Central Acellular Zone Research Articles

A Correlation of Pathological Characteristics and Immuno Histo Chemistry (IHC) Based Biomarker Expression in Triple Negative Breast Carcinomas

Background and aim: Triple-negative breast cancer (TNBC) is defined as a group of breast carcinomas that are negative for expression of hormone receptors estrogen receptor (ER) or progesterone receptor (PR) and human epidermal growth factor receptor 2 (Her2). In India, several reports have suggested that TNBC incidence is higher and up to 31%. Histological features of triple-negative breast cancer are reported to be common with those of basallike subtype, comprising of high-grade invasive ductal carcinoma, no special type, invasive ductal carcinoma with a large central acellular zone, typical medullary carcinoma, and metaplastic carcinomas. In the present study, we aimed to correlate the pathological characteristics and evaluate IHC based expression of basal type biomarkers in triple negative breast carcinomas. Our study showed heterogeneity in histology, most of the TNBC cases in our study were IDC, NOS and there were a slightly higher percentage of atypical medullary cases as compared to other studies. Most of the cases were high grade based on modified NBR grading and majority of them turned out to be basal like on IHC. Distinctly found in our cases which had metastatic axillary lymph node was, basal immune phenotype unlike the case in other studies which demonstrated a higher proportion of lymph node negativity. As expected a high proportion of triple negative tumors showed a consistent basal cytokeratin expression (CK5/6-66%, CK14-72%, CK17-68%). EGFR and p53 positivity did not show statistical significance between basal and non-basal groups. Proliferation marker Ki67 was statistically significant in basal like groups. Gene expression profiling is the gold standard for TNBC molecular subtype classification, however, IHC is an accepted 'surrogate marker' for identifying and classifying the 'basal like group'. Our findings suggest that pathologic characteristics cannot be used to accurately classify triple-negative breast cancer into basal and non-basal groups. Relevance to patients: DNA microarray based molecular profiling may not be accessible always in clinical settings, this study has emphasized that identification of basal like subtype of breast cancers can be done by doing easily available surrogate Immunohistochemical biomarkers on TNBC, and thus help to provide the patient with relevant target based therapeutic benefit.

ER-/PgR+ breast cancer is a separate entity characterized by distinct phenotype: Comprehensive reevaluation of cases from Polish and Hungarian centers.

e12554 Background: ER negative (-)/PgR positive (+) breast cancer (BC) is very uncommon and questioned by many experts. We comprehensively reevaluated ER-/PgR+ BCs in the large cohort from Polish and Hungarian centers. Methods: FFPE blocks from 105 ER-/PgR+ tumors (45 breast biopsies and 64 post-operative samples from tumors not exposed to systemic therapy) were collected from 10 Polish and 3 Hungarian centers. In 60 cases available original slides with ER/PgR staining underwent reevaluation by 3 pathologists (MK, RP, WB) for ER and PgR expression by ASCO/CAP criteria. Subsequently, all samples were stained with 3 antibodies against ER (Dako monoclonal (MC) mouse anti-ERα, clone 1D5; Dako MC rabbit anti-ERα, clone EP1; VENTANA Roche MC rabbit anti-ERα, clone SP1), and PgR (Dako MC mouse anti-PgR, clone 636). If available, > 1 tissue block was used (av. 2.04 blocks/case, range 1-6). In 5 cases ESR1/PGR/ERBB2/MKi67 mRNA was measured by the Xpert® Breast Cancer STRAT4 (Cepheid, Sunnyvale, CA, USA). Results: 13 cases were excluded from immunohistochemical steps of the study due to insufficient amount of tissue and 8 - due to misdiagnosis after ER/PgR reevaluation of original slides. After re-staining, 42 cases (41.5%) retained the original phenotype, in 34 (33.67%) the ER status was corrected to ER+, and 16 (15.84%) tumors were ER/PgR-double-negative. The general agreement between anti-ER clones was moderate (Fleiss’ κ = 0.54). There were 56 ER- and 16 ER+ cases across all three assays. Five cases showed ER positivity with 2 antibodies (either SP1/EP1 or SP1/1D5), 5 tumors reacted exclusively with SP1 clone, and 2 - with 1D5 clone. Xpert Breast Cancer STRAT4 confirmed the ER-/PgR+ phenotype in 4 of 5 analyzed cases. The confirmed ER-/PgR+ BCs were characterized by lower percentage of PgR+ cells (median 5%) than BCs reclassified to ER+ (median 70%) (p = 0.022) and higher Ki67 expression than ER+ cases (median 54.5% vs 25%, respectively; p = 0.003). 39 (92.85%) ER-/PgR+ BCs presented with grade 3. Besides “conventional” high-grade cancers, we identified two distinct morphologies of ER-/PgR+ BC: resembling apocrine carcinoma (n = 5, 11.9%) and carcinoma with central acellular zone (n = 4, 9.5%). Conclusions: ER-/PgR+ BCs confirmed in the current study were defined by high-grade histology, high proliferation index and low percentage of PgR+ cells. We postulate ER-/PgR+ BC is a real albeit rare entity, and its diagnosis should be made cautiously, utilizing retesting with an alternative tissue block and anti-ER antibody.

