Background

• Struma ovarii is the rare type of ovarian tumor with an intriguing background. It is classified as a specialized teratoma, a type of germ cell tumor, and is characterized by the presence of thyroid tissue within the ovary. The term “struma” is derived from Latin, meaning “swelling,” which aptly describes the enlarged appearance of the ovarian tissue affected by this tumor.
• Struma ovarii tumors are typically benign, but in some cases, they can exhibit malignant behavior. These tumors are unique in that they contain functional thyroid tissue, and in rare instances, patients with struma ovarii can experience symptoms of hyperthyroidism due to excess thyroid hormone production within the tumor. The background of struma ovarii highlights its rarity and the intriguing combination of ovarian and thyroid tissues within a single tumor, making it a fascinating subject of study in the field of gynecological and oncological pathology. 

Epidemiology

• Low Incidence: Struma ovarii accounts for only a small fraction of all ovarian tumors, representing a rare subset of ovarian neoplasms. It is estimated that struma ovarii occurs in less than 5% of all ovarian teratomas. 
• Predominantly Benign: The majority of struma ovarii cases are benign (non-cancerous) tumors. Malignant (cancerous) struma ovarii is much less common but does occur. 
• Age of Onset: Struma ovarii can affect women of various ages, but it is most diagnosed in women of reproductive age, typically between the ages of 20 and 50. However, it can occur in individuals of any age. 
• Bilateral and Unilateral Cases: Struma ovarii can affect one or both ovaries. Unilateral cases, where only one ovary is involved, are more common than bilateral cases. 
• Association with Other Ovarian Tumors: Struma ovarii can coexist with other types of ovarian tumors, particularly ovarian teratomas. Teratomas are tumors that contain a variety of tissues from different germ layers. Struma ovarii represents a unique component within these teratomas. 
• Thyroid Function: In some cases, the thyroid tissue within struma ovarii can be functional, leading to the production of thyroid hormones. This may result in hyperthyroidism, a condition characterized by an overactive thyroid gland. 

Anatomy

Pathophysiology

• Teratoma Formation: Struma ovarii is often associated with a type of ovarian tumor known as a teratoma. Teratomas are tumors that can contain a variety of tissues from different germ cell layers. In the case of struma ovarii, thyroid tissue is present within the teratoma. 
• Embryological Origin: The presence of thyroid tissue in the ovary is thought to result from embryological development. During early embryogenesis, thyroid tissue can become misplaced and end up in locations other than the neck. In the case of struma ovarii, thyroid tissue becomes incorporated into the developing ovary. 
• Functional Thyroid Tissue: In some cases, the thyroid tissue within the struma ovarii can be functional, meaning it is capable of producing thyroid hormones, primarily thyroxine (T4) and triiodothyronine (T3). This can lead to the development of hyperthyroidism within the individual, as excess thyroid hormones are produced by both the thyroid gland in the neck and the thyroid tissue within the ovary. 
• Hyperthyroidism: It is a condition characterized by an overactive thyroid gland that leads to an excess production of thyroid hormones. The presence of functional thyroid tissue within struma ovarii can contribute to hyperthyroidism in affected individuals. 
• Benign or Malignant Nature: Struma ovarii tumors can be either benign (non-cancerous) or malignant (cancerous). Most cases are benign, but malignant transformation can occur, leading to the development of thyroid cancer within the ovarian tissue. 
• Clinical Presentation: The clinical presentation of struma ovarii varies widely. In some cases, individuals may be asymptomatic, and the tumor is discovered incidentally during surgery or imaging. Others may present with symptoms related to ovarian enlargement, pressure on adjacent organs, or hyperthyroidism. 

