Background and purpose:Primary adrenal intravascular large B-cell lymphoma(IVLBCL)is rare and highly aggressive.Unfortunately,comprehensive and sufficient understanding of the disease is lacking.This study investigated the clinicopathological and molecular genetic characteristics of adrenal IVLBCL.Methods:Adrenal IVLBCL cases diagnosed from 2012 to 2023 were collected from Department of Pathology,Fudan University Shanghai Cancer Center.The clinical and histopathological features,immunophenotype,treatment and prognosis were analyzed.The molecular genetic characteristics were detected using next-generation sequencing(NGS).This study was approved by the Ethics Committee of Fudan University Shanghai Cancer Center(Ethics number:050432-4-2307E).Results:All of the 5 patients were male,with median age 52 years(ranged 50-82 years).Two cases had low-grade fever,1 case had abdominal pain,1 case was found by physical examination,and the information of the remaining one was unknown.Peripheral blood test showed elevated serum lactate dehydrogenase in 2 cases and adrenal dysfunction in 2 cases.On initial diagnosis,imaging tests displayed adrenal enlargement or masses with increased fluorodeoxyglucose(FDG)uptake.Bilateral adrenal glands were involved in 4 cases and only the right adrenal gland was involved in the other case.Morphologically,large atypical lymphocytes were confined to blood vessels,and fibrinous necrosis was observed in some cases.Immunohistochemical study revealed that CD20 was positive in all cases.Ki-67 proliferation index was high,all above 80%.80%(4/5)of the cases were of non-germinal-center B-cell-like(non-GCB)phenotype,100%(4/4)of the cases had MYC/BCL2 double expression.Endothelial cell markers staining indicated that most of the tumor cells were confined within the blood vessels in all cases.Follow-up data were available in 3 patients.One patient who underwent only surgical resection died 5 months after diagnosis,one achieved complete remission after surgery plus R-CHOP,and the other diagnosed by biopsy achieved a partial remission after R-CHOP.The 1-year overall survival rate was 66.7%,and overall survival was 5-87 months.NGS testing in 1 case showed missense mutations in MYD88 V217F,TP53,CDH1,ARID1B,MSH3,MLH3,PTPRK,CD22 and FLCN.Conclusion:Adrenal IVLBCL is rare and tends to occur in the middle-aged and elderly male.The majority of our patients were non-GCB phenotype,often accompanied by MYC/BCL2 double expression,and MYD88 non-L265P mutation was detected.Early diagnosis of adrenal IVLBCL is difficult due to its diverse clinical symptoms and lack of specificity.It is of great importance to accumulate more cases and further understand the clinicopathological and molecular genetic characteristics of this rare disease,which might not only help with early diagnosis,timely treatment and improvement of prognosis,but also provide a theoretical basis for further understanding the pathogenesis and development of the disease and exploring therapeutic targets.

Purpose To investigate the challenges associ-ated with HER2-low in breast cancer across hospitals of varying regions and grades in China.Drawing on the findings from this investigation,this study will integrate relevant clinical guide-lines,consensus statements,and literature advancements from both domestic and international sources to offer insights for de-veloping guidelines for HER2 detection in Chinese breast cancer cases.Methods The questionnaire implementation method was Tencent WeChat as the carrier and online survey in the form of electronic questionnaire.Results According to the annual HER2 testing results of various medical institutions,compared with HER2 immunohistochemistry(IHC)scores of 3+,HER2 IHC scores of 1+or 2+significantly increased in the proportion range of over 20％(P＜0.001).A total of 854 pathologists provided effective feedback for this survey,55.6％reported dif-ficulties in distinguishing between a score of 0 and 1+in certain cases,primarily due to issues related to staining percentage(83.4％)and the absence of an objective standard for weak staining(78.3％).Regarding testing procedures,417(50.5％)medical institutions used only HER2 IHC 3+as an external control,whereas 139(16.8％)set up a gradient of ex-ternal controls for HER2 IHC scores of 0,1+,2+,and 3+.68.5％of pathologists routinely adhered to the microscope mag-nification rule to assist in HER2 scoring.51.9％of pathologists support a three-category reporting model for HER2 status(nega-tive/low/positive).In cases exhibiting heterogeneity,56.3％of pathologists would accept reporting the percentages of different HER2 scores(0/1+/2+/3+).Conclusion The proportion of breast cancer patients with HER2-low is relatively high in China.Currently,there is no consensus on quality control stand-ards for the pathological diagnosis and testing procedures for HER2-low.Key diagnostic challenges include defining the lower limit of interpretation standards,standardizing testing proce-dures,establishing external controls,refining interpretation methods,and standardizing reporting practices.Given the publi-cation of the DESTINY-Breast06 study results during the revision period,there is an urgent need to develop a new edition of the Chinese guidelines for HER2 testing in breast cancer to provide clearer and more specific strategies.

