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IHC Panels with Reporting - Cervical Cancer

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Tumor immunohistochemistry panels.

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IHC Panels with Reporting - Cervical Cancer

  • Why is it done?
    • Immunohistochemistry (IHC) panels are tissue-based diagnostic tests that use antibodies to detect specific proteins and markers in cervical tissue samples to identify malignant cells and characterize cervical cancer.
    • Confirm diagnosis of cervical cancer and differentiate from benign lesions or other malignancies
    • Determine histological type (squamous cell carcinoma, adenocarcinoma, adenosquamous carcinoma, etc.)
    • Assess tumor grade and stage, which guides treatment planning and prognosis estimation
    • Evaluate HPV status and p16/Ki-67 expression as biomarkers for cervical cancer risk and viral etiology
    • Identify potential therapeutic targets for personalized treatment (e.g., PD-L1 expression, mismatch repair status)
    • Typically performed following histopathological examination when cervical cancer is suspected or confirmed on routine biopsies
  • Normal Range
    • Normal/Negative Results: Absence of malignant staining patterns; normal tissue architecture with appropriate marker expression consistent with benign cervical epithelium
    • Positive Results: Presence of tumor-associated markers indicating malignancy; specific immunoprofile consistent with cervical cancer (moderate to strong staining in >10% of cells for diagnostic markers)
    • Common IHC Markers Reported:
    • p16 (HPV-related marker): Positive in HPV-associated cervical cancers; strong, diffuse nuclear and cytoplasmic staining
    • Ki-67 (proliferation marker): High proliferation index (>30%) indicates malignancy; expressed as percentage of positive nuclei
    • CK7/CK20: Positive CK7, negative CK20 supports cervical origin in adenocarcinomas
    • HPV in situ hybridization (ISH): Positive indicates HPV DNA presence; reported as positive or negative
    • Markers for adenocarcinoma: CEA, MUC1, MUC2 (pattern helps differentiate adenocarcinoma subtypes)
    • PD-L1: Percentage of PD-L1 positive tumor cells (0%, 1-49%, ≥50%) guides immunotherapy eligibility
  • Interpretation
    • Squamous Cell Carcinoma (SCC) - Most Common Type (80-90%):
    • Positive for: p63, CK5/6, AE1/AE3 (pankeratin); p16 often positive indicating HPV association
    • Negative for: adenocarcinoma markers (CK7, CEA in most cases); mucin stains typically negative
    • Adenocarcinoma (10-15%):
    • Positive for: CK7, CEA, MUC1, MUC5AC; p16 positive in HPV-associated cases
    • Negative for: p63, CK5/6; CK20 typically negative (helps exclude colorectal origin)
    • Adenosquamous Carcinoma:
    • Mixed pattern: Both squamous markers (p63, CK5/6) and glandular markers (CK7, CEA) present in different tumor areas
    • HPV Status Interpretation:
    • HPV-positive (p16+): Indicates oncogenic HPV infection; associated with better prognosis and different treatment response in advanced disease
    • HPV-negative: Suggests alternative pathogenic mechanisms; may indicate adenocarcinoma in situ or gastric-type adenocarcinoma with poorer prognosis
    • Ki-67 Proliferation Index:
    • Low (<20%): Associated with lower grade, potentially better prognosis
    • High (>30%): Indicates aggressive behavior, higher grade tumors, and worse prognosis
    • PD-L1 Expression:
    • PD-L1 negative (0%): Limited benefit from PD-L1 checkpoint inhibitors alone
    • PD-L1 low (1-49%): May benefit from combined immunotherapy strategies
    • PD-L1 high (≥50%): Eligible for PD-L1 checkpoint inhibitor therapy; associated with active immune response
    • Mismatch Repair (MMR) Status:
    • Intact (positive for MLH1, MSH2, MSH6, PMS2): Normal mismatch repair; microsatellite stable
    • Deficient (loss of one or more MMR proteins): Microsatellite instability; potential candidate for immunotherapy
  • Associated Organs
    • Primary Organ:
    • Cervix (lower portion of uterus): The test evaluates tissue samples from the cervix to identify and characterize malignant transformation
    • Reproductive System Involvement:
    • Direct extension to uterine body, vagina, parametrium, and pelvic structures
    • Lymphatic spread to pelvic, obturator, and para-aortic lymph nodes
    • Distant metastases to bladder, rectum, lungs, liver, and bone (assessed independently, but IHC aids in confirming cervical primary)
