Malignant lymphoma of the cervix. An unusual presentation and a rare disease.

Malignant lymphomas arising in the uterus are uncommon and are more commonly seen in the cervix than the corpus. Involvement of the cervix as part of a systemic lymphoma is more common than primary lymphoma, but the cervix as the site of presentation is unusual. We report two cases of malignant lymphoma of the cervix. The first patient, a 52-year-old woman, was referred to colposcopy following persistent low grade dyskaryosis on cervical cytology. At colposcopy a Lletz biopsy was performed and a diagnosis of CIN 1 and focal CIN 2 was made. In addition the subepithelial zone revealed a non-Hodgkin's (NHL) B-cell follicular lymphoma. The patient was subsequently staged as NHL Stage 3E. The second patient, a 35-year-old woman, was referred to the gynaecology department with a history of abnormal vaginal bleeding and two abnormal smears. Subsequent cervical biopsy revealed a high grade, large cell, malignant lymphoma, diffuse, B-cell. The patient was staged as Stage IE. Primary lymphoma of the uterine cervix as illustrated in the second case is very unusual. One case had negative cytology and one case had abnormal cells of uncertain origin. This highlights the difficulty of diagnosing cervical lymphoma, a rare but treatable malignancy, on cytology and suggests that cervical biopsy is needed for the confirmation of the diagnosis.

Identification of vertical growth phase in malignant melanoma. A study of interobserver agreement.

Ninety-four H & E-stained slides of malignant melanoma were circulated to 6 pathologists in 2 university departments. For each slide, the growth phase of the lesion, Breslow thickness, and Clark level were determined by each observer. The aims of the study were to evaluate agreement between nonspecialist pathologists in identifying the vertical growth phase in malignant melanoma and to compare agreement for the growth phase with agreement for Breslow thickness and the Clark level. Our results show that although overall agreement for the growth phase is moderate, agreement between experienced observers is good. In fact agreement for the growth phase among this group was equal to the agreement for Breslow thickness. Overall agreement for Breslow thickness also was good but for the Clark level was only fair. These findings suggest that if the predictive value of the vertical growth phase proves to be robust, it will be used with an acceptable level of accuracy in routine diagnostic practice.

Ploidy profile of morphologically normal squamous epithelium adjacent to high grade cervical intraepithelial neoplasia.

We have investigated the ploidy profile of morphologically normal mucosa adjacent to high grade CIN (n = 16) and also from normal cervix (n = 18). DNA ploidy was assessed using flow cytometry and image analysis. All cases were diploid by both modalities. Our results show that morphologically normal squamous mucosa has a stable ploidy profile even when it lies adjacent to high grade CIN. This finding supports the view that high grade CIN is a neoplastic expansion of transformed cells rather than the result of a field change effect.

Mild abnormalities in liver histology associated with chronic hepatitis: distinction from normal liver histology.

BACKGROUND: Chronic hepatitis C virus infection associated with contaminated anti-D immunoglobulin has become an issue of recent concern. The clinical course of chronic hepatitis C infection is unpredictable and histological assessment is felt to be the most reliable means of assessing disease status. Semiquantitative scoring systems have been devised, which assess degree of necroinflammatory disease activity (grade) and extent of disease progression with fibrosis (stage) in chronic hepatitis. Often, using these systems, biopsies of anti-D associated chronic hepatitis C cases show mild changes only, with low scores. The significance of these low scores is uncertain. AIMS: To evaluate the significance of low scores in chronic hepatitis. METHODS: Liver biopsies were assessed from two groups of patients in whom liver histology would be expected to be normal: 30 cases of Gilbert's syndrome and 13 necropsy cases of young people (< 45 years) with no history or risk factors for liver disease. These biopsies were scored using the histological activity index of Knodell et al and its recent modification (separation of scores for grade and stage) by Ishak et al. RESULTS: Twenty of 30 cases of Gilbert's syndrome and 11 of the 13 necropsy cases had chronic hepatitis scores of 1 or 2, whereas only eight cases of Gilbert's and two necropsy cases had scores of 0. The remaining two Gilbert's cases had scores of 3 and 5. Similar results were found using both the histological activity index of Knodell et al and the method of Ishak et al. CONCLUSION: The finding of low but positive scores using these systems in people with normal liver histology questions the reliability and significance of finding such scores in patients with chronic hepatitis and is of particular concern in the evaluation of chronic hepatitis C infection.

