Classic Papillary Thyroid Carcinoma Research Articles

The expression of VISTA on CD4+ T cells associate with poor prognosis and immune status in non-small cell lung cancer patients.

V-domain immunoglobulin suppressor of T-cell activation (VISTA) is a novel negative immune checkpoint considered to be relevant to immunotherapy resistance and a potential target for immunotherapy. In this study, we investigated the relevance of VISTA expression on CD4+ T cells and clinical prognosis in non-small cell lung cancer (NSCLC) patients. Tumor tissue samples from 140 NSCLC patients were organized into a tissue microarray. The prognostic value of CD4+ VISTA+ T cells was analyzed through immunohistochemistry and multicolor fluorescence immunostaining. Fresh tumor tissue samples from 33 NSCLC patients were collected and similarly analyzed to confirm the immune state of patients with VISTA expression on CD4+ T cells by flow cytometry. CD4+ VISTA+ T cells were significantly more infiltrated in tumor tissues. The expression of VISTA on CD4+ T cells was correlated with the reduced overall survival of patients with NSCLC and presented a high rate of lymphocyte metastasis. The expression of VISTA on CD4+ T cells in tumor tissue showed low secretion of cytokines including IFN-γ, IL-2, IL-4, IL-10, IL-17, and IL-12p70. The expression of VISTA on CD4+ T cells could regulate tumor immunity and serve as a prognostic indicator for survival outcomes.

Does Locally Advanced Thyroid Cancer Have Different Features? Results from a Single Academic Center.

Background: Despite the fact that the majority of thyroid cancers are indolent, 15% of patients with well-differentiated carcinoma including papillary thyroid carcinoma (PTC) present with locally advanced thyroid cancer (LATC) at diagnosis. The current study analyzes a cohort of patients with LATC focusing on their risk for local recurrence, distant metastases, and overall survival. Materials and methods: From January 2010 to December 2020, 65 patients with LATC were retrieved, including 42 cases with preoperative cytological samples. BRAFV600E and TERT mutations were performed on both cytology and histopathology specimens in this cohort. Results: Among the 65 cases, 42 (65%) were women. The median age was 60.1 years. Histological diagnoses included 25 (38.4%) with classic PTC and 30 (46.1%) aggressive variants of PTC, mostly tall cell variant (17 cases, 26.1%). Multifocality was seen in 33 cases (50.8%). All patients had nodal metastases. The most common site of extrathyroidal extension was the recurrent laryngeal nerve (69.2%). Staging revealed 21 cases were stage I, none were stage II, 33 were stage III, and 7 were stage IVa and 4 stage IVb. No differences were found between well and poorly/undifferentiated thyroid cancers. Conclusion: These data suggest that locally advanced thyroid cancers, including variants of PTC, exhibit a more aggressive biological course and should accordingly be more assertively managed.

Evaluation of ITGA3 as a Biomarker of Progression and Recurrence in Papillary Thyroid Carcinoma.

ObjectiveTo investigate the expression of ITGA3 and its association with clinical outcomes in papillary thyroid carcinoma (PTC).MethodsThe expression level, association with clinicopathologic characteristics, co-expressed genes, signaling pathways of ITGA3 in thyroid cancer were comprehensively analyzed using bioinformatics analysis through multiple public gene databases. PTC specimens and cell lines were used to verify the results of bioinformatics analysis.ResultsData mining based on the Oncomine database revealed that ITGA3 expression in classical PTC and tall cell variant PTC was much higher than that in normal thyroid tissue except the follicular variant PTC. Analysis based on The Cancer Genome Atlas (TCGA) database showed that the expression of ITGA3 varies greatly in pathological stages, pathological types, tumor invasion stages, and lymph node metastasis stages of thyroid carcinoma. High expression level of ITGA3 was correlated with tumor regional invasion and lymph node metastasis. Multivariate analysis using logistic regression model showed that high expression of ITGA3 was a risk factor that associated with PTC recurrence and lymph node metastasis. Survival analysis showed that patients with high expression of ITGA3 in PTC had a poorer relapse-free survival (RFS) than patients with low expression of ITGA3 (P < 0.05). Immunohistochemistry experiments showed that the expression of ITGA3 in recurrent thyroid cancer tissues was stronger than that in no-recurrent thyroid cancer tissues (P < 0.05). Knockdown of ITGA3 by sh-RNA in PTC cell lines suppresses cell viability and invasive and migrating capacity.ConclusionITGA3 is overexpressed in PTC, especially in those with higher tumor invasion grades and lymph node metastasis, and was associated with recurrence and poor RFS of PTC. High expression of ITGA3 may have the potential role of predicting PTC recurrence and lymph node metastasis.

