[Paget's disease of the vulva: interest of sentinel lymph node analysis]. / Maladie de Paget de la vulve: intérêt de l'étude du ganglion sentinelle.

Paget's disease of the vulva is difficult to diagnose, as far as the extent of this lesion is concerned, since it is often coupled with invasive adenocarcinoma of the vulva. Thus, we present two cases of Paget's disease of the vulva, with use of sentinel lymph node analysis- a non-validated technique in this very context. Evaluation of sentinel lymph node may be useful in case of micro-invasive Paget's disease.

Follicle center lymphoma is associated with significantly elevated levels of BCL-6 expression among lymphoma subtypes, independent of chromosome 3q27 rearrangements.

The BCL-6 gene, located on chromosome 3q27, is implicated in the normal germinal center formation and is frequently rearranged in a wide spectrum of lymphomas. However the links between genetic alterations and expression of the gene are not clearly determined. We established a quantitative RT-PCR assay based on TaqMan technology to quantify BCL-6 mRNA expression in different subtypes of lymphomas and to compare the level of expression in lymphomas characterized by the presence or absence of BCL-6 translocation. Total RNA was extracted from 105 nodes biopsies (35 diffuse large B cell lymphomas (DLBCL); 26 follicle center lymphomas (FCL); 7 marginal zone lymphomas (MZL); 6 mantle cell lymphomas (MCL); 6 chronic lymphocytic leukemia (CLL); 5 T cell lymphomas (TCL); 7 classical Hodgkin diseases (HD); 6 nodal metastasis (NM); and 7 reactive hyperplasia (RH)). BCL-6 gene rearrangement was assessed by Southern blot analysis in 75% of 3q27(+) DLBCL (n = 20) cases and 67% of 3q27(+) cases (n = 10). The highest level of relative BCL-6 expression was observed in FCL (9.12 +/- 7.28) comparatively to the other lymphoma subtypes including DLBCL (2.53 +/- 1.82; P < 0.001), MCL (1.23 +/- 0.73), MZL (1.49 +/- 1.3), HD (1.60 +/- 1.00), TCL (1.75 +/- 1.64), but also RH (3.91 +/- 3.12) or NM (1.95 +/- 2.6). Among the 26 FCL cases, we observed a lower expression in grade 3 (n = 8) than in grade 1/2 (P < 0.001). Conversely, we failed to show any difference between 3q27(+) DLBCL and 3q27(-)DLBCL cases (P = 0.42). Paradoxically BCL-6 expression in 3q27(+) FCL (n = 10) was significantly lower than in 3q27(-) FCL cases (P = 0.035). Finally, this study showed that BCL-6 expression in lymphoma is largely independent of chromosome 3q27 rearrangement and is more related to the histological subtype. Clinical implication and alternative deregulation pathways of BCL-6 expression remain to be determined.

Non-Hodgkin's lymphoma of the testis: a retrospective study of 84 patients treated in the French anticancer centres.

Primary non-Hodgkin's lymphoma of the testicle is rare. We analysed cases treated in French anticancer centres from 1969 to 1995. All cases were reviewed and classified according to the R.E.A.L. Classification. Eighty-four cases were included in this study. The median age was 67 years (17-85). Disease was classified as stages I in 42 cases, stages II in 19 and stages III-IV in 23. Diffuse large B-cell lymphoma was diagnosed in 75% of cases. Treatment included orchidectomy and radiotherapy and/or chemotherapy. A complete response was obtained in 72.6% of the patient population and in 100%, 68% and 33% of stage I, II and III-IV disease respectively. Recurrence occurred in 32 cases and the most frequent site was the central nervous system: six of these patients presented stage I disease. Median overall survival was 32 months for the entire population, 52 months for stage I, 32 months for stage II, and 12 months for stage III-IV cases (P < 0.0001). Among patients presenting stage I disease, no difference was found between those treated with combined surgery and chemotherapy or surgery followed or not followed by radiotherapy. This study confirms that non-Hodgkin's lymphoma of the testicle carries a poor prognosis. Systemic adjuvant chemotherapy should be discussed because of the high recurrence rate. Inclusion of these cases in large co-operative prospective studies is recommended.

