The Clinical and Pathological Characteristics That Differentiate Cases With "Low Estrogen Receptor Expression" From Triple-Negative Breast Cancer.

Objective: Estrogen receptor (ER) expression is an immunohistochemical marker that is examined in all invasive breast cancers and has prognostic and predictive value. ER-positive breast cancers refer to those that show positivity for ER at 1% cellular expression or higher. The American Society of Clinical Oncology/College of American Pathologists guidelines suggest using the term "low ER-positive breast cancer" for tumors with ER expression between 1% and 10%. Low ER-positive breast cancers exhibit similarities, in terms of disease-free survival and overall survival rates, to triple-negative breast cancers (TNBCs) rather than ER-positive breast cancers. In this study, our aim was to compare the clinicopathological characteristics of low ER-positive breast cancer cases diagnosed and followed in our clinic with TNBCs. Materials and Methods: A total of 26 cases of low ER-positive breast cancer diagnosed at University of Health Sciences Turkey, Izmir Tepecik Training and Research Hospital between 2010 and 2016 were retrieved from hospital records. The relevant histopathology slides and blocks were retrieved and re-evaluated retrospectively through microscopic examination. Thirteen cases that met the criteria were included in the study. Additionally, a consecutive series of 13 TNBC cases that did not receive neoadjuvant treatment within the same time period were identified. Results: In the low ER-positive group, the presence of tumor necrosis, as well as histological grade, nuclear grade and Ki-67 proliferation index were significantly lower compared to the TNBC group. Ductal carcinoma in situ (DCIS) was significantly more common in the low ER-positive group compared to the TNBC group. There were no significant differences between the two groups in terms of tumor size, histological tumor type, axillary lymph node involvement, tumor margins, peritumoral and intratumoral inflammation, local recurrence, distant metastasis, survival, and other characteristics. Conclusion: Although our study consisted of a small number of cases, some features showed significant differences between low ER-positive breast cancers and TNBCs. Histological and nuclear grades, as well as the presence of a DCIS component, were associated with low ER-positive breast cancer. In contrast, the presence of tumor necrosis, as well as Grade 3 features and a high Ki-67 proliferation index indicated TNBC.

The Clinicopathologic Features of 22 Cases With Primary Invasive Papillary Carcinoma of the Breast Identified in 1153 Cases With Invasive Breast Carcinoma: Single-Center Experience.

Objective: Invasive papillary carcinoma (IPC) of the breast is an uncommon histologic subtype with limited data in the literature. The aim of this study was to increase the evidence base by presenting clinicopathological findings of cases diagnosed as IPC. Materials and Methods: Hematoxylin and eosin sections and immunostaining of surgical excision specimens diagnosed as invasive breast carcinoma were re-evaluated, retrospectively. Results: IPC was detected in 22 cases (1.9%), of which 7 (0.6%) had pure and 15 (1.3%) had mixed morphology. Histologic types accompanying IPC were: Invasive ductal carcinoma (IDC) (15/15); invasive micropapillary carcinoma (3/15); and pleomorphic lobular carcinoma (1/15). Patient ages ranged between 36 and 89 (median 56.5) and the tumor size from 8 to 70 mm (median 19 mm). The histologic grade was 3 in five cases, 2 in 13, and 1 in four cases. The nuclear grade was 3 in 10 cases and 2 in 12. The values of positivity for estrogen receptor, progesterone receptor, human epidermal growth factor receptor-2, and Ki-67 index indicated Luminal B phenotype in 16 (72.7%), triple-negative in 5 (22.7%), and Luminal A in 1 case (4.6%). Ductal carcinoma in situ was noted in 19 cases (86.4%). Conclusion: IPC was mostly detected as an accompanying carcinoma to IDC at postmenopausal ages and was mostly Luminal B phenotype with intermediate-to-high grade features.

Invasive Breast Carcinoma with Abundant Collagenous Stroma Shows Lower Level of CD68-Positive Tumor Associated Macrophages than Those of Invasive Carcinoma without Abundant Collagenous Stroma.

