Lymphocytic Thyroiditis Research Articles

Clinical-Pathological Features of Thyroid Neoplasms in Young Patients Diagnosed in a Single Center.

Background and objectives: The aim of this study was to evaluate the clinical-pathological profile in young patients with thyroid cancer. Materials and methods: We realized a retrospective study on patients with thyroid neoplasms who underwent surgery at the "Pius Brinzeu" County Clinical Emergency Hospital in Timisoara, Romania. A comparative analysis of some parameters between two groups, young patients (<45 years) versus patients ≥45 years, was performed. Results: A total of 211 patients met the study inclusion criteria, mostly females (86.26%) with a female/male ratio of 6.81:1. In patients <45 years old (25.64%), papillary thyroid carcinoma was identified in 51.85% of cases; in 53.85% of cases, the tumor was >1 cm; 13.46% had extrathyroidal extension (p = 0.0430); 21.15% capsule invasion (p = 0.1756); 23.08% lympho-vascular invasion (p = 0.0048); and 13.46% of cases locoregional nodal invasion (p = 0.0092). Conclusions: Thyroid cancer in young people was associated with chronic lymphocytic thyroiditis and tumor progression parameters, identifying more cases of extrathyroidal extension, locoregional nodal invasion, lympho-vascular invasion and perineural invasion in young patients compared to older ones. For a better understanding of this pathology and to improve diagnosis and therapeutic management, more studies are needed for these patients.

Coexistence of microfilaria and chronic lymphocytic thyroiditis: a rare case report

Filariasis is a common health problem in tropical countries of Southeast Asia. The commonest site of involvement is the lymphatic system where the adult worms can remain viable for long periods. Though the patients can remain asymptomatic, the clinical presentation with hydrocele, fever, localised swelling and/or lymphedema are commonly seen. Localization of the parasite at various other sites like breast, lungs, and thyroid have been uncommonly described. We report a case of an elderly female who presented with a large anterior neck mass associated with a recent history of change in voice. Radiological investigations revealed a soft tissue mass in the neck along with multiple lesions in the thyroid which were suspicious of malignancy. Fine needle aspiration cytology, however, revealed microfilariae coexisting with chronic lymphocytic thyroiditis. This case highlights the importance of critical screening of cytology smears to identify the parasites at unusual locations. A correct diagnosis on a simple and inexpensive investigation like fine needle aspiration cytology can help in administering appropriate therapy at the earliest and avoiding unnecessary interventions.

Cytological Grading of Lymphocytic Thyroiditis and Its Correlation With Biochemical Parameters: An Experience From a Tertiary Care Center in North India.

Chronic lymphocytic thyroiditis is the most common cause of acquired hypothyroidism. The clinical management of thyroid nodules, with or without chronic lymphocytic thyroiditis, mainly depends on clinical data, ultrasonography, and fine-needle aspiration cytology (FNAC), the latter being the gold standard for the pre-surgical diagnosis of thyroidal nodules. The grading of chronic lymphocytic thyroiditis can be divided into three categories. The spectrum of the thyroid profile can be correlated to the cytological diagnosis of chronic lymphocytic thyroiditis. This study aims to study the cytomorphology of various grades of chronic lymphocytic thyroiditis and its correlation with the hormonal profile. In this study, 44 patients with a diagnosis of lymphocytic thyroiditis on FNAC were included. The cases of lymphocytic thyroiditis were graded cytomorphologically, and correlation with the thyroid hormone profile was done. The majority of the patients were between 16 and 30 years age group, with a female predominance. The majority of the patients presented with diffuse enlargement of the thyroid gland. The maximum number of cases was graded in the grade II cytological category (70.46%). A hypothyroid profile was present in 63% of patients, followed by an euthyroid profile. The majority of patients with grade II thyroiditis also had a hypothyroid profile. However, no significant association was found between cytological grading and hormonal status. Cytological grading is a clear, easy-to-use diagnostic tool for confirmation of lymphocytic thyroiditis. However, the cytological grades show no statistically significant correlation with thyroid hormonal status. Lymphocytic thyroiditis should be diagnosed with a multidisciplinary approach, as clinical features and hormonal profile when used alone may result in a missed diagnosis.

Multi-UniFocality (MUF), in contrast to multifocality, in thyroid lesions: Relation to lymphocytic thyroiditis.

Whereas multifocality typically concerns papillary thyroid carcinoma (PTC) without specification of intrathyroidal metastatic or independent nature of tumor foci, the designation of the latter as Multi-UniFocal (MUF) may be relevant for select cases. A case series involving multifocal thyroid lesions with divergent histopathological morphology and/or molecular profile, with molecular evaluation of multiple individual tumor foci per patient based on a next-generation sequencing approach, was retrospectively reviewed. Twenty-five patient cases with multifocal thyroid lesions suggestive of MUF, with 2-6 (median 3) tumor foci per patient, were described. Tumor lesions comprised diverse histopathology, including PTC, (E)FVPTC, NIFTP, FA, FTC, and oncocytic. Morphologically similar and/or diverse tumor foci harbored different molecular alterations (suggestive of non-shared clonality); with(out) coexistent similar foci harboring identical molecular alterations; or (partly) shared molecular alterations. MUF was associated with chronic lymphocytic thyroiditis in almost half of the cases. The recognition of MUF may justify the independent clinical consideration per individual tumor focus; as separate lesions albeit within a multifocal context. The potential clinical relevance and prognostic value of MUF remain to be further established.

