Clinical relevance of immunohistochemical detection of multidrug resistance P-glycoprotein in breast carcinoma.

In 20 women with breast carcinoma, 17 of whom had locally advanced cancer and 3 of whom had confirmed metastases, the expression of P-glycoprotein was evaluated before the start of a chemotherapy regimen that included multidrug resistance-related drugs. With the use of the C494 monoclonal antibody in an avidin-biotin-immunoperoxidase technique, P-glycoprotein was detected in 17 of 20 tumor samples. Results were expressed in a semiquantitative manner, taking into account the number of positive tumor cells (N index) and the specific staining intensity (I index). The 17 patients with nonmetastatic cancer were followed from the first cycle of chemotherapy to cancer recurrence; subsequent to six cycles of chemotherapy, all of these patients except one were rendered clinically disease-free through surgery and/or radiation. The end point was defined as either local/regional recurrence or metastasis. Strong P-glycoprotein-positive staining in a majority of tumor cells (the N+/I+ phenotype) was significantly correlated with no initial response to chemotherapy (P less than .02) and with a shorter progression-free survival (P less than .02). Thus, the pretreatment evaluation of P-glycoprotein expression may be of prognostic value in patients with locally advanced breast cancer.

Effects of cyclosporine A on Ia antigen expression in N-nitroso-N-methylurea-induced rat mammary tumors.

Cyclosporine A (an immunosuppressive agent) decreases Ia lymphoid differentiation marker in female Sprague-Dawley rats with N-nitroso-N-methylurea-induced mammary tumors. Presence of lymphoid differentiation antigens was determined on mammary tumor cells and lymphoid cells from bone marrow, spleen, and peripheral blood by flow cytometric analysis. Quantification of Ia antigen expression was also performed by affinity chromatography and chromatofocusing in mammary tumors. A significant decrease in Ia antigen expression by mammary tumors of animals treated with cyclosporine A was noted with the two different methods. Cyclosporine A acts as an antagonist to prolactin receptors in such hormone-dependent mammary cancer. Our results should prove very useful in understanding the mechanisms of prolactin regulation of Ia antigen in tumorigenesis of the mammary gland.

Clonotypic heterogeneity in cutaneous T-cell lymphomas.

The antigen receptor genes studied (immunoglobulin gene for B-cells, and T-cell receptor -beta or -gamma gene for T-cells) represent the most powerful tools for diagnosing the clonality of a lymphoid lineage. We have clonotyped 23 cutaneous T-cell lymphomas and 5 were found to be clonotypically all heterogeneous. Analysis of each patient was performed either from serial skin biopsies taken several months apart or from different tumor samples. In these cases, T-cell lymphoma clonotypic heterogeneity was demonstrated and was especially evident when examining different tumor sites. Moreover, in one case, a biogenotypic population (immunoglobulin and T-cell receptor-rearranged) was found. This unexpected high frequency of T-cell clonal heterogeneity (22%) could be explained either by the evolution of subclones from a single undifferentiated malignant cell or by the independent transformation to cancer of 2 or more lymphocytes, though the latter seems less likely. Clonotypic heterogeneity seems to be as frequent in T-cell lymphomas with cutaneous lesions as in B-cell leukemias.

Expression of Tn antigen and N-acetyllactosamine residues in malignant and benign human breast tumors detected by lectins and monoclonal antibody 83D4.

Expressions of the carcinoembryonic Tn antigen studied with VVA-B4 and GSI-A4 lectins with the monoclonal antibody 83D4 and of N-acetyllactosamine residues with ECA and LSL lectins, were examined in 54 malignant or benign human breast tumors. Positive membrane labelling with lectins and 83D4 MAb occured in benign cases indicating that modification of glycoconjugates may precede the cytologic anomalies. In fibroadenoma, fibrocystic dystrophy, ductal hyperplasia and grade I invasive ductal carcinomas, the binding sites for all lectins and 83D4 MAb were essentially on the cell membrane with labelling of both apical and basolateral compartments. In grade II and III, the labelling involved the cytoplasm, and cell heterogeneity appeared. The disappearance of reactivity observed for a large proportion of cells at grade III may be due either to the loss of glycosyl-transferase, or to the lack of synthesis of the protein back-bone. Invasive lobular carcinomas showed labelling both on apical membrane and the outermost part of the cytoplasm with a distinct cell polarity. Lectin receptors are present at the surface of metastatic cells, possibly related to their involvement in adhesion.

