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Significant morphological, clinical and biological prognostic factors vary according to molecular subtypes of breast tumors, yet comprehensive analysis of such factors linked to survival in each group is lacking. Clinicopathological and micro-environmental criteria, estrogen (ER), progesterone (PR) receptors, HER2, Ki67, basal markers, CD24, CD44, ALDH1, BCL2, E-Cadherin and Trio were assessed in 1070 primary operable breast cancers from a single center according to five main molecular subtypes and associations with distant metastasis-free survival (DMFS) were examined. There were 682 (64 %) luminal A (LA), 166 (16 %) Luminal B HER2 negative (LBH-), 47 (4 %) Luminal B HER2 positive (LBH+), 108 (10 %) triple negative (TN) and 67 (6 %) HER2-enriched tumors (H2+). Median follow-up was 13.7 years. At 5 years, DMFS in LA (90 %) was better than in LBH- (80.9 %), hazard ratio (HR) = 2.22 [1.44-3.43] P < 0.001; LBH+ (74.5 %), HR = 3.14 [1.69-5.84] P < 0.001, TN (71.5 %) HR = 3.63 [2.34-5.63], P < 0.001; and H2+ (65.2 %), HR = 4.69 [2.90-7.59], P < 0.001. In multivariable analysis, factors associated with shorter DMFS varied according to molecular subtype, with tumor size being associated with shorter DMFS in the LBH-, LBH+ and TN groups and the Rho GEF Trio and BCL2 phenotypes in TN tumors only. These findings help to define new clinicophenotypic models and to identify new therapeutic strategies in the specific molecular subgroups.

Background: Despite entering complete remission after primary treatment, a substantial proportion of patients with early stage breast cancer will develop metastases. Prediction of such an outcome remains challenging despite the clinical use of several prognostic parameters. Several reports indicate that genomic instability, as reflected in specific chromosomal aneuploidies and variations in DNA content, influences clinical outcome but no precise definition of this parameter has yet been clearly established., Methods: To explore the prognostic value of genomic alterations present in primary tumors, we performed a comparative genomic hybridization study on BAC arrays with a panel of breast carcinomas from 45 patients with metastatic relapse and 95 others, matched for age and axillary node involvement, without any recurrence after at least 11 years of follow-up. Array-CGH data was used to establish a two-parameter index representative of the global level of aneusomy by chromosomal arm, and of the number of breakpoints throughout the genome., Results: Application of appropriate thresholds allowed us to distinguish three classes of tumors highly associated with metastatic relapse. This index used with the same thresholds on a published set of tumors confirms its prognostic significance with a hazard ratio of 3.24 [95CI: 1.76-5.96] p = 6.7 x 10(-5) for the bad prognostic group with respect to the intermediate group. The high prognostic value of this genomic index is related to its ability to individualize a specific group of breast cancers, mainly luminal type and axillary node negative, showing very high genetic instability and poor outcome. Indirect transcriptomic validation was obtained on independent data sets., Conclusion: Accurate evaluation of genetic instability in breast cancers by a genomic instability index (G2I) helps individualizing specific tumors with previously unexpected very poor prognosis.

Intraoperative examination of sentinel lymph nodes (SLN) in breast cancer can avoid a new surgical procedure in case of positive SLN, but its value, efficacy and the methods used are still controversial. The aim of our study was to evaluate the imprint cytology intraoperative method of SLN analysis performed at our institution. We did a retrospective study of the sentinel lymph node procedures performed during a period of 24  months on cT1N0 unifocal breast cancers. Intraoperative procedure was mainly by imprint cytology (touch prep). A SLN procedure was performed on 187 women with 360 SLN. Two hundred and seventy-seven SLN among 156 women were analyzed intraoperatively by touch prep. 19/48 positive SLN were detected by intraoperative touch prep (sensitivity 39.6%; specificity 100%; positive predictive value 100%; negative predictive value 88.7%, accuracy 89.5%). False negative rate of cytological intraoperative examination of SLN was 11,2% by SLN and 18,3% by patient. By univariate analysis, this rate significantly increased with lymphovascular invasion, tumor size cT1b and c and histological SBR grade 2 or 3. By multivariate analysis, only lymphovascular invasion was a predictive factor of intraoperative touch prep failure (OR = 3.3; IC 1.3-8.4). Intraoperative imprint cytology of SLN in breast cancer is associated with a high rate of false negativity that questions its use in this setting.

The necessity of excision is debatable when atypia are diagnosed at stereotactic vacuum-assisted breast biopsy (microbiopsy). Among the 287 surgical excisions performed at Institut Bergonié from 1999 to 2009, we selected a case-control study group of 151 excisions; 52 involving all the diagnosed cancers and 99 randomly selected among the 235 excisions without cancer, following atypical microbiopsy (24 flat epithelial atypia; 50 atypical ductal hyperplasia; 14 lobular neoplasia; 63 mixed lesions). Mammographical calcification (type, extension, complete removal) and histological criteria of epithelial atypia (type, number of foci, size/extension), topography and microcalcification extension at microbiopsy were compared according to the presence or absence of cancer at excision. Factors associated with cancer at excision were Breast Imaging Reporting and Data System (BI-RADS5) lesions, large and/or multiple foci of mammographical calcifications, histological type, number, size and extension of atypical foci. Flat epithelial atypia alone was never associated with cancer at excision. BI-RADS5, atypical ductal hyperplasia (alone or predominant) and >3 foci of atypia were identified as independent pejorative factors. There was never any cancer at excision when these pejorative factors were absent (n=31). Presence of one (n=59), two (n=23) or three (n=14) factors was associated with cancer in 24, 15 and 13 cases with an odds ratio=5.8 (95% CI: 3-11.2) for each additional factor. We recommend that mammographical data and histological characteristics be taken into account in the decision-making process after diagnosis of atypia on microbiopsy. With experienced senologists and strict histological criteria, some patients could be spared surgery resulting in significant patient, financial and time advantages.

Background: The objective of this retrospective study was to identify prognostic, diagnostic, and therapeutic disparities between younger (≤ 40 years) and older (> 40 years) women with ductal carcinoma in situ (DCIS) of the breast., Methods: From 1971 to 2001, all patients treated for DCIS at Institut Bergonié were included in our analyses. Follow-up data was collected over 10 years. We used univariate and multivariate analyses to investigate patient-, disease-, and treatment-related factors predictive of diagnostic, histological, therapeutic, and prognostic DCIS criteria., Results: A total of 812 patients were eligible including 731 women aged >40 years and 81 women ≤40 years. Younger women with DCIS were more likely to receive a mastectomy and less likely to receive radiotherapy. Young age and initial surgical treatment (lumpectomy and especially nonfree margins) were revealed as predictive of recurrence in multivariate analyses., Conclusions: Young age represents a recurrence risk independent of histological and clinical characteristics of the tumor. Initial treatment, especially for nonfree margins, is also a predictive factor. Appropriate initial surgery with particularly wide margins appears essential for the treatment of young women with DCIS.

