Six-year follow-up without recurrence after a carcinosarcoma of the breast: case report.

Carcinosarcoma (CS) of the breast is a rare entity (less than 0.2% of breast malignancies), characterized by the presence of a biphasic pattern of malignant epithelial and mesenchymal elements, and with a high risk of loco-regional recurrence. The diagnosis of CS of the breast is difficult and needs detailed histological investigations to differentiate it from other malignant breast tumors. Expertise and evidence-based information on optimal treatment is very limited due to the low incidence and inconsistent classification. The principles of treatment modalities seem to be similar to others breast malignancies. CS has a different biologic behavior from others breast cancers, being very aggressive in keeping with its high-grade mesenchymal stroma. Still many questions remain about its origin and optimal treatment modalities for better outcome. We report the case of CS of the breast without local or regional recurrence after six years of follow-up in an 82-year-old woman.

Comparison of liquid based cytology and histology for the evaluation of HER-2 status using immunostaining and CISH in breast carcinoma.

BACKGROUND: HER-2 amplification is an important prognostic biomarker and treatment determinant in breast carcinoma. AIMS: To correlate immunocytochemical (ICC) expression of HER-2 and gene amplification determined by chromogenic in situ hybridisation (CISH) using liquid based cytology (LBC) with immunohistochemistry (IHC) and CISH using histological samples of the same breast carcinomas. METHODS: Frozen sections and cytobrushings of 103 breast carcinomas were analysed. Four techniques were performed on each tumour: two on LBC samples (ICC, and CISH, both graded as positive, indeterminate, or negative) and two on histological samples (IHC and CISH). Two cell lines (MCF-7, negative; BT 474, positive) were used as controls for cytological analysis. A complementary fluorescence in situ hybridisation technique was carried out in histological samples with low amplification (4-10 dots/nucleus). RESULTS: Interobserver agreement for the four techniques calculated by the kappa coefficient indicated a substantial agreement. Nine cases failed in cytology because of poor cellularity. Among 94 cases, 19 were amplified; 73, 12, and 9 tumours were scored 0 or 1+, 2+, and 3+, respectively by IHC and 75, 13, and 6, respectively, by ICC. CISH found no amplification in 72 tumours. Correlations between the IHC and CISH results in the histological and cytological samples were always significant. CONCLUSIONS: Her-2 status could be determined in LBC samples and correlated well with reference histological methods using in situ hybridisation. ICC was less reliable because of the presence of the cytoplasmic membrane. However, these results should be confirmed by a large multicentre study.

Calibration of immunohistochemistry for assessment of HER2 in breast cancer: results of the French multicentre GEFPICS study.

AIMS: HER2 protein is over-expressed in 15-30% of breast carcinomas. Immunohistochemistry (IHC) is a common and inexpensive method able to specifically detect HER2 protein. However, lack of standardization of IHC has been considered responsible for discrepancies in HER2 status assessment performed by IHC and fluorescence in-situ hybridization (FISH). This prompted us to perform a multicentric IHC calibration test to achieve a maximum accuracy of HER2-IHC compared with HER2-FISH taken as the reference method. METHODS AND RESULTS: Twelve French laboratories participated in this study, including 119 cases of invasive breast carcinomas for which both fixed and frozen tissues were available. HER2 expression was determined in fixed tissues by individual in-house IHC techniques, using either CB11 (Novocastra, Newcastle, UK) or A0485 (Dako, Glostrup, Denmark) anti-HER2 antibodies. Two cut-off values were used: 10% and 60% of immunostained cells. In 116 of the 119 cases, HER2 gene status could also be determined by FISH on frozen sections, performed in a single laboratory. Results were centralized and compared. When suboptimal concordance between IHC and FISH was observed, IHC was calibrated and a second run was performed. The specificity, sensitivity and accuracy of IHC compared with FISH were noted before and after calibration. Forty-four out of 116 (38%) tumours showed HER2 gene amplification. Accuracy of IHC was complete in the first run for 6/12 laboratories. Calibration, necessary for the six others, relied mainly on the combination of a heat-induced epitope retrieval step with an increase of dilution of the primary antibody. In the second run, HER2 over-expression was found in 46 (40%) and 44 (38%) of the 116 cases, using 10% or 60% of stained cells as cut-offs, respectively. The corresponding accuracy rates were 93% and 95%. CONCLUSIONS: This study showed that a high accuracy of IHC could be obtained for the determination of HER2 status in all laboratories using their in-house IHC technique, provided that a calibration process was performed. Antigen retrieval procedure, high dilutions of anti-HER2 antibody and the use of specific controls were crucial for HER2-IHC calibration. A 95% accuracy rate of IHC, using FISH as gold standard, was obtained by considering immunolabelling HER2-IHC results as a continuous variable, and taking 60% invasive stained cells as the cut-off for HER2 over-expression.

[HER2 gene amplification assay: is CISH an alternative to FISH?]. / Recherche de l'amplification du gène HER2: la CISH est-elle une alternative à la technique FISH?

