Stains & CD markers
S100
Copyright: 2002-2024, PathologyOutlines.com, Inc.
PubMed Search: S100 stain
S100
Editorial Board Member: Borislav A. Alexiev, M.D.
Editor-in-Chief: Debra L. Zynger, M.D.
Last author update: 26 November 2019
Last staff update: 17 March 2023
Copyright: 2002-2024, PathologyOutlines.com, Inc.
PubMed Search: S100 stain
Table of Contents
Definition / general | Essential features | Interpretation | Uses by pathologists | Microscopic (histologic) images | Positive staining - normal | Positive staining - disease | Negative staining | Additional references | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Khan AM, Topilow AA. S100. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainss100.html. Accessed April 17th, 2024.
Definition / general
- Name is from its solubility in 100% saturated ammonium sulfate at neutral pH
- Family of multigenic group of nonubiquitous cytoplasmic homologous intracellular Ca2+ binding proteins with EF hand motifs and significant structural similarities at both protein and genomic levels
- Low molecular weights (9 -1 3 kDa) and are able to form heterodimers, homodimers and oligomeric assemblies
- S100 is composed of two main subunits, an alpha and a beta chain; most clinical stains use antibodies to the beta chain
- S100 protein family has 25 known members solely in vertebrates coded by unique genes
- There are 22 proteins (S100A1-A8, trichohylin, filaggrin and repetin) mapped onto chromosome locus 1q21, while the other proteins are located on chromosome loci 4p16 (S100P), 5q14 (S100Z), 21q22(S100B), Xp22(S100G), 5q13(S100Z), 7q22-q3(S100A11P) (Curr Mol Med 2013;13:24, Nat Rev Cancer 2015;15:96)
- Structurally similar to calmodulin and troponin-C but these proteins are cell specific and dependent upon environmental factors via cytokines, growth factors and toll-like receptors (TLR) ligands (Curr Mol Med 2013;13:24, Nat Rev Cancer 2015;15:96)
Essential features
- Family of multigenic group of nonubiquitous cytoplasmic homologous intracellular Ca2+ binding proteins with EF hand motifs and significant structural similarities at both protein and genomic levels
- Found in melanoma, nerve sheath tumors, clear cell sarcoma of soft tissue, various histiocytic tumors, glial tumors and myoepithelial tumors
- Aid in diagnosis of tumors of unknown origin and to show nerve sheath involvement
Interpretation
- Cytoplasmic and nuclear staining usually required to call positive
Uses by pathologists
- Marker of schwann cells and melanocytes; useful for evaluating nerve sheath tumors and melanoma
- Differentiate benign nerve sheath tumors (S100 strong and diffuse) from malignant peripheral nerve sheath tumors (typically weak or negative S100) (Am J Surg Pathol 2005;29:1042)
- Help differentiate between schwannoma (stains all cells) and neurofibroma (mixture of positive and negative cells)
- Distinguish Langerhans cell histiocytosis from other histiocytosis syndromes (Arch Pathol Lab Med 2015;139:1211)
- Identifying perineural involvement
- Myoepithelial cell marker and identification of tumors with myoepithelial cells
- MelanA and MART1 superior to S100 for evaluating sentinel lymph nodes for melanoma (Am J Surg Pathol 2001;25:1039)
Microscopic (histologic) images
Contributed by Arbaz M. Khan
Melanoma
Melanoma S100
Granular cell tumor
Granular cell tumor S100
Schwannoma
Schwannoma S100
Cases #6, #50, #54, #195, #218 and #252
Bladder paraganglioma S100
Breast granular cell tumor S100
Breast metaplastic carcinoma S100
Lymph node
mycobacterial
spindle cell
pseudotumor S100
Salivary gland epithelial myoepithelial carcinoma S100
Soft tissue plexiform schwannoma S100
AFIP images
Skin Langerhans cell histiocytosis S100
Positive staining - normal
- Neurons, schwann cells, melanocytes, glial cells
- Myoepithelial cells
- Adipocytes
- Langerhans cells, tissue dendritic cells and interdigitating dendritic cells
- Chondrocytes and notochordal cells
Positive staining - disease
- Mesenchymal:
- Nerve sheath tumors: schwannoma (diffuse), ganglioneuroma (diffuse), dermal nerve sheath myxoma, neurofibroma (predominantly positive with negative nonschwannian component)
- Malignant peripheral nerve sheath tumor (30 - 67% show any staining; low grade lesions typically diffuse and conventional high grade examples are weak / patchy) (J Clin Pathol 2003 Nov;56:826)
- Adipocytic component of lipogenic tumors