Pathologic diagnosis requires tissue fixation for histologic and immunohistologic analysis, and formalin is routinely used for this. The disadvantage of this fixative is its inability to preserve nucleic acids. Pathologic tumor diagnosis requires extensive molecular analyses, for which formalin fixation may be not adequate. Recently, an alcohol-based fixative (molecular fixative, MF) was described that allows nucleic acid preservation as well as histologic and immunohistologic studies. Moreover, the MF fixation processing system (Xpress) is fast and is well adapted to a routine process. We evaluated RNA and DNA quality within 1 month and after 1 year for 10 breast carcinomas and 20 sarcomas fixed in MF in comparison with the corresponding frozen tumors. The quality of DNA extracted from the MF-fixed tissue was similar to that extracted from the frozen tumors. The quality of RNA extracted from the MF-fixed tissue was lower than that of frozen tumors; nevertheless, a majority of RNA integrity number (RIN) values were greater than 7. Gene expression quantification by real-time polymerase chain reaction gave comparable results between tumors fixed with MF and frozen tumors. Tissue fixation at 4°C with the MF improved the RNA quality measured by the RIN value. However, after storage for 1 year at room temperature, although DNA quality was preserved, RNA extracted from tissues fixed with the MF was degraded. Tissue fixation with the MF is an important improvement for molecular pathologic diagnosis, enabling a combination of routine pathologic diagnoses and current molecular diagnoses if they are carried out near the processing time.

Background: Lymphovascular invasion (LVI) is a widely recognized prognostic factor in lymph node-negative breast cancers. However, there are only limited and controversial data about its prognostic significance in lymph node-positive patients., Methods: Among 931 patients operated on and monitored at the authors' institution for an invasive breast carcinoma between 1989 and 1992, all 374 lymph node-positive breast cancers entered the study (median follow-up, 126 months)., Results: LVI was present in 46% of tumors and was associated with age < or = 40 years (P = .02), high histological grade (P = .01), and negative estrogen receptor status (P = .032), but not with tumor size, number of involved lymph nodes, or HER-2/neu status. LVI was an independent prognostic factor for distant metastases (P = .002). Furthermore, in HER-2/neu-negative/hormone receptor-positive (n = 287) tumors, the number of independent prognostic factors (LVI, age, histological grade, number of involved lymph nodes, and tumor size) was associated with a 5-years metastasis-free survival ranging from 100% if no factors (n = 25) to 89% +/- 2% if 1 or 2 factors (n = 186) and 67% +/- 6 if 3, 4, or 5 factors (n = 76) were present (P < .001)., Conclusions: LVI is an independent prognostic factor in lymph node-positive breast cancer and merits further prospective investigations as a decision tool in the adjuvant chemotherapy setting.

Background: Adenoid cystic carcinoma (ACC) of the Breast is a rare tumour (less than 1 % of all breast carcinomas). The aim of this study was to determine the clinical, histological and immunohistochemical characteristics of these tumours., Methods: From the database of the Bergonié Institute of Bordeaux, 30 cases of ACC were identified. The clinical and histological features of these carcinomas were characterized. An immunohistochemical study was performed with the following antibodies: ER, PR, HER-2-neu, Vimentin, EGFR, P63, SMA, CK5/6, CK8/18, CK14, cKIT, MIB1, CD44 and CD24., Results: Thirty patients were included (median age 60.7 years). The 10 axillary lymph node dissections and two sentinel lymph procedures were negative. The architecture was frequently of a mixed type (26/30) and less often solid (4/30). Among the 23 patients for whom follow up was available (median follow-up: 84 months [2-288]), there were three local recurrences and three metastatic events. The tumors with recurrence and metastasis showed more necrosis, a mitotic count greater than 4/10hpf, and in one case perineural infiltration. All the tumours were ER, PR and Her-2-neu negative. Morphological and immunophenotypical analysis disclosed in each tumor, a basaloid and a luminal cell population with divergent immunophenotypical patterns., Conclusions: The mammary ACC is made of two cell types and is of good prognosis despite its triple negative phenotype, similar to the basal-like infiltrating carcinoma NOS. Axillary lymph node dissection is not recommended. Good local control by at least large lumpectomy with long-term follow-up is necessary., (Copyright (c) 2010 Elsevier Masson SAS. All rights reserved.)

Introduction: Breast carcinoma is the main malignant tumor occurring in patients with Cowden disease, a cancer-prone syndrome caused by germline mutation of the tumor suppressor gene PTEN characterized by the occurrence throughout life of hyperplastic, hamartomatous and malignant growths affecting various organs. The absence of known histological features for breast cancer arising in a PTEN-mutant background prompted us to explore them for potential new markers., Methods: We first performed a microarray study of three tumors from patients with Cowden disease in the context of a transcriptomic study of 74 familial breast cancers. A subsequent histological and immunohistochemical study including 12 additional cases of Cowden disease breast carcinomas was performed to confirm the microarray data., Results: Unsupervised clustering of the 74 familial tumors followed the intrinsic gene classification of breast cancer except for a group of five tumors that included the three Cowden tumors. The gene expression profile of the Cowden tumors shows considerable overlap with that of a breast cancer subgroup known as molecular apocrine breast carcinoma, which is suspected to have increased androgenic signaling and shows frequent ERBB2 amplification in sporadic tumors. The histological and immunohistochemical study showed that several cases had apocrine histological features and expressed GGT1, which is a potential new marker for apocrine breast carcinoma., Conclusions: These data suggest that activation of the ERBB2-PI3K-AKT pathway by loss of PTEN at early stages of tumorigenesis promotes the formation of breast tumors with apocrine features.

