bluuebunny/crossref_metadata_2025_split huggingface dataset:
Noninvasive Encapsulated Papillary RAS-Like Thyroid Tumor (NEPRAS)
Authors: Rosario Pedro Weslley , Mourão Gabriela Franco 
Published: May 2021

Abstract
Introduction: The diagnosis of thyroid tumors arising from follicular cells that are encapsulated/well delimited and noninvasive is a challenge. When unequivocal nuclear alterations are present, the final diagnosis can range from noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) and classical/encapsulated papillary thyroid cancer (PTC), including aggressive subtypes, to poorly differentiated carcinoma. As proposed recently, the presence of papillae in the absence of exuberant nuclear alterations (nuclear score 2), given that the other criteria for NIFTP are met, may not be sufficient for the diagnosis of PTC. This condition is called “noninvasive encapsulated papillary RAS-like thyroid tumor” (NEPRAS), whose nature would be borderline and not malignant. Revising our cases of tumors &gt; 1 cm that were diagnosed previously as PTC and that were encapsulated/well delimited and noninvasive, we found three cases of NEPRAS. We now revised our cases of tumors &gt; 1 cm diagnosed previously as well-differentiated tumor of uncertain malignant potential (WDT-UMP) because the nuclear alterations were not considered to be sufficient for the diagnosis of PTC on that occasion. Case: In a 29-year-old euthyroid male patient with a single thyroid nodule whose fine-needle aspiration had revealed indeterminate cytology, a single tumor measuring 3.2 cm was reclassified from WDT-UMP to NEPRAS. For this diagnosis, the tumor met the following criteria: encapsulation or clear demarcation, no vascular or capsular invasion, presence of papillae, &lt; 30% solid/trabecular/insular growth pattern, no tumor necrosis or high mitotic activity, and nuclear score 2. The BRAFV600E mutation was absent. The patient continues to show no signs of recurrence 7 years after lobectomy. Conclusion: Despite the presence of papillae, some tumors may be reclassified from malignant (encapsulated PTC) to borderline (NEPRAS). This proposal would result in a change of management, with the same implications as those seen for the change from noninvasive encapsulated follicular variant of PTC to NIFTP. References: Ohba K et al. Encapsulated Papillary Thyroid Tumor with Delicate Nuclear Changes and a KRAS Mutation as a Possible Novel Subtype of Borderline Tumor. J Pathol Transl Med. 2019;53:136-41 AND Rosario PW. Noninvasive encapsulated papillary RAS-like thyroid tumor (NEPRAS) or encapsulated papillary thyroid carcinoma (PTC). J Pathol Transl Med. 2020;54:263-4.
Papillary Thyroid Carcinoma With Axillary Lymph Node Metastasis
Authors: Khan Mehvish , Sperling Scott Brian 
Published: May 2021

Abstract
Papillary thyroid carcinoma (PTC) is typically known to be a non-aggressive form of thyroid follicular epithelial-derived cancer. It is characterized histologically by classic and variant forms. Metastases are uncommon and spread mainly via lymphatic channels to cervical lymph nodes and less commonly via hematogenous spread to lungs and bone. Axillary lymph node (ALN) metastasis is a rare sequela of disease presentation. A 59-year-old female presented for evaluation of shortness of breath and chest pain for one week. She had a longstanding history of hypothyroidism due to chronic lymphocytic thyroiditis which was stable on levothyroxine. Her physical exam revealed a firm mass on the inferior aspect of the left neck. Computed tomography (CT) angiogram ruled out pulmonary embolism but noted a superior mediastinal mass and significant left axillary and subpectoral adenopathy. Mammogram was negative for breast malignancy. Left axillary ultrasound showed a 1.1 x 1.8 x 