The poor responsiveness of infiltrating lobular breast carcinomas to neoadjuvant chemotherapy can be explained by their biological profile.

The aim of this study was to determine the chemosensitivity of infiltrating lobular breast carcinoma (ILC) in comparison with infiltrating ductal carcinoma (IDC). Between 1987 and 1995, 457 patients with invasive T2>3 cm-T4 breast carcinomas were treated with primary chemotherapy (CT), surgery, radiation therapy. Clinical response, the possibility of breast preservation, pathological response and survival were evaluated according to the histological type. In order to evaluate the biological differences between ILC and IDC patients and their implication with regard to tumour chemosensitivity, additional immunohistochemical stainings (oestrogen receptor (ER), Bcl2, p53, c-erbB-2 and Ki67) were performed on 129 pretherapeutical specimens. 38 (8.3%) ILC were diagnosed by core needle biopsy before CT. ILC was an independent predictor of a poor clinical response (P=0.02) and ineligibility for breast-conserving surgery after neoadjuvant chemotherapy (P=0.03). Histological and biological factors predicting a poor response to CT (histological grade, ER, Ki67 and p53 status) were more frequent in ILC than in IDC patients. After a median follow-up of 98 months (range: 3-166), the low chemosensitivity of ILC did not result in a survival disadvantage. Our results demonstrate that ILC achieved a lower response to CT than IDC because of their immunohistochemical profile. Preoperative CT did not allow a high rate of conservative treatment for ILC and therefore the use of neoadjuvant CT for ILC patients should be questioned.

Predictive factors for local recurrence in 2006 patients with surgically resected small breast cancer.

BACKGROUND: Analyses of predictive factors for local recurrences are important, as an increasing number of patients with early breast cancer opt for a breast-conserving procedure. This study investigates whether factors predictive of local recurrence differ between patients treated with conservative or radical surgery. PATIENTS AND METHODS: Two thousands and six patients with invasive breast carcinoma (< or =25 mm) were included. Of these patients, 717 were treated conservatively (lumpectomy and breast irradiation) and 1289 were treated with total mastectomy. All patients had axillary dissection and received lymph node irradiation if axillary nodes were positive. Most patients did not receive adjuvant chemotherapy or additive hormonal treatments. The mean duration of follow-up was 20 years. The main end point was the total local recurrence rate. The risk factors of local recurrence were estimated by multivariate analyses and interaction tests were used for intergroup comparisons. RESULTS: Statistically significant predictive factors for mastectomized patients were histological grade, extensive axillary node involvement (10 nodes or more), and inner quadrant tumors, which were of borderline significance. Young age, however, was not a prognostic indicator for local recurrence. The main statistically significant factor for patients treated with a conservative approach was young age (< or =40 years). These younger patients had a five-fold increased risk of developing a breast recurrence compared with patients older than 60 years. CONCLUSIONS: Younger patients with early breast cancer treated with breast-conserving surgery should in particular be followed up at regular intervals so that any sign of local failure can be diagnosed early.

["Micrometastases": the pathologist's point of view]. / "Micrométastases": le point de vue de pathologiste.

The development of cancer screening has led to the discovery of smaller tumours and less frequent dissemination to lymph nodes and organs that requires special techniques for detection. Numerous papers on micrometastases reflect a considerable amount of work devoted to detection methods, technical problems and the prognostic value of these lesions. Apart from cytological techniques, the pathologist can rely on two methods for the detection of micrometastases: serial slicing of paraffin-embedded blocks and immunohistochemistry. When these methods are combined, the detection rate is similar to that of biological methods and can attain levels as high as 60% for the sentinel node with the added vantage of being able to visualise cells. Despite an impressive body of studies, major disparities are found in detection rates and the prognostic value of micrometastases is not firmly established. In order to facilitate comparisons and analyses, it is essential to adopt a common terminology with precise definitions. The UICC advocates the use of the term micrometastasis which denotes a metastasis smaller than or equal to 2 mm in size. The potential aggressiveness of micrometastases is dependent on other poorly explored parameters such as the number of cells detected in the bone marrow or lymph node and the location of micrometastases. The new pTNM classification takes into account this latter parameter and distinguishes two categories of micrometastases: "isolated tumor cells" located in the lumen of vessels or sinuses and "micrometastasis" which has already invaded an organ. This classification warrants further analysis to determine the prognostic value of these categories. The next challenging problem consists in determining the key biological properties that account for distant dissemination.

