Mammary analog secretory carcinoma of the thyroid gland: A primary thyroid adenocarcinoma harboring ETV6-NTRK3 fusion.
ETV6-NTRK3 fusion was identified in several cancers including the recently described mammary analog secretory carcinoma (MASC) of the salivary glands and a minority of papillary thyroid carcinomas. We describe three cases of primary MASC of the thyroid gland and provide a detailed clinical and pathological characterization of the tumor morphology, immunoprofile, and genetic background. Immunohistochemistry for PAX8, TTF-1, thyroglobulin, mammaglobin, GCDFP-15, S-100 protein, and p63 was used to define the tumor immunophenotype. Fluorescence in situ hybridization for ETV6 rearrangement was performed in three, and the next-generation sequencing assay MSK-IMPACT™ (Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets) was performed in two cases. Primary MASC of the thyroid occurred in two women and one man, age 47-72 years. All patients presented with high T stage, infiltrative, locally aggressive tumors with extrathyroidal extension. Two cases were associated with well-differentiated papillary thyroid carcinoma. Histologically, they appeared as low-grade tumors, resembling MASC of the salivary glands and labeled positive for mammaglobin, GCDFP-15, S-100 protein, p63, weakly positive for PAX8, and negative for TTF-1 and thyroglobulin. Fluorescence in situ hybridization revealed ETV6 rearrangement in all cases. In two tested cases MSK-IMPACT™ confirmed the presence of ETV6-NTRK3 gene fusion. Two patients had at least two local recurrences, one was alive with disease, and one was alive and free of disease after 14 and 17 years, respectively. The third patient was alive and free of disease after 2 years. MASC of the thyroid is histologically, immunophenotypically, and genetically similar to its salivary gland counterpart. Thyroid MASC can be associated with a well-differentiated papillary thyroid carcinoma component, supporting follicular cell origin. Clinically, these carcinomas may show frequent recurrences but are associated with long-term survival. Patients with MASC of the thyroid may potentially benefit from Trk molecular-targeted therapy.
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Snjezana
S
Dogan
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Lu
L
Wang
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Ryan N
RN
Ptashkin
Department of Pathology, Good Samaritan Hospital, West Islip, NY, USA.
Robert R
RR
Dawson
Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Jatin P
JP
Shah
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Eric J
EJ
Sherman
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
R
R
Michael Tuttle
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
James A
JA
Fagin
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
David S
DS
Klimstra
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Nora
N
Katabi
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Ronald A
RA
Ghossein
D000230:Adenocarcinoma / Q000737:chemistry / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D050939:Gene Fusion; D015321:Gene Rearrangement; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D000069295:Mammary Analogue Secretory Carcinoma / Q000737:chemistry / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D010641:Phenotype; D013964:Thyroid Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D016896:Treatment Outcome; D020812:Receptor, trkC; D000097764:ETS Translocation Variant 6 Protein
D014408:Biomarkers, Tumor; D015514:Oncogene Proteins, Fusion; C484319:ETV6-NTRK3 fusion protein, human; D020812:Receptor, trkC; D000097764:ETS Translocation Variant 6 Protein