A single-point mutation in exon 15 of the BRAF gene has recently been reported in a high percentage in cultured melanoma cells and in 6 of 9 primary melanomas examined. To evaluate the impact of the T1796A BRAF mutation, we screened primary melanomas, various types of nevi and lesions where a melanoma developed in an underlying nevus. We could detect the mutation in 28 of 97 (29%) melanomas and in 39 of 187 (21%) nevi, including blue nevi (0/20) and Spitz nevi (0/69), which did not carry the mutation. In melanomas with an underlying nevus, either the mutation was present in both the laser-microdissected nevus cells and the laser-microdissected melanoma cells (3/14) or both lesions were negative for the BRAF mutation except one case. In conclusion, mutations in exon 15 of the BRAF gene are nonspecific for progression of a nevus to a melanoma. Other so far unknown cofactors seem to be of importance.

Infantile myofibromatosis is a distinctive type of fibromatosis that usually develops during the immediate perinatal period. There are variants with solitary and multiple tumors. Lesions confined to the skin, soft tissue, and bone carry a good prognosis, showing spontaneous regression. The prognosis, however, is much less favorable when visceral lesions are present and the outcome may be fatal. Only recently it became obvious that there is an adult counterpart of infantile myofibromatosis, characterized by solitary lesions that have a predilection for involve the dermis and show no tendency to regression, although they have an entirely benign biological behavior. These lesions have been named cutaneous myofibroma or solitary myofibroma of adults. We have studied the clinical, histopathological and immunohistochemical characteristics of 53 examples of cutaneous adult myofibroma. In addition, 2 cases were examined ultrastructurally. The patients were mostly adults with ages ranging from 6-83 years. The lesions presented as solitary, usually painless nodules of variable duration on the skin, usually located on the extremities. Histopathologically, four patterns were identified: nodular or cellular type, multinodular or biphasic type, leiomyoma-like or fascicular type, and vascular type. A correlation between the histopathologic pattern and the lesional age was observed: vascular type of cutaneous adult myofibroma in early lesions, nodular and multinodular lesions in fully developed lesions, and leiomyoma-like or fascicular type in late lesions. Immunohistochemically, the spindle cells were desmin negative, but expressed immunoreactivity for vimentin, pan-smooth muscle actin, and alpha-smooth muscle actin. Ultrastructurally, neoplastic cells showed characteristics of undifferentiated mesenchymal cells with features of fibroblasts, myofibroblasts and pericytes. Primitive vascular formations were seen in the form of irregular clefts between adjoining cells. We conclude that cutaneous adult myofibroma is a little-known benign vascular neoplasm probably derived from myopericytes.

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In a prospective audit, the prevalence, key causes and treatment of insomnia prior to admission were evaluated in a population of hospice patients using a questionnaire based on a review article of key features related to insomnia in the palliative care setting. Seventy-four patients completed the questionnaire. Fifty-two (70%) patients had insomnia symptoms. Uncontrolled physical symptoms, most often pain (15 patients), were the commonest cause of insomnia, cited by 31 (60%) sleep-disturbed patients. Thirteen (62%) of 21 patients who had been prescribed hypnotic medication reported an improvement with the prescribed medication. Twenty (38%) of the 52 patients with insomnia suggested that improved symptom control would improve their sleep, and only two (4%) suggested the need for more hypnotic medication. We conclude that insomnia is a common symptom in terminally ill patients and that improved symptom control should be a priority in the management of insomnia in this group of patients.