Atypical histiocytoid cells in fine-needle aspiration cytology of metastatic papillary thyroid carcinoma: A potential diagnostic pitfall.

Fine needle aspiration (FNA) cytology of cervical lymph nodes is an effective diagnostic tool to detect metastatic papillary thyroid carcinoma (PTC) when typical cytomorphologic features of PTC are observed. However, the presence of atypical histiocytoid cells (AHCs) due to cystic degeneration sometimes poses a diagnostic challenge. The purpose of this study was to evaluate the presence and cytomorphology of AHCs in metastatic PTC. We analyzed a total of 76 FNA cytological samples of cervical lymph nodes from 66 patients with metastatic PTC diagnosed during approximately 10-year period, from January 2010 to April 2020. Samples were either liquid based preparation (n=53) or conventional smear (n=23). AHCs were present in 38 (50%) of the 76 FNA cases and the remaining 38 cases showed classic PTC features. Among the 38 cases, eight displayed pure AHCs that constituted 10.5% of all the metastatic PTC in the lymph nodes. Pure AHCs were more commonly detected in the liquid based preparation (7/53, 13.2%) than the conventional smear (1/23, 4.3%). The remaining 30 cases had AHCs mixed with the characteristic PTC components. The presence of AHCs was found to be statistically associated with cystic background (p < .002). Metastatic PTC frequently exhibits cystic degeneration and the FNA cytology may not yield classic cytological features of PTC. Pure AHCs composed 10.5% of all cases and might be a potential pitfall for liquid based preparation in diagnosing metastatic PTC. The finding of AHCs within the cystic background should raise the concern of metastatic PTC.

Clinical and Sonographic Features of Noninvasive Follicular Thyroid Neoplasm With Papillary-Like Nuclear Features: A Retrospective Study.

This study was designed to investigate the clinical and sonographic features of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTPs) as compared with classical papillary thyroid carcinoma (cPTC), follicular adenoma (FA), and follicular thyroid carcinoma (FTC). A total of 178 patients were enrolled in this study. The clinical characteristics and sonographic features of thyroid nodules were compared between NIFTP and cPTC or FA/FTC. All nodules were reclassified according to the Thyroid Ultrasound Imaging Reporting and Data System and American Thyroid Association guidelines classification. The mean size of NIFTP was 29.91 ± 14.71 mm, which was larger than that of cPTC ( P = 0.000). Significant difference was found in lymph node metastases between NIFTP and cPTC ( P = 0.000). Most NIFTPs showed solid composition, hypoechoic echogenicity, smooth margin, wider than tall shape, none echogenic foci, absence of halo, and perinodular vascularity, which were similar with FA and FTC. Compared with NIFTP, hypoechoic and very hypoechoic, taller than wide, irregular margin, punctate echogenic foci, absence of halo, and low vascularity were more commonly observed in cPTC. There were statistical differences both in American College of Radiology Thyroid Ultrasound Imaging Reporting and Data System and in American Thyroid Association classification between NIFTP and cPTC ( P < 0.05), but there were no significant differences between NIFTP and FTC/FA ( P > 0.05). The ultrasonographic characteristics of NIFTP were obviously different from cPTC but overlapped with FTC and FA. Ultrasound could help increase preoperative attention of NIFTP in an appropriate clinical setting, which may lead to a more conservative treatment approach.

Comparison of the clinicopathological features and oncologic outcomes of the classic papillary thyroid carcinoma with tall cell features and tall cell variant.

