Adamantinoma of the tibia with pulmonary metastases and hypercalcemia.

Adamantinomas of long bones are rare primary malignant bone tumors. A case of a woman who died of pulmonary metastases of an adamantinoma of the tibia is presented. A unique feature of this case is the association with hypercalcemia. The association of hypercalcemia, hypophosphatemia, decreased parathyroid hormone levels and increased urinary cAMP excretion suggests a humorally mediated hypercalcemia. Histologic and ultrastructural analysis of the pulmonary metastases demonstrated that the tumor was composed of a heterogeneous cell population with mesenchymal and epithelial differentiation.

Cytogenetic investigation of a case of congenital fibrosarcoma.

Cytogenetic studies were performed on a fibrosarcoma of a newborn. Only numerical chromosome changes (+8, +11, +20) were identified in this rare but distinct soft tissue sarcoma that occurs in children less than 5 years old.

CEA and HMFG in hyperplastic and malignant lesions of the breast.

In order to evaluate a possible transition from proliferative lesions of the breast to ductal carcinoma in situ (DCIS), an immunohistochemical retrospective analysis was carried out. Twelve patients with hyperplasia without atypia, 11 patients with hyperplastic lesions with atypia, 21 patients with DCIS and 24 patients with invasive carcinoma were studied. The expression of carcino-embryonic antigen (CEA), a dedifferentiation marker, was investigated, applying one monoclonal antibody (Amersham). The expression of human milk fat globulin (HMFG), a differentiation marker, was studied by means of three monoclonal antibodies. The results reveal that no CEA activity can be demonstrated in normal and hyperplastic breast tissue, either with or without atypia. The monoclonal antibody was positive in 48% of DCIS and 50% of the invasive carcinomas. We failed to observe a correlation between the presence of CEA and the differentiation of the tumor. The application of this antiserum adds no substantial information about the phenotypic alterations during the progression from atypical hyperplasia to DCIS. HMFG was present in benign as well as in malignant breast lesions. Therefore, we conclude that HMFG is not useful for the evaluation of the phenotypic change from atypical hyperplasia to malignancy. However, as pointed out by others, it can be used in a diagnostic panel of different antibodies in the distinction between epithelial and non-epithelial lesions.

The Budd-Chiari syndrome caused by a zygomycete. A new pathogenesis of hepatic vein thrombosis.

The clinical history of a 60-year-old woman suffering from chronic lymphocytic leukemia with sudden deterioration and death is reported. The postmortem macroscopic and microscopic findings included pulmonary aspergillosis and pulmonary zygomycosis (mucormycosis). Hematogenous dissemination of the zygomycete causing cardiac zygomycosis, cerebral infarcts due to vascular occlusion by hyphae, and thrombosis of the major hepatic veins (Budd-Chiari syndrome) with submassive necrosis of the right liver lobe were also observed. To our knowledge, this is the second report dealing with occlusion of the hepatic veins caused by a fungus and the first study reporting the Budd-Chiari syndrome due to a mold of the subclass Zygomycetes.

Histogenesis of cholangiomas and cholangiocarcinomas in thioacetamide fed rats.

A sequential, histologic analysis of the livers of male albino rats chronically fed the hepatocarcinogen thioacetamide (TAA) is performed after one, two, three, four, eight and twelve months of treatment. Liver cell alterations present after one, two and three months consist of centrolobular liver cell degeneration and oval cell proliferation. After 8 months of TAA treatment, a variety of benign tumors (cystadenomas, angiomas, cholangiomas) is observed. From the 12th month all experimental animals develop cholangiocarcinomas. Pulmonary metastases are discovered after 15 months. The role of the oval cells in relation to the later appearing cholangiocarcinoma is discussed. A review of literature is given.

Cytophotometric studies of the nuclear DNA content in cartilaginous tumors.

The histopathological differentiation between chondromas and low-grade malignant chondrosarcomas can be difficult. For this reason we studied in 37 different cartilaginous tumors the mitotic index and the Feulgen DNA content using a scanning-integration cytophotometric technique. In 23 chondromas the Feulgen DNA content was diploid and showed a unimodal normal distribution. The number of mitoses was 0--0, 5%. The nuclei of a chondroblastoma were also diploid and the Feulgen DNA content was normally distributed. The mitotic index was 1% and few tetraploid nuclei, which were probably G2 nuclei, were observed. In two chondromyxoid fibromas, the average Feulgen DNA content was diploid and normally distributed. Several tetraploid nuclei were noted. The mitotic index was respectively 0.25% and 1.75%. Recurrence was noted in the first case. The Feulgen DNA content and mitotic index were clearly different in the chondrosarcomas. The distribution of the DNA content was bimodal or unimodal in low-grade chondrosarcomas. The mitotic index was less than 3%. In high-grade malignant chondrosarcomas, the histograms were broad unimodal or aneuploid. The mitotic index was above 5%.

The DNA content in cancer and dysplasia in chronic ulcerative colitis.

The nuclear DNA content was determined with a cytophotometric technique in colonic mucosa of 15 patients with long-standing ulcerative colitis. The epithelial lesions were classified into inactive colitis, low grade and high grade dysplasia and adenocarcinoma. The histogram pattern varied between narrow unimodal in quiescent colitis, broad unimodal in low grade dysplasia with some hypertetraploid values in three cases (27%) and aneuploid in 62.5% of the lesions with high grade dysplasia. In well-differentiated adenocarcinoma the histograms were broad unimodal, whereas the curves of moderately and poorly differentiated carcinomas were wider and aneuploid. The technique can be used for a prognostic purpose: in dysplastic lesions, the detection of aneuploidy is important because it is frequently found in the presence of invasion although it does not allow its prediction. Carcinomas with polyploid DNA distribution have a better outcome than tumours with aneuploid distribution.

