Struma ovarii pathophysiology

It is thought that struma ovarii is mediated by activation of the mitogen activated protein kinase signaling pathway as a critical step in tumorigenesis. Malignant struma ovarii (MSO) are rare tumors which arise from ectopic thyroid tissue in the ovary which is benign. The genes involved in the pathogenesis of malignant struma ovarii include BRAF (35% to 69%), RAS (10%), and RET (5% to 30%). On gross pathological examination, struma ovarii may be present as: Solid and cystic tumor, tumor with several nodules partially separated by gray whitish fibrous tissue, nodules appear tan-brown in color with small dark red areas, Cystic spaces filled with yellow-brown or straw-colored fluid, and focal areas of calcification. Microscopic pathology of struma ovarii is similar to the thyroid tissue with cellular solid or cystic cluster of variable size with cuboidal or columnar morphology and eosinophilic cytoplasm, round nuclei with finely granular chromatin, and Colloid presentation.

• Struma ovarii is a type of monodermal highly specialized ovarian teratomas, consist of mature thyroid tissue.
• It is thought that struma ovarii is mediated by activation of the mitogen activated protein kinase signaling pathway as a critical step in tumorigenesis. This process has been understood by molecular analysis of follicular cell derived thyroid carcinomas. ^[1]
• Malignant struma ovarii (MSO) are rare tumors which arise from ectopic benign thyroid tissue in the ovary. Malignant transformation of struma ovarii is not common and occurs in less than 5% of all cases, and it is even rarer to lead to metastatic disease (5–6%). ^{[2] [3]}
• In malignant struma ovarii (MSO), the cancer can spread to the contralateral ovary; also other sites such as abdominopelvic lymph nodes, the peritoneal cavity, lungs, scalp, brain, diaphragm, and liver may be involved. ^[4]
• Routes of metastasis are: ^{[5] [6] [7]}

• 1) Regional lymphatics to pelvic and paraaortic lymph nodes
• 2) Direct spread to the omentum, peritoneal cavity and the contralateral ovary
• 3) Hematologic dissemination to the bone, lung, liver and brain

• Malignant struma ovarii manifest as follicular carcinoma (causing peritoneal strumosis as a result of peritoneal spread), papillary carcinoma or follicular micro-carcinoma, a variant of papillary carcinoma (showing BRAF and RAS mutations) and rarely with carcinoid and along with lymphoma. ^{[8] [9]}

• The genes involved in the pathogenesis of malignant struma ovarii include BRAF (35% to 69%), RAS (10%), and RET (5% to 30%). ^[1]
• The development of malignant struma ovarii (MSO) along with papillary thyroid carcinomas (PTC) features is associated with mutations in the BRAF of the type which is commonly observed in PTC, therefore it suggests a common pathogenesis for all PTCs regardless of their location. On the contrary, mutations in the RET/RAS/RAF pathway are not observed in BSO (Benign Struma ovarii). ^[1]

The most important extra-ovaries associated conditions with stroma ovarri include:

• Adenomatous or colloid cervical goiters ^[10]
• Hyperthyroidism in postmenopausal woman ^[11]
• Pseudo-Meig’s syndrome ^[12]
• Hashimoto’s thyroiditis ^[13]
• Thyrotoxicosis ^[13]
• Peritoneal strumosis which are benign lesions^[14]

Struma ovarii can be seen associated with other ovarian diseases include: ^[15]

• Ovarian mature cystic teratoma
• Ovarian serous cystadenoma
• Ovarian mucinous cystadenoma
• Brenner’s tumor of ovary
• Carcinoid tumor

On gross pathological examination, struma ovarii may be present as: ^{[16] [17]}

• Solid and cystic tumor
• Tumor with several nodules partially separated by gray whitish fibrous tissue
• Nodules appear tan-brown in color with small dark red areas
• Cystic spaces filled with yellow-brown or straw-colored fluid
• Focal areas of calcification

Microscopic pathology of struma ovarii is similar to the thyroid tissue:

• Cellular solid or cystic cluster of variable size with cuboidal or columnar morphology and eosinophilic cytoplasm
• Round nuclei with finely granular chromatin
• Colloid is seen

May develop pathologies seen in the thyroid gland; for instance papillary thyroid carcinoma in a struma ovarii can be recognized in hematoxylin and eosin-stained tissue with branching papillae with atypical malignant cytologic features including nuclear groves, overlapping, and enlargement. ^[18]

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