Ovarian metastasis in a young woman with follicular thyroid carcinoma: A differential diagnosis with struma ovarii.

The prognosis of the follicular variant of papillary thyroid carcinoma (FVPTC) falls between that of classical papillary thyroid carcinoma (cPTC) and follicular thyroid carcinoma (FTC) (1). FVPTC has lower mortality and less frequent distant metastases than FTC, but higher mortality and more frequent distant metastases than cPTC. FVPTC has fewer lymph node metastases and less frequent infiltrative disease and extrathyroidal extension than cPTC, but more than FTC. But is it a hybrid disease or a mixture of diseases? The pathological appearance of a follicular-patterned tumor with the nuclear features of cPTC suggests that FVPTC is a hybrid. However, the heterogeneous nature of the disease and the mutational profile of FVPTC strongly suggest that it is a mixture of diseases (2). It is the intersection of classical descriptive pathology and modern molecular biology that permits an understanding of this group of diseases.

Sir, A 47-year-old female presented with pain in the right iliac fossa and excess menstrual bleeding since five months. Pain was non-radiating, gradual in onset and of moderate intensity. She was obese and anaemic. Abdominal examination revealed a single, soft to cystic, slightly mobile and non-tender mass in the right iliac fossa measuring 12x10cm. Examination of other systems were nil remarkable. Her haemoglobin was 11 gm/dl, TC, DC, Platelet count and urine examination was with in normal limits. Viral markers (VDRL, H.I.V and HBsAg) were nonreactive. Ultrasound abdomen revealed bulky anteverted uterus with fibroid in the anterior wall near the fundus and large right ovarian cyst. She was posted for total abdominal hysterectomy and right salpingoopherectomy. During surgery, there were no signs of capsular invasion or metastasis. Postoperative recovery is good. Gross examination revealed a 4cm size fibroid in the body of the uterus and right ovarian cyst of size 15x15x12cm. Cut section of right ovarian cyst showed grey brown solid area measuring 7x7x5cm and a unilocular cystic area filled with light brown colour fluid. Histopathology revealed follicular variant of papillary thyroid carcinoma arising from pre-existing struma ovarii of right ovarian cyst and interstitial leiomyoma of uterus [Table/Fig-1a-c] [Table/Fig-1a-d]: (a) Struma ovarii (HE (b-c) Thyroid type of papillary carcinoma (H&E, X100), (H&E, X400) - Microfollicles lined by cuboidal follicular ... To rule out occult teratocarcinomas, alpha-fetoprotein (2.02ng/ml) and alpha-1-antitrypsin (1.56g/dl) levels were estimated postoperatively, they were with in normal limits. Thyroid profile was within normal limits. To rule out occult primary, ultrasound neck and FNAC of thyroid was done and it revealed adenomatous goitre [Table/Fig-1d] Serum thyroglobulin levels were estimated after 6 months of the surgery they were within normal limits (2.8ng/ml). Struma ovarii is a monodermal variant of ovarian teratoma, which was composed of more than 50% of thyroid tissue. Malignant transformation of struma ovarii occurs rarely. Papillary and follicular thyroid carcinomas are the most frequent types of malignancy to occur in struma ovarii, whereas anaplastic and medullary carcinomas occur rarely [1]. A new variant of follicular carcinoma i.e. highly differentiated follicular carcinoma of ovarian origin (HDFCO) has been described by Roth and Karseladze which has an innocuous appearance, resembling that of nonneoplastic thyroid tissue in both the ovary and sites of dissemination [2]. Strumal carcinoid is a distinctive form of ovarian teratoma characterized by a mixture of thyroid tissue and carcinoid. Thyroid-type carcinoma can occur in strumal carcinoid [3]. Follicular variant of papillary thyroid carcinoma arising in struma ovarii exhibit diffuse positivity for CK19 and HBME-1(hector battifora mesothelial cell-1) which is similar to follicular variant of papillary carcinoma in cervical thyroid. Molecular analysis has revealed activating mutations of BRAF, NRAS, KRAS, RET/PTC and NTRK1 in approximately 70% of all follicular cell–derived thyroid carcinomas [1]. Surgical treatment includes total abdominal hysterectomy, plus bilateral salpingo-oophorectomy with omentectomy in postmenopausal women, or in premenopausal women who have completed childbearing [1]. Young women, with unilateral lesion without evidence of capsular invasion or gross metastasis, unilateral oophorectomy or strumectomy (cystectomy), should be performed for preservation of fertility [1]. Adjuvant therapy includes radioactive iodine ablation, external radiotherapy and chemotherapy. Radioactive iodine is the first-line therapy for treatment of recurrent disease [1]. Prognostic factors such as tumour size, extensive adhesions, capsular invasion, peritoneal dissemination, lymph nodal metastasis and solid histologic architecture were associated with an increased incidence of recurrence or metastasis. Anaplastic carcinoma is the most aggressive tumour type, followed by follicular, papillary and HDFCO is the least aggressive [4].