The tall cell variant (TCV) of papillary thyroid carcinoma (PTC) (TCVPTC) is the most common aggressive variant of PTC. Classic PTC with tall cell features (TCF) is defined as PTC with noticeable tall cells but the percentage of these cells is lower than that required for the diagnosis of TCVPTC. We aimed to investigate the potential differences between TCVPTC and classic PTC with TCF with respect to clinicopathological characteristics and oncologic outcomes. We retrospectively assessed 509 patients with TCVPTC or classic PTC with TCF who underwent thyroid surgery between January 2013 and December 2018 at the Seoul St. Mary's Hospital (Seoul, Korea). Clinicopathological characteristics and oncologic outcomes between TCVPTC and classic PTC with TCF were compared in terms of disease-free survival (DFS). The mean follow-up duration was 70.7±21.7 months. The mean tumor size was significantly larger in the TCVPTC group. There was no significant difference between the TCVPTC and classic PTC with TCF groups with respect to DFS. Tumor size >2 cm [odds ratio (OR), 1.922; P=0.019], bilaterality (OR, 1.668; P=0.030), extrathyroidal extension (ETE) (OR, 2.352; P=0.002), and lateral LN metastasis (OR, 1.700; P=0.045) were significantly associated with TCVPTC compared with classic PTC with TCF. TCVPTC and classic PTC with TCF have similar clinicopathological characteristics and oncologic outcomes. Therefore, we suggest a potential re-classification of classic PTC with TCF from low-risk to intermediate-risk category in the American Thyroid Association (ATA) risk stratification system.

Three-dimensional telomere profiles in papillary thyroid cancer variants: A pilot study.

Besides the two main histologic types of papillary thyroid carcinoma (PTC), the classical PTC (CL-PTC) and the follicular variant PTC (FV-PTC), several other variants are described. The encapsulated FV-PTC variant was recently reclassified as non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) due to its similarities to benign lesions. Specific molecular signatures, however, are still unavailable. It is well known that improper DNA repair of dysfunctional telomeres may cause telomere-related genome instability. The mechanisms involved in the damaged telomere repair processing may lead to detrimental outcomes, altering the three-dimensional (3D) nuclear telomere and genome organization in cancer cells. This pilot study aimed to evaluate whether specific 3D nuclear telomere architecture might characterize NIFTP, potentially distinguishing it from other PTC histologic variants. Our findings demonstrate that 3D telomere profiles of CL-PTC and FV-PTC were different from NIFTP and that NIFTP more closely resembles follicular thyroid adenoma (FTA). NIFTP has longer telomeres than CL-PTC and FV-PTC samples, and the telomere length of NIFTP overlaps with that of the FTA histotype. In contrast, there was no association between BRAF expression and telomere length in all tested samples. These preliminary findings reinforce the view that NIFTP is closer to non-malignant thyroid nodules and confirm that PTC features short telomeres.

High Incidence of Distant Metastasis Is Associated With Histopathological Subtype of Pediatric Papillary Thyroid Cancer - a Retrospective Analysis Based on SEER.

ObjectiveChildren with papillary thyroid cancer (PTC) have a higher invasive rate and distant metastasis rate, but the mortality rate is lower with unknown reasons. The majority of PTC cases comprise classical papillary thyroid carcinoma (CPTC) and follicular variant papillary thyroid carcinoma (FVPTC). This study aimed to determine the relationship between histopathological subtype and rate of distant metastasis and investigate factors influencing distant metastasis in pediatric PTC.MethodsA total of 102,981 PTC patients were recruited from SEER registry, 2004-2015. Proportion of distant metastasis between children (≤18 years) and adults with different histopathological subtypes was compared by propensity score matching. The cut-off age for distant metastasis in children was calculated by receiver operating characteristic (ROC) curve, and the risk factors for distant metastasis in pediatric patients were analyzed by logistic regression models.ResultsAmong the 1,484 children and 101,497 adults included in the study, the incidence of CPTC patients with distant metastasis in children was higher than that in adults (p<0.001). The ROC curve was calculated, which yielded a cut-off age for distant metastasis in CPTC children as 16 years old. In CPTC, the proportion of young children (2-16 years) with distant metastasis was higher than that of adolescents (17-18 years) and adults (>18 years) (both p<0.001). While there was no such trend in FVPTC. In young children (2-16 years), the incidence of CPTC with distant metastasis was higher than FVPTC (p=0.006). There was no difference between the proportion of CPTC and FVPTC with distant metastasis in adolescents (17-18 years) and adults. Logistic regression models revealed that extrathyroidal extension, lymph node metastasis and CPTC histopathological subtype were risk factors for distant metastasis in young children aged 2 -16 years.ConclusionsIn CPTC, the incidence of distant metastasis in young children (2-16 years) was significantly higher than that in adolescents (17-18 years) and adults (>18 years). In patients with distant metastasis aged 2-16 years, the proportion of CPTC was higer than that of FVPTC. Extrathyroidal extension, lymph node metastasis, and CPTC histopathological subtype were risk factors for distant metastasis in young children aged 2-16 years.

