Stains & molecular markers
S100


Topic Completed: 26 November 2019

Minor changes: 9 October 2020

Copyright: 2002-2020, PathologyOutlines.com, Inc.

PubMed Search: S100 [title] stain pathology

Farres Obeidin, M.D.
Arthur A. Topilow, M.D.
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Cite this page: Khan AM, Topilow AA. S100. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/stainss100.html. Accessed November 26th, 2020.
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
Negative staining
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?

  1. Basal cell carcinoma
  2. Melanoma
  3. Squamous cell carcinoma
  4. Mycoses fungoides
  5. Atypical fibroxanthoma
Board review answer #1
B. Melanoma

Reference: S100

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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?

  1. S100 positive, CK5/6 positive, p63 negative, GFAP negative
  2. S100 negative, HMB45 positive, TTF1 negative, CK20 negative
  3. S100 positive, HMB45 positive, CK7 negative, p63 negative
  4. S100 negative, TTF1 positive, SOX10 positive, AE1/AE3 negative
  5. S100 positive, CD21 positive, CD35 positive, Clusterin positive
Board review answer #2
C. S100 positive, HMB45 positive, CK7 negative, p63 negative

Reference: S100

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