struma ovarii associated with pseudo-meigs’ syndrome: a...

Struma Ovarii Associated with Pseudo-Meigs’ Syndrome: A Rare

Presentation of an Infrequent TumorSonia Chhabra, Namita Bhutani♦, Sunita Singh, Mansi Aggarwal,

Rajeev Sen

Department of Pathology, Post Graduate Institute of Medical Sciences (PGIMS), Rohtak, Haryana, India

Case ReportMiddle East Journal of Cancer; January 2017; 8(1): 49-55

♦Corresponding Author: Namita Bhutani, MD252, Kailash Hill, New Delhi110065, India Tel: +91-9873101393Fax: +91-1262-211308

Email: [email protected]

IntroductionMonodermal teratoma is a rare

ovarian tumor that shows thepresence of only a single type ofcellular component. When presentin >50% of only thyroid tissue as amajor cellular component, it is known

as a struma ovarii.1 Struma ovarii isthe most common type ofmonodermal teratoma and accountsfor 2.7% of all ovarian teratomas.2Mostly these are benign tumors,however, very rarely the malignantvariant may occur that represents0.01% of all ovarian tumors and 5%-

AbstractStruma ovarii is an uncommon highly specialized ovarian teratoma that accounts

for less than 5% of mature teratomas. It is composed predominantly of mature thyroidtissue. Thyroid tissue is observed in 5%-15% of teratomas; however, to qualify as astruma ovarii tumor, the thyroid proportion must comprise more than 50% of the overalltissue. The combination of pseudo Meigs'syndrome and elevation of CA 125 with strumaovarii is a rare condition that can mimic ovarian malignancy. The majority of strumasare benign, however occasionally malignant transformation may be seen. We havereported a case of benign struma ovarii that presented with the clinical features ofadvanced ovarian carcinoma: complex pelvic mass, gross ascites, bilateral pleuraleffusion, and markedly elevated serum CA 125 levels. The patient underwent totalabdominal hysterectomy and bilateral salpingo oophorectomy. Ascites and pleuraleffusion resolved completely, and the CA 125 levels have returned to normal followingsurgical excision. Patients with pseudo-Meigs’ syndrome may present a diagnosticproblem as they masquerade as carcinoma with malignant effusions. In addition, thecoexistence of struma ovarii and pseudo-Meigs’ syndrome is a very rare event. Weemphasize by this report that, despite its rarity, a differential diagnosis of strumaovarii should be included for an ovarian mass.

Keywords: Struma ovarii, Ovarian neoplasms, Postmenopausal women, Pseudo-Meigs' syndrome, Monodermal teratoma

Received: June 16, 2016; Accepted: November 5, 2016

Sonia Chhabra et al.

37% of all struma ovarii.3 The peak age incidenceof struma is in the fifth decade, but cases have beenreported in older post-menopausal women anduncommonly occur in pre-pubertal girls.4 Thepathophysiology has not been clearly defined.The concomitant presence of pseudo-Meigs’syndrome with struma ovarii is a rare occurrence.When coexisting with pesudo Meigs' syndromeand elevation of CA 125, struma ovarii is highlysuspected as an ovarian malignancy. The diagnosisof struma ovarii can only be made byhistopathology analysis.5 Preoperative diagnosisis difficult because ultrasonography (US),computer tomography (CT) and nuclear magneticresonance (NMR) are not specific enough. Withthese techniques, we can only see an adnexalmass that consists of solid and cystic parts.6 Onlypreoperative scintigraphy with iodine (I-131) canshow active thyroid tissue. In difficult cases,immunohistochemical stains for thyroidtranscription factor and/or thyroglobulin willconfirm the diagnosis of struma ovarii.7

The present article focused on a patient thatpresented with struma ovarii. The patient wasinitially thought to have an ovarian malignancyprior to surgery based on clinical examination,radiological findings, and raised CA 125 level.Nevertheless, this syndrome must be consideredin otherwise healthy postmenopausal women,who present with both new or recurrenthydrothorax and ascites as it might masquerade anovarian malignancy.8

Case ReportA 60-year-old postmenopausal female (gravida

6, para 4) presented to the gynecology outpatientwith complaints of pain and abdominal distentionfor the previous one month. She also complainedof increasing breathlessness of a ten-day duration.Abdominal examination revealed the presenceof ascites; per vaginal examination, there wasfullness in the left fornix. Ultrasonography of theabdomen and pelvis indicated a bulky left,heteroechoic ovarian mass that measured 9.4×9.0cm with solid and cystic components. The featureswere suggestive of ovarian malignancy withascites (Figure 1A).Chest x- ray depicted amassive pleural effusion (Figure 1B).Serum CA125 level was 425U/ml (normal:<35 U/ml). AFPand CEA levels were within normal limits, aswere the liver function tests.