Clinicopathological features and molecular characteristics of tall cell and hobnail variants of papillary thyroid carcinoma

Objective: To investigate the clinicopathological and molecular genetic characteristics of tall cell variant and hobnail variant of papillary thyroid carcinoma (PTC). Methods: Twenty-one cases of tall cell variant (TCV-PTC) of PTC (TCV-PTC) and ten cases of hobnail variant of PTC (HV-PTC), as the highly aggressive group, were collected from Xuanwu Hospital from August 2009 to August 2015. Twenty-two cases of follicular variant and 21 classical PTC cases were included as control. Relevant clinical and pathologic data were obtained, and in some cases, paraffin samples were selected for gene mutation spectrum analysis using second generation sequencing. Results: There were 18 males and 56 females; 57 patients were younger than 55 years of age, and 17 patients were 55 years or older. The mean tumor size was 1.6 cm for the high-aggressive group (TCV-PTC and HV-PTC), 1.1 cm for the follicular subtype, and 1.6 cm for the classical type. There were 54 cases with thyroid capsule invasion, 24 cases with extra-thyroidal invasion, and 45 patients with lymph node metastases. Regional recurrence occurred in 7 cases, no recurrence in 54 cases, and 13 patients were lost to follow-up. The highly aggressive group was more likely to show extra-thyroidal invasion, lymph node metastases and recurrence than those with classical PTC (P<0.05). Within this cohort, BRAF V600E mutation was detected in 53 cases and TERT promoter mutation in 6 cases. Compared with the single mutation group and no mutation group, BRAF and TERT promoter co-mutation group was more commonly detected in older age, male, larger tumor size and more prone to extra-thyroid invasion (P<0.05). In addition, among BRAF and TERT co-mutation cases, the highly-aggressive group accounted for the highest proportion (5/6). Conclusions: TCV-PTC and HV-PTC, as highly-aggressive variants of PTC, show more aggressive biologic behavior (more lymph node metastasis, external thyroid invasion and recurrences) than the classical and follicular variants of PTC. Coexisting BRAF and TERT promoter mutations may be associated with invasive biologic behavior.

Anaplastic spindle cell squamous carcinoma arising from classical papillary thyroid carcinoma with foci of columnar cell component: A case report

We report a case of the anaplastic spindle cell squamous carcinoma(SC) arising from classical papillary thyroid carcinoma(PTC) with foci of columnar cell component in a 69-year-old Chinese woman. The tumor of the right lobe was composed of spindle cell SC and PTC. Histologically,the spindle cell SC were arranged into bundles with marked cellular atypia, nuclear pleomorphism and more mitotic figures. The tumor of the left lobe was a PTC without any SC elements,which was composed of two components, namely classical and columnar cell variants PTC. The columnar cell elements occupied more than 20 % of PTC, which showed striking stratification of nuclei with no characteristic nuclei for the classical type of PTC. The patient has not received any other treatment after radical surgery. She had no tumor recurrence and other complications 13 months after operation. Only classical PTC but not columnar cell PTC and SC had been identified in 7 out of 50 excised cervical lymph nodes. In order to clarify the origin of PTC and spindle cell SC, we performed the BRAFV600E(c.1799 T > A) mutational analysis. The results of molecular analysis showed that BRAFV600E(c.1799 T > A) mutation existed in both components, which further confirmed that spindle cell SC was transformed from PTC.

Study of variants of papillary carcinoma of Thyroid with a special emphasis on NIFTP (Non-invasive Follicular Thyroid Neoplasm with Papillary like nuclear features)

Rapid advances have taken place in the classification of papillary thyroid neoplasms with reclassification and addition of new variants. One such change is the addition of a new entity called NIFTP (Non-invasive Follicular Thyroid Neoplasm with Papillary like nuclear features). So called recognising its non-malignant potential. The present study is a retrospective observational cohort study on thyroidectomy specimens collected between Jan 2018 to June 2021 focussing on variants of papillary carcinoma with special emphasis on recognising NIFTP – which has got good prognosis and is considered non-malignant. Out of the 40 cases of papillary neoplasms 36 were PTC and 4 were NIFTP. Among the PTC cases 27 were classic PTC, 4 were FVPTC (Follicular Variant of Papillary Thyroid Carcinoma) 3 were papillary microcarcinoma, 1 was Warthin like Variant of PTC and 1 was Encapsulated PTC. The Study concludes that special vigilance is required in strictly adhering to the criteria proposed by new 2017 WHO classification of Papillary tumours. Recognising NIFTP as it is a non-malignant entity should be given due importance.

