Granulomatous mastitis is an uncommon inflammatory disease that typically presents with painful breast lesions. Recent publications have brought to light a specific subset of granulomatous mastitis ...patients with a distinct histological pattern of disease termed, “cystic neutrophilic granulomatous mastitis” (CNGM). Although many cases of granulomatous lobular mastitis have been thought to be idiopathic, this rare subset of an uncommon disease has been linked to infections with Corynebacterium species. Herein, a cohort of CNGM patients from a large, tertiary care, North‐American, academic medical center is presented. Correlative demographic, clinical, radiographic, pathologic, microbiologic, management, and outcomes data are provided. Collaborative communication between specialists to accurately diagnose and manage these patients is essential to decreasing potential morbidity.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Aims
Mammary amyloid is an uncommon and easily overlooked pathological diagnosis with ambivalent presentation. Herein, we delineate the clinicopathological and radiographic characteristics of mammary ...amyloid.
Methods and results
The Department of Pathology database was searched from 1993 to 2019 for keywords ‘breast’ and ‘amyloid’, yielding 32 cases from 23 patients, including consultation cases. All patients were female, age range = 52–81 (mean = 67.4 years). The left breast was involved more than the right (43 versus 33%, respectively); bilateral amyloid involvement was also present (24%). Amyloid was most often associated with a benign histopathological diagnosis (57%), lymphoma in 39% all B cell lymphomas; five of nine were mucosa‐associated lymphoid tissue (MALT) lymphoma and rarely with a concurrent epithelial malignancy (invasive lobular carcinoma, 4%). Of the 14 patients with available clinical history, amyloid presented as a mass clinically or radiographically (six patients, 43%), as microcalcifications (five patients, 36%), and only occasionally as an asymmetry (14%) or fibroglandular density (7%). Microscopic examination detected microcalcifications in an additional nine cases (total 14 patients; 44% of the cohort). Interestingly, one patient had concurrent epithelial and haematological malignancy and amyloid within an axillary lymph node. Co‐morbidities included autoimmune diseases and multiple myeloma.
Conclusion
The majority of mammary amyloid cases are associated with benign histopathological findings, while imaging most frequently noted microcalcifications or mass lesions. To avoid overlooking amyloid as simply fat necrosis or fibroelastotic stromal change, a low threshold for performing ancillary stains should be considered in elderly women with benign core needle findings performed for mass lesions or microcalcifications.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Summary Doxycycline induced gastric injury is a rarely recognized side effect of a common medication. Only two cases have previously described the distinctive capillary degeneration identified in ...gastric mucosa. We expanded on this by describing additional involved sites, endoscopic findings and patient characteristics. Design Gastrointestinal biopsy materials for cases indexed with the word “doxycycline” were retrieved and the histology reviewed. The medical record was used to obtain clinical details. Three cases with biopsy materials were identified from the search and doxycycline ingestion was confirmed. All patients' gastric biopsies had small vessel injury with fibrinoid material around the vessel, and one patient had similar changes in the duodenum. Endoscopic findings included fundic and pyloric erosions and ulcers. One patient had a normal endoscopy on follow-up after drug cessation. Confirmation and increased understanding of this drug-specific injury pattern is important for patient management as cessation appears to result in symptom improvement and healing.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
ABSTRACT
