Struma ovarii pathophysiology: Difference between revisions
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{{CMG}}; {{AE}} {{ARK}} | {{CMG}}; {{AE}} {{ARK}} | ||
==Overview== | ==Overview== | ||
It is thought that | It is thought that struma ovarii is mediated by activation of the [[Mitogen-activated protein kinase|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]]. | ||
==Pathophysiology== | ==Pathophysiology== | ||
===Pathogenesis=== | ===Pathogenesis=== | ||
*It is thought that | * Malignant struma ovarii (MSO) are rare [[tumors]] which arise from [[ectopic]] thyroid tissue in the ovary which is benign. | ||
*Malignant transformation of | |||
*In | *It is thought that struma ovarii is mediated by activation of the [[Mitogen-activated protein kinase|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 carcinoma|thyroid carcinomas]]. <ref name="pmid17721188">{{cite journal |vauthors=Schmidt J, Derr V, Heinrich MC, Crum CP, Fletcher JA, Corless CL, Nosé V |title=BRAF in papillary thyroid carcinoma of ovary (struma ovarii) |journal=Am. J. Surg. Pathol. |volume=31 |issue=9 |pages=1337–43 |year=2007 |pmid=17721188 |doi=10.1097/PAS.0b013e31802f5404 |url=}}</ref> | ||
* | *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%). <ref name="pmid10366477">{{cite journal |vauthors=Dardik RB, Dardik M, Westra W, Montz FJ |title=Malignant struma ovarii: two case reports and a review of the literature |journal=Gynecol. Oncol. |volume=73 |issue=3 |pages=447–51 |year=1999 |pmid=10366477 |doi=10.1006/gyno.1999.5355 |url=}}</ref> <ref name="pmid27355004">{{cite journal |vauthors=Oudoux A, Leblanc E, Beaujot J, Gauthier-Kolesnikov H |title=Treatment and follow-up of malignant struma ovarii: Regarding two cases |journal=Gynecol Oncol Rep |volume=17 |issue= |pages=56–9 |year=2016 |pmid=27355004 |pmc=4913172 |doi=10.1016/j.gore.2016.05.014 |url=}}</ref> | ||
*In malignant struma ovarii (MSO), the cancer can spread to the contralateral [[ovary]]; also other sites such as abdominopelvic [[Lymph node|lymph nodes]], the [[peritoneal cavity]], [[lungs]], [[scalp]], [[brain]], [[diaphragm]], and [[liver]] may be involved. <ref name="pmid25474425">{{cite journal |vauthors=Luo JR, Xie CB, Li ZH |title=Treatment for malignant struma ovarii in the eyes of thyroid surgeons: a case report and study of Chinese cases reported in the literature |journal=Medicine (Baltimore) |volume=93 |issue=26 |pages=e147 |year=2014 |pmid=25474425 |pmc=4616397 |doi=10.1097/MD.0000000000000147 |url=}}</ref> | |||
*Routes of [[metastasis]] are: <ref name="pmid20119594">{{cite journal |vauthors=Yücesoy G, Cakiroglu Y, Muezzinoglu B, Besnili B, Yucesoy I |title=Malignant struma ovarii: a case report |journal=J. Korean Med. Sci. |volume=25 |issue=2 |pages=327–9 |year=2010 |pmid=20119594 |pmc=2811308 |doi=10.3346/jkms.2010.25.2.327 |url=}}</ref> <ref name="pmid2910784">{{cite journal |vauthors=Rosenblum NG, LiVolsi VA, Edmonds PR, Mikuta JJ |title=Malignant struma ovarii |journal=Gynecol. Oncol. |volume=32 |issue=2 |pages=224–7 |year=1989 |pmid=2910784 |doi= |url=}}</ref> <ref name="pmid11700816">{{cite journal |vauthors=Chan SW, Farrell KE |title=Metastatic thyroid carcinoma in the presence of struma ovarii |journal=Med. J. Aust. |volume=175 |issue=7 |pages=373–4 |year=2001 |pmid=11700816 |doi= |url=}}</ref> | |||
:*1) Regional [[lymphatics]] to [[pelvic]] and [[paraaortic lymph nodes]] | :*1) Regional [[lymphatics]] to [[pelvic]] and [[paraaortic lymph nodes]] | ||
:*2) Direct spread to the [[omentum]] | :*2) Direct spread to the [[omentum]], [[peritoneal cavity]] and the contralateral ovary | ||
