Malignant struma ovarii: a case report

Malignant struma ovarii is a rare form of the ovarian germ cell tumors. Hence, diagnosis and management of malignant struma ovarii have not been clearly defined. We present the case of a 34-year-old woman with papillary carcinoma arising in struma ovarii. The malignant component of this tumor was detected after laparoscopic removal, and a re-staging operation was performed afterwards. There was no evidence of clinical malignancy or metastases. In this paper, clinical features, treatment guidelines, diagnostic features, and immunohistochemical characteristics of this tumor are reviewed.     

Predominant Brenner Tumor Combined with Struma Ovarii Containing a Papillary Microcarcinoma Associated with Benign Peritoneal Strumosis: Report of a Case and Histologic Features

Brenner tumor and struma ovarii, two uncommon ovarian tumors arising alone or together with dermoid cysts or adenomas, are both rare entities. Both tumors rarely become malignant and rarely metastasize. Few published reports describe coexisting Brenner tumor and malignant struma ovarii. Patients in whom these malignancies coexist only occasionally have peritoneal spreading, strumosis, or a history of thyrotoxicosis. The patient we describe, a 74-year-old woman, presented with a 2 months’ history of lower abdominal pain and episodic intestinal subocclusion due to a complex pelvic mass. The mass consisted predominantly of a Brenner tumor associated with struma ovarii containing a single small island of thyroid tissue that had undergone malignant transformation into a well-differentiated papillary carcinoma and also normal thyroid tissue that had spread to the peritoneum. The patient underwent radical surgical treatment and after 7 years follow-up is disease free.     

RAS Mutation-Positive Follicular Variant of Papillary Thyroid Carcinoma Arising in a Struma Ovarii

Struma ovarii is an ovarian mature teratoma composed exclusively or predominantly of thyroid tissue. Malignant transformation of struma ovarii is rare and poorly understood, although this process is thought to be similar to carcinogenesis in malignant tumors of differentiated thyroid tissue originating in the thyroid gland. Genetic alterations in the mitogen-activated protein kinase pathway, including mutations of BRAF, RAS, and RET genes, have been implicated in the development of differentiated thyroid carcinoma arising in the thyroid gland. We report here a case with RAS mutation detected in a malignant struma ovarii. The patient is a 38-year-old female who had a 2.4 cm ovarian cyst noted incidentally on a first trimester ultrasound. She proceeded to ovarian cystectomy post-delivery, with pathologic examination detecting a papillary thyroid carcinoma, follicular variant, arising in a cystic teratoma. The tumor was tested for BRAF, RAS, and RET/PTC mutations. HRAS codon 61 mutation was identified. This is the first report of RAS mutation detected in the follicular variant of papillary carcinoma arising in a struma ovarii. It provides evidence that tumors developing in this setting involve molecular mechanisms similar to those implicated in tumors developing in the thyroid gland.     

Unilateral malignant struma ovarii in a case of bilateral ovarian teratoma with raised CA-125 level: a rare case with treatment dilemmas

Struma ovarii are specialized form of mature ovarian teratoma comprised predominantly of thyroid tissue (>50%). Most of the struma ovarii are benign; rarely can they undergo malignant transformation. Elevated CA-125 levels with benign struma ovarii have been seen in only 5 cases in literature. The association of malignant struma ovarii and high CA-125 levels with pseudo-Meig syndrome has been reported in only 2 cases in English literature. We describe a case of a 46-year-old multigravida who presented with an abdominal mass and raised CA-125 levels. Radiological investigations revealed bilateral cystic adnexal masses with ossified elements on left side suggesting a teratoma. Intraoperative frozen section and final pathology revealed bilateral teratoma with follicular variant of papillary thyroid carcinoma arising in the left ovary. To the best of our knowledge, this is the first case of malignant struma ovarii in combination with bilateral teratoma. The dilemmas related to preoperative diagnoses with elevated CA-125 levels, mimicking an epithelial ovarian neoplasm; intraoperative frozen section consultation; management and follow-up issues in this rare malignancy are discussed.     