Struma ovarii has elicited considerable interest because of its many unique features since Ludwig Pick first elucidated its relationship to teratoma in the early part of the 20th century. In this article, we report 3 cases of papillary and 1 of follicular thyroid carcinoma; 2 of these cases were associated with mature cystic teratoma. Metastases occurred in 2 patients, and 1 died of neoplasm. In regard to the occurrence of thyroid-type carcinoma in struma ovarii, precise terminology should be used, and the expression malignant struma ovarii was avoided as a diagnostic term. Upon review of the literature, papillary carcinoma and follicular carcinoma are the most frequent types of malignancy to occur in ovarian struma; other forms of thyroid carcinoma occur only rarely. The diagnostic criteria for cases of papillary carcinoma are similar to those described in the cervical thyroid gland and are based primarily on nuclear and architectural features. In reference to follicular carcinoma, invasion into the surrounding ovarian tissue, vascular invasion, or metastasis is evidence of malignancy. Histological malignancy in a struma does not necessarily equate with biological malignancy, and the majority of thyroid-type carcinomas do not spread beyond the ovary. Occasionally, metastases of ovarian struma have an innocuous histological appearance, and such cases are referred to as highly differentiated follicular carcinoma of ovarian origin (HDFCO). Because its histological appearance resembles that of nonneoplastic thyroid, HDFCO characteristically cannot be diagnosed until the neoplasm spreads beyond the ovary. In this article, we apply the term typical thyroid carcinoma to those forms of thyroid malignancy arising in ovarian struma that closely resemble the types described in the cervical thyroid gland to distinguish them from HDFCO. Typical follicular carcinoma is more aggressive than the somewhat more common papillary carcinoma, and HDFCO is the least aggressive of these tumor types. Cases of thyroid-type carcinoma arising in the ovary sometimes lack evidence of preexisting struma. The more aggressive thyroid-type neoplasms can arise in thyroid tissue within a mature cystic teratoma, or they may overgrow and replace the struma. Primary thyroid-type carcinoma must be distinguished from rare instances of ovarian metastases that originate in the cervical thyroid gland and the less differentiated forms from other ovarian neoplasms such as clear cell adenocarcinoma and tumors with an oxyphilic appearance. In the differential diagnosis with other ovarian neoplasms, cases of thyroid-type carcinoma associated with strumal carcinoid should not be diagnosed as malignant strumal carcinoid because the latter diagnosis might lead to suboptimal therapy.

Follicular Thyroid Tumors with the PAX8-PPARγ1 Rearrangement Display Characteristic Genetic Alterations