Nonrandom changes of chromosome 10 in bladder cancer. Detection by FISH to interphase nuclei.

Fluorescence in situ hybridization (FISH) to interphase nuclei has been a valuable method for examining the chromosome copies in tumor cells in clinical practice. Twelve cases of transitional cell carcinoma (TCC) of the bladder were investigated with a biotin-labeled repetitive DNA probe to detect numerical aberrations of chromosome 10 in interphase nuclei. The cells containing one fluorescent signal were screened in two of seven non-invasive tumors and in four of five invasive tumors. Two patients presented two FISH spots of different sizes. More than two signals were seen in one invasive tumor. The findings suggest that partial or complete loss of a chromosome 10 is a nonrandom aberration in bladder cancer.

Structural and numerical aberrations of chromosome 22 in a case of follicular variant of papillary thyroid carcinoma revealed by conventional and molecular cytogenetics.

This study reports a case of papillary carcinoma with vesicular components showing multiclonal aberrations of chromosome 22 as revealed by RHG-banding cytogenetics and by fluorescence in situ hybridization (FISH; whole chromosome 22 and BCR-ABL-specific locus probes, multi-FISH). Four clones with chromosome 22 changes as the sole abnormality were seen. The main abnormal clone lacked the whole chromosome 22. A del(22)(q11) was observed in a second group of cells. The third clone had an idic(22). Finally, FISH revealed a fourth abnormal cell population with a der(17)t(?17;22). Some of these chromosome 22 alterations have been described in other solid tumors such as meningiomas and neurinomas, suggesting a common genetic pathway of tumor progression occurring in a multistep process. Chromosome 22 changes do not seem to be involved in pure papillary thyroid tumors and therefore could be related to the maintenance of a follicular-type histological pattern.

Hydantoin-induced cutaneous pseudolymphoma with clinical, pathologic, and immunologic aspects of Sézary syndrome.

BACKGROUND: The phenytoin-induced hypersensitivity syndrome is characterized by the development of fever, rash, lymphadenopathy, and hepatitis associated with leukocytosis and eosinophilia. This article describes the unusual occurrence of a pseudo-Sézary syndrome in the days following the introduction of phenytoin treatment. OBSERVATION: A phenytoin-induced erythroderma developed in a 60-year-old woman the histologic, cytologic, and immunologic characteristics of an erythrodermal cutaneous T-cell lymphoma of the Sézary syndrome type with lymph node involvement. The dramatic improvement after withdrawal of drug therapy and the absence of recurrence 5 years after led us to consider it as a hydantoin-induced pseudolymphoma. CONCLUSIONS: Although lymph node pseudolymphomas induced by phenytoin are well known, few cases of hydantoin-induced mycosis fungoides have been reported in the literature. We present herein the first case of a Sézary-like syndrome associated with phenytoin therapy. Such a patient must be monitored regularly because of the risk of a true malignant lymphoma developing even many years later.

Differences in Epstein-Barr virus expression between primary and secondary cutaneous angiocentric lymphomas. French Study Group of Cutaneous Lymphomas.

BACKGROUND: Epstein-Barr virus (EBV) has been demonstrated in angiocentric immunoproliferative lesions, suggesting that it could be a causative factor. We investigated for the presence of EBV in 12 primary and 2 secondary cutaneous angiocentric lymphomas (CALs). OBSERVATIONS: In the 2 secondary CALs, strong reactivity for EBV RNAs and latent membrane protein 1 were detected on paraffin-embedded sections. In contrast, 10 of 12 primary CALs were completely negative for EBV RNAs and latent membrane protein 1. In 2 primary CALs, EBV RNAs and latent membrane protein 1 were detected in few tumor cells. In the group of primary CALs, 8 of 12 were still alive at last follow-up, 3 died of systemic lymphoma, and 1 died of another cause, whereas both patients with secondary CALs died of disease within 1 year. CONCLUSION: Differences in the presence of EBV and clinical behavior between primary and secondary CALs suggest that different mechanisms are operative in the pathogenesis of these conditions, and indicate that the 2 groups should be considered separately.