MR Imaging Features of Triple-Negative Breast Cancers

Triple-negative (TN) breast cancers, which are associated with a more aggressive clinical course and poorer prognosis, often present with benign imaging features on mammography and ultrasound. The purpose of this study was to compare the magnetic resonance imaging features of TN breast cancers with estrogen (ER) and progesterone (PR) positive, human epidermal growth factor receptor (HER2) negative cancers. Retrospective review identified 140 patients with TN breast cancer who underwent a preoperative breast MRI between 2003 and 2008. Comparison was made to 181 patients with ER+/PR+/HER2- cancer. Breast MRIs were independently reviewed by two radiologists blinded to the pathology. Discrepancies were resolved by a third radiologist. TN cancers presented with a larger tumor size (p = 0.002), higher histologic grade (<0.001), and were more likely to be unifocal (p = 0.018) compared with ER+/PR+/HER2- tumors. MRI features associated with TN tumors included mass enhancement (p = 0.026), areas of intratumoral high T2 signal intensity (p < 0.001), lobulated shape (p < 0.001), rim enhancement (p < 0.001), and smooth margins (p = 0.005). Among the TN tumors with marked necrosis, 26% showed a large central acellular zone of necrosis.

Clinicopathologic characteristics of STAT1 positive/interleukin-8 negative subgroup in triple negative breast cancer defined by surrogate immunohistochemistry.

The aim of this study was to define immune-related triple negative breast cancer (TNBC) using immunohistochemistry for STAT1, CD20, CD3, IL-8, and IFN-γ and to assess its clinicopathologic characteristics. Tissues from 133 cases of TNBC were used for a tissue microarray. Expression of STAT1, CD20, CD3, IL-8, and IFN-γ were evaluated by immunohistochemical staining of the tissue microarrays. Immune-related type was defined as TNBC which was positive for STAT1 and negative for IL-8. A separate assessment of IL-8 and STAT1 status in tumor and stroma compartment was used to further classify immune-related type into tumor-based and stroma-based immune-related TNBC. Stroma-based, immune-related TNBC showed a significantly smaller central acellular zone (p=0.043), more lymphocytic infiltration (p⟨0.001), higher CD20 index (p=0.001), and higher CD3 index (p=0.018) than stroma-based, non-immune-related TNBC. IL-8 was independently associated with shorter disease-free survival (Hazard ratio: 3.804, 95% CI: 1.234-11.729, p=0.020) and shorter overall survival (Hazard ratio: 3.434, 95% CI: 1.132-10.414, p=0.029). Immune-related proteins such as STAT1, IFN-γ, IL-8, and CD20 were variably expressed in TNBCs. Stroma-based, immune-related TNBC (when positive for stromal STAT1 and negative for stromal IL-8) showed significantly higher lymphocytic infiltration including both CD3 positive T cell and CD20 positive B cell.