:*3) [[Hematologic]] dissemination to the [[bone]], [[lung]], [[liver]] and [[brain]] | :*3) [[Hematologic]] dissemination to the [[bone]], [[lung]], [[liver]] and [[brain]] | ||
*Malignant struma ovarii | *Malignant struma ovarii manifest as [[Follicular carcinoma of the Thyroid|follicular carcinoma]] (causing [[peritoneal]] strumosis as a result of [[peritoneal]] spread), [[Papillary carcinoma of the thyroid|papillary carcinoma]] or follicular micro-carcinoma, a variant of [[Papillary carcinoma of the thyroid|papillary carcinoma]] (showing [[BRAF]] and [[RAS]] mutations) and rarely with [[Carcinoid syndrome|carcinoid]] and along with [[lymphoma]]. <ref name="pmid24783110">{{cite journal |vauthors=Sinha NK |title=Struma ovarii with elevated ca-125 levels and ascites mimicking advanced ca ovary |journal=J Clin Diagn Res |volume=8 |issue=3 |pages=140–1 |year=2014 |pmid=24783110 |pmc=4003614 |doi=10.7860/JCDR/2014/8005.4138 |url=}}</ref> <ref name="pmid19471561">{{cite journal |vauthors=Yoo SC, Chang KH, Lyu MO, Chang SJ, Ryu HS, Kim HS |title=Clinical characteristics of struma ovarii |journal=J Gynecol Oncol |volume=19 |issue=2 |pages=135–8 |year=2008 |pmid=19471561 |pmc=2676458 |doi=10.3802/jgo.2008.19.2.135 |url=}}</ref> | ||
==Genetics== | ==Genetics== | ||
* | *The [[genes]] involved in the [[pathogenesis]] of malignant struma ovarii include [[BRAF]] (35% to 69%), [[RAS]] (10%), and [[RET gene|RET]] (5% to 30%). <ref name="pmid17721188">{{cite journal |vauthors=Schmidt J, Derr V, Heinrich MC, Crum CP, Fletcher JA, Corless CL, Nosé V |title=BRAF in papillary thyroid carcinoma of ovary (struma ovarii) |journal=Am. J. Surg. Pathol. |volume=31 |issue=9 |pages=1337–43 |year=2007 |pmid=17721188 |doi=10.1097/PAS.0b013e31802f5404 |url=}}</ref> | ||
*The development of malignant struma ovarii (MSO) along with [[Papillary thyroid carcinoma|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 gene|RET]]/[[RAS]]/RAF pathway are not observed in BSO (Benign Struma ovarii). <ref name="pmid17721188">{{cite journal |vauthors=Schmidt J, Derr V, Heinrich MC, Crum CP, Fletcher JA, Corless CL, Nosé V |title=BRAF in papillary thyroid carcinoma of ovary (struma ovarii) |journal=Am. J. Surg. Pathol. |volume=31 |issue=9 |pages=1337–43 |year=2007 |pmid=17721188 |doi=10.1097/PAS.0b013e31802f5404 |url=}}</ref> | |||
*The development of | |||
==Associated Conditions== | ==Associated Conditions== | ||
*[[Adenomatous]] or colloid cervical goiters | *[[Adenomatous]] or colloid cervical goiters <ref name="pmid5448747">{{cite journal |vauthors=Kempers RD, Dockerty MB, Hoffman DL, Bartholomew LG |title=Struma ovarii--ascitic, hyperthyroid, and asymptomatic syndromes |journal=Ann. Intern. Med. |volume=72 |issue=6 |pages=883–93 |year=1970 |pmid=5448747 |doi= |url=}}</ref> | ||
*[[Hyperthyroidism]] in [[postmenopausal]] woman | *[[Hyperthyroidism]] in [[postmenopausal]] woman <ref name="pmid19955234">{{cite journal |vauthors=Nonne N, Ameyar-Zazoua M, Souidi M, Harel-Bellan A |title=Tandem affinity purification of miRNA target mRNAs (TAP-Tar) |journal=Nucleic Acids Res. |volume=38 |issue=4 |pages=e20 |year=2010 |pmid=19955234 |pmc=2831319 |doi=10.1093/nar/gkp1100 |url=}}</ref> | ||
*Pseudo-Meig's syndrome <ref name="pmid22436494">{{cite journal |vauthors=Mostaghel N, Enzevaei A, Zare K, Fallahian M |title=Struma ovarii associated with Pseudo-Meig's syndrome and high serum level of CA 125; a case report |journal=J Ovarian Res |volume=5 |issue= |pages=10 |year=2012 |pmid=22436494 |pmc=3350392 |doi=10.1186/1757-2215-5-10 |url=}}</ref> | *Pseudo-Meig's syndrome <ref name="pmid22436494">{{cite journal |vauthors=Mostaghel N, Enzevaei A, Zare K, Fallahian M |title=Struma ovarii associated with Pseudo-Meig's syndrome and high serum level of CA 125; a case report |journal=J Ovarian Res |volume=5 |issue= |pages=10 |year=2012 |pmid=22436494 |pmc=3350392 |doi=10.1186/1757-2215-5-10 |url=}}</ref> | ||
