Comparative performance of insulinoma‐associated protein 1 (<scp>INSM1</scp>) and routine immunohistochemical markers of neuroendocrine differentiation in the diagnosis of endocrine <scp>mucin‐producing</scp> sweat gland carcinoma

Parra, Ourania; Linos, Konstantinos; Yan, Shaofeng; Lilo, Mohammed; LeBlanc, Robert E.

doi:10.1111/cup.13831

Cited by 7 publications

(24 citation statements)

References 25 publications

(63 reference statements)

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“…Therefore, including INSM1 as part of a larger panel of immunostains can be helpful in the diagnosis of MCC. INSM1 positivity was more intense than that of other NE markers in the hidrocystoma-like component of cystic endocrine mucin-producing sweat gland carcinoma [ 75 ]. Squamous cell carcinoma is sometimes focally and weakly positive for INSM-1 [ 53 ].…”

Section: Insm1 Expression In Skin and Skin Appendagesmentioning

confidence: 99%

INSM1, a Novel Biomarker for Detection of Neuroendocrine Neoplasms: Cytopathologists’ View

Maleki

Nadella

et al. 2021

Diagnostics

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Background: Insulinoma-associated protein 1 (INSM1) has been considered as a novel immunostain for neuroendocrine tumors (NETs) and is hypothesized to be more reliable than first-generation NET biomarkers, such as CGA (chromogranin A), SYP (synaptophysin) and CD56 (neural cell adhesion molecule). In this review, we summarize existing literature on INSM1′s reliability as an immunostain for detection of various NETs, its results in comparison to first-generation NET biomarkers, and its expression in both non-NETs and benign tissues/cells on cytology specimens (cell blocks/smears).

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Section: Insm1 Expression In Skin and Skin Appendagesmentioning

confidence: 99%

INSM1, a Novel Biomarker for Detection of Neuroendocrine Neoplasms: Cytopathologists’ View

Maleki

Nadella

et al. 2021

Diagnostics

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“…Expanding the spectrum of tumors beyond MCC in which INSM1 may be expressed, in the current issue, Parra et al 7 show that INSM1 is expressed in primary cutaneous endocrine mucin‐producing carcinoma (PCEMPC). They also examined it in a small number of primary cutaneous mucinous carcinoma (PCMC), which are closely related tumors; however, most investigators consider PCMC to be a frankly invasive and more aggressive tumor 8‐10 .…”

Section: Figurementioning

confidence: 93%

“…Although lack of staining for antigens such as CK20 and CDX2 can be utilized to exclude a metastatic carcinoma from the colon or other gastrointestinal sites, and negative staining for throid transcription factor 1 and other markers such as napsin can help to rule out a lung carcinoma, the differential diagnosis with breast carcinomas is much more difficult. Unlike MCC, in which CK20 is a specific marker not expressed in most other tumors in the differential diagnosis, PCEMPC and PCMC are usually positive for many immunoreactants which overlap with breast tumors, including GATA‐3, CK7, ER, PR, and even GCDFP‐15 and mammaglobin 7‐10 . Therefore, additional markers such as INSM1 may potentially be helpful in the differential diagnosis with metastatic breast carcinoma; however, INSM1 has not been well characterized yet in breast tumors, and some breast carcinomas can show neuroendocrine differentiation and positivity for corresponding markers including INSM1 1,7,11 …”

Section: Figurementioning

confidence: 99%

“…Unlike MCC, in which CK20 is a specific marker not expressed in most other tumors in the differential diagnosis, PCEMPC and PCMC are usually positive for many immunoreactants which overlap with breast tumors, including GATA-3, CK7, ER, PR, and even GCDFP-15 and mammaglobin. [7][8][9][10] Therefore, additional markers such as INSM1 may potentially be helpful in the differential diagnosis with metastatic breast carcinoma; however, INSM1 has not been well characterized yet in breast tumors, and some breast carcinomas can show neuroendocrine differentiation and positivity for corresponding markers including INSM1. 1,7,11 In summary, INSM1 is a sensitive and specific nuclear marker of neuroendocrine differentiation.…”

mentioning

confidence: 99%

“…[7][8][9][10] Therefore, additional markers such as INSM1 may potentially be helpful in the differential diagnosis with metastatic breast carcinoma; however, INSM1 has not been well characterized yet in breast tumors, and some breast carcinomas can show neuroendocrine differentiation and positivity for corresponding markers including INSM1. 1,7,11 In summary, INSM1 is a sensitive and specific nuclear marker of neuroendocrine differentiation. In cutaneous pathology, it is has been shown to be strongly positive in the vast majority of cases of MCC, PCEMPC, and PCMC, and may be useful for confirming the diagnosis in these tumors; however, it must be kept in mind that it cannot be utilized alone, as it does not exclude other primary and metastatic tumors with neuroendocrine features from the differential diagnosis.…”

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confidence: 99%

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Insulinoma‐associated 1: A sensitive marker of neuroendocrine differentiation in cutaneous and metastatic neuroendocrine tumors

