[Carcinoma in situ. Prognostic factors].
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Biomedical subjects
Publications and source records attributed to M Trojani.
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Eight cases of breast myofibroblastomas are reported: two in men and six in post-menopausal women. This study and a review of the 19 published cases permit to define more precisely the particular features of this rare and benign mesenchymal tumour. Good demarcation, lack of necrosis and nuclear atypia argue for the benign nature of the lesion. It is made up of spindle cells (mainles myofibroblasts) which are positive for vimentin and not for S 100 protein or epithelial markers. Alpha-smooth muscle cell actin and desmin labelling are heterogeneous. This immunohistochemical study underlines the variable results of myofibroblasts for smooth muscle markers reflecting different degrees in their differentiation, without resolving the question of their origin. A simple surgical excision is required for this benign lesion. No recurrence has never been observed.
A patient's admission to an ICU should benefit the patient (either short or long term). Consequently patients admitted to the ICU should be only those neurological-neurosurgical ones with one or more organ failure who need immediate or prolonged therapy with adequate monitoring and technical support not available in other wards. Normally admission depends on may other factors, the most important ones seem to be medico-legal responsibilities of the possible refusal of admission even if due to clinical reasons, organizational problems such as equipment and bed availability. There is a need for pre- and post-surgical monitoring for high risk patients. We routinely admit patients to our ICU according to the following directions: respiratory and or cardio-circulatory failure connected to the neurological pathology, impaired consciousness, neurological signs and symptoms indicating deterioration, loss of airway protective reflexes, seizured in neurological-neurosurgical patients, severe electrolyte, metabolic or nutritional disturbances which may affect the CNS; neurosurgical postoperative control, performance of complex techniques (central venous and arterial catheterization, ICP monitoring), management of multiorgan donors suitable for therapeutic transplant. The groups of pathologies observed in our ICU during 1991 where the follow-up: 442 neurological-neurosurgical patients--head trauma 141 (32%)--cerebral tumours 88 (19.9%)--vasculopathies 135 (30.6%)--others 77 (17.5%). 228 (51.5%) patients stayed for a period less than three days. According to our experience we can affirm that causes for patient's admission to neuro-ICUs are various, the legal organizational reasons have a great importance compared to the clinical ones.
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Benign lymphocytic angiitis and granulomatosis is a T-cell lymphoproliferative disorder confined to the lung and corresponding to a low-grade angiocentric immunoproliferative lesion. Controversy remains as to whether these lesions are lymphomas. We report such a case in an 8-year-old patient with Burkitt's lymphoma in remission who presented with persistent bronchopneumopathy and bilateral pulmonary infiltrates on tomodensitometry. Surgical resection revealed the histologic changes of benign lymphocytic angiitis and granulomatosis. Immunohistochemistry showed no aberrant pan T-cell marker loss. Genetic analysis of frozen tissue by Southern blot DNA hybridization with probes to T-cell receptor beta- and gamma-chain genes and to the immunoglobulin heavy chain joining region gene (JH) identified no clonal rearrangement. Search for Epstein-Barr virus-DNA sequences by in situ hybridization and Southern blot analysis provided negative results. Our data imply that lowgrade angiocentric immunoproliferative lesions are not exclusively lymphomas but might represent a borderline lymphoproliferative disease (seen in the course of many diseases), perhaps corresponding to host immune response.
Special techniques such as serial macroscopic sectioning (SMS) or immunohistochemical staining (IH) improve the detection rate of micrometastases but this detection is of value only if it improves the prediction of recurrence and survival. We first studied the prognosis of 120 patients with a single micrometastasis detected by SMS in a series of 1,680 primary operable breast carcinoma with a median follow-up of 7 years. A significant difference in recurrence (P = 0.005) and in survival (P = 0.0369) was found between node-negative patients and those with one single SMS micrometastasis, but SMS micrometastases were not a predicting factor by multivariate analyses according to the Cox model. We then studied the prognostic significance of patients with a micrometastasis detected by IH in node-negative carcinoma: 37 micrometastases from a series of 89 invasive lobular carcinoma (ILC) and 13 single micrometastases from a series of 129 invasive ductal carcinoma (IDC). In the ILC group, IH micrometastases had no prognostic value (median follow-up: 9.3 years). In the IDC group, IH micrometastases were correlated with recurrences (P = 0.01) and were the most significant predicting factor, but were less correlated with survival (median follow-up: 15.6 years). Three main points emerge from this study: (1) SMS micrometastases have a prognostic significance and macroscopic sectioning is recommended as a routine technique not requiring excessive work. (2) IH micrometastases in infiltrating lobular carcinoma have no prognostic significance. (3) The value of IH is debatable in infiltrating ductal carcinoma, since the technique is of principal use in predicting recurrences. It should therefore be carefully assessed vs other prognostic factors currently under study.
