[Retrospective analysis of 108 ductal carcinomas in situ of the breast treated by radiosurgery association]. / Analyse rétrospective de 108 carcinomes canalaires in situ mammaires traités par association radiochirurgicale.

PURPOSE: To evaluate survival and prognostic factors of 108 patients with clinically or mammographically detected ductal carcinoma in situ (DCIS), treated from 1980 to 1996 by complete local excision followed by external irradiation. PATIENTS AND METHODS: The median age was 51 (range 37-80). All the patients underwent surgery consisting of a wide resection of the mammary gland harbouring the tumour. The surgical specimens were sent to the pathologists to get information on histology and margin clearance; all the slides were reviewed by one of us to assess the tumoral diameter. External beam therapy was delivered within 8 weeks after surgery. The prescribed irradiation dose was 50 Gy in 25 fractions to be given in 5 weeks. The median duration of follow-up was 93 months (range 40-173). RESULTS: There were nine patients with local recurrence (8.3%); three patients had local recurrence of DCIS and six patients developed invasive breast cancer. The treatment of local recurrence consisted of mastectomy with or without axillary dissection (eight cases) and quadrantectomy (one case). The 5-year and 10-year ipsilateral recurrence-free rate was respectively 92 and 89%. The 10-year cause specific survival was 100%. In univariate analysis, size>or=10 mm, age<45 years old and margin status were significant P=0,02, P=0,03, P=0,005; margin status was significant in multivariate analysis (P<0,02). CONCLUSION: These results are in keeping with those of the literature. They could be improved by the mass screening campaign, which is going on since January 1990 among women aged 50-74 years.

Tubulin detyrosination is a frequent occurrence in breast cancers of poor prognosis.

Tubulin, the dimeric subunit of microtubules, is a major cell protein that is centrally involved in cell division. Tubulin is subject to specific enzymatic posttranslational modifications including cyclic tyrosine removal and addition at the COOH terminus of the alpha-subunit. Tubulin is normally extensively tyrosinated in cycling cells. However, we have previously shown that detyrosinated tubulin accumulates in cancer cells during tumor progression in nude mice. Tubulin detyrosination, resulting from suppression of tubulin tyrosine ligase and the resulting unbalanced activity of tubulin-carboxypeptidase, apparently represents a strong selective advantage for cancer cells. We have now analyzed the occurrence and significance of tubulin detyrosination in human breast tumors. We studied a total of 134 breast cancer tumors from patients with or without known complications over a follow-up period of 31 +/- 10 months. The mean age of the patients at the time of diagnosis was 57 years. For each patient, detailed data concerning the histology and extension of the tumor were available. Tumor cells containing detyrosinated tubulin were visualized by immunohistochemical staining of paraffin-embedded tissue sections. Cancer cells with detyrosinated tubulin were observed in 53% of the tumors and were predominant in 19.4% of the tumors. Tubulin detyrosination correlated to a high degree of significance (P < 0.001) with a high Scarf-Bloom-Richardson (SBR) grade, a known marker of tumor aggressiveness. Among SBR grade 1 tumors, 3.8% were strongly positive for tubulin detyrosination compared with 65.4% of the SBR grade 3 tumors. The SBR component showing the strongest correlation with tubulin detyrosination was the mitotic score. In the entire patient population, neither the SBR grade nor the detyrosination index had significant prognostic value (P = 0.11, P = 0.27, respectively), whereas a combined index was significantly correlated with the clinical outcome (P = 0.02). A preliminary subgroup analysis indicated that tubulin detyrosination may define high- and low- risk groups in breast cancer tumors with an SBR grade of 2. Our study shows that tubulin detyrosination is a frequent occurrence in breast cancer, easy to detect, and linked to tumor aggressiveness.

[Contribution of ultrasonography-guided microbiopsy in breast diseases]. / Apport de la micro-biopsie échoguidée dans la pathologie mammaire.

