Struma ovarii pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aravind Reddy Kothagadi M.B.B.S[2]
Overview
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.
Pathophysiology
Pathogenesis
- 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]
Genetics
- 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]
Associated Conditions
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
Gross Pathology
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
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]
References
- ↑ 1.0 1.1 1.2 Schmidt J, Derr V, Heinrich MC, Crum CP, Fletcher JA, Corless CL, Nosé V (2007). "BRAF in papillary thyroid carcinoma of ovary (struma ovarii)". Am. J. Surg. Pathol. 31 (9): 1337–43. doi:10.1097/PAS.0b013e31802f5404. PMID 17721188.
- ↑ Dardik RB, Dardik M, Westra W, Montz FJ (1999). "Malignant struma ovarii: two case reports and a review of the literature". Gynecol. Oncol. 73 (3): 447–51. doi:10.1006/gyno.1999.5355. PMID 10366477.
- ↑ Oudoux A, Leblanc E, Beaujot J, Gauthier-Kolesnikov H (2016). "Treatment and follow-up of malignant struma ovarii: Regarding two cases". Gynecol Oncol Rep. 17: 56–9. doi:10.1016/j.gore.2016.05.014. PMC 4913172. PMID 27355004.
- ↑ Luo JR, Xie CB, Li ZH (2014). "Treatment for malignant struma ovarii in the eyes of thyroid surgeons: a case report and study of Chinese cases reported in the literature". Medicine (Baltimore). 93 (26): e147. doi:10.1097/MD.0000000000000147. PMC 4616397. PMID 25474425.
- ↑ Yücesoy G, Cakiroglu Y, Muezzinoglu B, Besnili B, Yucesoy I (2010). "Malignant struma ovarii: a case report". J. Korean Med. Sci. 25 (2): 327–9. doi:10.3346/jkms.2010.25.2.327. PMC 2811308. PMID 20119594.
- ↑ Rosenblum NG, LiVolsi VA, Edmonds PR, Mikuta JJ (1989). "Malignant struma ovarii". Gynecol. Oncol. 32 (2): 224–7. PMID 2910784.
- ↑ Chan SW, Farrell KE (2001). "Metastatic thyroid carcinoma in the presence of struma ovarii". Med. J. Aust. 175 (7): 373–4. PMID 11700816.
- ↑ Sinha NK (2014). "Struma ovarii with elevated ca-125 levels and ascites mimicking advanced ca ovary". J Clin Diagn Res. 8 (3): 140–1. doi:10.7860/JCDR/2014/8005.4138. PMC 4003614. PMID 24783110.
- ↑ Yoo SC, Chang KH, Lyu MO, Chang SJ, Ryu HS, Kim HS (2008). "Clinical characteristics of struma ovarii". J Gynecol Oncol. 19 (2): 135–8. doi:10.3802/jgo.2008.19.2.135. PMC 2676458. PMID 19471561.
- ↑ Kempers RD, Dockerty MB, Hoffman DL, Bartholomew LG (1970). "Struma ovarii--ascitic, hyperthyroid, and asymptomatic syndromes". Ann. Intern. Med. 72 (6): 883–93. PMID 5448747.
- ↑ Nonne N, Ameyar-Zazoua M, Souidi M, Harel-Bellan A (2010). "Tandem affinity purification of miRNA target mRNAs (TAP-Tar)". Nucleic Acids Res. 38 (4): e20. doi:10.1093/nar/gkp1100. PMC 2831319. PMID 19955234.
- ↑ Mostaghel N, Enzevaei A, Zare K, Fallahian M (2012). "Struma ovarii associated with Pseudo-Meig's syndrome and high serum level of CA 125; a case report". J Ovarian Res. 5: 10. doi:10.1186/1757-2215-5-10. PMC 3350392. PMID 22436494.
- ↑ 13.0 13.1 Morrissey K, Winkel C, Hild S, Premkumar A, Stratton P (2007). "Struma ovarii coincident with Hashimoto's thyroiditis: an unusual cause of hyperthyroidism". Fertil. Steril. 88 (2): 497.e15–7. doi:10.1016/j.fertnstert.2006.11.095. PMC 2753978. PMID 17276434.
- ↑ Butt, Jennifer L; Wantenaar, Tanya I (2016). "The diagnosis and management of struma ovarii". Southern African Journal of Gynaecological Oncology. 8 (1): 24–26. doi:10.1080/20742835.2016.1180776. ISSN 2074-2835.
- ↑ Dujardin MI, Sekhri P, Turnbull LW (2014). "Struma ovarii: role of imaging?". Insights Imaging. 5 (1): 41–51. doi:10.1007/s13244-013-0303-3. PMC 3948908. PMID 24357453.
- ↑ Piérard GE, Piérard-Franchimont C (1987). "[Acute and chronic borrelioses transmitted by ticks along the Meuse River and in bordering regions]". Rev Med Liege (in French). 42 (3): 101–6. PMID 3563194.
- ↑ Gaitan E, Cooksey RC, Meydrech EF, Legan J, Gaitan GS, Astudillo J, Guzman R, Guzman N, Medina P (1989). "Thyroid function in neonates from goitrous and nongoitrous iodine-sufficient areas". J. Clin. Endocrinol. Metab. 69 (2): 359–63. doi:10.1210/jcem-69-2-359. PMID 2753978.
- ↑ Alvarez DM, Lee V, Bhatt S, Dogra VS (2011). "Struma ovarii with papillary thyroid carcinoma". J Clin Imaging Sci. 1: 44. doi:10.4103/2156-7514.84322. PMC 3272908. PMID 22315711.