1.9 cm enlarged lymph node. Thyroid ultrasound showed a 3 mm nodule on the left lower pole and a 3.7 x 2.9 x 2.1 cm heterogeneous and irregular mass in the left neck. Positron emission tomography/CT showed increased uptake in left lower paratracheal, left supraclavicular and axillary lymph nodes. Fine needle aspiration of the left neck mass and left ALN confirmed metastatic papillary carcinoma. She underwent total thyroidectomy, left modified neck, central neck, and left ALN dissection along with partial esophageal wall excision. Intraoperatively, she was found to have a multifocal tumor in the left thyroid lobe with the largest dimension of 1 cm. Surgical pathology noted that the primary tumor in the left thyroid was classic type of papillary carcinoma, and the metastatic tumor in the lymph nodes was of tall cell variant. I-123 thyroid uptake and scan after surgery showed low residual thyroid uptake of 0.6%. She underwent adjuvant ablation with 155 millicuries (mCi) of radioiodine (RAI or I-131) following levothyroxine withdrawal protocol. Post ablation therapy thyroid uptake and scan showed no radiotracer uptake within the thyroidectomy bed. According to the American thyroid association (ATA) risk stratification system, she was categorized as high risk. This case illustrates that PTC may exceptionally spread to axillary lymph nodes. Physiologic flow is centripetal to the jugulosubclavian junction and there is no communication between cervical and axillary lymphatics. However malignant tumors can alter and partially block lymphatic pathways, resulting in ALN metastasis in a retrograde direction. This case also demonstrates that PTC can be transformed into aggressive forms associated with worse prognosis such as tall cell variant. Further comprehensive monitoring and management approaches are needed to plan treatment and gauge prognosis of patients with PTC who present with ALN metastasis.
Primary Thyroid Lymphoma: Maintaining Diagnostic Scrutiny
Authors: Chang Diana Juhee , Mosaferi Tina , Kim Sarah Sangnim Rhee 
Published: May 2021

Abstract
Background: Primary thyroid lymphoma (PTL) is a rare condition representing &lt;5% of thyroid malignancies with diffuse large B-cell lymphoma (DLBCL) as the most common subtype (1). Although not commonly managed in the endocrine sphere, identification is paramount to prognosis and treatment. We present a case of PTL to highlight the importance of diagnostic scrutiny and clinical follow up.
Clinical Case: A 69-year-old man with a history of Hashimoto’s thyroiditis presented with an enlarging neck mass. The patient noted development of a left-sided anterior neck mass 3 days prior to seeking care. He denied compressive symptoms and B symptoms (weight loss, fevers, and night sweats). Physical exam revealed a large, firm left-sided thyroid nodule. Serum studies were notable for TSH 39.1 mcIU/mL (0.30-4.7 mcIU/mL), FT4 0.9 ng/dL (0.80-1.70 ng/dL), and TPO Ab 127 IU/mL (&lt;=20 IU/mL). Levothyroxine 100 mcg daily was started. Neck ultrasonography showed a 54 mm hypoechoic, solid left thyroid nodule without calcifications. No abnormal cervical lymph nodes were present. FNA revealed a mixed population of small lymphocytes with no monoclonal B cell population or T cell aberrancies on flow cytometry. In the setting of ongoing nodular growth, the patient underwent core needle biopsy which revealed DLBCL (Ki67 proliferation index &gt;80%, EBV-EBER negative). For diagnostic confirmation and staging, a whole-body FDG-PET scan was performed with an intensely FDG-avid left thyroid mass and no metabolic evidence of additional lymphoproliferative disease. Bone marrow biopsy did not show lymphomatous involvement. The patient was diagnosed with primary thyroid lymphoma and started on chemotherapy with R-CHOP.