Most Her2 testing guidelines recommend that all cases scoring Her2 2+ by immunohistochemistry should be analyzed by fluorescent in situ hybridization (FISH) to determine HER2 status to confirm eligibility for Trastuzumab therapy in breast cancer. The aim of our study was to determine HER2 gene and chromosome 17 (CEN17) status in a series of 108 Her2 2+ consecutive cases and study the correlation between pathological characteristics of the tumors and HER2 amplification. Invasive breast cancers were tested by FISH using the Dako HER2 FISH pharmDx kit. The Her2 immunohistochemistry protocol was performed using the polyclonal AO485 antibody (Dako) diluted to 1:1500. HER2 and CEN17 status were correlated to tumor SBR grade, mitotic count, estrogen receptor, progesterone receptor status and percentage of Her2 immunohistochemistry-positive cells. Following Food and Drug Administration guidelines, ie, HER2/CEN17 ratio >or=2 and an HER2 copy number >4, amplified cases were observed in 36 (33%) and 49 (45%) cases, respectively, and following American Society of Clinical Oncology/College of American Pathologists guidelines, ie, HER2/CEN17 ratio >2.2 and an HER2 copy number >6, amplified cases represented 30 and 24% of the study population, respectively. Chromosome 17 polysomy (CEN17 >2.25) was observed in 39 (36%) tumors. Significant positive correlations were found between FISH HER2 amplified cases and Her2 immunostaining >60% (P=1.1.10(-5)), SBR grade 3 (P=0.0001), nuclear atypia (P=0.03) and mitotic count (P=0.008). By multivariate analysis, Her2 immunostaining >60% (P<10(-3)) and SBR grade 3 (P<10(-3)) were independent factors predicting HER2 amplification status irrespective to cutoff guidelines. All SBR grade 3 cases with more than 60% Her2+ cells had an HER2/CEN17 ratio >or=2, only one had a ratio

Peritumoral emboli assessed on hematoxylin-eosin-stained slides are taken into account for treatment of patients with operable breast cancer. We assessed whether immunostaining with D2-40 improves the prognostic significance of emboli in a group of tumors with a large immunohistochemical sampling and a long-term follow-up. Topography, number, and extension of hematoxylin-eosin and D2-40 emboli were compared in 94 node-negative breast cancers (median number of immunostained slides per tumor: 3). Metastasis-free survival of patients with or without hematoxylin-eosin and/or D2-40 emboli were evaluated (median follow-up of 178 months). Hematoxylin-eosin emboli were detected in 14 (15%) tumors and were located at distance from the tumor. D2-40 emboli were detected in 39 (41%) tumors and was often multiple (n=30), extensive (n=23), located within (n=13), close to (n=10) or at distance from the tumor (n=16). The 12 distant hematoxylin-eosin and D2-40 emboli were located in the same vessels (seven missed at the first hematoxylin-eosin examination and secondarily diagnosed by D2-40 staining). A difference in metastasis-free survival was found only between patients with no D2-40 emboli and those with distant D2-40 emboli (P=0.02). D2-40 emboli located within or close to the tumor had no prognostic value. Comparing the metastasis-free survival of patients with or without hematoxylin-eosin emboli, the prognostically unfavorable significance of hematoxylin-eosin emboli was improved when taking into account the seven patients with missed emboli at the first examination and secondarily diagnosed by D2-40 staining (P=0.006 vs 0.003). To conclude, D2-40 increases the diagnostic sensitivity of emboli in breast carcinoma and the high incidence of D2-40 emboli might be related to the number of immunostained slides per case. Nevertheless, only distant D2-40+ emboli had a prognostic impact. In practice, D2-40 might be useful to detect missed hematoxylin-eosin emboli especially in cases without any other prognostically unfavorable criterion.

Aims: To assess the impact of cytokeratin (CK) 5/6 and E-cadherin immunohistochemistry on diagnostic agreement of non-invasive proliferative breast lesions., Methods and Results: Twenty pathologists classified 105 cases of non-invasive proliferative breast lesions into 10 diagnostic categories. One haematoxylin and eosin (H&E) slide of each case was analysed on a first round and one H&E slide with corresponding CK5/6 and E-cadherin immunohistochemistry was analysed on a second round. Interobserver reproducibility for category-specific and management-specific lesions was measured on each round. CK5/6 and E-cadherin had little impact on diagnostic agreement, which remained moderate between the first and second rounds (overall kappa coefficients of 0.47 and 0.53, respectively, P = NS). Levels of agreement slightly improved for lesions with specific CK5/6 and E-cadherin immunoprofiles (usual ductal hyperplasia, atypical ductal hyperplasia, atypical lobular hyperplasia, lobular carcinoma in situ, non-high-grade ductal carcinoma in situ), but the differences observed were not statistically significant. However, diagnostic agreement improved when lesions were grouped according to their management category (overall kappa coefficients of 0.58 and 0.66 in the first and second rounds, respectively)., Conclusions: CK5/6 and E-cadherin immunohistochemistry has little impact on interobserver reproducibility for non-invasive breast lesions. Diagnostic agreement can, however, be improved by grouping lesions in management categories.

Background: In routine practice, the distinction between isolated tumor cells (ITC) and micrometastases (MIC) in patients with breast cancer is sometimes difficult to discern. The authors assessed differences in classifying patients according to the American Joint Commission on Cancer (AJCC) and the International Union Against Cancer (UICC) definitions and method of sizing., Methods: We assessed the characteristics of metastatic deposits in only 1 involved lymph node in 337 patients with operable breast cancer (median follow-up, 15.3 years). When sizing multiple clusters, either the diameter of the area with close clusters (Method 1) or the size of the largest cluster (Method 2) was taken into account. Patients were classified and their survival was assessed according to the 2 sizing methods and the criteria used for definitions (size in AJCC; size and topography in UICC)., Results: With the AJCC definitions, 32 patients would be differently classified according to the method of sizing. With the UICC definitions, some patients with parenchymal ITC would be classified as pN1mi, 38 by Method 1 and 53 by Method 2. Some pathologists would classify the 66 patients who had isolated capsular vascular invasion as pN0. Classification was uncertain in 136 (40%) to 151 (45 %) patients. Survival was not significantly different between pN0(i+) and pN1(mi) patients., Conclusions: The distinction between ITC and MIC was often difficult and without any prognostic significance. Precise guidelines are more useful for staging than for therapy. Thus, complete axillary dissection is usually performed in pN0(i+) and pN1(mi) patients, whereas chemotherapy is not indicated or debatable when MIC is the only 1 pejorative criterion.

Objectives: To analyze the characteristics and to establish prognosis factors for 52 men suffering from breast cancer from 1980 to 2004., Patients and Methods: Men treated for breast cancer (invasive or in situ). A retrospective study analyzed clinical and histological characteristics, and treatment procedures. The probability of survival or recurrence was calculated using the Kaplan-Meier method. Prognostic factors were studied using the Log Rank test., Results: The mean age of our patients was 63.5 years old. In 73.1% of cases, subaerolar tumors were the initial symptoms, the average size was 30.31 mm. Among patients, 17 (32.7%) had T1, 19 (36.5%) T2, two (3.8%) T3 and 14 (26.9%) T4. The most represented histological type was the infiltrative ductal carcinoma (84.6%). The spread rate to axillary lymph nodes was 63.6%. The hormone dependency of these tumors was proven in 84.6% of cases. Overall survival rate were about 69% at five years and 32% at 10 years. The spread to lymph node and to derm, the clinical stage were significant factors influencing disease free survival. None of these factors had any significance regarding overall survival., Discussion and Conclusion: Male breast cancer is a rare disease (about 1% of breast cancer) with a poor prognosis (32% 10 years disease free survival). An early diagnosis and better knowledge of the disease would certainly lead to improvement of prognosis.