Etiology

• Embryological Factors: One widely accepted theory is that struma ovarii arises from embryological factors. During embryonic development, tissues can sometimes become displaced or mislocated. In the case of struma ovarii, thyroid tissue that would typically be found in the neck may become incorporated into the developing ovarian tissue. 
• Mature Teratoma: Struma ovarii is often associated with ovarian teratomas, which are tumors composed of a mixture of tissues derived from different germ cell layers. It is believed that thyroid tissue can be a component of mature teratomas. These teratomas may contain various differentiated tissues, including hair, teeth, and thyroid tissue. 
• Metaplasia: Some researchers suggest that the presence of thyroid tissue within the ovary may be due to metaplasia, a process in which one type of tissue transforms into another. In this case, it is proposed that the normal ovarian tissue undergoes metaplastic changes, leading to the development of thyroid tissue within the ovary. 
• Genetic Factors: While there is no specific genetic mutation known to cause struma ovarii, there may be genetic factors that predispose individuals to develop ovarian teratomas, including those with thyroid tissue. Genetic studies continue to explore potential genetic associations. 
• Hormonal Factors: these factors may also play a role in the development of struma ovarii. The presence of functional thyroid tissue within the ovary can lead to the production of thyroid hormones. This can result in hyperthyroidism, an overactive thyroid gland, which may influence the growth and function of the ovarian tumor. 

Genetics

Prognostic Factors

Benign Struma Ovarii: 

• Tumor Size: In benign cases, smaller tumor sizes typically have a more favourable prognosis. Larger tumors may be associated with increased pressure on adjacent structures, leading to symptoms and complications. 
• Histology: The histological characteristics of the tumor can influence prognosis. Struma ovarii with well-differentiated thyroid tissue is less likely to be associated with malignancy. 
• Functional Status: The functional status of the thyroid tissue within the tumor can impact prognosis. Non-functional thyroid tissue is associated with a better prognosis, while functional tissue may lead to hyperthyroidism and require additional management. 
• Bilateral vs. Unilateral Involvement: Unilateral involvement (affecting one ovary) is more common and typically has a better prognosis than bilateral involvement (affecting both ovaries). 
• Surgical Resection: Complete surgical resection of the tumor is the primary treatment for benign struma ovarii. The prognosis is generally excellent when the entire tumor is removed during surgery. 

Malignant Struma Ovarii: 

• Histological Subtype: The specific histological subtype of thyroid cancer within the struma ovarii can significantly impact prognosis. Some subtypes, such as papillary thyroid carcinoma, tend to have a more favourable prognosis compared to others. 
• Stage at Diagnosis: The stage of malignancy at the time of diagnosis plays an important role in prognosis. Early-stage malignant struma ovarii (confined to the ovary) has a better prognosis than advanced-stage cases with spread to surrounding tissues or distant metastasis. 
• Tumor Size: Larger malignant tumors can be associated with a less favourable prognosis, as they are more likely to invade adjacent structures and may be harder to completely resect. 
• Response to Treatment: The response of malignant struma ovarii to various treatments, such as surgery, radioiodine therapy, and chemotherapy, can impact prognosis. 
• Age and General Health: The age and overall health of the individual can influence the ability to tolerate and respond to treatment, which may affect prognosis. 
• Thyroid Hormone Production: In some malignant cases, the thyroid tissue within struma ovarii can produce thyroid hormones, leading to hyperthyroidism. The management of hyperthyroidism alongside cancer treatment can be challenging and may influence prognosis. 

Clinical History

Age: 

• Struma ovarii can occur at any age, but it is most diagnosed in women of reproductive age, between ages of 20 and 50. 
• It can, however, affect individuals of all age groups, including adolescents and older adults. 

Physical Examination

Medical History: 

• The healthcare provider begins by taking a detailed medical history, including information about the patient’s symptoms, menstrual history, previous surgeries, and any relevant medical conditions. 

General Physical Examination: 

• A general physical examination may be performed to assess the patient’s overall health, including vital signs like blood pressure, heart rate, and temperature. 

Abdominal Examination: 

• The abdomen may be examined for any signs of abdominal distension, masses, tenderness, or discomfort. However, these findings are usually non-specific. 

Pelvic Examination: 

• A pelvic examination may be conducted to assess for any signs of pelvic masses, tenderness, or abnormalities. Struma ovarii is not typically palpable during a pelvic examination. 

Thyroid Examination: 

• Although struma ovarii is an ovarian tumor containing thyroid tissue, it does not cause thyroid-related physical findings, such as an enlarged thyroid gland (goiter) or neck masses. Thyroid function is usually evaluated through blood tests, not physical examination. 