Conclusion: PTL commonly presents as a rapidly enlarging, painless neck mass that may be accompanied by B symptoms. Hashimoto’s thyroiditis is a known risk factor. Our case in particular required more diligence in the setting of an FNA with mixed lymphoid cells and negative flow cytometry. Initial differential diagnosis included intrathyroidal lymph node, Hashimoto’s thyroiditis, thyroid adenoma/malignancy with a false FNA, and lymphoma. Notably, FNA biopsy is only associated with 71% sensitivity in diagnosing PTL, whereas core biopsy has a 93% sensitivity rate (2). Upon histopathologic disease diagnosis, collaboration with oncology is needed for further staging and initiation of chemotherapy +/- radiation.
References: (1) Pavlidis ET, Pavlidis TE. A Review of Primary Thyroid Lymphoma: Molecular Factors, Diagnosis and Management. J Invest Surg. 2019;32(2):137-142. (2) Diaconescu MR, Costea I, Glod M, Diaconescu S. An Unwonted Clinicopathological Subtype of Thyroid Primary Lymphoma. Chirurgia. 2016;111(5):428-431.
Radioactive Iodine Resistant Papillary Thyroid Cancer “Redifferentiated” With Dabrafenib
Authors: Zayouna Christine , Sonnabend Hajerah , Amblee Ambika 
Published: May 2021

Abstract
Background: Differentiated thyroid cancers (DTC) make up 95% of all thyroid cancers. Radioactive iodine therapy (RAI Rx) is an integral part of DTC management. However, 5-15% of DTC and 50% of metastatic DTC become resistant to RAI Rx and carries a 10-year survival of only 10%. One of the newer therapeutic options target “redifferentiation” of the tumor using RAI sensitizers, notably with short-term use of tyrosine kinase inhibitors (TKI). Clinical Case: A 62-year-old women with a 3-year history of Papillary TC s/p surgery (Sx) and 175 mCi RAI presented to establish care and was found to have bulky palpable disease in her left lateral neck. Imaging showed bilateral enlarged lymph nodes in the neck and multiple bilateral pulmonary nodules. Her stimulated thyroglobulin (TG) level was 5341 (1.59 - 50.03 ng/dL) with negative TG antibodies. Bone scan showed no evidence of bone mets. She underwent repeat neck dissection (49 positive lymph nodes) and was BRAF V600E positive. Post-Sx her non-stimulated (NS) TG was 340 ng/dL (0.00 - 41.00 ng/mL) and she received 200mCi RAI Rx with post-Rx whole body scan (WBS) showed uptake only in the thyroid bed. Imaging 6 months later showed stable lung nodules but increase in lymphadenopathy in the neck and her NS-TG was 181 ng/dL. She received 250 mCi of RAI Rx, 10 months after the first dose. Post Rx WBS again showed uptake only in the neck. Her non-stim TG, 9 months later was still high at 130 ng/dL. Given the discordant imaging and TG findings, functional imaging was done which showed multiple avid lesions in bone and lymph nodes confirming the diagnosis of radioiodine-refractory (RAI-R) DTC. Given BRAF V600E positive status, she received Dabrafenib 150 mg PO BID for 6 weeks followed by RAI 300 mCi. Post-RAI WBS showed extensive uptake in base of skull, sternum, cervical spine and right supraclavicular area. Six months post Dabrafenib and RAI, her NS-TG had come down from 130 to 25.7 ng/dL and imaging showed stable structural disease. Her TG levels and imaging have remained stable over the last 18 months indicating both biochemical and structural response to Dabrafenib. Conclusion: The goal of TKIs in redifferentiation of RAI-R DTC is to target specific molecular mechanisms to render the tissue sensitive to RAI. There are several published trials using TKIs for redifferentiation based on the mutation present. Dabrafenib alone and in combination with other TKI’s (Vemurafenib, Trametinib) followed by RAI has shown some response in 60-70% of treated patients with RAI-R tumors. In a study with 10 RAI-R patients with BRAF V600E mutations, dabrafenib used as a radiosensitizer showed RAI uptake in 60%. Three months post Rx, 2 of 6 had a reduction in disease burden while the other 4 had stable disease. Redifferentiation Rx can be successful in slowing disease progression and could be an option in the treatment of RAI-R DTC before initiation of long term TKI Rx.