OBJECTIVE: To assess the usefulness of core biopsy under ultrasonography (CBUS). MATERIALS AND METHODS: 165 US guided breast lesions biopsies were reviewed. Forty-eight underwent surgery and the 117 remaining cases were followed up for at least one year. Forty-four lesions were malignant and 89 were no palpable. Lesion size ranged from 3 to 35 mm (mean 14.8 mm). Core biopsy was performed with an automatic device with a 18 Gauge needle using a long-throw (2.2 cm excursion). Needle length was 10 cm. At least two passes were performed. RESULTS: Five false negatives were obtained which were all explained. All the infiltrative carcinomas without microcalcifications as mammographic sign were correctly diagnosed. A resolutive hematoma was the only complication to occur. None of the lesions with follow up showed any evolution. With CBUS, sensitivity for malignancy was 91% and specificity 100%. This is in agreement with previous studies. CONCLUSION: Methodology and indications of such core biopsies are peculiar. Actually, the lesion must be seen with ultrasonography and should not be superficial, be correlated with microcalcifications, or be a cyst even with a thick content. This method is safe and comfortable. It is not expensive when compared with surgery or stereotaxy. It should avoid useless surgical open biopsies as it allows histologic diagnosis with Scarff and Bloom grading and hormonal receptor status. So, US guided core-biopsy should contribute to increase the predictive positive value of surgical biopsy in senologic screening.

Prognostic value of quantitative cytometry in a series of 415 T1T2/N0N1/M0 breast cancer patients--preliminary results.

Identifying prognostic markers in local regional breast carcinomas remains an important challenge today. DNA content obtained by flow cytometry, has been found to be of prognostic value; results with other methods remain less clear. This report describes DNA image cytometry patterns which are assessed with respect to disease-free survival. From June 1982 to December 1992, 415 patients under 75 years of age, without any previous or synchronous carcinoma, suffering from an invasive breast cancer classified as T1 (52.8%), T2 (47.2%), N0 (65.1%) N1 (34.9%), MO according to clinical TNM staging, were enrolled in this study. The median age was 53 (28-75) and 58.8% of the patients were premenopausal; 85.3% underwent a breast conservative procedure and 14.7% a modified radical mastectomy followed by postoperative irradiation. Histological axillary lymph node status, Scarff-Bloom grade and/or cytological grade and, oestrogen receptor content were used in decision-making for adjuvant treatment: hormonotherapy (48%) or chemotherapy (18.8%). Imprints were taken from the macroscopically visible lesion at the time of surgery, and a Feulgen staining was carried out on air dried smears to be analysed using the Samba 200 cell image processor (Alcatel TITN, France). Five parameters were systematically assessed: proliferation index; DNA histogram, integrated optical density, DNA malignancy grade, ploidy balance. With a median follow-up of 36 months (0-105), proliferation index (P = 0.0008), DNA histogram (P = 0.0017), integrated optical density (IOD) (P = 0.018) and DNA malignancy grade (P = 0.017) had a significant prognostic value on disease-free survival estimated by the Kaplan-Meier method. When these parameters were included in a Cox proportional regression hazards model, PR (P = 0.01), Scarff-Bloom histological grading (P = 0.02), axillary clearance (P = 0.04) were significant; however, in the same model, taking into account the axillary lymph node histological status, IOD was significant for pN- patients (P = 0.03), and proliferation index (P = 0.03) was significant for pN+. Such results need to be updated with a longer median follow-up, but they suggest that the mean DNA content, as measured by the integrated optical density (IOD), should be considered when deciding on medical adjuvant treatment with respect to patients with a negative axillary clearance.

[Prognostic value of quantitative DNA analysis, expressed in integrated optical density, in a series of 415 T1-T2, N0N1, M0 UICC breast cancers]. / Valeur pronostique du contenu en ADN, exprimé dans la densité optique intégrée, dans une série de 415 cancers du sein T1-T2, N0N1, M0 UICC.

From June 1982 to December 1992, 415 patients less than 75 years of age, without any previous or synchronous carcinoma, suffering from an invasive breast cancer classified as T1 (52.8%), T2 (47.2%), NO (65.1%) N1(34.9%), MO according to clinical TNM staging, were enrolled in this study. The median age was 53 (28-75), and 58.8% of the patients were menopaused; 85.3% underwent a breast conservative procedure and 14.7% a modified radical mastectomy followed by postoperative irradiation. Histological axillary lymph node status, Scarff-Bloom grade and/or cytological grade, estradiol receptor content, were used to set up medical adjuvant treatment: hormonotherapy (52%) or chemotherapy (18.8%). Imprints were taken from the macroscopically visible lesion at the time of surgery, and a Feulgen staining was done on air dried smears to be analyzed using the Samba 200 cell image processor (Alcatel TITN, France). Five parameters were systematically assessed: proliferation index, DNA histogram, integrated optical density, DNA malignancy grade, and policy balance. With a median follow-up of 36 months (0-105), proliferation index (P = 0.0008), DNA histogram (P = 0.0017), integrated optical density (P = 0.018), DNA malignancy grade (P = 0.017) have a significant prognostic value on disease free survival estimated by the Kaplan-Meir method. When these parameters were included in a Cox proportional regression hazards model, Scarff-Bloom histological grading (P = 0.002), positives nodes (P = 0.02), optical integrated density (P = 0.045) were significant. Such results need to be updated with a longer follow-up, but they suggest that the mean DNA content, as measured by the integrated optical density (IOD), has to be considered when deciding on medical adjuvant treatment with respect to patients with a negative axillary clearance.