The HER2 proto-oncogene encodes a transmembrane protein, which is considered to function as a growth factor receptor. Overexpression of this protein found by immunohistochemistry in about 20% of infiltrating breast carcinomas, has a predictive value of response to treatment by trastuzumab, an anti-HER2 humanized monoclonal antibody. Search for HER2 gene amplification is necessary to adapt the immunohistochemical technique quality and also in the cases of delicate analysis or weak overexpression. It is usually carried out by Fluorescence In Situ Hybridization (FISH). A more recent hybridization technique, named CISH because of its chromogenic revelation is an alternative method, which gives highly correlated results with FISH. We present details of this technique, which may be more familiar for the pathologists than FISH, because reading analysis is similar to that of immunohistochemical staining.

[Do indications remain for total mastectomy for cancer?]. / Que reste-t-il des indications de mastectomie totale pour cancer?

Does radical mastectomy for cancer remain needed? Breast conserving treatment may be achieved by surgery, primary chemotherapy followed by radiotherapy and surgery. This article attempts at defining (according to clinical and pathological parameters of the tumor and patient's characteristics), when conservative treatment is not allowed and radical mastectomy must be performed. Mastectomy must be performed first when there are multiple tumors or a tumor too large with respect to the breast volume or diffuse microcalcifications on mammograms. Sometimes the stage of pregnancy, a personal history of collagen vascular disease or prior radiotherapy or the willing of the patient lead to perform radical mastectomy. Secondary mastectomy is necessary in case of failure of conservative treatment or recurrence after breast conserving treatment.

Remaining indications for total mastectomy in breast carcinoma

Does radical mastectomy for cancer remain needed? Breast conserving treatment may be achieved by surgery, primary chemotherapy followed by radiotherapy and surgery. This article attempts at defining (according to clinical and pathological parameters of the tumor and patient's characteristics), when conservative treatment is not allowed and radical mastectomy must be performed. Mastectomy must be performed first when there are multiple tumors or a tumor too large with respect to the breast volume or diffuse microcalcifications on mammograms.ometimes the stage of pregnancy, a personal history of collagen vascular disease or prior radiotherapy or the willing of the patient lead to perform radical mastectomy.econdary mastectomy is necessary in case of failure of conservative treatment or recurrence after breast conserving treatment.

Chronology of combined chemotherapy (5FU) and radiotherapy. II. In vivo study.

In a previous study, we reported that repeated combined chemotherapy and radiotherapy, and a single combined treatment had different consequences. In this study the effect of the chronology of the repeated combined treatments was tested, i.e. it was determined whether the treatment is more efficient when the first treatment is Fluorouracil or irradiation, or when they are given simultaneously. It was first demonstrated that, under our conditions, neither radiotherapy nor chemotherapy were chronodependent. The combined treatments were more efficient that the single treatment although their chronology had no significant consequences. Nevertheless, the simultaneous treatment appeared slightly better than the administration of Fluorouracil 6 h before or 6 h after irradiation. These results confirm our in vitro experiments.

Medullary carcinoma of the breast. A multicenter study of its diagnostic consistency.

Nine pathologists from different institutions reviewed in a double-blind study 16 breast tumors previously indexed as typical medullary carcinoma, atypical medullary carcinoma, or infiltrative ductal carcinoma. A set of 16 slides was circulated two times among the nine pathologists. The diagnoses of typical and atypical medullary carcinomas were based on a definition given by Ridolfi et al. The interobserver and intraobserver agreement was low, with a kappa value of less than .50. The only histological criterion that had more than 50% agreement was the presence or absence of an in situ component in the tumor, assuming that the disagreement of one pathologist is accepted. This study is a snapshot of the problems encountered in the diagnosis of typical medullary carcinoma in a routine context and it shows high levels of variations in diagnostic consistency.

[Limited lumpectomy combined with peroperative curietherapy for conservative treatment of breast cancer]. / Tumorectomie limitée associée à la curiethérapie per-opératoire pour le traitement conservateur du cancer du sein.

Lumpectomy together with axillary clearance and radiotherapy is a good alternative to Patey's operation for treating early cancers of the breast. In any case it has not been definitely worked out how much should be removed. In certain patients not much needs to be removed, in other larger areas of tissue need to be excised. We present our technique for carrying out limited lumpectomy which is carried out at the same time as radiation therapy making it possible to perform a less radical clearance. The results in the first 17 patients we have followed up with a mean of 4.5 years are very encouraging. There was only one local recurrence; this was some distance away from the area of the lumpectomy. The limits for the method are determined by the examination that is carried out on the margins that have been removed and on the availability of a team comprising surgeon, histopathologist and radiotherapist.

Apparent lack of usefulness of monoclonal antibody Ki-67 in thyroid tumour pathology. Relation to histological typing and classification.

In order to test its potential application to thyroid tumour pathology, the monoclonal antibody Ki-67 was used to demonstrate immunohistochemically proliferating cells in 31 non neoplastic and neoplastic lesions of the thyroid. Twenty benign lesions were negative. Of the 11 malignant tumors, 4 papillary, 2 follicular and 1 medullary carcinomas were also negative; only 3 follicular and 1 medullary carcinomas were positive. Moreover, no correlation was found between Ki-67 immunostaining status and histological typing or pTNM pathological classification in the 11 malignant tumors.