Purpose To examine the contemporary state of pathological diagnosis for granulomatous lobular mastitis(GLM)in China.Methods Pathologists from across the nation were invited to engage in an online questionnaire survey,which ad-dressed pertinent topics such as the frequency of GLM diagnosis cases,the modalities of pathology reporting,and advancements in etiological research.The collected data were analyzed utili-zing the x2 test or Fisher's exact test.Results A survey of 702 pathologists included 26.9％(189/702)chief physicians,43.3％(304/702)deputy chief physician,26.1％(183/702)attending physicians,and 3.7％(26/702)residents.Partici-pants were from tertiary general hospitals(77.6％,545/702),traditional Chinese medicine hospitals(7.7％,54/702),ma-ternal and child specialty hospitals(6.1％,43/702),and on-cology specialty hospitals(4.0％,28/702).In 2023,there were over 45,000 mastitis diagnoses.A significantly higher per-centage of chief physicians(60.8％,115/189)and deputy chief physicians(52.6％,160/304)could diagnose specific mastitis types compared to attending and resident physicians(x2=23.537,P＜0.001),with"GLM"being the most common diagnosis(55.1％,81/147).In diagnostic work,78.06％(548/702)of pathologists consider patient clinical information,19.2％(135/702)screen specimens for pathogens using special staining,only 6.0％(42/702)of pathologists indicated that their hospitals routinely perform tissue culture for pathogens,with corynebacterium being the most common.Additionally,11.4％(80/702)reported that clinicians regularly test serum sex hormones,most frequently for elevated prolactin,while 7.1％(50/702)check autoimmune status,frequently detecting antibodies without clinical symptoms.Chief physicians had a significantly better understanding of the etiology of GLM com-pared to other physicians(x2=11.969,P=0.003;P=0.007).A majority of pathologists indicated a lack of guidelines for GLM pathology diagnosis(49.4％,347/702)and report standards(76.4％,536/702).Nearly all(97.4％)agreed on the need to establish a consensus for GLM diagnosis.Conclu-sion GLM pathological diagnosis is currently inconsistent and lacks standardization,highlighting the urgent need for a guiding consensus for pathologists.

