Insulinoma-associated protein 1 is a sensitive and specific marker of neuroendocrine lung neoplasms in cytology specimens

Our plain-English summary of Insulinoma-associated protein 1 is a sensitive and specific marker of neuroendocrine lung neoplasms in cytology specimens, by E.E. Doxtader, S. Mukhopadhyay (Cancer Cytopathology, 2018).

The study

• Authors: E.E. Doxtader, S. Mukhopadhyay
• Journal: Cancer Cytopathology
• Published: 2018;126(4):243-252
• Cited by: 46 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Recent studies suggest that insulinoma-associated protein 1 (INSM1) is a sensitive and specific marker of neuroendocrine neoplasms. The aims of this study were to determine whether INSM1 can be reliably used in cytology (Cellient) cell blocks, to ascertain whether staining correlates with paired surgical pathology specimens, and to compare its sensitivity and specificity with those of synaptophysin (SYN), chromogranin (CHR), and CD56 for neuroendocrine lung tumors.

Methods: Seventy-four primary lung neoplasms diagnosed on cytology were stained with INSM1, SYN, CHR, and CD56: 41 small cell lung carcinomas (SCLCs), 1 large cell neuroendocrine carcinoma (LCNEC), 10 carcinoid tumors, 11 adenocarcinomas, 9 squamous cell carcinomas, 1 mesothelioma and 1 poorly differentiated non-small cell lung carcinoma, not otherwise specified. In 20 cases, a paired surgical pathology specimen was also stained with INSM1.

Results: INSM1 was positive in 48 of 52 primary lung neuroendocrine neoplasms (92%), including 38 of 41 SCLCs (93%), the only LCNEC (100%), and 9 of 10 carcinoid tumors (90%), and it was negative in all 22 non-neuroendocrine primary lung tumors. For SCLC, the sensitivity of INSM1 (93%) was lower than the sensitivity of CD56 (100%), equal to the sensitivity of SYN (93%), and higher than the sensitivity of CHR (35%). For carcinoid tumors, the sensitivity of INSM1 (90%) was lower than the sensitivity of all other markers (100% each). The specificity of INSM1 for neuroendocrine neoplasms as a group was 100%. INSM1 staining was concordant with surgical pathology specimens in all 20 paired cases.

Conclusions: INSM1 can be used in cytopathology cell blocks, and it is sensitive and highly specific for neuroendocrine lung tumors. INSM1 staining in cytology cell blocks correlates well with surgical pathology specimens. Cancer Cytopathol 2018;126:243-52. © 2018 American Cancer Society.

© 2018 American Cancer Society.

In plain English

This laboratory study of a diagnostic stain did not examine asbestos exposure. The authors searched Cleveland Clinic records for cytology samples (loose cells rather than tissue) from 74 primary lung tumors diagnosed from May 2015 to September 2017. Fifty-two were neuroendocrine (41 small cell lung carcinomas, 10 carcinoid tumors, 1 large cell neuroendocrine carcinoma). The other 22 were not, including one mesothelioma. Staining for a protein called INSM1, done on every sample, was compared with three older markers, which were not always done. INSM1 was positive in 48 of 52 neuroendocrine tumors (92%), including 38 of 41 small cell carcinomas (93%) and 9 of 10 carcinoid tumors (90%). It was negative in all 22 other tumors, including the mesothelioma. Its specificity was 100%, versus 95% for synaptophysin and CD56. In all 20 cases with matching surgical tissue, INSM1 results in cytology and tissue agreed. The authors concluded that INSM1 can be used on cytology cell blocks and is sensitive and highly specific for neuroendocrine lung tumors. They noted that the study included small numbers of other tumor types.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective diagnostic study comparing immunohistochemical stains on cytology cell blocks from lung tumors identified through a laboratory records search
• Who was studied: Cytology samples from 74 primary lung neoplasms at the Cleveland Clinic, Cleveland, Ohio. Fifty-two were neuroendocrine: 41 small cell lung carcinomas, 1 large cell neuroendocrine carcinoma and 10 carcinoid tumors. Twenty-two were non-neuroendocrine: 11 adenocarcinomas, 9 squamous cell carcinomas, 1 mesothelioma and 1 poorly differentiated non-small cell lung carcinoma, not otherwise specified. The samples came from 42 women and 32 men aged 29 to 87 years.
• Exposure: No asbestos or other environmental exposure was studied. The 'test' was staining with insulinoma-associated protein 1 (INSM1), compared with three traditional neuroendocrine markers: synaptophysin (SYN), chromogranin (CHR) and CD56. The methods say all cases were stained with all four. However, the tables show that INSM1 was done on all 74 tumors, while the traditional markers were not done on every case.
• Main results:
  • INSM1 was positive in 48 of 52 primary lung neuroendocrine neoplasms (92%). This included 38 of 41 small cell lung carcinomas (93%), 9 of 10 carcinoid tumors (90%) and the only large cell neuroendocrine carcinoma.
  • All 22 non-neuroendocrine tumors were negative for INSM1, including the single mesothelioma.
  • For small cell lung carcinoma, the sensitivity of INSM1 (93%) was lower than that of CD56 (100%), equal to that of SYN (93%) and higher than that of CHR (35%).
  • For carcinoid tumors, the sensitivity of INSM1 (90%) was lower than that of each of the other markers (100% each).
  • For neuroendocrine lung tumors as a group, the sensitivity of INSM1 (92%) was lower than that of CD56 (100%), comparable to that of SYN (94%) and higher than that of CHR (49%). The group totals were tested on different numbers of tumors: 52 for INSM1, 51 for SYN and CHR, and 50 for CD56.
  • One small cell lung carcinoma was stained only for INSM1; the three traditional markers were not done.
  • The specificity of INSM1 for neuroendocrine lung tumors was 100%. This was similar to CHR (100%) and higher than SYN (95%) and CD56 (95%).
  • INSM1 results in cytology samples agreed with INSM1 results in the matching surgical tissue in all 20 paired cases.
  • In all 5 INSM1-positive paired cases, the percentage of stained tumor cells was lower in the cytology cell blocks than in the surgical specimens.
• The authors' conclusion: The authors concluded that INSM1 can be used in cytopathology cell blocks and is sensitive and highly specific for neuroendocrine lung tumors.
• Limitations the authors state:
  • The study included relatively small numbers of the other tumors that a pathologist might confuse with small cell carcinoma.
  • The authors did not focus on, or deliberately include, diagnostically difficult tumors.
  • Only a limited number of cases had matching cytology and surgical tissue for comparison.
  • The authors stated that data from other investigators are needed to determine whether INSM1 is better than the traditional markers.
  • The authors stated that the antibodies need separate validation in alcohol-fixed cytology material.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer.

Medical terms in this study, explained in our Lexicon: Neoplasm, Cytology, Cell Block, Pathology, Carcinoma, Adenocarcinoma, Squamous Cell Carcinoma, Mesothelioma.

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