Other invasive carcinoma subtypes, WHO classified


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Gary Tozbikian, M.D.

Last author update: 2 November 2021
Last staff update: 10 March 2023

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PubMed Search: Secretory breast carcinoma[TIAB]

Gary Tozbikian, M.D.
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Cite this page: Tozbikian G. Secretory. website. Accessed July 13th, 2024.
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 coding
  • ICD-O: 8502/3 - secretory carcinoma of breast
Clinical features
  • Histologic examination of tissue with immunohistochemistry, demonstration of ETV6-NTRK3 gene fusion by fluorescent in situ hybridization
Radiology description
Radiology images

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Hypoechoic lesion on ultrasound

Case reports
Clinical images

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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 is 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. and Case #8

Glands and solid nests

Tumor cells with vacuolated cytoplasm

Low nuclear grade, no mitoses

Microcystic pattern Microcystic pattern

Microcystic pattern

Extracellular secretory material Extracellular secretory material

Extracellular secretory material

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Solid pattern



Molecular / cytogenetics description
Molecular / cytogenetics images

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

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FISH with disrupted ETV6 gene

Sample pathology report
  • Breast, right, 3:00, ultrasound guided core biopsy:
    • Secretory carcinoma, 0.7 cm in greatest length
    • Estrogen receptor: negative (0%)
    • Progesterone receptor: negative (0%)
    • HER2: negative (score 0)
Differential diagnosis
Board review style question #1

Secretory carcinoma 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
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