A case of HER-2(+) squamous cell breast carcinoma: an unusual presentation of an unusual clinical entity.
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Aged↗
Biomedical subjects
N Apostolikas
Publications and source records attributed to N Apostolikas.
First-line chemotherapy with docetaxel and cisplatin in metastatic breast cancer.
The purpose of this study was to evaluate the efficacy and tolerance of combined treatment with docetaxel-cisplatin as first-line chemotherapy in patients with metastatic breast cancer (MBC). Consecutive eligible chemonaive patients received docetaxel 75 mg/m(2) on day 1 and cisplatin 75 mg/m(2) on day 2 every 3 weeks for 6 cycles, with prophylactic recombinant human granulocyte colony-stimulating factor (rHuG-CSF) on days 4-11. Thirty-two patients (64%) had received prior adjuvant chemotherapy; these included 16 (32%) who had received anthracyclines. In 50 evaluable patients with a median age (range) of 56 (31-72) years, the overall response rate was 68% (95% CI, 55-81%), with 7 (14%) complete and 27 (54%) partial responses. Stable and progressive disease was observed in 10 (20%), and 6 (12%) patients, respectively. The median duration of response was 10 months, and the median time to progression was 39 weeks. Grade 3/4 hematological toxicity included--neutropenia in 9 patients (18%), anemia in 2 (4%) and thrombocytopenia in 1 (2%). One patient (2%) with febrile neutropenia required hospitalization. Grade 3/4 nonhematological toxicities included nausea/vomiting in 18%, nephrotoxicity in 14%, asthenia (4%), and neurotoxicity (2%). Toxicity was common in older patients (>56 years). There were no treatment-related deaths. A combination of docetaxel-cisplatin with rHuG-CSF support is well tolerated and effective as first-line chemotherapy in MBC.
Adult↗
Multiple cutaneous acral metastases in a woman with breast adenocarcinoma treated with pegylated liposomal doxorubicin: incidental or aetiological association?
This paper reports the case of a 45-year-old female with histologically documented, multiple cutaneous metastases in the palmar and plantar surface of the fingers and toes originating from a breast adenocarcinoma after treatment with a docetaxel and pegylated liposomal doxorubicin regimen. The rarity of such a metastatic pattern from breast cancer and the eventual association with the chemotherapy administered are thoroughly discussed.
Antibiotics, Antineoplastic↗
Consistency of staining and reporting of oestrogen receptor immunocytochemistry within the European Union--an inter-laboratory study.
To assess the variability of oestrogen receptor (ER) testing using immunocytochemistry, centrally stained and unstained slides from breast cancers were circulated to the members of the European Working Group for Breast Screening Pathology, who were asked to report on both slides. The results showed that there was almost complete concordance among readers (kappa=0.95) in ER-negative tumours on the stained slide and excellent concordance among readers (kappa=0.82) on the slides stained in each individual laboratory. Tumours showing strong positivity were reasonably well assessed (kappa=0.57 and 0.4, respectively), but there was less concordance in tumours with moderate and low levels of ER, especially when these were heterogeneous in their staining. Because of the variation, the Working Group recommends that laboratories performing these stains should take part in a external quality assurance scheme for immunocytochemistry, should include a tumour with low ER levels as a weak positive control and should audit the percentage positive tumours in their laboratory against the accepted norms annually. The Quick score method of receptor assessment may also have too many categories for good concordance, and grouping of these into fewer categories may remove some of the variation among laboratories.
Breast Neoplasms↗
Ameloblastomas of the jaws: clinico-pathological review of 11 patients.
AIMS: The ameloblastoma is an uncommon benign odontogenic neoplasm of the maxillofacial region constituting less than 1% of tumours of the oral cavity. The purpose of this paper is to discuss and evaluate the surgical treatment and the outcome from a series of 11 patients with ameloblastomas. METHODS: Between the years 1995 and 2003, 11 patients (eight female and three male) aged 17-86 years (mean 52.7) suffering from ameloblastomas of the jaws were seen in our Department. RESULTS: Ten patients were treated surgically. In eight of those radical surgery was applied. Patients with maxillary tumours were subjected to hemimaxillectomy and local excision. Radical treatment with segmental resection of the mandible was performed in six patients with multilocular (solid) mandibular ameloblastomas, with immediate reconstruction of the defect. Follow-up ranged from 3 months to 7.5 years. CONCLUSION: Multilocular (solid) type of tumours should be approached with radical surgical treatment. Enucleation and rarely marsupialization can be applied selectively to unilocular ameloblastomas.
