Cutaneous lesions in a case of acute megakaryoblastic leukaemia.

We describe the case of a 68-year-old woman who presented with asymptomatic skin nodules and symptoms of anaemia, and was found to have acute megakaryoblastic leukaemia with fibrosis, a condition now believed to correspond to the former diagnosis of acute myelofibrosis. There is only one previous report of skin lesions developing in this condition.

Soft tissue cervical metastases of squamous carcinoma of the head and neck.

Some 497 of 3085 patients with squamous cell carcinoma of the head and neck treated between 1963 and 1990 had a later radical neck dissection at some time after initial treatment. The histological slides were all reviewed, firstly to confirm the presence of squamous cell carcinoma within the neck, and secondly to ascertain whether the metastasis was to soft tissue, to a lymph node or to both. The presence of extracapsular rupture in lymph node deposits was also assessed. Of the 497 patients, 138 had soft tissue deposits only, and 359 had nodal deposits only. Of the patients with nodal deposits 165 had extracapsular rupture and 194 did not. The 5-year survival of the 138 patients with soft tissue metastases was 27% compared with 33% for patients with extracapsular rupture and 50% for patients with no extracapsular rupture. Weighted logistic regression showed that soft tissue deposits were significantly more common in patients in poor general condition, plus poorly differentiated squamous cell carcinoma plus T4 tumours (P < 0.005), and in patients with poorly differentiated squamous cell carcinoma plus T4 tumours (P < 0.025). Cox's multivariate analysis with backward elimination showed that gender, histological differentiation, site of primary tumour and age of patient had no statistically significant effect on survival. The number of nodes (P < 0.0001), the presence of extracapsular rupture (P < 0.0001) and the presence of soft tissue free metastases (P < 0.001) were all highly significant. The N-status at recurrence also reached statistical significance (P < 0.0001).

A comparison of cellular proliferation markers in squamous cell carcinoma of the head and neck.

Head and neck squamous cell carcinoma has a relatively good prognosis but treatment may be at the expense of function and quality of life. Various host and tumour parameters have been studied in an attempt to predict the course of the disease but without success. It has been hoped that laboratory based methods, particularly those based on molecular biology, may prove more useful. Cell kinetic parameters are studied in this paper. The present study includes 75 patients with a proven squamous cell carcinoma of the head and neck at various sites and undergoing various forms of treatment. The patient's mean age was 62 years and the median survival rate 45 months. Immunohistochemical techniques using Ki67 and PCNA were compared with flow cytometric analysis which included the BRDU labelling index, the duration of S phase, ploidy and potential doubling time. The median PCNA index was 560 and the Ki67 index 298. These indices varied between 980 and 150 for PCNA and 808 and 110 for Ki67. The BRDU labelling index measured by flow cytometry was 8.9 with a range from 25 to 1.6 and the duration of S phase was 14.8 hours. The PCNA index failed to correlate with any host or tumour factors and this failure was also seen in Ki67 indices and also in the flow cytometric parameters. There was a strong correlation between PCNA and Ki67 expression (p < 0.0001). Neither PCNA nor Ki67 values were significantly different between irradiated and nonirradiated tissues nor in sites or in patients who later developed lymph node metastases.(ABSTRACT TRUNCATED AT 250 WORDS)

Pretransplant clinicopathological correlation in end-stage primary pulmonary hypertension.

The aim of the study was to see if there was any correlation between the histopathology, ultrastructure, pulmonary endocrinology and clinical manifestations of end-stage primary pulmonary hypertension. Twenty patients undergoing heart-lung transplantation for the disease were studied. The nature and duration of symptoms and signs, results of haematological, electrocardiographic, radiographic, echocardiographic and haemodynamic studies, and the response of patients to vasodilators were compared with data from histopathological and ultrastructural study of lungs removed at transplantation. Length of clinical history and clinical evidence of severe disease were not necessarily associated with advanced histopathology, nor did the presence of small, contracted muscular pulmonary arteries imply responsiveness to vasodilators. Numbers of gastrin-releasing peptide-containing pulmonary endocrine cells were greater in lungs in which there was activity of myofibroblasts in pulmonary arterial vessels, and correlated negatively with mean pulmonary artery pressure and pulmonary artery systolic pressure. Whereas the prognosis of primary pulmonary hypertension cannot as yet be defined by other than its clinical manifestations, intimal proliferation as well as vasoconstriction may be important in its pathogenesis. The release of gastrin-releasing peptide from pulmonary endocrine cells may possibly be involved in this process.

Has the cellular proliferation marker Ki67 any clinical relevance in squamous cell carcinoma of the head and neck?

Over the years many laboratory factors have been studied with a view to predicting the course of head and neck cancer. The lack of success prompted the application of various measures of cell kinetics to this topic. The present study includes 79 patients with a proven squamous cell carcinoma of the head and neck at various sites and having various treatments. Ki67 staining was carried out using the avidin-biotin complex method and counts recorded per 1000 tumour cells. The patients' mean age was 61 years and the 5 year survival was 54% (95% CI, 29-73%). The median Ki67 index was 278 representing the number of cells stained positively per 1000 tumour cells. The minimum staining was 82 and the maximum 808 with a lower quartile of 95 and an upper quartile of 452. The Ki67 index failed to correlate with any host or tumour factors. In addition, median Ki67 values were not significantly different between irradiated tissue and non-irradiated tissue, between sites nor between patients who did and did not later develop lymph-node metastases. Of particular relevance is that Ki67 value did not correlate with survival. Data was further analysed using Cox's proportional hazards model for survival. Ki67 had no significant effect on survival. It is concluded that Ki67 index is of no value in predicting the course of squamous cell carcinoma of the head and neck.

