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Novel Pattern of Nuclear Staining With ROS1 Immunohistochemistry: A Case Report.

Diane M Wilcock1, Deepika Sirohi2,3, Kristina Moore1

  • 1The Institute for Experimental Pathology, ARUP Laboratories, Salt Lake City, Utah, USA, aruplab.com.

Case Reports in Pulmonology
|June 8, 2026
PubMed
Summary
This summary is machine-generated.

A rare nuclear staining pattern on ROS1 immunohistochemistry (IHC) in lung adenocarcinoma was linked to an unusual NMP1::ROS1 gene rearrangement. This finding challenges typical ROS1 IHC interpretation and highlights the need for comprehensive molecular testing.

Keywords:
FISHHCC-78 cell lineIHCROS1lung adenocarcinomanonsmall cell lung cancernuclear staining 5′ deletion

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Area of Science:

  • Oncology
  • Molecular Pathology
  • Genetics

Background:

  • ROS1 rearrangements are key drivers in non-small cell lung cancer (NSCLC), guiding targeted therapy decisions.
  • Standard ROS1 immunohistochemistry (IHC) typically shows cytoplasmic and/or membranous staining patterns.

Purpose of the Study:

  • To report an unusual case of lung adenocarcinoma with a distinct nuclear ROS1 IHC staining pattern.
  • To investigate the underlying genetic alterations associated with this atypical staining.

Main Methods:

  • Utilized ROS1 immunohistochemistry (IHC) for initial screening.
  • Performed ROS1 fluorescence in situ hybridization (FISH) for gene rearrangement analysis.
  • Conducted next-generation sequencing (NGS) for comprehensive molecular profiling.

Main Results:

  • The lung adenocarcinoma exhibited a strong, unusual nuclear staining pattern on ROS1 IHC.
  • ROS1 FISH revealed an isolated 3' signal pattern, suggesting rearrangement or deletion.
  • NGS identified a rare NMP1::ROS1 gene rearrangement.

Conclusions:

  • This case highlights a rare NMP1::ROS1 rearrangement presenting with atypical nuclear ROS1 IHC staining in lung adenocarcinoma.
  • The findings underscore the importance of considering molecular testing when IHC results deviate from expected patterns.
  • Accurate identification of ROS1 rearrangements is critical for patient eligibility for ROS1-directed therapies.