bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of Differential Diagnosis of Thyroid Nodules by Shear Wave Elastography, the Stiffness Map
Authors: Yoo Myung Hi , Kim Hye Jeong , Choi In Ho , Park Suyeon , Yun Sumi , Park Hyeong Kyu , Byun Dong Won , Suh Kyoil
Published: May 2021

Background: Fine-needle aspiration (FNA) is the first step in the differential diagnosis of thyroid nodules. However, malignancy rate of the indeterminate FNA is reported as 20-50 %. We aimed to evaluate the efficacy of shear wave elastography (SWE), the map of stiffness in the differential diagnosis of the histopathology of thyroid nodules. Methods: We retrospectively reviewed the medical records of 258 consecutive patients who visited the thyroid clinic for thyroid nodules and who underwent SWE before ultrasound-guided FNA and/or core-needle biopsy. We analyzed the EI using the total nodular region of interest method by the Q-Box Trace program. Thyroid nodules were divided in to 4 categoies according to maximum elasticity (EMax) and nodule depth/width (D/W) ratio; Category 1 (EMax ≥42.6 kPa & D/W<0.9), Category 2 (EMax <42.6 kPa & D/W<0.9), Category 3 (EMax ≥42.6 kPa & D/W≥ 0.9) and Category 4 (EMax<46.2 kPa & D/W≥ 0.9). The cutoff value of EMax was set using ROC curve analysis to predict follicular neoplasm (FN) from nodular hyperplasia (NH). Cutoff value ​​for nodule D/W ratio was set using ROC curve analysis to differentiate malignant nodule. Results: FN showed the lowest EMax among all pathologies and lower EMax than NH (p<0.05). FN was distributed mostly in the category 2 (70%) and NH was distributed mainly in the category 1 (73.9%). CLT belonged mostly to the category 1 (57.1%). PTC belonged in majority to the category 3 (58.9%) and the rest.to the category 1 (25%). So NH was the most frequent pathology group in category 1.FN was the most frequent pathology group in the category 2 and PTC was the most frequent pathology group in the category 3. Conclusion: SWE showed characteristic patterns of various pathology groups reflecting the degree of fibrosis and the information of EMax and nodule depth/width (D/W) ratio determining the category was useful to predict the pathology of thyroid nodules along with the advantage of noninvasiveness.
PD-L1 Expression in Papillary Thyroid Cancer
Authors: Joshi Tripti , Gupta Ruta , Olaya A Luisa Fernanda , Yu Bing , Gargya Ash , McLennan Susan , Chua Elizabeth Lian
Published: May 2021

There is limited data on prevalence of PD-L1 expression in papillary thyroid cancer (PTC). Anti- PD-L1 therapy is now being trialled for head and neck cancers including thyroid cancer. Whether presence of PD-L1 staining in PTC might result in a better response to anti-PD-L1 therapy is uncertain.

We evaluated the frequency of tumoral PD-L1 expression using standard antibody (SP263) and clinicopathologic factors including mutation status - BRAF, NRAS, KRAS using OncoFocus Mass Array System in an Australian PTC cohort with low or high risk of recurrence /treatment response as per 2015 ATA guidelines.

The cohort had 128 patients; 66% were females; 40% had both multifocal and bilateral PTC; 47% had low recurrence risk, of whom 92% had excellent treatment response; 34% had high recurrence risk, of whom 37% had structural incomplete treatment response. There was nil (0%) PD-L1 staining in 59%, 1% staining in 20%, 5-10% staining in 11%, >10% staining in rest of the cohort; 30%, 40% and 70% staining was seen in 2% each. PD-L1 in immune cells was positive in 62%. There was no significant association between PD-L1 tumour status and age, gender, size of tumour, multifocality, bilaterality, both multifocality and bilaterality, lymphovascular invasion, perineural invasion, extrathyroidal extension (ETE), histological variants, risk stratification, treatment response, metastases or mutation status. Among PD-L1 negative vs positive patients, BRAFV600E was present in 64.9% vs 67.5%, NRAS in 8.8% vs 0% and nil mutation in 26 % vs 33 % p=0.15. The staining thresholds were chosen according to existing literature. When analysed according to the percentage of PD-L1 staining (0%, 1-10% and >=10% thresholds), there was no significant association between PD-L1 staining category and other features, except for ETE (35% vs 65% vs 27%; p=0.007), a relationship that remained significant in a multivariable-adjusted model (OR 9.9, p=0.04). PD-L1 staining thresholds of <5% and >=5% were significantly associated with the size of tumour (24.7±15.4 vs 33.3±21.8; p=0.02) and histological variants (57 % vs 61% for classic variants and 27% vs 11% for follicular variants, p=0.03).

