A case report of malignant struma ovarii with papillary thyroid carcinoma.

Key clinical message: Struma ovarii (SO), is a rare and specialized ovarian teratoma. The treatment is controversial depending on the risk of recurrence and metastasis. Here a SO with papillary thyroid carcinoma is reported and the approach is thoroughly discussed. Abstract: Struma ovarii (SO) is a highly specialized ovarian teratoma primarily composed of thyroid tissue. Clinical features associated with SO include lower abdominal discomfort, unusual vaginal bleeding, ascites, and hyperthyroidism. While SO rarely transforms into malignancy, the optimal degree of treatment remains controversial due to the varying risks of recurrence and metastasis. In this report, we present the case of a 64-year-old woman experiencing abdominal pain and diagnosed with SO, accompanied by papillary thyroid carcinoma. We thoroughly discuss the evaluation and management of this rare condition.

Highly differentiated follicular carcinoma of the ovary with omental and peritoneal spread in a 22-year-old girl; A diagnostic and counseling challenge.

INTRODUCTION AND IMPORTANCE: Highly differentiated follicular carcinoma of the ovary (HDFCO) is a rare type of thyroid carcinoma originating from struma ovarii, consisting of benign-appearing thyroid follicles spread outside the ovarian tissue. CASE PRESENTATION: We present a 22-year-old girl who underwent left salpingo-oophorectomy, omental, and peritoneal biopsies for a complex left ovarian mass. Microscopic examination and Immunohistochemical staining led to the diagnosis of HDFCO with tumor deposits affecting the omental and peritoneal biopsies. The patient was counseled about the nature of her disease and the recommended treatment. Thyroidectomy was performed later, revealing a normal thyroid gland. The patient received an ablative dose of radioactive iodine (150 mci) and a suppressive dose of levothyroxine. This is one of the youngest reported patients ever. CLINICAL DISCUSSION: To our knowledge, the patient presented in this case report is one of the youngest patients ever reported in the literature. In the recent WHO Classification of Female Genital Tumors, the term highly differentiated follicular carcinoma arising from struma ovarii (HDFCO) was introduced, to emphasize its low-grade malignant behavior. Due to its rare incidence, there is no standard treatment strategy, but a plan based on surgical intervention is suggested. CONCLUSION: Malignant struma ovarii should be put in the differential diagnosis in young patients with suspicious ovarian masses. Adequate patient counseling remains a cornerstone in the journey of management.

Presentation and treatment of two cases of malignant struma ovarii.

BACKGROUND: Malignant Struma Ovarii (MSO) is a rare type of germ cell tumour which is diagnosed postoperatively on surgical pathology specimens by the presence of differentiated thyroid cancer in mature cystic teratomas in the ovaries. Treatment and follow-up procedures are not clearly established due to the paucity of MSO cases. CASE 1: A 44-year-old multiparous female presented with an irregular period. Ultrasound showed a left ovarian lesion mostly a dermoid cyst, however, CT showed a 3.8 × 2.7 × 4 cm complex cystic lesion with thick septation and enhancing soft tissue component. Laparoscopic left salpingo-oophorectomy was performed and histopathology showed a follicular variant of papillary thyroid carcinoma arising in a mature cystic teratoma. Peritoneal cytology was positive for malignancy. A thyroid function test was normal before surgery. Total thyroidectomy was performed followed by radioactive (RAI) iodine therapy. Later, a total laparoscopic hysterectomy and right salpingo-oophorectomy were performed. There is no evidence of recurrent disease during the 26-months follow-up. CASE 2: A 46-year-old single female presented with left lower abdominal pain that had persisted for 2 months. Imaging revealed an 8 × 9 × 9.5 cm left ovarian mass. Laparoscopic left salpingo-oophorectomy was performed and histopathology showed mature cystic teratoma with small papillary thyroid cancer. CT showed no evidence of metastatic disease. Later, the patient had a total thyroidectomy followed by radioactive (RAI) iodine therapy. She was started on thyroxine and later had total abdominal hysterectomy and right salpingo-oophorectomy. CONCLUSION: MSO is a very rare tumour. Preoperative diagnosis is very difficult because of the nonspecific symptoms and the lack of specific features in imaging studies. Also, there is no consensus on the optimal treatment of women with MSO. Our two cases add to the limited number of MSO cases.