Papillary Thyroid Carcinoma with Desmoid-Type Fibromatosis: Review of Published Cases.

Simple SummaryPapillary thyroid cancer (PTC)-desmoid type fibromatosis (DTF) is one of the rarest variants of PTC. The diagnosis is histological, and detecting a mutation of CTNNB1 in the mesenchymal component is highly suggestive of PTC-DTF. The treatment is essentially surgical. We conducted a review of all cases of PTC-DTF found in the English literature and our aim is to describe patient’s characteristics, histology, immunohistochemistry and somatic mutations of every case.Desmoid-type fibromatosis (DTF) is a very rare variant of papillary thyroid carcinoma (PTC). It is essentially a dual tumor with a component of classical PTC with malignant epithelial proliferation (BRAF-mutated) and another component of mesenchymal proliferation (CTNNB1-mutated). We conducted a literature review on PTC-DTF. In total, 31 articles were identified, that together reported on 54 patients. The mean age was 47 years, with a 2.2:1 female predominance. No ultrasound features were found to be helpful in differentiating PTC-DTF from other PTC variants. Of the 43 cases that reported histological details, 60% had locally infiltrative disease (T3b or T4). Around 48% had cervical lymph node metastases, but none had distant metastases. While PTC-DTF may be locally more aggressive than classic PTC, its overall behavior is similar and can include extrathyroidal extension and lymph node metastases, which may contain a stromal component and show extranodal invasion. The mainstay of treatment for PTC-DTF is surgery, and the DTF component is not expected to be sensitive to radioactive iodine. External radiotherapy, non-steroidal anti-inflammatory drugs, tyrosine kinase inhibitors and chemotherapy have also been used in selected cases. Due to the rarity of these tumors and the lack of specific treatment guidelines, management should be discussed in a multidisciplinary team.

Expression of cancer stem cell markers in tall cell variant papillary thyroid cancer identifies a molecular profile predictive of recurrence in classic papillary thyroid cancer

BackgroundTall cell variant of papillary thyroid carcinoma is an aggressive subtype of papillary thyroid carcinoma. We examined expression of cancer stem cell markers in tall cell variant compared with other well-differentiated thyroid cancers. MethodsExpression of cancer stem cell markers was examined in 572 thyroid tumors from The Cancer Genome Atlas Thyroid Cancer database and tall cell variant and papillary thyroid carcinoma tumors by immunohistochemistry. ResultsExpression of the PROM1 gene, encoding the cancer stem cell marker CD133, was elevated in tall cell variant compared to classic papillary thyroid carcinoma in a large cohort of unmatched samples from The Cancer Genome Atlas Thyroid Cancer database (P < .001). By immunohistochemistry in age and stage matched samples, CD133 protein was confirmed to be significantly increased in tall cell variant versus classic papillary thyroid carcinoma (P = .006). Analyzing all thyroid cancers, high PROM1 expression was associated with worse disease-specific survival. Optimal cutoffs were determined to define a tall cell variant-like cancer stem cell signature characterized by high PROM1, high ALDH1A3, and low CD24 expression. Classic papillary thyroid carcinoma with a tall cell variant-like gene signature had worse recurrence disease-free survival compared to classic papillary thyroid carcinoma with a non-tall cell variant signature (P = .02). ConclusionTall cell variant of papillary thyroid carcinoma has increased expression of cancer stem cell markers compared to classic papillary thyroid carcinoma. The tall cell variant-like cancer stem cell gene signature identified a molecular subtype of classic papillary thyroid carcinoma that has a worse recurrence-free survival.