The FERM domain containing protein Kindlin‐3 has been recognized as a major regulator of integrin function in hematopoietic cells, but its role in neoplasia is totally unknown. We have ...examined the relationship between Kindlin‐3 and breast cancer in mouse models and human tissues. Human breast tumors showed a ~7‐fold elevation in Kindlin‐3 mRNA compared with nonneoplastic tissue by quantitative polymerase chain reaction. Kindlin‐3 overexpression in a breast cancer cell line increased primary tumor growth and lung metastasis by 2.5‐ and 3‐fold, respectively, when implanted into mice compared with cells expressing vector alone. Mechanistically, the Kindlin‐3‐overexpressing cells displayed a 2.2‐fold increase in vascular endothelial growth factor (VEGF) secretion and enhanced β1 integrin activation. Increased VEGF secretion resulted from enhanced production of Twist, a transcription factor that promotes tumor angiogenesis. Knockdown of Twist diminished VEGF production, and knockdown of β1 integrins diminished Twist and VEGF production by Kindlin‐3‐overexpressing cells, while nontargeting small interfering RNA had no effect on expression of these gene products. Thus, Kindlin‐3 influences breast cancer progression by influencing the crosstalk between β1 integrins and Twist to increase VEGF production. This signaling cascade enhances breast cancer cell invasion and tumor angiogenesis and metastasis.—Sossey‐Alaoui, K., Pluskota, E., Davuluri, G., Bialkowska, K., Das, M., Szpak, D., Lindner, D. J., Downs‐Kelly, E., Thompson, C. L., Plow, E. F. Kindlin‐3 enhances breast cancer progression and metastasis by activating Twist‐mediated angiogenesis. FASEB J. 28, 2260–2271 (2014). www.fasebj.org
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Secretory breast carcinoma (SBC) is a rare form of breast cancer found in both children and adults, and is the most common breast cancer in the pediatric population. Although SBC usually carries a ...favorable prognosis, there have been reported cases of axillary and distant metastases. Surgery is the primary mode of treatment, however, there exists variability within the literature surrounding the management of SBC. We report a case of an 8‐year‐old girl who presented with a firm, mobile, palpable breast mass. Ultrasonography was performed, followed by local excision, with surgical pathology concerning for SBC. The patient was definitively treated with mastectomy and sentinel lymph node (SLN) biopsy. She received no adjuvant therapies and 2 years later, remains disease free. Herein, we review the literature, curate data from 89 reported cases of pediatric and adult SBC, and address some of the controversy surrounding its treatment. From this review we conclude that patients with SBC should be reviewed at multidisciplinary treatment planning conference, undergo surgery with mastectomy or lumpectomy with SLN biopsy, and have long‐term postoperative follow‐up.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Currently, over half of breast cancer cases are unrelated to known risk factors, highlighting the importance of discovering other cancer-promoting factors. Since crosstalk between gut microbes and ...host immunity contributes to many diseases, we hypothesized that similar interactions could occur between the recently described breast microbiome and local immune responses to influence breast cancer pathogenesis.
Using 16S rRNA gene sequencing, we characterized the microbiome of human breast tissue in a total of 221 patients with breast cancer, 18 individuals predisposed to breast cancer, and 69 controls. We performed bioinformatic analyses using a DADA2-based pipeline and applied linear models with White's t or Kruskal-Wallis H-tests with Benjamini-Hochberg multiple testing correction to identify taxonomic groups associated with prognostic clinicopathologic features. We then used network analysis based on Spearman coefficients to correlate specific bacterial taxa with immunological data from NanoString gene expression and 65-plex cytokine assays.
Multiple bacterial genera exhibited significant differences in relative abundance when stratifying by breast tissue type (tumor, tumor adjacent normal, high-risk, healthy control), cancer stage, grade, histologic subtype, receptor status, lymphovascular invasion, or node-positive status, even after adjusting for confounding variables. Microbiome-immune networks within the breast tended to be bacteria-centric, with sparse structure in tumors and more interconnected structure in benign tissues. Notably, Anaerococcus, Caulobacter, and Streptococcus, which were major bacterial hubs in benign tissue networks, were absent from cancer-associated tissue networks. In addition, Propionibacterium and Staphylococcus, which were depleted in tumors, showed negative associations with oncogenic immune features; Streptococcus and Propionibacterium also correlated positively with T-cell activation-related genes.