Inference of the Basal Epithelial Phenotype in Breast Carcinoma from Differential Marker Expression, Using Tissue Microarrays in Triple Negative Breast Cancer and Women Younger than 35

Basal-cell phenotype breast carcinoma has been associated with high-grade and metaplastic morphology, expression of basal-type cytokeratins, uniform negativity for ER and HER2, and decreased overall survival. Breast cancers occurring in young women are usually T2 disease at presentation, high-grade and of poor prognosis. We compared two groups of breast cancers, (a) ER-, PR-, HER2- (triple negative) [TNBrCa] and (b) non-triple negative breast cancers (non-TNBrCa) occurring in women under 35, using tissue microarray technology to characterize expression of the basal/myoepithelial cytokeratins (CK5/6, CK7, and CK14), luminal cytokeratins (CK8, CK18, and CK19), EGFR, p-cadherin, c-kit, p63, and p53. We also sought to identify characteristic histomorphologic features indicative of basal-like phenotype. The triple negative group showed preferential staining versus the age <35 group for CK5/6 (22% versus 4% p = 0.05), CK14 (44% versus 15%, p = 0.013), EGFR (83% versus 24%, p < 0.0001) and c-kit (19% versus 0% p = 0.026). Conversely, non-TNBrCa in women younger than 35 demonstrated increased expression of the luminal CK8 (92% versus 60%) compared with the triple negative patients (p = 0.006). The TNBrCa have characteristic histologic features including higher tumor grade, pushing tumor border, geographic necrosis, syncytial growth pattern, brisk mitotic activity, lack of/minimal in situ component, medullary-like and metaplastic differentiation. Invasive carcinomas in women younger than 35 usually have an associated in situ component, prominent nucleoli, central acellular fibrotic zone, and infiltrative tumor border. Triple negativity for ER/PR/HER2 coupled with EGFR, c-kit, and basal/myoepithelial cytokeratins (CK5/6, CK14) expression, and distinctive histomorphologic features predict morphology consistent with basal-cell phenotype.

Id4 protein is highly expressed in triple-negative breast carcinomas: possible implications for BRCA1 downregulation

BRCA1 germline mutation carriers usually develop ER, PR and HER2 negative breast carcinoma. Somatic BRCA1 mutations are rare in sporadic breast cancers, but other mechanisms could impair BRCA1 functions in these tumors, particularly in triple-negative breast carcinomas (TNBCs). Id4, a helix-loop-helix DNA binding factor, blocks BRCA1 gene transcription in vitro and could downregulate BRCA1 in vivo. We compared Id4 immunoreactivity in 101 TNBCs versus 113 non-TNBCs, and correlated the results with tumor morphology and immunoreactivity for CK5/6, CK14, EGFR, and androgen receptor (AR). Id4 was present in 76 out of 101 (75 %) TNBCs: 40 (40 %) TNBCs displayed Id4 positivity in >50 % of neoplastic cells, 23 (23 %) in 5-50 %, and 13 (13 %) in <5 %. In contrast, only 6 (5 %) of 113 non-TNBCs showed focal Id4 positivity, limited to fewer than 5 % of the tumor (p < 0.0001). Id4 expression significantly associated with high histologic grade (p = 0.0002) and mitotic rate (p = 0.006). Id4 decorated all 12 TNBCs with large central acellular zone of necrosis in our series, with positive staining in 10-90 % of the cells. Id4 signal strongly correlated with cytokeratin CK14 reactivity (p < 0.0001), but not with CK5/6 and EGFR. All apocrine carcinomas in our series were positive for AR and most for EGFR, but they were negative for CK5/6, CK14, and Id4, with only two exceptions. Our results document substantial expression of Id4 in most TNBCs, which could result in functional downregulation of BRCA1 pathways in these tumors.

Immunohistochemical study of metaplastic carcinoma and central acellular carcinoma of the breast: central acellular carcinoma is related to metaplastic carcinoma

Metaplastic breast cancers (MBCs) [spindle cell carcinoma (SpCC), squamous cell carcinoma (SCC), and matrix-producing carcinoma (MPC)] and invasive carcinomas with central acellular zones (CACs) were analyzed with respect to biological potential by immunohistochemical analyses. Specimens from 40 patients [20 with MBCs (7 with SCC, 6 with SpCC, 5 with MPC, and 2 with mixed type)] and 20 with CACs were analyzed using antibodies to cytokeratin (CK) 8, 5/6, 14, AE1/AE3, 34αE12, involucrin, c-kit, vimentin (VIM), alpha-smooth muscle actin, p63, epidermal growth factor receptor, epithelial cell adhesion molecule, and estrogen receptor (ER)/progesterone receptor (PR)/HER2. Expression of CK5/6, 34βE12, VIM, nuclear p63, and cytoplasmic p63 was significantly higher with MBCs than CACs (38%/13%, 70%/43%, 85%/33%, 68%/40%, and 48%/18%, respectively). Other markers were expressed at various levels in these tumors, but the difference between them was not significant. Eighteen MBC and 8 CAC cases were triple (ER/PR/HER2) negative; 17 MBCs and 7 CACs were basal-like tumors. Several differences were seen in MBCs and CACs, but they were heterogeneous, differentiating multipotentially into mesenchymal, myoepithelial, basal-like phenotypes with "stem cell-like" features. Thus, CACs are related to MBCs by immunohistochemical analyses as well as according to morphological findings.