Cytological examination of the ascitic andpleural fluid revealed the presence of reactivehyperplastic mesothelial cells, however malignantcells were not seen. Hence, the diagnosis of non-inflammatory serous effusion was suggested.Ultrasound guided fine needle aspiration fromthe ovarian mass showed degenerated cells withindistinct cytomorphological details in anamorphous background.

The patient was scheduled for an exploratorylaparotomy with a vertical supraumbilical midlineincision for diagnostic and therapeutic purposes.She had ascites and 1000 ml of straw colored

Middle East J Cancer 2017; 8(1): 49-5550

Figure 1B. Chest x-ray showing massive pleural effusion.Figure 1A. Ultrasonography of abdomen and pelvis revealing asolid- cystic mass in left ovary with ascites.

Struma Ovarii Associated with Pseudo-Meigs’ Syndrome

fluid was drained upon entrance into the peritonealcavity. A 20×10 cm mixed cystic solid neoplasmarose from the left ovary. We received a specimenof hysterectomy with bilateral salpingo-oophorectomy. The left ovarian mass was partiallycystic, solid in consistency, and measured17×10.5×9 cm. On the cut surface, we observeda multicystic appearance with a few solid areas(Figure 2A, B). The cysts contained thickbrownish colloid-like fluid. The specimen wasextensively sampled.

Microscopic observation of the tumor indicateda lobular growth pattern composed of thyroidfollicles that resembled normal thyroid tissue.The cells were cuboidal to columnar and displayeda prominent component of cells with oxyphiliccytoplasms. The follicles contained dense colloid.The nuclei were typically round to oval withminimal cytologic atypia and rare mitotic figures.The intervening stroma was scant (Figure 3A,B). It was confirmed to be colloid on periodic acid-Schiff (PAS) staining (Figure 4A, B). There wereno visible features suggestive of malignancy suchas invasion of the stroma, blood vessels, andcapsule. Immunohistochemistry (IHC) analysesshowed positive TTF-1 and thyroglobulin innormal thyroid follicles (Figure 5A, B). Hence, adiagnosis of monodermal teratoma struma ovariiwas made. We considered the clinical presentationof the patient (hydrothorax, ascites, and a benignovarian tumor other than a fibroma) anddetermined that this was a rare association ofpseudo-Meigs’ syndrome with struma ovarii.

The patient recovered uneventfully and wasdischarged on day 7 post operatively. Recovery

was rapid with no evidence of re-accumulation ofthe pleural effusion or ascites. At the 6- weekfollow up, the patient was clinically well withno evidence of disease on physical examinationand a normal CA 125 level (8.0 U/ml).

DiscussionThe coexistence of a pelvic tumor, hydrothorax,

and ascites has been known since the late 19th

century. Meigs and Cass described the features ofthe disease in 1937. This disease was named“Meigs’ syndrome” by Roads in the same year.9Today, Meigs’ syndrome is defined as a triad ofbenign ovarian fibroma, hydrothorax, and asciteswhich resolves spontaneously after resection of theovarian tumor. Whereas, pseudo-Meigs’ syndromeis the co-existence of hydrothorax, ascites, andother ovarianor pelvic tumors. The associationof pseudo-Meigs’ syndrome with struma ovarii isa rare condition. Thus far only 10 to 11 caseshave been reported in the English literature.2

