IHC single marker with reporting S100 Protein

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IHC Single Marker with Reporting S100 Protein - Comprehensive Medical Test Information Guide

Section 1: Why is it done?
- Test Overview: This immunohistochemistry (IHC) test detects and visualizes S100 protein expression in tissue samples using specific antibodies. S100 protein is a calcium-binding protein family expressed in various cell types, particularly useful for identifying neural, glial, and melanocytic differentiation.
- Primary Indications: Diagnosis of melanoma and other melanocytic lesions; identification of neural and nerve sheath tumors (schwannomas, neurofibromas); classification of salivary gland tumors; diagnosis of Langerhans cell histiocytosis; evaluation of lymphomas with specific phenotyping; assessment of clear cell sarcoma and other soft tissue neoplasms
- Clinical Circumstances: Performed on tissue samples obtained from biopsies or surgical specimens; typically ordered when morphologic examination is inconclusive; used to confirm suspected diagnoses and guide treatment planning; useful in differentiating benign from malignant lesions; employed in tumor marker studies for prognosis assessment
- Typical Timing: Usually performed within 1-2 weeks of tissue collection; results typically available within 3-5 business days after analysis; may be expedited for urgent cases; part of routine histopathologic examination in most pathology laboratories
Section 2: Normal Range
- Reporting System: IHC results are reported as either POSITIVE or NEGATIVE, rather than numerical values. This is a semi-quantitative assessment based on cellular localization and staining intensity.
- Normal (Negative) Result: Indicates absent or minimal S100 protein expression in the tissue sample. Most benign epithelial tissues and many normal tissue types show negative staining. This finding may help exclude certain diagnoses or support alternative diagnoses.
- Abnormal (Positive) Result: Indicates presence of S100 protein expression in tissue cells. Staining pattern may be diffuse (widespread), focal (limited areas), or strong/weak based on intensity. Positive results support diagnosis of S100-expressing tumors including melanomas, neural tumors, and specific lymphoid neoplasms.
- Staining Intensity Grading: 1+ (weak), 2+ (moderate), 3+ (strong) staining intensities; percentage of positive cells may also be reported (0%, 1-25%, 26-50%, 51-75%, 76-100%). Strong and diffuse positivity (3+, >75% of cells) is more diagnostically significant than weak or focal staining.
- Control Interpretation: Results are interpreted with positive and negative control tissues run concurrently. Positive controls validate antibody function; negative controls confirm specificity. Valid results require appropriate control reactivity.
Section 3: Interpretation
- Positive S100 Result: Suggests melanocytic differentiation (melanoma vs benign nevi), neural origin (schwannoma, neurofibroma), or lymphoid processes (specific lymphoma subtypes). In melanomas, strong diffuse S100 positivity is typical and helps confirm diagnosis. May also indicate Langerhans cell histiocytosis or certain salivary tumors depending on morphology.
- Negative S100 Result: Makes melanocytic origin less likely; helps exclude neural tumors; reduces likelihood of S100-dependent diagnoses. May support alternative diagnoses such as carcinomas or other non-melanocytic malignancies. However, negative results must be correlated with morphology and clinical context.
- Staining Pattern Significance: Diffuse staining (>75% cells positive) indicates strong marker expression; focal/scattered positivity (<50% cells) may represent neoplastic subset or reactive cells; membranous vs cytoplasmic localization may provide additional diagnostic information; granular/paranuclear patterns may suggest specific cell types.
- Factors Affecting Results: Tissue fixation quality and duration; antigen retrieval method; antibody dilution and quality; incubation times and temperatures; detection system used; background staining in inflamed tissues; crush artifacts or poor tissue preservation; previous therapies affecting marker expression
- Clinical Significance in Context: S100 is sensitive but not specific for melanoma (also positive in benign nevi, desmoplastic melanoma); loss of S100 expression may indicate dedifferentiation or certain spindle cell carcinomas; must be used in conjunction with other IHC markers (Melan-A, SOX10, HMB-45) for accurate diagnosis; clinical and morphologic correlation essential for proper interpretation
Section 4: Associated Organs
- Primary Organ Systems: Integumentary system (skin); nervous system (peripheral nerves, CNS); lymphoid system (lymph nodes, spleen); salivary glands; soft tissues (sarcomas); eye (uveal melanoma); gastrointestinal tract; respiratory system; hematopoietic system
- Common Associated Conditions: Cutaneous and mucosal melanomas; acral and deep penetrating melanomas; uveal and conjunctival melanomas; benign and dysplastic nevi; schwannomas (vestibular and non-vestibular); neurofibromas (dermal and plexiform); malignant peripheral nerve sheath tumors; Langerhans cell histiocytosis; angiomyolipoma; clear cell sarcoma; certain T-cell lymphomas; myxoid liposarcoma