[Modulation of indications of adjuvant hormone therapy with tamoxifen in T1T2/N0N1 breast cancers. Preliminary results of a multicenter study with 695 cases]. / Modulation des indications de l'hormonothérapie adjuvante par le tamoxifène dans les cancers du sein T1T2/N0N1. Résultats préliminaires d'une étude multicentrique de 695 cas.

From 1982 to 1990, patients less than 75 years, without any previous or synchonous carcinoma, suffering from an invasive breast cancer classified as T1T2/N0N1/MO according to clinical TNM staging, were enrolled in this study; 82.4% underwent a breast conservative procedure and 17.2% a modified radical mastectomy followed by a postoperative irradiation. Histological axillary lymph node status, Scarff-Bloom grade and/or cytological grade, estradiol receptor content, were used to define three groups of patients. The breakdown of patients is not well balanced: 416 women were included in group I (N-, grade I II, ER+) when there was no adjuvant medical treatment, 110 in group II (N-, grade III, ER+), 169 in group III (N+ < or = 3, grade I II, ER+). Patients from the latter two groups were receiving tamoxifene, 20 mg per day for 2 years; Those women not menopaused received first a pelvic irradiation. With a median follow-up of 35 months (1-138) the overall survival is respectively for the three groups 95%, 96%, 96% (P = 0.5) and the disease free survival 86%, 93%, 90% (P = 0.1). The actuarial local regional remission rate is 94%, 97%, 99% (P = 0.07). Such results need to be updated with a longer follow-up, but they show the ability of adjuvant hormonotherapy to tailor the short term survival thanks to prognostic factors.

Lack of prognostic value of epidermal growth factor receptor in a series of 229 T1/T2, N0/N1 breast cancers, with well defined prognostic parameters.

The prognostic value of epidermal growth factor receptor (EGF-R) was prospectively assessed in a series of 229 clinical T1-T2, N0-N1 breast carcinomas diagnosed between May 1987 and October 1989. EGF-R expression was determined by measuring the specific Bmax of 125I EGF to tumor plasma membrane preparations. Tumor with a Bmax > or = 3 fmol/mg of protein were considered positive with regard to EGF-R expression. With a median follow-up of 34 months, the 3-year overall and disease-free survivals are respectively 92% and 88% for EGF-R < or = 3, and 91% and 86% EGF-R > 3 fmol, showing no significant difference, even when comparing axillary lymph node status. We did not succeed in finding an EGF-R cut-off value which might be significant in univariate analysis. Multivariate analysis of our data indicates that pT (p = 0.001), pN (p = 0.04), and Scarff-Bloom grade (p = 0.04) are the only significant predictors of disease-free survival among the parameters investigated in this study.

[Detection of glial fibrillary acidic protein in central nervous tumors using an immunohistochemical method. Preliminary study of 33 cases (author's transl)]. / Le diagnostic des tumeurs nerveuses centrales par un marqueur de la protéine gliofibrillaire acide. Etude préliminaire d'une série de 33 cas.

Thirty-two cases of human central nervous tumor and one experimental glioma were studied in fixed paraffin or epon embedded tissues using the peroxidase-antiperoxidase method. The present study confirms the usefulness of immunohistochemical methods for the diagnostic evaluation of neuro-epithelial neoplasms. The authors also include some prognostic and histogenetic comments about glial tumors.

[Collar-stud tumour composed of combined neurilemmona and haemangioma elements. Clinicopathological study of one case with mediastinal and intraspinal localization (author's transl)]. / Tumeur en sablier à contingent schwannoglial et hémangiomateux. A propos d'une observation anatomo-clinique a localisation médiastinale et intrarachidienne.

