bluuebunny/crossref_metadata_2025_split huggingface dataset:
PSAT386 Thyroglossal Duct Carcinomas: Systematic Review and Meta-analysis of 550 Cases Reported in the Literature
Authors: Paparodis Rodis , Zoupas Ioannis , Jaume Juan , Livadas Sarantis , Karvounis Evangelos , Bantouna Dimitra , Imam Shanawaz 
Published: November 2022

Abstract

Introduction
Thyroglossal duct (TGD) carcinoma is an uncommon entity, located in the TGD remnant, and is diagnosed in patients undergoing evaluation of the neck for midline swelling, or incidentally after removal of a TGD cyst. Despite the presence of multiple publications on the topic, no systematic characterization of these tumors has been performed to date. The present study aims to characterize the tumors found patients diagnosed with TGD remnant malignancies.

Methods
We performed a systematic search for the term "Thyroglossal duct" in Pubmed, Embase and Cochrane databases on December 1, 2021 and retrieved 1229 records. We included all manuscripts containing cohorts, case reports or case series, when the manuscript or its abstract was available in English, Italian, French or Spanish language. We reviewed the demographics, the histological report of the thyroglossal duct and the thyroidectomy specimen (when this was performed) and the features of tumor aggressiveness, when these were available.

Results
We incorporated data from 366 manuscripts, comprising 1202 patients operated for TGD disease. Out of these, n=550 cancers were identified, consisting of n=475 (86.4%) Papillary thyroid carcinomas (PTC), n=8 Follicular thyroid carcinomas (FTC) (1.5%), n=5 Hürthle cell carcinomas (HCC) (0.9%), n=27 Squamous cell carcinomas (SCC) (4.9%), n=2 poorly differentiated/anaplastic thyroid carcinomas (ATC) (0.4%), n=1 Adeno-SCC (0.18%), n=1 Adenocarcinoma (0.18%), n=12 synchronous PTC/FTC (2.2%), n=1 synchronous PTC/SCC (0.18%) and n=18 of unclear histological diagnosis (4.75%). N=173/446 (38.8%) patients were males and n=273/446 (61.2%) were females; gender was not available in n=104 cases. Mean cancer size was 1.4±1.4cm (range 0.01-7.0cm); n=88/173 (50.9%) were microcarcinomas (&lt;1cm). Distant metastasis was present in n=7 patients (1.3%). Lymph node involvement was reported in n=76/286 cases (26.6%); extrathyroidal extension was present in n=75/234 cases (32.1%); capsular invasion was present in 72/142 cases (50.7%). Adjuvant therapy with I-131 was used in n=131/550 cases (23.8%).

Conclusions
TGD remnant cancers include various tumors, with histology and features of aggressive behavior similar to what we see in thyroid cancer cases. More research is needed to enhance our understanding of the mechanisms involved in the pathogenesis and malignant behavior of these infrequently identified tumors.
Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
LBSUN345 Diagnostic Dilemma In A Case of Vipoma
Authors: Priyadarshini Shista 
Published: November 2022

Abstract

Introduction
Vasoactive intestinal polypeptide secreting tumors (VIPoma) are rare neuroendocrine tumors that have nonspecific features of watery diarrhea, hypokalemia and achlorhydria. With an incidence of 1 in a million per year, it is diagnosed based on serum VIP levels (&gt;75pg/ml) followed by imaging studies to localize the tumor and look for metastases. We present a challenging case of VIPoma that was successfully managed with surgical exploration despite classic yet nonspecific clinical features and poor evidence on imaging.