From 1975 to 1988, 144 patients naive of treatment, with non-metastatic soft tissue sarcoma were treated at Fondation Bergonié by surgery, followed by radiotherapy and without chemotherapy. An analysis of prognostic variables was done on this population to determine patients for whom an adjuvant chemotherapy would be relevant. Prognostic variables in overall survival (OS), metastasis-free survival (MFS), disease-free and local free recurrence survivals were analysed by univariate and multivariate analysis. In multivariate analysis using Cox's model, only tumour depth and tumour grade were significant with the MFS end point, while tumour depth, tumour grade and tumour site were significant when considering OS. A predictive stratification for patients is proposed: a favourable prognostic group with grade 1 tumour or superficial, grade 2 tumour (5-year OS: 97.8%; 5-year MFS: 100%); an intermediate prognostic group with deep, grade 2 tumour or superficial, grade 3 tumour (5-year OS: 58.8%; 5-year MFS: 48.1%); and finally a poor prognostic group with deep, grade 3 tumour (5-year OS: 31.7%; 5-year MFS: 34.1%). Patients in the intermediate and poor prognostic groups who present a high metastatic risk are to be considered for adjuvant chemotherapy trials.
Adenomyoepithelioma of the breast is a rare tumor that, on the basis of histologic, immunohistochemical, and ultrastructural features, has a bicellular pattern of epithelial and myoepithelial cells regularly distributed in tubular structures. Until now, this tumor was thought to be a benign or low-grade malignant lesion because of possible local recurrences (7 recurrent cases of 60 in the literature). Only one of these cases had nodal involvement, thereby suggesting the possible malignancy of this lesion. This paper reports the first documented case of malignant adenomyoepithelioma with lung metastases presenting the same biphasic pattern as the primary tumor.
We report the case of a 42-year-woman treated for an appendicular carcinoid tumor with bilateral ovary metastases and mesenteric node involvement. After a systematic mammography, an infraclinical lesion of the breast was detected. Mammographic and echographic images revealed nodular mass with possibly malignant features. Fine-needle aspiration biopsy indicated malignancy. The definitive diagnosis of breast metastasis of a carcinoid tumor was made by biopsy. This case is related to 14 previously published cases. The authors emphasize the importance of making a precise histological diagnosis to avoid overtreatment of a metastatic lesion.
During a period of 15 years, 6 cases of dedifferentiated liposarcomas were found among 542 cases of adult soft tissue sarcomas, 77 of which were liposarcomas. They were huge tumors of the retroperitoneum, containing distinct areas of well-differentiated liposarcoma most often of sclerosing type and malignant fibrous histiocytoma or undifferentiated sarcoma most often of high grade malignancy. Immunohistochemistry on the dedifferentiated component showed a positivity with anti-vimentin and alpha-1-antichymotrypsin in 5 cases and with anti-alpha smooth muscular actin in 4 cases. Three patients developed local recurrence and a fourth one quickly died with bone metastasis. Other types of dedifferentiated sarcomas, the process of dedifferentiation and links between malignant fibrous histiocytoma and dedifferentiated sarcomas are discussed.
An immunohistochemical study of 5 cases of adenoid cystic carcinoma (ACC) of the breast was performed with antibodies against keratin, EMA, vimentin, S-100 protein, alpha-smooth muscle actin and collagen IV. Results show the following: 1) ACC may be diagnosed and differentiated from ductal carcinoma (invasive or in situ). The key to diagnosis is positivity within tumor masses of alpha-smooth muscle actin, a specific marker for myoepithelial cells. Actin-rich cells are not generally observed in ductal carcinomas, except at the periphery of a few invaded ducts, corresponding to a residual myoepithelial cell layer. Other markers may be positive in both ACC and ductal carcinoma; these are not specific and only the percentage and distribution of positive cells are helpful for diagnosis (small clusters of keratin-positive cells in ACC "versus" most positive cells in ductal carcinoma). 2) The functional pleomorphism of the cell population is underlined with cells differentiating towards epithelium and myoepithelium stained by corresponding markers, and undifferentiated cells unstained by any marker. These results confirm the value of an immunohistochemical study in the diagnosis of ACC of the breast.
Eight patients with breast metastases from primary tumors other than breast carcinoma were studied: 3 malignant melanomas, 2 rhabdomyosarcomas, 1 malignant mesothelioma, 1 appendiceal carcinoid, and 1 epidermoid cervical carcinoma. All had mammographic, histopathologic, and immunohistochemical examinations. The main problem was differential diagnosis from primary breast carcinoma. History of extramammary primary tumor was helpful but breast metastasis was the first clinical feature in 2 cases. Patients had noticed palpable, round, rapid growth masses which were mammographically benign. Pathologic diagnosis was difficult and immunohistochemical studies necessary, whenever the proliferation had histologic features of primary breast carcinoma or when no primary tumor was known. However, some histologic features were of value for diagnosis of metastasis: atypical histologic features for a primary breast carcinoma, a well-circumscribed tumor with multiple satellite foci, the absence of an intraductal component, and the presence of many lymphatic emboli. In adults, the most frequent types of tumors metastasizing in the breast are malignant melanoma and neuroendocrine-like tumors, especially small cell carcinoma and carcinoid. In children, rhabdomyosarcoma is the most common. Accurate diagnosis of breast metastasis is important to avoid unnecessary mastectomy and to implement an appropriate systemic therapy.