Adolescent↗
Discrepancies in current practice of pathological evaluation of sentinel lymph nodes in breast cancer. Results of a questionnaire based survey by the European Working Group for Breast Screening Pathology.
AIMS: To evaluate aspects of the current practice of sentinel lymph node (SLN) pathology in breast cancer via a questionnaire based survey, to recognise major issues that the European guidelines for mammography screening should address in the next revision. METHODS: A questionnaire was circulated by mail or electronically by the authors in their respective countries. Replies from pathology units dealing with SLN specimens were evaluated further. RESULTS: Of the 382 respondents, 240 European pathology units were dealing with SLN specimens. Sixty per cent of these units carried out intraoperative assessment, most commonly consisting of frozen sections. Most units slice larger SLNs into pieces and only 12% assess these slices on a single haematoxylin and eosin (HE) stained slide. Seventy one per cent of the units routinely use immunohistochemistry in all cases negative by HE. The terms micrometastasis, submicrometastasis, and isolated tumour cells (ITCs) are used in 93%, 22%, and 71% of units, respectively, but have a rather heterogeneous interpretation. Molecular SLN staging was reported by only 10 units (4%). Most institutions have their own guidelines for SLN processing, but some countries also have well recognised national guidelines. CONCLUSIONS: Pathological examination of SLNs throughout Europe varies considerably and is not standardised. The European guidelines should focus on standardising examination. They should recommend techniques that identify metastases > 2 mm as a minimum standard. Uniform reporting of additional findings may also be important, because micrometastases and ITCs may in the future be shown to have clinical relevance.
Biomarkers, Tumor↗
Pathological work-up of sentinel lymph nodes in breast cancer. Review of current data to be considered for the formulation of guidelines.
Controversies and inconsistencies regarding the pathological work-up of sentinel lymph nodes (SNs) led the European Working Group for Breast Screening Pathology (EWGBSP) to review published data and current evidence that can promote the formulation of European guidelines for the pathological work-up of SNs. After an evaluation of the accuracy of SN biopsy as a staging procedure, the yields of different sectioning methods and the immunohistochemical detection of metastatic cells are reviewed. Currently published data do not allow the significance of micrometastases or isolated tumour cells to be established, but it is suggested that approximately 18% of the cases may be associated with further nodal (non-SN) metastases, i.e. approximately 2% of all patients initially staged by SN biopsy. The methods for the intraoperative and molecular assessment of SNs are also surveyed.
Breast Neoplasms↗
Preoperative work-up of early cervical cancer (stages Ib-IIa).
OBJECTIVE: To determine the effectiveness of preoperative investigations in early cervical cancer. MATERIALS: We retrospectively reviewed the medical records of 309 patients with previously untreated early cervical carcinoma who completed pretreatment evaluation at "St. Savas" Cancer Hospital of Athens and "Metaxas" Memorial Hospital of Peireas between January 1986 and September 1, 2000. Ages ranged from 18-77 years old with a mean age of 48 and S.D. of 12.25. FIGO staging was Ib (200 pts.), IIa (105 pts.), IV (4 pts.). Histologic type was squamous (267 pts.), adenoid (35 pts.), adenosquamous (7 pts.). The patients were clinically examined and routinely evaluated with blood work-up, chest X-ray, IVP, abdominal CT scan, barium enema, sigmoidoscopy, cystoscopy, and/or urine cytology. Patients with early stage cervical carcinoma were treated with Wertheim-Meigs radical hysterectomy and pelvic lymphadenectomy, while those with advanced stage cervical carcinoma were treated with radiotherapy and chemotherapy. RESULTS: In urinary tract investigation, CT showed a sensitivity of 100% and a specificity of 99.67%. In gastrointestinal tract investigation CT showed a sensitivity of 50% and a specificity of 99.67%. When we compared the histologic findings of the pelvic lymph nodes that were extracted in surgically treated patients with the preoperative CT findings, we found that CT had a sensitivity of 63.33% and a specificity of 88.57%. CONCLUSION: In our series of patients with early stage cervical carcinoma, imaging and endoscopic tests added limited information over pelvic examination and altered in four cases (1.29%) the choice of the appropriate treatment modality. CT scans proved adequate in this series of patients in the evaluation of the bladder and colon. All other tests could have been performed only when CT was suspicious of invasion. Moreover, CT served as a baseline examination for future comparative studies in the follow-up of patients.
