[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.

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.

[Extra-articular cervical synovial sarcomas. Review of the literature apropos of 2 cases]. / Les synovialosarcomes cervicaux extra-articulaires. Revue de la littérature à propos de deux observations

Two cases of extra-articular synovial sarcoma are reported together with a review of the literature. The analysis of 44 cases shows that this tumor appears among young people particularly between 10 and 30 years of age and is twice more frequent among males. There can be metastasis mostly in lungs (11 times), which can sometimes appear much later (more than 10 years after the first diagnosis). The 5-year survival rate is here, 13/18; this is higher than for similar tumors located in the juxta-articular area. The great size of the tumoral nodule (more than 5 centimeters) is of a bad omen for the prognosis. As regards therapy, isolated surgical exeresis seems to have given results at least as good as these of surgery associated to radiotherapy. In all cases, the diagnosis is based on a light microscopic study which shows two tightly linked histological patterns: a proliferation of fusiform cells and glandular like formations. This feature is not definitely pathognostic and is very similar to tumors of glandular origin, with myoepithelial proliferation. Some examples could indeed be classified as extra-articular cervical synovialo-sarcoma. They could originate in pharyngeal and laryngeal mucous glands. This histogenetic hypothesis could account for the highly favorable evolution of some cases which were reported as synovialo-sarcoma.

[Extraneural metastasis of central nervous system tumours (author's transl)]. / Les métastases extranevraxiques des tumeurs du système nerveux central.

Extraneural metastases of central nervous system tumours are very rare (248 of histologically proven examples in the literature). They are mainly in adult males and in the following descending order of frequency: gliomas (39.5%), meningeal tumours and sarcomas (28.2%), neuronal tumours (14.1%), lymphomas-microgliomas (12.5%), pineal tumours (4%) and melanomas (1.6%); 10 cases out of 248 developed through a shunt. 19 were observed without any surgical operation. There are still many uncertainties about their pathogenesis. It seems however that in some tumours the increased survival time and the repetition of the craniotomy favorises the metastasis.

[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.

[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.

[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.

[The metastatic potential of primary central nervous tumours (author's transl)]. / Le potentiel métastatique des tumeurs primitives du systeme nerveux central.

Anatomical and clinical findings in 9 cases of primary brain tumors with metastases within (7 cases) or outside of (2 cases) the nervous system are reported. A review of the published literature revealed 248 cases of histologically-confirmed central nervous system tumors with metastases outside of the nervous system. These secondary sites are seen more frequently in adult males. Their frequency, in descending order, was gliomas (39,5 p. 100), meningeal tumors and sarcomas (28,2 p. 100), neuronal tumors (14,1 p. 100), lymphoma-microgliomas (12,5 p. 100), pineal body tumors (4 p. 100), and melanomas (1,6 p. 100). Ten cases out of 248 developed through a shunt. Nineteen cases were discovered without any surgical operation. There are still many unknown factors concerning their pathogenesis. It appears, however, than in some series of patients the prolongation of the survival-rate and the late effects of surgical operation are positive factors for metastatic dissemination.

[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.

[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.

Sarcoma arising in oligodendroglioma of the brain: a case with intramedullary and subarachnoid spinal metastases.

A case of sarcoma arising in a left temporal oligodendroglioma is described in a 39-year-old male. The postoperative evolution was marked by a paraplegia linked to medullary and subarachnoid metastases. Then a relapse of the cerebral tumor occurred, and the patient died 6 months after the onset of the symptoms. Histologically, the mesenchymal component appeared fibrosarcomatous and angiosarcomatous. Those facts argue in favor of the histogenic hypotheses put forward in exceptional cases previously described, according to which the sarcoma develops from vascular elements of the glioma.

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.

[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.

[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.

Primary malignant melanoma of the cerebellum: a case with metastases outside the nervous system.

A case of primary intracranial melanoma in a 65-year-old female is described. A complete postmortem examination revealed multiple metastases in the liver, and eliminated the possibility of an extraneural primary melanoma. A review of the literature confirmed that such cases are highly exceptional, and that an exhaustive autopsy including particularly the eyes is indispensable to substantiate the diagnosis. When these conditions are fulfilled, there is no reason not to consider the eventuality of visceral deposits from a primary melanoma of the central nervous system.

[Obliterating parietal hemodissection or vertebro-basilar dissecting aneurysm]. / Hémodissection pariétale oblitérante ou anévrisme disséquant vertébro-basilaire

The authors report the pathological and clinical findings of a dissecting aneursym of the basilar artery in a 32 year old man up till then in good health, who died two months later. The pathological study showed bilateral lesions of osteo-malacia in the neighborhood of the pons due to hemo-dissection affecting the right vertebral artery just before it enters the dura-mater, then its intra-cranial portion, the basilar trunk and the first part of the right posterior cerebral artery. The originality of this case resides in the finding of segmental stenosing panarteritis of the same right vertebral artery in the segment which precedes dissection. On this occasion, the authors carried out a review of the literature and considered a few comments on the etiology, the pathology, clinical findings and classification of this unusual disease.

[Primary "muscle" tumors or tumors with a myosarcomatous component of the central nervous system. General review and attempt at classification based on 2 anatomo-clinical observations]. / Les tumeurs "musculaires" ou à composante myosarcomateuse primitives du système nerveux central. Revue générale et essai de classification basés sur deux observations anatomo-cliniques.

The authors report the first two French cases of primary rabdomyosarcoma of the central nervous system. They then review the literature on muscle tumours or primary myosarcomas of the nervous system of which 29 cases have now been published. From the point of view of morphology and classification, one should distinguish firstly, purely mesenchymatous tumours (rhabdomyosarcomas, leiosarcoma, mesenchymoma) and secondly, composite tumours of connective tissue or spino-epithelial tumours (medullomyoblastomas, neuromyoblastomas, gliomyosarcomas). Their histogenesis occurs from the ectomesenchyme of the neural crests.

[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.