Impact of immunohistochemical markers, CK5/6 and E-cadherin on diagnostic agreement in non-invasive proliferative breast lesions.

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.

[Male breast cancer: a review of 52 cases collected at the Institute Bergonié (Bordeaux, France) from 1980 to 2004]. / Cancers du sein chez l'homme: à propos de 52 cas pris en charge à l'institut Bergonié de Bordeaux entre 1980 et 2004.

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.

Risk factors for recurrence and metastasis after breast-conserving therapy for ductal carcinoma-in-situ: analysis of European Organization for Research and Treatment of Cancer Trial 10853.

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.

Current treatment of Hodgkin's disease.

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.

Obvious peritumoral emboli: an elusive prognostic factor reappraised. Multivariate analysis of 1320 node-negative breast cancers.

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.

Malignant adenomyoepithelioma of the breast. An immunohistochemical, cytophotometric, and ultrastructural study of a case with lung metastases.

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.

Analysis of 676 cases of ductal carcinoma in situ of the breast from 1971 to 1995: diagnosis and treatment--the experience of one institute.

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.

Prognostic value of phenotyping by Ber-H2, Leu-M1, EMA in Hodgkin's disease.

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.

Adenoid cystic carcinoma of the breast. Value of immunohistochemical study in diagnosis.

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 incidence of cancer in contralateral reduction mammaplasty after mastectomy and reconstruction of the removed breast.

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.

The value of immunohistological techniques in undifferentiated cancers.

From 1980 to 1984, we observed 144 undifferentiated cancers, of which 116 (0.9% of all cancers treated during this period) were treated in our center. Immunohistochemical study classified 130 tumors (90%), which comprised 82 non-Hodgkin's lymphomas (57%), 32 carcinomas (22%), 7 melanomas (5%), 7 sarcomas (5%) and 2 others (1%). Sixty-nine patients, with the diagnostic problem of non-Hodgkin's lymphoma versus carcinoma, which was solved by immunohistology, were followed up for 44 +/- 20 months. Lymphomas (57 cases) had a better clinical course than carcinomas (11 cases), and a clinical course similar to high-grade lymphomas identified by conventional histology. For 66 patients with the same problem, the treatment was started before the immunohistochemical diagnosis. This treatment was inappropriate in the light of the correct diagnosis in 16 of 66 cases (24% of all cases).

[Analysis of 1125 partial breast resections for diagnostic purposes. Occurrence of cancer and its histology]. / Analyse de 1 225 exérèses mammaires partielles à visée diagnostique. Incidence du cancer et contexte histologique.

One thousand two hundred and twenty-five partial breast resections, examined in serial gross sections have been retrospectively reviewed. The percentage of benign lesions in comparison with malignant lesions is 70 per cent-30 per cent. The percentage of malignant lesions is maximum (43%) in clustered microcalcifications which are so the best criteria of malignancy. A diagnosis of non infiltrating carcinoma has been misdiagnosed at the first examination in 6 per cent of cases. This misdiagnosis is partially explained by very small foci of carcinoma and recent recognition of certain histological types of early carcinoma. It must be noticed the unsuspected frequence of carcinoma (17%) detected by random in ipsilateral breast tissue from plastic surgery, after controlateral reconstruction for carcinoma. The analysis of benign lesions associated with carcinoma shows a significative frequent association with carcinoma in two types of lesion: radial scar and late phase of blunt duct adenosis.

[Contribution of drill-biopsies to pre-treatment investigation of breast adenocarcinomas (author's transl)]. / Apport de la drill-biopsie dans le bilan préthérapeutique des adénocarcinomes mammaires.

The sensitivity of drill-biopsies (Rousseau's technique) was studied before using them routinely in pre-treatment investigation of breast adenocarcinomas. Results of histological examination, and estrogen (ER) and progesterone (PR) receptors levels obtained preoperatively by this technique, were compared with those from the corresponding mastectomy or tumourectomy specimens in 85 cases. Cytological examination of the various specimens, performed on prints, was used to compare their cellular density. Measurement of receptors included the determination of cytosolic and nuclear sites, and was performed by the single point dextran charcoal method. The limits of positivity established for ER and PR were 10 and 15 fM/mg protein respectively. The results showed sensitivity of 91.8 p. cent for pathology examinations; furthermore, the Scarff-Bloom-Richardson histoprognosis grading could be performed satisfactorily on drill-biopsy specimens. No significant difference was observed between the percentage of positivity for ER and PR from surgical and drill-biopsy specimens. Good correlation existed between values obtained from drill-biopsy and from surgery both for ER (r = 0.86, p less than 10(-5)) and PR (r = 0.86, p less than 10(-5)).

