Objective:To investigate the clinicopathological features and differential diagnosis of breast angiomatosis.Methods:Six cases of breast angiomatosis diagnosed at the Department of Pathology, the Seventh Medical Center, People′s Liberation Army General Hospital and the Department of Pathology, Dongzhimen Hospital, Beijing University of Chinese Medicine from January 2011 to December 2023 were evaluated and reviewed.Results:All patients were female with an average age of 46 years at presentation, ranging from 25 to 62 years. The most common clinical presentation was a palpable unilateral breast mass with diameter ranging from 7 to 14 cm, and the average size was 11 cm. Histologically, all cases were composed of variably-sized ectatic, thin-walled blood vessels with minimal to no apparent smooth muscle, lined by flat normochromic endothelium without atypia, and diffusely infiltrating the breast stroma. Where present, the lesional vessels infiltrated between and around terminal duct lobular units but not into individual intralobular stroma. Immunohistochemical staining for CD31, CD34, Factor Ⅷ, Fli-1 and D2-40 revealed positive expression in vascular and/or lymphatic endothelial cells. Additionally, the Ki-67 proliferation index was found to be less than 1%.Conclusions:Angiomatosis of the breast is a rare benign vascular lesion. Distinguishing it from low-grade angiosarcoma requires careful consideration of the growth pattern, atypical features, and Ki-67 proliferation index.

Auditory neuropathy spectrum disorder (ANSD) represents a variety of sensorineural deafness conditions characterized by abnormal inner hair cells and/or auditory nerve function, but with the preservation of outer hair cell function. ANSD represents up to 15% of individuals with hearing impairments. Through mutation screening, bioinformatic analysis and expression studies, we have previously identified several apoptosis-inducing factor (AIF) mitochondria-associated 1 (AIFM1) variants in ANSD families and in some other sporadic cases. Here, to elucidate the pathogenic mechanisms underlying each AIFM1 variant, we generated AIF-null cells using the clustered regularly interspersed short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system and constructed AIF-wild type (WT) and AIF-mutant (mut) (p.‍T260A, p.‍R422W, and p.‍R451Q) stable transfection cell lines. We then analyzed AIF structure, coenzyme-binding affinity, apoptosis, and other aspects. Results revealed that these variants resulted in impaired dimerization, compromising AIF function. The reduction reaction of AIF variants had proceeded slower than that of AIF-WT. The average levels of AIF dimerization in AIF variant cells were only 34.5%‍‒‍49.7% of that of AIF-WT cells, resulting in caspase-independent apoptosis. The average percentage of apoptotic cells in the variants was 12.3%‍‒‍17.9%, which was significantly higher than that (6.9%‍‒‍7.4%) in controls. However, nicotinamide adenine dinucleotide (NADH) treatment promoted the reduction of apoptosis by rescuing AIF dimerization in AIF variant cells. Our findings show that the impairment of AIF dimerization by AIFM1 variants causes apoptosis contributing to ANSD, and introduce NADH as a potential drug for ANSD treatment. Our results help elucidate the mechanisms of ANSD and may lead to the provision of novel therapies.
Humans ; Apoptosis Inducing Factor/metabolism* ; NAD/metabolism* ; Dimerization ; Apoptosis

Auditory neuropathy spectrum disorder (ANSD) represents a variety of sensorineural deafness conditions characterized by abnormal inner hair cells and/or auditory nerve function, but with the preservation of outer hair cell function. ANSD represents up to 15％ of individuals with hearing impairments. Through mutation screening, bioinformatic analysis and expression studies, we have previously identified several apoptosis-inducing factor (AIF) mitochondria-associated 1 (AIFM1) variants in ANSD families and in some other sporadic cases. Here, to elucidate the pathogenic mechanisms underlying each AIFM1 variant, we generated AIF-null cells using the clustered regularly interspersed short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system and constructed AIF-wild type (WT) and AIF-mutant (mut) (p.T260A, p.R422W, and p.R451Q) stable transfection cell lines. We then analyzed AIF structure, coenzyme-binding affinity, apoptosis, and other aspects. Results revealed that these variants resulted in impaired dimerization, compromising AIF function. The reduction reaction of AIF variants had proceeded slower than that of AIF-WT. The average levels of AIF dimerization in AIF variant cells were only 34.5％?49.7％ of that of AIF-WT cells, resulting in caspase-independent apoptosis. The average percentage of apoptotic cells in the variants was 12.3％?17.9％, which was significantly higher than that (6.9％?7.4％) in controls. However, nicotinamide adenine dinucleotide (NADH) treatment promoted the reduction of apoptosis by rescuing AIF dimerization in AIF variant cells. Our findings show that the impairment of AIF dimerization by AIFM1 variants causes apoptosis contributing to ANSD, and introduce NADH as a potential drug for ANSD treatment. Our results help elucidate the mechanisms of ANSD and may lead to the provision of novel therapies.

