Other carcinoma subtypes, WHO classified

Secretory carcinoma

Editorial Board Member: Emily S. Reisenbichler, M.D.
Deputy Editor-in-Chief: Debra L. Zynger, M.D.
Gary Tozbikian, M.D.

Topic Completed: 1 May 2018

Minor changes: 14 May 2021

Copyright: 2003-2021,, Inc.

PubMed Search: Secretory breast carcinoma

Gary Tozbikian, M.D.
Page views in 2020: 8,273
Page views in 2021 to date: 7,381
Cite this page: Tozbikian G. Secretory carcinoma. website. Accessed October 25th, 2021.
Definition / general
  • Rare subtype of low grade, translocation associated invasive breast carcinoma
  • Tumor with microcystic, solid and tubular architecture, composed of vacuolated tumor cells producing intracellular and extracellular secretions
  • Generally triple negative with basal-like phenotype (Mod Pathol 2012;25:567)
  • First described by McDivitt and Stewart in 1966 (JAMA 1966;195:388)
Essential features
  • Rare, < 1% of breast cancers
  • Most common primary pediatric breast cancer, but can occur at any age
  • Circumscribed margins, solid nests, cysts and gland formation with PAS+ intraluminal secretions
  • Tumor cells with abundant vacuolated or granular cytoplasm, low nuclear grade
  • Generally triple negative for estrogen receptor, progesterone receptor and HER2
  • Most tumors have translocation yielding ETV6-NTRK3 fusion gene
  • Associated with a favorable prognosis in younger patients
  • Originally named juvenile breast carcinoma, the terminology was changed to secretory carcinoma after reports of the tumor occurring in adults
ICD-0 coding
Clinical features
Radiology description
Radiology images

Images hosted on other servers:
Missing Image Missing Image

Hypoechoic lesion on ultrasound

Case reports
Clinical images

Images hosted on other servers:
Missing Image

Breast mass involving skin

Gross description
Microscopic (histologic) description
  • Well circumscribed with pushing borders but may be infiltrative at periphery
  • Central sclerosis may be observed
  • Architecture is usually microcystic, solid or tubular or admixture of all 3 patterns
  • Can display peripheral papillary architecture
  • Low grade cytologic atypia, bland uniform nuclei, low mitotic rate
  • Histologic hallmark are the presence of tumor cells with vacuolated, foamy cytoplasm and abundant intracellular and extracellular pale blue to dense pink secretions which are periodic acid Schiff (PAS) positive and diastase resistant (JAMA 1966;195:388, Mod Pathol 2012;25:567)
  • Often an in situ component (Mod Pathol 2009;22:291)
Microscopic (histologic) images

Contributed by Gary Tozbikian, M.D.

Glands and solid nests

Tumor cells with vacuolated cytoplasm

Low nuclear grade, no mitoses, 40x

Secretory carcinoma 4x

Secretory carcinoma 10x

Secretory carcinoma 20x

Secretory carcinoma PAS-D 20x

Secretory carcinoma S100 20x

Case #8
Missing Image Missing Image

Images hosted on other servers:
Missing Image


Missing Image

Well differentiated but invasive glands

Missing Image

PAS, S100, E-cadherin

Missing Image


Missing Image

S100, EMA, pan cytokeratin, ER

Positive stains
Molecular / cytogenetics description
Molecular / cytogenetics images

Images hosted on other servers:
Missing Image

Karyogram with t(12;15)(p13;q25)

Missing Image

FISH with disrupted ETV6 gene

Differential diagnosis
  • Acinic cell carcinoma: cells with clear cytoplasm (hypernephroid pattern), expresses proteins of the salivary gland counterpart of acinic cell carcinoma (e.g. alpha-1-chymotrypsin, salivary gland amylase, lysozyme), lacks the t(12;15) translocation
  • Invasive ductal carcinoma, NOS type: lacks vacuolated cytoplasm and secretions, typically conventional Triple Negative Breast Cancer (TNBC) are high grade, not cytologically bland as in secretory carcinoma
  • Cystic hypersecretory hyperplasia: cysts containing abundant, homogenous intraluminal secretions resembling thyroid colloid, cells lining cysts are bland, flat or cuboidal/columnar cells lacking vacuolated / granular cytoplasm, presence of intact myoepithelial cell layer
  • Glycogen-rich carcinoma: PAS positive, diastase-sensitive secretions, can demonstrate any grade of nuclear atypia
  • Lipid-rich carcinoma: demonstrates Oil Red O positive cytoplasmic vacuoles, negative or only focal PAS positivity, can demonstrate any grade of nuclear atypia
Board review style question #1
    This breast tumor is associated with which cytogenetic abnormality?

  1. 1q chromosomal gains and 16q chromosomal losses
  2. HER2 gene amplification
  3. t(12;15)(p13;q25), resulting in ETV6-NTRK3 fusion gene
  4. t(6;9)( q22-23;p23-24) resulting in fusion of MYB and NFIB
  5. TP53 mutation
Board review style answer #1
C. Secretory carcinoma of breast is associated with t(12;15)(p13;q25), resulting in ETV6-NTRK3 fusion gene

Comment Here

Reference: Secretory carcinoma of breast
Board review style question #2
    What histological and immunophenotypic features are most likely to be observed in a breast secretory carcinoma?

  1. Abundant PAS+, diastase sensitive secretions
  2. High grade cytologic atypia with brisk mitotic activity
  3. Irregular clusters of epithelial cells floating in pools of extracellular mucin
  4. Low grade cytologic atypia, triple negative for ER, PR and HER2
  5. Negative for basal-like markers CK5 / 6 or CK14
Board review style answer #2
D. Secretory carcinoma of breast is most likely to show low grade cytologic atypia, triple negative for ER, PR and HER2

Comment Here

Reference: Secretory carcinoma of breast
Back to top
Image 01 Image 02