The monoclonal antibody Ki67 recognizes an antigen expressed in all phases of the cell cycle except Go. It has been used in 141 biopsies from 138 patients with non-Hodgkin's lymphoma to identify proliferating cells in histological sections. A Ki67 index (the number of Ki67 positive tumour cells divided by the sum of Ki67 positive and negative tumour cells) has been derived by counting 1000 cells in each case. A correction for the presence of non-tumour cells has been incorporated by counting non-tumour cells in serial sections stained with a panel of other antibodies. A very strong correlation between a low Ki67 index (less than 20 per cent) and low grade histology and a high Ki67 index (greater than 20 per cent) and high grade histology was found (Chi2 = 98.0). Ninety-one patients could be analysed for survival and those with low grade lymphoma (n = 38) who had a relatively high Ki67 index (greater than 5 per cent) had a worse survival than those with an index of less than 5 per cent (p less than 0.05). In contrast, there was a trend for those patients with high grade disease with a very high Ki67 index (greater than 80 per cent) to have a better survival than those with a lower index (less than 80 per cent). The patients with high grade disease who achieved complete remission or good partial remission and had a Ki67 index of less than 80 per cent were more likely to relapse than those with an index of greater than 80 per cent (p less than 0.04). These findings could not be explained by the effect of other prognostic factors such as age, stage, or serum albumin. While the use of Ki67 immunostaining has potential drawbacks, it appears to be a simple and reproducible method of determining a tumour proliferative index which provides relevant clinical data.
One hundred forty-eight patients with newly diagnosed follicular lymphoma were treated over a 12-year period. Twenty-two patients received radiotherapy for stage I and II disease, followed by adjuvant chemotherapy in 14 patients. One hundred thirteen were treated at presentation with short courses of chemotherapy, most often with single-agent chlorambucil for bulky stage II and stages III and IV disease. Thirteen patients were managed expectantly until there was evidence of disease progression. The median survival was 9 years. Patients treated with radiotherapy for stage I and II disease had an 83% relapse-free survival, but those with bulky stage II or stages III and IV disease treated with chemotherapy pursued a remitting and relapsing course with a 70% response rate at initial and subsequent retreatments, but a median duration of remission of 4 years in stage III and 1 year in stage IV disease (P = .041). Patients were observed in relapse and retreatment was administered as appropriate, once every 33 months on average. Poor prognosis patients could be identified by a combination of the presentation characteristics: B symptoms, hepatosplenomegaly, anemia, and abnormal liver function. These factors predicted a poor response to treatment and correlated with a short survival. Histologic subgroups were not associated with differences in survival, but transformation to a diffuse high-grade lymphoma was observed in 23 of the 72 patients (32%) at risk, with a median follow-up of 6 years and 6 months, and was associated with a very poor prognosis. The present treatment strategy has proved successful for most patients with localized disease and those older patients with indolent small volume disseminated follicular lymphoma. New approaches are being investigated for the younger poor prognosis patients.
WE have seen three examples of a tumour of the foot which does not appear to be described in the literature. Probably, as we shall see, it is no more than a carcinoma of the skin. But two at least of our cases (One we Only know as a specimen) caused both clinicians and pathologists concerned considerable difficulty in diagnosis and treatment, and we and characteristically sickly smell of sebum oozed out of these sinuses like toothpaste from a tube. The mass extended right through the foot, and appeared on the size and extent it did not appear to be destroying bone, tendon, nerve, or any other important structure. It had been present two years, and had recurred after an excision elsewhere a year earlier. Several biopsies had failed to provide a firm diagnosis. Search for possible very unusual variant on the old theme of squamous dorsum (Fig. 279) between the toes, but despite its FIG. 278.-Care I . Plantar view of the foot when first The small depressions on the summits of several of seen. the hossy projections are sinus openings.have some evidence that similar tumours, though rare, have been seen elsewhere and caused similar difficulties ; we believe therefore they deserve description. CASE REPORTSCase I.-CLINICAL HISTORY.-A man of 64 presented himself to one of us (I. A.) in 1950 with a very curious swelling of the fore part of the left foot (Figs. 278, 279). It formed a bulbous mass on the sole, covered with skin but with many sinuses, most of the latter opening each at the apex of a separate bulge. It was ' squashy ' in consistency, and on pressure greasy material with the appearance FIG. z79.-Cuse I . Dorsal view. (The small black lesion is a benign melanoma, unrelated to the main tumour.)infective agents proved fruitless. Finally, the mass continuing to enlarge and the foot being useless, mid-leg amputation was carried out. Convalescence was complicated by fracture through an area of Paget's disease in the tibia of the opposite leg, but the patient was ultimately able to walk well and is now, three years after the operation, fit and free from metastases. PAmoLoGY.-Several biopsies were available for study, but they add no information, and description will be confined to the amputation specimen. This showed no abnormalities except for the mass in the foot. The external appearance of this corresponded to the clinical description. The foot was frozen and then sawn into sagittal slices (Fig. 280). The tumour was then seen to be well-defined, filling and expanding the soft tissues of
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