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Biomedical subjects

J M Guinebretière

Publications and source records attributed to J M Guinebretière.

At least 19 recordsLinked to original sources

Response to neoadjuvant chemotherapy in lobular and ductal breast carcinomas: a retrospective study on 860 patients from one institution.

BACKGROUND: We compared the impact of neoadjuvant chemotherapy on pathologic response and outcome in operable invasive lobular breast carcinoma (ILC) and invasive ductal breast carcinoma (IDC). PATIENTS AND METHODS: We extracted from our database all patients with pure invasive lobular (n=118, 14%) or pure invasive ductal carcinomas (n=742, 86%). Their treatment included neoadjuvant chemotherapy, adapted surgery, radiotherapy and adjuvant hormonal treatment. RESULTS: Compared with IDC, ILC presented with larger tumors (T3: 38.1% versus 21.4%, P=0.0007), more N0 nodes status (55.9% versus 43.3%, P=0.01), less inflammatory tumors (5.9% versus 11.8%, P=0.01), more hormone receptor positivity (65.5% versus 38.8%), lower histological grade (P<0.0001). Final surgery was a mastectomy in 70% of patients with ILC (34% were reoperated after initial partial mastectomy) and in 52% of IDC after 8% of reoperation (P=0.006). A pathological complete response (pCR) was achieved in 1% of ILC and 9% of IDC (P=0.002). The outcome at 60 months was significantly better for ILC, but histologic type was not an independent factor for survival in multivariate analysis. CONCLUSIONS: ILC appeared less responsive to chemotherapy but presented a better outcome than IDC. While new information on biological features of ILC is needed, we consider that neoadjuvant endocrine therapy in hormone receptor-positive ILC may be a more adapted approach than neoadjuvant chemotherapy.

Breast Neoplasms↗

[Local recurrence of ductal carcinoma in situ after conservative breast surgery: mammographic appearance].

OBJECTIVE: To review the mammographic features of local recurrences of DCIS treated conservatively. MATERIALS AND METHODS: Thirty-five patients treated conservatively for a DCIS have presented subsequently a local recurrence. Three patients had double metachronous and one a bi-focal recurrence. The mammographic appearances of these 39 recurrences were analyzed retrospectively and compared to initial mammograms. RESULTS: Median delay to recurrence was of 47 months (interval 8-240 months). Two-thirds of the recurrent lesions were similar to the initial presentation, of which 90% occurred at the lumpectomy site. In 18/ 35 cases (51%), an intra-ductal component was found at histological diagnosis and among these 11/18 (61%) were strictly intra-ductal. CONCLUSION: Local recurrences of DCIS are proteiform. However, the majority of which, occurring at the lumpectomy site were similar to the primary tumor, raising again the hypothesis of incomplete eradication even when the margins were considered free.

Adult↗

Use of radiology for the pathologist in the management of breast lesions.

Today radiology is an essential step in the pathological analysis of breast biopsies. It is determinant at each stage of the management of non palpable lesions, clusters of microcalcifications and opacities, whether this concerns the needle biopsy or the surgical excision. Firstly, an X-ray is necessary to ensure that the core needle biopsy specimen has been adequately sampled and when samples with microcalcifications are selected by the radiologist, management can be more specific and accurate. In the case of surgical specimens, the X-ray confirms the presence of the radiographic abnormality or the clip indicating the site of the surgical excision which guides sampling. Some radiographic features also provide information on underlying pathologies allowing management to be adapted accordingly. Radiographs are also important to ensure that microscopically detected microcalcifications or lesions exactly correspond to the radiographic abnormality in size and location. The paraffin block can also be X-rayed to select those containing microcalcifications for additional slicing. It is also important to identify the presence of modifications caused by the core needle biopsy (fibrosis, haemorrhage and inflammation) and to carefully recognize displacement of epithelial cells and pseudo-emboli resulting from the needle procedure. Such correlation between radiology and pathology is essential so that appropriate management of the specimen can be adapted and to avoid pitfalls arising from pre-operative procedures.

Biopsy, Needle↗

Normal and pathological breast, the histological basis.

Breast tissue is heterogeneous, associating connective and glandular structures, which grow and change cyclically under hormonal regulation. Hormones are also thought to be the main determinant of the major benign and malignant pathologies encountered in the breast. Benign lesions are more frequent and fibrocystic changes are by far the most common among them. They usually associate different entities, (adenosis, fibrosis, cysts and hyperplasia) but vary in intensity and extension. Thus, their clinical and radiographic presentation is extremely different from one patient to another. Adenofibroma is the most frequent tumour. It also undergoes modifications according to hormonal conditions. About 90% of malignant tumours are primary carcinoma. The incidence of intra-ductal carcinoma has risen dramatically since the development of screening because of its ability to induce calcification. Two mechanisms could be involved in the formation of calcification: one active (tumour cell secretion of vesicles), the other passive (necrotic cell fragments are released). Invasive carcinoma comprises numerous histological types. Stromal reactions essentially determines their shape: a fibrous reaction commonly found in ductal carcinoma creates a stellate lesion while other stroma, inflammatory (medullary carcinoma), vascular (papillary carcinoma) or mucinous determine nodular lesions whose borders push the surrounding tissue. The histological features which give rise to the radiographic pattern will be emphasised.

