The sequence of events in haematogenous metastasis from colonic carcinoma was analysed, using 1541 necropsy reports from 16 centres. The findings are consistent with the cascade hypothesis that metastases develop in discrete steps, first in the liver, next in the lungs and finally, in other sites. Deviations of necropsy findings from the cascade model are largely explained on the basis of false negative reports. In only 216 of 1194 cases was there suggestive evidence that metastatic patterns (excluding lymph nodes) were causally related to lymphatic or non-haematogenous pathways. The incidence of metastatic involvement in 'other' (quaternary) sites correlated with target organ blood-flow (ml min-) per g, only when bone marrow and thyroid were excluded. In the thyroid the incidence was lower than expected on the basis of blood flow per g tissue; this may indicate that the thyroid is an unfavourable site for metastatic growth of colonic carcinoma. In the bone marrow it is higher; the latter may be due to delivery of cancer cells via both arterial blood and the vertebral venous plexus. Recognition of this pattern of metastases in the bone marrow could be important with respect of diagnosis and therapy, in patients with colonic carcinoma.
The metastatic behaviour of renal cell carcinoma has been studied in a series of 687 necropsies. The observations were consistent with the concept of "metastatic inefficiency", in that in 295 cases, including 25 with renal vein invasion, there were no detectable metastases. In the present series, renal vein involvement was not an important prognostic factor in stage 1 or 2 disease. In 73% of cases without lung metastases there were none in other sites, and in 84% of those with lung metastases there were others elsewhere, consistent with a metastatic "cascade" in which metastases first developed in the lungs and were later detected in other organs. However, the observations did not permit discrimination between anatomic cascades, in which other organs were seeded from metastasizing pulmonary metastases, and temporal cascades, in which the other were seeded at the same time as the lungs, but with fewer cancer cells. The patterns of arterial metastasis were consistent with the "seed-and-soil" hypothesis, and a novel index was developed to quantify differential organ "soils". The contralateral kidney was not the best soil for metastases from renal carcinoma. Given the presence of lymph node metastasis, the probability of heamatogenous metastasis is 90%. However, in the absence of nodal metastasis, approximately half the cases had haematogenous metastasis.
Measurement of the area of the tumour deposits present in routine sections from the axillary nodes from a series of 1069 breast cancer patients showed that 138 cases had a single micrometastasis (0.2 cm2 or less), while in 29 a similar load was spread over two or more nodes. These 167 cases represent 15% of the patients in the series. Twentyfive of them had died of breast cancer within a mean follow-up of 6 years. They had smaller micrometastases than those surviving (P < 0.0025). Histological examination in the 138 with single micrometastases showed that two variants were present. In one, tumour growth was confined to the capsular lymphatics and/or the subcapsular sinus. In the other, tumour growth was present in the nodal lymphoid tissue, and, on occasion, at the other sites as well. Those with growth in the lymphoid tissue had a better prognosis than those without (P < 0.0035). Prognosis in the former was comparable to that in the node-negative cases, while in those lacking such growth it was similar to that in the node-positive. The presence of these two variants could explain divergent reports in the literature on prognosis in cases with micrometastases. While the mechanisms behind this apparent paradox remain speculative, the observation can be of diagnostic interest in routine surgical pathology.
Metachromasia of the connective tissue in 50 human breast carcinomas following staining with toluidine blue was associated with mast cell degranulation and granular depletion. When present at the tumour edge it marked areas of infiltrative growth, accompanied by a mild vascular response consistant with the release of vasoactive substance from the mast cells. The rôle of this inflammatory response in local tumour spread is discussed.
A simple method of preparing axillary nodes from breast cancer patients for routine histology is presented. It is based on appreciation of nodal anatomy and the pathophysiology of tumour growth in them. Current methods assume that the latter is a random process, but this is not so. It has long been known that tumour cells enter via the afferent lymphatics. They may also exit by the efferent. It has not been generally realized that these vessels enter/leave the node in the same plane of section, or that a section in this plane, a hilar section, is theoretically the one of choice for the identification of tumour cells in the node. It is shown here that use of hilar sections alone allows the identification of tumour-free and tumour-bearing nodes, as well as the tumour status of the efferent vessels, with considerable certainty. The use of random sections, in contrast, carries a high risk of false negative reporting.
Analysis of the clinical and post-mortem assessment of the underlying cause of death in 742 autopsies showed that over- and underdiagnosis cancelled each other out in the majority of the main diagnostic groups, so there was little difference in the total number of cases recorded in the different groups after clinical and post-mortem investigation. However, in the individual case the reliability of the clinical diagnosis varied greatly with the nature of the diagnosis and its degree of certainty. Reliability was for example high with clinically certain arteriosclerotic heart disease and low with cerebrovascular disease. Underdiagnosis of lung cancer is still a problem. Lack of interest in autopsy investigation may be reflection of lack of clinical involvement or therapeutic frustration rather than the use of sophisticated diagnostic procedures, as has been assumed by previous authors. It is suggested that the idea of selection of cases for autopsy should be replaced by selection of autopsies for microscopic investigation on the basis of the macroscopic post-mortem findings. It is suggested also that clinicians might profitably attend autopsies on patients in their sphere of interest that were not admitted under their care.
Aims-To consider the prognostic role of oestrogen receptor and progesterone receptor status in relation to the age at surgery, length of follow up and lymph node status.Methods-The study population comprised 977 patients with histologically confirmed breast carcinoma, with a median follow up of nine years. The actuarial life table method was used to test for survival differences. The Cox proportional hazard model was used to test for interaction effects between each hormone receptor and age, lymph node status and length of follow up. As the analysis involved multiple subgroups, significance was set at the 1% level (p < 0.01). Results-When the patients were subdivided into groups according to lymph node status and age, progesterone and oestrogen receptor status predicted prognosis in middle aged (46-60 years) patients with lymph node positive breast cancer. Their prognostic effect in this subgroup, however, was restricted to the first five years after surgery. Progesterone receptor status was the strongest predictor of outcome. Few reports have focused on the effect of oestrogen and progesterone receptor status in relation to age. Shek et al'6 showed a weak effect for oestrogen receptor status in patients aged 45 years or less, whereas the strongest effect was found in those between 45 and 54 years of age. We have shown that oestrogen, progesterone and androgen receptor status are more important in predicting five year survival in patients aged 60 years or less than in those over 60.'7 The association with age became even stronger after consideration of lymph node status and tumour diameter. As this study included 269 patients only, it did not permit further subdivision according to age. By excluding the need for androgen receptor status in the present study we could increase the study population to 977 and follow up to about nine years. ConclusionBased on these considerations we hypothesise that the prognostic importance of oestrogen and progesterone receptor status should be examined in middle aged patients separately, taking lymph node status and length of follow up into consideration. Identification of interactions between these variables would allow these well established prognostic markers to be used more precisely in patients with breast cancer. MethodsThe study population comprised 977 patients with unilateral breast cancer treated by modified radical mastectomy with axillary dissection. All types of histologically confirmed infil-920 on 12 May 2018 by guest. Protected by copyright.
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