Purpose To investigate the challenges associ-ated with HER2-low in breast cancer across hospitals of varying regions and grades in China.Drawing on the findings from this investigation,this study will integrate relevant clinical guide-lines,consensus statements,and literature advancements from both domestic and international sources to offer insights for de-veloping guidelines for HER2 detection in Chinese breast cancer cases.Methods The questionnaire implementation method was Tencent WeChat as the carrier and online survey in the form of electronic questionnaire.Results According to the annual HER2 testing results of various medical institutions,compared with HER2 immunohistochemistry(IHC)scores of 3+,HER2 IHC scores of 1+or 2+significantly increased in the proportion range of over 20％(P＜0.001).A total of 854 pathologists provided effective feedback for this survey,55.6％reported dif-ficulties in distinguishing between a score of 0 and 1+in certain cases,primarily due to issues related to staining percentage(83.4％)and the absence of an objective standard for weak staining(78.3％).Regarding testing procedures,417(50.5％)medical institutions used only HER2 IHC 3+as an external control,whereas 139(16.8％)set up a gradient of ex-ternal controls for HER2 IHC scores of 0,1+,2+,and 3+.68.5％of pathologists routinely adhered to the microscope mag-nification rule to assist in HER2 scoring.51.9％of pathologists support a three-category reporting model for HER2 status(nega-tive/low/positive).In cases exhibiting heterogeneity,56.3％of pathologists would accept reporting the percentages of different HER2 scores(0/1+/2+/3+).Conclusion The proportion of breast cancer patients with HER2-low is relatively high in China.Currently,there is no consensus on quality control stand-ards for the pathological diagnosis and testing procedures for HER2-low.Key diagnostic challenges include defining the lower limit of interpretation standards,standardizing testing proce-dures,establishing external controls,refining interpretation methods,and standardizing reporting practices.Given the publi-cation of the DESTINY-Breast06 study results during the revision period,there is an urgent need to develop a new edition of the Chinese guidelines for HER2 testing in breast cancer to provide clearer and more specific strategies.

Purpose To examine the contemporary state of pathological diagnosis for granulomatous lobular mastitis(GLM)in China.Methods Pathologists from across the nation were invited to engage in an online questionnaire survey,which ad-dressed pertinent topics such as the frequency of GLM diagnosis cases,the modalities of pathology reporting,and advancements in etiological research.The collected data were analyzed utili-zing the x2 test or Fisher's exact test.Results A survey of 702 pathologists included 26.9％(189/702)chief physicians,43.3％(304/702)deputy chief physician,26.1％(183/702)attending physicians,and 3.7％(26/702)residents.Partici-pants were from tertiary general hospitals(77.6％,545/702),traditional Chinese medicine hospitals(7.7％,54/702),ma-ternal and child specialty hospitals(6.1％,43/702),and on-cology specialty hospitals(4.0％,28/702).In 2023,there were over 45,000 mastitis diagnoses.A significantly higher per-centage of chief physicians(60.8％,115/189)and deputy chief physicians(52.6％,160/304)could diagnose specific mastitis types compared to attending and resident physicians(x2=23.537,P＜0.001),with"GLM"being the most common diagnosis(55.1％,81/147).In diagnostic work,78.06％(548/702)of pathologists consider patient clinical information,19.2％(135/702)screen specimens for pathogens using special staining,only 6.0％(42/702)of pathologists indicated that their hospitals routinely perform tissue culture for pathogens,with corynebacterium being the most common.Additionally,11.4％(80/702)reported that clinicians regularly test serum sex hormones,most frequently for elevated prolactin,while 7.1％(50/702)check autoimmune status,frequently detecting antibodies without clinical symptoms.Chief physicians had a significantly better understanding of the etiology of GLM com-pared to other physicians(x2=11.969,P=0.003;P=0.007).A majority of pathologists indicated a lack of guidelines for GLM pathology diagnosis(49.4％,347/702)and report standards(76.4％,536/702).Nearly all(97.4％)agreed on the need to establish a consensus for GLM diagnosis.Conclu-sion GLM pathological diagnosis is currently inconsistent and lacks standardization,highlighting the urgent need for a guiding consensus for pathologists.

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.

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.

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.
Asian Continental Ancestry Group* ; Breast Neoplasms* ; Breast* ; Checkpoint Kinase 2 ; Cytoplasm ; DNA Damage* ; DNA Repair ; DNA* ; Estrogens ; Genes, BRCA1 ; Genes, BRCA2 ; Humans ; Immunohistochemistry ; Phosphotransferases ; Rad51 Recombinase ; Receptor, Epidermal Growth Factor

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.

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.