Cassarino

2020

J Cutan Pathol

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Insulinoma-associated 1 (INSM1) is a nuclear zinc finger transcription factor, which is a sensitive and specific marker of neuroendocrine differentiation. INSM1 binds to DNA and is involved in the expression of multiple neuroendocrine-related genes, including those encoding for chromogranin and synaptophysin; it also regulates other proteins such as cyclin D1 involved in the cell cycle. 1-3 INSM1 was first discovered in human glucagonoma and insulinoma tumor tissues, and has been shown to be expressed in normal development of endocrine and neural tissues, benign neuroendocrine cells, and neuroendocrine tumors in many organ systems, including the lung, pancreas, thyroid, adrenal gland, pituitary gland, central nervous system, and gastrointestinal tract. 1-3 It is typically expressed in carcinoid tumors, pheochromocytomas, insulinomas, medulloblastomas, neuroblastomas, pituitary adenomas and carcinomas, small cell carcinomas, and large-cell neuroendocrine carcinomas, among others. 1-6 Although this marker has been shown to be expressed in neuroendocrine cells and tumors in many other organ systems, in the skin, INSM1 has been mostly studied in Merkel cell carcinoma (MCC). Strong staining has been reported in the majority of cases, in which it can be useful to confirm neuroendocrine differentiation. 1,4-6 It is also helpful to exclude other tumors which may be considered in the differential diagnosis, such as basal cell carcinoma, poorly differentiated primary and metastatic carcinomas (other than neuroendocrine carcinomas), melanoma, and lymphomas, most of which are negative for this marker (although the numbers of cases of these other tumors analyzed so far is quite small). 4-6 It is a more sensitive and specific neuroendocrine marker than traditional neuroendocrine stains such as CD56, chromogranin, and synaptophysin, which are cytoplasmic markers. In addition, CK20 staining can be very focal and difficult to identify in some cases of MCC. In contrast, INSM1 has been reported to show stronger and more diffuse staining than these other markers in most MCC cases. 4-6 In addition, the nuclear staining is easier to detect in small, often crushed biopsies, and does not show as much non-specific background staining as the cytoplasmic markers. To date, including all of the studies on INSM1 in MCC, it has been reported positive in 100 (99%) out of 101 cases published. 1,4-6 No cases of

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Utility of Insulinoma-Associated Protein 1 (INSM1) and Mucin 2 (MUC2) Immunohistochemistry in the Distinction of Endocrine Mucin-Producing Sweat Gland Carcinoma From Morphologic Mimics

Quattrochi

Russell‐Goldman

2021

The American Journal of Dermatopathology

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:Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is a rare low-grade adnexal malignancy with a predilection for the eyelids of elderly White women, which is associated with invasive mucinous carcinoma with endocrine features in one-third of cases. EMPSGC is characterized by the presence of neuroendocrine differentiation and mucin production. However, EMPSGC displays a variety of architectural patterns including solid, cribriform, papillary, and cystic growth. In addition, EMPSGC may also display nonendocrine cytologic features, such as apocrine change. Because of their variable appearance, EMPSGC can show significant morphologic overlap with certain histologic mimics, namely basal cell carcinoma, hidrocystoma, apocrine hidradenoma, and tubular adenoma. In addition, the often limited sampling of this anatomically delicate area can make the diagnosis of EMPSGC challenging. EMPSGC expresses neuroendocrine markers, including synaptophysin and chromogranin, often in a focal distribution. However, insulinoma-associated protein 1 (INSM1) has been found to be a more sensitive marker for EMPSGC. Recent studies have also demonstrated the expression of the gel-forming mucin 2 (MUC2) in EMPSGC, possibly signifying a lacrimal or conjunctival origin of these neoplasms. In this article, we discuss EMPSGC in the context of its histologic mimics (BCC, hidrocystoma, apocrine hidradenoma, and tubular adenoma) and we investigate the utility of the immunohistochemical expression of INSM1 and MUC2 in the distinction of EMPSGC from them. We demonstrate that INSM1 and MUC2 can reliably distinguish EMPSGC from these histologic mimics.

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Comparative performance of insulinoma‐associated protein 1 (INSM1) and routine immunohistochemical markers of neuroendocrine differentiation in the diagnosis of endocrine mucin‐producing sweat gland carcinoma

Cited by 7 publications

References 25 publications

INSM1, a Novel Biomarker for Detection of Neuroendocrine Neoplasms: Cytopathologists’ View

INSM1, a Novel Biomarker for Detection of Neuroendocrine Neoplasms: Cytopathologists’ View

Insulinoma‐associated 1: A sensitive marker of neuroendocrine differentiation in cutaneous and metastatic neuroendocrine tumors

Utility of Insulinoma-Associated Protein 1 (INSM1) and Mucin 2 (MUC2) Immunohistochemistry in the Distinction of Endocrine Mucin-Producing Sweat Gland Carcinoma From Morphologic Mimics

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