Secretory carcinoma of breast with predominant microcystic morphology： report of two cases and literature review

Abstract

Abstract:

Secretory carcinoma of breast (SCB) is a rare salivary gland-type malignant tumor of the breast. This study reports two female patients with SCB admitted between 2019 and 2023, both presenting with breast masses. Breast ultrasonography indicated a BI-RADS category Ⅲ heterogeneous hyperechoic nodule in one case and a BI-RADS category Ⅳa hypoechoic nodule in the other. Histopathological examination showed that the maximum tumor diameters were 13 mm and 14 mm, respectively, with grayish-white cut surfaces, moderate consistency, and well-defined margins. Tumor cells exhibited mild to moderate atypia, with round or oval nuclei and a single small nucleolus. The cytoplasm was eosinophilic or vacuolated, and cells were arranged in microcystic, solid, or papillary patterns, with some showing cystic, hypersecretory lesion morphology. Eosinophilic secretions were observed within the lumens, and stromal fibrous tissue hyperplasia with hyaline degeneration was noted. Immunohistochemistry showed tumor cell expression of S100, pan-TRK, CD117, CK5/6, and GATA3, with low expression of ER and AR, and no expression of GCDFP-15, PR, or HER2. The Ki-67 proliferation index was approximately 5%. Alcian blue staining and periodic acid-Schiff staining showed positively stained secretions both within the cytoplasm and extracellularly. Molecular testing showed ETV6-NTRK3 gene fusion in both patients. A literature review of Chinese and English publications from 2020 to 2024 revealed 438 reported SCB cases, among which 80 had relatively complete clinicopathological and immunophenotypic data. This study summarized the clinicopathological characteristics, immunophenotypes, and molecular alterations of the 80 cases together with the two cases from our hospital, totaling 82 cases. The results showed expression rates of S100, pan-TRK, and GATA3 at 97%, 95%, and 100%, respectively. Approximately 50% of the cases showed low to moderate ER expression, about 20% showed low PR expression, and HER2 was generally negative. Molecular testing indicated that 98% of the cases had the characteristic ETV6-NTRK3 gene fusion, and two cases also had TERT promoter or PDGFR mutations.

Key words:Secretory carcinoma of breast,Clinical pathology,Immunophenotype,Molecular testing

CLC Number:

WEI Jingjing, YIN Haoqiang, WANG Yanwen, ZHANG Xiaoyun. Secretory carcinoma of breast with predominant microcystic morphology： report of two cases and literature review[J]. Journal of Diagnostics Concepts & Practice, 2025, 24(03): 349-354.

Figures/Tables8

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Table 1

Summary of clinical pathology, immunophenotype, and molecular characteristics of 82 cases of SCB patients

临床病理、免疫表型及分子特征	数据/例数
中位年龄（范围）	43岁（3~85岁）
男性/女性(n)	1∶20
病理特征[n（%）]
微囊/蜂窝状	76（95%）
腺样/腺管状	61（76%）
实性	50（64%）
乳头状	46（58%）
免疫指标[n（%）]
ER	43（52%）
PR	15（18%）
HER2	2（2%）
Ki-67≤15%	41（70%）
S100	71（97%）
CK5/6	24（80%）
Pan-TRK	35（95%）
EGFR	6（60%）
CD117	11（65%）
GCDFP15	5（20%）
GATA3	16（100%）
基因改变[n（%）]
ETV6-NTRK3改变	58（98%）
伴PDGFR突变	1（1%）
伴TERT启动子突变	1（1%）

