Invasive breast lobular carcinoma with extracellular mucin: a clinicopathological analysis / 中华病理学杂志

Objective@#To study the clinicopathological features of invasive lobular carcinoma (ILC) of the breast with extracellular mucin and outcomes of patients.@*Method@#Clinicopathological features and clinical follow-up (39-123 months and a median follow-up of 55 months) of seven ILC with extracellular mucin were obtained. Hematoxylin-and-eosin (H&E) and immunohistochemistry (IHC) stained sections were reviewed, and fluorescence in situ hybridization (FISH) assay was performed for tumors with HER2 IHC 2+. Patient prognosis was analyzed and literatures related to ILC with extracellular mucin were reviewed.@*Results@#All seven patients were female, aged from 43 to 73 years (median age, 55 years). The tumors ranged in size from 1 to 5 cm (median size 2 cm). All seven cases were of histological grade 2. Most areas of the tumors presented with the morphology of classic ILC, and variable amount of extracellular mucin were observed focally. In six cases, part of the tumor cells contained intracellular mucin, and the nucleus were pushed to one side of the cells, creating the impression of signet-ring cells. Two patients had lymph node metastases at diagnosis, and developed liver and bone metastases at 38th and 48th month, respectively, after surgery, and died at 48th and 123th month, respectively. While the other five patients, except one lost to follow-up, had been disease-free during the follow-up period. IHC results showed estrogen receptor (ER) and progesterone receptor (PR) positivity in 7/7 and 6/7 cases, respectively. Tumors of six patients were HER2 IHC 0/1+. The remaining one was HER2 IHC 2+, while FISH assay revealed HER2 gene amplification in that tumor. The proportion of cases with HER2-positivity was 1/7. The proliferation index Ki-67 ranged from less than 5% to 30%, and Ki-67 less than or equal to 10% were in 5/7 cases. According to the 2013 St. Gallen International Expert Consensus on breast cancer, all tumors were of luminal types; of those, two were luminal A and five were luminal B.@*Conclusions@#ILC with extracellular mucin tends to occur in women over 50 years old. All tumors in the study are grade 2 classic ILC, with signet-ring cells as a common feature. All seven tumors are classified as luminal types, with luminal B as the main molecular subtype.

Expression of DNA Damage Response Proteins and Associations with Clinicopathologic Characteristics in Chinese Familial Breast Cancer Patients with BRCA1/2 Mutations / 한국유방암학회지

PURPOSE: The characteristic expression of DNA damage response proteins in familial breast cancers with BRCA1, BRCA2, or non-BRCA1/2 mutations has not been analyzed in Chinese patients. Our study aimed to assess the differential expression of microcephalin 1 (BRIT1), ATM serine/threonine kinase (ATM), checkpoint kinase 2 (CHEK2), BRCA1, RAD51 recombinase (RAD51), and poly (ADP-ribose) polymerase 1 (PARP-1) and establish the profile of Chinese familial breast cancers with different mutation status. METHODS: We constructed five tissue microarrays from 183 familial breast cancer patients (31 with BRCA1 mutations; 14 with BRCA2 mutations, and 138 with non-BRCA1/2 mutations). The DNA response and repair markers used for immunohistochemistry analysis included BRIT1, ATM, CHEK2, BRCA1, RAD51, and PARP-1. The expressions of these proteins were analyzed in BRCA1/2 mutated tumors. The association between pathologic characteristics with BRCA1/2 mutation status was also analyzed. RESULTS: In familial breast cancer patients, BRCA1 mutated tumors were more frequent with high nuclear grade, estrogen receptor/progesterone receptor/human epidermal growth factor receptor 2 negative, low Ki-67, and positive CK5/6. BRCA1 mutated tumors had lower CHEK2 and higher cytoplasmic BRIT1 expression than BRCA2 and non-BRCA1/2 mutation tumors. BRCA2-associated tumors showed higher CHEK2 and cytoplasmic RAD51 expression than those in other groups. Nuclear PARP-1 expression in BRCA1/2-associated tumors was significantly higher than in non-BRCA1/2 mutation tumors. Moreover, we found quite a few of negative PARP-1 expression cases in BRCA1/2 mutated groups. CONCLUSION: The clinicopathologic findings of BRCA1-associated Chinese familial breast cancers were similar to the results of other studies. Chinese familial breast cancer patients with BRCA1/2 mutations might have distinctive expression of different DNA damage response proteins. The reduced expression of PARP-1 in Chinese BRCA1/2 mutated breast cancer patients could influence the therapeutic outcome of PARP-1 inhibitors.