Objective: To investigate the clinicopathologic features and possible causes of granulomatous lobular mastitis(GLM). Methods: Three hundred cases of GLM were collected from surgical specimens diagnosed at Longhua Hospital, Shanghai University of Traditional Chinese Medicine from January 2015 to November 2017. Morphologic features were reviewed using HE staining. A total of 116 cases were investigated by Gram staining. The expression of CD3, CD20, CD68, IgG, IgG4, CD38 and CD138 was detected by immunohistochemical staining. Results: The age of the patients was 23 to 47 years and the median age was 32 years. All patients were female, 96.7% (290/300) had a history of lactation.There were 143 cases of left breasts, 138 cases of right breast and 19 cases of bilateral breasts. Serum prolactin increased in 39.7%(119/300) patients. Within 15.7%(47/300) of patients were associated with nodular erythema or joint swelling and pain of the lower extremities. Pathological observation showed that lobular-centric suppurative granulomatous inflammation, accompanied by dilatation of intralobular and interlobular ducts. There were 16 cases accompanied with duct ectasia. Immunohistochemistry showed CD3-positive lymphocytes were more than CD20-positive lymphocytes in the peripheral aggregation zone of neutrophils within granulomatous lesions. Gram positive bacteria were found in the lipid vacuoles of the 51.7%(60/116) patients. Conclusions GLM has distinctive histologic features. It may be related to corynebacterium infection, or accompanied by the increase of serum prolactin and erythrocyte sedimentation rate. The age, location and history of the disease are importance in the diagnosis and differential diagnosis.

Objective To investigate the clinicopathologic features and possible causes of granulomatous lobular mastitis(GLM). Methods Three hundred cases of GLM were collected from surgical specimens diagnosed at Longhua Hospital, Shanghai University of Traditional Chinese Medicine from January 2015 to November 2017. Morphologic features were reviewed using HE staining. A total of 116 cases were investigated by Gram staining. The expression of CD3, CD20, CD68, IgG, IgG4, CD38 and CD138 was detected by immunohistochemical staining. Results The age of the patients was 23 to 47 years and the median age was 32 years. All patients were female, 96.7% (290/300) had a history of lactation.There were 143 cases of left breasts, 138 cases of right breast and 19 cases of bilateral breasts. Serum prolactin increased in 39.7%(119/300) patients. Within 15.7%(47/300) of patients were associated with nodular erythema or joint swelling and pain of the lower extremities. Pathological observation showed that lobular?centric suppurative granulomatous inflammation, accompanied by dilatation of intralobular and interlobular ducts. There were 16 cases accompanied with duct ectasia. Immunohistochemistry showed CD3?positive lymphocytes were more than CD20?positive lymphocytes in the peripheral aggregation zone of neutrophils within granulomatous lesions. Gram positive bacteria were found in the lipid vacuoles of the 51.7%(60/116) patients. Conclusions GLM has distinctive histologic features. It may be related to corynebacterium infection, or accompanied by the increase of serum prolactin and erythrocyte sedimentation rate. The age, location and history of the disease are importance in the diagnosis and differential diagnosis.

