Objective:To investigate the clinicopathological features, immunohistochemical characteristics, and differential diagnosis of low-grade adenosquamous carcinoma of the breast arising from benign sclerosing lesions.Methods:Twelve cases of low-grade adenosquamous carcinoma arising from benign sclerosing lesions of the breast were collected, which were diagnosed from January 2010 to December 2023 at the Seventh Medical Center of the Chinese People′s Liberation Army General Hospital. Their clinical manifestations, histopathological morphology, and immunohistochemical characteristics were analyzed and related literatures were reviewed.Results:All the 12 patients were females with a median age of 42 years (21-60 years). Five of the 12 cases had coexisting complex sclerosing lesions, 5 with sclerosing adenosis, 1 with sclerosing intraductal papilloma, and 1 with ductal adenoma. Microscopically, low-grade adenosquamous carcinoma grew infiltratively in multinodular and sclerosing lesions. The carcinomatous component was characterized by small irregular glandular structures, tubular formations, solid nests, clusters, or a single tumor cell. The epithelium showed varying degrees of squamous differentiation. The carcinoma was surrounded by fibroadenomatoid and desmoplastic lesions. The invasive neoplastic component typically infiltrated normal breast structures, and might infiltrate nerves and adipose tissue. There were lymphocytic aggregates commonly seen at the periphery. By immunohistochemistry, the tumor cells of all 12 cases showed diffuse and strong immunopositivity for CK5/6; negative expression of ER, PR and HER2; and variable expression of myoepithelial markers such as SMA, calponin, SMMHC and others. There was varied staining pattern of tumor cells for p63. CK8/18 (or CK7) was variably positive or negative. The proliferative index measured by Ki-67 was low.Conclusions:Low-grade adenosquamous carcinoma of the breast is a rare variant, which is found to coexist with other benign sclerosing lesions and can be easily missed and/or misdiagnosed. Their invasive growth pattern, presence of sweat duct-like structures and immunophenotypic profile are key features for appropriate diagnosis.

Objective:To investigate the morphological changes and immunophenotypic characteristics of eosinophilic coarse granules in the cytoplasm of epithelial cells of breast adenosis, and their clinicopathological significance.Methods:A total of 64 cases containing eosinophilic coarse granules in the cytoplasm of breast epithelial cells admitted to the Department of Pathology of the Seventh Medical Center of People′s Liberation Army General Hospital and the Department of Pathology of Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University for admission and consultation from December 2019 to August 2023 were collected. The distribution and morphological characteristics of eosinophilic coarse granules in the epithelial cytoplasm in 64 cases of breast adenosis were observed. Some cases underwent immunohistochemical staining of lysozyme, α-antitrypsin, α-antichymotrypsin, cathepsin D, EMA, panCK, ER, PR, AR, GCDFP-15, Syn, CgA, NSE, CD68, S-100, anti-mitochondrial antibody, p63, and SMA; and some cases were stained with mucicarmine, and AB-PAS histochemical staining before and after amylase digestion.Results:The eosinophilic coarse granules in the breast epithelial cytoplasm of 64 cases were seen accidentally, of which most (43 cases) were located in adenosis adjacent to the intraductal papilloma. By HE sections, eosinophilic coarse granules were found with diffuse distribution in the cytoplasm, which were round in varying sizes, pink-bright red, and with a certain degree of refractivity. The size of the coarse granules could be divided into three types: small, medium and large. The medium to large granules were more prominent in the lesions. The eosinophilic coarse granules were all positive for lysozyme, α-antitrypsin, α-antichymotrypsin, cathepsin D, EMA and S-100. ER and PR were all nonclonal positive in glandular epithelial cells. Histochemical stains for PAS were all positive before and after digestion of amylase. AR, GCDFP-15, Syn, CgA, NSE, CD68 and anti-mitochondrial antibodies were all negative; mucicarmine and AB staining were also negative.Conclusions:The morphological characteristics and immunophenotype of cytoplasmic eosinophilic coarse granules in the epithelial cells of breast adenosis are the same as those of zymogen granules, their existence may be a non-specific morphological change, representing a metaplasia of breast epithelial cells. Positive results for lysozyme, antichymotrypsin, etc. cannot be considered evidence of specific cell differentiation. For the diagnosis of acinar cell carcinoma, it should be combined with morphological characteristics, immunohistochemical characteristics, etc. to make a comprehensive analysis.