Clinicopathologic features of breast lymphoma in core needle biopsy / 中华病理学杂志

Objective@#To investigate the clinicopathologic features and differential diagnosis of breast lymphoma in core needle biopsy.@*Methods@#Seventy-two cases of breast lymphoma in core needle biopsy between 2011 and 2016 were extracted from the pathology database of Fudan University Shanghai Cancer Center. The clinicopathologic features were analyzed. The histological diagnosis of the tumors was based on the WHO classifications of tumors of hematopoietic and lymphoid tissues. Immunohistochemistry and molecular methods were performed to detect related antigens and genes.@*Results@#Seventy-one patients were female and one was male. The median age was 54 years. The tumors were located in the right breast in 32 (44.4%) patients and in the left breast in 40 (55.6%) patients. Seven patients had a previous history of lymphoma. Most of the cases presented as a single and painless breast mass. Sixty-three patients received systemic treatment, and nine patients received systemic therapy after excision. The common morphological feature was that single tumor cells infiltrated the stroma, without cohesiveness between tumor cells, and lacking glandular or nested epithelioid structures. The normal ductal and lobular structures of the mammary gland were typically preserved. The tumor cells in some cases were distributed in single rows, and should be differentiated from invasive carcinoma. All cases were positive for LCA, negative for CK. Sixty-eight cases were classified as B-cell lymphoma, including 63 cases (87.5%) of diffuse large B-cell lymphoma (DLBCL; including 3 cases of EBV-positive DLBCL and 60 cases of DLBCL, NOS), two cases of Burkitt lymphoma, one case of mantle cell lymphoma, one case of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue and one case of precursor B lymphoblastic leukemia/lymphoma. The remaining cases included two peripheral T-cell lymphoma (NOS), one extranodal NK/T cell lymphoma, nasal type and one myeloid sarcoma. In 63 cases of DLBCL, 22 cases (34.9%) expressed germinal center B-cell-like (GCB) phenotype and 41 cases (65.1%) showed non-germinal center B-cell-like (non-GCB) phenotype.@*Conclusions@#Core needle biopsy could be the preferred method for diagnosis of breast lymphoma. Diffuse large B-cell lymphoma is the most common histologic type of breast lymphoma, and non-GCB subtype is more frequent than GCB subtype.

Clinicopathologic study of infiltrating epitheliosis of the breast / 中华病理学杂志

Objective@#To evaluate the morphological and immunohistochemical features of infiltrating epitheliosis and its differential diagnosis.@*Methods@#Nine consultation and routine cases of infiltrating epitheliosis diagnosed from January 2015 to December 2016 in Fudan University Shanghai Cancer Center were collected. All tissues were formalin-fixed paraffin-embedded and routinely HE stained. The HE slides were reviewed. Immunohistochemical staining of CKpan, CK7, CK19, CK5/6, CK14, p63, SMMHC, Calponin, ER, PR, HER2, Ki-67 and S-100 protein was performed using Ventana BenchMark automated immunostainer.@*Results@#The morphological features of infiltrating epitheliosis included: (1) Florid proliferation of epithelial cells forming solid nests or papillary, glandular and cord-like pattern. The proliferative cells possessed nuclei of varying size and shape without atypia. (2) The stroma was altered, showing varying degrees of fibrosis or sclerosis. (3) The proliferative epithelial nests might flow into the spaces within small ducts and lobules at the periphery of the lesion, resulting in pseudo-infiltration. Immunohistochemically, infiltrating epitheliosis was non-uniformly positive for ER/PR, and was positive for high molecular weight CK5/6 and CK14. Myoepithelial markers p63, SMMHC and Calponin demonstrated intact, partial or entire loss of myoepithelial cells around the epithelial nests. The loss of myoepithelial markers staining was more frequent at the periphery of the lesion. The most important differential diagnoses included invasive ductal carcinoma, ductal carcinoma in situ (DCIS), and low grade adenosquamous carcinoma, etc.@*Conclusions@#Infiltrating epitheliosis is an important pseudo-infiltrating lesion. The lack of atypia, non-uniform ER/PR expression, positivity for high molecular weight cytokeratins, and the intact to partial to entire loss of myoepithelial markers around the proliferating cell nests are the key points to differentiate it from invasive carcinomas and DCIS.