Nomograms to predict ipsilateral and contralateral central lymph node metastasis in clinically lymph node-negative patients with solitary isthmic classic papillary thyroid carcinoma

BackgroundIsthmus-originating papillary thyroid carcinoma has unique clinicopathological characteristics. There are no specific guidelines regarding the extent of surgery for isthmic papillary thyroid carcinoma. We aimed to evaluate the characteristics of clinically lymph node–negative patients with solitary isthmic papillary thyroid carcinoma and to determine the best surgical protocol for these patients. MethodsA total of 904 patients diagnosed with solitary papillary thyroid carcinoma who underwent surgery were retrospectively reviewed. These patients were divided into the isthmic group (246 patients) or lobar group (658 patients). We compared the 2 groups and conducted a multivariate analysis to assess risk factors for ipsilateral and contralateral central lymph node metastasis in isthmic papillary thyroid carcinoma patients. Nomograms for predicting central lymph node metastasis in isthmic papillary thyroid carcinoma patients were developed and internal calibration was performed for these models. ResultsIsthmic papillary thyroid carcinoma patients have a significantly higher incidence of extrathyroidal extension and central lymph node metastasis than do lobar papillary thyroid carcinoma patients. For isthmic papillary thyroid carcinoma patients, sex, BRAF V600E mutation, chronic lymphocytic thyroiditis, tumor size, margin, and extrathyroidal extension were independent risk factors of ipsilateral central lymph node metastasis. Body mass index, BRAF V600E mutation, tumor size, location, and extrathyroidal extension were independent risk factors of contralateral central lymph node metastasis. All the above factors were incorporated into nomograms, which showed the perfect discriminative ability. ConclusionBased on the predictive nomograms, we proposed a risk stratification scheme and corresponding individualized surgical treatment based on different nomogram scores. In the debate about prophylactic central neck dissection among clinically lymph node-negative patients with solitary isthmic papillary thyroid carcinoma, our nomograms provide the balance to avoid overtreatment and undertreatment through personal risk assessment.

DIFFERENCES IN AGE CHARACTERISTICS, TUMOR MACROSCOPIC SIZE AND HORMONE PROFILE BETWEEN CLASSIC PAPILLARY CARCINOMA PATIENTS AND FOLLICULAR VARIANTS IN Dr. KARIADI HOSPITAL, SEMARANG

Background: New cases of Papillary Thyroid Carcinoma and Carcinoma patients at Dr. Kariadi Hospital, Semarang is quite high, where the most types are Classical Papillary Thyroid Carcinoma and Follicular Variant Papillary Thyroid Carcinoma. On the other hand, in diagnosing PTC, histopathological examination which is a gold standard sometimes has a subjective value. Therefore, it is necessary to have a correlation with the clinical characteristics of the patient in order to get a correct diagnosis. Aim: Understanding the differences in age characteristics, tumor macroscopic size and hormone profile between Classical Papillary Thyroid Carcinoma and Follicular Variant patients at Dr. Kariadi Hospital, Semarang. Method: Analytic observational research with cross sectional design. The number of samples was 38 medical records in which 18 cases of Classic Papillary Thyroid Carcinoma and 20 cases of Follicular Variant Papillary Thyroid Carcinoma. Data with a nominal scale, namely age were analyzed using the Fisher exact test, while the data with a numerical scale, namely the macroscopic size of the tumor and the hormone profile, were tested for normality of Saphiro Wilk then continued with the Mann-Whitney test. Result: Based on the Fisher exact test, there was significant difference (p = 0,009) between age characteristics and Classical Papillary Thyroid Carcinoma and Follicular Variant. In the Mann-Whitney test there was no significant difference (p = 0.3) between the macroscopic size of the classical papillary carcinoma and follicular variant and there was no significant difference TSHs (p = 0.501) and fT4 (p = 0.953) hormone profiles between Classic Papillary Thyroid Carcinoma and Follicular Variants. Conclusion: There was significant difference between the characteristics of age at diagnosis, and there was no significant difference between the macroscopic size of the tumor and the hormonal profile of Classical Papillary Carcinoma and Follicular Variants in Dr. Kariadi Hospital, Semarang.

Malignant struma ovarii: From case to analysis.

To evaluate the clinico-pathologic features, treatment options, prognostic factors, and survival outcomes of malignant struma ovarii based on a systematic literature review in association with our case study. A systematic review of the medical literature was performed to identify articles about malignant struma ovarii from January 1983 until July 2020. We evaluated 178 cases. The 5-year progression-free survival (PFS) and overall survival (OS) of the entire cohort was 72.5% and 91%, respectively. In univariate analysis, younger age (<43 years), whole strumal cyst diameter >95 mm, presence of a histologic type other than papillary classic-type thyroid carcinoma within the tumor and lymphovascular space invasion were related to poor PFS. Patients who received radioactive iodine ablation (RIA) before the treatment failure had significantly higher PFS than those who did not receive RIA (94.9% vs. 64.8%, p= 0.041, respectively). In univariate analysis, PFS was significantly higher in patients who underwent gynecologic surgery followed by thyroidectomy and RIA compared with those who had surgical treatment only (94.5% vs. 64.3%, p= 0.05, respectively). However, this result could not be identified as an independent prognostic factor in multivariate analysis (p= 0.207). Younger age and absence of capsular involvement were related to significantly increased OS. Histologic type was the only independent prognostic factor for PFS (hazard ratio: 3.30, 95% confidence interval: 1.122-9.748; p= 0.030) CONCLUSION: The most common histologic subtype was the papillary classic type. The presence of a histologic type other than the classic papillary thyroid carcinoma within the tumor was an independent adverse prognostic factor.