Identification of Germline FOXE1 and Somatic MAPK Pathway Gene Alterations in Patients with Malignant Struma Ovarii, Cleft Palate and Thyroid Cancer.

Germline variants in the FOXE1 transcription factor have been associated with thyroid ectopy, cleft palate (CP) and thyroid cancer (TC). Here, we aimed to clarify the role of FOXE1 in Portuguese families (F1 and F2) with members diagnosed with malignant struma ovarii (MSO), an ovarian teratoma with ectopic malignant thyroid tissue, papillary TC (PTC) and CP. Two rare germline heterozygous variants in the FOXE1 promoter were identified: F1) c.-522G>C, in the proband (MSO) and her mother (asymptomatic); F2) c.9C>T, in the proband (PTC), her sister and her mother (CP). Functional studies using rat normal thyroid (PCCL3) and human PTC (TPC-1) cells revealed that c.9C>T decreased FOXE1 promoter transcriptional activity in both cell models, while c.-522G>C led to opposing activities in the two models, when compared to the wild type. Immunohistochemistry and RT-qPCR analyses of patients' thyroid tumours revealed lower FOXE1 expression compared to adjacent normal and hyperplastic thyroid tissues. The patient with MSO also harboured a novel germline AXIN1 variant, presenting a loss of heterozygosity in its benign and malignant teratoma tissues and observable ß-catenin cytoplasmic accumulation. The sequencing of the F1 (MSO) and F2 (PTC) probands' tumours unveiled somatic BRAF and HRAS variants, respectively. Germline FOXE1 and AXIN1 variants might have a role in thyroid ectopy and cleft palate, which, together with MAPK pathway activation, may contribute to tumours' malignant transformation.

Role of gene sequencing in classifying struma ovarii: BRAF p.G469A mutation and TERT promoter alterations favour malignant struma ovarii.

AIMS: Struma ovarii (SO) are rare, accounting for 0.3-1% of ovarian tumours, and include benign and malignant lesions. In most cases, histology is not predictive of clinical outcome and prognosis. The prognosis of histologically malignant thyroid-type carcinomas can indeed be excellent, while SO, composed of normal thyroid tissue, can recur and are designated highly differentiated follicular carcinoma of the ovary. Clearer diagnostic criteria are therefore required. METHODS AND RESULTS: We retrospectively studied 31 SO using DNA and RNA sequencing with pan-cancer gene panels, including eight biologically malignant SO (BMSO) defined based on ovarian serosal or extra-ovarian dissemination at presentation or during follow-up, 10 stage IA histologically malignant SO (HMSO) with thyroid-type carcinoma morphology and 13 biologically and histologically benign SO (BSO), with none of the above-mentioned characteristics. Molecular alterations were observed in 87.5% of BMSO, 70% of HMSO and 7.7% of BSO (P < 0.001). All patients with a peritoneal dissemination at presentation or during follow-up had at least one gene alteration. BRAF mutations (44.5%) were only observed in malignant forms (HMSO and BMSO) and TERT promoter alterations (25%) only in cases of BMSO. The BRAF p.G469A mutation, which is extremely rare in thyroid carcinomas, was the molecular alteration most frequently associated with malignant SO (28.5%). CONCLUSION: Our results highlight the clinical utility of molecular sequencing in SO, based on this limited number of cases. However, as malignant SO evolve slowly, more extensive molecular studies in SO with more than 10 years' follow-up are required to draw any conclusions on the prognostic value of the associated gene alterations.

An unusual case of three concomitant primary solid cancers with unique histopathological characteristics.