Chronic Lymphocytic Thyroiditis with Oncocytic Metaplasia Influences PD-L1 Expression in Papillary Thyroid Carcinoma.

Despite the increasing recognition of PD-L1 as predictor of immunotherapeutic response in various malignancies, its role and prognostic significance in thyroid cancer remain underexplored and subject to debate. This study begins to address this gap by comprehensively analyzing PD-L1 expression in papillary thyroid carcinoma (PTC) and investigating its correlation with key clinicopathological variables. We conducted immunohistochemistry (IHC) to assess PD-L1 expression in whole-tissue sections from 121 primary papillary thyroid carcinoma (PTC) cases. We then analyzed the correlations between PD-L1 expression and various clinicopathological variables. PD-L1 expression was detected in 33.1% of papillary thyroid carcinomas (PTCs), predominantly exhibiting weak to moderate intensity. Notably, this study found no significant correlation between PD-L1 expression and various clinicopathological variables. The lack of association with traditional factors such as age, sex, histological subtype, and tumor size suggests the complex and multifaceted nature of PD-L1 regulation in PTC. Multivariate logistic regression analysis identified chronic lymphocytic thyroiditis with oncocytic metaplasia as the sole independent predictor of PD-L1 expression (P = 0.014), underlining the potential influence of the tumor microenvironment on immune checkpoint expression in PTC. Our study underscores the intricate interplay between chronic lymphocytic thyroiditis with oncocytic metaplasia and PD-L1 expression in papillary thyroid carcinoma. The observed link suggests a potential avenue for therapeutic intervention using anti-PD-1/PD-L1 therapies in surgery-refractory PTC. Understanding the dynamics of immune checkpoint regulation in the context of the tumor microenvironment is crucial for devising effective treatment strategies. Future research endeavors should delve deeper into the molecular mechanisms underlying this interaction and explore its implications for patient outcomes. As the field of immunotherapy continues to evolve, our findings contribute valuable insights into the complex immunological landscape of thyroid cancer.

Unveiling Variations: A Comprehensive Comparison of Five Globally Used Thyroid Cytology Reporting Systems With Histopathological Correlation.

Introduction Accurate cytological assessment is pivotal for managing thyroid lesions and various global reporting systems are in use, such as the globally acclaimed The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC), alongside other reporting systems namely, the Japanese Reporting System for Thyroid Aspiration Cytology (JRSTAC), Italian Consensus for the Classification and Reporting of Thyroid Cytology (ICCRTC), the UK Royal College of Pathologists System for Reporting Thyroid Cytopathology (UK RCPath), the Royal College of Pathologists of Australasia and Australian Society of Cytology Classification System (RCPA/ASC). Notably, variations exist among these systems which are influenced by country-specific statistics. Given the lack of large-scale data in India and the difference in prevalence of diagnostic entities compared to the western population, this study aimed to identify reporting systems suitable for the Indian population focusing on distinguishing neoplastic from non-neoplastic lesions. Materials and methods A cross-sectional analysis of 40 thyroid cytology cases with histopathological correlation was conducted. Pathologists independently assessed cytology slides using JRSTAC, ICCRTC, RCPA/ASC, UK RCPath and TBSRTC. Five performance indicators, sensitivity, specificity, positive predictive value (PPV) of neoplastic conditions, negative predictive value (NPV) of non-neoplastic conditions, diagnostic accuracy and two quality indicators, percentage of Atypia of undetermined significance (AUS) and AUS/Malignant ratio were analyzed and compared. Results Among 40 cases, 22 cases were neoplastic (16 papillary thyroid carcinoma, six follicular adenoma) and 18 non-neoplastic (14 multinodular goiter, four lymphocytic thyroiditis). Specific patterns emerged in cases labeled "Non-diagnostic", prompted questions about categorizing inadequately cellular cases as "benign" in light of the presence of specific findings. All reporting systems showed 100% specificity in detecting non-neoplastic and neoplastic conditions in Category 1 and Category 6 respectively. Performance and quality indicators varied among reporting systems with TBSRTC (PPV of neoplastic cases 85.71%, NPV of non-neoplastic cases 70.58%, specificity 85.7%, sensitivity 70.58%, diagnostic accuracy 60%, AUS percentage 22.5% and AUS/Malignant ratio 3%) and RCPA/ASC (PPV of neoplastic cases 76.47%, NPV of non-neoplastic cases 70.58%, specificity 75%, sensitivity 72.2%, diagnostic accuracy 62.5%, AUS percentage 15% and AUS/Malignant ratio 3%) showing better results. Conclusion Among the five thyroid cytology reporting systems studied, TBSRTC and RCPA/ASC showed better overall performance results and quality indicators were close to benchmark. Better performance by TBSRTC 2023 could be due to the detailed criterion mentioned per category with subcategorization of AUS and suspicious for malignancy by features of cytological and architectural atypia. Similarly, RCPA/ASC has subcategorized AUS with defined criteria and certain background features were included as an isolated criterion for the suspicious for malignancy category. These defined criteriaoutlined in TBSRTC and RCPA/ASC played a crucial role in minimizing and reclassifying cases from the indeterminate categories (AUS and suspicious for malignancy) into well-defined categories with established management protocols.