Primary hepatic leiomyosarcoma.

Hepatomegaly was noted in a 63-year-old man who presented with an exacerbation of chronic pulmonary disease. A diagnosis of hepatic leiomyosarcoma was made by fine needle aspiration biopsy. Intensive investigations failed to reveal a primary source. The patient was treated conservatively.

Proliferation indexes--a comparison between cutaneous basal and squamous cell carcinomas.

AIMS: To compare differences in cell proliferation indexes and apoptotic indexes between cutaneous basal and squamous cell carcinomas, in an attempt to suggest an explanation for the differences in their biological behaviour. METHODS: Forty cases of cutaneous basal cell carcinoma (BCC) and 40 cases of moderately and well differentiated squamous cell carcinoma (SCC) were retrieved from the archives. Sections, 4 microns thick, were cut from formalin fixed, paraffin wax embedded tissue in each case and stained with haematoxylin and eosin. These were then examined for mitotic and apoptotic figures per 1000 cells. Sections from the same cases were also immunostained with the mouse monoclonal antibody Ki67 (MIB1); positive nuclear staining was counted per 1000 cells. RESULTS: No significant differences were found between the mitotic indexes and apoptotic indexes in these tumours. There was, however, a significant difference in Ki67 (MIB1) staining, with greater staining in the squamous cell carcinomas. CONCLUSION: Estimation of the mitotic and apoptotic indexes did not reveal any differences between these two tumour types. The proliferation indexes, assessed by Ki67 immunostaining, did differ. This may be one of the factors underlying the more aggressive behaviour of SCC.

Influence of test duration and event specificity on maximal accumulated oxygen deficit of high performance track cyclists.

This study examined the relationship between the time required to fully utilise the maximal accumulated oxygen deficit (MAOD) and event specificity of track cyclists. Twelve track endurance and 6 sprint high performance track cyclists performed four treatments of 70 s, 120 s, 300 s and 115% VO2max of maximal cycling on an air-braked ergometer. Peak blood lactate was measured immediately after each test with VO2 kinetics being assessed during the 115% VO2max time to exhaustion test. When the two cycling groups were combined there was no significant difference in the MAOD when assessed under the four different exercise durations. However, when the groups were analysed separately the following results were apparent: (1) the sprint cyclists achieved a significantly greater MAOD (66.9 +/- 2.2 ml.kg-1) compared to the track endurance cyclists (57.6 +/- 6.7 ml.kg-1) when a 70 s test duration was employed (2) even though the track endurance cyclists achieved their greatest MAOD during the 300 s test protocol (62.1 +/- 11.0 ml.kg-1), it was not significantly different to the MAOD's measured during the three other test durations and (3) the sprint cyclists recorded their greatest MAOD during the 70 s supramaximal test protocol (66.9 +/- 2.2 ml.kg-1). This was not significantly different to the 120 s test MAOD, but it was significantly higher than the MAOD values recorded during the 115% VO2max and 300 s test durations. There was no significant difference between the two groups in the peak post-exercise blood lactate concentrations for any of the tests and only the 70 s test produced a significant correlation between peak blood lactate and the MAOD. The VO2 kinetics (VO2 t1/2) of the sprinters was significantly slower than that of the track endurance cyclists (26.3 +/- 2.3 vs 23.9 +/- 2.8 s.). The findings of this study demonstrate that sprint cyclists can fully express their anaerobic capacity within an event specific 70 s all-out test and that these cyclists progressively decrease their anaerobic capacity during a 120 s, 115% VO2max (mean time = 210 s) or 300 s test, despite giving all-out efforts. Conversely, track endurance cyclists achieve their highest mean score during an event specific 300 s test and their lowest during a 70 s test. These findings have important implications when testing high performance cyclists for determination of MAOD, with the implication that it is necessary to assess MAOD under exercise conditions (i.e., duration, pacing) specific to the cyclist's chosen event.

The pathology of cervical cancer.

The significant changes over the last decade in the CIN/cervical carcinoma area have involved the increasing recognition of many cervical carcinomas as adenocarcinomas, rather than squamous cell type, and their propensity for arising in young women. Another area of interest is the deployment of new molecular techniques that are unveiling the role of oncogene co-factors (e.g. HPV, p53) in the biologic evolution of CIN and hopefully glandular dysplasia.

