The genetics of cutaneous melanoma

Although germline mutations in CDKN2A are present in approximately 25% of large multicase melanoma families, germline mutations are much rarer in the smaller melanoma families that make up most individuals reporting a family history of this disease. In addition, only three families worldwide have been reported with germline mutations in a gene other than CDKN2A (i.e., CDK4). Accordingly, current genomewide scans underway at the National Human Genome Research Institute hope to reveal linkage to one or more chromosomal regions, and ultimately lead to the identification of novel genes involved in melanoma predisposition. Both CDKN2A and PTEN have been identified as genes involved in sporadic melanoma development; however, mutations are more common in cell lines than uncultured tumors. A combination of cytogenetic, molecular, and functional studies suggests that additional genes involved in melanoma development are located to chromosomal regions 1p, 6q, 7p, 11q, and possibly also 9p and 10q. With the near completion of the human genome sequencing effort, combined with the advent of high throughput mutation analyses and new techniques including cDNA and tissue microarrays, the identification and characterization of additional genes involved in melanoma pathogenesis seem likely in the near future.     

Wounds and malignancy

Due to the prevalence of skin cancers, health care practitioners involved with wound management are likely to encounter cutaneous malignancies as part of their practice. This article focuses on 2 ways in which malignancies and wounds are related: the malignant degeneration of chronic wounds into cancer and malignancies that present as chronic wounds. The most common scenario in which chronic wounds have been associated with the development of squamous cell carcinoma is in the presence of chronic osteomyelitis. However, wounds secondary to burns, trauma, radiotherapy, and diabetes are also at risk for malignant degeneration. It is often difficult to distinguish malignant transformations from primary malignant ulcers. Given the uncommon nature of degeneration of a chronic wound or a malignancy presenting as a chronic wound, some suggest that only suspicious wounds undergo biopsy. Primary malignancy should be considered if the ulcer has a relatively short duration and the patient does not have a history of prior radiotherapy. Until recently, amputation has been the treatment of choice for squamous cell carcinomas that arose within chronic wounds associated with chronic osteomyelitis; however, other reports have shown that other methods of ensuring complete local excision are also useful.     

Genetically confirmed clinical Huntington's disease with no observable cell loss

Huntington's disease (HD) results from neurodegeneration of the neostriatum. The mutation on chromosome 4 is an expansion in a triplet repeat (CAG)(n) located within the IT15 gene. Only six patients have been reported with clinical features of HD in association with limited neuropathology. Of these, only one has had the diagnosis confirmed by genetic (DNA) testing. We describe a patient with the clinical phenotype and genetically confirmed HD but unexpected limited neuropathology. The patient was seen because of aggressive behaviour and memory problems of two years duration. The differential diagnosis included HD although there was no family history. DNA testing was positive for the HD mutation. Clinical follow up three months later confirmed classic features of HD. Progression of the disease was rapid with death three years later. Neuropathology revealed a largely intact neostriatum with bilateral ischaemic damage and cell loss in the external globus pallidus. Such pathology alone could explain the clinical features of HD. This is only the second report of genetically confirmed clinically manifest HD with little evidence of HD neuropathology. There are several unusual features which could not have been predicted by the clinical picture, in particular the progressive course of bilateral ischaemic changes restricted to the external globus pallidus. The potential to miss other HD cases at post-mortem examination, and the implications of this for family members, are discussed.     

Mucoepidermoid carcinoma (adenosquamous carcinoma) treated with Mohs micrographic surgery

BACKGROUND: Mucoepidermoid carcinoma (MEC), sometimes referred to as adenosquamous carcinoma (ASC), is a common malignant tumor of the salivary glands that can also develop from the esophagus, lacrimal passages, lung, upper respiratory tract, pancreas, prostate and thyroid. Rarely, MEC will present primarily in the skin. CASE: We present a case of primary MEC of the lower eyelid treated successfully with Mohs micrographic surgery. RESULTS: Mohs micrographic surgery was performed because of the highly aggressive and unpredictable nature of this tumor. The tumor was completely excised using Mohs with negative margins achieved in three stages. The patient has been disease free for 3 years since the surgery. CONCLUSION: We offer Mohs as an option for treating MEC.