Sex cord-stromal tumors (SCSTs) are a rare group of growths originating in the reproductive organs, specifically the ovaries in females and the testes in males. They develop from supportive tissues (stroma) and hormone-producing cells (sex cords). While some SCSTs are benign, others are malignant and may require more extensive management. These tumors are distinct from more common ovarian or testicular cancers.
Types of Sex Cord-Stromal Tumors
Sex cord-stromal tumors are broadly classified based on their origin within either the ovaries or the testes, each with distinct subtypes. Ovarian SCSTs include granulosa cell tumors, Sertoli-Leydig cell tumors, and thecoma-fibroma group tumors. Granulosa cell tumors are the most frequently encountered subtype, arising from granulosa cells. These are further divided into adult granulosa cell tumors, which usually affect middle-aged and older women, and juvenile granulosa cell tumors, more commonly seen in younger individuals and girls.
Sertoli-Leydig cell tumors are another rare ovarian subtype, characterized by a mixture of Sertoli and Leydig cells. Thecomas and fibromas originate from theca cells and fibroblasts. Most fibromas are benign and typically do not produce hormones, unlike the more hormonally active thecomas.
Testicular SCSTs primarily include Leydig cell tumors and Sertoli cell tumors, both developing from the supportive cells within the testes. Leydig cell tumors are the most common type of testicular SCST, while Sertoli cell tumors are the second most prevalent.
Hormonal Effects and Symptoms
Many sex cord-stromal tumors produce hormones. Tumors like granulosa cell tumors and thecomas often secrete excess estrogen. In postmenopausal women, this can cause abnormal uterine bleeding and may increase the risk of endometrial hyperplasia or carcinoma. Younger girls might experience precocious puberty, with symptoms like breast swelling, pubic hair development, and vaginal bleeding.
Conversely, Sertoli-Leydig cell tumors, steroid cell tumors, and some Leydig cell tumors often produce excess androgens. This can cause virilization in women, leading to hirsutism, acne, a deepening voice, menstrual irregularities, clitoromegaly, male-pattern baldness, and breast atrophy. In boys, Leydig cell tumors can lead to early puberty or gynecomastia.
Diagnosis and Staging
Identifying a sex cord-stromal tumor begins with a physical examination and a detailed review of a patient’s symptoms, which often include abdominal pain or swelling, alongside any hormonal changes. Imaging techniques such as ultrasound are commonly the first step to locate and visualize the tumor within the pelvis or abdomen. More detailed cross-sectional imaging, including computed tomography (CT) scans or magnetic resonance imaging (MRI), are also utilized to assess the tumor’s size, characteristics, and any potential spread.
Blood tests play a role in the diagnostic process, measuring levels of hormones like estrogen and testosterone. Specific tumor markers, such as inhibin A and B, CA125, and anti-Müllerian hormone (AMH), are also often checked, as inhibin levels can be elevated in granulosa cell tumors. The definitive diagnosis of an SCST is established through pathological examination of tissue samples, usually obtained during surgical removal of the tumor or, less commonly, through a biopsy.
If a sex cord-stromal tumor is found to be malignant, a staging process is undertaken to determine the extent of its spread. For ovarian tumors, this often follows the International Federation of Gynecology and Obstetrics (FIGO) staging system, classifying the tumor from Stage 1 (confined to the ovary) to Stage 4 (spread to distant organs). Surgical staging procedures typically involve peritoneal washings and biopsies of various abdominal surfaces; lymph node involvement in these tumors is considered rare.
Treatment Approaches
The primary treatment for sex cord-stromal tumors is surgical removal. For ovarian tumors, this may involve an oophorectomy (removal of the affected ovary and fallopian tube). If the tumor is localized to one ovary and fertility preservation is desired, a unilateral oophorectomy may be performed. For postmenopausal women or those with more extensive disease, a total hysterectomy and bilateral salpingo-oophorectomy is standard.
For testicular tumors, the main treatment is an orchiectomy (surgical removal of the affected testicle). In select cases of small, benign Leydig cell tumors, testis-sparing surgery may be considered. Following surgery, further treatment may be necessary for malignant tumors with spread or high recurrence risk. Chemotherapy, often using platinum-based regimens, may be recommended for advanced or high-risk disease. Hormone therapy or radiation therapy are less common but may be considered for residual or chemotherapy-resistant cases.
Prognosis and Recurrence
The long-term outlook for individuals with sex cord-stromal tumors is generally favorable, especially when benign or early-stage malignant and completely removed. Prognosis depends on tumor type, stage, and completeness of surgical removal. For instance, the five-year survival rate for stage I ovarian SCSTs is often very high, exceeding 90%.
Some sex cord-stromal tumors, particularly adult granulosa cell tumors, have a potential for late recurrence, even decades after initial treatment. This highlights the importance of prolonged and consistent follow-up care for patients.