DCIS histopathology from a historical perspective.

Ductal carcinoma in situ (DCIS) represents a biologically and morphologically heterogeneous disease. It is characterized by a proliferation of presumably epithelial malignant cells confined within the lumens of the mammary ducts, without evidence of invasion beyond the basement membrane into the adjacent breast stroma. With the widespread use of screening mammography, a dramatic change has occurred in the frequency, management and types of DCIS detected. Historically, there has been some confusion regarding the definition of DCIS and the terminology associated with the histological types of DCIS. In this review, DCIS histopathology from a historical point of view is presented.

p53/MDM-2 immunohistochemical expression correlated with proliferative activity in different subtypes of human sarcomas: a ten-year follow-up study.

The aim of this study was the evaluation of p53/MDM-2 protein overexpression in different subtypes of human sarcomas, and their correlation with proliferative activity and patient outcome. We selected 40 cases of human sarcomas comprising 6 malignant fibrous histiocytomas (MFH), 1 fibrosarcoma, 1 dermatofibrosarcoma protuberans, 5 liposarcomas, 9 leiomyosarcomas, 1 rhabdomyosarcoma, 3 synovial sarcomas, 2 osteosarcomas, 1 chondrosarcoma, 4 Ewing's sarcomas, 2 Kaposi's sarcomas, 1 malignant haemangiopericytoma, 1 phylloides cystosarcoma, 1 neuroblastoma, 1 chordoma and 1 unclassified sarcoma. All the immunohistochemical markers, which had been used for the characterization of these sarcomas were re-examined. Additionally, the Streptavidin-Biotin peroxidase method was performed on paraffin sections using the monoclonal antibodies: anti-p53 antibody DO7, anti-MDM-2 antibody IF2 and anti-Ki-67 antibody MIB-1. According to our results, p53 protein nuclear expression was detected in 20% (8/40) of the tumours (1 fibrosarcoma, 2 liposarcomas, 1 leiomyosarcoma, 1 rhabdomyosarcoma, 2 Ewing's sarcomas and 1 unclassified sarcoma). MDM-2 nuclear staining was determined in 7.5% (3/40) of the cases (1 MFH and 2 liposarcomas). A high proliferative index was demonstrated in 27.5% (11/40) of the tumours (2 MFH, 4 leiomyosarcomas, 1 rhabdomyosarcoma, 1 osteosarcoma, 2 Ewing's sarcomas and 1 unclassified sarcoma). p53 overexpression was associated with high tumour grade (p < 0.05) and MIB-1 expression was correlated with reduced survival (p < 0.05), but p53 overexpression was not significantly associated with either MIB-1 score or with overall survival of the patients. In conclusion, from this limited and heterogeneous sample of cases, we suggest that the p53/MDM-2 pathway is involved in the tumourigenesis of several sarcoma subtypes, but it is unclear if the overexpression of these genes may become prognostic marker for patients affected with these highly aggressive tumours.

Immunophenotype, ras oncogenes and p53 onco-suppressor gene in benzo(a)pyrene induced malignant soft tissue tumours in Wistar rats.