“High-grade” central acellular carcinoma and matrix-producing carcinoma of the breast: correlation between ultrasonographic findings and pathological features

High-grade carcinoma with a large central acellular zone (central acellular carcinoma, CAC) and matrixproducing carcinoma (MPC) are aggressive tumors that both have a central myxomatous acellular zone. Their characteristic morphology may be useful in diagnostic imaging. Ultrasonographic findings based on the Breast Imaging Recording and Data System (BI-RADS) and detailed histological features were evaluated in 11 cases of CAC and 2 cases of MPC to characterize their features. Safranin-O staining was undertaken for the evaluation of central acellular zones in these tumors. Overall, ultrasonography demonstrated heterogeneous hyperechoic lesions in the center of the hypoechoic mass. Posterior echo enhancement was observed in all but 1 case. One case was classified as malignant and the others as "borderline." Histologically, cancer tissue was located in the periphery of the tumor with a ring-like structure and fewer cellular central areas comprising hyaline cartilage myxoid material such as those stained by safranin-O. The present study showed that the pathological findings of CACs and MPCs accurately reflect the ultrasonographic findings. Tumors that showed hyperechoic areas in the center of the hypoechoic mass, with posterior echo enhancement indicating acellular zones composed by myxochondroid material, and that were also relatively round on ultrasonography may be benign, but evaluation is required to exclude CAC and MPC.

Triple‐negative breast cancer: Histological subtypes and immunohistochemical and clinicopathological features

To reveal heterogeneous properties of triple-negative (TN) breast cancers (estrogen receptor negative, progesterone receptor negative and HER2 negative) and to clarify whether the developmental pathways to TN breast cancer are single or multiple, we conducted clinicopathological and immunohistochemical studies on TN breast cancers, with special reference to comparison of the invasive component (iIC) and the ductal component (dcIC) of invasive TN breast cancer and pure TN ductal carcinoma in situ (TNDCIS). Tumor tissues were obtained from 97 patients with TN invasive carcinoma and 10 patients with TNDCIS. Two histological subclassifications, "atypical" medullary carcinoma (type A, n=16) and carcinoma with a central acellular zone (type B, n=11), were distinguished from conventional ductal carcinoma. Other invasive ductal carcinomas were classified as type C (n=64) and special types were classified as type D (n=5). The follow-up period for the 96 patients ranged from 5 to 147.8 months (mean, 47.6 months). Out of 97 cases, dcIC was present in 29 (30%) cases and type A and B had significantly few ductal components, 0% and 18%, respectively. There were only six (6%) cases with non-TN cells in dcIC and TN cells in iIC and five of them were type C. In 13 (13%) cases, epidermal growth factor receptor (EGFR) expression existed only in iIC. Therefore, most of the TN carcinoma develops originally and rapidly invades at the early stage, especially in types A and B. The relapse rate of type B was the highest (36.4%) and the overall survival of patients with type B was the shortest (P=0.02), which indicates that the prognosis of type B is significantly worse than the other types.

Clinicopathological characteristics of triple-negative breast cancers

Triple-negative breast cancer (TNBC) is defined as a group of breast carcinomas that are negative for expression of hormone receptors and HER2. Although patients with TNBC tend to have a poor prognosis, only chemotherapy is expected to be effective because no therapeutic targets have yet been established. DNA microarray analyses have proved that TNBCs are composed of the basal-like subtype and normal breast (or unclassified) subtype, the former being correlated with an aggressive clinical course. Histological types of TNBCs are reported to be common with those of basal-like subtype, comprising high-grade invasive ductal carcinoma, no special type [solid-tubular carcinoma (or atypical medullary carcinoma), invasive ductal carcinoma with a large central acellular zone], typical medullary carcinoma, and metaplastic carcinomas. The basal-like subtype is characterized by the expression of myoepithelial/basal markers and molecular changes including TP53 gene mutations, BRCA1 inactivation, and many chromosomal alterations. New target molecules for the treatment of TNBCs are under extensive investigation, and their clinical application is awaited.