BACKGROUND AND AIM OF THE WORK: The significance of association between cancer and its stromal microenvironment has been recognized. We aimed to investigate the immunohistochemical staining features of D2-40 (podoplanin), SMA (smooth muscle actin) and CD68 (pan-macrophage marker) in patients with early stage invasive breast cancer with/out peritumoral PASH-like stroma. METHODS: The H&E sections of core needle biopsy specimens of invasive breast carcinomas diagnosed during one-year time period were reviewed in terms of the presence of accompanying PASH-like stroma retrospectively. Cases with similar pattern of growth in their surgical excision materials were included. Eight cases were grouped as 'Invasive tumor with PASH-like stroma' and 21 cases as 'Invasive tumor without PASH-like stroma', consecutively. The results of immunohistochemical staining for D2-40, SMA and CD68 were noted semiquantitatively as 'negative','weak', moderate' or 'strong'. RESULTS: CD68 was found significantly lower in invasive tumor with peritumoral PASH-like stroma than those of tumor without PASH-like stroma. No significant differences were found for SMA and D2-40 between two groups.  Conclusions: Tumor-associated macrophages (CD68 positive) in tumor stroma have been demonstrated in association with tumor behavior in several studies. The presence of peritumoral PASH-like stroma, which is poorly staining for CD68, might be a morphological clue for the behavior of tumor.

The Expression of Galectin-3 in Tumor and Cancer-Associated Fibroblasts in Invasive Micropapillary Breast Carcinomas: Relationship with Clinicopathologic Parameters.

OBJECTIVE: Galectin-3 affects tumor progression and cell surface polarization by expressing from the tumor and cancer-associated fibroblasts (CAFs). Therefore, it may have a role on micropapillary carcinomas (IMPC), which have characteristic morphological features. The aim was to investigate the expression levels of Galectin-3 within tumor and peritumoral CAFs in IMPC, and to compare with expression in invasive ductal carcinomas (IDC). MATERIALS AND METHODS: Hematoxylin and Eosin-stained preparations of resection materials examined between 2010-2016 were re-evaluated. Thirty-four IMPC cases and 34 IDC cases with similar molecular subtype distribution to IMPC were compared. Galectin-3 levels were evaluated with a calculated H-score in tumor and semi-quantitatively in CAFs. RESULTS: While tumoral Galectin-3 expression levels were higher in IMPCs compared to IDCs, there was no difference for Galectin-3 expression in CAFs between the two histologic types. However, there was no significant relationship between tumoral Galectin-3 expression and clinicopathological parameters in IMPCs. When the subjects were divided into two groups, depending on their Galectin-3 status regardless of histological types, the loss of Galectin-3 expression in tumor was found to be related to larger tumor size/advanced pT stage and a greater number of metastatic nodes. Additionally, expression of Galectin-3 in CAFs was found to be associated with distant metastasis. CONCLUSION: IMPC showed prominent Galectin-3 expression in tumor compared to IDC. However, independent from the histological type, whereas the loss of Galectin-3 expression in tumor showed an association with larger tumor size and higher number of metastatic axillary lymph nodes, the presence of Galectin-3 expression in CAFs showed an association with distant metastasis.

The association of 18F-fluorodeoxyglucose PET/computed tomography parameters with tissue gastrin-releasing peptide receptor and integrin αvß3 receptor levels in patients with breast cancer.

OBJECTIVE: Gastrin-releasing peptide receptor (GRPR) and integrin αvß3 receptors are significantly associated with primary breast cancer, neovascular endothelial, and metastatic tumor cells. We aimed to evaluate GRPR and integrin αvß3 receptor staining, F-FDG uptake patterns and possible prognostic factors in breast cancer. METHODS: Ninety lesions of 87 subjects diagnosed with breast cancer were included in this prospective study. The sections were stained with GRPR and integrin αvß3. Subjects were divided into four molecular subgroups: luminal A, luminal B, triple negative and HER2. PET/CT imaging was performed on all subjects. The groups were compared in terms of GRPR and integrin αvß3 staining properties, possible prognostic factors and mean SUVmax values. RESULTS: Increased F-FDG uptake was significantly associated with estrogen receptor and progesterone receptor negativity. Molecular subtypes were significantly associated with mean integrin scores (P = 0.030), while histopathological subtypes were significantly associated with mean GRPR scores (P = 0.029). Increased integrin αvß3 expression is significantly associated with ER and PR negativity. Additionally, GRPR score was significantly correlated with estrogen receptor and progesterone receptor expression scores and a negative statistically significant correlation was detected between integrin and progesterone receptor scores. Mean primary lesion SUVmax had a statistically significant positive correlation with integrin αvß3 score. CONCLUSION: GRPR and integrin αvß3 expression results are complementary to F-FDG PET/CT findings, and are also significantly correlated with hormone receptors associated with aggressive subtypes. These results may pave the way for GRPR and integrin αvß3 targeted imaging with Ga-labeled molecules and systemic radionuclide treatment with Lu-labeled compounds.