[Evaluation of the role of MRI at 1.5 T in the staging of the initial extension of cancer of the uterine cervix]. / Evaluation du rôle de la RM à 1,5 T dans le bilan d'extension initial des cancers du col utérin.

To evaluate the sensibility and specificity of MRI in the initial staging of carcinoma of the uterine cervix, a retrospective study of 41 patients (48 MR scans) was undertaken. The sensitivity of T2-weighted images in the detection and determination of tumor location was 90% and specificity was 100%. On T2-weighted images, the signal intensity of the tumor was high in 64%. Determination of tumor size was correct in 80%. The ability of MRI to demonstrate the extension to the uterine corpus was acceptable with a sensitivity of 63% and a specificity of 100%. The extra-uterine extension was difficult to appreciate especially for parametrial, vaginal and bladder involvement with a sensitivity of 38%, 43 and 67% respectively. Concerning the lymph nodes involvement, the sensitivity was 38%. The results of this study point out the ability of MRI to evaluate the size and location of the tumor. The accuracy of MRI to appreciate the involvement of the parameters, vagina and bladder is disappointing.

Melanin production in black medullary thyroid carcinoma (MTC).

Melanin production by two medullary carcinomas of the thyroid is reported and discussed. In both tumours, melanin and calcitonin could be detected in the same cells.

Mucin histochemistry of heterotopic gastric mucosa of the upper esophagus in adults: possible pathogenic implications.

The mucin profile of 24 endoscopic biopsies of heterotopic gastric mucosa (HGM) of the upper esophagus in adults and a control group of ten cases of Meckel's diverticula containing heterotopic gastric mucosa were studied with two combined histochemical methods: alcian blue pH 2.5/PAS and high iron diamine/alcian blue pH 2.5. The clinical and light microscopic features of the 24 HGM cases were also reviewed. In addition to overall secretion of neutral mucins by the 24 HGM cases, mucin histochemistry showed prominent secretion of acidic mucins in 19 of 24 HGM cases (79%), with sulphomucins in 11 of 24 HGM cases (45.8%). This mucin profile of HGM was unlike that of either normal gastric mucosa or heterotopic gastric mucosa in Meckel's diverticula. Moreover, a comparison between the mucin profile and clinical features of HGM and Barrett's esophagus showed certain similarities. The data suggest a physiopathologic link between HGM and Barrett's esophagus.

Lymphoid follicular proctitis. A condition different from ulcerative proctitis?

A heterogeneous group is formed by patients presenting with clinical features suggestive of inflammatory bowel disease limited to the rectum and whose rectal biopsies show lymphoid follicular hyperplasia of the mucosa. All these cases are traditionally considered as one variant of chronic ulcerative colitis, so-called ulcerative proctitis. Twenty such cases were critically assessed on clinical, endoscopic, and histologic grounds, as well as on response to treatment and follow-up data. While 11 patients showed clinicopathologic features consistent with typical chronic ulcerative colitis, the other nine patients appeared to form a different group, for which the term "lymphoid follicular proctitis" seemed justified. Lymphoid follicular proctitis was, overall, characterized by rectal bleeding, a congested and granular mucosa without ulceration, abnormal and coalescing hyperplastic lymphoid follicles without acute inflammation, and failure to respond to local steroid therapy. The nature of lymphoid follicular proctitis is uncertain at present but seems unrelated to chronic ulcerative colitis.

[Papillary carcinoma of the thyroid: development of the histological criteria for diagnosis. Study of 29 cases and review of the literature]. / Le carcinome papillaire de la thyroïde: évolution des critères histologiques du diagnostic. Etude de 29 cas et revue de la littérature.

Papillary carcinoma (PAP) is the most frequent malignant tumour of the thyroid. PAP and follicular carcinoma of the thyroid are two biologically different tumours, without any intermediate or mixed form. Therefore the differentiation between PAP and follicular carcinoma is essential. The histological diagnosis of PAP is based upon several criteria, the most important being the papillae, the "ground glass" nuclei, and the psammoma bodies. The value of the "ground glass" nuclei in the diagnosis of PAP has been particularly emphasized in the last 10 years. The need to take into account all the diagnostic histological criteria of PAP is necessary in the definition of the different variants of PAP, particularly its follicular variant. We report 28 cases of PAP and one case of insular carcinoma, the latter probably originating from a PAP. "Ground glass" nuclei often associated with "grooved nuclei", were identified in the paraffin sections of 7 PAP. One case was classified as a follicular variant of PAP. Psammoma-bodies were seen in 6 PAP. Eleven PAP were less than 1 cm in diameter (microPAP). One microPAP presented with important lymph node metastases and blood vessels' involvement; 2 others microPAP arose in a vesicular adenoma. Six PAP were entirely encapsulated, without any lymph node metastasis or vessel invasion. Six PAP presented with lymph node metastases associated with lymphatic and/or blood vessels invasion. Lymphatic and blood vessel invasion was seen more often in association with PAP extending to the thyroid capsule. The histological classification and prognostic criteria are discussed and compared with those previously described in the literature.