Stains & molecular markers
S100


Topic Completed: 26 November 2019

Revised: 26 November 2019

Copyright: 2002-2019, PathologyOutlines.com, Inc.

PubMed Search: S100 [title] stain pathology

Arthur A. Topilow, MD
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Cite this page: Khan AM, Topilow AA. S100. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainss100.html. Accessed December 6th, 2019.
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 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, schwannoma, neurofibroma, malignant peripheral nerve sheath tumor, paraganglioma stromal cells, histiocytoma and clear sarcoma
  • Aid in diagnosis of tumors of unknown origin, to show nerve sheath involvement
Interpretation
  • Cytoplasmic and nuclear staining usually required to call positive
Uses by pathologists
  • Common marker of neural tissue / lesions and melanoma
  • Differentiate plexiform schwannoma (S100+) from malignant peripheral nerve sheath tumor (weak / negative / patchy) (Am J Surg Pathol 2005;29:1042)
  • MelanA and MART1 appear to be 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
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Melanoma

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Melanoma S100

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Granular cell tumor

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Granular cell tumor S100

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Schwannoma

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Schwannoma S100



Cases #6, #50, #54, #195, #218, #252
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Bladder paraganglioma S100

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Breast granular cell tumor S100

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Breast metaplastic carcinoma S100

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Lymph node
mycobacterial
spindle cell
pseudotumor S100

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Salivary gland epithelial myoepithelial carcinoma S100

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Soft tissue plexiform schwannoma S100

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Skin Langerhans cell histiocytosis S100

Positive staining - normal
Positive staining - disease
  • Adenoid cystic carcinoma
  • Chondroid tumor
  • Chordoma
  • Clear cell sarcoma
  • Dendritic cell tumor
  • Glial tumors
  • Granular cell tumor (Arch Pathol Lab Med 2004;128:771)
  • Langerhans cell tumors
  • Lipogenic tumors
  • Malignant peripheral nerve sheath tumor (50%)
  • Melanoma (95%, including desmoplastic and spindle cell tumors); S100- melanomas often had prior S100+ metastases, often are ocular (Hum Pathol 2005;36:1016)
  • Mycobacterial spindle cell pseudotumor in lymph nodes
  • Myoepithelial tumors
  • Neural tumors: schwannoma, neurofibroma
  • Paraganglioma / pheochromocytoma: sustentacular cells
  • Perivascular epithelioid cell tumors (angiomyolipoma, clear cell "sugar" tumor, lymphangioleiomyomatosis, PEComas)
  • Rosai-Dorfman disease
  • Sex cord stromal tumors
Negative staining
  • Fibroblasts, fibroblastic reticulum cells, perineural cells
  • Atypical fibroxanthoma
  • Cardiac sarcomas
  • Myofibroblastoma
  • Solitary fibrous tumor
  • Xanthoma
Board review 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
Board review answer #1
B. Melanoma

Reference: S100

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Board review 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
Board review answer #2
C. S100 positive, HMB45 positive, CK7 negative, p63 negative

Reference: S100

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