[Standards, options, and recommendations for the radiotherapy of patients with endometrial cancer. FNCLCC (National Federation of Cancer Campaign Centers) and CRLCC (Regional Cancer Campaign Centers)]. / Standards, Options et Recommandations pour la radiothérapie des patientes atteintes de cancer de l'endomètre.

OBJECTIVES: To develop clinical practice guidelines according to the definitions of the Standards, Options and Recommendations project for the radiotherapy of carcinoma of the endometrium. METHODS: Data were identified by searching Medline and personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to independent reviewers, and to the medical committees of the 20 French Cancer Centres. RESULTS: The main recommendations for the radiotherapy of carcinoma of the endometrium are: 1) For grade 1 and 2 stage IA tumours, follow-up alone is standard as additional treatment. For grade 1 and 2 stage IB tumours, vaginal brachytherapy or follow-up alone are options. For grade 3, stage IB tumours and stage IC disease, there are two treatment options: external pelvic radiotherapy with a brachytherapy boost or vaginal brachytherapy. 2) Treatment for stage II disease can be preoperative when stage II disease has been suggested by a positive endometrial curettage. Postoperative vaginal brachytherapy is given for stage IIA tumours if the penetration of the myometrium is less than 50% or if the tumour is grade 1 or 2. In the case of deep penetration, or higher grade disease, or for stage IIB external radiotherapy with brachytherapy boosting must be undertaken routinely. 3) After surgery, for stage IIIA disease, either external pelvic radiotherapy or abdomino-pelvic radiotherapy is indicated, along with medical treatment in certain patients. For stage IIIB tumours, postoperative external radiotherapy with brachytherapy (if possible) should be undertaken. For stage IIIC tumours, standard treatment is external (pelvic or pelvic and para-aortic) radiotherapy followed or not by a brachytherapy boost. In case of extrauterine sites involved abdomino-pelvic irradiation is recommended. 4) Standard treatment for inoperable stage I and II disease is external radiotherapy and brachytherapy. For patients with inoperable stage III or IV disease, treatment is often symptomatic, combining external radiotherapy and medical treatment.

[Standards, Options and Recommendations for the surgical management of carcinoma of the endometrium]. / Standards, Options et Recommandations pour la prise en charge chirurgicale des patientes atteintes de cancer de l'endomètre.

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines according to the definitions of the Standards, Options and Recommendations project for the surgical management of carcinoma of the endometrium. METHODS: Data were identified by searching Medline and personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to independent reviewers, and to the medical committees of the 20 French Cancer Centres. RESULTS: The main recommendations for the surgical management of carcinoma of the endometrium are: 1) where-ever possible, surgery is the primary treatment of both localised and advanced disease; 2) surgery is performed according to the stage of the cancer and the status of the patient; 3) surgery for stages I and II disease entails total abdominal hysterectomy and bilateral salpingo-oophorectomy. A modified radical hysterectomy is undertaken in cases of macroscopic cervical involvement. An omenectomy is recommended for serous papillary types. Pelvic lymphadenectomy for the purposes of precise staging is undertaken if the patient is of good performance status and without bad pronostic factors. Para-aortic lymphadenectomy can be undertaken to determine involvement of para-aortic nodes; 4) surgery for stages III and IV: radical surgery must be undertaken if at all possible with additional treatment as indicated. In the case of advanced disease, debulking surgery is indicated.

Chromosome abnormalities in peripheral T-cell lymphoma.