Histological differences between invasive ductal carcinoma with a large central acellular zone and matrix‐producing carcinoma of the breast

Carcinoma with a large central acellular zone (central acellular carcinoma, CAC) and matrix-producing carcinoma (MPC) have been recently noted as basal-like-type breast cancers, but the two entities are often confused. To clarify their histological differences, the histopathological sections of 15 CAC and seven MPC were examined and the following features were compared by reviewing slides: (i) mode of invasion; (ii) alteration of cancer cell adhesion in the transitional area between cellular and acellular zones; (iii) staining of the stromal matrix; (iv) lymphocyte infiltration; and (v) tumor grade. Complete agreement was required between two observers for the assessments of these features. All CAC had relatively sharp margins but showed infiltrative growth accompanied by eosinophilic intercellular matrix. In CAC there was abrupt transition between peripheral cellular and central acellular zones without alteration of cancer cell adhesion. In contrast, all MPC showed expansive growth with a well circumscribed margin, accompanied by basophilic and myxoid intercellular matrix. In MPC there was gradual transition from cellular to acellular areas with gradual loss of cancer cell adhesion. Histological grade 3 and peripheral lymphocyte infiltration were common features. It is suggested that CAC and MPC are histologically distinct entities, and that the aforementioned features are helpful for differential diagnosis.

Clinicopathological study of invasive ductal carcinoma with large central acellular zone: Special reference to magnetic resonance imaging findings

Invasive ductal carcinoma (IDC) with central acellular zone is sometimes encountered, but its clinicopathological features have not yet been fully investigated. The clinicopathological features of 10 resected cases of IDC with a large central acellular zone were investigated. The tumor size ranged from 6 to 28 mm with a mean of 14.3 +/- 6.9 mm. Contrast-enhanced magnetic resonance imaging (MRI) showed a ring-like appearance in the tumor. Sagittal fat-suppressed T2-weighted MRI had very high to intermediate signal intensity in a central area. Histologically, cancer tissue was located in the periphery of the tumor with a ring-like pattern and a large central area was occupied by acellular amorphous tissue that was strongly stained by alcian blue. Lymph vessel permeation was seen in eight cases. Among the tumors with focal enhancement in the central areas >1 cm in diameter on contrast MRI, marked increase of microvessel was observed in the enhanced spot. The mean of p53 and Ki-67 labeling indices was 56.2% and 36.3%, respectively. IDC with a large central acellular zone presenting with characteristic MRI should be noted as a new morphological entity.

Morphological and immunophenotypic analysis of breast carcinomas with basal and myoepithelial differentiation

The aim of this study was to assess the morphological characteristics and immunohistochemical profile of breast carcinomas with basal and myoepithelial phenotypes to obtain a better understanding of their biological behaviour and nature. One thousand nine hundred and forty-four invasive breast carcinomas were examined, using tissue microarray (TMA) technology and immunohistochemistry, to identify those tumours that showed basal and myoepithelial phenotypes, and their immunophenotype profile was characterized using a variety of markers. In addition, haematoxylin and eosin-stained sections of these tumours were studied for several morphological parameters. The findings were correlated with patient and tumour characteristics and outcome data. Tumours were classified into two groups: (1) tumours with basal phenotype [expressing one or both basal markers (CK5/6 and/or CK14)] and (2) tumours with myoepithelial phenotype (expressing SMA and/or p63). Group 1 was further subdivided into two subgroups: (A) dominant basal pattern (more than 50% of cells positive) and (B) basal characteristics (10-50% of cells positive). Group 1 tumours constituted 18.6% (8.6% and 10% for groups 1A and 1B, respectively) and group 2 constituted 13.7% of the cases. In both groups, the most common histological types were ductal/no specific type, tubular mixed and medullary-like carcinomas; the majority of these tumours were grade 3. There were positive associations with adenoid cystic growth pattern, loss of tubule formation, marked cellular pleomorphism, poorer Nottingham prognostic index, and development of distant metastasis. In addition, associations were found with loss of expression of steroid hormone receptors and FHIT proteins and positive expression of p53 and EGFR. The most common characteristics in group 1 were larger size, high-grade comedo-type necrosis, development of tumour recurrence, and absence of lymph node disease. Group 2 tumours were more common in younger patients and were associated with central acellular zones, basaloid change, and positive E-cadherin protein expression. Group 1 characteristics were associated with both reduced overall survival (OS) [log rank (LR) = 22.5, p < 0.001] and reduced disease-free interval (DFI) (LR = 30.1, p < 0.001), while group 2 characteristics showed an association with OS (LR = 5, p = 0.02) but not with DFI. Multivariate analysis showed that basal, but not myoepithelial, phenotype has an independent value in predicting outcome. Breast cancers with basal and myoepithelial phenotypes are distinct groups of tumours that share some common morphological features and an association with poor prognosis. The basal rather than the myoepithelial phenotype has the strongest relationship with patient outcome.