Thyroid Lymphoma: A Rare Cause of Thyroid Malignancy
Authors: Cartwright Carmen , Lekprasert Patamaporn 
Published: May 2021

Abstract
Background: Primary Thyroid Lymphoma is rare accounting for 2-5% of all thyroid malignancies and less than 2% of extranodal lymphomas. Data has suggested annual incidence to be 2 per 1 million. (1)
Clinical Case: A 72-year-old female with coronary artery disease, hyperlipidemia and hypothyroidism was diagnosed with extranodal follicular cell lymphoma of the breast. FDG-PET showed evidence of diffuse avidity within her thyroid gland, with SUV of 13.8. She denied any drastic change in the size of her neck or any compressive symptoms. Thyroid ultrasound performed months before her diagnosis of lymphoma, showed a two-fold increase, most notable to the right lobe compared to prior imaging; her gland remained otherwise unchanged with heterogenous echotexture.
Fine needle aspiration and flow cytometry were obtained on thyroid tissue that showed follicular cell lymphoma. She was started on single-therapy Rituxan regimen with oncology. Several months later appearance and examination of her neck had improved with decrease in size of thyroid gland.
Repeat FDG-PET scans, with the most recent being 11 months after starting Rituxan therapy, showed reduction in the avidity within the thyroid gland and decreasing size; with SUV of 7.8.
Repeat thyroid ultrasound continued to show heterogeneous echotexture with overall decrease in volume in gland size by nearly 50% within the right lobe and approximately 30% within the left lobe.
Conclusion: Thyroid lymphoma should be suspected in a rapidly enlarging thyroid gland with or without pain or compressive symptoms. However, we propose that it should also be considered in the setting of FDG-PET avidity in thyroid tissue in setting of clinical suspicion.
Diffuse FDG-PET scan avidity in the thyroid gland does not automatically equate to malignancy as prospective and retrospective information has shown that diffuse uptake can be seen incidentally, in cases of diffuse goiter, Graves disease or chronic lymphocytic thyroiditis and that the uptake has been seen to range between 5.6-16.8 SUV. (2) The American Thyroid Association 2015 thyroid cancer guidelines propose that if diffuse uptake is seen within the thyroid gland on PET imaging that thyroid ultrasound imaging and functional testing be undertaken. If imaging shows findings suggestive of only chronic lymphocytic thyroiditis (diffuse heterogeneous gland) that no further action is required. In this patient a different approach was taken with investigations pursued in the setting of enlarging thyroid gland on imaging and known extranodal lymphoma allowing for ultimate diagnosis.
References: 1. Stein, S., et al. “Primary Thyroid Lymphoma: A Clinical Review.” The Journal of Clinical Endocrinology & Metabolism, vol. 98, no. 8, 2013, pp. 3131-3138
2. Karantanis, D., et al. “Clinical Significance of Diffusely Increased 18F-FDG Uptake in the Thyroid Gland.” Journal of Nuclear Medicine, vol. 48, no. 6, 2007, pp. 896-901
Graves’ Disease, a Late Complication of Chronic Graft vs Host Disease
Authors: Kreit Helen , Rehman Aziz Ur , Bright Tamis Marie 
Published: May 2021

Abstract
Introduction: Graft-versus-host disease (GVHD), a complication of bone marrow transplant (BMT), occurs when the donor white blood cells attack the recipient’s host cells and can occur acutely or chronically several years post-transplant. It is very rare for chronic GVHD to cause hyperthyroidism due to Grave’s disease and thyrotoxicosis years after BMT. Hyperthyroidism after BMT is thought to occur by GVHD or by donor’s auto-reactive lymphocytes transferred to recipient, with majority of cases occurring with donors that have an underlying autoimmune thyroid condition.
