Stains & CD markers
INSM1
Copyright: 2019-2024, PathologyOutlines.com, Inc.
PubMed Search: INSM1[TIAB]
INSM1
Author: Lisa Rooper, M.D.
Deputy Editor-in-Chief: Debra L. Zynger, M.D.
Last author update: 1 June 2018
Last staff update: 8 August 2023
Copyright: 2019-2024, PathologyOutlines.com, Inc.
PubMed Search: INSM1[TIAB]
Table of Contents
Definition / general | Essential features | Pathophysiology | Clinical features | Uses by pathologists | Prognostic factors | Interpretation | Microscopic (histologic) images | Positive staining - normal | Positive staining - tumors | Negative staining - normal | Negative staining - tumors | Board review style question #1 | Board review style answer #1Cite this page: Rooper LM INSM1. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainsinsm1.html. Accessed May 6th, 2024.
Definition / general
- Insulinoma associated protein 1
- Previously abbreviated as IA1
Essential features
- Nuclear marker of neuroendocrine differentiation with equivalent or better sensitivity and specificity compared to synaptophysin, chromogranin and CD56
- Expressed in a broad spectrum of neuroendocrine tumors (including small cell carcinoma, large cell neuroendocrine carcinoma and well differentiated neuroendocrine tumor / carcinoid tumor of various sites, paraganglioma / pheochromocytoma, Merkel cell carcinoma, olfactory neuroblastoma and medullary thyroid carcinoma)
- Also expressed in normal adult neuroendocrine tissues (adrenal medulla, pineal gland, pituitary gland, gastrointestinal enterochromaffin cells, pancreatic islet cells, thyroid C cells) and developing neurons
Pathophysiology
- Zinc finger transcription factor originally isolated from pancreatic insulinomas (J Biol Chem 1992;267:15252)
- Transcriptional repressor that regulates entry into cell cycle and controls expression of neuroendocrine phenotype in normal tissues (Biochem J 2006;397:169, J Biol Chem 2009;284:5574)
- Plays a vital role in development of normal neuroendocrine cells throughout body (Genes Dev 2006;20:2465, Development 2008;135:473, J Comp Neurol 2008;507:1497, Neural Dev 2011;6:6)
- Regulates the development of neuroendocrine differentiation in various tumor types (Am J Pathol 2015;185:3164)
Clinical features
- Proposed as promoter for targeted gene therapy for small cell lung carcinoma (Cancer Gene Ther 2006;13:375)
Uses by pathologists
- Identification of neuroendocrine differentiation in a wide range of tissues and tumor types (Am J Clin Pathol 2015;144:579)
- Diagnosis of high grade neuroendocrine carcinoma that is negative for synaptophysin and chromogranin (Am J Surg Pathol 2017;41:1561, Am J Surg Pathol 2018;42:665)
- Identification of immature neuronal differentiation in brain tumors and developing brain tissue (J Neuropathol Exp Neurol 2018;77:374)
- Differentiates carcinoid tumorlet from pulmonary meningothelial-like nodule (Histopathology 2018;72:1067)
- Differentiates extraskeletal myxoid chondrosarcoma from most histologic mimics (Mod Pathol 2018;31:744)
Prognostic factors
- High expression of INSM1 is associated with increased progression free survival and chemosensitivity in small cell lung carcinoma (Oncotarget 2017;8:73745)
- Higher expression in midgut gastrointestinal neuroendocrine carcinomas with metastases compared to those not yet metastasized (Am J Clin Pathol 2015;144:579)
Interpretation
- Nuclear stain
Microscopic (histologic) images
Contributed by Lisa M. Rooper, M.D.
Small cell carcinoma (lung)
Large cell neuroendocrine carcinoma (lung)
Atypical carcinoid tumor (lung)
Olfactory neuroblastoma
Pituitary adenoma
Pancreatic neuroendocrine tumor
Paraganglioma (carotid body)
Middle ear adenoma
Thyroid C cell hyperplasia
Positive staining - normal
- Adrenal: medulla (Am J Clin Pathol 2015;144:579)
- Brain: pineal gland, pituitary gland, developing neurons in external granular cell layer of fetal cerebellum and subventricular zones (J Neuropathol Exp Neurol 2018;77:374)
- Gastrointestinal tract: enterochromaffin cells (Am J Clin Pathol 2015;144:579)
- Pancreas: islet cells (Am J Clin Pathol 2015;144:579)
- Thyroid: C cells (Am J Surg Pathol 2018;42:665)
Positive staining - tumors
- Adrenal: pheochromocytoma (100%), neuroblastoma (75%) (Am J Clin Pathol 2015;144:579)
- Brain: medulloblastoma (87%), central neurocytoma (100%), pituitary adenoma (100%), pineal parenchymal tumor (43%), CNS embryonal tumor, NOS (43%), glioblastoma (44%) (J Neuropathol Exp Neurol 2018;77:374)