This is the first study to our knowledge that analysed PD-L1 staining based on the risk stratification categories. The majority of PTC showed negative or low staining intensity for PD-L1 expression. There was no significant association between PD-L1 staining, clinicopathologic characteristics and mutation status of the PTC. Relatively less ETE was seen in the group that showed >=10% and also >=5% PD-L1 staining as compared to the group that showed 1% <10% and 1% to <5% staining which is an interesting observation and needs further investigation. The significant variation in reported PD-L1 staining in current literature reiterates that the method is yet to be optimised. Moreover the relationship between PD-L1 staining and PTC remains to be further investigated.
Recurrence Factors and Characteristic Trends of Papillary Thyroid Cancer Over Three Decades
Authors: Chatchomchuan Waralee , Thewjitcharoen Yotsapon , Karndumri Krittadhee , Porramatikul Sriurai , Krittiyawong Sirinate , Wanothayaroj Ekgaluck , Vongterapak Somboon , Butadej Siriwan , Veerasomboonsin Veekij , Kanchanapituk Auchai , Rajatanavin Rajata , Himathongkam Thep
Published: May 2021

Background: The prevalence of thyroid cancer is rising worldwide. Although thyroid cancer has a favorable prognosis, up to 20% of patients experienced recurrent disease at some point during follow-up. The present study aimed to examine the recurrent factors that determined the outcomes of papillary thyroid cancer (PTC) and the characteristic trends in Thai patients over the last 30 years in a single institute. Methods: We reviewed the clinical data of all patients with PTC who were treated between 1987 and 2019. Clinical characteristics, epidemic trends, factors associated with the persistent or recurrent disease, disease-specific survival rate and disease-free survival rate were analysed. Results: A total of 235 patients with PTC who were registered between 1987 and 2019 were reviewed. The mean age was 41.0 ± 14.3 years, with a mean follow-up of 113 months. Papillary thyroid microcarcinoma (PTMC) was consistently increased and accounted for 21.4% (50/235) of total cases. According to American Thyroid Association (ATA) risk stratification, high ATA risk was found 24% of all PTMCs in the last decade, and 16.7% of these patients experienced local recurrence during the follow-up period. Coexistence with Hashimoto’s thyroiditis (HT) was found in one-fifth of the patients with PTC and was correlated with a low recurrent rate (HR 0.21, p = 0.009). Factors associated with the persistent or recurrent of disease included age > 55 years and high ATA risk. The overall disease-free survival rate and disease-specific survival rate were 77.4% and 98.3%, respectively. Conclusions: The prognosis of PTC is generally considered favorable. However, more than one-third of patients with PTMC demonstrated more aggressive clinical behavior, particularly in the last decade of the study. Coexistence with HT might contribute to a better prognosis in cases of PTC.
Research on Clinical, Subclinical Characteristic of Incidental Thyroid Nodules
Authors: Nguyen Bay Quang
Published: May 2021

Background: Incidental thyroid nodules has become more prevalent in recent years due to applying diagnostic imaging tests. Many studies show that the rate of thyroid cancer in this group of patients is relatively high. Objective: To assess patients with incidentally detected thyroid nodules, including those who were diagnosed with thyroid cancer. Materials and Methods: A cross-sectional study, which involved 208 patients with 389 thyroid nodules detected by thyroid ultrasound. All patients have thyroid function tests. 272 nodules were performed fine-needle aspiration. Patients with thyroid cancer were assessed histopathology after removal. Results: The participants’ mean age was 47.22 ± 12.02. The female / male ratio is 6.7/1. No patients had history of head and neck irradiation or living in epidemiological areas with high prevalence of goiter. TSH level: 96.2% normal, 2.4% low, 1.4% high. In thyroid cancer group: 100% of patients had normal thyroid function. Nodule characteristics on ultrasound: Majority of thyroid nodules had diameters less than 1.5 cm (85.6%), multi-nodularity(52.9%). The largest carcinoma nodule was 2.35 cm, 22.2% of patients with thyroid cancer had ≥ 3 nodules. The malignancy rate of TIRADS 5 was 70.6%. FNA results of 272 thyroid nodules: the majority were Bethesda II (74,2%); the incidence of carcinoma (Bethesda V, VI) is 17.4%. 36 patients account for 17,3%, with 42 nodules were performed surgery, the results of histopathology were 100% of papillary thyroid carcinoma, which was consistent with cytological results. Conclusion: Thyroid nodules are common in women patients at the age of 31-60 with normal thyroid function. Most of them are <1.5 cm in size. There are 17.3% of patients were thyroid carcinoma.
A Rare Case of T-Cell Histiocyte Rich Large B-Cell Lymphoma of the Thyroid in a Patient With Hashimotos
Authors: Zainal Abir , Maradana Jhansi , Torres Mira
Published: May 2021