Adolescent↗
Causes of inconsistency in diagnosing and classifying intraductal proliferations of the breast. European Commission Working Group on Breast Screening Pathology.
It is now widely recognised that classifying ductal carcinoma in situ (DCIS) of the breast and diagnosing atypical ductal hyperplasia are associated with significant interobserver variation. Two possible reasons for this inconsistency are differences in the interpretation of specified histological features and field selection where morphology is heterogeneous. In order to investigate the relative contribution of these two factors to inconsistent interpretation of intraductal proliferations, histological sections of 32 lesions were sent to 23 European pathologists followed 3 years later by images of small parts of these sections. Kappa statistics for diagnosing hyperplasia of usual type, atypical ductal hyperplasia and ductal carcinoma in situ were 0.54, 0.35 and 0.78 for sections and 0.47, 0.29 and 0.78 for images, respectively, showing that most of the inconsistency is due to differences in morphological interpretation. Improvements can thus be expected only if diagnostic criteria or methodology are changed. In contrast, kappa for classifying DCIS by growth pattern was very low at 0.23 for sections and better at 0.47 for images, reflecting the widely recognised variation in the growth pattern of DCIS. Higher kappa statistics were obtained when any mention of an individual growth pattern was included in that category, thus allowing multiple categories per case; but kappa was still higher for images than sections. Classifying DCIS by nuclear grade gave kappa values of 0.36 for sections and 0.49 for images, indicating that intralesional heterogeneity has hitherto been underestimated as a cause of inconsistency in classifying DCIS by this method. More rigorous assessment of the proportions of the different nuclear grades present could lead to an improvement in consistency.
Breast↗
Cytogenetic findings in a malignant fibrous histiocytoma of the breast.
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Breast Neoplasms↗
Consistency achieved by 23 European pathologists from 12 countries in diagnosing breast disease and reporting prognostic features of carcinomas. European Commission Working Group on Breast Screening Pathology.
A detailed analysis of the consistency with which pathologists from 12 different European countries diagnose and classify breast disease was undertaken as part of the quality assurance programme of the European Breast Screening Pilot Network funded by the Europe against Cancer Programme. Altogether 107 cases were examined by 23 pathologists in 4 rounds. Kappa statistics for major diagnostic categories were: benign (not otherwise specified) 0.74, atypical ductal hyperplasia (ADH) 0.27, ductal carcinoma in situ (DCIS) 0.87 and invasive carcinoma 0.94. ADH was the majority diagnosis in only 2 cases but was diagnosed by at least 2 participants in another 14, in 9 of which the majority diagnosis was benign (explaining the relatively low kappa for this category). DCIS in 4 (all low nuclear grade) and invasive carcinoma (a solitary 1-mm focus) in 1. The histological features of these cases were extremely variable; although one feature that nearly all shared was the presence of cells with small, uniform, hyperchromatic nuclei and a high nucleo-cytoplasmic ratio. The majority diagnosis was DCIS in 33 cases; kappa for classifying by nuclear grade was 0.38 using three categories and 0.46 when only two (high and other) were used. When ADH was included with low nuclear grade DCIS there was only a slight improvement in kappa. Size measurement of DCIS was less consistent than that of invasive carcinoma. The majority diagnosis was invasive carcinoma in 57 cases, the size of the majority being 100% in 49. The remainder were either special subtypes (adenoid cystic, tubular, colloid, secretory, ductal/medullary) or possible microinvasive carcinomas. Subtyping was most consistent for mucinous (kappa, 0.92) and least consistent for medullary carcinomas (kappa, 0.56). Consistency of grading using the Nottingham method was moderate (kappa=0.53) and consistency of diagnosing vascular invasion, fair (kappa=0.38). There was no tendency for consistency to improve from one round to the next, suggesting that further improvements are unlikely without changes in guidelines or methodology.