Case Report: We report a 62 year old male who presented with palpitations, tremors, sweating, weight loss, and anxiety for 3 weeks. Past medical history was significant for allogenic BMT due to AML 14 years ago, which was further complicated by GVHD of eye, liver and skin. Physical exam was negative for thyromegaly or thyroid tenderness. Initial work up showed TSH 0.03 (normal 0.4-5.0 MUI/l), free T4 3.32 (normal 0.6-1.2 ng/dl), TSI 194 % (normal &lt;140 %). Ultrasound revealed a diffuse hypervascular thyroid gland with numerous avascular cystic areas in both lobes and increased homogenous, symmetrical uptake consistent with Graves’ disease was noted on radioactive iodine uptake scan. With clinical suspicion of GVHD leading to Graves’ disease with subsequent thyrotoxicosis, he was started on methimazole. However, due to persistent increase in transaminases, concern for agranulocytosis with methimazole, and risk of developing worsening GVHD of the skin or eye with radioactive iodine therapy, he underwent total thyroidectomy. His pathology showed bilateral lymphoepithelial lesions with florid follicular hyperplasia, marked monocytoid hyperplasia, and Germinal B cells positive for CD10 and negative for BCL2. Lymphoepithelial lesions can be seen in chronic lymphocytic thyroiditis due to persistent inflammation.
Conclusion: This case raises the question on the etiology of thyroid nodules and Graves’ disease occurring after BMT. We believe that his pathology findings may be due to chronic GVHD. Hyperthyroidism after BMT is extremely rare, with only a few case reports documenting this phenomenon. We believe that our patient developed hyperthyroidism 14 years after BMT most likely as a sequela of chronic GVHD with underlying immune dysregulation leading to formation of TSI and thyroiditis due to cellular invasion. This suggest a multifactorial etiology of hyperthyroidism in patients with GVHD. However, more prospective studies are required to the explain etiology of hyperthyroidism in GVHD. Moreover, such patients should be closely monitored for development of thyroid dysfunction or thyroid nodules.
A Case of Atypical Thyroid Storm Presentation With Subsequent DIC, Hypoglycemia, Kidney Failure and Shock Liver
Authors: Xue Liang , Singh Samar 
Published: May 2021

Abstract
Background: Thyroid storm is a rare and life-threatening emergency requiring prompt intervention that is diagnosed based on a combination of clinical, physical and biochemical findings. Presented here is a case of thyroid storm which proved a diagnostic challenge due to its atypical presentation and whose management was further complicated by uncommon sequelae including DIC, hypoglycemia, kidney failure and shock liver. Clinical Case: A 37-year-old female with Graves’ disease presented to the Emergency Department with a chief complaint of facial swelling with concern for recent food allergy. Initial labs revealed elevated fT4 of 5.17 ng/dL (n 0.6-1.12 ng/dL) and suppressed TSH &lt;0.01 uIU/mL (n 0.45-4.12 uIU/mL), but otherwise normal range BMP and CBC. While awaiting admission in the ED, she had normal cognition, stable vitals and scored 25 per Burch-Wartofsky scale. Given significant thyrotoxicosis and history of non-compliance with Graves’ treatment, patient was nevertheless empirically started on treatment for suspected thyroid storm in addition to treatment for possible allergic reaction. In the ED patient suddenly went into cardiac arrest with ROSC achieved after 2 rounds of CPR. Following ROSC, labs showed BG of 24 mg/dL (n&lt;115 mg/dL), WBC to 24 thousand/mcL (n 4.0-10.5 thousand/mcL), lactate &gt;10 mmol/L (n&lt; 2mmol/L), D-dimer &gt;20,000 ng/mL (n&lt;500 ng/mL), AST 1869 U/L (n&lt;52 U/L). Patient underwent a prolonged hospital course requiring treatment for hypoglycemia, shock liver, acute kidney injury, heart failure, atrial fibrillation, DIC and embolic CVA. Her initial shock liver improved and transitioned into a cholestatic picture, prompting a change in her thionamides from PTU to Methimazole, then back to PTU later on. Her multi-organ failure improved gradually over 3 weeks with mechanical ventilation, CRRT, blood transfusion, stress dose steroids and comprehensive critical care treatment. Patient was eventually discharged with close endocrine, ENT, cardiology, and neurology follow up. Conclusion: In diagnosing and treating this rare but life-threatening endocrine emergency, a strong clinical suspicion should not be detracted by an atypical presentation and prompt action is needed. It is vital to remember that this is first and foremost a clinical diagnosis that can be further supported with laboratory and physical findings. Furthermore, this case is an example of the extent of multi-organ failure that can result from thyroid storm.
