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IHC single marker with reporting Synaptophysin

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Tumor marker staining.

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IHC Single Marker with Reporting Synaptophysin - Comprehensive Medical Guide

  • Why is it done?
    • Synaptophysin is a neuroendocrine marker used in immunohistochemistry (IHC) to identify and classify tumors with neuroendocrine differentiation
    • Diagnosis of neuroendocrine tumors (NETs) in various organ systems including lung, pancreas, gastrointestinal tract, and thyroid
    • Differentiation of neuroendocrine carcinomas from other malignant tumors
    • Classification and grading of small cell lung cancer (SCLC) and other high-grade neuroendocrine carcinomas
    • Evaluation of poorly differentiated or undifferentiated tumors to establish neuroendocrine origin
    • Performed on tissue samples obtained through biopsy or surgical resection specimens
    • Typically ordered when initial histological examination suggests neuroendocrine differentiation
  • Normal Range
    • Negative Result: No staining or minimal background staining in tumor cells; indicates absence of neuroendocrine differentiation
    • Positive Result: Brown cytoplasmic staining in neuroendocrine cells; indicates presence of synaptophysin and neuroendocrine differentiation
    • Intensity Scoring: 0 (negative), 1+ (weak), 2+ (moderate), 3+ (strong); based on chromogenic detection intensity
    • Distribution Assessment: Focal (limited areas), diffuse (widespread), or scattered positivity; reported as percentage of positive cells
    • Units of Measurement: Immunohistochemical staining percentage (0-100%); intensity score on ordinal scale
    • Normal Interpretation: Negative or focal weak staining in non-neuroendocrine tissues; positive staining in normal neuroendocrine cells (pancreatic islets, enteric neurons, adrenal medulla)
  • Interpretation
    • Positive/Strong Staining (3+): Consistent with neuroendocrine tumor; high likelihood of neuroendocrine differentiation; supports diagnosis of small cell carcinoma, carcinoid tumor, or other NET subtypes
    • Moderate Staining (2+): Indicative of neuroendocrine differentiation; typically considered positive in diagnostic context; may require correlation with morphology and additional markers
    • Weak Staining (1+): Borderline positivity; may indicate partial or low-level neuroendocrine differentiation; correlation with clinical context and additional immunostains recommended
    • Negative Staining (0): Absence of neuroendocrine marker expression; argues against neuroendocrine origin; tumor likely has non-neuroendocrine differentiation
    • Diffuse vs. Focal Staining: Diffuse pattern (>50%) more supportive of primary neuroendocrine tumor; focal staining may suggest mixed histology or secondary neuroendocrine features
    • Clinical Correlation Essential: Synaptophysin results must be integrated with morphologic findings, clinical presentation, and other immunohistochemical markers (chromogranin A, CD56, Ki-67) for accurate diagnosis
    • Grading Correlation: Combined with Ki-67 proliferation index to stratify NETs into low, intermediate, or high-grade categories affecting prognosis and treatment
    • Technical Factors: Fixation artifacts, antigen retrieval variations, and antibody specificity may influence results; internal positive controls verify technical adequacy
  • Associated Organs
    • Primary Organ Systems: Pulmonary (lungs), gastrointestinal (stomach, small intestine, colon), pancreatic, hepatic, and thyroid systems
    • Small Cell Lung Cancer (SCLC): Highly aggressive malignancy; synaptophysin typically positive (75-95% of cases); poor prognosis with early metastatic spread
    • Large Cell Neuroendocrine Carcinoma (LCNEC): High-grade pulmonary malignancy; synaptophysin positive; rapid progression and poor survival outcomes
    • Carcinoid Tumors (Typical and Atypical): Low to intermediate grade NETs; synaptophysin positive in 90-100% of cases; generally better prognosis than high-grade NETs
    • Pancreatic Neuroendocrine Tumors (PNETs): Include insulinomas, gastrinomas, glucagonomas; synaptophysin positive; variable clinical behavior from indolent to highly aggressive
    • Gastrointestinal NETs: Enterochromaffin cell tumors; synaptophysin typically positive; location and size determine metastatic potential and prognosis
    • Medullary Thyroid Carcinoma (MTC): Neuroendocrine malignancy of thyroid C-cells; synaptophysin positive; associated with RET mutations and MEN 2 syndrome
    • Pheochromocytoma and Paraganglioma: Catecholamine-secreting neuroendocrine tumors; synaptophysin positive; high metastatic potential in some cases
    • Merkel Cell Carcinoma: Rare cutaneous neuroendocrine malignancy; synaptophysin positive; aggressive behavior with early lymph node involvement
    • Potential Complications: Carcinoid syndrome (flushing, diarrhea, wheezing), hormonal hypersecretion syndromes, metastatic disease with multi-organ involvement, increased anesthetic risks
  • Follow-up Tests
    • Additional Immunohistochemical Markers: Chromogranin A, CD56, Ki-67 (proliferation index), CK7, CK20, TTF-1 for tumor subtyping and grading
    • Hormone and Biomarker Testing: Serum chromogranin A, 24-hour urine metanephrines, gastrin, insulin, 5-HIAA (5-hydroxyindoleacetic acid) depending on tumor location
    • Molecular Testing: RET mutations (medullary thyroid carcinoma), SDHB/SDHD mutations (paraganglioma), MEN1 gene analysis, Next-generation sequencing for therapy guidance
    • Imaging Studies: Somatostatin receptor imaging (octreoscan), CT/MRI for staging, PET-CT, endoscopic ultrasound for anatomic localization
    • Flow Cytometry: For selected cases requiring further phenotypic characterization and exclusion of hematologic malignancies
    • Clinical Surveillance: Periodic assessment for tumor progression, metastatic disease monitoring, symptomatic recurrence screening
    • Histologic Repeat Sampling: May be indicated if initial sampling inadequate or diagnosis remains uncertain after initial IHC panel
    • Monitoring Frequency: Dependent on tumor grade and stage; high-grade NETs require frequent imaging and laboratory surveillance; low-grade tumors may be monitored less frequently
  • Fasting Required?
    • Fasting: No - IHC is a tissue-based immunohistochemical test performed on biopsied or surgically removed tissue samples; fasting is not applicable
    • Tissue Sample Collection: Obtained through diagnostic or therapeutic procedures (endoscopic biopsy, transbronchial biopsy, surgical resection, fine needle aspiration)
    • Pre-procedure Preparation (if biopsy indicated): Fasting may be required depending on biopsy type and location (e.g., upper endoscopy typically requires 6-8 hour fasting); follow specific procedural guidelines provided by healthcare facility
    • Medications: For tissue-based testing only: no specific medication restrictions; however, anticoagulants may need adjustment if invasive biopsy required - consult physician
    • Sample Preservation: Tissue fixed in 10% neutral buffered formalin immediately after collection; proper fixation critical for optimal immunohistochemical staining
    • Patient Instructions: Follow healthcare provider directions for the specific diagnostic or therapeutic procedure requiring tissue sampling; ask about procedure-specific requirements
    • Ancillary Serologic Testing: If simultaneous blood tests ordered (chromogranin A, hormone levels), fasting requirements depend on specific tests - typically 8-12 hour overnight fast recommended

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