A tumour in the breast: vaccination granuloma as a differential diagnosis.

AIMS: Breast cancer is the most frequent type of cancer in women; special attention is therefore paid to tumours in the breast region. Vaccination granuloma is a differential diagnosis of tumours in the upper part of the breast. METHODS: All granulomatous lesions in the breast region since 1970 were retrieved from the files of the Departments of Pathology at Odense University Hospital and Svendborg Hospital. RESULTS: Fourteen cases with a histology compatible with vaccination granuloma were found. Eight patients had a known history of tetanus vaccination. The tumours were ovoid, or even rod-shaped, and measured between 8x3 mm and 12x10 mm. Histologically, there were necrotic foci surrounded by histiocytes, lymphocytes, and plasma cells. Aluminium was detected by staining with solochrome azurine. CONCLUSIONS: The possibility of a vaccination granuloma should be kept in mind in patients with a palpable tumour in the upper part of the breast, as well as in mammography screening conditions and in follow-up patients after previous treatment for breast cancer.

MIB-1 expression in breast carcinomas with medullary features. An immunohistological study including correlations with p53 and bcl-2.

Typical medullary carcinoma (TMC) is usually considered to have a more favourable prognosis than other types of infiltrating breast carcinomas. This is a biological paradox, since its clinical behaviour is not in agreement with its anaplastic morphology and high mitotic rate. It should be remembered that neoplastic growth reflects cell production minus cell loss, the latter being achieved by apoptosis. At present, bcl-2 oncogene (apoptosis inhibitor) and p53 gene are assumed to be involved in the regulation of cell death and tumour proliferation. Sixty breast carcinomas, initially indexed as medullary carcinomas, were re-classified using the diagnostic criteria given by Ridolfi. This review yielded 13 typical (TMC), 24 atypical (AMC), and 23 non-medullary carcinomas (NMC). Following antigen retrieval by microwave treatment, immunohistochemical analyses, using MIB-1, p53 and bcl-2 monoclonal antibodies were performed on serial sections from formalin-fixed, paraffin-embedded specimens. TMC revealed the highest incidence of intense p53 positivity, and the highest mean MIB-1 index, and absence of the apoptosis-inhibitor protein bcl-2. These results suggest the presence of a higher overall cell turnover in TMC than in AMC and NMC. Increased apoptosis balancing the increased cell proliferation might be among the possible explanations for the more favourable prognosis in TMC.

Prognostic comparison of three classifications for medullary carcinomas of the breast.

The aim of this study was to make prognostic comparisons between the modified scheme of Pedersen et al. the definitions of Tavassoli and the Ridolfi criteria for medullary carcinomas. Sixty breast carcinomas primarily diagnosed as medullary carcinomas were reclassified into typical medullary carcinoma (TMC), atypical medullary carcinoma (AMC) and non-medullary carcinoma (NMC) according to the three classifications. The Ridolfi classification proved to be superior to the two other schemes in discriminating survival differences between the three groups TMC, AMC and NMC. All 13 patients with TMC are still alive indicating an excellent prognosis, while 29% and 39% of the 47 patients in the AMC and NMC category, respectively, have died of their disease. In the simplified system of Pedersen et al. the survival at 10 years for TMC patients decreased to 75% and no significant survival difference between the three groups could be demonstrated. As the prognosis for AMC proved to be worse compared to TMC and in fact was similar to NMC with values of 43% at 10 years in the Ridolfi classification, we find no reasons to maintain this category. We conclude that as long as no alternative and more easily applicable diagnostic method exists, pathologists should still apply the Ridolfi criteria on these tumours with medullary features leaving two diagnostic possibilities: TMC or NMC (i.e. poorly differentiated ductal carcinoma). Only lesions that fulfil all six criteria without any doubt should be diagnosed as TMC, thus avoiding overdiagnosis and a resulting risk of undertreatment.

[Patients with early stages of endometrial cancer should be spared adjuvant radiotherapy. Danish Endometrial Cancer Group]. / Patienter med tidlige stadier af endometriecancer bør skånes for adjuverende strålebehandling.