Understanding and approach of Ayurveda management towards a unique case of Hashimoto Thyroiditis - A Case Report

Hashimoto thyroiditis is also known as chronic autoimmune thyroiditis and chronic lymphocytic thyroiditis, is an autoimmune disease in which thyroid cells are destroyed via cell and antibody-mediated immune processes. It is the most common cause of hypothyroidism in developed countries. The Pathophysiology of Hashimoto Thyroiditis involves the formation of antithyroid antibodies that attack the thyroid tissue, causing progressive fibrosis. The condition is sometimes not diagnosed until late in the disease process. The most common laboratory findings demonstrate elevated Thyroid-Stimulating Hormone (TSH) and low Thyroxine (T4) levels, coupled with increased anti thyroid peroxidase (anti-TPO) antibodies. In Ayurveda, it can be correlated with Rasavaha Sroto Vikara, Dhatwagnimandya, Vataja Pandu, Pittavruta Vata based on symptoms. Case Report: In this present study a female patient aged 37 years, known case of Hashimoto Thyroiditis since 8 years was treated with Shiro Takradhara, Sarvanga Abhynaga, Virechana and specific Shamanaushadhi’s as per signs and symptoms. Results: After 2 months of treatment there was a significant reduction in the signs and symptoms of the disease with 70% improvement in the condition.

Evaluating the Influence of Hashimoto's Thyroiditis on Clinico-Pathological Characteristics and Prognostic Outcomes of Middle Eastern Differentiated Thyroid Carcinoma.

Hashimoto's thyroiditis (HT), also known as chronic lymphocytic thyroiditis, represents the most prevalent autoimmune thyroid disorder globally. The potential influence of HT on the clinical and pathological attributes, as well as the clinical outcomes of differentiated thyroid carcinoma (DTC), remains a point of ongoing debate within the medical community. The central focus of this study was to analyze the influence of HT on clinico-pathological characteristics and its prognostic impact in a large cohort of DTC from Middle Eastern ethnicity. Design, Patients, Measurements. An extensive analysis involving 1822 DTC patients was conducted to determine the association with clinico-pathological characteristics as well as prognosis, using Chi-square tests and Kaplan-Meier curves. 23.9% (435/1822) of DTC patients were diagnosed with HT. Univariate analysis revealed a positive correlation between presence of HT and clinico-pathological factors such as female gender, younger age, and early stage tumor. In contrast, HT demonstrated a negative association with several aggressive clinical features, including extrathyroidal extension, distant metastasis, recurrent/persistent disease and high-risk categorization by the American Thyroid Association (ATA) guidelines. Despite HT being associated with favorable clinico-pathological features in Middle Eastern DTC patient, our study found no significant influence on overall survival or recurrence-free survival. The finding of an association between HT and favorable clinico-pathological characteristics, but lack of impact on prognosis, underscores the complexity of HT-DTC relationship, necessitating further comprehensive research to fully understand these interactions.

Occult Filariasis in a Case of Lymphocytic Thyroiditis Diagnosed on Fine Needle Aspiration Cytology: An Unusual Finding of Dual Pathology

Filariasis is a common public health problem in Southeast Asia. The two species of worms most commonly associated with this disease are Wuchereria bancrofti and Brugia malayi. Cases of microfilaraemia have also been reported from atypical sites in the past. None of the previously reported cases of microfilaria in the thyroid gland have described occult filariasis against a background of lymphocytic thyroiditis. The authors present a case of incidental microfilaria in a case of lymphocytic thyroiditis, diagnosed on fine needle aspiration cytology of thyroid swelling in a female, a coexistence of dual pathology. There has been no case in literature where filariasis was reported against a background of lymphocytic thyroiditis. Peripheral blood examination also did not show any evidence of filariasis.

Construction of a nomogram for central lymph node metastasis in papillary thyroid cancer based on gender grouping.

