Biomedical subjects
Publications and source records attributed to G Contesso.
The different pathologic aspects of bone and soft-tissue sarcomas are discussed: usefulness of special techniques, particularly immunohistochemistry, histologic classification and grading, diagnosis of frozen sections and assessment of treatment effects, particularly of postoperative chemotherapy.
Ewing's sarcoma (ES) of bone may occasionally display rosette-like textures mimicking Homer-Wright ones, as seen in neuroectodermic neoplasms (neuroblastoma, peripheral neuroepithelioma). Of a group of 39 cases of ES, reviewed with electron microscopic study, the authors have isolated five atypical ES, which histologically also possessed neuroectodermic traces. These tumors were composed of small round blue cells with rosette-like figures and cytoplasmic glycogen. The immunohistochemical analysis showed positivity for neuron-specific enolase (NSE) as well as for HNK-1 (leu-7) monoclonal antibody. Electron microscopic examination confirmed the tumor cell as being of small round type, with a dense chromatine pattern and the presence of isolated dendritic processes, as well as synaptic-like buttons; intermediate filaments, neurotubuli, and dense-core neurosecretory granules also were seen. Moreover, in two cases basement-like condensations surrounded some cells. Scanning electron microscopic study in one case confirmed the presence of rosette-like figures and cell elongations with short dendritic projections of the cytoplasm. Clinically and radiologically these cases showed features similar to ES of bone; one case, located in the chest wall, had a local relapse after treatment, with the histologic features of a pleomorphic neuroblastoma. The authors conclude that these tumors resemble closely immature neuroepithelioma of soft tissue but, being primary to bone, are superimposable on those described as "neuroectodermal tumors of bone."
Evidence that supports the use of systemic, presurgical induction chemotherapy to render soft tissue sarcomas resectable or to minimize the extent of surgical excision is presented. Induction chemotherapy was administered in 34 cases of nonmetastatic soft tissue sarcomas. All patients had large tumors for which only mutilating surgery, if any, was possible. In 21 patients, a combination of Adriamycin (doxorubicin), cyclophosphamide, cisplatin, vindesine, and DTIC (DCPAV) produced two complete remissions (CR) and 6 partial remissions (PR). A combination of cyclophosphamide, vincristine, Adriamycin, and DTIC (CYVADIC) produced three PR in eight patients, and a combination of Adriamycin and ifosfamide (AI) produced two PR in five patients. After two to seven cycles of chemotherapy, 24 patients underwent surgery. In 19, gross tumor excision was performed; 12 proved to be microscopically fully resected. Disease in two patients entered CR with chemotherapy alone, but surgery was performed in both patients as well. Irradiation was administered in ten patients to produce or insure CR (eight cases of residual disease postoperatively), and in two patients with unresectable disease. Four patients with disease in CR after surgery also received radiation due to the initial massive tumor size. The Kaplan-Meier survival curves at 2 years showed 18% total survival in the patients in whom CR of disease was not achieved, and 80% survival in patients with disease in CR. Of the 22 patients with disease in CR (by all means), disease-free survival was 1 to 44 months (mean, 13.7). Disease currently remains in CR in ten patients with a mean follow-up of 13.6 months (3 to 34 months from end of therapy). Ten patients had a local recurrence following a CR after 3 to 44 months (mean, 15.3 months).
Fourteen telangiectatic osteosarcomas are reported. They are rare, clinically and radiologically aggressive lesions, involving mainly the femurs of young patients, often misdiagnosed as aneurysmal bone cysts. An explanation for a characteristic early radiological appearance consisting of regular parallel striations of the shaft is suggested.
We have previously described a secreted glycoprotein of mol. wt 52,000 (52-kDa protein) which is induced by estrogen in some human breast cancer cell lines. This protein has been identified as the proenzyme of a lysosomal cathepsin-D-like protease which is secreted in large proportions in breast cancer cells. To determine which information may be generated by this marker when detected in mammary tumors, in comparison with hormone receptors, we used monoclonal antibodies interacting specifically with the 52-kDa protein and its related cellular processed products (mols. wts 48 and 34 kDa). A high concentration of this protein has been shown in proliferative ductal mastopathies and cysts, suggesting its value in detecting high-risk mastopathies. We now present the immunoperoxidase distribution of this protein in breast carcinoma compared to the cytosolic hormone receptors assayed in parallel. In 232 breast cancers, no correlation was found between the cellular 52-kDa protein content and cytosolic estrogen or progesterone receptor concentrations. This absence of correlation was also shown by the constitutive production of this protein by estrogen-receptor-negative breast cancer cell lines and confirmed by double immunostaining of breast cancer cell aspirates showing a dissociation between the cytoplasmic staining of this 52-kDa lysosomal protease and the nuclear staining of the estrogen receptor. These clinical results, associated with the in vitro mitogenic and proteolytic activities of this protein, strongly suggest that the 52-kDa protein staining in tissue is associated with tumor proliferation and/or invasion, rather than with hormone responsiveness.