Neurological Examination: 

• In rare cases, struma ovarii can produce neurological symptoms due to hormonal imbalances. A neurological examination may be performed if the patient presents with relevant symptoms. 

Breast Examination: 

• Struma ovarii itself does not typically affect breast tissue. However, healthcare providers may conduct a breast examination as part of a general physical assessment. 

Age group

Associated comorbidity

• Individuals with struma ovarii may or may not have significant associated comorbidities. 
• In some cases, there may be a history of thyroid disorders, such as autoimmune thyroiditis (Hashimoto’s thyroiditis) or Graves’ disease, which can influence the development of thyroid tissue within the ovaries. 

Associated activity

Acuity of presentation

• Asymptomatic: Some individuals may have no noticeable symptoms and may only discover the tumor incidentally during routine gynecological exams or imaging studies conducted for unrelated reasons. 
• Chronic Symptoms: Others may experience chronic, nonspecific symptoms such as abdominal discomfort, pelvic pain, bloating, or irregular menstrual cycles. These symptoms might be attributed to the presence of the ovarian mass. 
• Hyperthyroidism: In cases where the thyroid tissue within the struma ovarii is functional, individuals may present with symptoms of hyperthyroidism, including rapid heart rate, weight loss, anxiety, heat intolerance, and sweating. 

Differential Diagnoses

• Ovarian Teratoma: Struma ovarii is often associated with ovarian teratomas, which are tumors composed of various tissues derived from different germ cell layers. Ovarian teratomas can contain structures such as hair, teeth, and sometimes thyroid tissue. Distinguishing between struma ovarii and other types of ovarian teratomas is essential. 
• Ovarian Cyst: Functional ovarian cysts, such as follicular or corpus luteum cysts, can cause pelvic pain and discomfort similar to that of struma ovarii. Imaging studies, like ultrasound, are used to differentiate between cystic lesions and solid tumors. 
• Ovarian Cancer: Ovarian cancer can present with symptoms similar to those of struma ovarii, such as abdominal pain, bloating, and irregular menstrual cycles. Imaging studies and tumor markers (e.g., CA-125) are essential for distinguishing between ovarian cancer and benign ovarian tumors. 
• Endometrioma: Endometriomas are cysts that form when endometrial tissue grows within the ovaries. They can cause pelvic pain, especially during menstruation. Imaging studies and clinical evaluation help differentiate endometriomas from solid ovarian masses like struma ovarii. 
• Functional Ovarian Tumors: Benign functional tumors, such as granulosa cell tumors, thecomas, or fibromas, can develop in the ovaries and cause symptoms similar to struma ovarii. Imaging and pathological assessment are necessary for accurate diagnosis. 
• Ectopic Thyroid Tissue: While extremely rare, thyroid tissue can occasionally be found in other sites within the body, such as cervical lymph nodes or the mediastinum. Ectopic thyroid tissue should be considered in cases of thyroid-like tissue outside the normal anatomical location. 

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

Diagnosis and Evaluation: 

• Imaging Studies: Radiological imaging, such as ultrasound, CT scans, or MRI, is often used to visualize the ovarian tumor and assess its characteristics. 
• Thyroid Function Tests: Blood tests to measure thyroid hormone levels are performed to evaluate thyroid function and rule out primary thyroid disorders. 

Surgical Intervention: 

• Ovarian Tumor Removal: The cornerstone of treatment for struma ovarii is surgical removal of the affected ovary, a procedure known as oophorectomy. In some cases, if the tumor is large, malignant, or there is a concern about recurrence, a hysterectomy with bilateral salpingo-oophorectomy may be recommended. 
• Lymph Node Dissection (if indicated): In cases where there is a concern about lymph node involvement or malignancy, lymph node dissection may be performed. 

Postoperative Management: 

• Thyroid Hormone Replacement (if indicated): In some cases, patients with struma ovarii may require thyroid hormone replacement therapy if their thyroid function is compromised due to the tumor or if the thyroid gland is removed during surgery. 
• Radioactive Iodine Therapy (if indicated): For malignant struma ovarii or cases with metastasis, radioactive iodine therapy may be considered as a follow-up treatment to destroy any remaining tissue and cancer cells. 

