Single genetic mutations can account for melanocytic naevi.

BACKGROUND: The nature of melanocytic naevi is unknown notwithstanding their considerable significance for clinician and pathologist and despite the wealth of existing knowledge about melanocyte biology. OBJECTIVES: To investigate how far a simple mutational model can explain the clinical and pathological features of melanocytic naevi, in particular their pattern of onset and frequency. METHODS: I have constructed a model of the development of the adult melanocyte population from a single stem cell. The total cutaneous melanocyte population in a human adult is already known, as well as the range of spontaneous mutation rates at a given gene site. For each cycle of mitosis during the post stem-cell expansion of the melanocyte population, I calculate the accumulated number of cells likely to be mutated at a particular (although unknown) gene site. The results are interpreted in the light of a hypothesis that each of these mutant melanocytes will go on to form a melanocytic naevus. Comparisons are made with neurofibromas, occurring in type 1 neurofibromatosis and as sporadic lesions. RESULTS: A single genetic mutation in melanocyte precursors is found to be sufficient to explain the clinical and pathological features of melanocytic naevi. CONCLUSIONS: I propose that melanocytic naevi are a consequence of single spontaneous genetic mutations which inevitably occur during the development of the adult population of cutaneous melanocytes.

The pathology of acute hepatic disintegration in hereditary haemorrhagic telangiectasia.

AIMS: Hereditary haemorrhagic telangiectasia is a rare inherited disease in which telangiectases affect skin, mucous membranes and the gastrointestinal tract. Hepatic involvement is common but usually asymptomatic. We report a case of acute hepatic disintegration in hereditary haemorrhagic telangiectasia, document the histopathological findings and present a hypothesis to explain them. METHODS AND RESULTS: The patient presented at the age of 34 years with abdominal pain, leading to the surgical removal of a severely inflamed gallbladder. Signs of liver damage became increasingly apparent over the next few weeks, with disruption of the intrahepatic biliary tree and marked vascular shunting, necessitating liver transplantation. Six months after the transplant a diagnosis of hepatic hereditary haemorrhagic telangiectasia was made. The principal features of hepatic hereditary haemorrhagic telangiectasia are periportal telangiectases and sinusoidal congestion and dilatation. Acute hepatic disintegration is characterized by disruption of liver structure, hepatocyte necrosis, haemorrhage and extravasation of bile. CONCLUSIONS: Periportal telangiectases in a liver biopsy are highly suggestive of hereditary haemorrhagic telangiectasia. Acute hepatic disintegration is likely to be a consequence of rupture of telangiectases and ischaemic necrosis of intrahepatic bile ducts. Patients with hereditary haemorrhagic telangiectasia are at risk of acute hepatic disintegration following intra-abdominal sepsis.

Recurrence of Kikuchi's lymphadenitis after 12 years.

A 40 year old woman developed recurrent Kikuchi's disease 12 years after the original episode. The recurrence affected the same site (axilla) and occurred after the longest delay so far recorded in a European resident. Care must be taken to avoid misdiagnosis of Kikuchi's disease as lymphoma.

Two cases of primary hyperparathyroidism associated with primary cutaneous lymphoma.

Primary hyperparathyroidism has been described previously in association with malignancy, but to our knowledge has not been reported in association with primary cutaneous lymphoma. We report two cases of parathyroid adenoma with primary cutaneous lymphoma, the first in a 42-year-old woman with CD30-negative cutaneous large cell lymphoma, and the second in a 67-year-old man with mycosis fungoides and CD30-positive anaplastic large cell lymphoma.

Junctional epidermolysis bullosa: a mild variant in two Indian sisters.

Two sisters developed a bullous skin disease in early childhood. The disease had features of junctional epidermolysis bullosa but differed clinically from previously recorded variants.

Intralaryngotracheal thyroid.

A case of intralaryngotracheal thyroid in a 57-year-old man is presented. The treatment modalities are considered and the previous literature is reviewed.

High-grade non-Hodgkin's lymphoma complicating polypoid nodular lymphoid hyperplasia and multiple lymphomatous polyposis of the intestine.