Detection of Epstein-Barr virus in invasive breast cancers.

BACKGROUND: Epstein-Barr virus (EBV) may be a cofactor in the development of different malignancies, including several types of carcinomas. In this study, we investigated the presence of EBV in human breast cancers. METHODS: We used tissues from 100 consecutive primary invasive breast carcinomas, as well as 30 healthy tissues adjacent to a subset of the tumors. DNA was amplified by use of the polymerase chain reaction (PCR), with the primers covering three different regions of the EBV genome. Southern blot analysis was performed by use of a labeled EBV BamHI W restriction fragment as the probe. Infected cells were identified by means of immunohistochemical staining, using monoclonal antibodies directed against the EBV nuclear protein EBNA-1. RESULTS: We were able to detect the EBV genome by PCR in 51% of the tumors, whereas, in 90% of the cases studied, the virus was not detected in healthy tissue adjacent to the tumor (P<.001). The presence of the EBV genome in breast tumors was confirmed by Southern blot analysis. The observed EBNA-1 expression was restricted to a fraction (5%-30%) of tumor epithelial cells. Moreover, no immunohistochemical staining was observed in tumors that were negative for EBV by PCR. EBV was detected more frequently in breast tumors that were hormone-receptor negative (P =.01) and those of high histologic grade (P =.03). EBV detection in primary tumors varied by nodal status (P =.01), largely because of the difference between subjects with more than three lymph nodes versus less than or equal to three lymph nodes involved (72% versus 44%). CONCLUSIONS: Our results demonstrated the presence of the EBV genome in a large subset of breast cancers. The virus was restricted to tumor cells and was more frequently associated with the most aggressive tumors. EBV may be a cofactor in the development of some breast cancers.

[Primary cutaneous leiomyosarcoma: 32 cases]. / Léiomyosarcomes cutanés primitifs: 32 cas.

BACKGROUND: Superficial leiomyosarcomas are rare tumors, which may be confined to the dermis or extend to subcutaneous tissues. PATIENTS AND METHODS: We report the results of a retrospective study of 32 patients treated for leiomyosarcomas through a twenty-two year period (from 1975 to 1997). RESULTS: Mean age was 45 years, with 50 p. 100 of patients less than 35 years of age. Forty seven percent of the tumors were located on the lower limbs and mean diameter was 2.8 cm. Three clinical types have been isolated: nodule beneath normal epidermis (50 p. 100), purple nodule ulcerated or not (28 p. 100), swelling tumor (22 p. 100). Sixteen percent were intradermal, whereas sixty nine percent involved subcutaneous tissues. With regard to tumor grade, 37 p. 100 of tumors were grade I, 44 p. 100 of tumors were grade II, and 19 p. 100 were grade III. Immunohistochemical staining showed positive reactions for all tumors with anti-vimentin and anti-alpha smooth muscle actin. Main treatment was complete surgical excision. Follow-up informations were available for all patients and 75 p. 100 of them had a follow up period longer than a year. Five patients with leiomyosarcomas involving the subcutis developed local recurrences, and two of them died of the disease. DISCUSSION: Leiomyosarcomas can occur at any age without predominant sex-ratio. Main prognostic factors are tumor size, distal location, depth of tumor invasion and pathological grade. Immunohistological staining with anti-alpha smooth muscle actin is more sensitive and specific than with anti-desmin or anti-HHF 35. Main treatment is surgical excision with wide margins.

Does long-term exposure to gel-filled silicone implants increase the risk of relapse after breast cancer?