    • Diseases/Conditions Associated with Abnormal Results:
    • Cervical squamous cell carcinoma (most common; HPV-related in >90% of cases)
    • Cervical adenocarcinoma (including mucinous, endometrioid, clear cell, and adenosquamous subtypes)
    • Adenocarcinoma in situ (AIS) - precancerous lesion with high risk of progression
    • Human papillomavirus (HPV) infection - oncogenic types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68)
    • Persistent HPV infection leading to malignant transformation (typically 10-20 year progression)
    • Potential Complications and Risks Associated with Abnormal Results:
    • Local invasion: Tumor extension into bladder, rectum, and pelvic sidewall causing functional impairment
    • Metastatic spread: Regional and distant lymph node involvement; systemic dissemination affecting survival and treatment options
    • Hemorrhage and infection: Tumor necrosis and ulceration causing vaginal bleeding, infection, and sepsis risk
    • Ureteral obstruction: Tumor compression causing hydronephrosis and renal dysfunction
    • Radiation and chemotherapy toxicity: Treatment-related morbidity based on tumor grade, stage, and molecular profile
  • Follow-up Tests
    • Imaging Studies:
    • MRI pelvis: Gold standard for tumor size assessment, parametrial involvement, and local staging
    • PET-CT (FDG-PET): Detects lymph node metastases and distant spread; helps determine appropriate treatment field
    • CT chest/abdomen: Screens for metastatic disease, particularly in stage IB2 and beyond
    • Laboratory/Molecular Tests:
    • HPV genotyping (if not already performed): Determines specific HPV type (16, 18, or other types) for prognostic stratification
    • Next-generation sequencing (NGS): Identifies additional mutations (TP53, PIK3CA, PTEN, KRAS, etc.) for targeted therapy eligibility
    • Tumor mutational burden (TMB): Predicts immunotherapy response when PD-L1 status is ambiguous
    • Additional IHC Panels:
    • HER2 testing: For cases with glandular differentiation to assess HER2-directed therapy potential
    • Estrogen/Progesterone receptor testing: Relevant for adenocarcinoma subtypes in select cases
    • Clinical Follow-up and Monitoring:
    • Baseline staging assessment: Within 4-6 weeks of diagnosis to establish TNM stage and determine treatment plan
    • Treatment response monitoring: Imaging 3-4 months after completion of radiation/chemotherapy to assess therapeutic efficacy
    • Surveillance imaging: Every 3-6 months for first 2 years, then annually for 3-5 years to detect recurrence
    • Tumor markers (SCC antigen, CEA): Serial measurement during follow-up in select cases; elevation may indicate recurrence before imaging findings
    • Related Complementary Tests:
    • Conventional cytology/Liquid-based cytology: Prior or concurrent cervical screening results for context
    • Colposcopy with biopsy: Direct visualization and tissue sampling if cancer diagnosis not yet confirmed
    • Histopathology report: Complete histomorphologic assessment providing context for IHC interpretation and grade determination
  • Fasting Required?
    • Fasting Required: No
    • IHC panels are performed on tissue samples already obtained through biopsy or surgical procedures, not on blood samples. Therefore, fasting is not required.
    • Biopsy Procedure Preparation:
    • Informed consent required: Patient must understand the biopsy procedure risks and benefits before tissue collection
    • Anticoagulant discontinuation: If patient takes warfarin, aspirin, or NSAIDs, discuss with physician; may need temporary cessation to reduce bleeding risk during colposcopic/excisional biopsy
    • Timing of biopsy: Avoid during heavy menstrual flow; optimal timing is mid-cycle to luteal phase for visibility
    • Vaginal preparation: Do not use tampons, douches, or vaginal medications for 24 hours before procedure
    • Clothing: Wear easily removable clothing; gown provided for procedure
    • Pain management: May use topical anesthetic (4% lidocaine) or local injection of 1% lidocaine during procedure; acetaminophen/ibuprofen available pre-procedure
    • Post-Biopsy Instructions:
    • Avoid intercourse, tampons, douches for 1-2 weeks post-biopsy to allow healing
    • Expect mild vaginal bleeding/spotting for several days after biopsy; contact provider if bleeding is heavy or prolonged
    • Results typically available within 5-10 business days; will be discussed with clinician for treatment planning

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