Frequent KIT and epidermal growth factor receptor overexpressions in undifferentiated‐type breast carcinomas with ‘stem‐cell‐like’ features

It was hypothesized that four histopathological types or subtypes of breast carcinoma were undifferentiated types characterized by bidirectional differentiation toward both luminal epithelial and myoepithelial cells and had characteristic molecular changes: invasive ductal carcinoma (IDC) with a large central acellular zone, atypical medullary carcinoma (a subgroup in Grade 3 solid-tubular carcinoma), matrix-producing carcinoma, and spindle-cell carcinoma (or carcinoma with spindle-cell metaplasia). In 32 cases of the undifferentiated type and 37 cases of the relatively differentiated types, we immunohistochemically examined the expressions of myoepithelial markers and KIT, epidermal growth factor receptor (EGFR), and c-erbB-2 oncoproteins. Vimentin, S-100, and alpha-smooth muscle actin were positive in 28 (88%), 22 (69%), and 15 (47%) of the undifferentiated types, but were positive in seven (19%), one (3%), and one (3%) of relatively differentiated types (P < 0.0001). KIT and EGFR overexpressions were detected more frequently in the undifferentiated types (34 and 88%, respectively) than in relatively differentiated types (3 and 3%, respectively) (P < 0.0001, for both). In 11 (85%) of 13 cases with KIT overexpression, EGFR overexpression concurred. c-erbB-2 overexpression was almost equally detected in both the undifferentiated and relatively differentiated types, and did not correlate with KIT or EGFR overexpression. Phosphotyrosine was detected in 16 (67%) of 24 cases with KIT, EGFR, and/or c-erbB-2 overexpression but only in six (18%) of 34 cases without KIT, EGFR, or c-erbB-2 overexpression (P = 0.0002). The undifferentiated-type breast carcinomas appeared to show mammary epithelial stem cell-like features, and they could be identified by KIT and/or EGFR overexpressions.

Invasive ductal carcinoma of the breast with large central acellular zones (ring carcinoma): imaging and clinical findings in eight cases

To review the mammographic and ultrasound appearances in patients who have invasive ductal carcinoma with a central acellular zone (ring carcinoma), as this feature has been reported to be associated with a poorer outcome. Eight patients were identified with ring carcinomas. Two breast radiologists reviewed their mammograms and ultrasound images. Patient records were reviewed to assess outcome. All patients had lesions deep within the breast, adjacent to the chest wall, five lesions were incompletely visualised on mammography. The appearance was of a circumscribed or obscured mass, without microcalcification. Five patients had ultrasound demonstrating a solid well-circumscribed hypoechoic microlobulated lesion. In our series of patients who have a ring carcinoma of the breast, mammographic and ultrasound appearances were similar in all cases and lacked the typical features of malignancy.

Invasive Ductal Carcinoma of the Breast with a Large Central Acellular Zone Associated with Matrix-producing Carcinoma

Matrix-producing carcinoma is a variant of metaplastic carcinoma of the breast that consists of overt carcinoma with direct transition to a cartilagenous and osseous stromal matrix. A clinicopathological association between MPC and high-grade invasive ductal carcinoma with a large central acellular zone has been recently discussed. However, few reports have ever shown the radiological, pathological and immunohistochemical correlation of this unique tumor. We present a case of 27-year-old woman with matrix-producing carcinoma with a large central acellular zone, which was characterized by a large homogeneous hypodense center with well-marginated, ring-like enhancement on contrast enhanced computerized tomography.