Introduction: Struma ovarii is a rare monodermal variant of ovarian teratoma diagnosed when thyroid tissue is more than 50% of the overall tissue. It represents only 1% of all ovarian tumors. The vast majority of struma ovarii are benign (95%); however, malignant tumors have been reported in a small percentage of cases. The most common type is papillary carcinoma(PTC), followed by typical follicular carcinoma found in the pathology after surgical oophorectomy. We report a case of malignant struma ovarii with follicular carcinoma in the setting of additional micro PTC found after total thyroidectomy. Case report: A 48-year-old female presented with right-sided pelvic pain and a mobile pelvic mass. Pelvic MRI showed noted a large complex solid mass with cystic components in the right adnexa. It measured 7.7 x 8.4 x 6.7 cm. Subsequently, the patient underwent a robotic hysterectomy, bilateral salpingo-oophorectomy (TAHBSO), bilateral pelvic and para-aortic lymph node sampling, omentectomy and resection of nodules. Final pathology noted an ovary with struma ovarii with well-differentiated follicular carcinoma, peritoneal nodules containing thyroid tissue and benign lymph nodes. Subsequently, iodine 123 SPECT CT showed physiologic uptake in the thyroid with increased uptake in the pelvis, right perirectal region indicating residual thyroid tissue. The patient underwent total thyroidectomy with radioactive ablation with I131 (154.7 mCi). Pathology detected incidental 0.5mm micro PTC and it was classified as staged pT1aN. 6 months postoperatively, thyroglobulin (Tg) and Tg antibodies were undetectable with no abnormalities found on repeat whole-body scans. The patient has been following up with no new issues for the past 5 years indicating a good prognosis with low risk of recurrence. Discussion and Conclusion: In the literature, Struma ovarii containing thyroid-type carcinoma and papillary or follicular thyroid carcinoma metastasizing to the ovary has been documented. The standard treatment of a patient with malignant struma ovarii is TAHBSO and complete surgical staging, including peritoneal washings for cytology, pelvic and para-aortic lymph node sampling, and omentectomy. In cases with the residual malignant disease after surgery, total thyroidectomy and radioactive ablation are recommended. Our case is a unique case given the presence of 2 different thyroid carcinoma in the same patient. In addition, our patient had multiple risk factors for recurrence including large lesions>4 cm, extra ovarian extension, and the coexisting synchronous primary thyroid cancer, however, she had a good prognosis with no recurrence during the 5 years follow up period.

Clinicopathologic significance of histologic vascular invasion in papillary and follicular thyroid carcinomas.

Background: Thyroid neoplasm is the commonest endocrine neoplasm. More than 80% of thyroid malignancies are papillary thyroid carcinoma (PTC) followed by follicular carcinoma (FC). The diagnosis of papillary thyroid carcinoma is based on characteristic nuclear morphology of a thyroid neoplasm. In contrast, follicular variant of PTC may cause, if the nuclear features of PTC are insufficiently appreciated, severe problems in differentiating from follicular thyroid carcinoma. Several immunohistochemical (IHC) markers such as P63 and CD56 have been recommended to differentiate between this two thyroid malignancies with overlapping histomorphology. Objectives: Our aim was to identify the possible diagnostic role of P63 and CD56 immunoexpression that distinguish PTC, including the follicular variant from follicular thyroid carcinoma. Methods: This cross-sectional descriptive study was conducted in the Department of Pathology, Rajshahi Medical College from March 2020 to February 2022. A total of 44 cases, histologically confirmed as papillary and follicular thyroid carcinoma were included in the study. Immunohistochemistry was done for P63 and CD56 from selected paraffin blocks. Results: Histologically, 39 cases were diagnosed as papillary thyroid carcinoma (27 were classical PTC & 12 were FVPTC) and the rest 5 were follicular thyroid carcinoma. In this study, mean age of the patients was 40.86 ± 6.57 years (SD) and male to female ratio was 1:2.4. P63 showed 74.4% positivity with papillary thyroid carcinoma. Positive immunoreactivity of P63 was highly significant in distinguishing papillary from follicular thyroid carcinoma (P=0.003). Combined P63 positive CD56 negative (P=0.048) and P63 negative CD56 negative immunoexpression (P=0.039) were statistically significant in differentiating papillary from follicular thyroid carcinoma. Conclusion: This study suggested that the use of P63 and CD56 may be helpful in the diagnosis of papillary and follicular thyroid carcinoma along with histopathological examination and their combination may also help in this purpose.

