Secretory carcinoma

Breast malignant, males, children
Carcinoma subtypes
Secretory carcinoma

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

Revised: 10 July 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 September 26th, 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
Most tumors have translocation yielding ETV6-NTRK3 fusion gene
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)
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 and surgical treatment 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% (Breast 2012;21:350)
Distant metastases have been reported (World J Surg Oncol 2005;3:35)
Outcome may be better in patients < 20 years old (Hum Pathol 1999;30:1435)
Limited data regarding patterns of use and analysis of effectiveness of adjuvant radiation and chemotherapy

Radiology description

Variable, nonspecific with reports ranging from presentation 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)

Radiology images

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Hypoechoic lesion on ultrasound

Case reports

6 year old girl treated with mastectomy and sentinel lymph node dissection (Pediatr Surg Int 2015;31:677)
13 year old boy with secretory breast carcinoma (Breast Cancer Res Treat 2012;133:813)
24 year old man with axillary lymph node metastasis (Int J Clin Exp Pathol 2015;8:3322)
41 year old man man with long term follow up of secretory breast carcinoma (Future Oncol 2015;11:1767)
53 year old woman with 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)

Clinical images

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Breast mass involving skin

Gross description

Small, well circumscribed, mobile mass
Median size 1.9 - 2.4 cm (J Surg Oncol 2016;113:721, Breast 2012;21:350)
Often central, located near the areola

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

Images hosted on PathOut server:

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 of the Week #8

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H&E, PAS

Microcystic glands with eosinophilic secretions

Well differentiated but invasive glands

PAS, S100, E-cadherin

S100+

S100, EMA, pan cytokeratin, ER

Positive stains

S100 (Mod Pathol 2012;25:567, Mod Pathol 2009;22:291), although expressed frequently in acinic cell carcinoma and in 30% of invasive ductal carcinoma NOS so not useful for these differentials
CK5 / CK6, 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, SOX10 (Mod Pathol 2017;30:1086)
GATA3 (Mod Pathol 2017;30:1086)
PAS (Periodic Acid-Schiff) positive and diastase resistant

Negative stains

Triple negative or focal / weak (44 – 64%) for ER, PR and HER2 (Mod Pathol 2012;25:567, Mod Pathol 2017;30:1086, 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 in 75 - 92% of cases (J Pediatr Surg 2000;35:765, Cancer Cell 2002;2:367, Genes Chromosomes Cancer 2004;40:152)
Lacks the complex genomic alterations such as high mutational burden, frequent copy number alterations or 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)

Molecular / cytogenetics images

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

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

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