Effects of N-nitroso-N-methylurea on mammary and pituitary glands of young female Sprague-Dawley rats.

Female Sprague-Dawley rats aged 50 days received 3 intravenous injections of N-nitroso-N-methylurea, 5 mg/100 g of body weight at 4 weekly intervals. When the first palpable mammary tumours appeared, with an incidence of 50 to 60% after the third injection, rats were randomized into 8 groups: group 1 was treated with 17 beta-estradiol; group 2 received progesterone; group 3 received in association 17 beta-estradiol + progesterone; group 4 was treated with tamoxifen. In group 5, rats received ovine prolactin. In groups 6 and 7, female rats were bred. Group 8, as a control group, received no hormonal treatment. Other control groups of 8 rats aged 140 days were made up of rats receiving 17 beta-estradiol alone (group 9) and rats receiving only ovine prolactin (group 10). The last group was kept without any treatment (group 11). The incidence of mammary tumours was followed in groups 1 to 8. All pituitary glands and mammary tumours were removed and weighed when rats were sacrificed after the last hormonal injection in each group. Light microscopy allowed the anatomopathologist to classify all removed mammary tumours in each group as adenocarcinoma. Light and electron microscopies with all pituitary glands in groups 1 to 11 showed no abnormality. The distribution of the pituitary weights was between 4.0 to 6.8 mg per 100 g of body weight. No adenomas were detected in the pituitary glands of the 5-month-old Sprague-Dawley rats receiving N-nitroso-N-methylurea.

[Round cell liposarcoma. Histopathologic and ultrastructural study of a case developed within the framework of a lipomatosis]. / Liposarcome à cellules rondes. Etude histopathologique et ultrastructurale d'un cas développé dans le cadre d'une lipomatose.

The authors report one case of round cells liposarcoma developing in a patient with multiple lipomas. Some clinical and ultrastructural aspects allow to focus the discussion on the histogenesis and the exact position of this tumor in the histologic classification of liposarcomas.

[Ultrastructure of bronchial biopsies obtained by fibroscopy during a remission between crises in asthmatic adults]. / Etude ultrastructurale de biopsies bronchiques obtenues au cours d'une fibroscopie effectuée en période d'accalmie intercrise chez des asthmatiques adultes.

This study describes the ultrastructure of bronchial biopsies from ten patients with bronchial asthma in remission. The superficial submucosa was the seat of a cellular infiltration: the plasma-cells are the most numerous. Light microscopy shows thickening of bronchial basement membrane. By electron microscopy, the basement membrane appears intact and the thickness consists of collagen fibrils in plexiform arrangement. The epithelium shows goblet cells and basal cells hyperplasia and lesions of the ciliated cells. The defects in the ciliary ultrastructure are: compound cilia, abnormal cilia and internalized cilia. They can be regarded as non specific lesions. Two types of cells infrequent in the bronchial mucosa are found: one characterized by apparition of a dictyosome with mucous secretion; the second by defects of the cellular membrane and little electron dense cytoplasm. These two types of cells show a "mitochondrial barrier" like the ciliated cells. This study reveals that numerous lesions are seen in the bronchial mucosal of patients with severe asthma even in remission.

[Giant cell arteritis of the uterus. Apropos of a case]. / "Artérite à cellules géantes" de l'utérus. A propos de 1 cas.

Histopathologic examination can sometimes provide unexpected indications. In this report giant cell arteritis of uterine vessels was found. It permitted to explain biological abnormalities presented by the patient who suffered of a particularly inflammatory syndrome. These abnormalities had been initially attributed to repetitive urinary infections due to third-degree uterine prolapse (associated bladder prolapse). The diagnosis of periarteritis nodosa (P.A.N.) was supported with the results of muscular biopsy. This diagnosis was confirmed by evolution: it showed secondary renal and hepatic damages. Finally three months after corticotherapy was undertaken, the general state was very improved.