Between June 1970 and April 1982, 592 patients with unilateral T1 and small T2 breast cancers were managed conservatively at the Institut Gustave-Roussy. The treatment policy for the axilla was to perform a lower axillary dissection and to proceed to axillary clearance ( +/- radiotherapy) in patients with axillary invasion by tumor (N+). Some N+ patients had only lower axillary dissection and radiotherapy. Five hundred fifty-eight patients underwent axillary surgery which was a lower axillary dissection in 374 patients (67%) and axillary clearance in 184 patients (33%). There was axillary invasion in 198 cases (36%). Only five patients relapsed in the axilla and the probability of axillary relapse at 5 years was 1.2%. There were no axillary relapses in N+ patients who had had an axillary clearance whether irradiated or not. The incidence of upper limb complications was significantly greater in patients undergoing axillary surgery and radiotherapy compared with axillary surgery alone (p less than 0.0001). It is concluded that a lower axillary dissection accurately identifies N-patients and an axillary clearance in N+ patients ensures good local control and avoids the morbidity associated with axillary irradiation.
In a study of 1,010 patients with solitary, unilateral, nonmetastatic breast cancer, the histologic grade, assessed by a multifactorial analysis (Cox model) to study its significance with other prognostic factors, was found to be an important, independent factor. For 612 operable patients, two laboratory characteristics, the number of histologically positive nodes and the histologic grade, were the most valuable predictors. These two factors alone form a predictive index that may be an excellent and simple guide for the clinical decision of subsequent therapy. For 398 patients with inoperable breast cancer (ie, tumor greater than or equal to 7 cm, N2-3, inflammatory, skin fixation, and clinically rapidly growing forms), the histologic grade (performed on drill or cutting needle biopsy) was again a most important (and with inflammatory forms the most important) predictor of prognosis in these patients. Our data support that performing our modified histoprognostic grading of Scarff and Bloom is simple, reproducible, incurs no additional cost, may be carried out in the simplest histology laboratory, and finally, defines an important risk factor in all patients. It should be routine for all breast cancer specimens. Furthermore, studies of adjuvant therapy should stratify patients for this variable.
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From September 1963 to January 1968, 243 patients with operable breast cancer were included in a randomized trial designed to compare classical radical mastectomy (RM) alone to extended mastectomy (EM), i.e. RM plus internal mammary dissection. One hundred and seventeen patients underwent RM, and 126 EM. After a mean follow-up time of 20 years, no significant differences were observed between the two treatment groups for overall survival, for the relapse-free survival rates, nor for distant metastasis, or locoregional recurrence rates. From a regression model, significant interactions were found between risk of death, EM, and both nodal status and site of the tumour. When compared to RM, EM significantly decreased the risk of death for patients with internal or medial tumour and positive axillary nodes (P = 0.05). No beneficial effect of EM was observed for any of the other patients; on the contrary, EM seemed to increase the risk of death for the patients with external tumour and negative axillary nodes (P = 0.07).
Most pathological changes in the mammary gland that are not tumours are fibrocystic diseases. Their classifications, at first purely descriptive, can now be used to predict the risks of cancer. All the same, there is no real parallel between these classifications and the difficulties in differential diagnosis that these lesions present for the pathologist. This is so true that the risk has to be defined by more objective markers than one morphological finding.
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The pathologist today has an important role in the treatment of osteosarcoma. He contributes during the operation by advising about the extent of the tumour and after the operation by studying the operative specimen to assess the extent of the tumour, and, when primary chemotherapy has been used, to estimate the effectiveness of the treatment by counting the percentage of viable tumour cells so that the type of chemotherapy used subsequently can be adapted to the situation. Only trained teams can make the best use of these studies.
This report describes an isolated case of cardiac metastasis of a myxoid liposarcoma that was successfully resected by surgery after clinical and ultrasound diagnosis. Although cardiac metastases are rarely diagnosed during patients' lifetimes, a search should be made for such lesions whenever cardiac disorders appear suddenly in cancer patients. Echocardiography appears to be one of the best investigative techniques for such purposes. Despite generally poor therapeutic results, surgical resection occasionally permits long periods of survival.
Tumor grade has been proposed as an essential factor in the staging of patients with soft tissue sarcomas. In a previous study, a histopathologic grading system using the evaluation of tumor differentiation, mitosis count, and tumor necrosis was described. The current study was conducted to test its reproducibility. The pathologic sections of 25 soft tissue sarcomas were submitted to a study group composed of 15 pathologists who had not been involved in the development of the grading system. The results were compared with those of a panel group. The crude proportion in agreement observed between the study group and the panel group was 81% for the evaluation of tumor necrosis, 74% for tumor differentiation, and 73% for the mitosis count. The crude proportion in agreement for the tumor grade was 75%, which was significantly better than the crude agreement rate of 61% for the diagnosis of histologic type (P = 0.001). A kappa statistical analysis, to check the possibility of chance-related concordance, showed a proportion in agreement of 68%. A two-way variance analysis showed that the homogeneity of the evaluation of tumor grade is impaired by tumor-related and observer-related factors. However, an improvement may be obtained by better training of pathologists. We conclude that the tumor grading system developed inside the French Federation of Cancer Centers, although perfectible, already provides reliable prognostic information and its use in prospective clinical studies may provide more information about its clinical usefulness.