Case Discussion
A 78-year-old Caucasian woman presented with persistent secretory diarrhea for 2 months. Past medical history was significant for intractable peptic ulcer disease and Billroth II reconstruction. Laboratory investigations showed severe hypokalemia (2.1 mmol/l), serum bicarbonate 13 and chloride 117. Blood glucose and calcium levels were within normal range. Stool studies confirmed secretory diarrhea with stool osmotic gap of 10 mOsm/kg but no growth. Serum gastrin, parathyroid hormone, chromogranin and urine 24-hour 5-hydroxy indoleacetic acid (5-HIAA) levels were within normal limits. Plasma VIP levels were elevated at 79 pg/mL. Computed tomography of the abdomen and pelvis did not show any evidence of pancreatic tumor or biliary ductal dilatation. Endoscopic ultrasound could not fully evaluate the head of pancreas but showed unremarkable liver, pancreatic body and tail. Capsule endoscopy was unremarkable as well. An octreotide scan, however, demonstrated increased activity near the head of the pancreas and abdominal aorta. As clinical picture and octreotide scan findings were consistent with VIPoma, operative exploration for possible pancreaticoduodenectomy was pursued. No evidence of palpable or occult metastatic disease was found; but intraoperative color doppler ultrasound localized two lesions less than 1 cm in size at the level of the uncinate process and ampulla. An open pancreaticoduodenectomy was performed and the existing Billroth II anatomy was modified to accommodate pancreatojejunostomy, gastrojejunostomy and choledochojejunstomy. A jejunostomy tube was placed for enteral access. At 2-month post-operative follow-up, the patient had significant improvement of his diarrhea. Radiographic resolution was noted on repeat octreotide scan 4 months following resection.

Conclusion
VIPomas are usually diagnosed by elevated VIP levels and imaging studies are used to localize the tumor for further treatment. However, this case highlights that in secretory diarrhea with elevated VIP level and no alternate diagnosis, despite negative imaging studies further exploration with octreotide scan is warranted. Surgical exploration may show the site of lesion and appropriate surgical intervention may lead to resolution of VIPoma.
Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
ODP541 Burr Under the Saddle: A Case of Sellar Plasmacytoma
Authors: Alkaissi Hussam , Kubbar Alaa , Gliwa Agnieszka 
Published: November 2022

Abstract

Background
Sellar and parasellar plasmacytoma is a rare tumor that often poses a diagnostic challenge as it can often be misdiagnosed as a nonfunctioning pituitary adenoma. Here we present a case of sellar plasmacytoma and point to clues helping establish the diagnosis.

Clinical case
60-year-old male presented with two weeks of worsening morning headache followed by eyelid drooping. A physical exam was notable for left-sided ptosis, mydriasis, poor pupillary light reflex, and otherwise normal eye movement in cardinal positions . Head CT revealed 33×32×30 mm sellar mass; thus endocrinology team was consulted for evaluation. Further workup revealed normal TSH, free T4, ACTH and morning cortisol, FSH, LH, and IGF-1. He had a minimal elevation of prolactin levels at 33 ng/ml after serial dilutions (reference range: 2-17.7 ng/ml). We noticed the patient had an elevated serum protein concentration of 10.6 g/dl (reference range: 6.4-8.3 g/dl) with an albumin level of 4 gm/dl with an elevated gamma gap at 6.6 g/dl, suggestive of elevated gamma globulins. Serum protein electrophoresis showed an M-spike of 3.8 g/dl, and urine was positive for Bence Jones protein. Brain MRI with and without contrast showed homogeneously enhancing mass mainly within the sphenoid sinus extending down to the clivus, isointense on T1, hyperintense on T2 with no diffusion restriction, encasing the left internal carotid artery with intact pituitary and optic chiasm. Transsphenoidal biopsy showed sheets of plasma cells. Immunohistochemistry showed lambda light chain only and negative for kappa light chain. Flow cytometry was positive for CD38, CD138, CD200, and CD56, confirming a diagnosis of plasmacytoma. Fluorescent in situ hybridization was positive for FGFR3-IGH t(4;14) translocation, indicating a higher risk. Otherwise, beta-2-microglobulin, lactate dehydrogenase, and albumin were within normal. Initial management included pulsed dexamethasone of 40 mg for four days, followed by a taper with skull base radiotherapy, a total of 3500 cGy. Ptosis and eye movement gradually improved. The patient was discharged to start bortezomib-based treatment by the oncology team.
Clinical lesson: Based on large case series, sellar plasmacytoma often presents as headache (70%), visual changes (77%), and hyperprolactinemia (38%). Imaging shows clinal invasion (74%), cavernous sinus invasion (49%), encasement of the internal carotid artery (17%) [1]. The differential diagnosis for such findings on imaging includes nonfunctioning pituitary adenoma, chordoma, and meningioma. Special attention to gamma gap, urinary, and serum protein electrophoresis can urge to perform a biopsy to prove the diagnosis of plasmacytoma and avoid delay in therapy. Reference: 1. Lee J, Kulubya E, Pressman BD, et al. Sellar, and clival plasmacytomas: case series of 5 patients with systematic review of 65 published cases. Pituitary. 2017;20(3): 381-392. doi: 10.1007/s11102-017-0799-5
Presentation: No date and time listed
OR16-2 Steroid Receptor Co-Activator Complexes Regulate Metabolic PFKFB Enzymes to Drive Therapy Resistant ER+ Breast Cancer
Authors: Benner Elizabeth , Dos Santos Camila , Hagen Kyla , Lange Carol , Ostrander Julie , Temiz Nuri , Trousdell Marygrace , Truong Thu 
Published: November 2022