No evidence of endometriosis within serous and mucinous tumors of the ovary

Ovarian endometriosis can transform into malignant tumors. The author retrospectively examined HE slides of 112 serous tumors and 75 mucinous tumors for the existence of ovarian endometriosis. When endometriosis is present within the tumors, the term "endometriosis-derived tumor" was applied. When endometriosis is recognized adjacent to the tumor, the term "endometriosis-associated tumor" was used. Of the 112 serous tumors (46 benign, 18 borderline, and 50 malignant), 4 (3.5%) (2 benign and 2 malignant) were endometriosis-associated tumors. None was endometriosis-derived tumor. Of the 75 mucinous tumors (30 benign, 26 borderline, and 19 malignant), 4 (5%) (1 borderline and 3 benign) were endometriosis-associated tumors. No tumors showed endometriosis-derived tumors. The data suggest that endometriosis does not transform into serous and mucous tumors. The author felt the limitation of retrospective survey, because the limited numbers of slides (5 to 15) were obtained from each tumor. The author also felt that endometriosis can be difficult to discern because of degenerative changes and other similar lesions such as fallopian tube, fimbria, inclusion cysts, rete ovarii, paraovarian cyst, and Müllerian ducts remnants. Prospective study using whole ovarian examination is required.     

非特异性类固醇细胞瘤临床病理特点

目的探讨非特异性类固醇细胞瘤的临床、病理学特征,以及诊断、鉴别诊断和治疗方法。方法对1例非特异性类固醇细胞瘤进行HE和免疫组化EliVision法染色,并复习文献。结果肿瘤呈实性,境界清楚,偶尔呈分叶状。其肿瘤细胞的形态大致为两种,一种为具有嗜酸胞质颗粒的细胞,另一种为胞质透亮的细胞。此肿瘤的恶性程度与肿瘤大小、核非典型性程度、核分裂象多少、出血、坏死等有关。肿瘤细胞免疫组化α-inhibin、calretinin、Melan-A阳性表达。非特异性类固醇细胞瘤需要与广泛黄素化的颗粒细胞瘤、卵泡膜细胞瘤、富于脂质的Sertoli细胞瘤和原发性或继发性的黑色素瘤相鉴别。治疗方法主要取决于肿瘤的良恶性。结论非特异性类固醇细胞瘤占类固醇细胞肿瘤的56%,是类固醇细胞肿瘤中最常见的类型,免疫组化有助于诊断。     

Malignant struma ovarii: a case report and review of the literature

A 45-year-old woman with papillary carcinoma arising in struma ovarii which involved one ovary without dissemination is presented. Total abdominal hysterectomy and bilateral salpingo-oophorectomy were performed. Histopathological examination revealed malignant struma ovarii of the papillary type. The flow cytometric analysis revealed an hypodiploid DNA content (DNA index:0.67). Since these are rare tumors, there is no universal exact protocol for the treatment and follow-up of patients with malignant struma ovarii. More data are needed to determine the prognosis and management in preferring mode of therapy.     

Benign and malignant struma ovarii

Three cases of struma ovarii are reported, two of which were benign, and one which was malignant. Immunoperoxidase studies confirmed that the tumors secreted triiodothyronine and thyroxine, but no carcinoembryonic antigen nor alpha-fetoprotein. In the case of the malignant struma ovarii, the patient's thyroid was histologically normal, and thus the possibility of a metastasis to the ovary from a primary thyroid carcinoma was excluded.     

Ovarian cystic tumor composed of Brenner tumor and struma ovarii

Ovarian tumor composed only of Brenner tumor and struma ovarii is very rare; only 6 cases have been reported in the English literature, to the best of the author's knowledge. A 66-year-old woman underwent right oophorectomy because of torsion of right ovarian cyst. Macroscopically, the ovarian cyst was hemorrhagic and red. Cystic content was hemorrhagic fluid. Microscopically, the cyst walls were composed only of Brenner tumor (50% in area) and struma ovarii (50% in area). Hemorrhage and ischemic changes were seen. Other elements were not recognized. No malignant transformation was noted. These two elements were separately present, and no mergers between them were recognized. Immunohistochemically, the Brenner tumor element was positive for cytokeratins (AE1/3 and CAM5.2) and Ki67 (labeling=3%), but negative for thyroglobulin, TTF-1, p53, CA125, and vimentin. The struma ovarii element was positive for cytokeratins (AE1/3 and CAM5.2), thyroglobulin, TTF-1 and Ki67 (labeling=5%), but negative for p53, CA125 and vimentin. The findings suggests that there were cases of ovarian cyst composed only of Brenner tumor and struma ovarii, that such a case may be monodermal mature cystic teratoma or the Brenner tumor element was derived from surface epithelium in the preexisting struma ovarii, and that such a tumor manifest as cystic torsion.     