- Diagnostic Applications: Differentiating melanoma from carcinoma; identifying neural differentiation in sarcomas; confirming Langerhans cell origin in histiocytosis; phenotyping lymphomas; identifying granular cell tumors; assessing clear cell lesions; recognizing desmoplastic melanoma; evaluating metastatic unknown primary tumors
- Prognosis and Complications: S100-positive melanomas with strong diffuse staining typically carry higher risk for metastasis; loss of S100 expression may indicate aggressive behavior; Langerhans cell histiocytosis positive for S100 may have multisystem involvement; nerve sheath tumors showing S100 positivity have malignant potential requiring surveillance; abnormal expression patterns guide treatment decisions and follow-up protocols
- Clinical Complications: Diagnostic errors if results misinterpreted without clinical correlation; potential for unnecessary treatment if over-interpreting positive results in benign lesions; missed diagnoses if negative results in desmoplastic or poorly differentiated tumors; regional lymph node metastases requiring sentinel lymph node biopsy; systemic dissemination requiring advanced imaging; development of drug resistance in treated tumors
Section 5: Follow-up Tests
- Complementary IHC Markers: Melan-A (MART-1) for melanocytic confirmation; HMB-45 to assess maturation and differentiation; SOX10 for neural crest derived tumors; Mitf for melanoma vs other tumors; Ki-67 for proliferation assessment and prognosis; p16 for dysplasia evaluation; claudin-1 and other markers for specific differential diagnoses
- Molecular Testing: BRAF V600E mutation testing in melanomas; KIT mutation analysis in acral/mucosal melanomas; NRAS mutations for risk stratification; NF1 testing for neurofibromas; molecular testing for lymphomas; gene fusion studies for sarcomas; NGS-based panel testing for comprehensive genomic profiling
- Imaging Studies: Sentinel lymph node biopsy (SLNB) for stages IB-III melanomas; CT chest/abdomen/pelvis for metastatic staging; MRI brain for CNS involvement; PET-CT for detecting distant disease; ultrasound for regional lymph node assessment; dermoscopy for follow-up of skin lesions
- Clinical Follow-up: Regular skin examinations every 3-12 months based on risk; ophthalmologic examination for intraocular involvement; annual dermatology surveillance; monitoring for recurrence and metastatic disease; assessment of treatment response in managed cases; long-term follow-up for late recurrences (>5 years)
- Additional Tissue Studies: Electron microscopy for ultrastructural evaluation; flow cytometry for lymphoid lesions; fluorescence in situ hybridization (FISH) for chromosomal abnormalities; digital image analysis for quantification of marker expression; repeat biopsies if initial findings inconclusive
- Monitoring Frequency: High-risk melanomas: clinical examination every 3-6 months for 2-3 years, then annually; intermediate-risk: every 6-12 months; low-risk: annual surveillance indefinitely; sentinel node positive cases: more intensive monitoring; metastatic disease: baseline imaging with serial reassessment every 3-6 months during treatment
Section 6: Fasting Required?
- Fasting Requirement: NO - Fasting is NOT required for this test. IHC single marker S100 protein testing is performed on tissue samples, not blood or body fluids. The test analyzes fixed tissue specimens obtained via biopsy or surgical procedures.
- Tissue Specimen Handling: Tissue samples must be promptly fixed in appropriate formalin-based fixative (typically 10% neutral buffered formalin); adequate fixation time required (minimum 6-24 hours depending on tissue thickness); proper specimen labeling with patient identification and anatomic location; preservation of tissue quality through appropriate collection and transport methods
- Pre-Procedure Preparation: If biopsy required: follow physician instructions for biopsy preparation; no specific dietary restrictions; normal medications may be continued unless specified by physician; anticoagulant management per institutional protocol; clothing that allows easy access to biopsy site; arrange transportation if sedation planned
- Medication Considerations: No medications need to be withheld for tissue analysis; anticoagulants/antiplatelet agents may require adjustment if biopsy planned; consult with physician regarding aspirin, warfarin, or DOAC management; immunosuppressive therapies may be continued unless specified otherwise; prior or concurrent chemotherapy/immunotherapy does not contraindicate testing
- General Instructions: Inform pathology of relevant clinical history (previous treatments, suspected diagnoses); provide complete clinical indication for testing; ensure specimen undergoes appropriate processing and sectioning; special stains or techniques communicated to laboratory; patient may resume normal activities immediately after tissue collection unless instructed otherwise
- Post-Collection Care: Biopsy site wound care per provider instructions; monitor for signs of infection; keep biopsy area clean and dry; avoid strenuous activity if surgical biopsy performed; contact physician if excessive bleeding, infection, or unusual symptoms develop; no dietary or activity restrictions for laboratory analysis itself

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