The status of central lymph nodes is crucial for determining the surgical approach to papillary thyroid carcinoma (PTC). Because of the differences between genders in central lymph node metastasis (CLNM), we aimed to construct separate predictive models for CLNM according to gender. In our study, a total of 1258 PTC patients who underwent thyroid cancer surgery from September 2021 to March 2023 were analyzed retrospectively. The data were analysed univariately and multivariately using SPSS software grouped according to gender and nomograms of CLNM were plotted using R software. The variables included in this study were sex, Age, body mass index, Diabetes, chronic lymphocytic thyroiditis (CLT), Suspicious central lymph node (SCLN), A/T, Margin, Microcalcification (MC), BRAF, Number, Location, CLNM. The preoperative nomogram in male patients included four clinical variables: CLT, Margin, Number, Size. The preoperative nomogram of female patients included six clinical variables: Age, SCLN, Margin, MC, Number, Size. The calibration curves showed great agreement in both the training group and the validation group. The decision curve analysis showed the feasibility of nomogram in predicting CLNM in both man and woman. Based on the successful establishment of nomogram, we can analyze the variability of CLNM between male and female, which may provide clinicians with personalized clinical schemes in the treatment of PTC.

Clinical value of Cyclin D1 and P21 in the differential diagnosis of papillary thyroid carcinoma

BackgroundWith the continuous discovery of new borderline thyroid lesions and benign and malignant “gray areas”, coupled with the limitations of traditional immune indicators, the differential diagnosis of papillary thyroid carcinoma (PTC) has become more difficult. Cyclin D1 and P21 are cell cycle regulators involved in the occurrence and metastasis of multiple tumors, including PTC, but their specific functions are unclear.MethodsIn our study, immunohistochemical staining was used to explore the expression of Cyclin D1 and P21 in PTC, paracancerous tissue, follicular adenoma (FA) and papillary thyroid hyperplasia. In addition, their relationship with the clinicopathological features of PTC and their differential diagnostic value in distinguishing between intralymph node PTC metastases and intralymph node ectopic thyroid tissue were studied.ResultsAmong 200 primary PTC lesions, Cyclin D1 and P21 were found to be expressed in 186 (93.00%) and 177 (88.50%), respectively, and their expression levels were significantly higher in PTC tissue than in adjacent tissue, FA tissue and papillary thyroid hyperplasia tissue (P < 0.05). The expression levels of Cyclin D1 and P21 were positively correlated with tumor size and lymph node metastasis (P < 0.05) but not with sex, age, number of tumor lesions, histological subtype, chronic lymphocytic thyroiditis or TNM stage (P < 0.05). The expression levels of Cyclin D1 and P21 were significantly correlated (P < 0.05). The positivity rates of Cyclin D1 and P21 in intralymph node PTC metastases were 97.96% (48/49) and 89.80% (44/49), respectively, which were significantly higher than those in intralymph node ectopic thyroid tissue (P < 0.05). The sensitivity (Se) and negative predictive value (NPV) of Cyclin D1 and P21 detection alone or in combination were higher than those of the combined detection of the classical antibody markers CK19, HBME-1 and Galectin-3. Besides, the Se, Sp, PPV and NPV of Cyclin D1 and P21 in differentiating intralymph node PTC metastases and intralymph node ectopic thyroid tissue were higher.ConclusionsThe results of our study show that Cyclin D1 and P21 are highly sensitive and specific markers for the diagnosis of PTC that are superior to traditional classical antibodies. And, these two markers are of great value in the differential diagnosis of intralymph node PTC metastases and intralymph node ectopic thyroid tissue.

Grading of Hashimoto’s thyroiditis in cytology and its association with ultrasonographic and biochemical parameters

Introduction and Aim: In the post-iodization period, Hashimoto's thyroiditis (HT) is most likely the most prevalent cause of goitre and hypothyroidism, particularly in women of reproductive years. This study was undertaken to grade HT on Fine Needle Aspiration Cytology smears and determine their usefulness in predicting thyroid damage in association with clinical history, radiological and biochemical findings. Materials and Methods: Total of 151 cases were diagnosed cytologically in duration of over 2 years as Hashimoto’s thyroiditis/lymphocytic thyroiditis. Cytology scoring technique was used to analyse smears and were correlated with radiological, biochemical findings and were evaluated statistically by ANOVA and Kruskal Wallis tests. Results: In the current study, the most frequent group of individuals with Hashimoto's thyroiditis were between the ages of 40 and 50. Females (145 cases, 96%) were commonly affected and the commonest presentation was a diffuse (125 cases ,82.8%) thyroid enlargement. Cytological grading of Hashimoto’s thyroiditis were as follows,54 (35.8%) patients were Grade I, 81(53.6%) patients were Grade II thyroiditis and 16 (10.6%) patients were Grade III thyroiditis. Biochemically, 78 (56.5%) of the cases were hypothyroid, 51 (37%), euthyroid, and 9 (6.5%) were hyperthyroid. Ultrasonography revealed 76 (50.3%) patients with hypoechoic micronodules, 71 (47%) with echogenic septae, 101 (66.9%) with increased vascularity, and 6 (4%) with normal findings. The grades of lymphocytic thyroiditis and the biochemical data were found to be statistically significant (p=0.001). Furthermore, there was a strong correlation between the grades and specific ultrasound findings, such as echogenic septae (p=0.042) and diffuse hypoechogenicity (p=0.046). Conclusion: Cytological scoring system in Hashimoto’s thyroiditis can predict thyroid functional status and aid in determining the severity of the disease.