Breast↗

Intralesional Ethibloc injections in primary aneurysmal bone cysts: an efficient and safe treatment.

OBJECTIVE: Ethibloc is a fibrogenic and thrombogenic agent recently proposed for the treatment of bone cysts. The purpose of this study is to report the results of direct Ethibloc injection in primary aneurysmal bone cyst (ABC) in children. DESIGN AND PATIENTS: Seventeen patients, aged from 2 to 18 years (mean 8 years), were treated with either a single injection (14 patients) or supplementary injections (3 patients) of Ethibloc. The histological diagnosis was assessed following surgical biopsy and was retrospectively reviewed. The mean follow-up was 5 years (range 18 months to 11 years). RESULTS: At 5 year follow-up, 14 of 17 patients demonstrated complete healing manifest by increased cortical and septal thickening. Surgical excision was required in three patients, in two of whom the ABC increased rapidly in size despite the injection, and in one of whom the healing was incomplete. We observed inflammatory reactions in 16 of 17 patients with local pain and fever. Three patients developed a small cutaneous fistula which resolved spontaneously in a few weeks. No major complications such as deep infection, pulmonary embolism, epiphyseal necrosis or malignant degeneration were observed. CONCLUSION: Percutaneous direct Ethibloc injection is a safe, efficient and noninvasive treatment for ABC. The authors highlight the frequent local reactions.

Adolescent↗

Histological findings in surgical specimens after core biopsy of the breast.

Pathological changes induced by needling procedures found in breast surgical specimens are rare but can induce misinterpretation or compromise the definitive histological analysis. These abnormal findings depend on the interval between the core biopsy and excision. Early findings are local haemorrhage, disrupted tissue and epithelial cell displacement, whereas, fibrosis, fat necrosis and inflammatory reaction are observed later in time. The radiologists must be aware of these histological pitfalls and must consider the benefits of their core biopsies (indications, surgeon's question, number of samples).

Biopsy↗

Imaging and management of nonpalpable lesions of the breast.

Mammography remains the primary imaging modality for the evaluation of breast disease. Its performance level is clearly related to strict quality control measures and comprehensive diagnostic imaging. Ultrasonography remains an adjunct tool for analysing nonpalpable and palpable masses; diagnostic criteria for benign lesions must be strictly applied. Reliable histologic diagnosis is possible with percutaneous large needle core biopsies; benign findings should always be correlated with imaging data and follow-up is essential to detect delayed false negatives. MR imaging is still under evaluation for most indications. Its high sensitivity and negative predictive value are of particular interest for the detection or elimination of breast cancer in selected populations.

Biopsy, Needle↗

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.

Adult↗

["Micrometastases": the pathologist's point of view].

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.

Antibodies, Neoplasm↗

[Standards, options and recommendations: practice guidelines for difficult diagnosis in surgical pathology or cytopathology in cancer patients].

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993 is a collaboration between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines according to the definitions of the Standards, Options and Recommendations project for difficult diagnoses in surgical pathology or cytopathology in cancer patients. METHODS: Data were identified by searching Medline and using the personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to 71 independent reviewers. RESULTS: The main recommendations to prevent and reduce the number of difficult diagnoses in surgical pathology or cytopathology are: 1) The development of quality insurance programs with use of written procedures in each pathology laboratory (standard). 2) The knowledge of clinical data in order to explain surgical pathology or cytopathology results (standard). 3) The availability of complementary patient informations (radiologic data . . .) can be useful to explain surgical pathology or cytopathology results (option). The main recommendations to detect lesions associated with difficult diagnosis in surgical pathology or cytopathology are: 1) Tumor types known as potential difficult diagnosis in surgical pathology or cytopathology should be reviewed by a second pathologist. 2) The systematic second reviewing for every case is expensive but has to be done when the difficulty is know (sarcoma, lymphoma . . .) by experienced pathologists. The main recommendations to solve difficult diagnosis in surgical pathology or cytopathology are: 1) Block recuts, use of special techniques (immunocytohistochemistry and molecular biology), additional data from clinicians, second opinion by a local pathologist, or new specimen can be required for establishing the diagnosis (options). 2) Outside second opinion by expert pathologist has to be considered once the other steps did not allow to establish surgical or cytopathology diagnosis (recommendations, expert agreement).

