Can a familial gastrointestinal tumour syndrome be allelic with Waardenburg syndrome?

Familial gastrointestinal stromal tumours (GISTs) are rare but otherwise well-characterized tumour syndromes, most commonly occurring on a background of germline-activating mutations in the tyrosine kinase receptor c-KIT. The associated clinical spectrum reflects the constitutive activation of this gene product across a number of cell lines, generating gain-of-function phenotypes in interstitial cells of Cajal (GIST and dysphagia), mast cells (mastocytosis) and melanocytes (hyperpigmentation). We report a three-generation kindred harbouring a c-KIT germline-activating mutation resulting in multifocal GISTs, dysphagia and a complex melanocyte hyperpigmentation and hypopigmentation disorder, the latter with features typical of those observed in Waardenburg type 2 syndrome (WS2F). Sequencing of genes known to be causative for WS [microphthalmia transcription factor (MITF), Pax3, Sox10, SNAI2 ] failed to show any candidate mutations to explain this complex cutaneous depigmentation phenotype. Our case report conclusively expands the clinical spectrum of familial GISTs and shows a hitherto unrecognized link to WS. Possible mechanisms responsible for this novel cause of WS2F will be discussed.

Immunogold-silver staining by capillary action.

The authors have developed an improved method for immunogold-silver staining of paraffin sections. Using a manual capillary action staining system, they were able to simplify the technical aspects of the procedure, permitting rapid processing of large batches of slides with better reproducibility. Background staining was decreased by use of buffers containing a detergent. The use of a light-stable silver reagent permitted greater control of the enhancement stage. The method yielded a high degree of contrast with negligible nonspecific staining. Sensitivity was comparable to that obtained with conventional enzymatic immunostaining. However, the authors noted that trypsinization of sections was rendered unnecessary for those antigens for which such pretreatment was usually required, and the need for special fixatives could be eliminated. The method was also applicable to immunostaining of frozen sections. Immunogold-silver staining by capillary action deserves consideration as an alternative to existing immunohistochemical methods in diagnostic histopathology.

Use of antibodies to carcinoembryonic antigen and human milk fat globule to distinguish carcinoma, mesothelioma, and reactive mesothelium.

Antibodies raised against human milk fat globule (HMFG 1 and 2) and carcinoembryonic antigen were used in an immunoperoxidase technique to differentiate mesothelioma, carcinoma, and benign, reactive mesothelium. Sixteen mesotheliomas, 27 lung carcinomas, and 13 specimens of reactive mesothelium were examined. Staining for carcinoembryonic antigen was not seen in reactive mesothelium or mesothelioma but was present in 22 of 27 carcinomas. Mesothelioma and carcinoma usually stained with HMFG 1 and 2; reactive mesothelium did not. These three antibodies may help to distinguish carcinoma, mesothelioma, and reactive mesothelium.

A case of attempted suicide by self-hanging.

A young man arrived at the accident and emergency department after attempting suicidal self-hanging. He was cyanosed and showed severe respiratory distress. His posture, hyperreflexia and state of consciousness suggested decerebration. A dire prognosis was expected. Four days later he recovered. No residual physical or mental sequelae were found during follow up. The "post-suspension syndrome" in our case was similar to those recorded in several continental reviews. Apart from a case report of a "miraculous deliverance" following an unsuccessful judicial hanging at Oxford in 1650, no other report of this syndrome has been made in the English literature. This syndrome has an excellent prognosis and requires very little active intervention to ensure a favourable outcome.

Immunohistochemical demonstration of alpha-1-antitrypsin and alpha-1-antichymotrypsin in normal human endometrium.

Forty-five specimens of endometrium, consisting of 10 proliferative, 10 each of early, mid-, and late secretory, and five menstrual phase, were examined with antibodies to alpha-1-antitrypsin (A1AT), alpha-1-antichymotrypsin (A1ACT), muramidase, and serum 22, using an indirect peroxidase-antiperoxidase immunoperoxidase technique. Five postmenopausal and 10 pregnancy endometria were also examined. Very few macrophages were detected. Other stromal cells, however, in premenopausal, nonpregnant endometrium, stained strongly for A1AT and A1ACT but not with the other two antisera. Stromal cells following the menopause did not stain nor did the decidual cells of pregnancy. Only rare, isolated epithelial cells or whole glands stained for A1AT and A1ACT. The function of these antiproteases in endometrium may be to regulate the protease activity of the implanting blastocyst or the immunological response to it.

alpha-1-Antitrypsin, alpha-1-antichymotrypsin, actin, and myosin in uterine sarcomas.

Fourteen cases of mixed müllerian tumour (MMT) of the endometrium, six stromal sarcomas, five uterine leiomyosarcomas, and five leiomyomas were examined, using an immunoperoxidase technique, for the presence of alpha-1-antitrypsin (A1AT), alpha-1-antichymotrypsin (A1ACT), actin, and myosin. In addition, six cases of endometrial adenocarcinoma were examined for the presence of A1AT and A1ACT. Eleven MMT were positive for A1AT and 13 for A1ACT. All stromal sarcomas, four adenocarcinomas, four leiomyomas, and three leiomyosarcomas were positive for both. All leiomyomas and leiomyosarcomas were positive for myosin as were seven. MMT and three stromal sarcomas. Four leiomyomas, four leiomyosarcomas, six MMT, and three stromal sarcomas were positive for actin. These findings are related to those in the normal uterus and their practical and theoretical significance discussed.

Dermal cylindromas originate from the eccrine sweat gland.

Ten dermal cylindromas have been studied using histological, ultrastructural and immunocytochemical techniques. The clinical data from the ten patients have also been reviewed. The results indicate histogenesis from the intradermal coiled duct region of the eccrine sweat gland.

Primary lymphoma of the central nervous system: a case report.

A 46-year-old female presented with a 1-week history of mental change, confusion and headaches. Investigations revealed evidence of sterile meningitis. CAT scanning of the brain demonstrated marked contrast enhancement around the ependyma, and later examinations showed extension of the process deep into the white matter, Cerebral biopsies were non-diagnostic and, despite ventricular drainage and treatment with antibiotics and high dose steriods, the patent died. At postmortem there was extensive tumour tissue distributed in a butterfly shape around the ventricles, and microscopy revealed typical apperances of primary CNS lymphoma. On the basis of the experience of this case and a review of recent literature, it is suggested that the CAT scan appearances of this tumour are quite typical, and that cranial irradiation may be justified in the absence of specific histological diagnosis.

Leiomyosarcoma of the uterus with giant cells resembling osteoclasts.

A case of leiomyosarcoma of the uterus with osteoclast-like giant cells was examined by light and electron microscopy, histochemistry, and immunoperoxidase techniques. A panel of antibodies was used, including monoclonal antibodies raised against various macrophage determinants and PD 7/26, which detects a leucocyte-common antigen. The giant cells contained nonspecific esterase, stained with PD 7/26 and with two antimacrophage antibodies. These findings strongly suggest that these giant cells are derived from macrophages.