Introduction: T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) is a rare form of large B-cell lymphoma, which usually involves the lymph nodes exclusively. We describe a patient with Hashimoto’s thyroiditis who was discovered to have THRLBCL arising from the thyroid. Clinical Case: A 78-year-old female with a history of Hashimoto’s thyroiditis noted increase in the size of her left thyroid lobe for two months despite normal TSH on Levothyroxine, prompting an ultrasound which revealed several enlarged left sided cervical lymph nodes and an enlarged left thyroid gland. Cytology from an FNA of a left level 3 lymph node showed atypical lymphoid infiltrate featuring scattered large atypical cells in a background of small lymphocytes. Immunohistochemical testing was PAX5+, CD30- and CD15-. Cytology from an FNA of left thyroid revealed identical changes and immunohistochemistry demonstrated PAX5+ and CD20+. Concurrent flow cytometric studies demonstrated increased CD4 to CD8 ratio among T cells. Excisional biopsy of a left cervical lymph node confirmed a diagnosis of THRLBCL. PET/CT exhibited lymphadenopathy above her diaphragm and splenic involvement. Her bone marrow biopsy was negative for involvement. She was deemed Stage III with international prognostic index (IPI) of 2 corresponding with low-intermediate risk. She was commenced on chemotherapy R-CHOP with plan to complete 6 cycles. Discussion: THRLBCL is characterized by scattered atypical B lymphocytes on a background of T lymphocytes and histiocytes. Usually, T-cells are predominantly CD8+, in contrast to our patient. Some studies identified cases of predominant CD4+ and PD1+ T cells. Cytology revealed scattered small B-cells and large B-cells, a feature that is not typically seen in THRLBCL. A diagnosis of diffuse transformation of nodular lymphocyte predominant Hodgkin lymphoma was considered but the diffuse proliferation outside of CD21+ and involvement of the thyroid is not compatible with such diagnosis. Similarly, a diagnosis of follicular helper T-cell lymphoma with admixed large B-cells was considered but while PD1+ CD4+ T cells are present, there was no aberrant antigen expression by flow cytometry or T cell clonality. THRLBCL mainly involves lymph nodes and presents at advanced Ann Arbor stages with high IPI. Malignant lymphomas of the thyroid gland are exceedingly rare, accounting for 2% of thyroid cancers, out of which the literature reveals a single case report of THRLBCL arising from the thyroid. THRLBCL represents an aggressive form of lymphoma and is treated according to stage-matched DLBCL, although the effects of Rituximab in this population is variable. Conclusion: Hashimoto’s is considered a risk for thyroid lymphoma usually diffuse large B-cell lymphoma and MALT lymphoma. We present a rare case of THRLBCL occurring in the setting of Hashimoto’s with acute thyroid gland enlargement.
Breaking the 2015 ATA Recommendation for Medullary Thyroid Cancer (MTC) Guidelines. Case Report
Authors: Mardones Adelqui Sanhueza
Published: May 2021

Male patient, 49 years old. Thyroid US with a suspicious nodule. Fine Needle Aspiration Biopsy (FNAB) suggest MTC, with a pre-operative serum calcitonin (CTN) of 591 pg/mL. Total thyroidectomy with central and bilateral dissection was performed. Biopsy. Results: MTC in left thyroid nodule of 2,6 cm without metastasis in 29 lymph nodes. In the follow up, undetectable serum CTN for 6 years. In 2015 serum CTN of 4.7 pg/mL and Carcinoembryonic antigen (CEA) 1.2 ng/mL. Evolution of serum markers in table 1.

Along with the rise of markers, the neck US showed bilateral subcentimetric LN in the group IV. In the follow-up, the size is stable; FNAB of the LN in different centers don′t show any sign of malignancy, along with undetectable CTN levels in the sample. The doubling time of CTN and CEA (March 2020): 16 and 51.3 months respectively. Given the lack of cervical compromise and going against MTC ATA 2015 recommendations, a neck and thorax CT, hepatic MRI and bone scintigraphy were ordered, despite not presenting CTN levels >150 pg/mL. The hepatic MRI shows 3 hypervascular hepatic lesions, which are recommended to be contrasted with a liver-specific agent (gadoxetic acid) to improve characterization of the lesions. Thanks to this procedure, 4 focal lesions are discovered, one larger than 10 mm, without contrast agent retention, suggests metastasis. PET 68Ga-DOTATATE: 2 focal lesions with overexposure of somatostatin receptors in the hepatic parenchyma, which correlate to known lesions, with SUVmáx of 6,8 y 7,3. After an evaluation by a surgeon, surgery is done in July 2020 removing 5 lesions; the biopsy confirmed MTC metastasis. Conclusions: the clinical guidelines may give general direction and allow to manage cases based on evidence; however, they must always be used considering the context of each particular case. In this one, if the guidelines had been strictly followed, it would not have been possible to detect the hepatic metastases within the window of opportunity to achieve a surgical resection with curative intent.

Table1. Mar15 CTN 7,3 Pro- CTN 0,12 CEA 1,2. Oct15 CTN 16,1 Pro- CTN 0,15 CEA 0,7. Jan16 CTN 17 Pro- CTN 0,18 CEA 0,5. Jul16 CTN 17,9 Pro- CTN 0,18 CEA 1,6. Nov16 CTN 20,7 Pro- CTN 0,33 CEA 1,8. Aug17 CTN 35,2 Pro- CTN 0,4 CEA 1,8. Jun18 CTN 42,5 Pro- CTN 0,34 CEA 1,8. Nov18 CTN 50,7 Pro- CTN 0,57 CEA 1,8. Mar19 CTN 59,5 Pro- CTN 0,52 CEA 2,4. Nov19 CTN 80,7 Pro- CTN 0,66 CEA 2,4. Mar20 CTN 111 Pro- CTN 0,8 CEA 2,9. Normal Values: CTN < 2 pg/mL, Pro- CTN < 0,12 ng/mL, CEA < 0,1 ng/mL
Calcitonin Non-Secreting Mixed Medullary-Papillary Thyroid Carcinoma: Report of a Rare Entity and Therapeutic Implications
Authors: Oleinikov Kira , Grozinsky-Glasberg Simona , Atlan Karine , Maimon Ofra , Popovtzer Aron , Weinberger Jeffrey M , Hirshoren Nir
Published: May 2021