[Lymphoid depletion type 4 Hodgkin disease. Anatomoclinical review of 35 cases]. / Maladie de Hodgkin type 4 à déplétion lymphoïde. Révision anatomoclinique de 35 cas.

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.

[Axillary lymph nodes in breast cancer. Comparison of standard histological analytical technics and macroscopic serial sections]. / Ganglions axillaires dans les cancers du sein. Comparaison des techniques d'analyse histologique standard et en coupes macroscopiquement sériées.

Lymph nodes in breast cancer have been examined by two histological techniques in 324 patients who underwent axillary node dissection. A routine pathologic examination consisted in the examination of only one pathological section while in the other, the lymph nodes were macroscopically serially sectioned. With the latter, an increase of 18.8 per cent in the number of detected metastases was noted. However this increase can be considered of prognostic and therapeutic importance only in 8.6 per cent of cases: half corresponding to those cases in which more than the initial threshold number of three lymph nodes were found, the other half corresponding to those cases in which one lymph node was found while the initial examination was negative. In the latter case, the increase of lymph node involvement was mainly due to "clandestine" metastases, i.e. lymphatic embolisation of micrometastases.

[Histological types of 876 breast cancers according to the 1981 WHO classification]. / Types histologiques de 876 cancers du sein selon la classification de l'OMS 1981.

This work presents the results of the classification by histological types of 876 cancers, operated on between November 1979 and December 1982, according to the new WHO's classification of 1981. Noninfiltrating cancers represent 6.5 per cent of the total. Among the infiltrating cancers (93.5%), the individualization of the type "infiltrating duct carcinoma with a marked intraductal component" (14.5%) is interesting for this form justifies a special treatment in consideration of its multicentric and sometimes bilateral character. Its purely quantitative criteria of definition is subject to criticism and discussion.

[Primary malignant non-Hodgkin's lymphoma of the breast. A study of 5 cases]. / Lymphomes malins non hodgkiniens primitifs du sein. Etude de cinq cas.

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.

[Osteoclastic type giant cell carcinoma of the breast]. / Carcinome mammaire à cellules géantes de type ostéoclasique.

Five cases of mammary carcinoma with osteoclast-like giant cells are reported. This study as well as review of the literature underline characteristic features of this rare histological type of carcinoma: a round well-circumscribed dense nodule of benign appearance on mammograms in half of the cases; brown colour of tumour specimens; stromal hypervascularity; negativity of epithelial, vascular and most histiocytic immunohistochemical markers in giant cells; positivity of leucocyte common antigen and vimentin in giant cells. Giant cells most probably originate from the fusion of histiocytic type mononucleated stromal cells, but results of immunohistochemical stainings cannot actually bring formal arguments to support this hypothesis.

[Dedifferentiated liposarcoma. A clinico-pathologic study of 6 cases]. / Liposarcome dédifférencié. Etude anatomoclinique de 6 cas.

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.

[Histological changes after chemotherapy of soft tissue sarcomas in the adult]. / Modifications histologiques après chimiothérapie des sarcomes des tissus mous de l'adulte.

The variations of histologic patterns inside the primary tumor have been studied in 15 patients with locally advanced soft tissue sarcomas who were given induction (neo adjuvant) chemotherapy. Increase of tumor necrosis and decrease of tumor cellularity were the predominant aspects identified. The mitosis count tend to be lower, while the nuclear atypies and the number of giant malignant cells tend to increase. In 2 cases, a better tumor differentiation, attributable to the induction chemotherapy was noted. In 10/15 cases, it was concluded to a tumoricidal effect of the chemotherapy. According to tumor grade, 6 among 10 patients with grade III tumor presented a histological response (greater than 50 p. cent of tumor destruction) while none among 5 lesions of grade I or II exhibited a response of such a level. So, the histological study allows an evaluation of the response to chemotherapy which usefully completes the clinical appreciation, and that may be useful for the selection of postoperative adjuvant treatment, as it is in osteosarcomas.