Fine needle aspiration cytology of salivary gland lesions reported immediately in a head and neck clinic.

This paper describes the application of fine needle aspiration cytology (FNAC) performed on 92 patients with salivary gland lesions in a Head and Neck Surgery Clinic. The aspirates were immediately reported by a cytopathologist and the reports conveyed to the surgeon during the same clinic visit. FNAC results were then compared with histology in those patients who underwent surgery and with the clinical course of the disease at subsequent clinic visits in patients where surgery was not performed. The cytological diagnosis was incorrect in five cases, one of which was a false negative result. There were no false positive results. The sensitivity was 90.9 per cent and the specificity 100 per cent. This rapid report system of fine needle aspiration cytology has been found to be safe, free of complications, and helpful in the planning of treatment.

Expression of the cell-cell adhesion molecule E-cadherin in squamous cell carcinoma of the head and neck.

The expression of the cell-cell adhesion molecule E-cadherin has previously been shown to be reduced in poorly differentiated squamous cell carcinoma of the head and neck and absent in nodal metastases. Twenty-eight patients with previously untreated squamous cell carcinoma of the head and neck, 22 of whom had nodal metastases at presentation, were investigated for E-cadherin expression using the monoclonal antibody 6F9, specific for human E-cadherin. Reduced expression was seen in the poorly differentiated primary tumours, compared with well differentiated tumours, but this trend was not statistically significant. E-cadherin expression was present at a reduced level in nodal metastases. It was also noted that, where both the primary tumour and corresponding nodal metastasis were investigated, E-cadherin expression was identical for both samples. The degree of E-cadherin expression did not correlate with survival. These data confirm a reduction in E-cadherin expression in poorly differentiated tumours. There was no correlation between E-cadherin expression and any of the host, tumour and treatment factors associated with malignancies of the head and neck region.

Value of grading squamous cell carcinoma of the head and neck.

We report a series of 3,294 patients with squamous cell carcinoma of the head and neck seen by one of us between 1963 and 1990. Two thousand and seven patients had a histologically proven and graded, but previously untreated, squamous cell carcinoma of the mucosal surfaces of the head and neck. These tumors had been graded previously by many different pathologists in many different hospitals, both in the United Kingdom and the United States, as well as continental Europe, over this period. Of the host factors both sex and age were associated with differentiation: 34% of patients less than age 50 had a well-differentiated tumor compared with 44% greater than age 50; 32% of women had a poorly differentiated tumor compared with 26% of men. General condition had no correlation with degree of differentiation. Site was closely associated with grading: well-differentiated tumors were more common in the mouth and larynx and poorly differentiated tumors in the pharynx. Furthermore, of poorly differentiated tumors, 19% arose from areas normally lined by keratinized squamous epithelium, 22% from a nonkeratinized area, 36% from respiratory epithelium, and 45% from areas normally covered by lymphoid epithelium. T stage had no significant correlation with differentiation. However, 46% of patients with poorly differentiated tumors had a nodal metastasis at presentation compared with only 28% of well-differentiated tumors. Distant metastases at presentation were found in 3.4% of poorly differentiated tumors compared with 1.8% of well-differentiated tumors. The survival fell significantly from 33% for well-differentiated tumors to 27% for poorly differentiated tumors. The recurrence rate at the primary site rose from 25% for well-differentiated tumors to 27% for poorly differentiated tumors, and recurrence in the lymph nodes rose from 26% to 30%. Both differences were just significant.

Pulmonary endocrine cells in hypertensive pulmonary vascular disease.

A study was made of the number of pulmonary endocrine cells, immunoreactive for gastrin-releasing peptide (bombesin) or calcitonin, in the terminal bronchioles of 39 cases of pulmonary vascular disease. In 25 of these, the form of vascular disease was plexogenic pulmonary arteriopathy, primary in 12 and secondary in 13, while the remaining 14 subjects had a wide range of other varieties of hypertensive pulmonary vascular disease. We found that pulmonary endocrine cells, especially those containing bombesin, were increased in number in both the primary and secondary forms of plexogenic pulmonary arteriopathy but not in other varieties of pulmonary hypertension. The prominent bombesin-containing cells were found in cases with cellular plexiform lesions but occurred even more prominently at an earlier stage when vascular smooth muscle cells were migrating from the inner media into the intima.

The histopathology of 36 cases of plexogenic pulmonary arteriopathy.

A detailed histopathological study was made of the lungs of 36 cases of plexogenic pulmonary arteriopathy coming to combined heart-lung transplantation. It revealed two dissimilar processes involved in the pathogenesis of this disease. One comprised histological appearances consistent with constriction of muscular pulmonary arteries, a condition that would be likely to be reversed by pulmonary vasodilators. The other was the proliferation of myofibroblasts in the intima and lumen of pulmonary arteries, a disorder of growth unlikely to be influenced by this type of therapy. In previous ultrastructural studies we have shown that the source of these cells of muscular pedigree is muscle cells from the inner half of the media which migrate into the intima through gaps in the inner elastic lamina. In the present study we found a similar proliferation of myofibroblasts in the intima, not only of pulmonary arteries, but also of pulmonary veins, in plexogenic pulmonary arteriopathy. Arterial thrombi found were considered to be a complication rather than a cause of plexogenic pulmonary arteriopathy. Siderophages, cholesterol granulomas and focal fibrosis in the lung were considered to be a consequence of intrapulmonary haemorrhage early in the course of the disease. It is concluded that, while plexogenic pulmonary arteriopathy has an important vasoconstrictive element, it is also based on a disorder of growth of cells of muscular pedigree. This view has clear implications for the therapy of primary plexogenic pulmonary arteriopathy.