New insights into histopathological features of Warthin-like papillary thyroid carcinoma

Background. The Warthin-like variant of papillary thyroid carcinoma (WLPTC) is a rare papillary thyroid carcinoma that is considered to be a subtype of the oncocytic variant. Purpose of the study: to present the diagnostic and clinical features, the oncological and surgical management of a patient with WLPTC as well as its discussion with other relevant studies. Materials and methods. We report a case of Warthin-like papillary thyroid carcinoma in a 31-year-old woman with Hashimoto thyroiditis. Results. The patient was admitted to the hospital with the presence of a node in the thyroid gland. Thyroid ultrasound showed a 24-mm nodule with oval shape and irregular contours in the left lobe. A fine-needle aspiration biopsy was performed, and a diagnosis of papillary thyroid carcinoma was made. The patient underwent thyroidectomy, bilateral modified and central neck dissection, lymphadenectomy. Histopathological examination suggested a WLPTC coexisting with chronic thyroiditis, metastases to the lymph nodes 2, 3, 4 on the left and 6 neck compartments. The patient underwent postoperative I131 ablation therapy. Conclusions. WLPTC is a recently described variant of papillary thyroid cancer that is frequently associated with lymphocytic thyroiditis. The correct cytological and histomorphological features are of utmost importance to render the diagnosis of WLPTC for better management. A surgical and postoperative treatment is identical to that in classic differentiated thyroid cancer, having a favorable outcome due to a low recurrence rate. A surgical management should be thyroidectomy and dissection of central neck compartment as well as lateral dissection in cases of suspicions for metastases in the lymph nodes or metastases confirmed preoperatively by a fine-needle aspiration biopsy.

Clinical and molecular impact of concurrent thyroid autoimmune disease and thyroid cancer: From the bench to bedside.

The recent incorporation of immune checkpoint inhibitors targeting the PD-1 (programmed cell death receptor 1) and CTLA-4 (cytotoxic T lymphocyte antigen 4) pathways into the therapeutic armamentarium of cancer has increased the need to understand the correlation between the immune system, autoimmunity, and malignant neoplasms. Both autoimmune thyroid diseases and thyroid cancer are common clinical conditions. The molecular pathology of autoimmune thyroid diseases is characterized by the important impact of the PD-1/PD-L1 axis, an important inhibitory pathway involved in the regulation of T-cell responses. Insufficient inhibitory pathways may prone the thyroid tissue to a self-destructive immune response that leads to hypothyroidism. On the other hand, the PD-1/PD-L1 axis and other co-inhibitory pathways are the cornerstones of the immune escape mechanisms in thyroid cancer, which is a mechanism through which the immune response fails to recognize and eradicate thyroid tumor cells. This common mechanism raises the idea that thyroid autoimmunity and thyroid cancer may be opposite sides of the same coin, meaning that both conditions share similar molecular signatures. When associated with thyroid autoimmunity, thyroid cancer may have a less aggressive presentation, even though the molecular explanation of this clinical consequence is unclear. More studies are warranted to elucidate the molecular link between thyroid autoimmune disease and thyroid cancer. The prognostic impact that thyroid autoimmune disease, especially chronic lymphocytic thyroiditis, may exert on thyroid cancer raises important insights that can help physicians to better individualize the management of patients with thyroid cancer.

Cytopathology of primary sclerosing mucoepidermoid carcinoma with eosinophilia of the thyroid: a multi-institutional case series and review of literature

Sclerosing Mucoepidermoid Carcinoma with Eosinophilia (SMECE) of the thyroid is an extremely rare tumor that exhibits unique histologic characteristics and is nearly always associated with lymphocytic thyroiditis (LT). However, the cytomorphologic and clinicopathologic characteristics of SMECE have only been described in rare case reports. Authors' institution laboratory information systems were searched for records of SMECE between 2012 and 2023. Literature review was performed using keywords "Sclerosing mucoepidermoid carcinoma with eosinophilia", "thyroid", and "cytopathology" to search through institution electronic library databases for relevant articles. A total of 19 cases were identified, 3 unpublished in the authors' archives and 16 in the literature which had fine needle aspiration (FNA) material or cytologic features available for review, and were comprised of 3 males and 16 females. The common cytomorphologic characteristics of SMECE included fragments or loose clusters of intermediate-type epidermoid cells in a background of prominent LT and eosinophils. Overt keratinization, mucinous cells, and extracellular mucin were not commonly encountered, resulting in diagnostic challenges, especially if eosinophils associated with epithelial cell clusters were rare. The cases were reported as "Nondiagnostic" (1 case), "Atypia of Undetermined Significance" (4 cases), "Suspicious for Malignancy" (3 case), or "Malignant" (11 cases). The clinical course of SMECE of the thyroid varied and distinct cytomorphologic characteristics in a subset of patients who experienced aggressive disease raises the possibility of different prognostic grades. Cases with keratinized squamous cells and necrosis mimic anaplastic (undifferentiated) thyroid carcinoma, but the clinical history and radiologic findings can be helpful to exclude this diagnosis.