Breast Diseases↗
The extent of surgery and prognosis of patients with phyllodes tumor of the breast.
In an attempt to clarify the controversial issues related to prognosis and therapeutic aspects of phyllodes tumors (PT), we retrospectively reviewed all cases of PT treated in our hospital during the last fifteen years. Re-examining the pathology material we found 84 cases, while thirteen more cases which had been initially classified as fibroadenomas with areas of phyllodes tumor were rejected from the analysis because they were classified as fibroadenomas. Based on the criteria proposed by Azzopardi and Salvadori and adopted by WHO, we found 55 benign PT (65.14%), 14 borderline PT (16.6%), and 15 malignant PT (17.8%). The median age of the patients with benign PT was 34 years, compared to 46.5 years for those with borderline tumors and 52 years for those with malignant. The median size of benign tumors was 3 cm, 9.5 cm for borderline, and 7.25 cm for malignant. Out of 55 patients with benign PTs, 37 underwent wide local excision and the remaining 18, with small tumors, underwent enucleation. In this group of patients, there was no recurrence after a median interval of 6.65 years. Eleven patients with borderline PT underwent wide local excision and three mastectomy; one immediately after an incomplete PT excision and the remaining two 8 months and 2 years later due to a locally recurrent PT (the last one proven histologically in the permanent biopsy of the recurrence to be malignant). Twelve patients with malignant PT underwent mastectomy, either during the same operation or following the results of the permanent section biopsy. Three more patients with malignant PT underwent wide local excision. The size of the tumor in these patients was relatively small and the pathology report indicated clear margins with normal breast tissue surrounding the tumor. One patient with 8 cm diameter malignant PT, who underwent mastectomy, passed away sixteen months later from widely spread metastases. Applying the criteria of Azzopardi and Salvadori, each case of PT can be managed successfully avoiding unnecessary mastectomies.
Adult↗
Different patterns of stromal and cancer cell thymidine phosphorylase reactivity in non-small-cell lung cancer: impact on tumour neoangiogenesis and survival.
Angiogenesis is recognized as an important step in tumour pathogenesis that is related to invasion and metastatic spread and which consequently results in poor clinical outcome. In this study, we have examined the role of tumour stroma-activated fibroblasts and macrophage infiltration in the development of the angiogenic and metastatic phenotype in non-small-cell lung cancer (NSCLC). A total of 141 cases of early stage I-II NSCLC treated with surgery alone were analysed. The JC-70 (anti-CD31) MAb was used for the assessment of vascular grade. The P-GF.44C MAb was used to assess thymidine phosphorylase (TP) reactivity in cancer cells, stromal fibroblasts and macrophages. Cancer cell TP overexpression related to high vascular grade and to advanced T stage (P = 0.0004 and P = 0.02). Expression of TP in stromal fibroblasts also correlated with high angiogenesis (P = 0.01), but was independent of cancer cell expression. Fibroblast TP overexpression was related to abundant stroma (P = 0.003), suggesting that TP may be a marker of active stroma. Moreover, intense macrophage infiltration was associated with fibroblast TP reactivity, regardless of the amount of stroma, suggesting that macrophages may be a major contributor to TP expression in stroma. Survival analysis showed that cancer cell TP overexpression was related to poor prognosis (P = 0.005). Although stroma TP is related to angiogenesis, in the low vascular grade group it defined a group of patients with better prognosis (P = 0.02). It may be that fibroblast TP reactivity is an indirect marker of tumour infiltration by functional macrophages, which have an antitumour effect. We conclude that stromal macrophage and fibroblast TP reactivity may have an important role in non-small-cell lung cancer behaviour. Understanding the role of stromal fibroblasts and inflammatory cells and their interaction with oncoprotein expression is essential for the elucidation of lung cancer pathogenesis.
Adenocarcinoma↗
Cytogenetic comparison of primary tumors and lymph node metastases in breast cancer patients.