This study analyzes the occurrence of epithelial atypia in 2,833 serially sectioned surgical breast biopsies (SB) performed for microcalcifications (median number of blocks per SB:26) and the occurrence of subsequent cancer after an initial diagnosis of epithelial atypia (median follow-up 160 months). Epithelial atypia (flat epithelial atypia, atypical ductal hyperplasia, and lobular neoplasia) were found in 971 SB, with and without a concomitant cancer in 301 (31%) and 670 (69%) SB, respectively. Thus, isolated epithelial atypia were found in 670 out of the 2,833 SB (23%). Concomitant cancers corresponded to ductal carcinomas in situ and micro-invasive (77%), invasive ductal carcinomas not otherwise specified (15%), invasive lobular carcinomas (4%), and tubular carcinomas (4%). Fifteen out of the 443 patients with isolated epithelial atypia developed a subsequent ipsilateral (n = 14) and contralateral (n = 1) invasive cancer. The high slide rating might explain the high percentages of epithelial atypia and concomitant cancers and the low percentage of subsequent cancer after a diagnosis of epithelial atypia as a single lesion. Epithelial atypia could be more a risk marker of concomitant than subsequent cancer.

While awaiting a molecular classification of breast epithelial atypia, the authors give some guidelines about their management, in reference to studies in literature and to their own experience at the Institut Bergonié. This experience is based on the analysis of 2,833 serially sectioned surgical breast biopsies performed for micro-calcifications without any palpable mass (median number of blocks per biopsy: 26) in patients with a long median follow-up (160 months). Some guidelines are given about the application of the WHO classification of atypical non invasive proliferative breast lesions, measurement of atypical ductal hyperplasia, management of patients with epithelial atypia on core needle biopsies and management of surgical biopsies corresponding to re excision to set out a small concomitant close cancer, present in nearly one third of the cases. Indeed, epithelial atypia could be more a risk marker of concomitant than subsequent cancer.

Introduction: Typical medullary breast carcinoma (MBC) has recently been recognized to be part of the basal-like carcinoma spectrum, a feature in agreement with the high rate of TP53 mutations previously reported in MBCs. The present study was therefore designed to identify phenotypic and genetic alterations that distinguish MBCs from basal-like carcinomas (BLC)., Methods: Expression levels of estrogen receptor (ER), progesterone receptor (PR), ERBB2, TP53, cytokeratins (KRTs) 5/6, 14, 8/18, epidermal growth factor receptor and KIT, as well as TP53 gene sequence and high-density array comparative genomic hybridization (CGH) profiles, were assessed and compared in a series of 33 MBCs and 26 BLCs., Results: All tumors were negative for ER, PR and ERBB2. KRTs 5/6 were more frequently expressed in MBCs (94%) than in BLCs (56%) (p = 0.0004). TP53 mutations were disclosed in 20/26 MBCs (77%) and 20/24 BLCs (83%). Array CGH analysis showed that a higher number of gains (95 regions) and losses (34 regions) was observed in MBCs than in BLCs (36 regions of gain; 13 regions of losses). In addition, gains of 1q and 8q, and losses of X were found to be common to the two groups, whereas gains of 10p (53% of the cases), 9p (30.8% of the cases) and 16q (25.8% of the cases), and losses of 4p (34.8% of the cases), and amplicons of 1q, 8p, 10p and 12p were the genetic alterations found to characterize MBC., Conclusion: Our study has revealed that MBCs are part of the basal-like group and share common genomic alterations with BLCs, the most frequent being 1q and 8q gains and X losses; however, MBCs are a distinct entity within the basal-like spectrum, characterized by a higher rate of KRT 5/6 expression, a higher rate of gains and losses than BLCs, recurrent 10p, 9p and 16q gains, 4p losses, and 1q, 8p, 10p and 12p amplicons. Our results thus contribute to a better understanding of the heterogeneity in basal-like breast tumors and provide potential diagnostic tools.

We retrospectively analysed mammographies of 909 ductal carcinoma in situ (DCIS) (1980-1999) and compared our results to those of literature. Microcalcifications were present in 75% of the cases, and soft-tissue abnormalities in 27% cases with association with calcifications in 14% of cases. Palpable masses were found in 12% of the cases and nipple discharge was present in 12% of the cases. The radiographic-pathologic correlation allowed to suspect the DCIS "aggressiveness" on radiologic signs. Granular, linear, branching and/or galactophoric topography of the microcalcifications were correlated with necrosis, grade 3, comedocarcinoma type. A number of microcalcifications higher than 20 was correlated with necrosis and grade 3. Mammographic size was correlated to histologic size. Masses were correlated with grade 1. A diagnosis strategy can be proposed with a multidisciplinar approach.

Background: The authors applied the sixth edition of the American Joint Committee on Cancer (AJCC) classification system to their previously published group of patients with breast carcinoma who had immunohistochemically detected lymph node metastases., Methods: The original lymph node-negative slides from 218 patients, including 129 patients with infiltrating duct carcinoma (IDC) and 89 patients with infiltrating lobular carcinoma (ILC), were reviewed and then destained to perform immunohistochemistry. Each tumor cell deposit was measured. Single tumor cells could not counted or measured (because the distance separating the most distant cells could be > 2.0 mm), but they were separated into Class 1 (sparse) and Class 2 (numerous). According to the AJCC classification, isolated tumor cells (ITCs) should be classified as pN0(i+) when they measure < or = 0.2 mm and pN1mi when they measure < or = 2.0 mm but > 0.2 mm., Results: ITCs were found in 13 IDCs (10%) and in 37 ILCs (41%) and corresponded in IDCs to a single deposit of a few tumor cells that measured < or = 0.2 mm (associated with a single tumor cell in 3 tumors) and were classified as pN0(i+). In ILCs, ITCs corresponded to single tumor cells with an irregular distribution throughout the entire lymph node section (24 ITCs and 13 ITCs in Class 1 and Class 2, respectively) and were difficult to classify., Conclusions: The results suggest that there are 2 categories of pN0(i+): measurable tumor cell deposits < or = 0.2 mm, which were found exclusively in IDCs; and nonmeasurable ITCs, which were found in ILCs and rarely in IDCs. The new classification is difficult to apply to ITCs that are detected by immunohistochemistry in ILCs., (Copyright 2005 American Cancer Society.)