Capgras syndrome and confabulation unfurling anti NMDAR encephalitis with classical papillary thyroid carcinoma: First reported case

Anti NMDA Receptor encephalitis (ANMDARE) is an immune mediated disease of the central nervous system, caused by circulating antibodies against the NMDA receptor present on neuronal surface. It is known to cause a spectrum of disease ranging from mild behavioral and psychiatric manifestations to full blown seizures, dyskinesias and altered sensorium. It can also be paraneoplastic presentation of a hidden tumor, most commonly ovarian teratoma. Here we present a case of ANMDARE with intriguing presentation of Capgras syndrome and confabulations, who was found to have a malignant papillary thyroid carcinoma, which has been rarely reported.

Incidental Diffuse Sclerosing Variant Papillary Thyroid Cancer in Grave’s Disease

The diffuse sclerosing variant papillary thyroid carcinoma (DSPTC) is an uncommon form of this neoplasm. Some studies describe its high propensity for tumor invasion, metastasis, and mortality compared with classic papillary thyroid carcinoma. Histologic features of DSPTC may resemble diffuse inflammation as seen with Grave’s or Hashimoto’s thyroiditis, which makes initial diagnosis challenging.A 27-year-old female with Noonan’s Syndrome was evaluated on an outpatient basis after developing atrial fibrillation de novo. Thyroid function tests were consistent with hyperthyroidism with TSH: <0.005 (n: 0.300-3.000 uIU/mL), FT4: 3.59 (0.71-1.85 ng/mL) and FT3: 16.77 (n: 2.0-7.0 pmol/L). Diffuse goiter was noted on physical exam, but no ophthalmopathy or dermopathy was present. TRAB and TSI were elevated at 38.4 (n: <16%) and 423% (n: <140%) respectively. A twenty-four-hour radioiodine uptake was 48% (n:10-35%) and described as essentially homogenous with two foci of decreased radiotracer concentration suggestive of cold nodules. Thyroid ultrasound showed diffuse nodularity bilaterally with associated clusters of calcifications and no discrete nodules. No abnormal appearing lymph nodes were identified. Fine-needle aspiration of both nodular areas was positive for DSPTC. Total thyroidectomy with central neck dissection was performed. Gross and microscopic post-surgical pathology confirmed the presence of diffuse sclerosing papillary thyroid cancer, along with local metastasis to one central lymph node. Patient was scheduled for radioactive iodine therapy.Diffuse sclerosing variant is considered an aggressive histotype of papillary thyroid cancer. Ultrasound features include diffuse scattered microcalcifications with or without discrete nodules that may be confused with chronic inflammatory changes. Despite the limited number of cases, DSPTC is recognized to have specific characteristics, a high female to male ratio, and a young patient age. DSPTC has a high potential for aggressive biologic behavior if not treated promptly at the time of diagnosis. When suspected, total thyroidectomy with lymph node excision followed by radioiodine therapy has been proposed as the correct management to decrease the risk of persistent or recurrent disease.

A Case of Diffuse Sclerosing Variant of Papillary Thyroid Cancer: An Aggressive Variant Presenting With Recurrent Locoregional Nodal Disease

