for an adenomatoid tumour, it is frequently mistaken for adrenocortical tumours or a pheochromocytoma clinically and radiologically.

An unusual case of laryngeal spindle cell carcinoma metastasising to the orbit and heart.

We report the first case in the world literature of laryngeal spindle cell carcinoma metastasising to the orbit. A 65-year-old woman was previously treated for T3 N0 Mx laryngeal spindle cell carcinoma, with laryngectomy and post-operative radiotherapy. Five months following this treatment, she developed proptosis, diplopia and reduced right visual acuity, secondary to an enlarging mass within the right orbit. This was biopsied, and subsequent histology confirmed a diagnosis of metastatic spindle cell carcinoma. Subsequent post-mortem examination demonstrated additional pulmonary, hepatic and cardiac metastatic disease, in the absence of any other primary tumour or locoregional disease. The radiological investigation of patients with laryngeal spindle cell carcinoma is discussed and contrasted with that of laryngeal squamous cell carcinoma.