Objective:To investigate the clinicopathological features, immunohistochemical characteristics, and differential diagnosis of low-grade adenosquamous carcinoma of the breast arising from benign sclerosing lesions.Methods:Twelve cases of low-grade adenosquamous carcinoma arising from benign sclerosing lesions of the breast were collected, which were diagnosed from January 2010 to December 2023 at the Seventh Medical Center of the Chinese People′s Liberation Army General Hospital. Their clinical manifestations, histopathological morphology, and immunohistochemical characteristics were analyzed and related literatures were reviewed.Results:All the 12 patients were females with a median age of 42 years (21-60 years). Five of the 12 cases had coexisting complex sclerosing lesions, 5 with sclerosing adenosis, 1 with sclerosing intraductal papilloma, and 1 with ductal adenoma. Microscopically, low-grade adenosquamous carcinoma grew infiltratively in multinodular and sclerosing lesions. The carcinomatous component was characterized by small irregular glandular structures, tubular formations, solid nests, clusters, or a single tumor cell. The epithelium showed varying degrees of squamous differentiation. The carcinoma was surrounded by fibroadenomatoid and desmoplastic lesions. The invasive neoplastic component typically infiltrated normal breast structures, and might infiltrate nerves and adipose tissue. There were lymphocytic aggregates commonly seen at the periphery. By immunohistochemistry, the tumor cells of all 12 cases showed diffuse and strong immunopositivity for CK5/6; negative expression of ER, PR and HER2; and variable expression of myoepithelial markers such as SMA, calponin, SMMHC and others. There was varied staining pattern of tumor cells for p63. CK8/18 (or CK7) was variably positive or negative. The proliferative index measured by Ki-67 was low.Conclusions:Low-grade adenosquamous carcinoma of the breast is a rare variant, which is found to coexist with other benign sclerosing lesions and can be easily missed and/or misdiagnosed. Their invasive growth pattern, presence of sweat duct-like structures and immunophenotypic profile are key features for appropriate diagnosis.

Objective:To investigate the morphological changes and immunophenotypic characteristics of eosinophilic coarse granules in the cytoplasm of epithelial cells of breast adenosis, and their clinicopathological significance.Methods:A total of 64 cases containing eosinophilic coarse granules in the cytoplasm of breast epithelial cells admitted to the Department of Pathology of the Seventh Medical Center of People′s Liberation Army General Hospital and the Department of Pathology of Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University for admission and consultation from December 2019 to August 2023 were collected. The distribution and morphological characteristics of eosinophilic coarse granules in the epithelial cytoplasm in 64 cases of breast adenosis were observed. Some cases underwent immunohistochemical staining of lysozyme, α-antitrypsin, α-antichymotrypsin, cathepsin D, EMA, panCK, ER, PR, AR, GCDFP-15, Syn, CgA, NSE, CD68, S-100, anti-mitochondrial antibody, p63, and SMA; and some cases were stained with mucicarmine, and AB-PAS histochemical staining before and after amylase digestion.Results:The eosinophilic coarse granules in the breast epithelial cytoplasm of 64 cases were seen accidentally, of which most (43 cases) were located in adenosis adjacent to the intraductal papilloma. By HE sections, eosinophilic coarse granules were found with diffuse distribution in the cytoplasm, which were round in varying sizes, pink-bright red, and with a certain degree of refractivity. The size of the coarse granules could be divided into three types: small, medium and large. The medium to large granules were more prominent in the lesions. The eosinophilic coarse granules were all positive for lysozyme, α-antitrypsin, α-antichymotrypsin, cathepsin D, EMA and S-100. ER and PR were all nonclonal positive in glandular epithelial cells. Histochemical stains for PAS were all positive before and after digestion of amylase. AR, GCDFP-15, Syn, CgA, NSE, CD68 and anti-mitochondrial antibodies were all negative; mucicarmine and AB staining were also negative.Conclusions:The morphological characteristics and immunophenotype of cytoplasmic eosinophilic coarse granules in the epithelial cells of breast adenosis are the same as those of zymogen granules, their existence may be a non-specific morphological change, representing a metaplasia of breast epithelial cells. Positive results for lysozyme, antichymotrypsin, etc. cannot be considered evidence of specific cell differentiation. For the diagnosis of acinar cell carcinoma, it should be combined with morphological characteristics, immunohistochemical characteristics, etc. to make a comprehensive analysis.

In the past decade, breast pathology in China has made significant progress in diagnostic standards, technological applications, scientific research, and discipline development. The histopathological diagnostic system has been continuously refined, with the implementation of relevant guidelines and expert consensus enhancing standardization and reproducibility of diagnostic results. Immunohistochemistry and molecular testing technologies have become increasingly sophisticated, with emerging biomarkers such as low HER2 expression and PIK3CA mutations gradually integrated into clinical decision-making, promoting the advancement of precision therapy. The application of digital pathology and image-assisted analysis has steadily expanded, providing new tools to improve diagnostic efficiency and consistency. The national breast pathology group has actively advanced the development of tiered diagnostic systems, workforce training, and public education, effectively strengthening diagnostic capabilities at the grassroots level. Looking ahead, the integration of multidimensional data, optimization of auxiliary diagnostic systems, and interdisciplinary collaboration are expected to drive the continued development of breast pathology in China.

In the past decade, breast pathology in China has made significant progress in diagnostic standards, technological applications, scientific research, and discipline development. The histopathological diagnostic system has been continuously refined, with the implementation of relevant guidelines and expert consensus enhancing standardization and reproducibility of diagnostic results. Immunohistochemistry and molecular testing technologies have become increasingly sophisticated, with emerging biomarkers such as low HER2 expression and PIK3CA mutations gradually integrated into clinical decision-making, promoting the advancement of precision therapy. The application of digital pathology and image-assisted analysis has steadily expanded, providing new tools to improve diagnostic efficiency and consistency. The national breast pathology group has actively advanced the development of tiered diagnostic systems, workforce training, and public education, effectively strengthening diagnostic capabilities at the grassroots level. Looking ahead, the integration of multidimensional data, optimization of auxiliary diagnostic systems, and interdisciplinary collaboration are expected to drive the continued development of breast pathology in China.

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.