DNA quantification is technically feasible and of value in cervical smear samples: possible applications for determination of progression in low grade dyskaryosis.

This study evaluates the feasibility of DNA analysis of cervical intraepithelial neoplasia III (CIN III) lesions on cervical smear and formalin-fixed paraffin-embedded tissue (FFPET) blocks with a view to extending this type of analysis to milder grades of dyskaryosis. DNA ploidy was determined by image analysis using a CAS 200 Image Analyser. Seventeen patients with a diagnosis of CIN III were studied. Results show that all smear and tissue samples were non-diploid with nine aneuploid and eight tetraploid lesions. In 6/7 patients whose smears and corresponding biopsies were examined there was complete agreement as to the DNA profile. We conclude that DNA quantification is technically feasible in archival, routinely prepared cervical smears. This technique should now be applied to CINI and CINII cervical smears to determine if it is of value in identifying those lesions that will progress to CIN III. This study is particularly timely with the possibility in the near future of estimation of ploidy by image analysis using instruments such as the Highly Optimized Microscope Environment (HOME) system.

Cytoplasmic c-erbB-2 protein expression correlates with survival in Dukes' B colorectal carcinoma.

The prognostic significance of c-erbB-2 expression was studied in paraffin wax embedded colorectal cancer tissue using a monoclonal antibody. One hundred and sixty-four patients with Dukes' B disease were studied. Membranous staining was not detected in any case. Cytoplasmic c-erbB-2 staining was seen in 55 cancers (33.5%). Cytoplasmic staining was unrelated to patient age (P = 0.31), sex (P = 0.69), tumour site (P = 0.69), size (P = 0.57), histological grade (P = 0.42) or ploidy status (P = 0.21) but was found more frequently in obstructing cancers (P = 0.03). Mean follow up of the patient population was 6.3 years. Five-year-survival estimated by the Kaplan-Meier life-table method was 47% for those with cytoplasmic c-erbB-2 staining and 77% for those without (log rank analysis; P < or = 0.0001). Stepwise regression analysis identified c-erbB-2 staining (relative risk, 2.51; P = 0.0005) and bowel obstruction (relative risk, 1.99; P = 0.015) as independent predictors of survival. It is suggested that cytoplasmic c-erbB-2 expression may provide a useful marker of tumour behaviour in Dukes' B colorectal cancer.

Aerobic and anaerobic indices contributing to track endurance cycling performance.

A group of 18 male high performance track endurance and sprint cyclists were assessed to provide a descriptive training season specific physiological profile, to examine the relationship between selected physiological and anthropometric variables and cycling performance in a 4000-m individual pursuit (IP4000) and to propose a functional model for predicting success in the IP4000. Anthropometric characteristics, absolute and relative measurements of maximal oxygen uptake (VO2max), blood lactate transition thresholds (Thla- and Th(an),i), VO2 kinetics, cycling economy and maximal accumulated oxygen deficit (MAOD) were assessed, with cyclists also performing a IP4000 under competition conditions. Peak post-competition blood lactate concentrations and acid-base values were measured. Although all corresponding indices of Thla- and Th(an),i occurred at significantly different intensities there were high intercorrelations between them (0.51-0.85). There was no significant difference in MAOD when assessed using a 2 or 5 min protocol (61.4 vs 60.2 ml.kg-1, respectively). The highest significant correlations were found among IP4000 and the following: VO2max (ml.kg-2/3.min-1; r = -0.79), power output at lactate threshold (Wthla) (W; r = -0.86), half time of VO2 response whilst cycling at 115% VO2max (s; r = 0.48) and MAOD when assessed using the 5 min protocol (ml.kg-1; r = -0.50). A stepwise multiple regression yielded the following equation, which had an r of 0.86 and a standard error of estimate of 5.7 s: IP4000 (s) = 462.9 - 0.366 x (Wthla) - 0.306 x (MAOD) - 0.438 x (VO2max) where Wthla is in W, MAOD is in ml.kg-1 and VO2max is in ml.kg-1 x min-1.(ABSTRACT TRUNCATED AT 250 WORDS)