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Reviewer: Nat Pernick, M.D. (see Reviewers page)
Revised: 2 January 2013, last major update January 2013
Copyright: (c) 2002-2012, PathologyOutlines.com, Inc.
PubMed Search: S-100 [title]
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● Acidic protein, 100% Soluble in ammonium sulfate at neutral pH (derivation of name)
● S100 protein family is multigenic group of nonubiquitous cytoplasmic EF-hand Ca2+-binding proteins, sharing significant structural similarities at both genomic and protein levels; S100 protein family has 24 known human members each coded by a separate gene; at least 19 on chromosome 1q21 (Hepat Mon 2012;12:e7240)
● Helps regulate cell contraction, motility, growth, differentiation, cell cycle progression, transcription and secretion
● Structurally similar to calmodulin

Uses by pathologists

Interpretation: cytoplasmic and nuclear staining usually required to call positive
● Common marker of neural tissue / lesions and melanoma
● Differentiate plexiform schwannoma (S100+, Am J Surg Pathol 2005;29:1042) from MPNST (weak / negative / patchy)
● MelanA and MART1 appear to be superior to S100 for evaluating sentinel lymph nodes for melanoma (Am J Surg Pathol 2001;25:1039)

Micro images

Quality control images (various)

Adrenal gland: ganglioneuroma is S100+

Adrenal gland: pheochromocytoma-sustentacular cells are S100+

Bladder: paraganglioma and paraganglioma-site unspecified

Breast: basal-like invasive ductal carcinoma (has S100+ myoepithelial phenotype)

Breast: granular cell tumor

Breast: liposarcoma - lipoblasts are S100+ (figure 4)

Breast: malignant adenomyoepithelioma - S100+ in benign areas

Breast: metaplastic carcinoma

Breast: myoepithelial carcinoma

Breast: Paget's disease is S100-

Cervix: plexiform neurofibroma and Pacinian corpuscles are S100+ (figures 3/4)

CNS: Rosai-Dorfman

Colon: schwannoma

Heart: granular cell tumor

Larynx: granular cell tumor

Lymph nodes: mycobacterial spindle cell pseudotumor

Lymph nodes: Omenn's syndrome - interdigitating reticulum cells are S100+

Nasal cavity: olfactory neuroblastoma

Oral cavity: S100 demonstrates perineural invasion in squamous cell carcinoma (fig 2B)

Prostate: sclerosing adenosis

Salivary gland: epithelial myoepithelial carcinoma

Skin: granular cell tumor

Skin: Langerhans cell histiocytosis-tumor cells are strongly S100+

Skin: melanoma and nevus cells

Skin: melanoma, desmoplastic

Soft tissue: arteriovenous vascular malformation has small nerve bundle that is S100+

Soft tissue: chondrosarcoma

Soft tissue: MPNST

Soft tissue: plexiform schwannoma

Testis: Cowden's syndrome patient has S100+ adipocytes

Testis: Large cell calcifying Sertoli cell tumo

Positive staining - normal

● Neural crest derived tissue: Schwann cells, melanocytes, glial cells
● Skin apocrine and eccrine glands
● Adipocytes, chondrocytes, dendritic cells, Langerhans cells, macrophages, myoepithelial cells
● Some breast epithelial cells

Positive staining - disease

● Adenoid cystic carcinoma
● Chondroid tumors
● Chordoma
● Clear cell sarcoma
● Dendritic cell tumors
● 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
● Paragangliomas: 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

End of Stains > S100

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