RETROVIRUS PARTICLES IN SPONTANEOUSLY OCCURRING AND RADIATION-INDUCED TUMORS IN ddY MICE

Among spontaneously occurring tumors, pulmonary tumor, malignant lymphoma, mammary tumor, and ovarian tumor were the major ones in 232 ddY female mice. The former three tumors appeared significantly earlier and the latter one increased in incidence in 229 mice given 600 R whole or 800 R partial body (tunk) x-irradiation at the age of 10 weeks. Five tumors were examined electronmicroscopically from each tumor type of both the spontaneously occurring and radiation-induced tumors. G type virus particles were present only in the malignant lymphoma and B particles in the mammary, ovarian and pulmonary tumors, which are all of epithelial character. Thus, as far as we were concerned in this mouse strain, B particles were produced preferentially in epithelial cells and C particles in non-epithelial cells. The retrovirus particles were found in the same frequency, namely, 10 of 20 tumors examined in both the tumor groups. From our results, the intervention of virus in radiation carcinogenesis still remains in question.     

Gonadal tumor with granulosa cell tumor features in an adult testis

Granulosa cell tumor is almost exclusively an ovarian tumor. Rare cases of granulosa cell tumor have been reported involving the testes. We report a testicular gonadal stromal tumor with granulosa cell differentiation in a 54-year-old white man. The tumor was discovered by an ultrasound evaluation for left hydrocele. The patient was clinically asymptomatic. On frozen section, the initial impression was a malignant lymphoma. Final histology on the orchiectomy specimen showed a gonadal stromal tumor with granulosa cell features. Immunohistochemical studies excluded malignant lymphoma and germ cell tumors, consistent with a stromal tumor. This case report illustrates the challenges for the pathologist in making an accurate diagnosis in unusual testicular tumors.     

Coexisting Brenner tumor and struma ovarii in the right ovary: case report and review of the literature

A bilateral ovarian tumor composed of mixed Brenner tumor and struma ovarii in the right ovary and mature cystic teratoma in the left ovary, is described. Mixed Brenner tumor and struma ovarii is rare; eight cases are reviewed. In this case, in addition to the typical Brenner tumor and struma ovarii, some nests composed of both Brenner tumor and struma ovarii in one nest were found in the right ovarian tumor. Immunohistochemically, the struma ovarii is stained for thyroglobulin, and Brenner nests showed various degrees of positive stain for thyroglobulin, which is a specific finding. Brenner tumor, in this case, may produce thyroglobulin or have a receptor to thyroglobulin or analog of thyroglobulin. The origin of mixed Brenner tumor and struma ovarii may be germ cell, as described in some literature, or the Brenner tumor may be of a metaplastic nature, although the Brenner tumor is fourfold the size of struma ovarii in the case presented.     

Ovarian cysts in MRL / MpJ mice are derived from the extraovarian rete: a developmental study

MRL/MpJ (MRL) mice, commonly used as a model for autoimmune disease, have a high frequency of ovarian cysts originating from the rete ovarii. In the present study, to clarify how the rete ovarii, which are remnants of mesonephric tubules during embryogenesis, progress to cystic formation with aging, the morphology of MRL rete ovarii was analyzed and compared with that of normal C57BL/6N (B6) mice. In B6 mice, the rete ovarii consisted of a series of tubules, including the extraovarian rete (ER), the connecting rete (CR), and the intraovarian rete (IR), based on their location. Whereas the ER of B6 mice was composed of highly convoluted tubules lined by both ciliated and non-ciliated epithelia, the tubules in the CR and IR had only non-ciliated cells. In MRL mice, dilations of the rete ovarii initiated from the IR rather than the ER or CR. Although the histological types of cells lining the lumen of the rete ovarii were the same as those in B6 mice, the ER in MRL mice showed a variety in morphology. In particular, the connections between the ER and ovary tended to disappear with increasing age and the development of ovarian cysts. Furthermore, the epithelium lining the large ovarian cysts in MRL mice had ciliated cells forming the cluster. On the basis of these findings, it is suggested that cystic changes of the rete ovarii in MRL mice are caused by the dilations of the IR with invasion of the ER and CR into the ovarian medulla. These data provide new pathological mechanisms for ovarian cyst formation.     