This study, the largest to date comparing healthy versus cancer-associated breast microbiomes using fresh-frozen surgical specimens and immune correlates, provides insight into microbial profiles that correspond with prognostic clinicopathologic features in breast cancer. It additionally presents evidence for local microbial-immune interplay in breast cancer that merits further investigation and has preventative, diagnostic, and therapeutic potential.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
WAVE3, an actin cytoskeleton remodeling protein, is highly expressed in advanced stages of breast cancer and influences tumor cell invasion. Loss of miR‐31 has been associated with cancer progression ...and metastasis. Here, we show that the activity of WAVE3 to promote cancer cell invasion is regulated by miR‐31. An inverse correlation was demonstrated between expression levels of WAVE3 and miR‐31 in invasive versus noninvasive breast cancer cell lines. miR‐31 directly targeted the 3'‐UTR of the WAVE3 mRNA and inhibited its expression in the invasive cancer cells, i.e., miR‐31‐mediated down‐regulation of WAVE3 resulted in a significant reduction in the invasive phenotype of cancer cells. This relationship was specific to the loss of WAVE3 expression because re‐expression of a miR‐31‐resistant form of WAVE3 reversed miR‐31‐mediated inhibition of cancer cell invasion. Furthermore, expression of miR‐31 correlates inversely with breast cancer progression in humans, where an increase in expression of miR‐31 target genes was observed as the tumors progressed to more aggressive forms. In conclusion, a novel mechanism for the regulation of WAVE3 expression in cancer cells has been identified, which controls the invasive properties of cancer cells. The study also identifies a critical role for WAVE3, downstream of miR‐31, in the invasion‐metastasis cascade.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The American Society of Clinical Oncology/College of American Pathologists updated the human epidermal growth factor receptor 2 (HER2) breast carcinoma testing guideline in 2018 to address issues ...from uncommon HER2 fluorescence in situ hybridization (FISH) results. Based on the 2013 American Society of Clinical Oncology/College of American Pathologists guideline, cases wherein the HER2/chromosome 17 centromere (CEP17) ratio of 2.0 or more with an average HER2 copy number of less than 4.0 were considered in situ hybridization (ISH) positive. Under the 2018 guideline, such cases are classified as ISH Group 2 and are no longer considered eligible for anti-HER2 therapy when the corresponding HER2 immunohistochemistry result is 0, 1+, or 2+.
To assess the clinical, pathologic, and treatment aspects of patients with ISH Group 2 results.
We retrospectively reviewed HER2 FISH results at our center between January 2012 and December 2014 and identified and characterized cases with ISH Group 2 results.
Thirty-nine cases with ISH Group 2 results from 39 patients were reviewed. Twenty of 39 (51%) patients received anti-HER2 therapy. Patients treated with HER2-targeted therapy were less likely to have hormone receptor-positive tumors, compared with patients without anti-HER2 treatment, though not significantly (P = .30). The only significant difference between the 2 patient groups was receipt of cytotoxic chemotherapy treatment (P < .001). Overall, clinical outcome was similar between the 2 groups (P > .99).
This retrospective study with median follow-up of at least 6 years shows patients with ISH Group 2 tumors had similar clinical outcomes, irrespective of HER2-targeted therapy. Further analysis in the prospective setting would provide valuable data that would potentially inform clinical decision making.
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DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
The Uniform Approach to Breast Fine Needle Aspiration Biopsy was put forward by a learned group of breast physicians in 1997. This landmark manuscript focused predominantly on diagnosis and reporting ...of mammary epithelial lesions. Today, most American practitioners turn initially to core biopsy rather than aspiration biopsy for the first line diagnosis of solid breast lesions; however, recent efforts from the International Academy of Cytology have produced a system called the Standardized Reporting of Breast Fine Needle Aspiration Biopsy Cytology (colloquially labeled in 2017 as the “Yokohama System”), suggesting a new interest in breast fine needle aspiration (FNA), especially in resource limited settings or clinical practice settings with experienced breast cytopathologists. Fibroepithelial lesions of the breast comprise a heterogeneous group of biphasic tumors with epithelial and stromal elements. Mesenchymal lesions of the breast include a variety of neoplasms of fibroblastic, myofibroblastic, endothelial, neural, adipocytic, muscular, and osteo‐cartilaginous derivations. The cytology of mesenchymal breast lesions is infrequently described in the literature and is mainly limited to case reports and small series. This illustrated review highlights the cytologic features of fibroepithelial and mesenchymal mammary proliferations and discusses differential diagnoses and histomorphologic correlates.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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