Potentially malignant oral lesions in Northern Ireland: size (extent) matters.

OBJECTIVES: We examined clinical parameters of patients from Northern Ireland with potentially malignant lesions (PML) to determine association with development of intraoral squamous cell carcinoma (SCC). DESIGN: retrospective, cross-sectional, population-based, clinically validated, laboratory-verified. SUBJECTS AND METHODS: All patients who had more than one incisional oral mucosal biopsy diagnosed from 1975-1991 were abstracted from a database of all PML and SCC and their clinical records and biopsies reviewed. Patients were excluded if there was priorlsynchronous SCC or radiotherapy, frictional keratosis or lichen planus, missing clinical records/biopsy material or follow-up of <24 months. From the 50 suitable patients, gender, age, smoking status, site, clinical appearance and extent of lesion(s), treatment and year of diagnosis were recorded. Patients who developed SCC from PML were compared with those who did not. RESULTS: Squamous cell carcinoma occurred significantly more often in patients with single rather than multiple PML, those with 'non-homogenous' PML and in patients diagnosed prior to 1980. In Cox's survival analysis, only the clinical extent was predictive of SCC. CONCLUSIONS: Of all the features considered in our series, size (extent) was the most important clinical factor in determining the risk of future SCC in PML, particularly when several adjacent anatomical sites were affected.

Vimentin expression does not assist in predicting survival in ductal carcinoma of the breast.

AIMS: To establish the value of vimentin expression in predicting survival in patients with breast cancer. METHODS: Five-year follow-up data were obtained for 68 patients with ductal carcinoma (NOS) of the breast in whom vimentin expression had been studied in fresh frozen and formalin-fixed, paraffin-embedded tissue. The predictive value on survival of tumour size, growth fraction (as assessed using the Ki67 monoclonal antibody), oestrogen receptor status and Bloom and Richardson grade of the primary tumour, and the presence or absence of lymph node metastases in axillary samples, were also studied. RESULTS: Twenty-two patients died of their disease within 5 years of diagnosis. Vimentin expression either on frozen or paraffin sections did not provide a statistically significant prediction of survival. On univariate analysis tumour grade, size and the presence of lymph node metastases provided prognostic information. Only lymph node status was of independent prognostic importance on multivariate analysis. CONCLUSIONS: Whilst these results confirm the value of established prognostic factors, they do not support the use of vimentin expression in either fresh or fixed tissue for the prediction of survival in ductal carcinoma (NOS) of the breast.

An unusual cause of biliary stricture in a patient with neurofibromatosis type 1.

The majority of biliary strictures occur as a consequence of iatrogenic injury to the extrahepatic biliary tract, with more than 80% following cholecystectomy. The laparoscopic era has led to heightened awareness of this problem. The occurrence of an iatrogenic stricture can be particularly devastating to both patient and surgeon. The literature highlights a number of factors involved in the aetiology of such traumatic stricture formation. We report an unusual case of a Bismuth 2 stricture of the proximal common hepatic duct,occurring in a patient with type 1 neurofibromatosis, following an iatrogenic bile duct injury that occurred during a laparoscopic cholecystectomy. Histological examination of the strictured region of bile duct removed at surgery demonstrated multiple neurofibromas of varying sizes present in the submucosa. Neurofibromatosis type 1 (von Recklinghausen disease) affects the gastrointestinal tract in up to 25% of cases, and in such cases is characterized by multiple submucosal neurofibromas. We believe this is the first reported case of a biliary stricture in a patient with neurofibromatosis type 1, which appeared to be as a consequence of neurofibromas in the submucosa of the bile duct.

The declining autopsy rate and clinicians' attitudes.

The autopsy rate has been declining worldwide for decades. This study determined the overall and differential autopsy rates for the Royal Victoria Hospital, Belfast for the years 1997-1999 inclusive. Trends were examined by comparison with previously collected data for the years 1990, 1991 and 1993. Reasons for the decline in autopsy rates as perceived by hospital clinicians were assessed by means of a questionnaire. Over the last decade, there has been a steady decline in the overall autopsy rate from 30.4% in 1990 to 18.4% in 1999. This is due to a decrease in the hospital autopsy rate from 21.6% in 1990 to 7.9% in 1999. The coroner's autopsy rate has remained comparatively unchanged at around 11%. The decline in the overall and hospital autopsy rates involves all of the principal bedholding directorates, but is most dramatic in medicine, surgery and intensive care, where hospital autopsy rates are currently 7% or less. The main reasons for this decline as perceived by clinicians are difficulty in obtaining consent from relatives and advances in modern diagnostic techniques. The findings of this enquiry are in keeping with trends elsewhere, despite repeated studies which clearly demonstrate the continuing value of the autopsy in clinical practice. Recent publicity concerning the retention of organs can only have an adverse affect. Pathologists and clinicians who value the autopsy must become actively engaged in both public and medical education. Renewed emphasis must be placed on the importance of the autopsy in teaching, training and clinically relevant research, and as a means of medical audit.