The neu-oncogene protein as a predictive factor for haematogenous metastases in breast cancer patients.

In a prospective study with a median follow-up of 13 months on a series of 71 breast cancer patients, 9 developed haematogenous metastases. The neu protein was found on the cell membranes in 27 of the 71 carcinomas (38%) by an immunohistochemical technique using a monoclonal antibody (MAb). Eight of the 9 patients with haematogenous metastases showed overexpression of the neu protein. Immunohistochemical staining of the cell membrane was inversely correlated with the oestrogen and the progesterone receptor status. There was no correlation with lymph-node involvement. The immunohistochemical detection of the neu protein in breast adenocarcinomas is an independent factor in predicting the patients at risk for haematogenous tumour spread and is therefore correlated with unfavourable prognosis.

M-cells are damaged and increased in number in inflamed human ileal mucosa.

Ileocolonoscopy and biopsies of patients with spondylarthropathy reveal gut inflammation in 62% of cases. In order to better understand the pathogenetic mechanisms of spondylarthropathy-related gut inflammation, the follicle-associated epithelium was examined. Biopsies from nine controls and 18 patients with spondylarthropathy were studied by electronmicroscopy. Membranous (M) cells were investigated in normal and inflamed ileum. In normal mucosa, M-cells were scarce whereas in inflamed mucosa their number was increased (up to 24% of follicle-associated epithelial cells). They showed a thin rim of cytoplasm covering groups of lymphocytes. In chronic ileitis, necrotic M-cells, rupture of M-cells and lymphocytes entering the gut lumen were observed. The bursting of M-cells at the top of the lymphoid follicles leads to interruption of the gut epithelial lining and gives the luminal content access to the lymphoid tissue. This pathogenetic mechanism may cause aphthoid ulcers.

Keratinocyte induced chemotaxis in the pathogenesis of Paget's disease of the breast.

In Paget's disease of the breast, the epidermis contains large clear neoplastic cells. To explain the pathogenesis of this disease, the immunohistochemical characteristics of these cells were investigated in 25 patients. The cytoplasmic presence of low molecular weight cytokeratin and the absence of high molecular weight cytokeratin in all cases confirmed the glandular origin of the Paget cells. Membrane over-expression of the neu-protein was established in 96% of cases. It was hypothesized that epidermal keratinocytes release a chemotactic factor which attracts neu-over-expressing breast carcinoma cells by chemotaxis into the epidermis. The biological assays showed that normal keratinocytes release one or more chemotactic factor(s) into their conditioned medium, which induced spreading and motility of neu-over-expressing SK-BR-3 human breast cancer cells. The conditioned medium of keratinocytes also attracted the SK-BR-3 cells by chemotaxis in a modified Boyden chamber. Furthermore, MCF-7 human breast cancer cells, which do not over-express the neu-protein, were not attracted by chemotaxis of conditioned medium of human keratinocytes. The involvement of the neu-protein in spreading, motility and chemotaxis is further indicated by the inhibition of these processes by monoclonal antibodies against the extracellular domain of the neu-protein. We conclude, therefore, that the Paget cells spread through the epidermis due to the motility induced by a chemotactic factor, which is released by epidermal keratinocytes and whose influence is mediated by the neu-protein.

Feulgen DNA content and mitotic activity in proliferative breast disease. A comparison with ductal carcinoma in situ.

Nuclear Feulgen DNA content was measured by cytophotometry and the number of mitoses per 40 high power fields was determined in hyperplastic and atypical hyperplastic lesions of fibrocystic disease in 18 patients, in ductal carcinoma in situ in 14 patients and in ductal carcinoma in situ associated with infiltrating carcinoma in 11 patients. These parameters were also investigated in the hyperplastic lesions accompanying ductal carcinoma in situ and ductal carcinoma in situ associated with infiltrating carcinoma. The nuclear Feulgen DNA content could not discriminate between atypical hyperplasia and ductal carcinoma in situ. Although differences in the mitotic count between hyperplastic and atypical breast lesions were not statistically significant, there was a statistically significant greater mitotic count in ductal carcinoma in situ alone or associated with infiltrating carcinoma. These findings suggest that the mitotic count is useful for the differential diagnosis between atypical hyperplasia and ductal carcinoma in situ. In addition, hyperplastic lesions associated with ductal carcinoma in situ, with or without infiltrating carcinoma, exhibited a statistically significant higher mitotic count than those in benign fibrocystic disease. Hyperplastic breast lesions exhibiting high mitotic counts may indicate the presence of a neighbouring ductal malignancy and suggest an increased proliferative activity in breast tissue in the neighbourhood of malignancy.

The distribution of oestrogen and progesterone receptors in the human endometrial basal and functional layer during the normal menstrual cycle. An immunocytochemical study.

The distribution of oestrogen and progesterone receptors in the human endometrial basal and functional layer during the normal menstrual cycle was investigated by means of an immunocytochemical technique. A cyclic pattern of receptor distribution was observed. The highest concentration of hormone receptors was observed in the basal layer, in accordance with the idea that this layer is the source of endometrial regeneration.

Topographical distribution of oestrogen and progesterone receptors in the human endometrium and fallopian tube. An immunocytochemical study.

The topographical distribution of oestrogen and progesterone receptors in the human endometrium and Fallopian tube was investigated by an immunocytochemical technique. A gradient of positively stained cells was observed: the highest oestrogen and progesterone receptor content was noted in the fundal part of the uterine cavity and the ampullar region of the Fallopian tube. The observed gradient is in keeping with biological and pathological events that occur in the human mullerian tract, e.g. fecundation, implantation and carcinogenesis.