The etiology of fluid accumulation in pseudo-Meigs’ syndrome is unclear. The most probablepathogenesis of peritoneal and pleural effusionsis ascribed to irritation of the peritoneum/pleuraby the tumor, obstruction of the lymphatics, toxins,and release of inflammatory products, hypoalbu-minemia, as well as discrepancies between thearterial supply and the venous and lymphaticdrainage.These effusions are derived from atransudative process and regress spontaneouslyafter removal of the neoplasm.10 However,detection of malignant cells in ascitic/pleural fluidis a marker of metastatic disease and a sign of poorprognosis. Benign effusions of pseudo-Meigs’

Middle East J Cancer 2017; 8(1): 49-55 51

Figure 2. Grossly the tumor is solid and cystic with greenish brown fluid filled areas.

ba

syndrome affect neither the disease stage norpatient prognosis.2 Ascites may be present in upto one-third of the cases of struma ovarii. Strumaovarii rarely present as pseudo-Meigs’ syndromein approximately 5% of the cases. Struma ovariimay also be associated with other ovarianneoplasms such as Brenner tumor, serouscystadenoma, mucinous cystadenoma, andmelanoma.4

Struma ovarii is a special type of monodermalteratoma, defined as a mature teratoma composedeither exclusively or predominantly of thyroidtissue.1 In the early 20th century, Pick firstrecognized that struma ovarii was composed ofthyroid tissue and has suggested that ovariangoitres are actually teratomas in which thyroidalelements have overgrown the other tissues.11 In1933, Plaut showed that the thyroid tissue instruma ovarii was morphologically, biochemically,and pharmacologically identical to the cervicalthyroid gland.12 Stuma ovarii has been reported tobe the most common type of monodermalteratoma, accounting for nearly 3% of all ovarianteratomas.1 It is defined as an ovarian teratomacomposed predominantly (over 50%) or entirelyof thyroid tissue or forms a macroscopicallyrecognisable component of mature cysticteratoma.1 Struma ovarii is the most commontype of ovarian tumour associated with peripheralsteroid cell formation.13 It occurs most commonlyaround the fifth decade of life. It is necessary todifferentiate struma ovarii from the 10% ofteratomas that contain an occasional focus ofthyroid tissue. The tumor usually occurs as a

pelvic mass that may be palpable on physicalexamination.

Ultrasound usually shows a complexappearance with multiple cystic and solid areasthat reflect the gross pathology. Nevertheless,Doppler flow may aid in the preoperativediagnosis of struma ovarii. Blood flow signals,detected from the center of the echoic lesion, andlow resistance to flow may be more common instruma ovarii. Magnetic resonance imaging ismore specific, with cystic spaces that show bothhigh and low signal intensities on T1- and T2-weighted images which arise from the gelatinouscolloid. Only preoperative scintigraphy withradioactive iodine (I131) of the minor pelvis canshow active thyroid tissue.The use of US, CT, andMR imaging features of ovarian teratomas can aidin differentiation and diagnosis.6

The struma ovarii on gross appearance usuallyhas a brown, solid, gelatinous sectioned surfacewith colloid filled cysts that are characteristic.The average reported size of the tumor is 10 cmin the largest dimension, mostly unilateral, withonly 9.1% bilateral, a right side predominance, andelevated CA 125 levels. The signs and symptomscaused by struma ovarii can be due to the presenceof the pelvic mass. Patients may present withclinical hyperthyroidism, ascites, pleural effusion,or no symptoms. The tumor may be functional inabout 8% of cases and possibly associated with anenlarged thyroid gland in 10%-15% of patients.8Surgical removal of the struma in such casesusually results in the resolution of symptoms.

On microscopic examination, it is composed of



Figure 3b. Struma ovarii (H&E, 100×).Figure 3A. Photomicrograph depicting colloid filled follicles ofvarying size (H&E, 40×).

53Middle East J Cancer 2017; 8(1): 49-55

mature thyroid follicles filled with eosinophiliccolloid and lined by cuboidal or columnar cellswith uniform rounded nuclei. Degenerativechanges such as fibrosis, calcification andaggregates of hemosiderin-laden macrophagesmay be present.14 Histopathology is theconfirmatory tool of diagnosis in all cases. Indifficult cases, immunohistochemical stains forthyroid transcription factor and/or thyroglobulinmay be decisive in establishing the thyroid natureof the epithelial lining.7 Our institute is primarilya surgical center without molecular methods ofdiagnosis. Hence, this study has been mainlyrestricted to immunohistochemical analysis.Extensive grossing is required to rule out anyother component like neural, cartilage, or skinwith adnexal tissue before labelling any ovariantumor as a monodermal teratoma.15