Data on chromosomal abnormalities in T-cell lymphomas are very rare as compared with those reported in B-cell lymphomas. We performed a cytogenetic study in 71 untreated patients with peripheral T-cell lymphoma, classified according to the criteria of the REAL classification. Fifty-seven patients (80.3%) had abnormal clones, whereas 9 karyotypes (12.7%) showed only normal metaphases; 5 karyotypes (7%) could not be analyzed. Recurrent numerical chromosomal abnormalities comprised +3 (21%), +5 (15.7%), +7 (15.5%), +21 (14%), -13 (14%), +8 (12.2%), +19 (12.2%), -10 (10.5%), and -Y (9% of male patients). Chromosomes involved in structural rearrangements were chromosome 6 (31.5%), mainly due to 6q deletions (19.2%), 1q (22.8%), 7q (22.8%), 9p (19.4%), 9q (19.2%), 4q (19.2%), 3q (19.2%), 2p (17.5%), 1p (17.5%), and 14q (17%). Trisomies 3 and 5 mainly correlated with angioimmunoblastic T-cell lymphoma. Isochromosome 7q, associated with trisomy 8, was present in two cases of hepatosplenic gamma/delta T-cell lymphoma. Rearrangements involving the location of T-cell receptor genes were rarely observed (chromosome band 7q35 was rearranged only in three cases, 14q11 in two cases, and 7p15 in none). No correlation could be found between the cytogenetic findings and histologic subgroup or clinical outcome in these patients. Further studies are needed to understand the significance of these abnormalities in peripheral T-cell lymphoma, and to reach a better evaluation of histologic correlations, as many differences persist between the two major classification systems, KIEL and REAL.

Human breast-cancer metastasis formation in a nude-mouse model: studies of hyaluronidase, hyaluronan and hyaluronan-binding sites in metastatic cells.

Few animal models are available to study metastasis formation. The purpose of the present study was to obtain a useful model of metastasis formation in nude mice in an attempt to analyze the stroma reaction and in particular the production and the expression of hyaluronan (HA), hyaluronidase, and HA-binding sites by cultivated cells, and HA and hyaluronectin (HN) in the invasive areas of tumors. Nude mice were subjected to i.p. injections of several human cancer cell lines (PLC/PRF/5, HepG2, CB 191, CB 193, PC3, CAL 51, SA 87 and SA 98), and formation of metastases was analyzed in different organs (lung, liver, kidney, spleen and axillary nodes) by immunohistochemical techniques. CAL 51, a breast-cancer-metastasis-derived cell line with a normal karyotype, produced i.p. tumors in 75% animals and metastases in 90% animals (detected in the liver and axillary nodes). Two modes of invasion by CAL 51 cells were observed in the liver: one, direct, from the surface of the liver and the other, indirect, via the bloodstream. HA and HN were strongly expressed at the invasion areas. A cell line derived from hepatic metastasis of CAL 51 (HMD CAL 51) presented an abnormal karyotype. HMD CAL 51 produced more hyaluronidase (12-fold) and HA (10-fold) and expressed more CD44 (1.6-fold) and other HA-binding sites (9.5-fold) than the established cell line CAL 51. Our results show that i.p. injection of the CAL 51 cell line into nude mice provides a useful model of metastasis formation. The passage of the CAL 51 cells from the primary state to the metastatic state was characterized by a dramatic increase of HA and hyaluronidase production, and expression of HA, HN and HA-binding sites.

[Intramedullary spinal cord metastasis and leptomeningeal involvement in Hodgkin's disease. Case report and review of the literature]. / Atteinte de la moelle épinière et envahissement méningé lors d'une maladie de Hodgkin. A propos d'un cas et revue de la littérature.

INTRODUCTION: Central nervous system, especially spinal cord involvement, is unusual in Hodgkin's disease. We report the case of a patient with refractory Hodgkin's disease who presented with intramedullary involvement. EXEGESIS: A 36-year-old woman presented with weakness of the right lower extremity and sphincter dysfunction 13 years after initial diagnosis of Hodgkin's disease. Magnetic resonance imaging showed intraspinal tumor with contrast enhancement extending from C7 to D1. Cerebrospinal fluid examination revealed the presence of Reed-Sternberg cells. Specific intramedullary spinal cord metastasis and leptomeningeal involvement were confirmed. Despite intrathecal chemotherapy the neurologic deficit progressed to paraplegia and the patient died 2 months later. CONCLUSION: Intramedullary spinal cord metastases rarely occur in the course of Hodgkin's disease. Except for the initial presentation, their prognosis is poor despite early diagnosis with magnetic resonance imaging. Other causes such as epidural cord compression, paraneoplasic myelopathy, granulomatous angiitis and radiation myelopathy are still delated.