Correlation between androgen receptor expression and surrogate molecular subtypes in invasive breast carcinoma / 中华病理学杂志

Objective@#To investigate androgen receptor(AR)expression in invasive breast carcinoma and the correlation with surrogate molecular breast carcinoma subtypes.@*Methods@#Immunohistochemical staining of AR and other biomarkers was performed in a cohort of 870 cases of primary invasive breast carcinomas collected from August to December, 2016. The association of AR expression with different histological and surrogate molecular subtypes was analyzed.@*Results@#The positive expression rate of AR in the immunohistochemistry-based surrogate subtypes was 96.3%(207/215) for Luminal A, 89.8%(378/421) for Luminal B, 82.4%(75/91) for HER2 overexpression and 37.1%(53/143) for triple negative breast carcinoma, with significant differences among the four groups (P<0.01). AR correlated positively with the expression of ER(P<0.01), PR(P<0.01), HER2(P=0.007), GATA3(P<0.01), GCDFP15(P<0.01)and mammaglobin(P<0.01), while negatively with the expression of Ki-67(P<0.01), CK5/6(P<0.01)and CK14(P<0.01).@*Conclusions@#AR exhibits a high expression in invasive breast carcinoma, which is mainly correlated with ER-positive breast carcinoma. Regardless of the relatively low expression rate, AR is a potential therapeutic target in triple negative breast carcinoma.

The clinicopathologic factors associated with nipple-areola complex involvement in breast cancer / 中国癌症杂志

Nipple-areola complex-sparing mastectomy (NSM) is a surgical procedure that allows the preservation of the skin and nipple-areola complex (NAC) in mastectomy. The use of NSM for breast cancer is still controversial. The appropriate standard for selecting patients with low risk of NAC involvement has not been well established. The clinicopathologicity characteristics of primary tumor (e.g., tumor-to-nipple distance, tumor location, tumor size, multicentricity, lymph node metastasis, lymphovascular invasion, grade, HER-2 status) have been reported to be associated with NAC involvement. Clinical evaluation of NAC, retroareolar tissue biopsy and evaluation of clinicopathologic characteristics of primary tumor are helpful to patient selection in current clinical practice of NSM. Further studies are still needed to establish uniform selection criteria for NSM in breast cancer patients.

Metastases to the breast from non-mammary malignancies: a clinicopathologic study of 28 cases / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the clinicopathologic characteristics and differential diagnosis of the metastases to the breast from non-mammary malignancies.</p><p><b>METHODS</b>Twenty-eight cases were collected from 2004 to 2012;microscopic pathologic examinations and immunohistochemistry (EnVision method) were performed.</p><p><b>RESULTS</b>(1) All except one patients were female, ranging from 16 to 77 years old (average 45.8 years). Twenty-six (92.9%) patients initially presented with the primary site lesions; while the other two (7.1%) patients initially presented with breast lesions. The mean interval from primary diagnosis to detection of metastatic breast lesions was 32 months (0-228 months). Fifteen patients (53.6%) had other metastases detected simultaneously or preceded the breast lesions. (2) Macroscopically, all the tumors were relatively circumscribed, with a mean diameter of 4.0 cm (0.6-12.0 cm). The histological types of the corresponding primary tumors were as follows: eight (28.6%) cases from lung adenocarcinoma, five (17.8%) from high-grade ovarian serous carcinoma, three (10.7%) from gastric adenocarcinoma, two (7.1%) from rectal adenocarcinoma, one (3.6%) from pancreatic neuroendocrine carcinoma, one (3.6%) from prostatic carcinoma, four (14.3%) from melanoma, and four (14.3%) from mesenchymal malignant tumors (three rhabdomyosarcomas and one epithelioid malignant peripheral nerve sheath tumor, MPNST). (3) Histologically, the metastatic tumors showed the morphologic characteristics of the primary tumors. Lymph-vascular invasion was observed in 19 cases. Immunohistochemical features of metastatic tumors were consistent with the primary tumors. Molecular markers for breast such as GCDFP15 and mammaglobin were negative. Metastatic tumors from lung adenocarcinoma expressed TTF-1 (8/8). Ovarian serous carcinoma metastases were positive for PAX8 (5/5) and WT1 (4/5). Gastric adenocarcinoma metastases were positive for CDX2 (3/3) and villin (1/3). Rectal adenocarcinoma metastases were positive for CDX2 (2/2). Pancreatic neuroendocrine tumor metastasis was positive for Syn and CgA (both 1/1). Prostate carcinoma metastasis was positive for AR, PSA and P504S (all 1/1). Melanoma metastases were positive for HMB45 (2/3) and S-100 protein (3/3). Rhabdomyosarcoma metastases were positive for vimentin, desmin and myoD1 (all 3/3). MPNST metastasis was positive for S-100 protein (1/1). (4) Follow-up data was available in 17 patients, with median follow-up time 54 months. The median survival from diagnosis to breast metastasis was 24 months.Seven of 17 patients died.</p><p><b>CONCLUSIONS</b>Metastases to the breast from non-mammary malignancies are rare and show pathologic features of primary tumors. It is usually presumed to be a primary breast carcinoma. Histopathologic features and clinical history in conjunction with the immunohistochemical results should be considered in differentiating a secondary mass from a primary breast carcinoma.</p>