Interphase cytogenetics of chromosomes 11 and 17 in fine needle aspirates of breast cancer.

The aims of this investigation were to compare quantitative with qualitative analysis of fluorescent in situ hybridization (FISH) centromere signals in interphase breast cancer cell nuclei and to evaluate the possible clinical utility of detecting numerical abnormalities of chromosomes 11 and 17 by FISH in the preoperative prediction of breast cancer histological grade. Commercial digoxigenin-labeled centromere probes to chromosomes 11 and 17 were hybridized to 69 malignant aspirates with histological follow-up. Aspirates were categorized as disomic or aneusomic for chromosomes 11 and 17 qualitatively; a subset of aspirates was also analyzed quantitatively. The quantitative and qualitative approaches resulted in almost identical categorisation. There was a significant association between the qualitative categorization of aspirates as aneusomic or disomic, the histological grade of the excised tumours (P = .0695, n = 69), and the cytological grade of the clinical aspirates (P = .006, n = 35). Although histological grade III tumors were almost invariably polysomic for one or both chromosomes, polysomy was also detected in grade I and II tumors. Qualitative FISH analysis was shown to be more sensitive than cytological grading in predicting histological grade III but was of lower specificity and was therefore not clinically useful.

Myoepithelial carcinoma (malignant myoepithelioma) of the parotid gland arising in a pleomorphic adenoma.

A myoepithelial carcinoma, a rare malignant salivary gland neoplasm, arose in a pleomorphic adenoma of the parotid gland. The initial tumour was a pleomorphic adenoma with epithelial and myoepithelial elements. Subsequently the tumour recurred twice and was characterised by invasion of the mandible. Histological examination of the second recurrence showed a malignant spindle cell neoplasm with an infiltrative growth pattern and a high mitotic rate. There was involvement of local lymph nodes. The immunophenotype was characteristic of myoepithelial differentiation: tumour cells stained positively with anticytokeratin antibodies, S-100 protein, alpha smooth muscle actin, and vimentin. Electron microscopy confirmed myoepithelial differentiation, with small foci of keratinocytic phenotype. Large numbers of tumour cell nuclei were reactive with the anti-p53 antibody, DO-7, in contrast to the two previous resections. Thus malignant transformation of a pleomorphic adenoma may involve myoepithelial as well as epithelial elements. Accumulation of p53 protein, perhaps through mutational events, may have played a role in this malignant transformation.

Malignant fibrothecomatous tumour of the ovary: diagnostic value of anti-inhibin immunostaining.

Malignant ovarian tumours of the fibrothecoma group are rare. The clinicopathological features of a case of ovarian malignant fibrothecoma in which there was metastatic disease in the small intestine and peritoneum at presentation are described. A number of differential diagnoses were considered but positive immunohistochemical staining of the resected ovarian and small intestinal neoplasms with anti-inhibin was of value in confirming a sex cord-stromal tumour and in excluding other lesions. The two tumours were also ultrastructurally identical. Classical malignant fibrothecomas are said to show four or more mitotic figures per 10 high power fields (HPF). Although the intestinal secondary was mitotically active, the primary ovarian tumour contained only one to two mitoses per 10 HPF, showing that formal mitotic counts are not an absolute indicator of malignant behaviour in this group of tumours.

Atypical carcinoid tumor of the larynx: an immunohistochemical, ultrastructural, and flow cytometric analysis.

The clinicopathologic features, including a detailed immunohistochemical, ultrastructural, and flow cytometric analysis, are described in three cases of atypical carcinoid tumor of the larynx. All patients had metastatic disease within cervical lymph nodes at presentation and eventually developed distant metastases. Special stains revealed focal intracytoplasmic mucin accumulation, and immunohistochemistry showed the tumors to be positive for CAM 5.2, CEA, chromogranin A, and calcitonin. In two cases, double-staining techniques revealed occasional cells that stained for both mucin and chromogranin A. The histochemical and immunohistochemical findings in these two cases were confirmed at the ultrastructural level, with most tumor cells containing many neurosecretory granules. Smaller numbers of cells contained mucin vacuoles and, in occasional cells, both mucin and neuroendocrine granules were identified. The three tumors exhibited positive staining with D07 (anti-p53), and flow cytometric analysis revealed DNA aneuploidy and polyploidy. The double-staining and ultrastructural features indicate that laryngeal atypical carcinoid qualifies for the designation of true amphicrine carcinoma. Further study is necessary to determine whether mutation of the p53 gene is important in the evolution of laryngeal neuroendocrine tumors and whether DNA aneuploidy or polyploidy identifies a subset of these tumors with a poor prognosis.

TP53 mutation in ovarian carcinoma.