In an attempt to create uniform nationwide guidelines for the management of all stages of endometrial carcinoma, and to limit the use of adjuvant radiation therapy in stage I disease to high-risk patients only, a protocol was developed by the Danish Endometrial Cancer group (DEMCA). From September 1986 through August 1988, 1214 women in Denmark with newly diagnosed carcinoma of the endometrium have been treated according to this protocol. This figure represents all endometrial carcinomas diagnosed in Denmark during this two-year period. The primary treatment was total abdominal hysterectomy and bilateral salpingo-oophorectomy, no preoperative radiation therapy was delivered. In 1039 cases no macroscopic residual tumour and/or microscopic tumor tissue in the resection margins was found following surgery. Based on surgery and histopathology, these patients were classified as: P-stage I low risk (n = 641), P-stage I high risk (n = 235), P-stage II (n = 105) and P-stage III, Group 1 (n = 58). No postoperative radiation therapy was given to P-I low risk cases. P-I high risk, P-II, and P-III (Group 1) cases received external radiation therapy. Recurrence rate at 68-92 months follow-up was 45/641 (7%) in P-I low risk, 36/235 (15%) in P-I high risk, 30/105 (29%) in P-II, and 27/58 (47%) in P-III (Group 1) cases. Fifteen of 17 vaginal recurrences in P-I low risk cases were salvaged (mean observation time 61 months). In this population-based investigation it has been shown that P-stage low-risk patients are adequately treated by total abdominal hysterectomy and bilateral salpingo-oophorectomy, and that no pre- or postoperative radiation therapy is necessary.

Medullary breast carcinoma vs. poorly differentiated ductal carcinoma: an immunohistochemical study with keratin 19 and oestrogen receptor staining.

Sixty breast carcinomas previously indexed as medullary carcinomas over a 24-year-period were reviewed and reclassified according to definitions suggested by Ridolfi et al. as typical medullary carcinoma, atypical medullary carcinoma, and non-medullary carcinoma. Paraffin sections of tumour tissue were examined by an avidin-biotin complex method using two keratin 19-specific monoclonal antibodies (BA17, DAKO and clone 170-2-14, Boehringer) and a monoclonal oestrogen receptor antibody (DAKO). For comparison 52 ductal carcinomas of grade II and grade III were immunostained as well. The results showed that all 60 tumours with medullary features and all 52 ductal carcinomas reacted moderately to strongly positive with anti-keratin 19 (Boehringer). The staining was diffuse in all cases, except one case of ductal carcinoma (grade III), which stained focally. Immunostaining with the second keratin 19 antibody (BA17) revealed similar results with positive staining in 59 (95%) cases of carcinomas with medullary features and 51 (98%) cases of ductal carcinomas. Only one case in each group did not express keratin 19 (BA17), one re-classified case of non-medullary carcinoma with neuroendocrine features and one case of ductal carcinoma of grade III. None of the 13 cases of typical medullary carcinoma were oestrogen receptor positive and only seven (12%) of the carcinomas with medullary features (2 atypical, 5 non-medullary) were oestrogen receptor positive with quantitative values from 20 to 100%. The 52 ductal carcinomas of grade II and III were oestrogen receptor positive in 56% and 47% of cases. It is concluded that keratin 19 staining is of no particular value in differentiating medullary from poorly differentiated ductal carcinoma. A carcinoma with positive oestrogen receptor staining is not likely to be a typical medullary carcinoma.

Acinic cell carcinoma with primary presentation in an intraparotid lymph node.

A rare case of a poorly-differentiated acinic cell carcinoma with primary presentation in a hyperplastic intraparotid lymph node, is reported. As the tumour mainly consisted of ductular and undifferentiated cells growing in solid cords, diagnosis was rendered difficult. Typical acinic cells were only rarely observed. In the multiple sections reviewed a single tumour nodulus occurred in salivary gland tissue outside the lymph node capsule. The possibility of a microscopic clinically occult primary acinic cell carcinoma that metastasized and presented primarily in an intraparotid lymph node, is mentioned. A multifocal origin in salivary tissue within and outside the intraglandular lymph node is another assumption, which is discussed. Differential diagnoses are mentioned and results of immuno- and histochemical studies are reported.

Screening for haemochromatosis: prevalence among Danish blood donors.