Background: Medullary thyroid carcinoma (MTC) is a relatively rare and aggressive form of thyroid malignancy arising from parafollicular cells. The biochemical hallmark of MTC is elevated serum calcitonin (CTN), which aids initial diagnosis and disease surveillance. An atypical form of calcitonin non-secreting MTC has been previously described, with just over 50 cases published in the literature. This case report of a true mixed medullary-papillary thyroid carcinoma with a non-secretory medullary component is exceptionally rare. Clinical Case: A 67-year-old male presented with new-onset hoarseness and was found to have a 4 cm thyroid nodule replacing the right lobe with associated ipsilateral cord paralysis and ipsilateral cervical lymphadenopathy. The patient had no family history of endocrinopathies. A diagnosis of MTC was rendered at core-needle biopsy, based on the characteristic morphological findings and positive immunohistochemistry (IHC) for calcitonin (CTN) and CEA. Cervico-thoracic CT demonstrated tracheal and esophageal involvement by the tumor. The serum CEA was 8.7 pg/ml [0-5]; however, serum CTN was undetectable < 2 pg/ml [2-8.2]. The patient subsequently underwent a total thyroidectomy with bilateral central neck dissection and right lateral neck dissection. Excision of the tumor necessitated the dissection of involved esophageal muscle from mucosa and removal of four tracheal rings with part of the cricoid. The surgical specimen demonstrated a single 3.6 cm tumor in the right thyroid lobe composed of medullary and papillary intermixed neoplastic cells (mixed MTC-PTC) with predominant medullary component and gross extrathyroidal extension. Positive IHC for calcitonin, CEA, and thyroglobulin confirmed the diagnosis. Out of ninety resected lymph nodes in total, five nodes were involved with medullary carcinoma (with extranodal extension), and three had papillary carcinoma micrometastases. Postoperatively, the patient underwent adjuvant external beam radiation to the surgical bed. At four-month follow-up, CEA levels were 1.4 pg/ml [0-5], TSH 0.04 µIU/ml [0.35-4.9] and thyroglobulin (Tg) with Tg Ab levels were undetectable. The patient continues close surveillance. Conclusion: Calcitonin non-secreting MTC management is challenging due to the lack of a reliable biomarker that aids initial diagnosis, surveillance, and prognostic stratification. Whether a rare form of non-secretory MTC represents a more aggressive variant is yet to be determined. The prognosis of patients with mixed MTC-PTC tumors appears to be driven by the medullary component that prioritizes the optimal surgical approach and further management.
Clavicular Metastasis as an Initial Presentation of Papillary Thyroid Cancer
Authors: Fung Russell K , Fasen Madeline , Warda Firas , Natter Patrick , Nedrud Stacey , Fernandes Rui , Alkhasawneh Ahmad , Gandhi Gunjan Yogendra
Published: May 2021

Background: Papillary thyroid cancer (PTC) metastases to the clavicular bone is rare. While the lung is considered the most common site of metastases from thyroid malignancy, osseous metastases, if seen, are usually observed at sites such as humerus, pelvis, radius, and scapula.

Clinical Case: A 44-year-old man presented with an enlarging right neck mass for six months after light trauma to that area. Other than mild pain in the described area, the patient reported 20 lbs of weight loss. Initial x-ray revealed a large soft tissue density mass that extended to the midline of the right proximal clavicle. Soft-tissue neck ultrasound noted a 5.4 x 3.6 cm mass extending from the thyroid with findings of increased vascularity and calcification. CT scan of the neck depicted the extension of the mass into the adjacent sternoclavicular junction with osteolysis of the middle third of the clavicle as well as the superior aspect of the sternal body. A fine needle aspiration of the mass revealed thyroid neoplasm with follicular features and positive immunostaining consistent with thyroid carcinoma. Chest CT showed invasion into the right proximal clavicle, tracheal deviation and extension into the mediastinum. The patient underwent a composite resection of the tumor, including a segmental osteotomy of approximately two-thirds of the medial clavicle. Post surgically the patient’s serum calcium was low at 7.9 mg/dL with a concurrently low PTH of 9 pg/mL and a low 25-hydroxyvitamin D of 16.8 ng/mL. Thyroglobulin was markedly high at 15655.0 ng/mL (confirmed on dilution), and thyroglobulin antibody < 1.0 IU/mL. Pathology report confirmed PTC with extra-thyroidal extension and involvement of clavicle (staged pT4a pN0), however margins and lymph nodes were negative for carcinoma with further genomic findings showing positive KRAS mutation. The patient’s post-operative course was complicated by a large expanding left neck hematoma after a fall; he was immediately readmitted with the hematoma subsequently safely evacuated. Levothyroxine has been held at this time with plans for radioactive iodine treatment eight weeks after surgery.

Conclusion: Bone metastases from differentiated thyroid cancer is rare, especially clavicular metastasis arising from PTC. Bone scintigraphy, x-ray and fine needle biopsy are some of the widely utilized methods employed in the evaluation of bone metastasis in the setting of thyroid malignancy. The prospect of recovery is generally favorable in cases of bone metastases, however various factors can affect prognosis and long-term outcomes.

Reference: Krishnamurthy A. Clavicle metastasis from carcinoma thyroid- an atypical skeletal event and a management dilemma. Indian J Surg Oncol. 2015;6(3):267-270. doi:10.1007/s13193-015-0387-y
Diagnosis of Medullary Thyroid Cancer During COVID-19 Pandemic, the Benefit of Using a Standardized Protocol
Authors: Mortensen Michael , Dong JiaXi , Vinales Karyne Lima , Correa Ricardo Rafael
Published: May 2021