SAT532 A Rare Case of Thyroid Carcinoma Noted in a Patient with Thyroid Nodule Showing Prior Benign Biopsy and Prior Negative Molecular Testing

Abstract Disclosure: M.M. Hillhouse: None. P. Madhavan: None. F.M. Woron: None. Background: Molecular studies have a high sensitivity for ruling out malignancy (1). This patient was diagnosed with the follicular variant of papillary thyroid carcinoma despite negative molecular testing and benign cytology in multiple prior biopsies. Clinical Case: 31 y.o. female with a past medical history of Hashimoto's disease on levothyroxine presented for follow up of thyroid nodules. She does not have a family history of thyroid cancer or personal history of neck radiation. The patient was noted to have a right thyroid nodule around 14 years of age and this was monitored during her childhood. The nodule measured 2.3 x 0.6 cm on ultrasound in 2015. The nodule measured 2.0 x 1.6 x 1.5 cm in 2017. FNA in 2017 revealed benign cytology (Bethesda II). On ultrasound in 03/2019, the nodule measured 2.2 x 1.5 x 1.8 cm. The nodule demonstrated a greater than 20% increase in all dimensions on ultrasound images in 12/2020 to 2.9 x 2.0 x 2.6 cm. A repeat ultrasound in 04/2021 demonstrated no significant change in size. Repeat FNA performed in 07/2021 demonstrated clusters of follicular cells in flat and microfollicular groups and was interpreted as atypia of undetermined significance (Bethesda III). AFIRMA testing was benign (∼4% of malignancy. The nodule increased in size to 3.5 x 2.6 x 3.1 cm on ultrasound in 07/2022. It appeared solid and hyperechoic and was classified as TI-RADS 3. A new 0.8 cm nodule on the left lobe was also identified. Repeat FNA of the right nodule in 09/2022 demonstrated macrophages, colloid and groups of follicular cells and was classified as non-diagnostic (Bethesda I). She reported difficulty breathing in the supine position and she underwent a right hemithyroidectomy and isthmusectomy in 11/2022. Pathology results were remarkable for invasive encapsulated follicular variant of papillary thyroid carcinoma with focal angioinvasion and tumor capsular invasion. The margins were negative for tumor. The parenchyma was consistent with lymphocytic thyroiditis. Ultrasound after interval right hemithyroidectomy in 12/2022 in an outside facility demonstrated an unchanged subcentimeter left thyroid nodule and multiple bilateral anterior cervical/level 6 lymph nodes suspicious for metastatic disease given the absence of hilum. Patient is currently undergoing repeat imaging and work up for the lymphadenopathy. Conclusion: This case study highlights the importance of maintaining high clinical suspicion for thyroid malignancy in cases of increasing thyroid nodule size and compressive symptoms despite negative cytological and molecular testing.

SAT580 Incidental Diagnosis Of Genetic Variant PTPN11 Noonan Syndrome With Multiple Lentigines, Sensorineural Hearing Loss And Rheumatoid Arthritis In Adult Female With Hashimoto’s Thyroiditis. Case Report

