Granulosa Cell Tumors Definition and Overview:  Granulosa cell tumors are rare, estrogen-secreting tumors that arise from the granulosa cells of the ovary. These tumors are part of the sexcord stromal tumors group and are known for their slow growth and potential for late recurrence. They are classified as a type of ovarian sexcord stromal tumor and can occur at any age but are most commonly diagnosed in women between 40 and 60 years old. Histological Features:  Histology: Granulosa cell tumors are characterized by the proliferation of granulosa cells, which are the cells that surround the developing oocytes in the ovarian follicles. These tumors typically show a trabecular or follicular pattern with cells arranged in nests or trabeculae. The cells have a round nucleus with longitudinal grooves (coffee bean nuclei) and abundant eosinophilic cytoplasm. The stroma often contains fibrous tissue, and the tumor may also exhibit areas of calcification or hemorrhage.  Variants: o Adult Granulosa Cell Tumor: The most common type, characterized by slow growth and indolent behavior. o Juvenile Granulosa Cell Tumor: A rare, more aggressive form often seen in prepubescent girls and adolescents, with a tendency for early metastasis. Etiology and Risk Factors:  Genetic Factors: Although not commonly inherited, mutations in the FSH receptor and alterations in PTEN have been identified in some cases. Genetic predisposition is less well-defined compared to other ovarian tumors.  Hormonal Factors: Granulosa cell tumors produce estrogen, leading to symptoms related to estrogen excess such as abnormal uterine bleeding or precocious puberty in younger patients.  Family History: While not strongly associated with hereditary syndromes, a family history of ovarian or breast cancer may be a consideration in some cases. Clinical Presentation:  Symptoms: Patients may present with a variety of symptoms, including abnormal vaginal bleeding, abdominal pain, a palpable abdominal or pelvic mass, and symptoms related to estrogen excess such as endometrial hyperplasia or precocious puberty.  Diagnosis: o Imaging: Ultrasound, CT scans, and MRI are used to visualize the tumor and assess its extent. Granulosa cell tumors may appear as solid or complex cystic masses. o Tumor Markers: Elevated serum levels of inhibin (particularly inhibin B) and estrogen can aid in diagnosis. However, inhibin levels are more specific to granulosa cell tumors. o Histopathology: Definitive diagnosis is made through biopsy or surgical resection, revealing the characteristic histological features of granulosa cell tumors. Treatment:  Surgical Management: The primary treatment is surgical, involving unilateral salpingo-oophorectomy (removal of the affected ovary and fallopian tube) and staging. For advanced cases, total abdominal hysterectomy with bilateral salpingo-oophorectomy (TAH-BSO) may be necessary.  Adjuvant Therapy: o Chemotherapy and Radiation: Generally reserved for advanced or recurrent disease, as granulosa cell tumors are often resistant to these treatments. The efficacy of adjuvant therapy is variable and depends on individual cases. o Hormonal Therapy: Estrogen-reducing therapies or hormonal agents may be used to manage estrogen-related symptoms. Prognosis:  Prognosis: Granulosa cell tumors typically have a favorable prognosis, with a 5-year survival rate of around 80-90%. However, the risk of late recurrence is significant, and long-term follow-up is essential. Prognosis may be influenced by factors such as tumor stage, grade, and completeness of surgical resection. Conclusion: Granulosa cell tumors are rare, estrogen-secreting ovarian tumors with distinctive histological features. They present with symptoms related to estrogen excess and require careful diagnosis through imaging, tumor marker assessment, and histopathological examination. Treatment primarily involves surgical resection, with additional hormonal or adjuvant therapies based on the extent of disease. Despite a generally favorable prognosis, long-term follow-up is crucial due to the risk of late recurrence.