- Breast: breast carcinoma with neuroendocrine differentiation (100%) (Am J Clin Pathol 2015;144:579)
- Gastrointestinal tract: gastrointestinal neuroendocrine tumors (95%), colonic adenocarcinoma with neuroendocrine differentiation (100%) (Am J Clin Pathol 2015;144:579)
- Gynecologic tract: cervical high grade neuroendocrine carcinoma (95%) (Mod Pathol 2018;31:744)
- Head and neck: small cell carcinoma (93%), large cell neuroendocrine carcinoma (100%), olfactory neuroblastoma (100%), teratocarcinosarcoma (100%), paraganglioma (100%), middle ear adenoma (100%), alveolar rhabdomyosarcoma (50%), SMARCB1 deficient sinonasal carcinoma (33%) (Am J Surg Pathol 2018;42:665)
- Lung: small cell carcinoma (95%), large cell neuroendocrine carcinoma (91%), atypical carcinoid (100%), typical carcinoid (100%) (Am J Surg Pathol 2017;41:1561)
- Mediastinum: large cell neuroendocrine carcinoma (100%), atypical carcinoid (100%) (Am J Surg Pathol 2017;41:1561)
- Pancreas: pancreatic neuroendocrine tumor (100%) (Med Mol Morphol 2018;51:32)
- Prostate: small cell carcinoma (77%) (Lab Invest 2017;97:262A)
- Skin: Merkel cell carcinoma (93%), endocrine mucin producing sweat gland carcinoma (100%) (J Cutan Pathol 2018;45:129)
- Soft tissue: extraskeletal myxoid chondrosarcoma (90%), ossifying fibromyxoid tumor (30%), Ewing sarcoma (30%), BCOR-CCNB3 sarcoma (20%) (Mod Pathol 2018;31:744)
- Thyroid / parathyroid: medullary carcinoma (100%) (Am J Surg Pathol 2018;42:665)
Negative staining - normal
- Adrenal: cortex (Am J Clin Pathol 2015;144:579)
- Brain: adult cerebellum, adult cortex (J Neuropathol Exp Neurol 2018;77:374)
- Breast: breast ductal epithelium (Am J Clin Pathol 2015;144:579)
- Gynecologic tract: endometrial glands, endometrial stroma, ovarian stroma (Am J Clin Pathol 2015;144:579)
- Lung: pneumocytes (Am J Clin Pathol 2015;144:579)
- Hematolymphoid: lymph nodes, tonsil (Am J Clin Pathol 2015;144:579)
- Pancreas: acinar epithelium, ductal epithelium (Am J Clin Pathol 2015;144:579)
- Prostate: prostate parenchyma (Am J Clin Pathol 2015;144:579)
- Skin: dermis, squamous epithelium (Am J Clin Pathol 2015;144:579)
- Soft tissue: bone, skeletal muscle, cartilage (Am J Clin Pathol 2015;144:579)
- Thyroid / parathyroid: thyroid follicular tissue, parathyroid tissue (Am J Clin Pathol 2015;144:579)
Negative staining - tumors
- Adrenal gland: adrenal cortical adenoma (0%) (Am J Clin Pathol 2015;144:579)
- Brain: ganglioglioma (7%), ependymoma (5%), pilocytic astrocytoma (0%) (J Neuropathol Exp Neurol 2018;77:374)
- Gastrointestinal tract: colonic adenocarcinoma (0%) (Am J Clin Pathol 2015;144:579)
- Head and neck: squamous cell carcinoma (2%), mucoepidermoid carcinoma (3%), adenoid cystic carcinoma (0%), polymorphous adenocarcinoma (0%), secretory carcinoma (0%), pleomorphic adenoma (0%), HPV related multiphenotypic carcinoma (0%), NUT carcinoma (0%), sinonasal undifferentiated carcinoma (0%), mucosal melanoma (0%) (Am J Surg Pathol 2018;42:665)
- Hematolymphoid: small lymphocytic lymphoma (0%) (J Cutan Pathol 2018;45:129)
- Lung: adenocarcinoma (3%), squamous cell carcinoma (4%) (Am J Surg Pathol 2017;41:1561)
- Pancreas: ductal adenocarcinoma (0%), acinar cell carcinoma (0%), solid pseudopapillary neoplasm (0%) (Med Mol Morphol 2018;51:32)
- Prostate: adenocarcinoma (9%) (Lab Invest 2017;97:262A)
- Skin: melanoma (0%) (Am J Clin Pathol 2015;144:579)
- Soft tissue: chondrosarcoma (0%), chordoma (10%), myxofibrosarcoma (0%), myxoid liposarcoma (0%), intramuscular mxyoma (0%), low grade fibromyxoid sarcoma (0%), myoepithelioma (5%), angiomatoid fibrous histiocytoma (0%), dedifferentiated liposarcoma (0%), CIC rearranged sarcoma (0%), synovial sarcoma (0%) (Mod Pathol 2018;31:744)
- Thyroid / parathyroid: papillary carcinoma (0%), follicular carcinoma (0%), follicular adenoma (0%), parathyroid carcinoma (0%), parathyroid adenoma (0%) (Am J Surg Pathol 2018;42:665)
Board review style question #1
Which of the following tumors should be negative for INSM1?
- Extraskeletal myxoid chondrosarcoma
- Middle ear adenoma
- Parathyroid adenoma
- Small cell carcinoma of the uterine cervix
- Well differentiated pancreatic neuroendocrine tumor, grade 1
Board review style answer #1
C. Parathyroid adenoma. Although parathyroid neoplasms frequently stain with the common neuroendocrine stain chromogranin, they are consistently negative for INSM1.
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Reference: INSM1
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