Insulinoma‐associated protein 1 is a robust nuclear immunostain for the diagnosis of small cell lung carcinoma in cytology smears

Abstract

Background In a significant percentage of patients with small cell lung carcinoma (SCLC), cytology samples represent the only source of tumor tissue. Ancillary immunocytochemistry (ICC) for neuroendocrine markers is an important adjunct for the diagnosis of SCLC. Insulinoma‐associated protein 1 (INSM1) is a novel neuroendocrine marker proposed as an economical single‐marker alternative to the traditional 3‐marker panel of chromogranin, synaptophysin, and CD56. To the authors’ knowledge, limited studies have evaluated INSM1 immunohistochemistry (IHC) for the diagnosis of SCLC and reported high sensitivities and specificities. The objective of the current study was to evaluate the sensitivity and specificity of INSM1 ICC on direct smears (DS) from patients with SCLC in comparison with IHC on small biopsies (SBs). Methods All available DS and SBs from patients with SCLC who were diagnosed over the previous year were retrieved. Immunostaining for INSM1 was performed on alcohol‐fixed DS and formalin‐fixed SBs wherever available. A total of 10 DS and SBs from patients with non–small cell lung carcinoma were included for comparison. Nuclear staining for INSM1 in ≥1% tumor cells was interpreted as positive. Results Among a total of 60 patients with SCLC who were included in the current study, a total of 37 underwent INSM1 IHC on SBs and 36 underwent INSM1 ICC on DS. ICC was noninterpretable in 3 DS due to necrosis. The sensitivity of INSM1 IHC was 97% (36 of 37 cases) whereas the sensitivity of INSM1 ICC was 91% (30 of 33 cases) for the diagnosis of SCLC. Among matched IHC and ICC results available for 11 patients, 91% of cases (10 of 11 patients) demonstrated concordant IHC‐ICC staining. All cases of non–small cell lung carcinoma were negative for INSM1 (100% specificity). Conclusions INSM1 appears to be a robust and reliable ICC marker for the confirmation of SCLC diagnosis on cytology smears.

Insulinoma‐associated protein 1 immunostaining for various types of neuroendocrine tumors on FNA smears

“…In another study that also used cell block tissues, INSM1 was positive in 97% of 32 SCLC cases with a diffuse and strong staining pattern 18 . A recent study evaluating INSM1 staining in 70 SCLC cases, 33 of which were stained on smears, reported that INSM1 staining was positive in 91% of cases 19 . In that study, 11 tumors had direct smears matched with small biopsy specimens, and only 1 of the tumors showed false‐negative INSM1 staining on a direct smear.…”

“…In addition, because the study consisted of cases with a known diagnosis of NET from various primary organ systems, the specificity of each marker could not be determined. Upon a careful review of the literature, we found that the reported specificity of INSM1 in a number of studies, including 2 cytology studies, was >95% 5‐9,12,14,17,19 . Notably, INSM1 can occasionally be reactive (usually weakly and focally) in non‐NETs, including squamous cell carcinomas and various salivary gland carcinomas of the head and neck 7 ; lung adenocarcinomas and squamous cell carcinomas 6,9 ; and adrenal cortical carcinomas, solid pseudopapillary neoplasms, cholangiocarcinomas, and adenocarcinomas of the colon, breast, and prostate 13,25 …”

“…Rodriguez et al 8 used cell blocks of 91 NETs from various sites, including the lungs, pancreas, and skin, and reported an overall sensitivity of 99% and a specificity of 97% for INSM1, which were higher than the sensitivity and specificity of SYN (95.4% and 66.7%), CG (82.5% and 75%), and CD56 (95.5% and 69.2%). To the best of our knowledge, the utility of INSM1 staining on direct smear tissue has been addressed in only 1 study, which included 37 small core biopsy samples and 33 direct smears of small cell lung carcinoma (SCLC) 19 . Positive INSM1 staining was noted in 97% of small core biopsy specimens and in 91% of direct smears.…”

Novel Cytological Model for the Identification of Early Oral Cancer Diagnostic Markers: The Carcinoma Sequence Model

“…However, there is little research on whether they are useful markers for the early detection of OSCC. Combining cytology and ICC to increase diagnostic accuracy has also been widely researched in other locations, but few studies have been conducted in the oral cavity [34,[44][45][46][47][48][49]. Our study thus offers a new cytological diagnosis tool for OSCC.…”

Diagnostic Utility of INSM1 in Medullary Thyroid Carcinoma

“…38 Recent studies demonstrated the diagnostic utility of INSM1 in other organs when the obtained tissue was scant in either a small biopsy or a cell block of cytology specimens as an alternative or effective stand-alone neuroendocrine marker. 13,15,33,39-43 Taken together, INSM1, especially when combined with either CT or mCEA, may potentially replace a panel of the traditional MTC markers or be the first line of choice among the MTC immunohistochemical markers when the obtained lesional tissue is quantitatively limited.…”