BACKGROUND: An increased risk of cancer and autoimmune diseases associated with gel-filled silicone implants, debated by FDA experts since 1991, has given rise to a profusion of literature on the subject. However, such effects have not been adequately investigated in patients with breast cancer. In a previous report we compared 146 breast cancer patients with gel-filled silicone implants for breast reconstruction to 146 control patients in whom no reconstruction had been performed. The observed results were reassuring, as the evolution of the disease after 10 years was better in the reconstruction group than in the control group. We now report the end results of this study with a median follow-up of 13 years after the breast reconstruction (range, 10-20 years). METHOD: The relative risks of detrimental events were estimated with Cox's Proportional Hazards Model, with stratification according to age at diagnosis. RESULTS: The risks of locoregional recurrences and distant metastasis were significantly lower in the BR group than in the control group. The risks of death, of a second breast cancer and of a second primary cancer at a site other than the breast were not significantly different between the two groups of patients. CONCLUSION: Long-term follow-up of patients exposed to gel-filled silicone implants confirms the absence of detrimental effects after breast cancer. The power of our study is, however, below that required to detect a very slight increase in the risks studied.

Adjuvant chemotherapy for primary cardiac sarcomas: the IGR experience.

The effect of additional treatments after surgery in patients with primary cardiac sarcoma (PCS) remains unknown. The present study aims to evaluate the benefit of chemotherapy in patients with non-metastatic cardiac sarcomas after optimal resection. Between October 1979 and December 1995, 15 patients with a median age of 45 (range 16-66) and a resected primary cardiac sarcoma [angiosarcoma (six), malignant fibrous histiocytoma (three), leiomyosarcoma (two), rhabdomyosarcoma (two), liposarcoma (one) and synoviosarcoma (one)] received a doxorubicin-containing regimen within 6 weeks of surgery. Adjuvant chemotherapy combinations included cyclophosphamide, vincristine and dacarbazine in four patients; ifosfamide in nine; methotrexate and vincristine in one; and doxorubicin alone in one patient. At present, 13 patients have relapsed (five during therapy), with a median time to progression of 10 months. Twelve patients developed local relapse, in four cases without metastatic disease. Two patients remain in complete remission 27 and 25 months after surgery. The median time to progression was shorter in patients presenting a cardiac angiosarcoma than other histological types (3 vs 14 months, P < 0.01). Twelve patients have died, with a median overall survival of 12 months. The 2-year survival rate is 26%. Survival was significantly longer for patients with completely resected tumours (22 vs 7 months; P = 0.02) and those who did not have angiosarcoma (18 vs 7 months; P = 0.04). In conclusion, post-operative conventional doxorubicin-based chemotherapy failed to modify the natural history of patients with resected cardiac sarcomas. Locoregional failure remains the main problem even after histologically complete resection. New approaches must be tested in patients with primary cardiac sarcoma.

[Pathological anatomy of breast cancers]. / Anatomie pathologique des cancers du sein.

Carcinomas are by far the most frequent malignant tumors of the breast. Screening by mammography has considerably increased the number of breast biopsies for mammographic abnormalities without a palpable mass. The role of the pathologist is to: 1. accurately diagnose specimens and ensure quality control, and 2. provide clinicians with all the informations required for staging and appropriate treatment without being led astray by the new prognostic factors based on biological markers in fashion.

Contralateral mastoplasty for breast reconstruction: a good opportunity for glandular exploration and occult carcinomas diagnosis.