Breast ; pathology ; Female ; Humans ; Reference Standards

Purpose To investigate the clinical pathological features, histologic features, and prognosis of solid papillary carcinoma ( SPC) of breast. Methods Nine cases of SPC of breast were analyzed by morphological observation, AB-PAS staining and immuno-histochemical MaxVision staining. The follow-up and analysis of the clinical datas of these nine cases were performed and relevant liter-atures were also reviewed. Results The age of 9 cases of SPC of breast ranged from 32 to 83 years old (mean age is 69. 2 years old). Three cases presented with nipple discharge. Nuclear levels of 9 cases were between low to mid-level. Seven cases were associated with intracellular and extracellular mucus secretion, two cases with calcification, and 3 cases with comedonecrosis. All of these nine cases were ER, PR positive and the positive rates were high ( >70%) , HER-2 was all negative. Syn expression in these nine cases were diffused positive except for one case showing focal positive, 4 with CgA diffused positive, 1 with partial positive and 4 were negative of CgA. Six patients had partial loss of the expression of myoepithelial markers, and 3 cases with complete myoepithelial expression. Ki-67 proliferation index was between 3% and 20%. Except for only one case with small area of invasive ductal carcinoma (IDC) (2 mm in great diameter) , all other cases were not associated with other types of breast cancer, sentinel lymph nodes and/or axillary/supracla-vicular lymph nodes metastasis. 8 patients accepted breast-conserving surgey, one case did not undergo radical mastectomy for small le-sion. All of these cases were accepted further endocrine drugs treatment and only one case accepted chemical therapy simultaneously because of the accompanied IDC. None of them was found to relapse for 3 to 61 months (mean 19. 6 months) of follow-up. Conclusion Nine cases of SPC of breast showed some characteristics such as relatively low nuclear level, often accompanied by intracellular and extracellular mucus secretion, positive for neuroendocrine marker, low lymph node metastasis rate, and no recurrence, which suggest that SPC may have a better clinical prognosis.

OBJECTIVETo investigate the pathology, diagnosis and differential diagnosis of carcinomas arising in fibroepithelial neoplasms of the breast.

METHODSMorphological observation and immunohistochemistry using MaxVision method were performed in fifty-four cases of carcinoma arising from fibroepithelial neoplasms of the breast from January 2003 to February 2014.

RESULTSThirty-eight cases of carcinoma arose from fibroadenomas. Twelve cases were classical lobular carcinoma in situ (LCIS). Twenty-one cases were ductal carcinoma in situ (DCIS), including four cases of low-grade, ten cases of intermediate-grade, six cases of high-grade and one case of apocrine. One case was mixed DCIS and LCIS. Three cases were infiltrating ductal carcinoma (IDC) accompanied with DCIS. One case was spindle cell metaplastic carcinoma. Sixteen cases arose from phyllodes tumours. Six cases arose from benign phyllodes tumours, including four cases of low-grade DCIS, one case of high-grade DCIS, and one case of classical LCIS with micro-invasion (diameter 0.9 mm). Three cases arose from borderline phyllodes tumours, including one case of classical LCIS, one case of intermediate-grade DCIS, and one case of invasive lobular carcinoma (ILC) with LCIS. Seven cases arose from malignant phyllodes tumours, including two cases each of low-grade DCIS and intermediate-grade DCIS, one case of high-grade DCIS, one case of apocrine DCIS, and one case of mixed IDC with DCIS. By immunohistochemistry, LCIS and ILC were diffusely positive for ER and PR. Low-grade DCIS was diffusely positive for ER and PR ( > 90%), intermediate-grade DCIS was 70%-90% positive, high-grade DCIS was negative for ER and 20%-30% positive for PR, apocrine DCIS was both negative, and IDC was 40%-90% positive. The spindle cell metaplastic carcinoma was negative for ER and PR, but showed diffuse or scattered positivity for CK5/6 and p63.

CONCLUSIONSCarcinomas arising from fibroepithelial neoplasms of the breast are rare, showing unusual clinical presentation, and are characterized by in situ or invasive carcinomas in a background of fibroepithelial neoplasms. The accurate diagnosis depends on the recognition of the background fibroepithelial neoplasms and assessment of the nature of the epithelial proliferation, supplemented by immunohistochemistry when necessary.

Breast Neoplasms ; pathology ; Carcinoma in Situ ; pathology ; Carcinoma, Ductal, Breast ; pathology ; Carcinoma, Intraductal, Noninfiltrating ; pathology ; Carcinoma, Lobular ; pathology ; Female ; Humans ; Immunohistochemistry ; Neoplasms, Fibroepithelial ; pathology ; Phyllodes Tumor ; pathology ; Rare Diseases ; pathology

Breast Neoplasms ; pathology ; Carcinoma in Situ ; metabolism ; pathology ; Carcinoma, Intraductal, Noninfiltrating ; metabolism ; pathology ; Carcinoma, Papillary ; metabolism ; pathology ; Collagen Type IV ; metabolism ; Female ; Humans ; Neoplasm Invasiveness ; pathology

Biopsy ; adverse effects ; Breast ; pathology ; radiation effects ; Breast Implantation ; adverse effects ; Breast Neoplasms ; drug therapy ; radiotherapy ; Drug-Related Side Effects and Adverse Reactions ; etiology ; Female ; Humans ; Iatrogenic Disease