INTRODUCTION AND IMPORTANCE: Struma Ovarii is a rare type of monodermal teratoma with at least 50 % of its mass being thyroid tissue. They make up <1 % of all ovarian tumours and 3 to 5 % of all ovarian teratomas. These tumours are usually benign but malignant transformation is seen in <5 % of cases. CASE PRESENTATION: We present the case of a 45-year-old lady with three synchronous primary cancers on a background of Struma Ovarii; primary lung adenocarcinoma, papillary thyroid carcinoma and ovarian teratoma. Over the course of 18 months, this lady underwent full pelvic clearance of malignant Struma Ovarii and lymph nodes, total thyroidectomy, and an anatomical lung resection. CLINICAL DISCUSSION: This case represents an incredibly rare condition of Struma Ovarii for which there is no firm management consensus. Furthermore, the uniqueness of three separate primaries has to the best of our knowledge not previously been reported in the literature. CONCLUSION: This reinforces the notion that in select patients, radical management with curative intent is entirely possible but requires complete multi-disciplinary and multi-modal sub-specialty collaboration.

Thyroid Carcinoma Arising From Struma Ovarii at Adolescence: A Challenging Case With Favorable Outcome.

Malignant struma ovarii (MSO) is a rare and aggressive ovarian tumor that mostly affects adults but can occur in adolescents. Prompt recognition, accurate diagnosis, and multidisciplinary management are essential for favorable outcomes. Herein, we report the youngest case of an 11-year-old girl with a large MSO. First, conventional imaging revealed a large left ovarian mass, leading to a left oophorectomy. Subsequently, histopathological examination confirmed papillary thyroid carcinoma within MSO. Thyroid and fertility-preserving surgery were chosen after multidisciplinary consultation. Despite challenges, the patient had a positive outcome with no recurrence after 36 months. Therefore, the adoption of less invasive surgical approaches and vigilant follow-up can achieve remission, but more research is needed to further enhance our understanding of the disease's risk stratification and optimal treatment strategies.

Follicular thyroid carcinoma within a struma ovarii: a case report.

Struma ovarii comprises 1% of all ovarian tumors and 3% of ovarian teratomas. It occurs in older females. Struma ovarii is often asymptomatic, unilateral, and accidentally detected through abdominal ultrasound or computed tomography. It presents with palpable abdominal pain or irregular menstrual cycles. Generally, it is treated with surgical resection, even though the best procedure in these cases remains under discussion. In this study, we present a case of a 28-year-old female with severe pain in the right iliac fossa. Physical examination and radiological images showed a large mass. A bilateral salpingo-oophorectomy with omentectomy, a total mass resection, and an abdominal hysterectomy were performed. A biopsy confirmed the diagnosis of a follicular thyroid tumor. The management decision is based on clinical and pathological data. This is particularly challenging due to its rarity and the insufficient guidelines regarding the management of this type of cancer.

Neoplasms in Struma Ovarii: A Review.

Struma ovarii is a well-known ovarian teratoma made up of benign thyroid tissue. These lesions demonstrate variable, normal architecture and normal thyroid immunohistochemical staining with positivity for TTF1, PAX8, and thyroglobulin. Though most are benign, some of these lesions can also present with a malignant component. Within this article, we review the most common diagnostic malignancies including papillary thyroid carcinoma, strumal carcinoid, highly differentiated follicular thyroid carcinoma, and other thyroid carcinomas. We additionally review the use of TTF1 staining to assist in differentiating these lesions from surrounding gynecologic epithelium, which is imperative in making such diagnoses. In highlighting these entities, we hope to provide practicing pathologists with an effective and concise review of these lesions to assist in more challenging cases of struma ovarii.

An Extremely Rare Case of Poorly Differentiated Thyroid Carcinoma Arising in Malignant Struma Ovarii and Concurrent Papillary Thyroid Carcinoma: A Case Study.