Hereditary haemochromatosis is an autosomal recessive disease that is genetically expressed by excessive accumulation of iron in the tissues, resulting in cirrhosis, diabetes mellitus, cardiomyopathy and hypogonadism. As the disease may be diagnosed before the appearance of symptoms, and prevented by repeated phlebotomies, there are strong implications for adoption of a screening procedure. Determinations of transferrin saturation (TS) and serum ferritin concentration (SF) were used to screen 4302 blood donors, who were selected for follow-up studies if they fulfilled any of the following three criteria: (i) TS greater than or equal to 0.7; (ii) TS greater than or equal to 0.5 together with SF greater than or equal to 150 micrograms l-1; (iii) SF greater than or equal to 300 micrograms l-1. A total of 58 subjects who fulfilled at least one of these criteria were reinvestigated, after which 18 individuals still fulfilled at least one criterion. Fifteen subjects having SF greater than or equal to 300 micrograms l-1 were offered liver biopsy and thirteen of these accepted. In one individual, no stainable iron was detected, and two subjects did not fulfil the previously established diagnostic criteria for the diagnosis of hereditary haemochromatosis. Ten subjects who had a high TS and liver iron grade 2-4 according to Bassett were classified accordingly as homozygotes. On the basis of these results, the prevalence of haemochromatosis in Denmark was estimated to be 0.0037-0.0046.

Iron storage disease in parents and sibs of infants with neonatal hemochromatosis: 30-year follow-up.

Neonatal hemochromatosis (NH), an uncommon and generally fatal disorder of infancy, is defined by hepatic disease of antenatal onset, generally manifest at birth, and by stainable iron in a tissue distribution like that seen in heritable adult-onset hemochromatosis (HH). It is not known if parents and sibs of infants with NH are at risk of iron storage disease in later life. We provide 30-year follow-up for iron overload of a family in which 6 of 9 children died in utero or early in the neonatal period. Four of the 6 came to autopsy, where severe liver disease was found; in 3 of the 4, autopsy material could be reviewed. These 3 children had NH. Studies 30 years later did not identify HH or other iron storage disease in the parents or surviving sibs. These findings suggest that first-degree relatives of persons with NH are not necessarily at increased risk of iron storage disease in later life.

Quality control of patho-anatomical diagnosis of carcinoma of the breast.

Three pathologists, especially interested in breast cancer, reexamined 379 random specimens of invasive breast cancer initially diagnosed at 27 pathological institutes; these were obtained from the computer register of the Danish Breast Cancer Cooperative Group (DBCG). The degree of variation between a) the primary diagnosis (the country as a whole) and each of the 3 pathologists and b) between the 3 pathologists mutually, has been studied with regard to the 2 main groups of carcinoma--infiltrating duct carcinoma (IDC) and infiltrating lobular carcinoma (ILC). The degree of variation was found to be similar between each of the 3 pathologists and the country as a whole, with a kappa value of approx. 0.3 for both types of carcinoma, and a considerably better interobserver variation between the 3 pathologists with a kappa value of approx. 0.7. The most important reason was that the 3 pathologists agreed on the occurrence of more than twice as many cases primarily diagnosed as ILC. A partial explanation is in fact that since the start of DBCG, reports have appeared of variants of ILC not previously known. The diagnosis of malignancy (carcinoma) was almost completely unambiguous.

A randomized study of cyclophosphamide and cis-platinum with or without doxorubicin in advanced ovarian carcinoma.

Two hundred sixty-seven patients with advanced epithelial ovarian carcinoma were randomized to cis-platinum and cyclophosphamide versus cis-platinum, cyclophosphamide, and doxorubicin. Complete pathological response, evaluated at second-look laparotomy and survival, showed no differences between the two treatment groups. Recurrence-free survival after negative second look was 61% at 24 months.

Needle puncture followed by pneumocystography of palpable breast cysts. A controlled clinical trial.