Clinicopathologic features of cystic hypersecretory lesion of the breast / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features, immunophenotype and differential diagnosis of cystic hypersecretory lesion (CHL) of the breast.</p><p><b>METHODS</b>Clinicopathologic and follow-up data of six cases of breast CHL in 2010-2013 were collected and reviewed.Immunohistochemical and mucinous staining was performed.</p><p><b>RESULTS</b>All six patients were female, age ranged from 37 to 71 years (average 49.3 years). Three cases were cystic hypersecretory hyperplasia (CHH), the other three cases were cystic hypersecretory carcinoma (CHC). Clinically the lesions presented as either breast mass or mammographic calcification.Grossly, the cystic hypersecretory lesions were poorly circumscribed, with multiple colloid containing cysts on the cut surface. Microscopically, the remarkable feature was numerous enlarged cysts which contained densely eosinophilic homogeneous secretion similar to the colloid seen in thyroid follicles, and calcification was seen in the cyst in one case. The secretion was D-PAS and mucicarmine positive. The lining epithelium of the cysts was uniformly flat, cuboid or columnar, and arranged in a monolayer. The cells may be arranged in turfs, solid or micropapillary patterns in CHH.In cases with dysplasia, the epithelium showed cytological and structural atypia, but the usual morphology of atypical dutal hyperplasia such as arcades, rigid bridges or cribriform pattern was less common. The three CHC included two invasive ductal carcinomas (IDC) and one ductal carcinoma in situ (DCIS).In CHL, there was immunoreactivity to S-100 protein, CK5/6 and CK14.Of the three CHCs, ER and PR were expressed in only one IDC.No HER2 expression was identified in the two invasive CHCs.One patient was lost to follow-up, and the rest were uneventful at 18 months.</p><p><b>CONCLUSIONS</b>CHL of the breast is a rare pathological entity. Multiple colloid-filled cysts is a unique histological feature. The epithelium of CHL may show usual hyperplasia, dysplasia or carcinoma.</p>

Comparison of clinicopathologic features of breast carcinoma in Shanghai Han and Xinjiang Uygur women / 中国癌症杂志

Background and purpose: Breast cancer is a group of heterogeneous diseases which has racial disparities. Our study was to elucidate the clinicopathologic features of breast carcinoma in Shanghai Han and Xinjiang Uygur women and to analyze the racial differences. Methods: In this study, 125 cases of breast invasive ductal carcinoma of Shanghai Han women and 85 cases of Xinjiang Uygur women were collected. The clinical stage was analyzed. Histological grading was observed. Immunohistochemical staining of ER, PR, HER-2, CK5/6, CK14, EGFR, Ki-67 was performed. Molecular subtypes were studied. Results:The average age of onset of breast cancer in Xinjiang Uygur women was younger than in Shanghai Han women (P<0.05), and Xinjiang Uygur women were more likely to be diagnosed at less than 35 years old (P<0.01). The proportion of stageⅠwas higher in Shanghai Han women (20.0%vs 8.2%), while the proportion of stageⅢwas higher in Xinjiang Uygur women (50.6%vs 27.2%) (P<0.01). The proportion of grade 2 was higher in Shanghai Han women (67.2% vs 43.5%), while the proportion of grade 3 was higher in Xinjiang Uygur women (47.1%vs 31.2%) (P<0.01). The proportion of luminal A subtype was higher in Shanghai Han women (36.8%vs 18.3%), while the proportion of basal-like subtype was higher in Xinjiang Uygur women (29.6%vs 12.0%) (P<0.01). The molecular subtype was associated with race and histological grade (P<0.05).Conclusion:There are racial differences in clinicopathologic features of breast carcinoma between Shanghai Han and Xinjiang Uygur women.