Objectives: To test a double histology reading system based on digitalized imaging for cancer diagnosis., Material and Methods: Pathology images of cancer diagnosis material were produced in real time by a digital imaging system integrated into the laboratory data processing system. Over a 30-day period, second readings were performed using the digitalized images. Cases with second readings were classified according to the aspect on the digitalized images as malignant tumor with histological type, malignant tumor with no other precision, and doubtful malignancy., Results: During the study period, 204 cases of cancer were diagnosed, including 178 with digitalized imaging (87%). Among the digitalized cases, 119 (67%) were classified as malignant tumor with histological type, 53 (30%) as malignant tumor with no other precision, and 6 (3%) as doubtful malignancy. The histology material of these latter cases were reviewed and corresponded to malignant tumors. Approximately 2 hours per week were devoted to the second readings., Conclusion: A integrated digitalized imaging system can participate in quality control of cancer diagnosis by allowing rapid efficacious second readings.

Breast papillary lesions are difficult to interpret and include a large variety of benign, atypical and malignant lesions. We report the case of a 41-Year-old woman presenting with an intracystic papillary carcinoma, in order to illustrate our pragmatic diagnostic approach, which includes the use of a decision tree, useful for differentiating the different types of breast papillary lesions.

Sentinel lymph node biopsy in breast cancer has changed pathology management of axillary lymph nodes by pathologists, but there is still no consensus either for serial sectioning nor for immunohistochemistry. We analyze: 1) data in the literature about the prognostic significance of micrometastases (pNlmi) and immunohistochemically detected infiltrating tumor cells (pN0(i+) in axillary lymph nodes. 2) management strategies at the Bergonié Institute and by other teams for axillary lymph nodes and sentinel lymph nodes. 3) questions and controversies on sentinel lymph node management and recommendations of the five main reference groups.

Axillary lymph node metastases detected by immunohistochemistry in standard node-negative patients with breast carcinomas (13 out of 129 infiltrating ductal carcinomas and 37 out of 89 infiltrating lobular carcinomas) do not have any prognostic significance in patients followed up for a long time (respectively 24 and 18 years). Moreover, their pejorative significance in the literature is debatable since the groups and events taken into account are heterogeneous., (Copyright 2002 Cancer Research UK)

Background: The significance of microinvasion is still debated and clinical management is controversial. The authors defined ductal carcinoma in situ with microinvasion (DCIS-MI) as DCIS with infiltration of the periductal stroma by a few tumor cells, singly (type 1) or in clusters (type 2). With this definition, the authors attempted to evaluate the clinical significance of microinvasion., Methods: The authors compared the clinical, pathologic features, and survival (median follow-up, 7.3 years) of 1248 patients with, respectively, DCIS (722 patients), DCIS-MI with microinvasion type 1 and type 2 (243 patients), and invasive ductal carcinoma in situ with a predominant DCIS component greater than or equal to 80% of the tumor (IDC-DCIS, 283 patients)., Results: Microinvasion was associated with DCIS histologic type, grade, and extent (respectively, P < 10(-8), P < 10(-3), P < 10(-4)). Axillary lymph node metastases were observed in a few patients with DCIS and DCIS-MI type 1 (respectively, 1.4% and none), in 10.1% with DCIS-MI type 2 and in 27.6% with IDC-DCIS. Metastasis free and overall survival probabilities were significantly different between three groups in the following order from best to worst prognosis: 1) the group comprising DCIS and DCIS-MI type 1, 2) the DCIS-MI type 2 group, and 3) the IDC-DCIS group., Conclusions: The authors' results suggest there are two types of DCIS-MI: 1) type 1 that behaves like DCIS and should be managed as such; 2) type 2 that is less pejorative than IDC-DCIS but is more so than type 1., (Copyright 2002 American Cancer Society.)

Six hundred seventy-six patients with ductal carcinoma in situ of the breast (DCIS) from 1971 to 1995 were included in the study. Computerized patient files were retrospectively analyzed. Clinical findings were less frequently reported to reveal DCIS after 1989. Positive mammographic findings were obtained in 87% of patients and were mainly represented by microcalcifications (79.4%). Treatment procedures were breast-conserving surgery (BCS) alone (37.5%), BCS followed by radiation (BCSR) (25.5%), or mastectomy (M) (37%). The actuarial local recurrence was 2.6% in the M group (94 months of follow-up), 14.5% in the BCS group (85,7 months of follow-up), and 7.5% in the BCSR group (78.8 months of follow-up). Predictive factors of recurrence in all patients were invaded margin status and age. In the BCS group, grade was also a predictive factor. The analysis per decade shows that the lesions currently diagnosed are less serious than those of the past. All the recurrence in patients with positive margins was in the same quadrant as the original lesion. This further emphasizes the need for clear margins.

Purpose: In view of the increasing number of patients treated with breast-conserving treatment (BCT) for ductal carcinoma-in-situ (DCIS), risk factors for recurrence and metastasis should be identified., Patients and Methods: Clinical and pathologic characteristics from patients with DCIS in the European Organization for Research and Treatment of Cancer trial 10853 (excision with or without radiotherapy) were related to the risk of recurrence. Pathologic features were derived from a central review of 863 of the 1,010 randomized cases (85%). The median follow-up was 5.4 years., Results: Factors associated with an increased risk of local recurrence in the multivariate analysis were young age (< or = 40 years) (hazard ratio, 2.14; P =.02), symptomatic detection of DCIS (hazard ratio, 1.80; P =.008), growth pattern (solid and cribriform) (hazard ratios, 2.67 and 2.69, respectively; P =.012), involved margins (hazard ratio, 2.07; P =.0008), and treatment by local excision alone (hazard ratio, 1.74; P =.009). The risk of invasive recurrence was not related to the histologic type of DCIS (P =.63), but the risk of distant metastasis was significantly higher in poorly differentiated DCIS compared with well-differentiated DCIS (hazard ratio, 6.57; P =.01)., Conclusion: Patients with poorly differentiated DCIS have a high risk of distant metastasis after invasive local recurrence. Margin status is the most important factor in the success of BCT for DCIS; additionally, young age and symptomatic detection of DCIS have negative prognostic value.