Introduction: The reported prevalence of malignancy in thyroid nodules ranges from 4% to approximately 10%, with a small percentage (~2-8%) being medullary thyroid cancer (MTC). During the COVID-19 pandemic, elective thyroid FNA was temporarily halted at our institution. In response to this, our institution has devised a new protocol to aid in the detection of MTC, which includes serum calcitonin measurement as a surrogate marker for potential MTC. A severely elevated calcitonin (>100 pg/mL) is considered for surgery even without FNA diagnosis. We present a case of MTC that was detected due to the adopting of this protocol during COVID-19 pandemic at the Phoenix VAMC. Case Presentation: 71 year old male with an incidentally noted 3.0 cm solid, hypoechoic nodule with internal calcification, TI-RADS category 5. TSH level was normal at 3.309 mIU/mL. The patient denied any personal or family history of thyroid cancer, MEN syndrome, radiation exposure, or compressive symptoms. Following established protocol published by our institution in clinical thyroidology we performed a serum calcitonin that came back elevated at 1515 pg/mL (normal < 10 pg/mL). Given the marked elevation in serum calcitonin levels and highly suspicious radiographic appearance of the thyroid nodule, we strongly suspected medullary thyroid cancer and elected to send him directly for total thyroidectomy without performing FNA. The patient underwent total thyroidectomy with central neck dissection. Pathology showed a 3.2 cm medullary thyroid carcinoma without extrathyroidal extension or perineural invasion. Lymphovascular invasion was present. 6/10 central comparement lymph nodes were positive for metastatic disease. Postoperative calcitonin level was 2 pg/mL. Discussion: Our patient had markedly elevated serum calcitonin levels in addition to a high-risk ultrasonographic features, which was highly suspicious for MTC. Per our COVID-19 protocol, we measured the serum calcitonin level to screen for MTC and then referred him directly to surgery without FNA given the high suspicion for MTC. By using this protocol, we were able to diagnose and treat MTC expeditiously. The measurement of serum calcitonin is still controversial in the U.S, with the ATA remaining equivocal on this method. We believe that our case can serve as a practical example that validates our institution’s use of calcitonin screening of thyroid nodules in diagnosing MTC during the COVID-19 pandemic.
Incidental Diffuse Sclerosing Variant Papillary Thyroid Cancer in Grave’s Disease
Authors: Canales Nicolle , Nieves Yadiel Rivera , Ortega Nydia Ivette Burgos , Castellano Janet Marie Colon , Cordero Nicole Hernández , Santini Alberto Javier Grana , Feliciano-Emmanuelli Melba , Gonzalez-Rodriguez Loida Alejandra , Alvarado Milliette , Ramirez Margarita , Carlo Victor J , Mojica Wilma Rodriguez , Pabón Marcel Mesa
Published: May 2021

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.
Papillary Thyroid Carcinoma Within Thyroglossal Duct Cyst
Authors: Anbari Raghda Al , Xhikola Majlinda , Kadiyala Sushma
Published: May 2021

A 55-year-old female with medical history of hypothyroidism and fibrocystic disease of the breast presented with complains of a painful anterior neck mass, difficulty swallowing and hoarseness of the voice. Symptoms had progressed over a period of 5 months. CT neck with contrast indicated the presence of an ectopic thyroid tissue anterior to the thyroid cartilage measuring approximately 1.7 x 1.2 x 3.1 cm, with indistinct inferior margins and internal calcifications. The hyoid bone or thyroid cartilage had no irregularities. The thyroid gland itself was unremarkable except for small complex thyroid nodules in both lobes. No masses within the pharynx or larynx were noted.

Family history was significant for lymphoma in her father.

On physical exam, a hard, mobile right anterior neck mass was appreciated. Labs showed normal TSH of 1.05 uIU/mL and normal free T4 of 1.2 ng/dL.

Further evaluation with a dedicated neck US showed a right submandibular mass, superior to the thyroid, lobulated and heterogeneous measuring 2.0 x 1.0 x 2.3 cm with multiple areas of calcifications and internal Doppler flow. The thyroid gland had normal size and texture with bilateral sub centimeter non-concerning nodules.

After ENT evaluation and an unremarkable flexible fiberoptic nasolaryngoscope, patient underwent surgical excisional biopsy of the neck mass. Pathology was consistent with thyroglossal duct cyst with the presence of thyroid follicles. An incidental finding of a 0.9 cm papillary microcarcinoma was noted, which was encapsulated with focal extracapsular follicular structures showing papillary nuclear features with no perineural or lymphovascular invasion. The tumor cells were immunoreactive for TTF-1 and PAX8.

Development of papillary thyroid cancer within the thyroglossal duct cyst is a rare event, reportedly occurring in 1% of thyroglossal duct cysts. There are no well-established management guidelines.

Current management strategies consist of monitoring with serial neck ultrasound versus total thyroidectomy with consideration of postsurgical I-131 treatment, based on pathology results. Our patient opted for undergoing total thyroidectomy.
Percutaneous Polidocanol Injection as an Alternative Treatment in Differentiated Thyroid Cancer Oligometastasis
Authors: Alvarez Castillo Marlen Alejandra , Palomo Antonio Segovia
Published: May 2021