Snail Family Transcription Factors Are Implicated in Thyroid Carcinogenesis

This study evaluated differences in Claudin-1 expression between follicular adenoma (FA), follicular thyroid carcinoma (FTC), follicular variant papillary thyroid carcinoma (FV-PTC), and papillary thyroid carcinoma (PTC). This study used a cross-sectional approach. Immunostaining using the polyclonal antibody Claudin-1 was performed on 75 samples divided into 20 samples for follicular adenoma, follicular thyroid carcinoma, papillary carcinoma, and 15 samples of follicular variant thyroid carcinoma, respectively. Claudin-1 expression is detected on the cytoplasmic membrane of tumor cells and appears to be varied among thyroid neoplasms. The claudin-1 expression score revealed a statistically significant difference between FA against FV-PTC, FA versus (vs) PTC, and FTC vs PTC, with median values of 4 vs 6 (p = 0.016), 4 vs 8 (p = 0.001), and 5 vs 8 (p = 0.002), respectively. However, there was no statistically significant difference in scores between the FA and the FTC (4 vs 5), or between the FTC and the FV-PTC groups (5 vs 6 (p=1,000). These results suggest that Claudin-1 may be capable of discriminating follicular adenoma from classic and follicular variant of papillary thyroid carcinoma. It can also differentiate follicular thyroid carcinoma and papillary thyroid carcinoma, especially for cases challenging to assess by hematoxylin and eosin staining. It still holds promise in providing targeted cancer therapy.

Struma ovarii (SO) is a rare ovarian tumor, constituting 1% of all ovarian tumors and 3% of ovarian teratomas, predominantly composed of thyroid tissue. While typically benign, SO can undergo malignant transformation. We report a case of a 41-year-old woman with a six-month history of abdominal distention. Imaging revealed a solid cystic mass in the right adnexa with ascites and elevated CA125 levels. The surgical intervention included a hysterectomy and bilateral salpingo-oophorectomy, with pathology confirming struma ovarii with follicular thyroid carcinoma. Postoperative recovery was uneventful, and all follow-up tests were normal. This case underscores the diagnostic challenge posed by SO due to its resemblance to ovarian cancer and highlights the importance of thorough exploration, pathological examination, and long-term follow-up. Serum thyroglobulin levels can be an effective marker for monitoring tumor recurrence. Our findings contribute to the understanding and management of SO with malignant transformation.

Objective To investigate the value of plasma microRNA (miRNAs, miR)-21 in differentiating thyroid follicular carcinoma from thyroid papillary carcinoma. Methods 45 patients with thyroid follicular carcinoma, 61 patients with thyroid papillary carcinoma and 50 normal subjects were selected as subjects. The expression of miR-21 in plasma was detected by real-time fluorescent quantitative polymerase chain reaction (FQ-PCR). Receiver operating characteristic (ROC) curve was established to analyze the cut-off value, sensitivity and specificity of miR-21 in differentiating thyroid follicular carcinoma from papillary thyroid carcinoma. Results The relative expression levels of miR in plasma of normal persons, follicular thyroid carcinoma and papillary thyroid carcinoma were 0.254±0.123, 4.047±1.499 and 1.274±0.581, respectively. There was significant difference among the three groups (P=0.010). The relative expression level of miR-21 in plasma of follicular thyroid carcinoma was significantly higher than that of papillary thyroid carcinoma. The relative expression of miR-21 in plasma of patients with thyroid papillary carcinoma was significantly higher than that of normal subjects (P=0.010). The ROC curves were established with plasma levels of miR as test variables and thyroid follicular carcinoma and thyroid papillary carcinoma as state variables. The area under the curve (AUC) was 0.931 [95% confidence interval (CI): 0.890-0.991]. The optimum cut-off value (Cut-off value) for differentiating follicular thyroid carcinoma from papillary thyroid carcinoma was 2.325. The sensitivity and specificity were 85.11% and 96.72% respectively, the positive predictive value and negative predictive value were 95.24% and 89.39% respectively, and the Yorden index was 81.83%. Conclusion Detection of the expression of microRNA-21 in plasma is helpful to differentiate follicular thyroid carcinoma from papillary thyroid carcinoma and to differentiate follicular thyroid carcinoma from follicular thyroid carcinoma. Key words: MicroRNA-21; Thyroid follicular carcinoma; Papillary thyroid carcinoma; Differential diagnosis