Ovarian tumors can be classified by their origin - epithelial tumors, germ cell tumors, and stromal tumors. Malignant struma ovarii (MSO) are 0.01% of all ovarian tumors. In order to be classified as a struma ovarii, more than 50% of the teratoma consists of thyroid tissue. The thyroid tissue in the struma ovarii exhibits the same histological and physiological properties as that of the cervical thyroid tissue. Poorly differentiated thyroid carcinoma (PDTC) is an extremely rare occurrence when arising from an MSO. Including this case report, there are only 10 reports of PDTC in the setting of MSO. Of these cases, this patient is the only one who presented with concurrent primary thyroid carcinoma (PTC). This case study examines how invaluable intra-professional collaboration is for appropriate diagnosis, along with attention to detail of identifying markers in pathology sections and use of the appropriate immunohistochemical analysis.

Incidence, clinical characteristics, and survival outcomes of ovarian strumal diseases: a retrospective cohort study.

BACKGROUND: Struma ovarii (SO) is a rare tumor and may transform into ovarian strumal carcinoid (OSC) and/or malignant struma ovarii (MSO), but the incidence, clinical characteristics, and survival outcomes have not been well defined. METHODS: We conducted a retrospective study of patients with ovarian strumal diseases treated in the our hospital between 1980 and 2022. Subgroup analyses of SO, OSC, and MSO were subsequently performed. RESULTS: A total of 275 cases (2.14%) were identified in a cohort of 12,864 patients with ovarian teratomas, where SO, OSC, and MSO accounted for 83.3%, 12.0%, and 4.7% of cases, respectively. There were no significant differences in age, tumor sizes, elevated tumor markers, and ascites among the three subgroups. At initial treatment, all patients with SO or OSC had FIGO stage I disease except one SO patient presenting metastatic disease, ten patients had MSO confined to the ovary, whereas other three patients had metastatic diseases. Two patients with SO respectively relapsed at peritoneum and anterior mesorectum, while none of the OSC patients presented tumor recurrence or death despite different surgical procedures employed. The 5-year recurrence-free survival rate was 88.9%, and only one death occurred at 9.5 years after diagnosis in patients with MSO. Radioiodine therapy showed satisfactory therapeutic efficacy, but these patients showed poor responses to the chemotherapy. CONCLUSION: 2.14% of ovarian teratoma could be classified as SO, of which 12.0% and 4.7% of SO may transform into OSC and MSO, repsectively. The survival outcomes were excellent even after SO transformed into OSC or MSO. SYNOPSIS: SO occupied 2.14% of ovarian teratoma, where 12.0% and 4.7% of SO may transform into OSC and MSO, respectively, and had excellent survival outcomes.

Struma Ovarii with Papillary Thyroid Carcinoma and Metastasis to the Appendix: A Case Report and Literature Review.

Struma ovarii is an infrequent type of teratoma arising from the ovary accounting for only 2% of all ovarian teratomas. These tumors have a benign biology with rare malignant transformation in about 3% of cases. The most common malignant transformation that arises from struma ovarii is papillary thyroid carcinoma. These neoplasms act in the same way as those arising from the thyroid gland, but due to the rarity of their occurrence there is still a debate over therapeutic options. We present a case of a 41-year-old Ethiopian Para IX woman presented with abdominal swelling for four years, accompanied by dull pain, satiety, and weight loss. Her vital signs were normal, and her abdominal examination revealed a large abdominopelvic mass. Her CA-125 was elevated, and her blood count, organ function tests, and serum electrolyte levels were normal. Abdominal ultrasound revealed a complex abdominopelvic mass with cystic and solid components, possibly ovarian teratoma. The patient underwent surgery, revealing a 14 by 10 cm right ovarian mass and a 3×3 cm appendiceal mass. Subsequently, total abdominal hysterectomy, bilateral salpingo-oophorectomy, total omentectomy, and appendectomy was done. Histopathologic evaluation revealed follicular proliferation of enlarged cells, with no papillary growth pattern. The case was diagnosed as malignant struma ovarii, a follicular variant of papillary thyroid carcinoma (FVPTC) with secondary deposits on the appendix. A complete thyroidectomy was done after the histopathology diagnosis. Malignant struma ovarii is rare making it challenging to treat since there are no established prognosticating histopathologic or clinical characteristics. The tumor size and metastasis determine the surgical treatment scope. Large-scale investigations are essential for prognostication and treatment options considering pathologic traits.