In a prospective analysis of 123 consecutive patients the current clinical and mammographic criteria of a cyst of the breast proved well-suited as a basis of selection for pneumocystography. Only about 12 per cent of the punctured lumps were solid, 9.8 per cent of them benign and 2.4 per cent malignant. The therapeutic effect was satisfactory, 94 per cent of the cysts not showing any recurrence after pneumocystography during a 6-month follow-up period with repeated palpation and mammography one and 6 months after the aspiration. The 6 per cent recurrences appeared within one month. The appearance of the aerogram was reliable in differentiating between a simple cyst and an intracystic lesion, whereas neither the tendency to recurrence nor the cytologic examination afforded a reliable basis of evaluation.

Carcinoma of the breast with stromal multinucleated giant cells.

Three cases of invasive mammary carcinoma with stromal osteoclast-like giant cells are reported. All the specimens were grossly of reddish-brown colour. On microscopical examination two were invasive ductal carcinomas and the third was of mixed ductal and mucoid type. In the stroma all specimens showed numerous osteoclast-like giant cells, vascular proliferation, and accumulation of haemosiderin pigment. Supplementary immunohistochemical and electron microscopical investigations indicated that the giant cells originated from mononuclear stromal cells with only slight histiocytic properties. The giant cell formation was probably induced by the infiltrating carcinomatous tissue which is also believed to induce new blood vessel formation. However, there is no evidence of a direct relationship between these features.

Myocardial angiolipoma.

Intramyocardial lipomas are rare, making up only one quarter of all cardiac lipomas which constitute less than 9% of all primary cardiac tumours. Vascular cardiac lipomas, corresponding in architecture to angiolipomas of the soft tissues, do not appear to have been reported previously. A case of an asymptomatic intramyocardial angiolipoma is reported in an 86-year-old woman who died of a ruptured abdominal aortic aneurysm.

Organochlorine compounds in human breast fat from deceased with and without breast cancer and in a biopsy material from newly diagnosed patients undergoing breast surgery.

Epidemiological studies have related the incidence of mammary cancer to the dietary intake of fat and/or meat. Since organochlorine compounds (e.g., polychlorinated biphenyls (PCB) and DDT (and its metabolite DDE] are accumulated in the adipose tissue it was tempting to suggest a relationship between levels of PCB and "DDT" (i.e., DDT + DDE) in breast fat tissue and the occurrence of mammary cancer. To elucidate this theory, the organochlorine levels of 14 breast fat tissue samples from breast cancer patients and similar samples from 18 deceased mammary cancer patients were compared to that of 21 similar samples from noncancer patients and finally to adipose tissue samples from 35 non-cancer autopsy specimens. No significant differences were traced. Thus it seems that the accumulation of PCB and DDT measured in breast fat tissue do not relate to the occurrence of mammary cancer.

Adenomyoepithelial adenosis and low-grade malignant adenomyoepithelioma of the breast.

Adenomyoepithelial adenosis of the breast is a form of adenosis not previously described. It is similar in several ways to microglandular adenosis, but one significant difference is the presence of myoepithelial cells. The present case originated as adenomyoepithelial adenosis in a 46-year-old woman. In the course of 18 years it proliferated and changed into a low-grade malignant adenomyoepithelioma. Electron microscopy confirmed the presence of myoepithelial cells in the adenosis, and immuno-histochemical study demonstrated cells containing actin (representing myoepithelial cells) in the adenosis as well as in the adenomyoepithelioma.

The predictive value of percutaneous biopsies from human renal allografts with early impaired function.

A semiquantitative histological analysis was performed on 84 percutaneous biopsies 0-60 days post transplant from 66 grafts with clinical rejection, decreasing graft function of unknown etiology or persisting anuria. The presence of 1 or more of 3 histological lesions was associated with 100% graft loss within 1 year. The lesions were: infarction, glomerular capillary thrombosis, and arterial/arteriolar thrombosis. Since the detection of these severe lesions only permitted prediction of an unfavourable course in 72% of all grafts that were subsequently lost, a system was elaborated utilizing the sum of scores of 12 histological and 4 clinical parameters. This system failed to improve the prognostic value of the biopsy since diagnostic specificity as well as sensitivity was slightly lower by this method. The conclusion is that a graft biopsy performed during early graft failure has a high predictive value for graft loss if infarction, arterial thrombosis or glomerular capillary thrombosis is present; however the predictive value of a negative test is low.