[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.

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.

[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.

Pseudoepitheliomatous hyperplasia in cutaneous T-cell lymphoma. A clinical, histopathological and immunohistochemical study with particular interest in epithelial growth factor expression. The French Study Group on Cutaneous Lymphoma.

Pseudoepitheliomatous hyperplasia has occasionally been reported in cutaneous T-cell lymphoma (CTCL). This association raises the question of the relationship between epidermal hyperplasia and the lymphomatous infiltrate. Because epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) have been demonstrated to be involved in epidermal proliferation through binding to EGF receptor (EGFr), we tested the hypothesis that these cytokines could be secreted by lymphomatous cells, and induce the overlying pseudoepitheliomatous hyperplasia. The purposes of this study were: (i) to describe the clinical and immunohistological features of pseudoepitheliomatous hyperplasia; (ii) to determine its frequency in a large series of CTCLs; and (iii) to evaluate the expression of EGF, TGF-alpha and EGFr in CTCL with or without pseudoepitheliomatous hyperplasia. Eleven cases of CTCL with pseudoepitheliomatous hyperplasia were collected from a series of 353 cases of cutaneous lymphoma registered from 1990 to 1996. They consisted of eight of 28 (28.5%) CD30+ large T-cell lymphomas and three of 148 (2%) cases of mycosis fungoides. Epidermal expression of EGF, EGFr and TGF-alpha was stronger in CTCL than in control normal human skin. Lymphomatous T cells expressed EGF and TGF-alpha whereas no expression of these cytokines could be detected in cutaneous and nodal B-cell lymphomas, nor in a normal lymph node. In addition, epidermal expression of EGFr was stronger in CTCL with pseudoepitheliomatous hyperplasia than in control cases of CTCL without pseudoepitheliomatous hyperplasia, suggesting that these cytokines, in association with other factors, are probably involved in the epidermal hyperplasia observed in some cases of CTCL.

[Expression of T and Tn antigens in breast cancers]. / Expression des antigènes T et Tn dans les cancers du sein.

Expression of carcinoembryonic Tn antigen studied with VVA-B4 and GSI-A4 lectins with the monoclonal antibody 83D4 and of T antigen with LDL and PNA lectins with the monoclonal antibody ZCMO4, were examined in 54 malignant or benign human breast tumors and for MCF-7, T47D and MCF-10A cell lines of human breast tumors origin. For breast tissues, positive membrane labelling with D-GalNAc alpha-O-ser/thr (Tn-antigen) specific lectins and 83D4 MAb occurred 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 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 cytoplasma, 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 glycosyltransferase, 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. In all cases, T or sialosyl-T antigens are present at the surface of tumors cells. All cell lines from breast tumors cultured in vitro were labelled with lectins and monoclonal antibodies. The simultaneous presence of Tn and T antigens on the cells, indicates that the expression of Tn antigen is due to a partial but non total deficiency in the beta-1- > 3 galactosyltransferase involved in T-antigen synthesis.

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.

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.

HTLV-I-associated lymphoma presenting as mycosis fungoides in an HTLV-I non-endemic area: a viro-molecular study.

Human T-lymphotropic virus type I (HTLV-I) is endemic in the Caribbean region, south-western Japan and Africa, and is associated with tropical spastic paraparesis and adult T-cell leukaemia/lymphoma (ATLL). Cutaneous forms of ATLL are sometimes indistinguishable from other cutaneous T-cell lymphomas (CTCL). We report a woman living in a non-endemic area for HTLV-I, with no risk factors for viral infection, who developed mycosis fungoides-like ATLL. The findings underline the usefulness of molecular biological techniques in distinguishing between mycosis fungoides and ATLL. We emphasize the need to establish the HTLV-I status of patients with CTCL, even in HTLV-I non-endemic areas, not only to establish a preventive policy in these countries, but also to further our knowledge of the lymphoproliferation spectrum associated with human retroviruses.

[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.

Epstein-Barr virus in familial Hodgkin's disease.

Hodgkin's disease (HD) has been found to be linked to Epstein-Barr virus (EBV). Familial HD (FHD) may be related to a possible unknown agent. We have determined whether EBV small RNAs (EBERs) were found in Reed-Sternberg cells from FHD. Five families were studied for histological subtype and EBER presence. There was a striking similarity in FHD subtypes of each family and 3/11 (27%) of the cases were EBER positive. In conclusion, EBV EBERs are only infrequently found in FHD and other factors including viruses different from EBV should be further investigated in FHD.

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.

[Uterine metastases originating from breast cancer. Apropos of 12 cases]. / Métastases utérines à point de départ mammaire. A propos de douze observations.

The authors report a retrospective clinicopathologic analysis based on 12 cases of uterine metastases from breast cancer. The myometrium was more often involved than the endometrium, and a metastatic lesion occurred in an interstitial leiomyoma in one case. Bilateral ovarian involvement was associated in 11 cases. The histopathological type was predominantly represented by invasive lobular breast cancer in 10 cases: in this series, 3 subtypes were identified, the solid variant (6 cases), the classical variant (2 cases), and the alveolar variant (2 cases). The steroid receptor status in the tumor specimens was found to be constantly positive. The literature concerning the pathologic diagnosis was reviewed: most breast cancers metastasizing to the female genital tract and to the peritoneal surface appeared to be invasive lobular cancers.

Oral florid papillomatosis.

A case of oral florid papillomatosis involving the superior and inferior alveolar ridges, the palate and the tongue in a young woman is presented. Histological examination showed papillary hyperplasia with marked acanthosis. The basement membrane remained intact. The patient was treated with a combination of recombinant-alpha 2a interferon and carbon dioxide laser surgery.

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.

Genotypic analyses of Richter's syndrome.

The authors report the immunogenotype of two cases of Richter's syndrome. The immunoglobulin gene rearrangement pattern obtained on Southern Blot analysis was found in both cases to be the same in leukemic blood cells and in the tissue involved by the lymphoma. The beta chain and gamma chain T-cell receptor gene rearrangement pattern exhibited a germ-line configuration in the peripheral blood cells and in the lymph node in Case 2, whereas in Case 1 the lymph node had a gene rearrangement in the beta chain, as well as in the gamma chain T-cell receptor, and the leukemic cells from bone marrow were found to be in a germ-line configuration for T-cell receptors (beta and gamma chains).

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.

Genotypic analyses of Hodgkin's disease.

In spite of the use of molecular biology, the cellular lineage and clonality of Reed-Sternberg cells, the abnormal cells of Hodgkin's disease, remain an enigma. We studied the pattern of rearrangements at immunoglobulin and T-cell receptor loci in 23 patients suffering from Hodgkin's disease. Two out of 23 patients exhibited immunoglobulin gene rearrangements. No rearrangements of the T-cell receptor beta-chain gene were detected in any patient examined. Our results showed no correlation between the presence of rearranged bands and the number of Reed-Sternberg cells.