Abstract Disclosure: M.M. Eid: None. T. Zahra: None. J. Vargas-Jerez: None. Introduction: Hashimoto’s thyroiditis (HT, chronic lymphocytic thyroiditis, autoimmune thyroiditis) and Rheumatoid arthritis (RA) are autoimmune disorders, affect mainly females (1). Noonan syndrome with Multiple Lentigines (NSML, Leopard Syndrome) is a rare multigenetic autosomal dominant disorder. It includes cerebrovascular and cardiac anomalies, facial phenotype, hearing abnormality and developmental delay (2). Case: 41 yo, Female with history of HT since 2002 (high TSH, thyroid peroxidase antibody more than 1000 u/ml, low FT4 and FT3) on levothyroxine 150mcg/day. Recently moved to the USA from EL Salvador. Presented for initial evaluation. Denied smoking, alcohol, allergy. Maternal aunt with thyroid disease. Had menstrual irregularities, no previous attempt to conceive. Review of system: 5 months of pain, swelling and morning stiffness for 1 hour in hand joints, hearing difficulty for 2 years, painless brown skin spots for years, childhood learning difficulty and constipation. Physical examination body weight 139Ib, height 162cm, Stable vitals, diffuse lentigines. Head: board forehead, hypertelorism, high arched eye brows, micrognathia, low set ears. Heart: normal heart sounds, no murmur. No thyromegaly, nystagmus or vertigo. Hand: swelling of metacarpophalangeal and proximal interphalangeal joints. Laboratory work up TSH 8 normal 0.27 to 4.2 uIU/ml, FT4 0.8 normal 0.9-1.8 ng/dl, A1C 5.7, positive rheumatoid factor 199IU/ml, anti-CCP antibody &amp;gt; 250U, ANA 1/320, ESR 61ml/hr, negative anti-tissue transglutaminase antibody, normal liver and kidney function tests and complete blood count. Hand X-ray: decrease joint space and bone erosion. Thyroid US: normal size, vascularity, no nodule. Normal Echocardiogram, EKG and chest X ray. Internal auditory canal MRI: no masses or abnormal enhancement. DEXA Scan: osteopenia of femur and lumbar spine. She was diagnosed with seropositive RA, B/L sensorineural hearing loss (SNHL) more on right side. Genetic test revealed heterozygous pathogenic variant of PTPN11 gene consistent with NSML and negative for Neurofibromatosis type 1. Kept on prednisone and methotrexate, levothyroxine was increased 162mcg/day. Conclusion: Autoimmune disorders have a common pathogenesis including humoral and cell mediated immunity, autoimmune oxidative stress, UV radiation exposure, genetic linkage and biochemical changes. Diagnosis of one autoimmune disorder increases the possibility of other autoimmune disorders (1). NSML has a variable presentation. PTPN11-NSML is usually associated with SNHL and cardiac anomalies as pulmonary stenosis. It is infrequent to diagnose NSML with HT and structurally normal heart like our case(2).

FRI568 Hashimoto’s Thyroiditis With Negative Antibodies In Association With Common Variable Immunodeficiency

Abstract Disclosure: I.C. Ebrahim: None. K.F. Brown: None. N.O. Vietor: None. T.D. Hoang: None. M.K. Shakir: None. Introduction: Common variable immunodeficiency (CVID) is associated with several autoimmune manifestations including Hashimoto’s thyroiditis (HT). We report a 47-year-old male with CVID and HT with negative thyroid antibodies (Abs). Case Report: A 47-year-old male, while undergoing coronary calcium scan in 2021, was found to have scattered lung nodules. Follow-up Ct scans showed interval increase in size of lung nodules and a PET scan confirmed bilateral lung nodules which demonstrated hypermetabolic activity and scattered hypermetabolic lymph nodes, suggesting infectious or inflammatory processes. PET scan also revealed thyromegaly with diffusely increased uptake, suggesting thyroiditis. Serum immunoglobulins were measured: IgA &amp;lt; 5 mg/dL (normal 70-400), IgG 334 mg/dL (normal 700-1600), and IgM &amp;lt; 25 mg/dL (normal 40-230). Serum immunoglobulins levels from depository serum samples collected in 2005 also showed similarly low values. CBC was normal, excluding any bone marrow disorders. There was no family history of immunodeficiency or thyroid disorders. On review of systems patients did not have any symptoms of hypothyroidism. Exam: thyroid 50-gms diffusely enlarged with no palpable nodules; heart and lung exam was normal. Laboratory tests including comprehensive metabolic panel, serum complement CH 50, leukemia/lymphoma panel, T/B - lymphocyte/Natkiller, CRP were all normal. Thyroid functions: TSH 5.6 mc1U/mL (0.27-4.2), Free T4 1.20 ng/dL (0.93-1.71), TPO Ab &amp;lt; 9 IU/mL (0-34), TG Ab &amp;lt; 1.0 1U/mL (0.0-0.9), thyrotropin receptor Ab &amp;lt; 0.3 IU/L (&amp;lt;1.0), thyroid stimulating immunoglobulin &amp;lt; 0.10 1U/L (0.06-0.55). Serum thyroid Ab levels from depository samples collected in 2005 also showed normal values. FNA of thyroid showed atypical lymphoid infiltrates and an excision biopsy of the thyroid isthmus confirmed lymphocytic thyroiditis. A PET avid right inguinal lymph node biopsy showed a reactive lymph node. Additional lab evaluation also showed low post vaccination pneumococcal titers. With pan-hypoglobulinemia and low vaccine response, a diagnosis of CVID was made. Patient preferred watchful waiting than iv immunoglobulin therapy. Additionally, the patient has HT with negative thyroid Abs and although patient had mild subclinical hypothyroidism patient elected no treatment. Common variable immunodeficiency (CVID) is the most frequent symptomatic primary immunodeficiency in adults. Autoimmune manifestations occur in 22% of CVID patients and these include autoimmune cytopenia, pernicious anemia, rheumatoid arthritis, vitiligo, and/or HT. Interestingly, our patient did not manifest any thyroid Abs thus it may be postulated that thyroid follicles destruction in HT is mediated predominantly by thyroid-specific B and T cells rather than by thyroid antibodies. Presentation: Friday, June 16, 2023

THU224 Is Chronic Lymphocytic Thyroiditis Associated With Aggressive Differentiated Thyroid Cancer In A Predominantly Hispanic Pediatric Population?