In spite of the fact that Hodgkin's disease (HD) remains still an enigma its management and treatment yield a cure rate of about 80% of all patients. However, this management has two limits: on one side favourable cases which should not be overtreated because of unacceptable side-effects, and on the other side very unfavourable cases which should be treated differently because of a very high rate of failure and/or relapse. Then it becomes necessary to precise as thoroughly as possible these two limits in order to choose the adequate treatment for the patient. Prognostic factors based on patient and disease characteristics allow a relatively exact classification of favourable and unfavourable cases. This distinction in two prognostic groups has therapeutic implications in terms of chemotherapy (regimen, duration) and radiotherapy (extension, doses). Other specific situations have to be considered, e.g. pediatric cases, pregnancy, old age and HIV-infected patients who need an adapted management according to very different situations.

Unlabelled: The Van Nuys prognostic index (VNPI) was thought to be useful for predicting response to radiotherapy and local recurrence of ductal carcinoma in situ (DCIS). We applied the VNPI under the conditions defined by Silverstein et al., in 367 retrospective DCIS entirely sectioned into serial macroscopic 2 mm slices (155 patients had radiotherapy, median follow-up 71 months). The percentage of positive blocks with DCIS was also estimated for each specimen with cut-offs at 30% and 60% to obtain three scores. One hundred and ninety five lesions had a low VNPI, 152 an intermediate VNPI, and 20 a high VNPI. There were 9% of local recurrences (half invasive, all in the group without radiotherapy) in the low VNPI group. The local recurrence rate increased with size (p = 0.001), with reduction of distance to margins (p = 0.05), with histologic grade (p = 0.02), with percentage of positive blocks (p = 0.0003) and with VNPI score (p = 0.03). The percentage of positive blocks was the only independent predictor for local recurrence (p = 0.0001)., Conclusion: (1) The VNPI was a local recurrence rate predictor between the low and the intermediate groups but in our series the low VNPI group had a surprisingly high local recurrence rate. (2) Only prospective studies will assess the importance of margin width and the role of radiotherapy in maintaining local control. (3) Estimation of the percentage of positive blocks is simple, may be an alternative when measurement of DCIS is difficult and should be taken into account.

To evaluate the prognostic relevance of Ki-67 and topoisomerase IIalpha expression in relation to tumor stage, grade, and hormone receptor content, 942 ductal infiltrating carcinomas of the breast were examined by means of the monoclonal antibodies Ki-S11 (Ki-67) and Ki-S4 (topoisomerase IIalpha). pS2, c-erbB2, and p53 were additionally considered as prognostic variables. The median follow-up time was 149 months. Eight-hundred-and-sixty-three tumors reacted with Ki-S11 and Ki-S4; the labeling indices of the two antigens were closely associated (r = 0.93). Both correlated positively with the tumor size, c-erbB2, and p53 expression, and negatively with patient age, hormone receptor content, and pS2 immunostaining. In the univariate analysis, Ki-S11 and Ki-S4 scores, nodal status, tumor size, tumor grade, and progesterone receptor content strongly predicted both overall and metastasis-free survival (p < 0.00001). Estrogen receptor status, p53, and c-erbB2 were of minor significance. Concerning overall survival, multivariate Cox regression analysis selected a Ki-S4 score >25% (p < 0.00001) next to the nodal status, and before tumor size, progesterone receptor content, and patient age. Independent predictors of the occurrence of distant metastases were nodal status, Ki-S4, tumor size, grade 1, and progesterone receptor negativity, in that order. The Ki-S11 score was of independent prognostic significance only if examined as a continuous variable. We conclude that topoisomerase IIalpha expression as assessed by monoclonal antibody Ki-S4 may add valuable information to current prognostic models for breast cancer. Its predictive value appears to be essentially related to the proliferative activity of tumor cells.

Objective: To assess the risk of local recurrence of intraductal carcinoma of the breast with a large series and a review of literature., Methods: We present a retrospective study of 331 cases treated for intraductal carcinoma of the breast. Only patients with at least 5 years follow-up were selected. We were specially interested in recurrence risk factors. In these patients with a long follow-up; pathology was reevaluated with new investigation technique., Results: After a median follow-up of 109 months, 40 local recurrences were observed; these lesions were invasive in 23 cases. Only one patient had recurrence after mastectomy. For the others, they had lumpectomy associated with radiotherapy in 12 cases. Histologic features, grade and therapeutic options were evaluated as risk factors of local recurrence., Conclusion: Follow-up after lumpectomy for intraductal carcinoma was studied. The status of tumor margins was important; irradiation appeared useful, specially in case of high grade carcinoma but further large prospective randomized studies are needed. The use of prognostic index is interesting, but there are still unanswered questions.

This study was conducted to determine the prognostic influence of obvious peritumoral vascular emboli as prospectively determined by a simple routine slide examination in patients with operable node-negative breast cancer. Obvious peritumoral emboli (OPE) were defined by the presence of neoplastic emboli within unequivocal vascular lumina (including both lymphatic spaces and blood capillaries) in areas adjacent to but outside the margins of the carcinoma. OPE were assessed routinely on 5 microns thick haematoxylin and eosin-stained sections for each of 1320 primary operable node-negative breast cancers from 1975 to 1992 at our institution. OPE and other prognostic variables (tumour size, SBR grade, oestrogen and progesterone receptor status) were correlated to overall survival (OS) and metastasis-free interval (MFI) by means of univariate and multivariate analysis with a median follow-up of 103 months. OPE were found in 19.5% of tumours. In univariate analysis, OPE were related to tumour size (P = 6.3 x 10(-5)) and histologic grade (P = 4.9 x 10(-7)). Statistically significant correlations were found with OS (P = 4.6 x 10(-5)) and MFI (P = 6.4 x 10(-9)). Furthermore, in multivariate analysis, OPE was an independent prognostic variable, the most predictive factor for MFI (P = 7.7 x 10(-7)) before tumour size and grade, and was second after tumour grade for OS (P = 0.002). This study on a large unicentric series and with a long follow-up confirms the prognostic significance of vascular emboli in patients with operable node-negative breast carcinoma. Importantly, vascular emboli were found to be accurately detectable by a simple routine and non-time-consuming method. Therefore, such obvious vascular emboli should be considered as an important cost-effective, prognostic variable in patients with node-negative breast carcinoma.

The development of breast cancer screening has radically changed the diagnostic approach to breast lesions. Stereotactic large-core breast biopsy was developed to reduce the number of unnecessary surgical excisional biopsies in the increasing number of patients with doubtful or suspicious mammogram findings. The methods used to evaluate this new technique are discussed, as well as results in terms of efficacy, factors that may influence efficacy, and difficulties in interpreting large-core biopsies. Recommendations regarding the harvesting and interpretation of stereotactic large-core biopsies are made.