Long-Term Follow-Up: 

• Monitoring: Patients who have undergone surgery for struma ovarii require long-term follow-up to monitor for any signs of recurrence or metastasis. 
• Thyroid Function Tests: Regular monitoring of thyroid function is important, especially in patients who have had thyroid tissue removed or if the tumor has affected thyroid function. 

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

nonpharmacological-treatment-of-struma-ovarii

Lifestyle modifications: 

• Thyroid Health Monitoring: struma ovarii is associated with thyroid tissue, individuals with this condition should have regular thyroid function tests to monitor thyroid hormone levels. Thyroid function should be managed by an endocrinologist or thyroid specialist if necessary. 

• Healthy Diet: A balanced diet with adequate iodine intake is important for thyroid health. Iodine is essential nutrient for production of thyroid hormone. However, excessive iodine intake can also have adverse effects on thyroid function, so it is essential to maintain a balanced approach. 
• Regular Exercise: Engaging in regular physical activity supports overall health and well-being, including metabolic health. Exercise helps with weight management and reduce the risk of metabolic disorders that may affect thyroid function. 
• Stress Management: Chronic stress can impact thyroid function, so practicing stress-reduction techniques like mindfulness, meditation, or yoga can be beneficial. 
• Medication Compliance: If thyroid hormone replacement therapy is prescribed, it is essential to take medications as directed by a healthcare provider to maintain optimal thyroid function. 

pharmacological therapy of Struma Ovarii

• Thyroid Hormone Suppression: In cases where the malignant struma ovarii is producing thyroid hormones, thyroid hormone suppression therapy may be initiated. Levothyroxine (thyroid hormone replacement medication) is administered to suppress the production of thyroid-stimulating hormone (TSH) and, consequently, reduce stimulation of any remaining thyroid tissue. 
• Radioactive Iodine (Radioiodine) Therapy: Radioactive iodine (RAI) therapy may be considered for individuals with malignant struma ovarii, particularly when there is evidence of residual disease or metastasis. RAI therapy targets and destroys any remaining thyroid tissue that may not have been completely removed during surgery. 
• Chemotherapy: In rare cases of aggressive or metastatic malignant struma ovarii, chemotherapy may be recommended. Chemotherapy agents like cisplatin or doxorubicin may be used as adjuvant therapy or when surgery and RAI therapy are not effective in controlling the disease. 

management-of-benign-struma-ovarii

• Surgical Removal (Oophorectomy): The primary treatment for benign struma ovarii is surgical removal of the affected ovary (oophorectomy). In some cases, when the tumor is large or there is suspicion of malignancy, removal of both ovaries and the uterus (hysterectomy) may be recommended. This decision is typically made based on the size and characteristics of the tumor. 
• Histological Examination: After surgery, the removed ovarian tissue is sent for examination to confirm diagnosis and ensure that no malignant components are present. Pathology reports provide important information about the tumor’s characteristics and guide further treatment decisions. 
• Follow-Up: Following surgery, patients are typically monitored through regular follow-up visits with their healthcare provider. These visits may include physical examinations and imaging studies to ensure there is no recurrence of the tumor. 
• Hormone Replacement Therapy (HRT): For premenopausal women who have one ovary removed, hormone replacement therapy may be considered to address potential hormonal imbalances and menopausal symptoms. 

management-of-peritoneal-strumosis

• Surgical Removal of Struma Ovarii: The primary treatment for struma ovarii is surgical removal of the ovarian tumor. This surgery may involve removing the affected ovary (oophorectomy) or the entire uterus with both ovaries (hysterectomy with bilateral salpingo-oophorectomy) if the tumor is malignant or extensive. 
• Exploration and Removal of Strumosis: During the surgical procedure to remove the struma ovarii tumor, the surgeon carefully examines the peritoneal cavity for any evidence of thyroid tissue dissemination or peritoneal strumosis. Any visible thyroid tissue is typically removed to the extent possible during the surgery. 
• Pathological Examination: Tissue samples from both the struma ovarii tumor and any peritoneal strumosis are sent for pathological examination. This examination helps confirm the diagnosis, assess the extent of thyroid tissue involvement, and determine whether the tumor is benign or malignant. 