Chromosome banding analysis of primary tumors and axillary lymph node metastases from 10 breast cancer patients revealed abnormal karyotypes in all samples with cytogenetic similarities between the primary tumor and the metastasis in all informative pairs. Although karyotypically unrelated clones were also found in the lymph node samples, they were less numerous than in the primary tumors, indicating that there was more genetic heterogeneity among the neoplastic cells in the primary than in the secondary tumors. On the other hand, some of the clones had become more complex in the metastases as a result of clonal evolution, and by and large these metastatic breast cancer cases had more karyotypic anomalies than do unselected primary breast carcinomas. Among the aberrations occurring more frequently, and that consequently may predispose to disease spread, were losses of chromosomes 17 and 22 and homogeneously staining regions, a cytogenetic sign of gene amplification.
Adult↗
Consistency achieved by 23 European pathologists in categorizing ductal carcinoma in situ of the breast using five classifications. European Commission Working Group on Breast Screening Pathology.
The increased detection of ductal carcinoma in situ (DCIS) by mammographic screening, the greater use of breast-conserving surgery, and the recognition that certain histological subtypes are associated with a greater risk of local recurrence has led to the formulation of several new classifications of DCIS in recent years. There are, however, no data concerning the degree of consistency with which these schemes can be applied by reasonable numbers of pathologists. Thirty-three cases of DCIS were thus examined by a working group of 23 European pathologists who categorized them using five recently published classifications: (1) that of the European Pathologists' Working Group based on differentiation (a combination of nuclear grade and cell polarization) with categories of poorly, intermediately, and well differentiated; (2) one based entirely on nuclear grade with categories of high, intermediate, and low, currently in use in the UK national and EC-funded breast screening programs; (3) the same classification in which only two categories, high nuclear grade and other, were used; (4) the Van Nuys system in which lesions are divided into high grade, non-high grade with necrosis and non-high grade without necrosis; and (5) a two-category classification based entirely on the presence or absence of comedo necrosis. Of the three systems with three categories, Van Nuys gave the highest overall kappa statistic of 0.42. Others gave similar values of 0.37 and 0.35 showing that assessing cell polarization in addition to nuclear grade neither improves nor worsens consistency. In all three systems, the middle category was associated with the lowest value for kappa. Of the two systems with two categories, that based on nuclear grade gave the highest overall kappa of 0.46 and that based on comedo necrosis the lowest of 0.34. The most robust histological features were thus high- and low-grade nuclei and necrosis as long as the latter did not involve the recognition of a comedo growth pattern. These values probably represent the maximum achievable, at least by reasonable numbers of pathologists in everyday practice. They are better than those previously reported for classification based entirely on architecture, but further improvement is needed.
Breast Neoplasms↗
Cytogenetic findings in phyllodes tumors of the breast: karyotypic complexity differentiates between malignant and benign tumors.
Clonal karyotypic abnormalities were detected in short-term cell cultures from six phyllodes tumors of the breast. Whereas all five benign tumors had simple chromosomal changes, the highly malignant one had a near-triploid stemline, indicating that karyotypic complexity is a marker of malignancy in phyllodes tumors. Interstitial deletions of the short arm of chromosome 3, del(3)(p12p14) and del(3)(p21p23),were the only aberrations in two benign tumors. Cytogenetic polyclonality was detected in three benign tumors: two had cytogenetically unrelated clones, whereas the third had three different, karyotypically related cell populations as evidence of clonal evolution. The finding of clonal chromosome abnormalities in both the epithelial and connective tissue components of the phyllodes tumors indicates that they are genuinely biphasic, that is, that both components are part of the neoplastic parenchyma.
Breast Neoplasms↗
[Guidelines for pathology--supplement to European guidelines for quality assurance in mammography screening. Report by the Pathology Working Group of the European Community].
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Biopsy↗
Preliminary findings on the expression of thymosin beta-10 in human breast cancer.
Paraffin sections from 30 human breast tissue specimens were stained with a specific antibody for thymosin beta-10, ATB10(38-43). The results showed that thymosin beta-10 was detected mainly in the malignant tissue, particularly in the cancerous cells, whereas the normal cell population around the lesions showed very weak staining. Also, the intensity of staining in the cancerous cells was proportionally increased with the increasing grade of the lesions.
Adult↗