Primary chemotherapy in operable breast invasive carcinoma enables tumour reduction and conservative surgery. In order to search for one or more biological factors capable of predicting tumour behaviour under primary chemotherapy, and subsequent patient survival, an immunohistochemical study was performed with specific antibodies to p53, c-erbB-2 (Her-2/neu), Mib1 (antiKi-67), pS2, GST pi, oestrogen receptors (ERs) and progesterone receptors (PRs). Core biopsies, obtained before primary chemotherapy, were available from a series of 128 breast invasive carcinomas treated between January 1985 and April 1989, with a median follow-up of 93.3 months. Univariate statistical analysis showed that negative ER detection by immunohistochemistry (IHC) was highly correlated with chemosensitivity (P = 0.001). A high percentage of Mib1-positive tumour cells (> 40%), as well as initial tumour size less than 4 cm, were also correlated with tumour responsiveness to chemotherapy (P = 0.009 and P = 0.03). By multivariate analysis IHC-ER, Mib1 and initial tumour size were independent predictors, the last parameter being the most important. Concerning subsequent patient survival, c-erbB-2 overexpression, as detected by IHC, was significant with respect to overall survival (OS) (P = 0.0006), disease-free interval (DFI) (P = 0.03) and metastasis-free interval (MFI) (P = 0.008) by univariate analysis. Furthermore, c-erbB-2 was the major independent prognostic factor for OS and MFI by multivariate analysis.

To assess the practical prognostic value of c-erbB2, we performed a study on 942 invasive ductal carcinomas treated with primary surgery between 1980 and 1986 in our center. We evaluated its expression by immunohistochemistry in paraffin-embedded tissue using a polyclonal antipeptide antibody. Of 942 tumors, 229 (24%) showed a positive membrane staining. We observed a significant association between c-erbB2 and Scarff-Bloom-Richardson grading (p < 0.0001) and a negative correlation between c-erbB2 and both estrogen and progesterone receptors (p < 0.0001). In our analysis, with respect to overall survival (OS), relapse-free survival (RFS), and metastasis-free survival (MFS), c-erbB2 was statistically significant (p < or = 0.0001) for the whole group and the node-positive subgroup. In multivariate analysis, c-erbB2 appeared to be an independent variable for RFS and MFS in the node-negative group. However, in our hands, c-erbB2 had a poor prognostic value in comparison with the classical prognostic variables such as histological grade, nodal status (N), hormonal receptor status (estrogen and progesterone receptors), and tumor size, and it did not supersede the classical parameters.

To assess the practical prognostic value of pS2, we evaluated its expression by immunohistochemistry in paraffin-embedded tissue from 942 previously untreated invasive ductal carcinomas (IDC) resected in our center between 1980 and 1986. Positive staining of tumor cells was found in 684 cases (73%), but most of the tumors contained only a small amount of positive cells. There was a negative correlation between pS2 and tumor size (p = 0.01) and histological grade (p < 0.0001), and a positive correlation between pS2 and hormonal receptor status (p < 0.001). With respect to overall survival, pS2 positivity was associated with a better prognosis for the whole group and the node-positive sub-group. However, in terms of relapse and metastasis, pS2 was not significant. Furthermore, in multivariate analysis including tumor size, nodal status, histological grade, ER status, PR status, chemotherapy, hormonal treatment, and pS2, the latter appears to be of no prognostic value.

P53 immunohistochemical detection using DO7 antibody on 942 cases of previously untreated breast invasive ductal carcinoma (IDC) with a median follow up of 117.9 months (89 to 160) was performed. Three hundred and three (32%) tumors were positive. All positive tumors were taken into account, positivity ranging from 1 to 100% of tumoral cells. The Chi square test showed significant negative correlation between p53 positivity and age (p = 0.01), estrogen receptor status (p < 0.0001), and progesterone receptor status (p = 0.0005), and significant positive correlation with tumor grade according to the Scarff, Bloom and Richardson system (SBR Grade) (p < 0.0001). There was no significant association with tumor size or nodal status. Concerning the univariate analysis, in the whole group and node-positive group (n = 544) p53 positivity was highly significant for overall survival (OS) (p < 0.0001 and p = 0.0003), disease-free interval (DFI) (p = 0.0001 and p = 0.0005), and metastasis-free interval (MFI) (p < 0.0001 and p = 0.0003). In the node-negative group (n = 398), p53 was significant with respect to OS (p = 0.01) and DFI (p = 0.04). P53 positivity came out as an independent prognostic parameter in the multivariate analysis in the whole group and the node-positive group, though of minor significance compared to axillary lymph node status, SBR grade, progesterone receptor status and tumor size.

The pathological material of 35 patients with Hodgkin's disease lymphocyte-depletion type (type 4) is reviewed with an immunohistochemistry study on paraffin-embedded sections. The new pathologic data are compared with clinical features. These 35 patients are 4.7% of 742 previously untreated patients managed in this institution from 1960 to 1991. The diagnosis of 31 of the 35 patients was rectified, 17 to non-Hodgkin's lymphoma (12 unclassifiable and five anaplastic Ki-1 positive) and 14 to another type of Hodgkin's disease (six nodular sclerosis and eight mixed cellularity). In four cases, the pathologic material was neither sufficient nor satisfactory to allow a clear-cut distinction between Hodgkin's disease and non-Hodgkin's lymphoma. The analysis of clinical data before and after pathological revision did not show any difference in clinical features, either between Hodgkin's disease "type 4" and other types (1, 2 or 3) or between cases with Hodgkin's disease and those with non-Hodgkin's lymphoma. There is, however, a significant male predominance for Hodgkin's disease versus non-Hodgkin's lymphoma (P = 0.029, exact Fisher test), and B symptoms in non-Hodgkin's lymphomas (P = 0.056), whereas B symptoms are commonly seen in advanced stages of Hodgkin's disease. It is emphasized that all Hodgkin's disease of lymphocyte-depletion type should be reviewed and discussed before any treatment, and this diagnosis actually means non-Hodgkin's lymphoma or other types of Hodgkin's disease.

Adenomyoepithelioma of the breast is a rare tumor that, on the basis of histologic, immunohistochemical, and ultrastructural features, has a bicellular pattern of epithelial and myoepithelial cells regularly distributed in tubular structures. Until now, this tumor was thought to be a benign or low-grade malignant lesion because of possible local recurrences (7 recurrent cases of 60 in the literature). Only one of these cases had nodal involvement, thereby suggesting the possible malignancy of this lesion. This paper reports the first documented case of malignant adenomyoepithelioma with lung metastases presenting the same biphasic pattern as the primary tumor.