Table 1

References25

[1]	MCDIVITT R W, STEWART F W. Breast carcinoma in children[J].JAMA,1966,195(5):388-390.
[2]	TAVASSOLI F A, NORRIS H J. Secretory carcinoma of the breast[J].Cancer,1980,45(9):2404-2413. doi:10.1002/1097-0142(19800501)45:9<2404::aid-cncr2820450928>3.0.co;2-8pmid:6445777
[3]	ZHAO Y Y, GE H J, YANG W T, et al. Secretory breast carcinoma: clinicopathological features and prognosis of 52 patients[J].Breast Cancer Res Treat,2024,203(3):543-551.
[4]	HASSAN N, IDAEWOR P, RASHEED N, et al. Paediatric and adolescent breast cancer: A narrative review[J].Cureus,2023,15(11):e48983.
[5]	SANLI A N, TEKCAN SANLI D E, ALTUNDAG M K, et al. Secretory Carcinoma of Breast: A Population-Based Study[J].Am Surg,2024,90(2):252-260.
[6]	NOVOCHADLO KLÜPPEL E, RODRIGUES DA COSTA L, MARQUETTO TOGNOLO C, et al. Secretory breast carcinoma in a male child: Case report and literature review[J].Int J Surg Case Rep,2020,73:310-314.
[7]	CABELLO C, ALVARENGA M, ALVARENGA C A, et al. Case report and review of the literature: secretory breast cancer in a 13-year-old boy--10 years of follow up[J].Breast Cancer Res Treat,2012,133(3):813-820.
[8]	杨玉萍, 吴泽虹, 李华鹃, 等. 乳腺分泌性癌多模态超声表现1例[J].中国临床案例成果数据库,2023,5(1):E02335-E02335.
	YANG Y P, WU Z H, LI H J, et al. Multimodal ultrasonic manifestations of secretory carcinoma of the breast: a case report[J].Chin Med Care Repository,2023,5(1):E02335-E02335.
[9]	马丽莉, 刘一雄, 郭双平. 具有乳头状形态特征的乳腺分泌性癌一例[J].中华病理学杂志,2021,50(10):1183-1185.
	MA L L, LIU Y X, GUO S P. Breast secretory carcinoma with predominant papillary morphology: report of a case[J].Chin J Pathol,2021,50(10):1183-1185.
[10]	余慧萍, 郑重, 濮晓红, 等. 具有囊性高分泌特点的乳腺分泌性癌1例[J].中国临床案例成果数据库,2022,4(1):E01658-E01658.
	YU H P, ZHENG Z, PU X H, et al. Secretory breast carcinoma with the feature of cystic hypersecretory[J].Chin Med Care Repository,2022,4(1):E01658-E01658.
[11]	YANG Y, WANG Z, PAN G, et al. Pure secretory carcinoma in situ: a case report and literature review[J].Diagn Pathol,2019,14(1):95. doi:10.1186/s13000-019-0872-7pmid:31443715
[12]	TOGNON C, GARNETT M, KENWARD E, et al. The chimeric protein tyrosine kinase ETV6-NTRK3 requires both Ras-Erk1/2 and PI3-kinase-Akt signaling for fibroblast transformation[J].Cancer Res,2001,61(24):8909-8916. pmid:11751416
[13]	HECHTMAN J F, BENAYED R, HYMAN D M, et al. Pan-Trk immunohistochemistry is an efficient and reliable screen for the detection of NTRK fusions[J].Am J Surg Pathol,2017,41(11):1547-1551. doi:10.1097/PAS.0000000000000911pmid:28719467
[14]	HARRISON B T, FOWLER E, KRINGS G, et al. Pan-TRK immunohistochemistry: A useful diagnostic adjunct for secretory carcinoma of the breast[J].Am J Surg Pathol,2019,43(12):1693-1700. doi:10.1097/PAS.0000000000001366pmid:31498178
[15]	SOLOMON J P, BENAYED R, HECHTMAN J F, et al. Identifying patients with NTRK fusion cancer[J].Ann Oncol,2019,30(Suppl 8):viii16-viii22.
[16]	HODA R S, BROGI E, PAREJA F, et al. Secretory carcinoma of the breast: clinicopathologic profile of 14 cases emphasising distant metastatic potential[J].Histopathology,2019,75(2):213-224. doi:10.1111/his.13879pmid:31012486
[17]	GRABENSTETTER A, D'ALFONSO T M. The role of novel immunohistochemical markers for special types of breast carcinoma[J].Adv Anat Pathol,2023,30(6):374-379.
[18]	KRINGS G, JOSEPH N M, BEAN G R, et al. Genomic profiling of breast secretory carcinomas reveals distinct genetics from other breast cancers and similarity to mammary analog secretory carcinomas[J].Mod Pathol,2017,30(8):1086-1099.
[19]	AMELINE B, SABA K H, KOVAC M, et al. NTRK fusions in osteosarcoma are rare and non-functional events[J].J Pathol Clin Res,2020,6(2):107-112.
[20]	刘嘉慧, 黄玲, 孙朝晖, 等. 核受体转录因子ERRα在肿瘤发生发展中的研究进展[J].重庆医科大学学报,2023,48(4):477-481.
	LIU J H, HUANG L, SUN C H, et al. Research advances of ERRα nuclear receptor transcription factor in cancer development and progression[J].J Chongqing Med Univ,2023,48(4):477-481.
[21]	LIAN J, WANG L X, GUO J H, et al. Secretory breast carcinoma in a female adult with liver metastsis: a case report and literature review[J].Diagn Pathol,2021,16(1):89. doi:10.1186/s13000-021-01156-6pmid:34629079
[22]	TANG H, ZHONG L, JIANG H, et al. Secretory carcinoma of the breast with multiple distant metastases in the brain and unfavorable prognosis: a case report and literature review[J].Diagn Pathol,2021,16(1):56. doi:10.1186/s13000-021-01115-1pmid:34162406
[23]	IORFIDA M, BAGNARDI V, ROTMENSZ N, et al. Outcome of male breast cancer: a matched single-institution series[J].Clin Breast Cancer,2014,14(5):371-377. doi:10.1016/j.clbc.2014.02.008pmid:24742826
[24]	徐艳, 石群立, 周晓军, 等. 男性乳腺分泌性癌一例[J].中华病理学杂志,2009,38(10):707-708.
	XU Y, SHI Q L, ZHOU X J, et al. A case of male breast secretory carcinoma[J].Chin J Pathol,2009,38(10): 707-708.
[25]	包丰昌, 王贇霞, 雷平冲, 等. 外周血淋巴细胞亚群与临床病理及磁共振特征联合预测乳腺癌Ki-67表达的临床研究[J].安徽医学,2023,44(12):1462-1466.
	BAO F C, WANG B X, LEI P C, et al. Clinical study on the prediction of Ki-67 expression in breast cancer by peripheral blood lymphocyte subsets, clinicopathologic and magnetic resonance features[J].Anhui Med J,2023,44(12):1462-1466.