This study was designed to identify the immunophenotypic characteristics of malignant soft tissue tumours, induced experimentally with benzo(a)pyrene (BaP), and to evaluate the immunohistochemical expression of the ras oncogene family and p53 onco-suppressor gene in these tumours, in association with prognostic factors. Seventy-five male Wistar rats were subcutaneous injected, dorsally, with a single dose of 10.08 mgr BaP. A solid, well-circumscribed tumour was formed at the injection site, in 70 of the animals, 80-100 days after the carcinogen's administration. The tumour as well as selected main organs were excised and studied after the animals' death. All the specimens were fixed in formalin 10%, embedded in paraffin and stained with H + E. The immunohistochemical avidin-biotin method was performed in the tumour sections, using the following monoclonal or polyclonal antibodies: vimentin, desmin, muscle specific actin (MSA), a-smooth muscle actin (SMA), myoglobin, smooth muscle myosin, a-1-antitrypsin, a-1-antichymotrypsin, S-100 protein, epithelial membrane antigen (EMA), K-ras, H-ras, Pan-ras and p53. The induced tumours of the animals were almost well-circumscribed, with a partly storiform cut surface. Histologically, their appearance was more conventional with high grade leiomyosarcomas; about half of them showed highly anaplastic areas, resembling other pleomorphic undifferentiated sarcomas. Pulmonary metastatic foci were detected in 37 animals. Immunohistochemically, all the tumours displayed positive expression of vimentin, MSA and SMA. Desmin was positively expressed in 40 tumours, smooth muscle myosin in 57 tumours and EMA in 12 tumours. All the tumours were negative for myoglobin, a-1-antitrypsin, a-1-antichymotrypsin and S-100 protein. In addition, five tumours showed a positive reaction for K-ras p21, 37 for H-ras p21, 41 for Pan-ras p21 and 14 for p53 protein. The overexpression of the oncoproteins H-ras p21 and Pan-ras p21 in these tumours was significantly associated with a non-advanced tumour stage (absence of metastatic focus). In conclusion, the histological as well as the immunophenotypic features of the induced tumours are more conventional with leiomyosarcomas mostly of high grade; many of them are "dedifferentiated". The identification of both ras and p53 gene products in these tumours indicates that alterations of these genes are common but not specific events, implicated in the tumourigenesis, which may become prognostic markers for this subtype of soft tissue sarcomas.

Primary angiosarcoma of the lung and pleura.

A 46 year old male smoker was admitted for severe continuing hemoptysis. Chest-X-rays and chest computed tomography revealed nodular infiltrates and bilateral hemothorax. Fiberoptic bronchoscopy resulted to non-diagnostic cytological and microbiological findings. Open lung and pleural biopsies after right thoracotomy revealed epithelioid angiosarcoma and further staging assessment showed secondary brain and liver foci. The patient received several courses of chemotherapy but he died one month later. The clinical, radiological, pathological, histochemical and therapeutic aspects of the disease are discussed. Angiosarcoma, a rare tumour with poor prognosis should be taken into consideration in the differential diagnosis of hemoptysis.

[A case of multifocal neurinoma of the femoral nerve associated with chronic myeloblastic dysplasia]. / Un cas de neurinome étagé ancien du nerf crural, associé à une dysplasie myéloblastique chronique.

A large multiple lobulated painless mass in the inguinal fossa, was investigated and removed, in a 58 years old patient with undiagnosed chronic myelodysplasia. The patient was initially referred to the urologic clinics for recurrent bleeding from the urinary tract, when the above mentioned and few smaller masses were palpated on the anterior aspect of the thigh. Clinical, laboratory and imaging investigation revealed enlargement of the spleen and the liver accompanied by relatively large and well separated tumors under the inguinal ligament extending to the upper thigh. From clinical history the patient had recurrent episodes of spontaneous bleeding from the nose and the bladder. He underwent open biopsy under general anesthesia where the inguinal tumor was found to be well encapsulated, firmly attached to a branch of the femoral nerve and loosely connected with the next mass that had similar characteristics. Intraoperative decision was made to excise the entire lesion which consisted of thirteen lobules of varying size, connected to each other as a chain. Histological examination revealed multifocal ancient neurilemona from a sensory branch of the femoral nerve. Further investigation of the patient for the episodes of hemorrhage and the enlargement of the spleen and the liver gave the diagnosis of chronic myelodysplasia. The patient was doing well one year after the excision of the tumor, and had an area with hypoesthesia above the knee. The concurrence of the two distinct neoplasms is discussed.

Biopsy-documented tuberculous pleural effusion in a patient with biopsy-proven coexisting sarcoidosis.

One year after treatment with corticosteroids for sarcoidosis, a patient presented with biopsy-documented tuberculous pleural effusion while characteristic histopathological findings of sarcoidosis coexisted in many tissues of peripheral organs. Tuberculous pleurisy developed in the presence of disseminated persistent sarcoidosis. Although the interaction of the pathophysiological mechanisms between these two entities is not clear, it is possible that the existence of one does not allow the clinical expression of the other.