Introduction: Differentiated thyroid cancer (DTC) presents central lymph node metastasis in 20-50% and lateral in 12-86% of patients, the treatment of choice is surgical reintervention but it carries a higher risk of complications secondary to fibrosis formation in the surgical bed. Alternative nonsurgical therapies such as percutaneous ethanol injection (PEI), radiofrequency or laser ablation have been described. Objective: To report a case of oligometastasis in CDT which underwent percutaneous polidocanol injection (PPI). Clinical Case: A 35-year-old female who underwent a total thyroidectomy in 06-2019 for papillary thyroid cancer (AJCC: stage I/ ATA: intermediate risk), and ablative dose of 150 mCi I131, under treatment with levothyroxine 150 mcg/d. Hospitalized 02-2020 for progressive dysphonia of 2 months of evolution, with studies of TSH 0.04 mIU/ml, TgAb 13 IU/ml, Tg 0.5 ng/ml and neck USG: right lymph node level III of 0.97 cm in short axis, suspected of malignancy. Tg washout 4743.72 ng/ml (positive), 1cc of 1% polidocanol is administered, guided by USG. 7 days later with 0.90 cm in short axis, a second dose of 1% polidocanol was administered and a new Tg washout was taken, 2.4 ng/ml (indeterminate). She was reevaluated in the first and fourth months of the procedure, with 0.10 cm in the short axis and complete disappearance of the lesion, respectively. Control studies at the fourth month of TgAb 13 IU/ml, Tg 0.4 ng/ml. Discussion: PEI is described for thyroid cysts and adenomas and for cervical lymph node metastases, this is a minimally invasive procedure in the treatment of lesions smaller than 10 mm but requires multiple sessions and it can cause pain due to extravasation, skin necrosis and damage to the recurrent laryngeal nerve. It requires a follow-up time of up to 65 months, producing a reduction in serum Tg less than 2.4 ng/ml, a decrease in the size of the lesion and disappearance in 46% of the cases. In our center we have experience with PPI in thyroid cysts and adenomas since 2017, this requires fewer sessions and a lower dose, obtaining results of volume reduction in thyroid cysts of 80%. In this case we observed a reduction of 90% in the first month and disappearance in the fourth month, with a significant decrease in Tg washout from the first administration. Conclusion: Polidocanol is safe and effective so it should be considered in the treatment of oligometastasis in DTC.
Solitary Fibrous Thyroid Tumor: A Case Report
Authors: Mohamed Abubakr H B , Qureshi Faisal , Eldin Randa Sharag
Published: May 2021

Introduction: Solitary fibrous thyroid nodules are rare tumors and can mimic benign thyroid goiter and neoplasms. Case Description45 years old Caucasian female, with no significant past medical history, who presented to endocrinologyclinic for left neck mass evaluation. She denied previous history of thyroid disease, weight loss, cold/heatintolerance, menstrual irregularity, toxic or obstructive thyroid related symptoms. Her family history issignificant for maternal pancreatic cancer. Clinical exam was unremarkable except for left thyroid mass. An initial thyroid ultrasound showed left thyroid nodule 20 x16 x 25 mm in size five years prior topresentation. Repeated Fine Needle aspiration yielded benign follicular cells, histiocytes and fewlymphocytes. The nodule continued to increase in size reaching 46 mm in the long axis per thyroidultrasound at presentation to clinic. Her TSH, FT4 and total T3 remained within normal ranges. She wasreferred for surgical evaluation and underwent left thyroid lobectomy. Pathology reported 50 mm wellcircumscribed intrathyroidal neoplasm composed of spindle cells with pauci to moderate cellularity with noincreased mitotic activity, nuclear atypia, or necrosis. Immunohistochemistry was positive for STAT 6 andCD34and negative for PAX-8, TTF-1, S100 and SMA. The patient remains euthyroid with no lymph nodeor organ involvement after 5 years from initial presentation. Discussion: Solitary fibrous tumors (SFT) of the thyroid are rare although they have been described in differentanatomic sites (1). It presents as slow growing, painless, non toxic nodule in middle age of both sexes (1,2). The diagnosis of these tumors via FNA is difficult due to cellular paucity. Histologic findings may bechallenging due to shared features with other thyroid undifferentiated, papillary and follicular cancervariants. Immunohistochemistry are warranted to assist in confirmation-STAT6 and CD34 (3). SFT tumorsare mostly benign tumors and carries favorable prognosis. References: (1) Thompson, L.D.R., Wei, C., Rooper, L.M. et al. Thyroid Gland Solitary Fibrous Tumor: Report of 3 Cases and aComprehensive Review of the Literature. Head and Neck Pathol13, 597–605 (2019)(2) Ghasemi-Rad M, Wang KY, Jain S, Lincoln CM. Solitary fibrous tumor of thyroid: a case report with review ofliterature. Clin Imaging. 2019;53:105–107. doi: 10.1016/j.clinimag.2018.09.011.(3) Matoso A, Easley SE, Mangray S, Jacob R, DeLellis RA. Spindle cell foci in the thyroid gland: an immunohistochemicalanalysis. Appl Immunohistochem Mol Morphol. 2011;19(5):400–7.
A Case of Rare Autoimmune Pancytopenia Due to Graves’ Disease
Authors: Wang Ally Wen , Mahajan Geeti , Etra Aaron , Saul Shira R
Published: May 2021

Introduction: Graves’ disease has been associated with cytopenias, most commonly anemia. Pancytopenia is a rare complication and is not often encountered.

