Secretory carcinoma of the breast and its histopathological mimics: value of markers for differential diagnosis.
OBJECTIVE
Secretory carcinoma (SC) is a rare histological type of breast cancer, and ETV6-NTRK3 gene fusion is highly specific to it. The differential diagnoses of SC include acinic cell carcinoma (ACCA) and cystic hypersecretory carcinoma (CHC), as well as invasive ductal carcinoma (IDC). For patients with these rare but distinctive histological subtypes, SC and its histopathological mimics should be differentiated from each other. However, differential markers have not yet been assessed systematically, and we aimed to identify and evaluate novel and existing markers.


RESULTS
We reviewed 19 cases diagnosed initially as SC using integrated diagnostic techniques, including morphology, immunohistochemistry and molecular pathology, and validated promising markers in 445 breast cancers. We reclassified 19 formerly diagnosed 'SCs' into nine SCs, three ACCAs, three CHCs, three IDCs and one microglandular adenosis. We confirmed that ETV6-NTRK3 gene rearrangement and amylase positivity are good diagnostic markers for SC and ACCA, respectively. Vacuolar staining for adipophilin, positivity for α-lactalbumin and negativity for ETV6 rearrangement are diagnostic markers for CHC.


CONCLUSIONS
In this study, we propose a panel of four markers (ETV6 rearrangement, amylase, α-lactalbumin and adipophilin) for distinguishing SC, ACCA, CHC and IDC. This simple but robust panel will serve pathologists well as a practical guide for reaching an appropriate diagnosis.
Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan; Department of Pathology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
Tomo
T
Osako
Kengo
K
Takeuchi
Rie
R
Horii
Takuji
T
Iwase
Futoshi
F
Akiyama
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics; D002277:Carcinoma / Q000175:diagnosis*; D018267:Carcinoma, Acinar Cell / Q000175:diagnosis; D018270:Carcinoma, Ductal, Breast / Q000175:diagnosis; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D055815:Young Adult; D020812:Receptor, trkC; D000097764:ETS Translocation Variant 6 Protein
D014408:Biomarkers, Tumor; D015514:Oncogene Proteins, Fusion; C484319:ETV6-NTRK3 fusion protein, human; D020812:Receptor, trkC; D000097764:ETS Translocation Variant 6 Protein
ETV6-NTRK3 gene rearrangement; acinic cell carcinoma; adipophilin; cystic hypersecretory carcinoma; secretory carcinoma