This short report describes the detection of mutations of the TP53 tumour suppressor gene in sporadic ovarian carcinomas using archival paraffin-embedded tissues and automated fluorescent DNA sequencing. TP53 mutations were detected in eight tumours. Missense mutations predominated and all were transitions. Mutations were commonest in late-stage serous tumours. In three cases, where tissue was available, the mutations were homogeneous throughout several sections of the bilateral ovarian tumours and in omental metastases. These data confirm the findings of previous investigations describing TP53 mutation in ovarian carcinoma and demonstrate that archival paraffin-embedded tissues can be used for such analyses.

The immunophenotype of human decidua and extra-uterine decidual reactions.

Decidua associated with products of conception from intra-uterine and extra-uterine gestations and decidualized tissue from the appendix, cervix and Fallopian tube were studied using a panel of antibodies and antisera. Immunolocalization of vimentin and desmin intermediate filament proteins and of alpha-1-antitrypsin and alpha-1-antichymotrypsin was identified in most of the 43 cases studied. Placental alkaline phosphatase, beta human chorionic gonadotrophin, cytokeratin, smooth-muscle actin and leukocyte markers (CD3, CD20, CD68) were also expressed in some cases. Occasional cases reacted for CD45 and S-100 protein. Similar reaction profiles were obtained at both intra-uterine and extra-uterine sites. The results show that extra-uterine mesenchymal cells which have undergone a decidual reaction correspond closely to their counterparts in the endometrial stroma. Since positive immunostaining within decidual cells for cytokeratins, placental alkaline phosphatase and beta human chorionic gonadotrophin indicates that trophoblastic cells are not exclusively recognized by these antibodies, their use does not permit the confident diagnosis of an intra-uterine gestation.

Endometrial stromal sarcoma with sex cord-like areas and focal rhabdoid differentiation.

An unusual uterine lesion is described in a patient with postmenopausal bleeding. Grossly, a yellow, polypoid mass projected into the uterine cavity. Histological examination showed a distinct biphasic pattern with areas of typical low-grade endometrial stromal sarcoma and areas where tumour cells were arranged in cords and trabeculae, resulting in a sex cord-like pattern. In these areas the cells assumed a rhabdoid morphology with eccentric vesicular nuclei, prominent nucleoli and eosinophilic hyaline cytoplasmic inclusions. Immunohistochemistry showed positive cytoplasmic staining of both components for vimentin, desmin and the cytokeratin marker CAM 5.2, but no staining for CEA and EMA. Electronmicroscopy revealed prominent paranuclear arrays of intermediate filaments. This is the second reported case of endometrial stromal sarcoma with rhabdoid differentiation and the first documented example of rhabdoid cells in sex cord-like areas. The report adds to the list of diverse neoplasms which may display a characteristic rhabdoid morphology and supports the hypothesis that extrarenal rhabdoid tumours are not a distinct clinicopathological entity. A diagnosis of malignant rhabdoid tumour of the uterus should be considered only when extensive sampling fails to disclose areas with an appearance typical of an endometrial stromal lesion.

p53 mutation, allele loss on chromosome 17p, and DNA content in ovarian carcinoma.

The aim of this investigation was to explore the relationships between p53 mutation, DNA aneuploidy, 17p deletions, and clinical stage in ovarian cancer. Nuclear suspensions were obtained by tissue disaggregation, stained with propidium iodide, and analysed on a Coulter EPICS Elite flow cytometer. DNA cell cycle analysis was performed using Multicycle software (Phoenix Flow Systems). DNA extracted from paraffin-embedded archival carcinomas/non-tumour tissue was used as template for PCR amplification of the microsatellite dinucleotide repeat polymorphism D17S513, a locus telomeric to p53 on 17p13.1. Allele loss at D17S513 was detected in 64.5 per cent of carcinomas (20 of 31 informative cases). DNA aneuploidy was detected in 20 of 54 (37 per cent) carcinomas. Eight of ten cases previously shown to harbour p53 mutations showed aneuploid DNA content. Although ten other DNA aneuploid cases had shown no p53 mutations, the results show a statistically significant association between p53 mutation and DNA aneuploidy (P < 0.01). Furthermore, the mean DNA index of the DNA aneuploid cases was significantly higher in p53 mutant cases compared with those showing no p53 mutation (P = 0.02). There was also a significant association between p53 mutations and stage, between ploidy and stage, and between allelic deletions at D17S513 or p53 and stage, but not between these allelic deletions and ploidy. p53 mutations appear to be associated with DNA aneuploidy in ovarian cancer independently of 17p deletions. p53 mutations, DNA aneuploidy, and 17p deletions are associated with late stage.

Parathyroid cyst of the thymus.

A case is described of primary hyperparathyroidism in a patient with both a parathyroid cyst within the thymus gland and a concomitant parathyroid adenoma. The parathyroid adenoma contained microcystic areas of degeneration, and it is thought that the parathyroid cyst reflected degenerative change in a pre-existing adenoma. Parathyroid cyst should be considered in the differential diagnosis of cystic lesions within the thymus. Fine needle aspiration and parathyroid hormone assay on cyst fluid may provide a preoperative diagnosis.