Three patients with multiple lymphoid polyps of the small intestine--two with nodular lymphoid hyperplasia and one with multiple lymphomatous polyposis--developed high-grade B-cell lymphomas. A literature search has revealed only 10 previous cases of nodular lymphoid hyperplasia complicated by lymphoma and none of an association between multiple lymphomatous polyposis and high-grade lymphoma.

Epithelioid sarcoma: a tumour of myofibroblasts.

A case of epithelioid sarcoma of scalp has been studied by light and electron microscopy, histochemistry and immunocytochemistry. The results suggest that epithelioid sarcoma is a tumour of myofibroblasts. The epithelioid appearance results from gross and disordered accumulation of cytoplasmic intermediate filaments (10 nm diameter), possibly of desmin type, producing the misleading light microscopical resemblance to epithelioid histiocytes and biphasic pattern of synovial sarcoma. The cause of the filament accumulation is unknown but it may represent a degenerative change leading to necrosis, a characteristic feature of epithelioid sarcoma.

Mode of cell death induced in human lymphoid cells by high and low doses of glucocorticoid.

The kinetics, specificity and morphology of cytolethal responses have been studied in human glucocorticoid-sensitive and -insensitive lymphoid cell lines (HLCL) and fibroblasts following treatment with high (10(-3)M) and low (10(-6)M) doses of steroid. The high dose cytolethal response appears non-specific occurring in all cell lines with every steroid tested. By contrast, the low dose (pharmacological) cytolethal response requires an active glucocorticoid and a sensitive HLCL. However, both high and low concentrations of steroid induce virtually identical morphological changes in dying cells and similar changes can be induced in cells killed by deliberate feed exhaustion. Although the morphological features in each case resemble apoptosis, the "programmed" physiological form of cell death, the intracellular events leading to cytolysis seem likely to differ. The earliest morphological changes presaging cell death comprise rounding up of cells and condensation of nuclear chromatin. Nuclear changes progress rapidly thereafter and appear to result from detachment of chromatin from the nuclear matrix. The low dose cytolethal response requires the continuous presence of glucocorticoid for periods in excess of 24h, prior to which cell growth appears unaffected. The constancy of this latent interval suggests glucocorticoids may influence some replication control mechanism unrelated initially to macromolecular biosynthesis.

Quantitative analysis of non-Hodgkin's lymphoma.

A preliminary attempt has been made to characterise a small series of non-Hodgkin's lymphomas (NHL) by morphometric means using the Quantimet 720 Kontron MOP/AMO3 image analysis systems. In most cases it was found that the distribution of nuclear area and correlation between mean nuclear area and frequency per unit field, corresponded closely with tumour classification determined by light microscopy. These results suggest that it may be possible to devise an objective and reproducible grading system for NHL using quantitative morphometric techniques.

Failure to detect circulating IgG or IgM antibodies to basal cell carcinoma by immunofluorescence.

Immunofluorescence techniques failed to reveal evidence of anti-tumour antibody in the sera of patients with basal cell carcinima. Although the presence of such antibodies has previously been associated with the absence of metastasis in malignant melanoma, other explanations for the low metaststic potential of basal cell carcinoma should be sought.

Hepatic damage associated with mineral oil deposits.

The case of a 33 year old male is reported. Hepatic inflammation and scarring were associated with deposits of mineral oil in portal triads. This is believed to be the first reported case of hepatic damage resulting from mineral oil accumulation. Possible sources of the oil are considered.

Cardiac tamponade and central venous catheters.

An analysis of the reports on 16 patients who developed cardiac tamponade, complicating the use of central venous catheters, showed that 14 died. The two survivors were treated by removal of the catheter and needle aspiration of the pericardial fluid. Some patients complained of warning symptoms such as nausea, pain, and dyspnoea, and the combination of tachycardia, hypotension, and raised venous pressure was common. We suggest that awareness of the hazard, radiographic visualization of the catheter tip, and expeditious treatment would reduce the mortality.