Evaluation of histopathological criteria for identifying nodenegative breast cancer witn high risk of early recurrence in the nsas-bc protocol study

The histopathological criteria for high-risk node-negative primary breast cancer stated in the National Surgical Adjuvant Study of Breast Cancer (NSAS-BC) protocol were used to grade a consecutive series of 488 cases at our hospital. To validate the criteria retrospectively, we examined the histological features of node-negative primary breast cancers which showed early relapse within 2 years after surgical therapy. Early relapse occurred in 12 patients, distant metastases in 11, and local recurrence in one. Among 278 cases followed for up to 1.5 years or longer, early systemic relapse was detected in 10 (5.8%) of 172 higher-grade tumors (9 invasive ductal carcinomas of nuclear grade 3 and one invasive ductal carcinoma of nuclear grade 2) and one stromal cell sarcoma. Among the 115 low-risk tumors, only one case (0.9%) of invasive ductal carcinomas with nuclear grade 1 showed early local recurrence. Early relapse occurred in only one (1.5%) of 67 tumors with an invasive component of 1.0 cm but in 11 (5.2%) of 211 tumors with an invasive component of 1.1 cm. The recurrence rate increased to 9.3% (8/86) when tumor invasion was 2.1 cm. In 12 cancers showing recurrence, strand structure, large central acellular zones, and squamoid features were histologically observed in four, two, and three cases, respectively. The present results confirmed the reported tendency of correlation between strand pattern and bone metastasis, large central acellular zones and lung and brain metastasis, and squamoid features and lung metastasis. Synchronous bilateral and unilateral multiple cancers were characterized by lower nuclear grades. At our hospital, the criteria used in the NSAS-BC protocol were demonstrated to identify node-negative cancers with high risk of early recurrence at a hospital level. To further identify groups prone to recurrence, longer follow-up would be necessary. In addition, the histological criteria could be improved to correlate with patient outcome more accurately.

Myoepithelial differentiation in high-grade invasive ductal carcinomas with large central acellular zones

We hypothesized that invasive ductal carcinomas (IDCs) with large central acellular zones comprising necrosis, tissue infarction, collagen, and hyaline material on their cut surfaces are formed in association with myoepithelial differentiation of the carcinoma cells. To verify this, the expression of S100 protein, α-smooth muscle actin (α-SMA), and glial fibrillary acidic protein (GFAP) and keratin 14, which has been shown to represent the myoepithelial immunophenotype, was examined immunohistochemically in 18 IDCs with such central zones covering more than 30% of each tumor area, 18 IDCs without such areas as negative controls, and 10 metaplastic carcinomas as positive controls for myoepithelial differentiation. Expression of S100, detected with a polyclonal antibody, S100-α, S100-β, α-SMA, GFAP, and keratin 14, was observed in 61%, 83%, 39%, 33%, 28%, and 39% of the IDCs with large central acellular zones, 17%, 44%, 6%, 6%, 0%, and 6% of the IDCs without such zones, and 80%, 70%, 50%, 100%, 80%, and 50% of the metaplastic carcinomas, respectively. We concluded that IDCs with large central acellular zones frequently contain carcinomas showing myoepithelial differentiation. Such histological and immunohistochemical features in IDCs would be expected to be clinicopathologically significant.

Cat-Scratch Disease

Biopsies of skin lesions in cat-scratch disease have received relatively little attention. This report describes the histologic changes in four primary skin lesions, one conjunctival lesion, and one intradermal skin test. The consistent changes observed were a central acellular zone of necrosis surrounded by histiocytes, giant cells, and a mantle of lymphocytes. These findings are equivalent to changes reported in lymph nodes from cat-scratch disease, and biopsy of skin lesions is a recommended step to be included with other diagnostic studies for cat-scratch disease.

Cat-scratch disease. Histopathologic changes in the skin.

Biopsies of skin lesions in cat-scratch disease have received relatively little attention. This report describes the histologic changes in four primary skin lesions, one conjunctival lesion, and one intradermal skin test. The consistent changes observed were a central acellular zone of necrosis surrounded by histiocytes, giant cells, and a mantle of lymphocytes. These findings are equivalent to changes reported in lymph nodes from cat-scratch disease, and biopsy of skin lesions is a recommended step to be included with other diagnostic studies for cat-scratch disease.