A Case of Parathyroid Adenoma Three Decades Post Radioactive Iodine Therapy: Is It Just a Coincidence or Real Risk?
Authors: Panjawatanan Panadeekarn , Sekar Vijaykumar , Hughes Joseph 
Published: May 2021

Abstract
Background: External radiation to the head and neck is a known risk factor for the development of parathyroid adenoma. But the incidence is very rare in internal radiation recipients. Here we describe a case of parathyroid adenoma after 30 years of radioactive iodine therapy for Graves’ disease.
Clinical Case: A 50-year-old female presented during an annual visit with progressive fatigue, polyuria, polydipsia, nocturia, muscle weakness, and some memory impairment. She had a past medical history of Graves’ disease treated with radioactive iodine therapy 30 years ago with subsequent hypothyroidism, controlled essential hypertension, asthma, and obesity BMI 32.5 kg/m2. There was no history of nephrolithiasis, fractures, pituitary tumor, or acid reflux. Family history was noted for thyroid diseases, no calcium issues or hyperparathyroidism. Neck examination did not reveal any thyromegaly or palpable nodule. Laboratory tests showed calcium 11.4 mg/dL (8.6-10.3), ionized calcium 6.1 mg/dL (4.2-5.4), parathyroid hormone 213.9 pg/mL (12-88), total vitamin D 22 ng/mL (31-100), TSH 0.47 uIU/mL (0.34-3.00), Free T4 1.1 ng/dL (0.6-1.6), creatinine 0.7 mg/dL (0.6-1.2), eGFR &gt;60 ml/min/1.73 m2, 24-hr urine calcium 405 mg (40-350). Bone density revealed T-score -4.9 at the lumbar spine, -2.8 at the total hip, -3.1 at the femoral neck, and -2.9 at distal 1/3 radius. Neck ultrasound showed atrophy of the thyroid gland with a lobulated hypoechoic area measuring up to 1.3 x 0.9 x 0.9 cm without internal blood flow at posterior inferior to the right lobe of the thyroid gland. Parathyroid SPECT/CT scan revealed no evidence of parathyroid adenoma. The hypoechoic lesion was suspected to be a lymph node according to imaging studies. However, according to laboratory and bone density results, we suspected primary hyperparathyroidism in which the patient required surgery due to current symptoms. The patient underwent surgery with an intraoperative finding of a nodule at the superior of the right parathyroid gland. A frozen section of the nodule was sent which confirmed parathyroid adenoma. The gland, weighted 483 mg, was removed with subsequent improvement of intraoperative parathyroid hormone level from 238.5 pg/mL to 26.5 pg/mL. Follow up calcium was at 9.5 mg/dL. The patient was supplemented with calcium and vitamin D afterward. Her symptoms improved significantly.
Conclusion: Hypercalcemia in a patient with prior history of radioactive iodine therapy should raise concern for parathyroid adenoma. Imaging of the parathyroid gland should be cautiously interpreted with laboratory tests as it could be a false negative. Due to patient met criteria for surgery, the surgical approach should be pursued for both diagnostic confirmation and definite treatment. Intraoperative parathyroid hormone monitoring is beneficial in equivocal imaging and in reflecting successful resection of uniglandular disease.