BRAF T1799A mutation occurring in a case of malignant struma ovarii

Struma ovarii is an extremely rare tumor that occasionally undergoes malignant transformation. Because struma ovarii is composed of thyroid tissue, it is conceivable that the pathogenetic events involved in thyroid follicular transformation may take place also in struma ovarii. The authors describe a case of a classical variant of papillary thyroid carcinoma arising in a struma ovarii of a 22-year-old female. The tumor was heterozygous for BRAF T1799A mutation. No ret/ PTC-1 or ret/PTC-3 rearrangements were detected. This finding would suggest that malignant struma ovarii is similar histologically and genetically to primary papillary thyroid carcinoma.     

Retiform uterine tumours resembling ovarian sex cord tumours. A comparative immunohistochemical study with retiform structures of the female genital tract

Aims:  To analyse both the clinicopathological and immunohistochemical findings in six cases of uterine tumours resembling ovarian sex cord tumours with a predominant epithelial retiform component resembling the rete ovarii (RUTROSCT) and to compare their immunophenotype with tissues containing retiform structures such as the normal rete ovarii, retiform Wolffian adnexal tumour (RWAT) and ovarian retiform areas of Sertoli-Leydig cell tumours (ORSLCT).
Methods and results:  Six RUTROSCTs were analysed. The average age of patients was 65 years, and all tumours behaved in a benign fashion. Four were intracavitary and two intramural. Two cases were misdiagnosed as malignant in endometrial biopsy specimens and one in the hysterectomy specimen. Histologically they had a tubulopapillary or glomeruloid formation; a sex-cord-like or endometrial stromal component was absent or comprised at most 30% of the tumour. RUTROCST showed consistent positivity for CAM5.2, cytokeratin (CK) 7, vimentin, calretinin, progesterone receptor and apical CD10. CD56 and α-inhibin were positive in half of the cases. Epithelial membrane antigen, desmin, smooth muscle actin and calponin were negative. Comparatively, rete ovarii and RWAT had a similar positivity for CK7, CD56, CD10 and calretinin. ORSLCT differed in its conspicuous positivity to CD56, CD10, α-inhibin and calretinin, but absent CK7 expression.
Conclusions:  RUTROSCTs have benign behaviour but may be confused with various uterine adenocarcinomas or metastases. Correct diagnosis should avoid overtreatment. The immunophenotype of retiform areas is similar to that of adult rete ovarii and RWAT with minor divergence from ORSLCT.     

Diagnosis of ovarian tumor by measuring tumor markers]

Values of CA125, CA19-9, TPA, CA72-4, BFP and LDH in sera were detected in 148 malignant ovarian tumors, 41 borderline malignant ovarian tumors, 71 benign ovarian tumors and 64 benign uterine diseases. A new cut-off value was determined by ROC graph for distinguishing malignant and borderline ovarian tumors from benign ovarian tumors. CA125 (cut off: 30 U/ml) was a highly sensitive marker for malignant and borderline malignant ovarian tumors, the value being 88.1% (52/59) and 81.8% (9/11), respectively. On the other hand, in 37 benign ovarian tumors, the positive rate was 21.6% and in 21 benign uterine diseases it was 52.4%. CA19-9 (cut off: 150 U/ml) was inferior to CA125, but it was an effective marker for mucinous ovarian tumors. TPA (cut off: 40 U/ml) was also a sensitive (84.7%, 50/59) marker of malignant ovarian tumors. CA72-4 (cut off: 4 U/ml) was a highly specific (87.0%, 60/69) marker of malignant ovarian tumors. Combination assays of CA125/CA19-9, CA125/TPA and CA125/CA72-4 were not effective. Usefulness of BFP for early malignant ovarian tumors was suggested. Seven cases of dysgerminoma showed extremely elevated LDH levels (1,248 +/- 886 IU/1/37 degrees C). Malignancy and histological type of ovarian tumors could be decided by combination assay of these tumor markers, before surgical operation.     