Case Presentation: A 54-year-old woman with history of multiple sclerosis on alemtuzumab was referred for abnormal thyroid function tests. At the initial visit, the patient reported a 20-pound unintentional weight loss, tremors, sweating and heat intolerance. She was 3 years post-menopausal and had no history of recent viral illness, contrast exposure or family history of thyroid disease. Physical exam revealed an anxious appearing woman with fine tremors in both hands, hyperreflexia but no lid lag or exophthalmos. Labs included TSH <0.005 uIU/mL (0.400-4.2), free T4 2.89 ng/dL (0.80-1.50), TSH receptor binding antibody 8.24 IU/L (< 2.00), TSI 7.27 IU/L (<0.56), WBC 2900/uL (4500-11000), ANC 1746/uL (1900 - 8000), hemoglobin 11.4 g/dL (11.7-15.0) and platelet 207,000/uL (150,000-450,000). Thyroid ultrasound noted sub-centimeter hypoechoic/cystic nodules and 24-hour thyroid uptake showed 56.4% symmetric uptake (upper limit of normal 30%). Due to leukopenia, the patient was started on propranolol and underwent radioiodine ablation with 14.8 mCI. Two weeks later, she reported easily bruising and gum bleeding and her blood work was significant for pancytopenia. The patient was referred to hematology and two bone marrow samples were obtained. Though MDS/MPN was initially suspected based on atypia in both specimens, there were no immunophenotypic, cytogenetic or molecular abnormalities suggesting a neoplastic process. Instead the patient was thought to have autoimmune pancytopenia secondary to Graves’ and the atypia was believed to be secondary to peripheral consumption. She was started on prednisone 1 mg/kg/day with resolution of her cytopenias.

Discussion: Graves’ disease has been associated with hematological abnormalities including isolated anemia (the most common), thrombocytopenia or leukopenia. Pancytopenia is an uncommon complication and is rarely described in the literature. The exact mechanism remains unclear, but may be related to either reduced production of hematopoietic cells from the bone marrow or increased destruction of mature hematopoietic cells due to autoantibodies. Since thyroid hormones are known to increase erythropoietin, this leads to an exaggerated consumption of iron, folic acid and vitamin B12 and can cause various forms of anemias. Leukopenia may be secondary to immunologic destruction whereas thrombocytopenia may be due to antiplatelet antibodies or increased splenic sequestration. Pancytopenia is rare. Our patient was treated with high dose prednisone with resolution of her pancytopenia, which suggests an autoimmune process as the mechanism. Our case showcases a rare complication of Graves’ disease and highlights that high dose steroid therapy may improve cytopenias associated with this condition.
A Case of Thyroid Eye Disease Revealed During Secondary Adrenal Insufficiency
Authors: Ibrahim Amira , Loseva Victoria
Published: May 2021

Introduction: Thyroid eye disease (TED) or Graves’ orbitopathy (GO) is an autoimmune disease of the retro-orbital tissues. GO is mostly associated with hyperthyroidism in 90% of patients; however, it may coexist with hypothyroid conditions in 5% of cases. Clinical Case: A 56-year-old male with a past medical history of autoimmune diseases including hypothyroidism and Ulcerative Colitis on chronic steroid therapy presented to the emergency department with nausea, fatigue, weight loss, and muscle weakness. The patient stated that his glucocorticoids were abruptly discontinued a month prior to his current presentation. On examination, vitals were stable. The patient was somnolent with a depressed mood. He had bilateral periorbital edema and bilateral eyeball protrusion, left more pronounced than right. Extraocular muscle movement revealed a delay in the lateral movement of the left eye causing double vision on exam. He had no starring look or lid lag. The thyroid gland was normal in size and contour. Initial Laboratories revealed a white blood cell count of 6.7 K/mcL (4-10 K/mcL) with 18% eosinophil count (0-5%). Cortisol at 8 AM was 2.9 mcg/dL (4.3 -22.4 mcg/dl). The patient was managed for secondary adrenal insufficiency and restarted immediately on Prednisone. A review of a recent CT scan of the head revealed bilateral proptosis with no signs of compressing lesions. Further thyroid studies revealed TSH of 2.9 mcIU/mL (0.3-3.7 mcIU/mL), free T4 of 0.8 ng/dL (0.75-2.0 ng/dL), free T3 of 1.6 ng/dL (2.4-4.2 ng/dL), TPO antibodies <0.3 IU/mL (0.0-9.0 IU/mL) and TSH receptor antibodies 0.90 IU/L (reference range <1.75 IU/L). The patient was then diagnosed with Hypothyroid Grave’s ophthalmopathy with negative antibodies given the evidence of proptosis on CT and exam revealing extraocular muscle movement restriction causing diplopia. The patient had a unique presentation of TED with hypothyroidism and asymmetric ophthalmic signs that were only manifested after the patient discontinued the prednisone and therefore unmasking the underlying disorder. Fortunately, in June of 2020, the US Food and Drug Administration (FDA) approved Teprotumumab (an insulin-like growth factor 1 [IGF-1] receptor inhibitor) for the treatment of Graves’ orbitopathy based on the findings from two 24-week trials comparing teprotumumab with placebo in 171 patients with active, moderate-to-severe orbitopathy. (1) Our patient was started on Levothyroxine along with Prednisone and referred for ophthalmology evaluation for possible qualification for Teprotumumab treatment. Conclusion: Clinician awareness of the unusual presentations of TED would allow for early recognition and prevention of progression, especially with the recently approved treatment modality. References: (1) Teprotumumab for Thyroid-Associated Ophthalmopathy. Smith TJ Et al. N Engl J Med. 2017;376(18):1748.
A Case of Thyroid Storm With Takotsubo Cardiomyopathy and Multi-Organ Failure: What Is the Primary Cause of Hemodynamic Instability and How Do We Treat it?
Authors: Purewal Tiffany , Lesniak Christopher , Ravin Andrew , Zin Khin , Holland Soemiwati W
Published: May 2021