Special techniques such as serial macroscopic sectioning (SMS) or immunohistochemical staining (IH) improve the detection rate of micrometastases but this detection is of value only if it improves the prediction of recurrence and survival. We first studied the prognosis of 120 patients with a single micrometastasis detected by SMS in a series of 1,680 primary operable breast carcinoma with a median follow-up of 7 years. A significant difference in recurrence (P = 0.005) and in survival (P = 0.0369) was found between node-negative patients and those with one single SMS micrometastasis, but SMS micrometastases were not a predicting factor by multivariate analyses according to the Cox model. We then studied the prognostic significance of patients with a micrometastasis detected by IH in node-negative carcinoma: 37 micrometastases from a series of 89 invasive lobular carcinoma (ILC) and 13 single micrometastases from a series of 129 invasive ductal carcinoma (IDC). In the ILC group, IH micrometastases had no prognostic value (median follow-up: 9.3 years). In the IDC group, IH micrometastases were correlated with recurrences (P = 0.01) and were the most significant predicting factor, but were less correlated with survival (median follow-up: 15.6 years). Three main points emerge from this study: (1) SMS micrometastases have a prognostic significance and macroscopic sectioning is recommended as a routine technique not requiring excessive work. (2) IH micrometastases in infiltrating lobular carcinoma have no prognostic significance. (3) The value of IH is debatable in infiltrating ductal carcinoma, since the technique is of principal use in predicting recurrences. It should therefore be carefully assessed vs other prognostic factors currently under study.

During a period of 15 years, 6 cases of dedifferentiated liposarcomas were found among 542 cases of adult soft tissue sarcomas, 77 of which were liposarcomas. They were huge tumors of the retroperitoneum, containing distinct areas of well-differentiated liposarcoma most often of sclerosing type and malignant fibrous histiocytoma or undifferentiated sarcoma most often of high grade malignancy. Immunohistochemistry on the dedifferentiated component showed a positivity with anti-vimentin and alpha-1-antichymotrypsin in 5 cases and with anti-alpha smooth muscular actin in 4 cases. Three patients developed local recurrence and a fourth one quickly died with bone metastasis. Other types of dedifferentiated sarcomas, the process of dedifferentiation and links between malignant fibrous histiocytoma and dedifferentiated sarcomas are discussed.

Eight patients with breast metastases from primary tumors other than breast carcinoma were studied: 3 malignant melanomas, 2 rhabdomyosarcomas, 1 malignant mesothelioma, 1 appendiceal carcinoid, and 1 epidermoid cervical carcinoma. All had mammographic, histopathologic, and immunohistochemical examinations. The main problem was differential diagnosis from primary breast carcinoma. History of extramammary primary tumor was helpful but breast metastasis was the first clinical feature in 2 cases. Patients had noticed palpable, round, rapid growth masses which were mammographically benign. Pathologic diagnosis was difficult and immunohistochemical studies necessary, whenever the proliferation had histologic features of primary breast carcinoma or when no primary tumor was known. However, some histologic features were of value for diagnosis of metastasis: atypical histologic features for a primary breast carcinoma, a well-circumscribed tumor with multiple satellite foci, the absence of an intraductal component, and the presence of many lymphatic emboli. In adults, the most frequent types of tumors metastasizing in the breast are malignant melanoma and neuroendocrine-like tumors, especially small cell carcinoma and carcinoid. In children, rhabdomyosarcoma is the most common. Accurate diagnosis of breast metastasis is important to avoid unnecessary mastectomy and to implement an appropriate systemic therapy.

An immunohistochemical study of 5 cases of adenoid cystic carcinoma (ACC) of the breast was performed with antibodies against keratin, EMA, vimentin, S-100 protein, alpha-smooth muscle actin and collagen IV. Results show the following: 1) ACC may be diagnosed and differentiated from ductal carcinoma (invasive or in situ). The key to diagnosis is positivity within tumor masses of alpha-smooth muscle actin, a specific marker for myoepithelial cells. Actin-rich cells are not generally observed in ductal carcinomas, except at the periphery of a few invaded ducts, corresponding to a residual myoepithelial cell layer. Other markers may be positive in both ACC and ductal carcinoma; these are not specific and only the percentage and distribution of positive cells are helpful for diagnosis (small clusters of keratin-positive cells in ACC "versus" most positive cells in ductal carcinoma). 2) The functional pleomorphism of the cell population is underlined with cells differentiating towards epithelium and myoepithelium stained by corresponding markers, and undifferentiated cells unstained by any marker. These results confirm the value of an immunohistochemical study in the diagnosis of ACC of the breast.

The purpose of this report is to assess whether phenotyping by three monoclonal antibodies routinely used in paraffin sections (Ber-H2-Leu-M1-EMA) and shown to be the most useful for diagnosis may be a predictive factor for recurrences. Among 563 patients diagnosed as having Hodgkin's disease (24% of whom had recurrence), we selected 153 patients with and without recurrence, with matching clinical stage. For all of these cases, histologic material was tested by immunostainings with satisfactory control samples. No phenotype was specific for Hodgkin's disease, although the phenotype Ber-H2-Leu-M1-EMA was predominant. No phenotype was found to be a predictive factor for recurrences, and none was unchanged during the clinical course, except when recurrence occurred as non-Hodgkin's lymphoma.

Five cases of primary non-Hodgkin's lymphomas of the breast (stage IE in the Ann Arbor staging system) are described. No clinical or radiological feature has permitted to make the diagnosis before surgery. Histologically, all lymphomas are diffuse and B type. Three cases are high grade lymphomas, one of lymphoblastic type. Two cases are of lymphoplasmacytoid type, one of them associated with an occult invasive ductal carcinoma within the same breast, the other changing in high grade lymphoma at the recurrence time. Three of them reveal histological aspects of lymphoepithelial lesions and appear as mucosa-associated lymphoid tissue lymphomas (MALT). The differential diagnosis with a carcinoma is now easily done by immunohistochemical techniques. The importance of a diagnosis before surgery by cytopunction and drill-biopsy has to be emphasized, to prevent an useless mastectomy.

Fourty-one patients underwent breast reconstruction after mastectomy for cancer and reduction plasty of the second breast, over a 36-month period. These plasties were performed only for reasons of asymmetry, in the absence of any positive preoperative finding. Histologic examination using semiserial sectioning of the whole excised sample detected a high frequency of unsuspected cancer 14/41 (34%). There was a strong predominance of in situ carcinomas 11/41 (27%) over invasive carcinomas 3/41 (7%). These results were compared with those of other bilateral cancer series. When such cancers were detected by random biopsies or mastectomies, the rate of in situ carcinomas was much greater than in cancers detected only by physical and mammographic examination.