Abstract Disclosure: N. Solano: None. D. Baboun: None. A. Martinez-Sanchez: None. A. Diaz: None. A. Carrillo-Iregui: None. F. Alkhoury: None. Background: The risk of developing papillary thyroid carcinoma (PTC) appears to be increased among patients with chronic lymphocytic thyroiditis (CLT). Studies in adults have shown that the presence of CLT is associated with less aggressive PTC; however, this correlation is unclear in pediatric patients. Objective: The purpose of this study is to determine a possible correlation between CLT and markers of aggression severity using histopathological findings, tumor size, and lymph node involvement among patients with differentiated thyroid carcinoma (DTC) in a free-standing children’s hospital with a predominantly Hispanic population. Methods: Upon Institutional Review Board approval, we performed a retrospective chart review from 2012-2022 of 55 patients with a final diagnosis of DTC. We analyzed the correlation between CLT and histopathological findings. Statistical analysis was performed by using t-tests and chi-squared tests. Results: The patients reviewed were between 8-20 years of age. Forty-nine (89.1%) patients identified as Hispanic, and 41 (74.6%) were females. Twenty-five (45.5%) patients had a diagnosis of CLT; 19 (76.0%) of these patients had classic PTC, 3 (12.0%) had the follicular variant of PTC, and 3 (12.00%) had another variant of PTC. Of the 30 (54.5%) patients who did not have CLT, 13 (43.3%) had the classic variant of PTC, 10 (33.3%) had the follicular variant of PTC, and 7 (23.3%) had another variant of PTC. The distribution of the histopathological findings was significant (p=.048). Patients with CLT had significantly smaller tumor sizes (1.8 vs. 2.5 cm, respectively [p=.048]). Of the 36 patients with lymph node involvement, 20 (55.6%) had CLT. Of the 19 patients without lymph node involvement, 5 (26.3%) had CLT. The association between the presence of CLT and lymph node involvement was significant (p=.038). Conclusions: In our population, patients with CLT had a significantly higher presence of the classic variant of PTC. Studies in adults have shown a tendency of these lesions to have a higher risk of disease than those with the follicular variant. Patients with CLT had a smaller tumor size, likely as a result of earlier detection of thyroid nodules due to frequent clinical evaluations and thyroid ultrasounds. However, patients with CLT tended to have a higher frequency of lymph node involvement. More studies with pediatric populations are needed to clarify the possible association between CLT and DTC. Presentation: Thursday, June 15, 2023

FRI509 A Girl With Trisomy 21 Presents With Van Wyk-Grumbach Syndrome

Abstract Disclosure: J. Hayes dorado: None. M. Calla Ayala: None. A. Colque Arias: None. K. Lanuza Gaite: None. M. Rossell Lopez: None. D. Frias Eid: None. Van Wyc-Grumbach syndrome (VWGS) is a rare presentation of long standing prepubertal hypothyroidism characterized by bilateral multicystic enlarged ovaries, vaginal bleeding and delayed bone age. It appeared that high TSH could produce FSH and LH like activity leading to multiple ovarian cysts. A 7-year-old girl with trisomy 21, presented with vaginal bleeding for 2 days prior to admission. Physical exam revealed bradycardia (68 bbm), apathy, sluggishness, as well as dry skin and eyelid oedema. She had no breast development nor pubic hair.Causes of vaginal bleeding such as trauma, possible abuse, foreign body insertion and urethral prolapse were excluded. There was no purpura or bleeding from other sites.The abdominal sonogram revealed bilateral ovarian cystic masses (V:17.29 cm3 and 16.48 cm3, right and left, respectively). Bone age was delayed almost 3 years behind her chronological age. Laboratory tests revealed TSH 860 μIU/mL, T4 0.71 μg/dL, FSH 8.12 mIU/mL, LH &amp;lt; 0.1 mIU/mL, estradiol 193 pg/mL, thyroid peroxidase Abs 184 IU/mL, thyroglobulin Abs 212 IU/mL, Β-hCG &amp;lt; 0.1mU/mL, confirming severe hypothyroidism. The girl was diagnosed with VWGS due to unrecognized chronic lymphocytic thyroiditis and LT4 treatment (75mug/OD) was initiated. The patient responded with complete remission of symptoms and regression of the ovarian cysts one month after initiation of treatment. It is very important to think of VWGS and investigate for thyroid status during the evaluation of ovarian cysts or isolated premature menarche. Early recognition can eliminate unnecessary surgery to remove ovarian cysts, as appropriate treatment with levothyroxine leads to complete remission of symptoms. Even when the diagnosis of VWGS is confirmed, practitioners must be watchful to consider surgical intervention in the presence of uncontrolled vaginal bleeding, hemodynamic instability, or failure of regression of ovarian cysts with exogenous thyroid hormone replacement. Presentation: Friday, June 16, 2023