Background: No previous study has investigated the computed tomography (CT) characteristics of follicular thyroid adenoma (FTA) and follicular thyroid carcinoma (FTC). This study aimed to compare the CT features of FTA and FTC. Methods: Eighty-seven consecutive patients with FTA or FTC that underwent preoperative neck CT from January 2006 to December 2013 were included. In each case, single radiologist retrospectively examined the corresponding neck CT under blinded conditions for the histopathological results. The CT features of FTA and FTC were evaluated, as well as the specific CT features for differentiating FTC from FTA. Results: After matching the CT and histopathological results, 55 FTAs and 25 FTCs in 80 patients were analyzed. No statistically significant differences were detected in patient age, gender, nodular size, or location between FTA and FTC patients. The most common CT features in both FTA and FTC included low attenuation, intraglandular configuration, smooth margin, round shape, absence of calcifications, and inhomogeneous enhancement. In particular, the prevalence of decreased, iso-, and increased enhancement was similar in both FTA and FTC. The prevalence of homogeneous attenuation in FTC was higher, whereas the prevalence of inhomogeneous attenuation in FTA was higher. The logistic regression analysis revealed no significant differences between FTA and FTC in any CT features, except for the pattern of attenuation (p = 0.002). Conclusion: No specific CT features of FTA and FTC were identified, and CT may be unhelpful for distinguishing FTC from FTA.

Objective: To explore the molecular characteristics of follicular variant papillary thyroid carcinoma (FVPTC), follicular thyroid adenoma (FTA) and follicular thyroid carcinoma (FTC), and investigate their role in tumorigenesis, differential diagnosis and prognosis evaluation in patients with follicular thyroid neoplasm. Methods: We retrospectively analyzed 50 surgical resection samples of follicular thyroid neoplasm. DNA was obtained from formalin-fixed, paraffin-embedded tissue, and subjected to next-generation sequencing (NGS) to analyze 50 hotspots for mutation in genes. Results: 47 samples passed quality control, including 29 FVPTCs, 8 FTAs and 10 FTCs. 75.9% of FVPTCs harbored mutated genes: BRAF V600E (31.0%, 9/29) was the most frequent, followed by TP53 (27.6%, 8/29), and N/KRAS (20.7%, 6/29). In contrast, 37.5% (3/8) FTAs carried NRAS Q61R mutation with 12.5% (1/8) FTA carrying mutated BRAF G466E. 20% (2/10) FTCs harbored NRAS Q61R mutation, and 20% (2/10) FTCs with TP53 mutations. BRAF V600E gene mutation only appeared in FVPTC, and was associated with age of onset and lymph node metastasis. There was no significant correlation between N/KRAS mutations and clinical pathologic features. Patients with lymph node metastasis group seems to have more TP53 mutation. Conclusions: BRAF V600E gene mutation can be used to identity FVPTC from FTA/FTC. N/KRAS mutations cannot be used as the exclusive indicator of benign and malignant in thyroid follicular tumor. TP53 mutations play an important role in the process of follicular thyroid neoplasm, indicating more aggressive behavior and poor prognosis.

Overexpression of mir-129-1, miR-146b, mir-183, and mir-197 in follicular thyroid carcinoma and adenoma tissues

Objective To study the appearance of follicular thyroid carcinoma (FTC) and medullary thyroid carcinoma (MTC) on color ultrasound and the value of differential diagnosis of ultrasound.Methods The data on 41 patients with FTC and 51 patients with MTC lesions were analyzed retrospectively.The ultrasound appearance and pathological features of these two types of cancer were compared.Results Follicular carcinoma had a higher incidence rate than medullary carcinoma in female (P＜0.05).Medullary carcinoma was easier to occur lymph node metastasis than follicular carcinoma (P＜0.05).Most of ollicular carcinomas had clear surroundings without interior calcification,while medullary carcinoma had unclear surroundings with internal calcification (P＜0.05).Blood supply to cancerous tissues also differed between the two types of cancer (P＜0.05).Conclusions Color ultrasound appearance is of significance in the differential diagnosis of follicular thyroid carcinoma and medullary thyroid carcinoma,which is helpful in the establishment of therapeutic regimens. Key words: Thyroid carcinoma; Follicular; Medullary