Secretory carcinoma

Breast malignant, males, children
Carcinoma subtypes
Secretory carcinoma

Author: Gary Tozbikian, M.D. (see Authors page)

Revised: 16 June 2018, last major update May 2018

Copyright: (c) 2003-2018, PathologyOutlines.com, Inc.

PubMed Search: Secretory breast carcinoma

Table of Contents

Cite this page: Tozbikian, G. Secretory carcinoma. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/breastmalignantjuvenile.html. Accessed June 18th, 2018.

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
Associated with a favorable prognosis in younger patients

Terminology

Originally named juvenile breast carcinoma, the terminology was changed to secretory carcinoma after reports of the tumor occurring in adults

ICD-0 coding

8502/3

Epidemiology

Rare, < 0.02% of all breast cancers (Breast 2012;21:350, J Surg Oncol 2016;113:721)
Initially described in children, most common childhood breast cancer (JAMA 1966;195:388)
Recent studies based on National Cancer Data Base (NCDB) and Survival, Epidemiology and End Results (SEER) reporting show mainly affects older patients, but with significantly younger median age (53 - 56 years) compared with invasive ductal carcinoma (Breast 2012;21:350, J Surg Oncol 2016;113:721)
Occurs in both sexes, male to female ratio 1:6 to 1:31 (World J Surg Oncol 2005;3:35, Mod Pathol 2012;25:567, J Surg Oncol 2016;113:721, Ann Oncol 2000;11:1343)

Clinical features

Tumor size, rates of axillary lymph node involvement, AJCC stage at presentation, pattern of surgical treatment therapy are similar to invasive ductal carcinoma (J Surg Oncol 2016;113:721)
Indolent clinical course, excellent prognosis (Cancer 1980;45:2404, Clin Cancer Res 2004;10:5367)
Five year overall survival: 87%
Five year disease specific survival: 94.4% (Breast 2012;21:350)
Distant metastases have been reported (World J Surg Oncol 2005;3:35)
Recent studies suggest outcome is age related (Hum Pathol 1999;30:1435)
Limited data regarding patterns of use and analysis of effectiveness of post operative radiation and adjuvant chemotherapy

Radiology description

Variable, nonspecific with several reports ranging from presentation of secretory carcinoma as a small, round, well circumscribed mass / nodular density to suspicious lesions with spiculated margins and microcalcifications on ultrasound and mammography (J Clin Ultrasound 2003;31:425, Breast J 2003;4:2000, Ann Surg Oncol 2002;9:663)

Case reports

6 year old girl with secretory breast carcinoma (Pediatr Surg Int 2015;31:677)
13 year old boy with secretory breast cancer (Breast Cancer Res Treat 2012;133:813)
24 year old man with secretory breast carcinoma and axillary lymph node metastasis (Int J Clin Exp Pathol 2015;8:3322)
41 year old man with with long term follow up of secretory breast carcinoma (Future Oncol 2015;11:1767)
53 year old woman with secretory breast carcinoma with a papillary predominant pattern (Histopathology 2017;71:488)
79 year old woman with a palpable breast mass (Rare Tumors 2016;8:6650)

Treatment

Surgical treatment, use of antihormonal targeted therapy similar to invasive ductal carcinoma (J Surg Oncol 2016;113:721)

Gross description

Small, well circumscribed, mobile mass
Median size 1.9 - 2.36 cm (J Surg Oncol 2016;113:721, Breast 2012;21:350)
Often central, located near the areola

Microscopic (histologic) description

Architecture is usually microcystic, solid or tubular or admixture of all 3 patterns
Can display peripheral papillary architecture
Well circumscribed with pushing borders but may be infiltrative at periphery
Central sclerosis may be observed
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 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

Images hosted on PathOut server:

Contributed by Gary Tozbikian, M.D.

Glands and solid nests

Tumor cells with vacuolated cytoplasm

Low nuclear grade

Case of the Week #8

Images hosted on other servers:

H&E, PAS

Arising within radial scar

Various images

Well differentiated but invasive glands

PAS, S100, E-cadherin

S100+

PAS+ diastase resistant secretions

S100, EMA, pan cytokeratin, ER

Positive stains

S100, mammaglobin (Mod Pathol 2012;25:567, Mod Pathol 2009;22:291)
CK5 / CK6 or EGFR (Mod Pathol 2012;25:567, Mod Pathol 2017;30:1086)
CK14 in 33% (Mod Pathol 2009;22:291)
CD117 (focal) (Mod Pathol 2009;22:291)
MUC4 and SOX10 (Mod Pathol 2017;30:1086)
GATA3 (Mod Pathol 2017;30:1086)

Negative stains

Generally triple negative for estrogen receptor, progesterone receptor and HER2 (Mod Pathol 2012;25:567, Mod Pathol 2017;30:1086)
Recent series have reported focal, weak estrogen receptor and progesterone receptor positivity in 44 - 64% of secretory carcinoma (J Surg Oncol 2016;113:721, Am J Surg Pathol 2015;39:1458, Hum Pathol 2003;34:1299)
p63 (Mod Pathol 2009;22:291)

Molecular / cytogenetics description

Associated with chromosomal translocation t(12;15)(p13;q25), resulting in ETV6-NTRK3 fusion gene (J Pediatr Surg 2000;35:765)
t(12;15) reported in 75 - 92% of secretory carcinoma (Cancer Cell 2002;2:367, Genes Chromosomes Cancer 2004;40:152)
Lacks the complex genomic alterations (high mutational burden, frequent copy number alterations, TP53 mutations) seen in conventional basal-like triple negative breast cancers (Mod Pathol 2017;30:1086, Am J Surg Pathol 2015;39:1458)
Lacks chromosomal alterations (1q gains and 16q losses) seen in low grade neoplasia pathway (Mod Pathol 2017;30:1086)

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;14) translocation
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
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
Lipid-rich carcinoma: demonstrates Oil Red O positive cytoplasmic vacuoles, negative or only focal PAS positivity, can demonstrate any grade of nuclear atypia

Additional references

IARC: WHO Classification of Tumours of the Breast, 4th Edition, 2012

Board review question #1

1q chromosomal gains and 16q chromosomal losses
HER2 gene amplification
t(12;15)(p13;q25), resulting in ETV6-NTRK3 fusion gene
t(6;9)( q22-23;p23-24) resulting in fusion of MYB and NFIB
TP53 mutation

Board review answer #1

C. t(12;15)(p13;q25), resulting in ETV6-NTRK3 fusion gene

Board review question #2

Abundant PAS+, diastase sensitive secretions
High grade cytologic atypia with brisk mitotic activity
Irregular clusters of epithelial cells floating in pools of extracellular mucin
Low grade cytologic atypia, triple negative for ER, PR and HER2
Negative for basal-like markers CK5 / 6 or CK14

Board review answer #2

D. Low grade cytologic atypia, triple negative for ER, PR and HER2