[Rare tumors of the cervix: three case reports: rhabdomyosarcoma, granulocytic sarcoma and lymphoma]. / Les tumeurs rares du col utérin. A propos de trois cas: rhabdomyosarcome, sarcome granulocytaire et lymphome.

Three rare cases of tumours of the cervix are reported: embryonal rhabdomyosarcoma, granulocyte sarcoma and lymphoma. There were particular problems with diagnosis in each case requiring histochemistry, immunohistochemistry and ultrastructure examinations. Embryonal rhabdomyosarcoma is a uncommon tumour in the adult. Clinically, there is a vegetative formation but no botryoid aspect. Striated muscle cell proliferation, suggested by the morphology of the malignant cells was confirmed by immunohistochemistry which demonstrated desmine and vimentine and by the ultrastructural study which demonstrated Z lines in the cytoplasm of the malignant cells. Granulocyte sarcoma is characterized by a non-tumoural non-destructive infiltration of inflammatory-like cells. Their granulocyte nature is confirmed by histochemistry, the Leder's reaction on frozen samples, immunohistochemistry (expression of NP57). Electron microscopy can also be used. The diagnosis of lymphoma is difficult due to the non-tumoural nature of the lymphomatous infiltration which can simulate inflammatory reaction. In our case, the diagnosis was made on the tumoural aspect of the biopsy made in the deep infiltration zone of an adjacent organ (bladder). Immunohistochemistry demonstrated the lymphoid nature of the tumour and identified a B phenotype. The ultrastructural study gave little information.

[Chondrosarcoma of the soft parts of the thoracic wall. Apropos of a case after surgery and irradiation of breast adenocarcinoma]. / Chondrosarcome des parties molles de la paroi thoracique. A propos d'un cas après adénocarcinome mammaire opéré et irradié.

We are reporting here a case of chondrosarcoma of the soft tissues of the thoracic wall. As far as we can tell it is the first case published in the world. The tumour appeared 13 years after radical mastectomy and radiotherapy for an adenocarcinoma of the breast. The tumor was greyish-white in appearance and hard, but friable and haemorrhagic. Clinically and biologically it looked like an inflammatory mass. This disappeared when the tumour had been removed but recurred 6 days post-operatively when nodules showing that it had permeated the tissues appeared. Histological and immunohistochemical examination confirmed the diagnosis. We discuss the clinical and histological aspects of the case and state what we found in the literature about other sarcomas that have followed adenocarcinomata of the breast that had been irradiated and operated on. The role of radiotherapy in bringing about this tumour is discussed, including the relationship between the site of the tumour and the dose and field of irradiation. The prognosis is particularly bad in this type of sarcoma which was induced by irradiation.

[Assessment of different histoprognosis grading systems for primary ovarian cancer: 100 patients given the same treatment for primary ovarian adenocarcinoma]. / Travail original présenté lors de la Société Française d'oncologie gynécologique des 5 et 6 novembre 1999. Evaluation de différents systèmes de grade histopronostique des cancers ovariens primitifs. Série de cent patientes traitées de façon homogène pour un adénocarcinome ovarien primitif.

BACKGROUND: Numerous grading systems have been proposed for invasive ovarian epithelial carcinoma. But, conflicting reports have been published addressing the value of grade as an independent prognostic factor. DESIGN: The present study investigated the consistency, reproducibility and prognostic value of four different grading systems in a series of 100 homogeneously treated (cytoreductive surgery & platinum based chemotherapy) patient. All the slides were reviewed in a double-blind manner by 3 pathologists, typed according to the WHO and graded. Multivariate assessment of survival time was performed with the Cox model. RESULTS: Population parameters - mean age: 60 years, - stage (FIGO) III & IV 85% - survival: 5 years OS: stage III & IV=22,5%. No significant difference for survival was observed when the patients were classified with any of the 4 grades evaluated. Prognostic factors: age<60 (p<0,001), optimal surgery (p<0,01), n+(p<0,02), necrosis>50% (p<0,04), mitotic count<15MF/10HPF (p<0,03) and vascular invasion (p<0,03). Those 3 parameters were assigned to a new highly relevant grade. At multivariate analysis, it was significantly associated with DFS and OS (p<0,01). CONCLUSION: Our grade is simple, useful for all histologic types, non subjective and reproducible. Further studies are warranted to confirm its clinical utility.