From 1963 to 1988, 281 patients with newly diagnosed follicular lymphomas were treated and followed at the Foundation Bergonié. Distribution of stages was: 72 I, 61 II, 83 III and 65 IV. Within stage III, two subgroups were retrospectively defined: stages III1 (32 cases) included patients with less than 8 involved sites, only 1 or 2 above diaphragm, and no spleen or mediastinal enlargement. Stage III2 (51 cases) included the remaining stage III cases. Median follow-up was 9 years. Complete remission (CR) rate was 82%. 10-year overall survival (OS) and time to treatment failure (TTF) rates were, respectively 38% and 29.5%. 10-year time to relapse (TTR) rate was 36%. Statistical analyses showed concordant results with two main prognostic factors: age (less than 60/greater than 60) and stage (I to III1/III2 and IV). Age was the most important factor for OS analysis and stage for CR and TTR analysis. This leads to only three prognostic groups with different outcome. The first includes younger patients (less than 60 years) with limited stages (less than or equal to III1); the second, patients either older than 60 or with advanced stages; the last, elderly patients with advanced stages. CR rates of these three groups were, respectively 97%, 75% and 57%. 10-year OS were, respectively 73.5%, 27% and 0%; 10-year TTR were 54%, 22% and 0%. These results have lead to data which are easy to handle and which can help to establish a rationale for further prospective trials.
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Between 1973 and 1977, 48 patients less than 65 years old with non-Hodgkin's malignant lymphoma (NHML) of poor prognosis (+/- high grade malignancy, +/- clinical stages III or IV, +/- first or repeated relapse) were included in a prospective clinical trial. After complete remission (CR), obtained with chemotherapy and radiotherapy, patients were randomized to receive bacillus Calmette-Guérin (BCG) or no further therapy. BCG was administered in weekly scarifications up to 3 years. Forty-three patients are assessable. Twenty-four patients have relapsed: nine out of 21 in the BCG group, and 15 out of 22 in the control group. There is a significant difference in favor of the BCG group in disease-free survival (P = .03). Twenty-one patients have died, 18 from NHML: seven in the BCG group, and 11 in the control group. There is a significant difference in favor of the BCG group for overall survival at 10 years (P = .05). A multivariate analysis points out BCG as a significant prognostic factor. Adjuvant BCG may improve particularly disease-free survival and overall survival for patients with clinical stages I and II or intermediate- and high-grade malignancy. These results suggest that in patients less than 65 years old with NHML of poor prognosis, BCG may significantly increase disease-free survival and overall survival.
The purpose of this report is to assess whether phenotyping by three monoclonal antibodies routinely used in paraffin sections (Ber-H2-Leu-M1-EMA) and shown to be the most useful for diagnosis may be a predictive factor for recurrences. Among 563 patients diagnosed as having Hodgkin's disease (24% of whom had recurrence), we selected 153 patients with and without recurrence, with matching clinical stage. For all of these cases, histologic material was tested by immunostainings with satisfactory control samples. No phenotype was specific for Hodgkin's disease, although the phenotype Ber-H2-Leu-M1-EMA was predominant. No phenotype was found to be a predictive factor for recurrences, and none was unchanged during the clinical course, except when recurrence occurred as non-Hodgkin's lymphoma.
Five cases of primary non-Hodgkin's lymphomas of the breast (stage IE in the Ann Arbor staging system) are described. No clinical or radiological feature has permitted to make the diagnosis before surgery. Histologically, all lymphomas are diffuse and B type. Three cases are high grade lymphomas, one of lymphoblastic type. Two cases are of lymphoplasmacytoid type, one of them associated with an occult invasive ductal carcinoma within the same breast, the other changing in high grade lymphoma at the recurrence time. Three of them reveal histological aspects of lymphoepithelial lesions and appear as mucosa-associated lymphoid tissue lymphomas (MALT). The differential diagnosis with a carcinoma is now easily done by immunohistochemical techniques. The importance of a diagnosis before surgery by cytopunction and drill-biopsy has to be emphasized, to prevent an useless mastectomy.
Angiosarcomas of the breast are exceedingly rare tumors that are only infrequently seen by pathologists examining fine-needle biopsy specimens. We report two cases in two women aged 52 and 57 years. Cytologic features are analyzed and differential diagnosis is discussed.