Stains & molecular markers
Pan-TRK (EPR17341) [NTRK]

Editorial Board Member: Michael R. Clay, M.D.
Editor-in-Chief: Debra L. Zynger, M.D.
Jessica L. Davis, M.D.

Topic Completed: 1 September 2018

Minor changes: 15 December 2020

Copyright: 2003-2021,, Inc.

PubMed Search: NTRK

Jessica L. Davis, M.D.
Page views in 2020: 3,757
Page views in 2021 to date: 169
Cite this page: Davis JL Pan-TRK (EPR17341) [NTRK]. website. Accessed January 19th, 2021.
Definition / general
Essential features
  • NTRK gene fusions (NTRK1/2/3) to a variety of gene partners are oncogenic drivers in several tumor types
  • In some tumor morphologies, NTRK fusions occur at a high frequency:
    • Infantile fibrosarcoma and other pediatric NTRK rearranged mesenchymal tumors
    • Cellular congenital mesoblastic nephroma
    • Secretory carcinomas (breast, salivary gland mammary analog secretory carcinoma and skin)
    • Lipofibromatosis-like neural tumor
    • Uterine sarcomas with NTRK fusions resembling fibromatosis
  • In some pediatric tumors, NTRK fusions occur with intermediate frequency:
    • Pediatric gliomas, pediatric papillary thyroid carcinoma, Spitz nevi
  • In other tumors, NTRK fusions occur very infrequently:
    • Adult gliomas, adult papillary thyroid carcinoma, colorectal carcinoma, lung adenocarcinoma, melanoma, leukemia and less commonly others
  • Recognition of NTRK fusion tumors had become increasingly important with the advent of targeted Trk inhibitors
Uses by pathologists
  • Tumors harboring NTRK1/2 fusions demonstrate cytoplasmic expression; rare perinuclear and nuclear membrane staining has been reported
  • Tumors harboring NTRK3 fusions demonstrate cytoplasmic or nuclear expression
Microscopic (histologic) images

Contributed by Jessica L. Davis, M.D.

Infantile fibrosarcoma

Infantile fibrosarcoma spectrum of tumors

Positive staining - tumors
Negative staining - tumors
Positive staining - normal
Negative staining - normal
Molecular / cytogenetics description
  • Fluorescence in situ hybridization (FISH) probes for NTRK genes are commercially available
  • Some NGS assays can detect / confirm NTRK fusions
Molecular / cytogenetics images

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Board review style question #1
    A 2 month old boy presents with a large intramuscular thigh mass with encasement of the femoral neurovascular bundle. Biopsy shows a spindle cell neoplasm with infiltrative borders into skeletal muscle and subcutaneous adipose tissue. By immunohistochemistry the tumor shows patchy expression of SMA, rare CD34 and diffuse expression of Pan-TRK. What is the most likely diagnosis?

  1. Cellular congenital mesoblastic nephroma
  2. Infantile fibrosarcoma
  3. Lipofibromatosis
  4. Myofibroma
Board review style answer #1
B. Infantile fibrosarcoma. Infantile fibrosarcoma is the most common soft tissue sarcoma of infancy. The morphology can be variable but typically presents with primitive to spindle cells in a myxoid to collagenized stroma; the diagnosis can be confirmed with Pan-TRK antibody staining. Tumors harbor an ETV6-NTRK3 fusion in ~70% of cases; however, recently other variant NTRK fusions have been described (Pediatr Dev Pathol 2018;21:68, Mod Pathol 2018;31:463).
Board review style question #2
    A 20 year woman presents with a breast mass and a needle core biopsy is performed demonstrating morphology suggestive of secretory carcinoma. Which stain combination would be most consistent with secretory breast carcinoma?

  1. Pan-TRK+, S100+, MUC4+, ER-, GATA3+
  2. Pan-TRK+, S100-, MUC4+, ER+, GATA3+
  3. Pan-TRK-, S100-, MUC4+, ER+, GATA3+
  4. Pan-TRK+, S100+, MUC4+, ER+, GATA3+
Board review style answer #2
A. Pan-TRK+, S100+, MUC4+, ER-, GATA3+. Secretory carcinomas of breast, salivary gland and skin are most commonly ETV6-NTRK3 driven tumors; rare ETV6 to other fusion partners have been described (Am J Surg Pathol 2015;39:602). Pan-TRK staining is seen, often with nuclear expression (NTRK3 fusion tumors). Breast secretory carcinomas also express S100, SOX10, MUC4 and GATA3 but are triple negative (ER/PR/HER2-).
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