management-of-malignant-struma-ovarii

• Surgical Extirpation: In cases of malignant struma ovarii, surgical management is the cornerstone of treatment. The extent of surgery depends on the stage and extent of the malignancy. It may include Total hysterectomy (removal of the uterus), Bilateral salpingo-oophorectomy, Lymph node dissection to assess for metastasis, Surgical debulking if there is a significant tumor burden. 
• Thyroid Hormone Suppression: In cases where the malignant struma ovarii is producing thyroid hormones, thyroid hormone suppression therapy may be initiated. This involves the administration of thyroid hormone replacement medication (e.g., levothyroxine) to suppress the production of thyroid-stimulating hormone (TSH), which can stimulate the growth of thyroid tissue. 
• Radioactive Iodine (Radioiodine) Therapy: Radioactive iodine (RAI) therapy may be considered for individuals with malignant struma ovarii, especially if there is evidence of residual disease or metastasis. RAI therapy is used to target and destroy any remaining thyroid tissue that might not have been removed during surgery. 
• Chemotherapy: In rare cases of aggressive or metastatic malignant struma ovarii, chemotherapy may be recommended as an adjuvant therapy or when surgery and RAI therapy are not effective in controlling disease. 
• Regular Monitoring: Individuals with malignant struma ovarii require close and ongoing monitoring by a multidisciplinary medical team, including gynecologic oncologists, endocrinologists, and radiologists. Monitoring includes regular physical examinations, imaging studies, and thyroid function tests. 

subsequent-treatment-based-on-the-recurrence-risk-of-struma-ovarii

Low Risk of Recurrence (Benign Struma Ovarii): 

• Observation and Monitoring: In cases of benign struma ovarii with low risk factors for recurrence, the primary treatment is surgical removal of tumor. Patients may undergo regular follow-up appointments often including physical examinations and imaging studies. 

Intermediate Risk of Recurrence (Malignant or High-Risk Features): 

• Radioactive Iodine Therapy: For cases of malignant struma ovarii or those with high-risk features, such as capsular invasion or lymph node involvement, radioactive iodine therapy (RAI) may be recommended. RAI is used to destroy any remaining thyroid tissue or cancer cells in the body.  
• Thyroid Hormone Replacement Therapy: Patients who have had their thyroid gland removed during surgery may require lifelong thyroid hormone replacement therapy to maintain normal thyroid function. 

High Risk of Recurrence (Extensive Disease or Distant Metastasis): 

• Chemotherapy: In rare cases where there is extensive disease, distant metastasis, or aggressive tumor behavior, chemotherapy may be considered. Chemotherapy is typically administered to target cancer cells throughout the body. 

control-of-hyperthyroidism-in-the-treatment-of-struma-ovarii

Thyroid Function Assessment: 

• Before surgery, thorough assessment of thyroid function is essential. Blood tests, including measurement of thyroid hormone levels (T3 and T4) and thyroid-stimulating hormone (TSH), should be performed to determine the severity of hyperthyroidism. 

Medical Management of Hyperthyroidism: 

• Depending on the severity of hyperthyroidism, medications may be prescribed to control thyroid hormone production and bring thyroid function within normal limits. Common medications for hyperthyroidism include: 
• Antithyroid Drugs: Medications like methimazole or propylthiouracil (PTU) can be used to reduce thyroid hormone production. 
• Beta-Blockers: These medications, such as propranolol, can help manage symptoms like rapid heartbeat and tremors associated with hyperthyroidism. 
• An endocrinologist or thyroid specialist typically manages the medical treatment of hyperthyroidism. 

Stabilization of Thyroid Function: 

• It is important to stabilize thyroid function and bring it within the normal range before proceeding with Non thyroid surgery. This may take several weeks, depending on the response to medications and the severity of hyperthyroidism. 

Medication

Future Trends

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References

• Struma Ovarii: A Report of Three Cases and Literature Review – PMC (nih.gov) 
• Struma ovarii: management and follow-up of a rare ovarian tumour – PMC (nih.gov)