Histopathological and Clinical Differences Between Primary Breast Carcinomas With Neuroendocrine Features and Primary Breast Carcinomas Mimicking Neuroendocrine Features.

We aimed to determine the histopathological differences between primary breast carcinomas with neuroendocrine features (NEBC) and carcinomas mimicking neuroendocrine features (NEBC-like). Twenty-three cases with NEBC, all showing positive staining for synaptophysin and/or chromogranin-A in ≥50% of tumor cells and 36 cases with NEBC-like (no staining for neuroendocrine [NE] markers but suspicious for NE morphology in terms of solid/trabecular growth patterns) were included in the study. Significant differences were found between the groups in terms of the patients' ages, histologic/nuclear grade of tumor, lymphovascular invasion, comedo-type ductal carcinoma in situ (DCIS), microcalcification, Ki-67 proliferation index, nuclear shape, and level of peritumoral lymphocytic infiltration. The presence of large-size solid cohesive groups of tumor cells; plasmocytoid, spindle, and/or columnar shapes of tumor cells; and eosinophilic-granular appearance of cytoplasm were mostly noted in the NEBC group. The presence of small- to medium-sized solid cohesive groups of tumor cells; high-grade histologic and nuclear features; clear cytoplasm; and round to ovoid nucleus were mostly noted in the NEBC-like group. No significant differences were found in terms of tumor size, ER/PR/HER2 status, as well as the presence of DCIS, elastosis, extracellular/intracellular mucin, signet ring cells, apocrine features, and accompanying papilloma or ductal ectasia. In conclusion, small- to medium-sized solid cohesive groups of tumor cells, high-grade features, clear cytoplasm, round to ovoid shape of nucleus, lymphovascular invasion, comedo-type DCIS, microcalcification, high level of Ki-67 proliferation index (≥20%), and moderate/strong level of peritumoral lymphocytic infiltration might support non-NE features in breast carcinomas.

CD10, TDAG51, CK20, AR, INSM1, and Nestin Expression in the Differential Diagnosis of Trichoblastoma and Basal Cell Carcinoma.

BACKGROUND: Trichoblastoma (TB) and basal cell carcinoma (BCC) are 2 different neoplasms composed of basaloid cells and have overlapping histopathological features. We compared the immunoexpression of CD10, T-cell death-associated gene 51 (TDAG51), cytokeratin 20 (CK20), androgen receptor (AR), insulinoma-associated protein 1 (INSM1), and nestin for the differential diagnosis of these tumors. MATERIALS AND METHODS: We assessed a total of 27 BCC and 27 TB cases, including 4 TB lesions in nevus sebaceous and 3 malignant TB lesions for CD10, TDAG51, CK20, AR, INSM1, and nestin expression. RESULTS: Staining for CK20, TDAG51, INSM1, and stromal CD10 was significantly more common in TB cases than in BCC cases ( P < .001). Epithelial CD10 and AR staining was significantly more common in BCC cases than in TB cases ( P < .001). The difference between the groups for nestin staining was not significant ( P > .05). Stromal CD10 staining was the most sensitive marker (96.3%) and INSM1 the least sensitive (55.6%) marker for TB. TDAG51 showed 100% specificity for TB. A larger number of CK20 positive cells was found in the cases associated with nevus sebaceous than in the other TBs. CONCLUSION: All the selected markers except nestin were useful for the differential diagnosis between TB and BCC. CD10 and TDAG51 were more useful than the other markers. The use of CK20 could be preferred in nevus sebaceous lesions. INSM1 was less effective in highlighting Merkel cells within the lesion than CK20.

Preventive role of superoxide dismutase on radiation-induced periprosthetic capsule development.