BACKGROUND: Exploration of the contralateral breast in case of breast cancer has been advocated by many investigators, based on the incidence of contralateral cancer expected to be around 10-15%. METHOD: From 1978 to 1993, 813 contralateral mammaplasties were performed to obtain symmetry in the course of breast reconstruction, including 373 mastopexies and 440 reduction mammaplasties (RMs). All these operations were performed in patients treated for a cancer of the opposite breast. Clinical and radiologic examination before the reduction mammaplasty showed tissue to be free of evident tumor. RESULTS: Twenty clinically and radiologically occult contralateral cancers were found in the reduction specimen (4.6%). Most of them were located in the lower and central quadrants (70%). The macroscopic size of the tumors varied from 3 to 16 mm. Twelve carcinomas were in situ, and eight cases were infiltrating. CONCLUSION: The symmetry procedure allows a good check-up of the glandular tissue of the contralateral breast at the time of the breast reconstruction, especially when there is no evidence of tumor. The different techniques of breast reduction provide specific possibilities for such exploration and should be chosen according to the preferential area that should be explored.

Predictive factors for complete removal in soft tissue sarcomas: a retrospective analysis in a series of 592 cases.

BACKGROUND AND OBJECTIVES: In order to specify the indications for conservative surgery and preoperative therapeutic approaches of soft tissues sarcomas (STS), we looked for the clinico-pathological parameters associated with the failure to obtain a complete removal (CRm) of the tumor. METHODS: We retrospectively analyzed a series of 592 cases of primary non-metastatic STS. Surgery was performed in 495 cases as a primary treatment and in 88 cases after chemo- or radiotherapy. Nine patients were treated by chemotherapy-radiotherapy. In a univariate analysis, 20 parameters were tested for their association with CRm. A multivariate analysis was then used to define the independent parameters linked to the achievement of a CRm. RESULTS: In the univariate analysis, 15 parameters were found to be linked to the achievement of a CRm. Three of them proved to be independent in the multivariate analysis: T in the TNM classification, tumor location, and tumor necrosis. By the combination of these risk factors, four groups of patients were defined, with respective rates of CRm of 97% (no factor), 95% (one factor), 70% (two factors), and 48% (three factors). CONCLUSIONS: The achievement of a CRm after surgery of STS depends not only on the accessibility of the lesion, but also on tumor aggressiveness, a reflection of which is necrosis. The detection of necrosis by imaging procedures may thus help predicting the resectability of tumors and defining the indications for neoadjuvant therapies, likely to broaden the use of conservative surgery.

[Angiosarcoma of the breast. Apropos of 8 cases and review of the literature]. / Les angiosarcomes du sein. Etude de 8 cas et revue de la littérature.

The 8 cases of primary breast angiosarcoma which were diagnosed, treated and had their follow-up at the Gustave-Roussy Institute between 1954 and 1995 are reported. The age at presentation ranged from 32 to 68 years. In 4 patients the vascular nature of their mammary lesion was conspicuous by a violaceous discolorations of the overlying skin. No patient had enlarged ipsilateral axillary lymph nodes. One patient had metastases. In 2 out of 5 patients who had a partial surgical or fine-needle biopsy before treatment, the diagnosis was missed, and adequate treatment was unduly delayed. The tumor most often presents as an ill defined area made of dense endothelium-lined papillae. A remarkable picture of "soap bubbles" has been identified in 4 cases. The "meshes" of fatty areas appear to be reinforced as they are infiltrated by tumor cells. This appearance may be specific of mammary angiosarcoma. By the French Cancer Centers' grading system for soft tissue sarcomas in general, grade is III in 3 tumors, II in 2 tumors, I in 3 tumors. Five tumors were treated by total mastectomy only. In 3 cases a total mastectomy was followed by radiation therapy to the chest wall. At diagnosis a chemotherapy was administered only to the patient who had metastases. Median disease-free survival was 9 months. Median overall survival was 13 months. From a review of the literature a simple mastectomy appears to be necessary as well as enough for local treatment. Patients with a grade III angiosarcoma of the breast should be included into a therapeutical trial of adjuvant chemotherapy for soft tissue sarcomas in general.

[Recurrence of giant-cell fibroblastoma as dermatofibrosarcoma protuberans in the adult]. / Récidive d'un fibroblastome à cellules géantes de l'enfant sous forme de dermatofibrosarcome protubérant à l'âge adulte.