RET/PTC rearrangement in papillary thyroid carcinoma arising in malignant struma ovarii with abdominal wall metastasis and cervical thyroid gland: a case report and review of the literature.

BACKGROUND: Struma ovarii refers to rare mature cystic teratomas containing at least 50% of thyroid tissue, and malignant transformation is known to be even rarer. The synchronous development of malignant struma ovarii and cervical thyroid carcinoma are also scarce and poorly understood due to limited data about molecular features. Here, we present the first report of RET/PTC 1 rearrangement in synchronous metastatic malignant struma ovarii to the abdominal wall and cervical thyroid cancer. CASE PRESENTATION: We described a 47-year-old multigravida woman with bilateral adnexal and lower abdominal wall masses detected during the evaluation of abnormal uterine bleeding. The patient underwent a hysterectomy, bilateral salpingo-oophorectomy, and surgical removal of abdominal wall mass. Then, the pathological evaluation revealed papillary thyroid carcinoma (PTC) within struma ovarii and metastatic PTC in the abdominal wall fibro adipose tissue. Further, cervical thyroid gland physical examination and ultrasound illustrated a nodule within the left lobe. Subsequently, a total thyroidectomy was performed, and a histological examination revealed PTC. Furthermore, all affected tissue, i.e., struma ovarii, abdominal wall metastasis, and cervical thyroid gland tested for BRAF and RAS mutations and RET/PTC 1 rearrangement. RET/PTC 1 rearrangement was identified among all three different sites. Finally, after six years of follow-up, the patient had no evidence of recurrence or distant metastasis. CONCLUSIONS: In light of these findings, malignant struma ovarii might yield a clue to cervical thyroid carcinoma, and the molecular analysis could provide valuable information for understanding the underlying mechanism, tumor clinicopathological behaviors, and prognosis.

Struma ovarii with synchronous ascites and elevated CA125 level: a retrospective cohort study.

BACKGROUND: Benign struma ovarii (SO) with synchronous ascites and elevated CA125 level is extremely rare that the incidence, clinical characteristics, and risk factors remain unclear. METHODS: We conducted a retrospective study of patients with SO treated in our hospital between 1980 and 2022. Logistic regression was used to identify potential risk factors for SO patients presenting with ascites and elevated CA125 levels. The receiver operating characteristic (ROC) curve was used to evaluate the predictive performance of the identified risk factors. RESULTS: A total of 21 patients with synchronous ascites and elevated CA125 levels were identified in 229 patients with SO, the crude incidence rate was 9.17%, and four patients (1.75%) had pseudo-Meigs' syndrome. Ascites were completely involuted within 1 month postoperatively and the serum CA125 level decreased to normal between 3 d and 6 weeks after surgery. Multivariate logistic regression showed that age ≥49 years (OR 3.71, 95% CI 1.29 - 10.64, p = 0.015), tumor size ≥10.0 cm (OR 8.79, 95% CI 3.05 - 25.35, p < 0.001), and proliferative SO (OR 11.16, 95% CI 3.01 - 41.47, p < 0.001) were the independent risk factors for patients presenting ascites and elevated CA 125 level. The ROC curve revealed that the predictive performance for age and tumor size was unsatisfactory with an area under the curve (AUC) was 0.646 and 0.682, respectively. Linear regression demonstrated that the serum CA125 level has a moderate positive correlation with the volume of ascites (log2CA125 = 0.6272*log2ascites + 2.099, p = 0.0001, R2 = 0.5576). CONCLUSIONS: Less than one-tenth of patients with SO would present ascites and elevated CA125 levels, while age ≥49 years, tumor sizes ≥10 cm, and the presence of proliferative SO were the risk factors.

Concurrent Intrathyroidal Follicular Variant of Papillary Thyroid Carcinoma with Malignant Struma Ovarii Presenting 12 Years After Initial Diagnosis.