Iatrogenic risks of endometrial carcinoma after treatment for breast cancer in a large French case-control study. Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC).

Since tamoxifen is widely used in breast cancer treatment and has been proposed for the prevention of breast cancer, its endometrial iatrogenic effects must be carefully examined. We have investigated the association between endometrial cancer and tamoxifen use or other treatments in women treated for breast cancer in a case-control study. Cases of endometrial cancer diagnosed after breast cancer (n = 135) and 467 controls matched for age, year of diagnosis of breast cancer and hospital and survival time with an intact uterus were included. Women who had received tamoxifen were significantly more likely to have endometrial cancer diagnosed than those who had not (crude relative risk = 4.9, p = 0.0001). Univariate and adjusted analyses showed that the risk increased with the length of treatment (p = 0.0001) or the cumulative dose of tamoxifen received (p = 0.0001), irrespective of the daily dose. Women who had undergone pelvic radiotherapy also had a higher risk (crude relative risk = 7.8, p = 0.0001). After adjusting for confounding factors, the risk was higher for tamoxifen users (p = 0.0012), treatment for more than 3 years (all p < 0.03) and pelvic radiotherapy (p = 0.012). Women who had endometrial cancer and had received tamoxifen had more advanced disease and poorer prognosis than those with endometrial cancer who had not received this treatment. Our results suggest a causal role of tamoxifen in endometrial cancer, particularly when used as currently proposed for breast cancer prevention. Pelvic radiotherapy may be an additional iatrogenic factor for women with breast cancer. Endometrial cancers diagnosed in women treated with tamoxifen have poorer prognosis. Women who receive tamoxifen for breast cancer should be offered gynaecological surveillance during and after treatment. A long-term evaluation of the risk-benefit ratio of tamoxifen as a preventive treatment for breast cancer is clearly warranted.

Increased hyaluronidase levels in breast tumor metastases.

Hyaluronidase, a matrix-degrading enzyme, was assayed in extracts from breast primary tumors and regional metastases using a pool of human sera as a standard. Optimal activities of tumor extracts and serum were found for concentrations of 0.15-0.20 M NaCl in pH 3.8-4.0 buffer. In evaluating contamination by serum due to vascular proliferation, we expressed our results as the ratio of the entire activity (mU/l extract) on serum albumin content of tumors (g/l). Median (interquartile range) activities were 9.02 (6.04-14.34) for primary tumors and 37.36 (24.06-99.63) mU/g albumin for metastases. The difference was significant. Zymographic analysis showed that 3 bands of activity were detected which corresponded to 68, 53 and 49 kDa for tumoral hyaluronidase. The same pattern was observed for cellular extracts of breast cancer cell line CAL51, demonstrating that hyaluronidase detected in tumor extracts had mainly a cellular origin. Our results suggest that hyaluronidase may be involved in the metastatic process.

Expression of opioid peptides in cells and stroma of human breast cancer and adenofibromas.

The expression of beta-endorphin, Met-enkephalin and Leu-enkephalin was studied in 63 malignant and benign human breast tumors using immunohistochemical methods. Among invasive ductal carcinomas, 93% were positive for beta-endorphin, 87% for Leu-enkephalin and 90% for Met-enkephalin, in both the tumor stroma and the cell bodies. Enkephalin was predominant in cells, whereas endorphin was predominant in stroma. Nearly the same distribution was found in adenofibromas. In pericancerous normal tissue, neuropeptides were predominantly expressed in the stroma. Although the neuropeptide expression is not cancer-specific, it could be cancer-related, since the results suggest that the neuropeptide expression could reflect the host response to cancer cells and not only the cancer cell activity. The possibility of a direct action of the nervous system on stroma reaction and then on cancer cells is discussed.

The Centre H. Becquerel studies in inflammatory non metastatic breast cancer. Combined modality approach in 178 patients.