The pattern of estrogen (ER) and progesterone receptors (PR) and their relationship to histo- and cyto-pathological parameters has been studied in 97 cases of benign breast disease and benign phyllode tumors (95 women, of whom 76 were premenopausal, and 2 men). Total (cytosolic + nuclear) ER and PR were assayed by a single-saturating dose method using a tris-KCl buffer. The cut-off between positive and negative ER and PR assay was 100 femtomoles/g tissue. All specimens were processed for histological examination: epithelial and fibroblastic proliferation, epithelial/stromal ratio and presence of focal or diffuse hyalinosis. In 33% of the 46 cases of fibrocystic disease one receptor at least was present (13% ER+, 31% PR+). All the 8 cases in which infiltrating epitheliosis was present were PR+ and 4 of them were also ER+. In 72% of the 31 fibroadenomas one receptor at least was present (19% ER+, 71% PR+). In all these cases levels of receptors were lower than in malignant tumors. An inverse correlation between PR + prevalence and fibrohyalinosis was observed; on the other hand a positive relationship between PR + and fibroblastic (p less than 0.001) or epithelial (p less than 0.01) proliferation was found. In all 5 benign phyllode tumors examined PR + were present at a very high level, almost as high as in malignant tumors. Of the 15 other benign breast lesions, all but one (1 hamartoma) were ER- and PR-.
A retrospective multifactorial analysis on 261 previously untreated patients with Ewing's sarcoma (Es) of bone has been carried out in order to ascertain the prognostic value of several histological variables on survival. Among those cases accepted as Es, 208 (80% of the patients) were considered to be "typical Es", while 40 (15%) displayed a large cell predominance, being subclassified as "atypical large cell Es". Furthermore, 13 patients (5%) possessed tumours of endothelial-like appearance. Eleven cases which displayed a mixed histological configuration were finally included within one of the three previous groups according to their predominant histological pattern. After adjustment for therapeutic regimens and initial location of the tumour, only two histological characteristics remain significant; i.e. the presence of necrosis (p = 0.002) and, to a lesser degree, the presence of filagree "en damier" pattern (p = 0.08), both of which are of poor prognostic value. From this study, it can be assumed that the morphological (and possibly histogenetical) heterogeneity of Es of bone has no prognostic influence on survival.
The extent of osteogenic sarcoma has been measured in 30 bones obtained after local resection and compared with pre-operative evaluation. In only one case was the articular cartilage involved and the whole joint was resected. Other cases with a metaphyseal localisation were treated by disarticulation. Articular cartilage appears to provide good protection against local extension. In contrast, the growth cartilage, which was present in 11 cases, was crossed by tumour on three occasions. In only one case of diaphyseal localisation was a resection made across the tumour which had been previously rendered necrotic by chemotherapy. In most of the diaphyseal localisations, the post-operative study revealed that the resection had been over-extensive. Tomodensitometry is not very reliable in the precise evaluation of the extent of diaphyseal involvement.
We report 7 cases of unusual fibroadenomas of the breast. They are characterized by an exuberant cellular proliferation within the ductal lumens. They appear in young women from 20 to 40 years old. These lesions are histologically identical to those described by Azzopardi (1979) under the name of "Argyrophilic cells in fibroadenomas" and by Eusebi and Azzopardi (1980) and by Govoni (1981) and called "Lobular endocrine neoplasia in fibroadenoma of the Breast". An immunohistochemical study reveals a major positivity of these cells, in all cases, with Antikeratin Antibody (anti Kl1) and with Epithelial Membrane Antigen (anti EMA) proving the epithelial origin of these cells. There cells cannot yet be regarded as belonging to the neuro-endocrine group, because of the negativity, in all cases of Grimelius and Bodian stains, and of the very heterogeneous positivity observed with Neuron-Specific Enolase antibody (anti NSE) and with anti Human Natural Killer antibody (anti HNK). These cellular proliferations seem to us, on the microscopical point of view related to the atypical epithelial hyperplasias of the breast, and different from the in situ lobular carcinoma. Thus we propose to call these lesions "variant of the breast fibroadenoma" characterized by an atypical epithelial clear cell hyperplasia. The treatment of these lesions merely consists of a lumpectomy. Only one case is associated with an eleven years free of disease follow-up: a follow-up comprised between on to fifteen months is observed in the others cases. The knowledge of these benign lesions appears to us very important, to avoid improper treatment caused by an erroneous diagnosis of carcinoma developing in a breast fibroadenoma.