- Chondroid tumors: enchondroma, osteochondroma, chondrosarcoma, chondromyxoid fibroma, chondroblastoma and mesenchymal chondrosarcoma (chondrocytic component only) (Arch Pathol Lab Med 2012;136:61)
- Notochordal tumors: benign notochordal cell tumor, conventional chordoma, chondroid chordoma (Mod Pathol 2008;21:1461)
- Clear cell sarcoma of soft tissue (Am J Surg Pathol 2008;32:452)
- Granular cell tumor (Arch Pathol Lab Med 2004;128:771)
- Biphenotypic sinonasal sarcoma (Arch Pathol Lab Med 2018;142:1196)
- Ossifying fibromyxoid tumor (Am J Surg Pathol 2008;32:996)
- Extraskeletal myxoid chondrosarcoma (31%) (Pathol Int 2005;55:453)
- Synovial sarcoma (34%) (Am J Clin Pathol 1999;112:641)
- Ewing sarcoma (variable) (Appl Immunohistochem Mol Morphol 2012;20:445)
- Perivascular epithelioid cell tumors (less commonly than other melanocytic markers; 33%) (Am J Surg Pathol 2005;29:1558)
- Mycobacterial spindle cell pseudotumor (Am J Surg Pathol 1992;16:276)
- Brain:
- Glial tumors: astrocytoma, oligodendroglioma, ependymoma
- Choroid plexus papilloma and carcinoma (Am J Surg Pathol 1986;10:394)
- Meningioma (Positive in ~70% of fibrous variant) (Appl Immunohistochem Mol Morphol 2015;23:215)
- Macrophage lineage:
- Interdigitating dendritic cell tumors (Am J Hematol 2007;82:725)
- Langerhans cell tumors (Am J Surg Pathol 2007;31:947)
- Rosai-Dorfman disease (Am J Surg Pathol 1992;16:122)
- Epithelial / myoepithelial:
- Melanoma (95%, including desmoplastic and spindle cell tumors); S100- melanomas often had prior S100+ metastases, often are ocular (Hum Pathol 2005;36:1016)
- Invasive breast carcinoma (subset; particularly basal-like subtype) (Contemp Oncol (Pozn) 2016;20:436)
- Metaplastic breast carcinoma (Diagn Pathol 2014;9:139)
- Myoepithelial tumors: myoepithelioma, myoepithelial carcinoma
- Salivary gland tumors with myoepithelial differentiation: pleomorphic adenoma, myoepithelioma, basal cell adenoma, adenoid cystic carcinoma, polymorphous adenocarcinoma, epithelial-myoepithelial carcinoma, sialoblastoma (Acta Histochem Cytochem 2012;45:269)
- Mammary analogue secretory carcinoma (Head Neck Pathol 2015;9:85)
- Others:
- Paraganglioma / pheochromocytoma: sustentacular cells
- Neuroendocrine tumors (subset, often focal) (Am J Surg Pathol 2005;29:1194)
- Sex cord-stromal tumors (variable in any of this category) (Mod Pathol 1997;10:693)
Negative staining
- Mesenchymal:
- Perineurioma (Am J Surg Pathol 2005;29:845)
- Cellular neurothekeoma (Am J Surg Pathol 2007;31:329)
- Fibroblastic reticular cell tumor (Am J Surg Pathol 1998;22:1048)
- Alveolar soft part sarcoma (Arch Pathol Lab Med 2015;139:1459)
- Rhabdomyoma (may be focally positive)
- Sinonasal glomangiopericytoma (Pathol Res Pract 2019;215:983)
- Clear cell sarcoma of the kidney (Arch Pathol Lab Med 2019;143:1022)
- Solitary fibrous tumor (Iran J Pathol 2016;11:195)
- Mammary type myofibroblastoma (Am J Surg Pathol 2016;40:361)
- Cellular angiofibroma (Am J Surg Pathol 2004;28:1426)
- Gastrointestinal stromal tumor (Transl Gastroenterol Hepatol 2018;3:27)
- Benign fibrous histiocytoma (Am J Dermatopathol 2001;23:104)
- Atypical fibroxanthoma (Anticancer Res 2015;35:5717)
- Macrophage lineage:
- Follicular dendritic cell tumors (may show rare positive cases) (Am J Hematol 2007;82:725)
- Erdheim-Chester disease (Blood 2014;124:483)
- Juvenile xanthogranuloma (rare positive but generally negative) (Am J Surg Pathol 2005;29:21)
- Xanthoma
- Salivary gland tumors without myoepithelial differentiation: salivary duct carcinoma, mucoepidermoid carcinoma, squamous cell carcinoma, oncocytoma / oncocytic carcinoma, Warthin tumor (Arch Pathol Lab Med 2015;139:55)
- Squamous cell carcinoma
- Lymphoma
Additional references
Board review style question #1
- Shown above is an S100 stain of a skin lesion. Which of the following tumors should be positive for S100?
- Basal cell carcinoma
- Melanoma
- Squamous cell carcinoma
- Mycoses fungoides
- Atypical fibroxanthoma
Board review style answer #1
Board review style question #2
- A biopsied lung lesion is radiographically suspected to be a metastasis of unknown primary. Which staining profile suggests that the tumor is melanoma?
- S100 positive, CK5/6 positive, p63 negative, GFAP negative
- S100 negative, HMB45 positive, TTF1 negative, CK20 negative
- S100 positive, HMB45 positive, CK7 negative, p63 negative
- S100 negative, TTF1 positive, SOX10 positive, AE1/AE3 negative
- S100 positive, CD21 positive, CD35 positive, Clusterin positive
Board review style answer #2