One hundred and seventy-eight patients with non metastatic inflammatory breast cancer (IBC) have been treated at the Centre H. Becquerel. Median follow up is 67 months (6-178). Every patient received neoadjuvant chemotherapy (mean number of cycles = 4; range: 2-8), followed by a loco regional treatment (radiotherapy = XRT or modified radical mastectomy = S), followed by adjuvant chemotherapy. During this period, the types of chemotherapy and locoregional treatment have been the following: Study I: 64 patients treated with CMF or AVCF and XRT; Study II: 83 patients, treated with either AVCF, FAC or VAC followed by S (n = 38) or XRT (n = 22) in case of complete or partial response, or followed by XRT (23) in case of initial supraclavicular lymph node involvement or lack of response after chemotherapy; Study III: 31 patients treated with FEC-HD + Estrogenic recruitment followed by S and XRT after adjuvant chemotherapy, except seven patients who received XRT (refusal of surgery). Although objective response rates (= 56.2, 73.5 and 93.5% for study I, II and III respectively) are statistically better in the 3rd study, this does not translate in dramatically different disease free survival (median = 16.7, 19 and 22.2 months respectively for study I, II and III) or overall survival (median = 25, 45.7 and 32.6 months respectively for study I, II and III). Analysis of subset of patients without supra clavicular lymph node involvement where neoadjuvant chemotherapy obtained at least a 50% response reveals a median disease free survival and median overall survival of respectively 38.3 and 60.1 months for patients who underwent S vs 19 and 38.3 months for those who received XRT (P = 0.15). These studies suggest that surgery has no deleterious effect on outcome of IBC. Advantage on disease free survival or overall survival from intensive chemotherapy in IBC remains to be proven with appropriate randomised trials.

[Mammographic aspects of Aschoff's proliferative centres]. / Aspects mammographiques des centres prolifératifs d'Aschoff.

The pseudotumoral feature of radial scar cause considerable diagnostic problems mammographically and at the extemporaneous examination. From a series of 28 cases, the authors confront their experience with classical mammographic data and emphasize: the difficulty in analysing the central area of the radiating structure, the possibility of glandular retraction, the relationship between spicules and radiolucent linear structures. These radiological criterias do not allow us to affirm the diagnosis. Extraction with histological examination of the operatory fragment is the only attitude.

Hyaluronan (hyaluronic acid) and hyaluronectin in the extracellular matrix of human breast carcinomas: comparison between invasive and non-invasive areas.

We performed quantitative determination of the distribution of hyaluronan (hyaluronic acid, HA) and the HA-binding protein, hyaluronectin (HN), 2 components of the extracellular matrix of tumor desmoplasia, within 71 human breast carcinomas. Results showed that HA and HN were more elevated in tumoral than in non-tumoral adjacent tissue, and that the peripheral invasive area of tumors contained increased levels of HA and HN as compared with the central non-invasive area (p less than 10(-3) and p less than 10(-5) respectively). HN and HA levels of 61 ductal carcinomas were related to the histological grade of tumors; no significant difference was found between grades for HA; HN was found to be significantly lower in grade III than in grade II tumors (p less than 0.01). HA and HN rates were correlated in grade I and grade II tumors and were not correlated in grade III. Mean percentage of HA saturation level by HN for whole tumors was found to be less than 4%, indicating that HA is essentially free of proteins and could be used as a target for cancer diagnosis or therapy.

[Granular cell tumors (Abrikossoff's tumors) of the breast. Apropos of 4 cases]. / Les tumeurs à cellules granuleuses (tumeurs d'Abrikossoff) à localisation mammaire. A propos de 4 cas.

Granular cell tumors are rarely localized in the breast gland because of diagnosis is difficult compared to breast skin lesions. Clinically and radiologically, pseudo-neoplastic aspect can be encountered. Differential diagnosis with an invasive carcinoma can be difficult on frozen section. But final histological analysis easily confirms the diagnosis. The treatment consists in local excision of the tumor. Today we can admit that granular cell tumors are derived from schwann cells.