[Intravascular leiomyomatosis of uterine origin. a case of pseudo-metastatic cavo-cardial thrombus]. / Léïomyomatose intravasculaire d'origine utérine. A propos d'un thrombus cavo-cardiaque pseudo-métastatique.

BACKGROUND: Leiomyomatosis is a benign smooth muscle tumor which can provoke serious complications in case of intracaval or intracardiac extension. CASE REPORT: A 61-year-old woman had undergone hysterectomy at the age of 45 years for a hemorrhagic fibroma. She underwent surgery for infiltrative breast cancer 3 months before hospitalization and was taking tamoxifen 30 mg/day. In the cancer context, the diagnosis of cavo-cardiac metastatic thrombus was proposed but not confirmed at pathology. The diagnosis of uterine tissue intravascular leiomyomatosis was established on the basis of pathology findings and immunohistochemistry results. DISCUSSION: Five other cases of leiomyomatosis after hysterectomy have been reported in the literature.

[Two cases of benign liver tumour in women on oral contraceptives (author's transl)]. / A propos de deux cas de tumeurs hépatiques bénignes chez des femmes sous contraceptifs oraux.

Two benign liver tumours are described in women who had taken oral contraceptives. These were cases of focal nodular hyperplasia and a liver cell adenoma. These lesions are benign, and were discovered on routine examination as they were not responsible for any clinical sign, as is usual except in cases of peritoneal rupture, where the patient presents with a dramatic hemoperitoneum. Oral contraceptive were found to be associated as in many recent cases. Oestro-progestins were found to be responsible for an increase in hepatic metabolism, which gave rise to biochemical, histological and sometimes clinical changes in the form of jaundice or a tumour. There is no proof of this mechanism but the supervision of women on contraceptives should include a search for a hepatic tumour for which surgical treatment is necessary to prevent complications.

PIP: 2 benign liver tumors, 1 nodular hyperplasia, and 1 liver cell adenoma, were observed in 2 young patients who had been on OC (Oral contraception). The lesions had not caused any clinical sign, and were discovered during routine examinations. The recent literature has published many instances of liver neoplasms associated to the use of OC. Estroprogestational agents are thought to be responsible for changes in hepatic metabolism causing clinical, histological, or biochemical changes. Their mechanism of action is not completely known, and their responsibility in causing such side effects cannot yet be proven. It is therefore imperative to keep women on OC under surveillance, and to routinely check for the development of hepatic tumors.

[Value of lumbo-aortic curettage in stage I and IIA tubal cancers]. / Intérêt du curage lombo-aortique dans les cancers tubaires stades I et IIA.

Results of a 7-year follow-up review of a patient with intratubal cancer and lumbo-aortic glands invasion are reported. The highly lympholytic character of these tumors and the existence of elective lumbo-aortic lymph node metastases suggest that surgery should include routine bilateral lumbo-aortic curettage in tubal cancer, particularly stages I and IIA. As well as providing improved assessment of degree of extension of the disease it can also avoid the frequently poorly tolerated abdominopelvic radiotherapy.

[Intravascular bronchioloalveolar tumor or I.V.B.A.T. Apropos of a case and review of the literature]. / "Intravascular bronchioloalveolar tumor" ou I.V.B.A.T. A propos d'un cas et revue de la littérature.

Intravascular bronchioloalveolar tumor is a rare tumour of the lung. Having observed a case detected during systematic examination in a 44-year old woman, the authors compare the radiological, clinical, histological and evolutive signs of the disease with those reported in the 40 cases published since the first description by Dail and Liebow, in 1975.