Diffuse sclerosing variant (DSV), a subtype of papillary thyroid carcinoma (PTC), has been considered more aggressive than classical PTC given that it usually presents with extrathyroidal invasion and lymph node metastasis at the time of diagnosis. Data about the risk of recurrence and prognosis is still debatable. Hence, we report a 29-year old woman with recurrent DSV-PTC that presented with pulmonary metastasis after multiple surgical interventions, radioactive iodine (RAI) therapy and a negative whole-body scan (WBS) ten months prior to this finding.A 29-year old woman without history of systemic illness, family history of thyroid cancer or neck radiation exposure, developed diffuse goiter at age 23. A thyroid and neck ultrasound revealed an enlarged heterogeneous thyroid gland with innumerable small bright echogenicities scattered throughout and bilateral neck adenopathy. No thyroid nodules were seen. Anti-thyroglobulin antibodies (anti-Tg Ab) were positive. A fine needle aspiration biopsy (FNAB) was positive for PTC with cytologic features suggestive of DSV. Subsequently, total thyroidectomy was performed, and 15 lymph nodes were positive for PTC. Thyroid suppression therapy was started maintaining goal of TSH <0.1ng/dL. Patient had a second neck dissection one month later, where 7 lymph nodes were positive for PTC. Pathology revealed chronic lymphocytic thyroiditis with bilateral multifocal PTC and staging pT3N1b. Two months after thyroidectomy, RAI therapy was provided with 153.6mCi of I-131. Post RAI therapy WBS and SPECT/CT demonstrated persistent metastasis to lymph nodes. After this finding, a third left neck dissection was done with additional lymph nodes resection positive for PTC. A second RAI therapy with 138mCi of I-131 was administered the following year. Continued surveillance suggested recurrence of PTC due to new suspicious nodules on neck along with increased anti-Tg Ab level from 44.64 to 95 IU/mL. FNAB confirmed PTC of five different locations of the thyroid bed. She had two additional neck dissections. Metastasis of lymph nodes was confirmed at multiple levels in the right neck and central compartment. Ten months after being without evidence of PTC recurrence in previous WBS and FDG-PET/CT, she started to develop hemoptysis. A neck and chest CT scan demonstrated innumerable bilateral hyperdensities consistent with pulmonary metastasis. At this time, TSH continued suppressed in 0.06 mIU/mL but, anti-Tg Ab had increased to 160 IU/mL.DSV-PTC has been shown to be at an advanced stage upon diagnosis. Furthermore, it has been documented that distant metastasis could also be present at this time with pulmonary metastasis being the most common. Nonetheless, some authors suggest that the advanced presentation could be due to delayed diagnosis rather than DSV intrinsic behavior. Besides its aggressive nature, DSV-PTC risk of recurrence remains controversial.

Not Your Typical “Lipoma”; An Unusual Case of Thyroid Cancer Presenting With a Skull Lesion

Abstract Background: Bone metastases from thyroid cancers tends to more commonly afflict the long bones, pelvis, ribs, vertebrae and sternum. Skull metastases are exceedingly rare being found in only ~2.5% of patients with thyroid cancer, more commonly in patients with Follicular thyroid carcinomas. We present an unusual case of thyroid cancer presenting with skull metastasis. Clinical Case: A 55 year- old male with a slowly growing skull lesion was referred to our center after an attempt to remove this scalp lesion was aborted as the lesion extended through a calvarial defect. This lesion was noted by the patient 1 year prior to presentation and was slowly growing in size. He opted for watchful monitoring as this was presumed to be a lipoma at the time. Imaging revealed a 6.4 x 4.6 x 6.3 cm lesion in the left parietal region with a large extra-axial and soft tissue components with intervening bone destruction as well as adjacent dural thickening. Differential for the lesion given the radiological appearance included meningioma, hemangiopericytoma, or an osseous/dural metastasis with an unclear primary malignancy. Excision of the extra-axial parietal lesion was consistent with metastatic thyroid carcinoma (follicular variant of papillary carcinoma). Further imaging revealed a multi nodular goiter with a prominent 6 cm left thyroid nodule. Patient had no obstructive symptoms. He underwent a total thyroidectomy with findings of a 6.8 cm minimally invasive follicular carcinoma with multifocal capsular invasion and a focus of vascular invasion. The right lobe revealed 1.5 cm classic PTC. Notably, margins were free of disease and cervical lymph nodes were negative for disease. Imaging revealed no other metastatic lesions. Patient received RAI after his total thyroidectomy and was started on suppressive doses of levothyroxine. He has been followed with annual MRI Brain, USG thyroid and Thyroglobulin levels and remains free of recurrence for the past 36 months. Conclusion: Thyroid cancer can present with skull metastasis without causing significant morbidity. This is a rare manifestation of disease and can be easily misdiagnosed. This case highlights the importance of keeping a broad differential when evaluating skull lesions.