Thyroid & parathyroid
Other uncommon thyroid carcinomas
Secretory carcinoma
Author: Andrey Bychkov, M.D., Ph.D.
Last author update: 1 November 2016
Last staff update: 6 April 2023
Copyright: 2002-2024, PathologyOutlines.com, Inc.
PubMed search: mammary analog secretory carcinoma thyroid
See also: Secretory carcinoma of salivary glands, Secretory carcinoma of breast
Table of Contents
Definition / general | Essential features | Terminology | Epidemiology | Sites | Pathophysiology / etiology | Diagrams / tables | Clinical features | Diagnosis | Laboratory | Radiology description | Prognostic factors | Case reports | Treatment | Gross description | Microscopic (histologic) description | Microscopic (histologic) images | Cytology description | Positive stains | Negative stains | Electron microscopy description | Molecular / cytogenetics description | Molecular / cytogenetics images | Differential diagnosisCite this page: Bychkov A. Secretory carcinoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/thyroidMASC.html. Accessed December 19th, 2024.
Definition / general
- Rare salivary gland type tumor arising in thyroid
- First described by Stevens et al. in 2015 (Mod Pathol 2015;28:1084)
Essential features
- Recently described rare cancer, originally reported in salivary glands, which is associated with ETV6-NTRK3 translocation
- Highly reminiscent of papillary thyroid carcinoma with oncocytic features, can be suspected by the presence of microcystic / cribriform pattern
- Important to differentiate from thyroid cancer because of likely aggressive course and ineffectiveness of radioactive iodine / RAI therapy
- Diagnosis: Mammaglobin+, Thyroglobulin-, TTF1-; also confirmed by molecular testing
Terminology
- MASC: mammary analog / analogue secretory carcinoma
Epidemiology
- Very rare; fewer than 10 cases described to date (Head Neck Pathol 2016 Sep 15 [Epub ahead of print])
- Middle age (range, 36 - 74 years old, mean 57 years old); F:M is 2.5
Sites
- MASC was originally described in salivary glands, and shares the same histology, immunophenotype and molecular background as secretory carcinoma of breast (Am J Surg Pathol 2010;34:599)
- Reported in major salivary glands (parotid > submandibular), occasionally in other head / neck locations (lip, palate and thyroid), also in skin
Pathophysiology / etiology
- Origin is debated (Head Neck Pathol 2016 Jul 11 [Epub ahead of print], Mod Pathol 2016;29:985):
- Primary thyroid tumor from ectopic salivary gland remnants, intra- or perithyroidal
- Metastatic from occult primary (salivary glands, breast)
- May have the same origin with papillary thyroid cancer, some MASCs coexist with PTC and share molecular aberrations
- Initiating molecular event is a chromosomal translocation t(12;15)(p12;q25) resulting in the ETV6-NTRK3 gene fusion
- Chimeric protein is a constitutively active protein tyrosine kinase with transformation activity
- ETV6-NTRK3 fusion is found in several malignancies other than MASC, e.g., secretory carcinoma of the breast, congenital fibrosarcoma, cellular or mixed mesoblastic nephroma, myeloid leukemias and papillary thyroid carcinoma (2% sporadic, 14% radiation induced) (Head Neck Pathol 2016;10:405)
Diagrams / tables
Images hosted on other servers:
ETV6-NTRK3 fusion
Clinical features
- Invasive / locally aggressive growth with nodal metastasis, 2 out of 7 reported cases were disseminated and fatal (in contrast to the indolent MASC of salivary gland)
- Frequent recurrences
Diagnosis
- On histopathology, confirmed by IHC and molecular testing
- Occult primary (breast, salivary glands) should be considered
Laboratory
- Recurrence after total thyroidectomy produce no elevated serum thyroglobulin
Radiology description
- Non RAI avid, both primary tumor and relapses / metastases
Prognostic factors
- Probably more aggressive than follicular derived, well differentiated thyroid tumors
Case reports
- 36 year old woman with MASC apparently arising in thyroid which progressed to fatal disseminated disease (Head Neck Pathol 2016;10;405)
Treatment
- Surgical excision, usually total thyroidectomy with lymph node dissection
- Does not respond to RAI (Head Neck Pathol 2016;10;405)
- ETV6-NTRK3 is a "druggable" fusion, Trk inhibitors are currently used for MASC patients in clinical trials (Mod Pathol 2016;29:985)
Gross description
- Poorly circumscribed solid white tan nodules (Head Neck Pathol 2016 Jul 11 [Epub ahead of print])
- Large (range = 2.4 - 7.0 cm, mean = 4.3 cm)
- Often extrathyroidal extension (Mod Pathol 2016;29:985)
Microscopic (histologic) description
- Invasive growth with multiple nodules in fibrotic stroma
- Complex architecture with microcystic / cribriform, solid, trabecular, tubular and papillary growth patterns
- Polygonal eosinophilic cells with vacuolated cytoplasm:
- Prominent single centrally placed nucleolus
- Abundant nuclear grooves (in all architectural patterns), rare pseudoinclusions
- Focal vesicular nuclei with chromatin clearing
- Sometimes apocrine-like capitations
- Cellular atypia is mild to focally moderate, rarely may have high grade features (increased mitoses and necrosis)
- Intraluminar (sometimes intracytoplasmic) colloid-like mucin secretions, from slightly pink watery to purple dense
- Stroma:
- Extensive fibrosis
- Few psammoma bodies
- Lymphoplasmacytic infiltrate and chronic lymphocytic thyroiditis in adjacent thyroid tissue
- Minor papillary thyroid carcinoma component can exist, either classic or follicular variant (Mod Pathol 2016;29:985)
Microscopic (histologic) images
Images hosted on other servers:
Morphology
MASC vs. PTC
Immunophenotype
Cytology description
- Hypercellular smear with sheets, caps, blunted papillary structures without fibrovascular cores ("tentacular nubbins") and loss of polarity (Diagn Cytopathol 2017;45:45)
- Round to oval nuclei with prominent grooves, vesicular to powdery chromatin, single central nucleoli and rare nuclear pseudoinclusions
- Abundant granular cytoplasm with vacuolation
- No increased colloid
Positive stains
- Mammaglobin
- GATA3, DOG1
- S100 is consistently positive, PAX8 variable, which is overlapped with papillary thyroid carcinoma (not helpful for differential diagnosis)
- Mucicarmine, PAS and PASD for secretions (mucin)
- Low Ki67 (1 - 7%) (Mod Pathol 2016;29:985)
Electron microscopy description
- Large number of secretory granules with extrusion into the intercellular spaces, well developed endoplasmic reticulum, lipid laden vacuoles and well formed microvilli (Int J Surg Pathol 2017;25:127)
Molecular / cytogenetics description
- FISH (on paraffin sections) to detect chromosome translocation t(12;15)(p12;q25)
- RT-PCR or NGS (RNA template) to detect ETV6-NTRK3 gene fusion
Molecular / cytogenetics images
Images hosted on other servers:
FISH (separate signals)
Differential diagnosis
- Both histology and cytology closely mimics papillary thyroid cancer
- Oncocytic PTC:
- Histology rarely shows unusual patterns (cribriform / microcystic), no intracytoplasmic secretions and capitation
- Absence of tentacular nubbins in smears
- Immunophenotype is inconsistent with MASC, IHC panel with mammaglobin and Tg / TTF1 can be used on surgical samples and FNA (cell block)
- Poorly differentiated thyroid carcinoma: high grade features like mitoses and necrosis, TTF1+ / Tg+ (evident or residual)
- Metastasis from salivary MASC and secretory carcinoma of breast should be excluded clinically (history, imaging)
