The hyperparathyroidism-jaw tumour (HPT-JT) syndrome is an autosomal dominant disorder characterized by parathyroid tumours, which are frequently carcinomas, and ossifying jaw fibromas. In addition, some patients may develop renal tumours and cysts. The gene causing HPT-JT, which is referred to as HRPT2 and is located on chromosome 1q31.2, encodes a 531 amino acid protein called PARAFIBROMIN. To date 42 mutations, of which 22 are germline, have been reported and 97% of these are inactivating and consistent with a tumour suppressor role for HRPT2. We have investigated another four HPT-JT families for germline mutations, searched for additional clinical phenotypes, and examined for a genotype-phenotype correlation. Mutations were found in two families. One family had a novel deletional-insertion at codon 669, and the other had a 2 bp insertion at codon 679, which has been reported in four other unrelated patients. These five unrelated patients and their families with the same mutation were not found to develop the same tumours, thereby indicating an absence of a genotype-phenotype correlation. An analysis of 33 HPT-JT kindreds revealed that affected women in 13 HPT-JT families suffered from menorrhagia in their second to fourth decades. This often required hysterectomy, which revealed the presence of uterine tumours. This resulted in a significantly reduced maternal transmission of the disease. Thus, the results of our analysis expand the spectrum of HPT-JT-associated tumours to include uterine tumours, and these may account for the decreased reproductive fitness in females from HPT-JT families.

Successful preoperative localization of parathyroid adenomas using Tc99m-sestamibi scanning is influenced by the cytological predominance of individual tumors. Negative scans might therefore be unavoidable in a subgroup of patients.

Background: This article presents the results and observed effects of the UK National Health Service Breast Screening Programme (NHSBSP) external quality assurance scheme in breast histopathology. Aims/Methods: The major objectives were to monitor and improve the consistency of diagnoses made by pathologists and the quality of prognostic information in pathology reports. The scheme is based on a twice yearly circulation of 12 cases to over 600 registered participants. The level of agreement was generally measured using k statistics. Results: Four main situations were encountered with respect to diagnostic consistency, namely: (1) where consistency is naturally very high-this included diagnosing in situ and invasive carcinomas (and certain distinctive subtypes) and uncomplicated benign lesions; (2) where the level of consistency was low but could be improved by making guidelines more detailed and explicit-this included histological grading; (3) where consistency could be improved but only by changing the system of classification-this included classification of ductal carcinoma in situ; and (4) where no improvement in consistency could be achieved-this included diagnosing atypical hyperplasia and reporting vascular invasion. Size measurements were more consistent for invasive than in situ carcinomas. Even in cases where there is a high level of agreement on tumour size, a few widely outlying measurements were encountered, for which no explanation is readily forthcoming. Conclusions: These results broadly confirm the robustness of the systems of breast disease diagnosis and classification adopted by the NHSBSP, and also identify areas where improvement or new approaches are required.

The role of angiogenesis and lymphangiogenesis in thyroid cancer pathogenesis has not been elucidated. Patterns for tumour behaviour and metastasic spread vary according to tumour type and whether differences in the angiogenic or lymphangiogenic phenotype influence the route for tumour metastases or determine a more aggressive behaviour has not been fully explored. The angiogenic and lymphangiogenic phenotypes of a large cohort of thyroid proliferative lesions (nZ191) were studied. Using immunohistochemistry for CD34, lymphatic vessel endothelial receptor-1 (LYVE-1) (specific markers for vascular and lymphatic endothelium respectively

Twenty-five granular cell tumours were stained with a panel of antibodies to histiocytic, muscle, neural, neural crest, epithelial and endothelial markers. Electron microscopy was also performed in six cases. Twenty-four of the cases were similar morphologically and immunocytochemically. One case with features of an endothelial origin is described. The present study strongly supports the viewpoint that granular cell tumours are a distinct entity rather than being the common appearance of a group of lesions of differing histogenesis. Origin from a neural crest-derived peripheral nerve-related cell is favoured.

We analysed telomerase activity in normal, benign and malignant breast tissues and in fine needle aspirates by a PCR-based assay. The tissue samples we used in this assay consisted of 20 cryostat sections, I0 pm thick, from each breast biopsy. This method was used to obtain effective extraction from small samples and to confirm the histological identity of the specimen by microscopical examination of serial sections. Fifty-two of 7 I breast carcinomas were positive for telomerase activity, and the intensity of this was strong in most cases, whereas all 6 samples of normal breast tissue and 17 of fibrocystic disease were negative and only I of I 5 fibroadenomas was positive. lnvasive ductal carcinomas were more frequently positive than invasive lobular carcinomas. There was no correlation of telomerase activity with turnour size or the occurrence of lymph node metastasis. Evaluation of our assay system showed that a signal of telomerase activity was detectable in extracts from single cryostat sections (< I mm2) of a cancer specimen and from as few as 4 cells of a human breast cancer cell line. On the basis of the above data, we applied this assay to fine needle aspirates of breast lesions. Ten of 15 aspirates which had been cytopathologically diagnosed as cancer were strongly positive, while 26 of 29 benign aspirates were totally negative and the remaining 3 showed only borderline activity. In 3 cases, the telomerase result could have helped establish a diagnosis when the cytological observations were inconclusive. Our results indicate that this sensitive assay could become a useful new modality for supplementing microscopic cytopathology in the detection of cancer cells in small tissue biopsies and fine needle aspirates.o 1996 Wiley-Liss, Inc.

Is quick, cheap, and accurate when used appropriately

Cytospin preparations were made from 102 serous effusions for immunocytochemical staining using a panel of monoclonal antibodies including a new monoclonal antibody Ber-EP4. On cytological examination, 32 fluids were reported to contain tumour cells consistent with metastatic adenocarcinoma; 66 contained benign cells only and three were reported to contain cells suspicious of malignancy. One effusion contained tumour cells consistent with malignant mesothelioma. Positive staining of the tumour cells with Ber-EP4 was observed in the 32 effusions (100%) which contained adenocarcinoma cells. No staining of the mesothelial cells in these 32 specimens was observed. Carcinoembryonic antigen, epithelial membrane antigen Ca2 and CD15 staining of tumour cells was noted in 53%, 50%, 50% and 9% of these cases, respectively. None of the mesothelial cells in the benign effusions stained with Ber-EP4. Nor did the malignant mesothelial cells in the only case of malignant mesothelioma. These findings suggest that Ber-EP4 is a valuable addition to antibodies available for the differential diagnosis of mesothelial cells and adenocarcinoma cells in serous effusions.