Humans↗

MR imaging of clear cell sarcoma (malignant melanoma of the soft parts): a multicenter correlative MRI-pathology study of 21 cases and literature review.

OBJECTIVE: To evaluate MR imaging and pathology findings in order to define the characteristic features of clear cell sarcoma of the soft tissues (malignant melanoma of the soft parts). DESIGN AND PATIENTS: MR examinations of 21 patients with histologically proven clear cell sarcoma of the musculoskeletal system were retrospectively reviewed and assessed for shape, homogeneity, delineation, signal intensities on T1- and T2-weighted images, contrast enhancement, relationship with adjacent fascia or tendon, secondary bone involvement, and intratumoral necrosis. In 19 cases the pathology findings were available for review and for a comparative MR-pathology study. RESULTS: On T1-weighted images, lesions were isointense (n=3), hypointense (n=7) or slightly hyperintense to muscle (n=11). Immunohistochemical examination was performed in 17 patients. All 17 specimens showed positivity for HMB-45 antibody. In nine of 11 lesions with slightly increased signal intensity on T1-weighted images, a correlative MR imaging-pathology study was possible. All nine were positive to HMB-45 antibody. CONCLUSIONS: Clear cell sarcoma of the musculoskeletal system often has a benign-looking appearance on MR images. In up to 52% of patients, this lesion with melanocytic differentiation has slightly increased signal intensity on T1-weighted images compared with muscle. As the presence of this relative higher signal intensity on T1-weighted images is rather specific for tumors displaying melanocytic differentiation, radiologists should familiarize themselves with this rare entity and include it in their differential diagnosis when confronted with a well-defined, homogeneous, strongly enhancing mass with slightly higher signal intensity compared with muscle on native T1-weighted images.

Adolescent↗

Histological type and syncytial growth pattern affect E-cadherin expression in a multifactorial analysis of a combined panel of sporadic and BRCA1-associated breast cancers.

E-cadherin is a prominent factor in maintaining the epithelial architecture, and loss of its normal function is considered to be a key element in cancer invasion. In breast cancer, correlation between alteration of E-cadherin expression and histological type has been reported, but associations with other parameters remain uncertain. To refine these findings and to explore the biological significance of features thought to result from alterations of cell-to-cell adhesion systems, rare in sporadic cases but more frequent in BRCA1-associated breast cancers (BRCA1-BCs), we investigated E-cadherin expression by immuno-histochemistry in a combined panel of 214 breast cancers enriched in hereditary cases (176 sporadic cases and 38 BRCA1-BCs). Following multivariate statistical analysis using a logistic regression model, only 2 parameters were significantly associated with loss of E-cadherin expression: lobular histological type (p < 0.0001), in agreement with previous results, and syncytial growth pattern (SGP) (p = 0.01). The latter result provides a biological basis for SGP, the cardinal feature of medullary breast carcinoma.

BRCA1 Protein↗

Novel indications for BRCA1 screening using individual clinical and morphological features.

Since there is a lack of common family profile among BRCA1-gene carriers, and since the risk of being a mutation carrier is not limited to women with a family history of breast or ovarian cancer, multivariate statistical analysis using the logistic-regression model was carried out, to discriminate between sporadic cases and BRCA1-breast cancers (BRCA1-BCs), especially when information about the family history of breast/ovarian cancer and ethnicity are irrelevant or unavailable, in order to offer specific medical treatment to this population. We examined 32 BRCA1-BCs selected at cancer genetic clinics and 200 consecutive controls without family history of breast cancer for age at onset and current morphological parameters. Following the multivariate analysis, 3 parameters only, namely, early age at cancer onset [odds ratio (OR) for each year = 1.16; p < 0.0001], estrogen-receptor negativity (OR = 5.7; p = 0.01) and poor differentiation (OR = 5; p = 0.03) were found significant factors for predicting BRCA1-carrier status. The expected impact in BRCA1 screening of our model was estimated using data on 5700 breast-cancer cases from a hospital-based registry. Only 50 and 15% of tumours with early age at onset below 35 years present one or the other 2 discriminant parameters respectively. Consequently, whereas the probability of finding a BRCA1 mutation is rated low (6.2%) when the sole criterion of early onset up to the age of 35 years is used, based on our model, in the sub-group of women with a tumor that is both estrogen-receptor-negative and poorly differentiated the mutation-detection rate is predicted to be above the 10% chance level recommended by the ASCO guidelines. This sub-group of women, representing about 1% of all breast-cancer cases in Western countries, consequently deserves to be tested.

Adult↗