Malignant transformation of the struma ovariiis rare and accounts for 0.01% of all ovariantumors. Struma ovarii may also harbor histologicalchanges identical to thyroid adenomas or beadmixed with a carcinoid (strumal carcinoid).The morphology of the thyroid tumors within the

struma is similar to the ectopic thyroid. Thethyroid tissue undergoes malignant changepredominantly to a papillary carcinoma.8

Serum tumor markers are useful in determiningpotential malignancy. CA 125 is a classical tumormarker effective in the surveillance of treatedepithelial ovarian cancers. However, CA 125 haspoor specificity in the diagnosis of epithelialovarian cancers, as its elevation may also beassociated with other malignancies and benign,physiological states that include pregnancy,endometriosis, and menstruation.16 Elevated CA125 accompanied by Meigs' syndrome is a rareclinical condition that has been reported in only27 cases. The exact reason for the elevated CA 125in Meigs' and pesudo Meigs' syndrome remainsunclear. A possible explanation proposed by Muiet al. is the irritation and subsequent inflammationof pleura and peritoneum produced by the presenceof free fluid in these spaces.5

Definitive therapy depends on the extent of thedisease and future childbearing wishes of thepatient. Simple salpingo-oophororectomy is thetherapy of choice for the vast majority of patients,


Figure 5B. On IHC, thyroglobulin positive (40×).Figure 5A. On IHC, TTF-1 positive (40×).

Figure 4B. PAS positive colloid in follicles (40×).Figure 4A. PAS positive colloid in follicles (40×).


since most cases are unilateral and benign. Totalhysterectomy with bilateral salpingo-oophorectomy is indicated for bilateral tumorsor in postmenopausal patients. In cases ofmalignant transformation, a combination ofcomplete tumor resection, total thyroidectomy,and adjuvant ablation is usually mandatory sinceevidence exists that struma ovarii behaves like itsthyroid counterparts. Careful postoperativemonitoring for any signs of hypothyroidism isrequired, as it may be the only functional thyroidtissue in the patient.17 Although elevated levels ofthyroglobulin have been demonstrated in bothbenign and malignant struma ovarii, after surgeryit can be an important tumor marker predictive ofrecurrence. An increase in serum thyroglobulinlevels should alert the clinician to diseaserecurrence. In case of a definite preoperativediagnosis, laparoscopic surgery can beimplemented, but the surgeon must be carefulnot to rupture the tumor intra-abdominally inorder to avoid dissemination, which could lead tomalignancy. Laparoscopic approach involveseither oophorectomy, which is recommended, orenucleation of the tumor as a fertility-preservingprocedure. When laparoscopy is performed andmalignant struma ovarii is confirmed postopera-tively, a second staging procedure should beperformed either as a laparotomy or laparoscop-ically. Prognosis is good after treatment.18

A postmenopausal female that presents with apelvic mass, ascites, pleural effusions, and elevatedCA 125 levels generally is highly indicative of amalignant process. A number of unique featureshave been identified in this patient. The rapidonset of symptoms, sinister ultrasound findings(marked ascites, a large solid, cystic mass in theleft adnexa), and a significantly elevated CA 125level were highly suspicious for an ovarianmalignancy. Although rare, struma ovariiaccompanied by pseudo Meigs' syndrome andelevated serum CA 125 should be considered inthe differential diagnosis of ovarian neoplasms.

ConclusionAlthough it has been more than 100 years

since the first description of struma ovarii, anumber of aspects remain enigmatic. This reportemphasizes that there are benign gynecologicalconditions that may show clinical, ultrasono-graphic, and biochemical signs suggestive ofmalignancy. The association of pseudo-Meigs’syndrome with struma ovarii is very rare. Weseek to emphasize by this report that, despite itsrarity, a differential diagnosis of struma ovariishould be included for an ovarian massaccompanied by pseudo Meigs' syndrome andelevated serum CA 125 levels.

Conflict of InterestNo conflict of interest is declared.

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struma ovarii associated with pseudo-meigs’ syndrome: a...

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