Cystic sebaceous tumors (CST) are well-circumscribed, large, deeply located dermal sebaceous proliferations with a cystic growth pattern. We identified 12 CST in 8 of 19 patients with Muir-Torre syndrome (MTS). We interpret CST as a tumor spectrum with clearly benign cystic sebaceous adenomas at one end and proliferative atypical cystic sebaceous tumors at the other. When examining these proliferative atypical tumors on morphologic criteria alone, the possibility of an evolving cystic sebaceous carcinoma cannot be excluded. We have not observed recurrences or metastases, indicating that these lesions are not highly malignant carcinomas. In 10 of 12 cases of CST, we examined microsatellite instability (MSI). All 10 examined examples of CST from patients with MTS showed MSI characteristic for hereditary nonpolyposis colorectal cancer (HNPCC), which is caused by autosomal dominant inherited DNA mismatch repair (MMR) defects. Mutational analysis of the MMR genes hMSH2 and hMLH1 had revealed different germline mutations in the hMSH2 gene in three of six examined patients with MTS with CST. We then found four more CST in patients without a history of internal malignancy. All four CST exhibited MSI. By mutational analysis in one of these patients we identified a truncating germline mutation in the MMR gene hMLH1. We conclude that CST is a marker for the mismatch repair-deficient subtype of MTS with a high risk for later internal malignancies. By recognizing CST, the histopathologist can suggest the great likelihood of MTS to the clinician.

Management during the diagnostic phase of MND is considered an important influence on the patient's further disease course. Guidelines for the management of MND have been developed, but little is known on how recommended practices influence patients' experience of a new diagnosis of MND. We undertook an interview-based study exploring issues surrounding the diagnosis of MND in a sample of consecutive patients recently diagnosed at a neurosciences centre. Data were analysed with Interpretative Phenomenological Analysis (IPA). Thirteen patients were recruited to the study. The major themes identified in descending order were 'Family/carers', 'Communication of the diagnosis', 'Reaction to the diagnosis', 'Physical difficulties', 'Time before diagnosis', 'Information', 'Future', 'Coping with the diagnosis' and 'Formal support'. Communication was perceived satisfactory if handled according to existing guidelines. Physical difficulties impacted considerably on patients' lives. Delays in the diagnostic process appeared in various interviews. Five patients were avoiding information following the diagnosis. Some patients commented on an increasing number of uncoordinated services becoming involved after their diagnosis. This study supports the current international guidelines for MND care around diagnosis from the patients' perspective and underlines the importance of a multi-disciplinary, coordinated approach for patients with MND from diagnosis onwards.

Thirty-four cases of fibrous histiocytoma (dermatofibroma) arising on the face are reported. These neoplasms occurred frequently in females (24 female, 10 male) and showed a broad age range (12 to 85 years; mean: 43.6 years, median: 41 years). The neoplasms originated on the forehead (nine cases), the cheek (eight cases), the eyebrow (four cases), the temporal region (three cases), the nose (two cases), and the ear (one case); in seven cases the location face was given only. Five of 27 cases with follow-up information (median: 5 years) recurred locally; in one case four recurrences were excised within 8 years. The majority of cases extended into the subcutis and deep soft tissue including striated muscle (50% of cases). Histologically, only the minority of cases was composed entirely of histiocytoid and spindle-shaped tumor cells arranged in a storiform growth pattern. In many cases cellular fascicles and bundles of spindle-shaped tumor cells were noted in addition to classical morphological features of fibrous histiocytoma. A moderate mitotic rate (mean: 2.97 mitoses in 10 HPFs) was observed, and in few cases increased atypia was evident. Frank tumor necrosis and/or vascular invasion were not identified. Immunohistochemical studies revealed Factor XIIIa positivity in 13 out of 17, focal CD68 positivity in 6 out of 10, and alpha-smooth muscle actin positivity in 16 out of 19 cases tested. These lesions should be distinguished from dermatofibrosarcoma protuberans, including its fibrosarcomatous variant, leiomyosarcoma, and low-grade myofibroblastic sarcoma. Cases of fibrous histiocytoma of the face have to be excised with wider margins in comparison with examples of classical fibrous histiocytoma occurring on the extremities because of diffuse infiltration, involvement of deeper structures, and an increased rate of local recurrences.

Our results, in conjunction with data from a previous investigation, suggest that the melanocytic proliferation of Spitz nevi might be induced by components of the RAS-RAF-ERK-MAP kinase pathway different from BRAF, possibly combined with other genetic aberrations. The lack of the T1796A BRAF mutation might be of practical importance in distinguishing Spitz nevi from other melanocytic lesions simulating Spitz nevi as a part of a future complex diagnostic assay.