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IHC single marker with reporting Inhibin Alpha
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IHC Single Marker with Reporting Inhibin Alpha
- Why is it done?
- Inhibin Alpha is a protein hormone produced primarily by granulosa cells of the ovary in females and by Sertoli cells in the testes in males. This immunohistochemical (IHC) marker is used to detect and identify cells expressing inhibin alpha in tissue samples.
- Primary indications include: diagnosis of ovarian sex cord-stromal tumors (granulosa cell tumors, thecomas, and related neoplasms), testicular Leydig cell tumors, adrenocortical carcinomas, and other neuroendocrine tumors that may express inhibin alpha.
- This test is performed when histopathologic examination of tissue biopsies or surgical specimens requires characterization of tumors or identification of specific cell types to establish or confirm diagnosis.
- Timing is typically when tissue samples are obtained during biopsy, surgical resection, or autopsy, and staining is performed during the pathological examination process.
- Normal Range
- Inhibin Alpha IHC is a qualitative test reported as either positive or negative staining, not quantitative with numerical values or units.
- Normal Result (Negative): Absence of inhibin alpha staining in tissues where it is not expected to be present. Most normal tissues do not express inhibin alpha except for specific cell types in the reproductive system and adrenal glands.
- Positive Result: Presence of inhibin alpha immunoreactivity detected in tissue cells. Staining intensity is typically reported on a scale (0 to 3+ or similar grading system) indicating the degree of positivity: negative, weak (1+), moderate (2+), or strong (3+).
- Interpretation depends on tissue type and clinical context. Expected positive staining occurs in granulosa cells, thecal cells, Leydig cells, and specific tumors derived from these cell types. Unexplained positivity in other cell types may indicate neoplastic transformation.
- Interpretation
- Strongly Positive (3+) Staining: Indicates abundant inhibin alpha expression. In the context of ovarian masses, strongly suggestive of granulosa cell tumor or other sex cord-stromal neoplasm. Supports diagnosis of hormonally active tumors.
- Moderate to Weak Positivity (1+ to 2+): Suggests inhibin alpha expression is present but at lower levels. May indicate differentiated tumors or mixed histology. Clinical interpretation requires correlation with morphologic findings and other immunohistochemical markers.
- Negative Staining (0): Absence of inhibin alpha expression. In suspected sex cord-stromal tumors, negative staining may favor alternative diagnoses such as epithelial ovarian tumors, germ cell tumors, or other neoplasms. Does not exclude diagnosis but reduces likelihood.
- Factors Affecting Results: Tissue fixation and processing quality, adequacy of antibody penetration, prior treatment effects (chemotherapy or radiation), tumor differentiation status, and heterogeneous expression within tumors may influence results.
- Clinical Significance: Positive inhibin alpha staining is highly specific for granulosa cell tumors and enhances diagnostic confidence. Often used in a panel with other markers (calretinin, SF-1, WT-1) to improve diagnostic accuracy and differentiate sex cord-stromal tumors from other ovarian neoplasms.
- Inhibin Alpha as a Tumor Marker: Beyond IHC staining, serum inhibin A and inhibin B levels may be elevated in granulosa cell tumors and can serve as biomarkers for disease recurrence or monitoring therapy response.
- Associated Organs
- Primary Organs: Ovaries (principal organ expressing inhibin alpha in granulosa and thecal cells), testes (Leydig and Sertoli cells), adrenal glands (zona reticularis and fasciculata).
- Sex Cord-Stromal Tumors of the Ovary: Granulosa cell tumors (adult and juvenile types) - most common inhibin alpha positive tumors, thecomas, fibrothecomas, Leydig cell tumors, Sertoli cell tumors, and mixed gonadal stromal tumors.
- Testicular Tumors: Leydig cell tumors frequently express inhibin alpha. Sertoli cell tumors may also show positive staining, aiding in differential diagnosis from germ cell tumors.
- Adrenocortical Carcinomas: Some adrenocortical tumors may express inhibin alpha, particularly those with specific differentiation patterns or hormone production profiles.
- Medical Conditions Associated with Abnormal Results: Ovarian tumors causing hyperandrogenism or virilization, endometrial hyperplasia and carcinoma (secondary to excess estrogen from inhibin-producing tumors), osteoporosis (from altered hormone levels), precocious puberty in children with juvenile granulosa cell tumors.
- Potential Complications: Delayed diagnosis of malignant tumors may allow progression. Hormonally active tumors can cause significant metabolic and reproductive complications. Recurrence risk requires long-term follow-up and monitoring.
- Systemic Effects: Tumors expressing inhibin alpha may produce systemic hormonal effects including estrogen and androgen excess, leading to reproductive dysfunction, infertility, abnormal bleeding, and metabolic disturbances.
- Follow-up Tests
- Complementary IHC Panels: Additional immunohistochemical markers recommended alongside inhibin alpha include calretinin, SF-1 (Steroidogenic Factor-1), WT-1, alpha-inhibin, and CD99 to increase diagnostic specificity for sex cord-stromal tumors.
- Serum Inhibin Levels: Baseline serum inhibin A and inhibin B measurements should be obtained at diagnosis for tumors expressing inhibin alpha. These serve as tumor markers for monitoring disease recurrence and treatment response.
- Hormonal Evaluation: If tumor expresses inhibin alpha, additional hormone studies may include estradiol, testosterone, DHEA-S, and 17-hydroxyprogesterone to assess hormone production and guide clinical management.
- Imaging Follow-up: CT or MRI of abdomen/pelvis for staging, assessment of metastatic disease, and baseline measurements for future surveillance comparisons.
- Monitoring Frequency: For diagnosed inhibin alpha-positive tumors, serum inhibin levels should be monitored every 3-6 months during initial surveillance, then annually for 5 years minimum or per institutional protocol. More frequent monitoring if levels are elevated or rising.
- Repeat Biopsy: If diagnosis remains uncertain or recurrence is suspected, repeat tissue sampling and IHC analysis may be warranted to confirm diagnosis or identify disease progression.
- Genetic Testing: For juvenile granulosa cell tumors or cases with atypical features, testing for mutations (such as CTNNB1 in adult type or DICER1 in juvenile type) may provide prognostic information.
- Clinical Assessment: Regular gynecologic or urologic examination, assessment for hormone-related symptoms, and evaluation for complications such as endometrial pathology.
- Fasting Required?
- Fasting Status: No fasting is required for the IHC single marker with reporting inhibin alpha test.
- Reason: This is an immunohistochemical test performed on tissue samples obtained through biopsy or surgical resection, not a blood-based test. Fasting status does not affect tissue staining or interpretation.
- Patient Preparation: No special dietary restrictions or pre-test fasting required. Standard preparation depends on the method of tissue acquisition (biopsy or surgery), which follows institutional protocols.
- Medications: Continue all regular medications unless otherwise directed by the physician obtaining the tissue sample. Anticoagulants should be discussed with the physician if biopsy is planned, as they may need temporary adjustment.
- Timing Considerations: Tissue should be processed promptly after collection (ideally within 1 hour for fresh tissue) to maintain optimal antigenicity. Formalin fixation is the standard for IHC processing and does not require patient fasting.
- Complementary Serum Testing: If serum inhibin alpha levels are also being measured concurrently, fasting may be recommended for that component (typically 8-12 hours), but this is separate from the tissue IHC analysis.
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