Giant cell fibroblastoma is a rare, subcutaneous tumor of children. Local recurrences frequently occur after surgical excision, occasionally taking the form of dermatofibrosarcoma protuberans. An immunohistochemical study is associated in this case report.

Polyhedral microcalcifications on mammograms: prevalence and morphometric analysis.

OBJECTIVE: The purpose of this study was to determine the incidence and the mammographic appearance of polyhedral microcalcifications. MATERIALS AND METHODS: Prospectively, we evaluated screening mammograms in 2000 women for polyhedral microcalcifications. The number of polyhedral microcalcifications on routine and magnification views was established, and a quantitative analysis was done to determine if the shape of the polyhedral microcalcifications varied in the different projections. The ratio between the longer axis (R) and the shorter axis (r) was calculated. RESULTS: Two radiologists detected at least two polyhedral microcalcifications on one projection in 58 (3%) women. The number of polyhedral microcalcifications detected ranged from 2 to 47 (mean, 8.2) for screening mammograms and from 2 to 62 (mean, 13.4) on magnification views. Polyhedral microcalcifications were bilateral in 22 cases, scattered in one breast in 19 cases, segmental in 10 cases, and grouped in a cluster in seven cases. Lateral projections showed more rhombohedral microcalcifications, and craniocaudal projections showed more square microcalcifications. CONCLUSION: The frequency of polyhedral microcalcifications is 3%. The shape of polyhedral microcalcifications varies: craniocaudal views show them to be square and lateral views show them to be rhombohedral.

Histology, immunohistochemistry, and electron microscopy of small round cell tumors of bone.

Small round cell tumors (SRCTs) of the bone make up a family of primary bone sarcomas with morphologically, biologically, and clinically specific features. Among them, Ewing's sarcoma (ES) is the most common entity, but several varieties such as atypical ES, large cell ES, and ES with neuroectodermal differentiation (peripheral primitive neuroectodermal tumor of the bone or neuroepithelioma of the bone) have been identified recently. Histology and electron microscopy together with the variable expression of several epitopes (as shown by immunohistochemistry, mainly HBA/71 [Mic2 antigen]) provide the basis for characterizing the group within the context of neuroectodermal-derived neoplasms. A number of other ES-like tumors with small round cells, mimicking those previously described, have been characterized; Askin's tumor of the thoracopulmonary region will be considered as an ES similar to those already described, but within a particularly anatomic location. On the other hand, the presence of an endothelial appearance within a poorly differentiated neoplasm may be present in some ES-like SRCTs (atypical ES with endothelial features). The differential diagnosis with other sarcomas defined by small round to spindle cell contours might prove difficult. Particular attention must be paid to small cell osteosarcoma and mesenchymal chondrosarcoma. Likewise, "primitive sarcoma of bone" is considered in this study because it is a very rare neoplasm differing from the formerly discussed types; its pluripotentiality provides this tumor a blastemic character and a multiphenotypic expression. Malignant non-Hodgkin's lymphoma is an unusual presentation when primary to the bone, previous to any other anatomic location. Several subtypes have been considered within a histology that encompasses that seen in lymph nodes.

Small round blue cell tumors in bone: prognostic factors correlated to Ewing's sarcoma and neuroectodermal tumors.

Ewing's sarcoma and peripheral neuroectodermal tumors are the most common small round blue cell tumors of bone. Accurate prognostic factors are required to define guidelines to standardize the treatment modalities and to adapt these modalities to the potential evolution of the disease. The various factors that have emerged in the literature as influences on the outcome of patients with Ewing's sarcoma or peripheral neuroectodermal tumors of bone are considered in this review. The presence of metastases at the clinical onset of the disease represents the most adverse prognostic factor. For nonmetastatic patients, axial location appears to be the most unfavorable factor, despite initial tumor volume, by showing that the tumor burden could be a more appropriate indicator of patient outcome. The importance of a local control of the disease by surgery has been emphasized, and the value of the histopathologic evaluation of the response to chemotherapy has been stressed.