A mediastinal and intraspinal collar-stud tumour in a 77 year-old-woman is reported. The orginality of this study comes from the histologic findings of a combined neurilemmoma and angioma. The authors also include a brief review of literature and clinicopathological and histogenetic comments, about these combined tumours.

[Astrocytic origin of a granular cell tumor of the cerebral hemispheres. Preliminary study of a case (author's transl)]. / Origine astrocytaire d'une tumeur à cellules granuleuses intracérébrale. Etude préliminaire d'une observation.

A case of intracerebral granular cell tumor is described in a 64 year-old woman. The originality of this study comes from the histological and histochemical evidence of its astrocytic origin. The authors also include clinical, pathological and histogenetic comments about this tumor.

Extraneural metastases of astrocytomas and glioblastomas: clinicopathological study of two cases and review of literature.

Two cases of intracranial gliomas with extraneural metastases are described. Case 1, studied with biopsy material only, was a left malignant astrocytoma from the area of the rolandic fissure with right cervical lymph nodes metastases in a 43-year-old man. Case 2 was a left temporal malignant astrocytoma in a 21-year-old woman. Fifteen days after craniotomy, a left submandibular lymph node metastasis appeared. Forty days after surgery, a ventriculoperitoneal shunt was performed. Fifty-four days after surgery, the patient died. Autopsy revealed three liver metastases. Our review of the literature consists of 72 autopsy cases with extraneural deposits. Thos metastases occurred mainly in adults (63/72) and among men (46/72). The primary glioma was supratentorial in 67 cases. Metastases were mainly pulmonary and pleural. The majority of patients (82.8%) died within 2 years after onset of symptoms. In 8 of the cases, metastasis developed without any craniotomy and in 8 other cases, through a shunt.

[Nervous system and lymphomatoid granulomatosis. Clinical, pathological and nosological considerations (author's transl)]. / Granulomatose lymphomatoïde et système nerveux. Aspects anatomo-cliniques et problèmes nosologiques.

This paper describes the first French case of lymphomatoid granulomatosis (LYG) in 46-year-old male. Autopsy revealed bilateral pulmonary involvement and multiple central nervous system (CNS) localizations. The originality of this study is due to 1st the scarcity of reported cases of LYG in Europe 2nd a detailed neuropathological study permitting diagnosis of multifocal central nervous involvement by LYG. In the literature only 12 previous cases of LYG have histologically proven CNS lesions. These lesions correspond to; 8 instances of LYG, one progressive multifocal leukencephalopathy,, one post-therapeutic disseminated necrotizing leukoencephalopathy, one immunoblastic sarcoma and one case of LYG associated with histiocytic malignant lymphoma. This paper also evokes clinical, histological, ultrastructural and prognostic characteristics of LYG gathered from the available literature. From a nosological point of view the relationship of LYG with Wegener granulomatosis, polymorphic reticulosis and certain lymphomas is still, to this day, not clearly established.

[Carcinoïd heart disease: clinical, light and electron microscopic study (author's transl)]. / Cardiopathies carcinoïdes. Etude anatomo-clinique et ultrastructurale.

The authors report a clinical and pathological case of carcinoïd heart disease in a 70-years old man. The primary carcinoïd tumor was ileal with both hepatic and neighbouring lymph node metastases. The clinical history was dominated by a typical carcinoïd syndrom biologically confirmed and accompanied by a tricuspid insufficiency. An autopsy permitted to described with precision the topography and extent of the cardiac affection. The originality of this work is due to the ultrastructural study which has rarely been done. This study permitted us to make some clinical histopathological, histogenetic and pathogenetic comments.

[Vertebro-basilar dissecting aneurysm : an anatomo-clinical case study fibrodysplasia of the left vertebral artery (author's transl)]. / Hémodissection vertébro-basilaire : une observation anatomo-clinique avec fibrodysplasie de l'artère vertébrale gauche.

A new anatomo-clinical case of vertebro-basilar dissecting aneurysm in a 43 year old woman is reported. The originality of this study comes from the autopsic discovery of an intimal fibro-dysplasia at the origin of the dissection in the left vertebral artery. The authors also included anatomoclinical and pathogenic comments about both the lesions discussed.