Follicle center lymphoma involving the female genital tract: a morphologic and molecular genetic study of three cases

Primary female reproductive system lymphomas are distinctly uncommon, and are defined as lymphomas that present primarily as gynecologic tumors. We describe 3 cases which presented in this location, 1 primary ovarian disease and 2 others presenting the initial manifestations of disseminated lymphoma. Clinical history, follow-up information, and paraffin embedded archival tissue were available for all 3 cases. A panel of immunoperoxidase studies and molecular genetic studies were performed for each case. The primary ovarian follicle center lymphoma was a grade III/III (large cell) while the cases representing secondary involvement were grade I/III (small cell). Immunohistochemistry demonstrated reactivity of the malignant cells in each case with CD20 and bcl-2. In the grade I/III cases the cells were immunoreactive for CD45RA and CD10. Molecular genetic analysis demonstrated the t(14;18) translocation in the case of primary ovarian follicle center lymphoma. Follicle center lymphoma uncommonly presents in the female genital system, and may rarely be primary to this site. Immunoperoxidase and molecular studies in concert with the morphology are invaluable in rendering a correct diagnosis and ensuring correct treatment of the patient.     

Case report: Malignant struma ovarii

Struma ovarii are specialized teratomas consisting of thyroid tissue with various microscopic features, ranging from benign to malignant. We report a rare form of malignant struma ovarii, composed exclusively of a follicular variant of papillary thyroid carcinoma with capsular invasion, which occurred in a 65-yr-old woman.     

Peptide Tyrosine Tyrosine-positive Ovarian Carcinoid Tumor Arising from a Dermoid Cyst

A case of ovarian carcinoid tumor of the trabecular type is presented. The small carcinoid tumor was found incidentally in a resected dermoid cyst. Histologically, the tumor was surrounded by a smooth muscle layer with focal stromal invasion. Non carcinoid papillary mucosa and a few small glands, simulating the mucosa of the fallopian tube and remnant miillerian glands, respectively, were also present adjacent to the carcinoid tumor and enclosed by the same smooth muscle layer. The tumor cells revealed argyrophilia, and were positive for peptide tyrosine tyrosine (PYY) in the cytoplasm and for CEA in part of the luminal surface. This case was considered to be a rare ovarian carcinoid tumor arising from a dermoid cyst, without association of struma ovarii. PYY may be a potential marker for determining the histogenesis of ovarian carcinoid tumors.     

Clinical significance of microsatellite instability in sporadic epithelial ovarian tumors

PURPOSE: We evaluated the expression of microsatellite instability (MSI) in sporadic ovarian tumors using 5 standard and 9 new MSI markers to determine the clinical significance of MSI in sporadic epithelial ovarian tumors. MATERIALS AND METHODS: MSI was examined in 21 borderline and 25 malignant ovarian tumors. Polymerase chain reaction (PCR) was performed using the 5 markers recommended by the National Cancer Institute (NCI) for colon cancer and 9 additional markers. MSI was determined using fractional analysis by mixing the PCR products and size markers. RESULTS: Using the 5 conventional MSI markers, MSI was found in 4 of 46 (8.6%) ovarian tumors, including 2 of 21 (9.5%) borderline ovarian tumors and 2 of 25 (8%) malignant ovarian tumors. Using the 9 additional MSI markers, MSI was observed in 7 of 46 (15.2%) ovarian tumors, including 3 of 21 (14.3%) borderline ovarian tumors and 4 of 25 (16%) malignant ovarian tumors. There was no statistically significant difference between MSI and clinicopathological factors, including histology and stage, although there was a trend toward an increased incidence of MSI in the serous type. CONCLUSION: MSI was infrequent in ovarian tumors, including both borderline and malignant tumors. MSI was found to be uncommon in sporadic ovarian tumors, even by using additional MSI markers. The clinical significance of MSI is not strong in patients with sporadic ovarian tumors.