Malignancy in struma ovarii is rare and observed in only 5%-10% of patients. Here, we present a patient with malignant struma ovarii and coexisting intrathyroidal papillary thyroid carcinoma, with recurrence (large pouch-of-Douglas mass) and metastases (bilateral pulmonary and iliac nodal metastases) presenting 12 y after surgery. The notable features in this case were a concurrent intrathyroidal follicular variant of papillary carcinoma; the highly functioning nature of the malignant lesions, characterized by a low level of thyroid-stimulating hormone even without thyroxine suppression; and the low-grade 18F-FDG avidity of these lesions, consistent with their well-differentiated nature. With the adoption of a multimodality approach (surgery, radioiodine scintigraphic evaluation, and multiple radioiodine therapies), the patient showed a progressive decrease in the functionality of the disease, prolonged progression-free survival, and a good quality of life with symptom-free status at 5 y.

A Curious Case of Omental Oxalate Crystals in a Patient With Struma Ovarii: Pointers to an Unusual Clinicopathological Scenario.

Percutaneous image-guided biopsies are becoming increasingly common in routine pathology practice, with the greater omentum emerging as a common target. We present herein an account of a middle-aged lady with a complex ovarian mass, omental thickening, and raised serum CA125; clinically suspected to have advanced ovarian malignancy. Fine needle aspiration cytology (FNAC) from the ovarian mass was inconclusive. Omental biopsy revealed only refractile, birefringent crystalline material with surrounding foreign body giant cell reaction; thus surprising the clinical team. Subsequent resection of the ovarian mass showed a teratoma composed exclusively of thyroid tissue, diagnosed as struma ovarii. The omental crystals, interpreted as calcium oxalate crystals, were possibly a consequence of colloid seeding during the ovarian mass FNAC.

Malignant Struma Ovarii (Papillary Carcinoma) with Hyperthyroidism: A Case Report and Literature Review.

Malignant struma ovarii (MSO) is an extremely rare monodermal ovarian teratoma. Preoperative diagnosis and intraoperative freezing diagnosis are exceedingly difficult due to the rarity of the disease and its clinically noncharacteristic manifestations with less than 200 reports in the current literature. In this paper, a case of MSO (papillary carcinoma) with hyperthyroidism was discussed in terms of its epidemiology, clinicopathology, molecular features, treatment, and prognosis.

Clinical Characteristics, Treatment, and Outcomes of Peritoneal Strumosis: A Report of Three Cases and Systematic Review.

Benign struma ovarii (SO) has a probability of metastasis named "peritoneal strumosis", which is extremely rare, such that the specific clinical characteristics, treatment options, and survival outcomes remain unclear. We screened three cases of peritoneal strumosis among 229 cases of SO treated in our hospital. Case 1 was a 36-year-old woman with extensive peritoneal seedings at initial presentation. The second one was a 49-year-old with trocar site implant 11 years after laparoscopic adnexectomy. Case 3 was a 45-year-old woman who had an isolated lesion at the anterior surface of the rectum after laparoscopic ovarian cystectomy for SO 14 years ago. These three patients underwent surgery without any adjuvant treatment and remained disease-free after 30 to 68 months. A systematic review was then conducted and another 16 cases were identified. More than half (10/19, 52.6%) of the patients had previous SO-related ovarian surgery. The median interval between prior SO-related surgery and the initial presentation of peritoneal strumosis was 10.0 years; both regional and distant metastasis, even in the liver, lung, and heart, could also be affected. Surgery was the mainstay therapy (18/19, 94.7%), in which six patients (6/19, 31.7%) were treated with total thyroidectomy (TT) followed by radioiodine (RAI) therapy. Postoperative chemotherapy was only applied in one patient, and the last one only received a diagnostic biopsy without further treatment. Recurrence was noted in two patients with a median recurrence-free survival of 12 years, where surgical excision and RAI were then performed. No death occurred after a mean follow-up of 53 months, where 12 patients achieved no evidence of disease and five were alive with the disease. Peritoneal strumosis has unpredictable biological behaviors and the crude incidence is approximately 1.3% in SO. Patients with peritoneal strumosis have excellent survival outcomes, irrespective of different treatment strategies employed. Surgery with personalized RAI should be preferred and long-term close monitoring is recommended.