Introduction: Thyroid storm is a rare but life-threatening emergency. Multi-organ failure has been recognized as the most common cause of death, but conventional therapies can be limited depending on the clinical presentation. We present a case of a patient in thyroid storm who rapidly developed multi-organ failure, preventing her from obtaining potentially life-saving treatment. Case Presentation: A 68-year-old female with a past medical history of hypertension, hyperlipidemia, and Grave’s disease, who was non-compliant with medications, presented to a facility for shortness of breath after the unexpected death of her husband. She was diagnosed with a non-ST elevation myocardial infarction and new onset heart failure. At that time, her TSH level was <0.010 uIU/mL and Free T4 was 1.80 ng/dL. Imaging revealed a significantly enlarged thyroid gland measuring 8cm by 6.6cm. She was started on methimazole and discharged home. A few days after discharge, she underwent a cardiac catheterization and was found to have Takotsubo cardiomyopathy. On presentation to our facility 2 weeks later, the patient was experiencing worsening shortness of breath and anxiety. She was found to have new-onset uncontrolled atrial fibrillation with rapid ventricular response and a blood pressure of 77/38 mmHg. The Burch-Wartofsky Point Scale was calculated to be 55 points, highly suggestive of thyroid storm. TSH was < 0.010 uIU/mL, total T4 was 16.63 ug/dL, and free T4 was 3.28 ng/dL. She was initiated on propylthiouracil, cholestyramine, hydrocortisone, and esmolol. Within 12 hours, she developed fulminant multi-organ failure requiring ventilatory support and vasopressors. She also developed ischemic hepatitis and propylthiouracil was discontinued. Urgent therapeutic plasma exchange (TPE) and continuous renal replacement therapy (CRRT) were later attempted but both therapies were not initiated due to severe hemodynamic instability. A bedside echocardiogram revealed an estimated ejection fraction of 20-25%. Due to worsening cardiogenic shock, she was evaluated for extracorporeal membrane oxygenation (ECMO) but was not a candidate. She instead underwent an emergent Impella device implantation. Despite this intervention, the patient’s clinical condition did not improve after multiple vasopressors, and the patient’s family opted for comfort-focused measures. The patient died after 1 day of hospitalization. Conclusion: A multimodality approach to treatment is recommended for patients with thyroid storm but underlying conditions such as Takotsubo cardiomyopathy and fulminant multi-organ failure may complicate the treatment plan. The complexity of this case highlights the need to understand relative contraindications to salvage therapies, such as TPE, and the role for other treatment options when patients present with co-existing multi-organ failure.
A Grave Initial Presentation of Graves’ Disease in a Patient With Moyamoya
Authors: Clutter Courtney , Jordan Morgan
Published: May 2021

Background: Moyamoya syndrome is chronic stenoocclusive disease involving the intracranial internal carotid arteries and their proximal branches along with an associated condition, such as hyperthyroidism1. The concurrence of moyamoya and Graves’ disease is rare. Ischemic stroke in moyamoya syndrome is postulated to be precipitated by thyrotoxicosis-induced hemodynamic instability. Clinical Case: A 63-year old Korean female with history of moyamoya disease with two prior ischemic strokes, hypertension and type 2 diabetes mellitus presented to the ER with 6 hours of left leg weakness and involuntary arm movements. A code stroke was activated and neurologic examination was notable for left leg paresis and left arm stereotypy. CT head showed loss of gray-white matter differentiation in the right frontal lobe concerning for acute ischemia. CT angiography of the head and neck noted diffuse stenosis of intracerebral vasculature and significant stenosis of the cavernous and supraclinoid portions of the internal carotid arteries. MRI brain later confirmed an acute infarct in the right ACA distribution. Neuroimaging incidentally showed a multinodular goiter with a 1.7 cm right thyroid nodule. Subsequently TSH was obtained and resulted as <0.030 mcIU/mL (0.27-5.00 mcIU/mL) with a reflex FT4 of >7.00 ng/dL (0.6-1.8 ng/dL). A review of her prior TFTs showed biochemical euthyroidism. Due to iodinated contrast administration on admission, RAIU scan was deferred. Thyroid ultrasound showed multinodular goiter with diffuse increased vascularity and multiple TI-RADS 4 and 5 nodules bilaterally. On further questioning, the patient reported tachycardia, diarrhea, weight loss and decreased appetite prior to hospitalization. A diagnosis of Graves’ disease was confirmed with TSI of 70.7 IU/L (0.00-0.55 IU/L). She was started on methimazole 20 mg twice daily and propranolol 20 mg q6h. FT4 downtrend from >7.00 to 3.3 ng/dL at time of discharge. Following four weeks of methimazole 20 mg daily, FT4 normalized to 1.70 ng/dL. The patient chose to continue antithyroidal drug therapy for treatment of Graves’ disease. Conclusion: Thyroid function assessment should be considered when evaluating a patient with moyamoya and acute ischemic stroke. If moyamoya syndrome associated with Graves’ disease is identified, treatment should be aimed at maintenance of euthyroidism. Reference: 1. Scott RM, Smith ER. Moyamoya disease and moyamoya syndrome. N Engl J Med. 2009 Mar 19;360(12):1226-37. Disclaimer: The views expressed herein are those of the authors and do not reflect the official policy or position of Brooke Army Medical Center, the U.S. Army Medical Department, the U.S. Army Office of the Surgeon General, the Department of the Army, the Department of the Air Force and Department of Defense or the U.S. Government.