BACKGROUND: Capsule fibrosis is the most important and annoying complication of breast implant surgery. Radiotherapy (RT) used in the local treatment of breast cancer has an increasing effect on the existing fibrous capsule; this is called radiation-induced fibrosis (RIF). In this randomized controlled experimental study, we aim to investigate the reduction effect of superoxide dismutase (SOD) on RIF. METHODS: Sprague-Dawley rats were randomized into four groups, all of which were subjected to implant surgery. No additional procedures were done for the control group. The other groups were the SOD group, the RT + SOD group, and the RT group. The capsules were evaluated histopathologically. RESULTS: Although SOD reduced surgery-induced capsule formation, it neither prevented nor reduced significantly RIF. CONCLUSIONS: In an experimental model that resembled breast cancer treatment, we concluded that SOD cannot reduce RIF but is effective in reducing capsular fibrosis around the silicone after implant surgery.

Primary breast carcinomas with neuroendocrine features: Clinicopathological features and analysis of tumor growth patterns in 36 cases.

Primary breast carcinoma with neuroendocrine features (NEBC) is an uncommon tumor. In the classification of WHO 2012, these tumors were categorized as: 1- neuroendocrine tumor, well-differentiated; 2- neuroendocrine carcinoma, poorly differentiated/small cell carcinoma; and 3- invasive breast carcinoma with neuroendocrine differentiation. In this study, we reviewed NEBC except poorly differentiated/small cell carcinoma variant in order to define the morphological growth patterns and cytonuclear details of these tumors. All breast surgical excision materials between 2007 and 2016 were re-evaluated in terms of neuroendocrine differentiation. Thirty-six cases showing positive staining for synaptophysin and/or chromogranin A in ≥50% of tumor cells were included in the study. All cases were female with a mean age of 67.4. Mean tumor diameter was 26 mm. Multifocality was noted in 5 cases. Grossly, they were mostly infiltrative mass lesions. T stages, identified in 34 cases, were as follows: 13 cases with pT1; 19 pT2 and 2 pT3. We described schematically 4 types of patterns depending on predominant growth pattern, except one case: 1) Large-sized solid cohesive groups (6 cases), 2) Small- to medium-sized solid cohesive groups with trabeculae/ribbons and glandular structures (6 cases), 3) Mixed growth patterns (20 cases), 4) Invasive tumor with prominent extracellular and/or intracellular mucin (3 cases). The tumor cells were mostly polygonal-oval with eosinophilic/eosinophilic-granular cytoplasm. The nuclei of tumor cells were mostly round to oval with evenly distributed chromatin. Only 5 cases showed high grade nuclear and histological features. Molecular subtypes of the cases were as follows: 33 luminal A, 2 luminal B, and 1 triple negative. NEBC should come to mind when a tumor display one of the morphological patterns described above, composed of monotonous cells with mild to moderate nuclear pleomorphism and abundant eosinophilic/eosinophilic granular or clear cytoplasm, especially in elderly patients.

Pseudoangiomatous Stromal Hyperplasia in Core Needle Biopsies of Breast Specimens.

BACKGROUND: Pseudoangiomatous stromal hyperplasia (PASH) is a benign lesion of myofibroblasts that is composed of a network of slit-like channels that resemble vascular spaces. The aims of this study were to document the frequency of PASH in core needle biopsy specimens (CNBS) of the breast, to describe which histopathologic findings coexist with PASH and to examine any endothelial cell differentiation. MATERIALS AND METHODS: We reevaluated hematoxylin and eosin-stained sections of all CNBS that were obtained during a 1-year period. First, we performed CD34 and CD31 immunostainings to highlight the areas of PASH, then performed D2-40/podoplanin (lymphatic endothelial marker) and Fli-1 (vascular endothelial cell marker) immunostains. RESULTS: The total number of CNBS was 412. Areas of PASH were noted in 37 of the 412 cases (9%), with a mean age of 38.5 years. The lesions that were described in association with PASH were "benign breast parenchyma with stromal fibrosis" (17/37; 46%), "fibroepithelial tumors" (17/37; 46%), "columnar cell changes (CCC)" (2/37; 5%), and "invasive carcinoma" (1/37; 3%). There were 2 cases of CCC within the foci of PASH (direct contact with PASH), and 8 additional cases of CCC that coexisted in the same specimen but were not in direct contact. There was no staining for D2-40 or Fli-1 within PASH foci. CONCLUSION: PASH lesions occurred with a frequency of 9% in CNBS and were mostly in association with benign breast lesions in premenopausal women. CCC was determined as an accompanying epithelial lesion within or near PASH areas. No obvious immunopositivity compatible with endothelial cell differentiation was revealed.