*[[Hashimoto's thyroiditis]] <ref name="pmid17276434">{{cite journal |vauthors=Morrissey K, Winkel C, Hild S, Premkumar A, Stratton P |title=Struma ovarii coincident with Hashimoto's thyroiditis: an unusual cause of hyperthyroidism |journal=Fertil. Steril. |volume=88 |issue=2 |pages=497.e15–7 |year=2007 |pmid=17276434 |pmc=2753978 |doi=10.1016/j.fertnstert.2006.11.095 |url=}}</ref> | *[[Hashimoto's thyroiditis]] <ref name="pmid17276434">{{cite journal |vauthors=Morrissey K, Winkel C, Hild S, Premkumar A, Stratton P |title=Struma ovarii coincident with Hashimoto's thyroiditis: an unusual cause of hyperthyroidism |journal=Fertil. Steril. |volume=88 |issue=2 |pages=497.e15–7 |year=2007 |pmid=17276434 |pmc=2753978 |doi=10.1016/j.fertnstert.2006.11.095 |url=}}</ref> | ||
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==Gross Pathology== | ==Gross Pathology== | ||
*On gross pathological examination, | *On gross pathological examination, struma ovarii may be present as : <ref name="pmid3563194">{{cite journal |vauthors=Piérard GE, Piérard-Franchimont C |title=[Acute and chronic borrelioses transmitted by ticks along the Meuse River and in bordering regions] |language=French |journal=Rev Med Liege |volume=42 |issue=3 |pages=101–6 |year=1987 |pmid=3563194 |doi= |url=}}</ref> <ref name="pmid2753978">{{cite journal |vauthors=Gaitan E, Cooksey RC, Meydrech EF, Legan J, Gaitan GS, Astudillo J, Guzman R, Guzman N, Medina P |title=Thyroid function in neonates from goitrous and nongoitrous iodine-sufficient areas |journal=J. Clin. Endocrinol. Metab. |volume=69 |issue=2 |pages=359–63 |year=1989 |pmid=2753978 |doi=10.1210/jcem-69-2-359 |url=}}</ref> | ||
:*[[Solid tumors|Solid]] and cystic tumor | :*[[Solid tumors|Solid]] and cystic tumor | ||
:*Tumor with several [[nodules]] partially separated by gray whitish [[fibrous tissue]]. | :*Tumor with several [[nodules]] partially separated by gray whitish [[fibrous tissue]]. | ||
:*[[Thyroid nodule|Nodules]] appear tan-brown in color with small dark red areas. | :*[[Thyroid nodule|Nodules]] appear tan-brown in color with small dark red areas. | ||
Revision as of 00:47, 24 August 2017
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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.
Pathophysiology
Pathogenesis
- Malignant struma ovarii (MSO) are rare tumors which arise from ectopic thyroid tissue in the ovary which is benign.
- 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 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
- 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 may also occur. [14]
- Struma ovarii can be seen associated with: [15]
- Serous cystadenoma
- Mucinous cystadenoma
- Brenner's tumor
- Carcinoid tumor
Gross Pathology
- 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 are observed.
Microscopic Pathology
- On microscopic histopathological analysis the tumor was initially diagnosed as granulosa cell tumor in frozen study but finally turned out to be Struma Ovarii which is the characteristic finding of Struma ovarii. [12]
- Hematoxylin and eosin-stained tissue helps analyze branching papillae with atypical cytologic features including nuclear groves, clearing, overlapping, and enlargement, consistent with papillary thyroid carcinoma arising in a struma ovarii. [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.
- ↑ 12.0 12.1 12.2 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.
- ↑ 18.0 18.1 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.