Abstract
Recurrence of metastatic breast cancer stemming from acquired endocrine and chemotherapy resistance remains a health burden for women with luminal (ER+) breast cancer. ER+ tumor cells can remain viable but quiescent for years to decades. Contributing factors to metastatic spread include the survival and expansion of breast cancer stem cells (CSCs). Breast CSCs are poorly proliferative and frequently exist as a minority population in recurrent tumors. Our objective is to define novel signaling pathways that govern therapy resistance in ER+ breast cancer. We previously showed that cytoplasmic complexes composed of steroid receptor (SR) co-activators, PELP1 and SRC-3, modulate breast CSC expansion through upregulation of the HIF-activated metabolic target genes PFKFB3 and PFKFB4. PELP1 interacts with PFKFB proteins, and inhibition of PFKFB3 and PFKFB4 kinase activity blocks PELP1-induced tumorspheres and protein-protein interactions with SRC-3. PFKFB inhibitors in combination with ER targeted therapies blocked proliferation and tumorsphere formation in multiple models of advanced breast cancer, including paclitaxel (TaxR) and tamoxifen (TamR) resistant models and ER+ patient-derived organoids (PDxO). Chemotherapy and endocrine therapy resistant models contained increased levels of cytoplasmic PELP1, PELP1/SRC-3 complexes, and phenocopied PELP1/SRC-3/PFKFB biology and CSC behavior. To better understand CSC-mediated pathways in the context of therapy resistance, we performed RNA-seq on 3D-cultured TaxR tumorspheres to enrich for CSCs. Pathway analysis revealed that TaxR tumorspheres upregulate stem (Sox2-Oct4-Nanog), HIF, and progesterone mediated pathways. Progesterone receptor (PR) is a known contributor to CSC populations, and we observed increased PR mRNA and protein expression in TaxR cells grown as tumorspheres. Additionally, in vivo emergence of circulating tumor cell (CTC) populations was observed in ER+ TaxR mammary intraductal (MIND) xenografts. Together, our data suggest that PELP1, SRC-3, and PFKFBs cooperate to drive ER+ tumor cells that include CSCs and CTCs. Our findings are applicable to therapy resistant models, indicating that SR co-activator complexes are a key mediator of resistance in ER+ breast cancer and may cooperate with PR to promote therapy resistant CSCs. Identifying non-ER pharmacological targets offers a useful approach to blocking metastatic escape from standard of care ER/estrogen (E2)-targeted strategies to overcome endocrine and chemotherapy resistance in ER+ breast cancer.
Presentation: Sunday, June 12, 2022 11:15 a.m. - 11:30 a.m.
OR30-3 Direct and VGLL1-Mediated Gene Regulation by GRHL2 During Mesenchymal to Epithelial Transition in Breast Cancer
Authors: Audemard Eric , Boucher Jonathan , Lemieux Sebastien , Mader Sylvie , Roux Philippe , Haidar Salwa 
Published: November 2022

Abstract
The transcription factor (TF) GRHL2 controls normal epithelial differentiation in different tissues. It is expressed in all breast cancer subtypes except those with a mesenchymal phenotype (claudin-low subtype), where its ectopic expression leads to induction of a mesenchymal-epithelial transition (MET) (1). Here we explored the mechanisms by which GRHL2 induces MET in claudin-low breast cancer cell lines using a combination of ChIP-seq and RNAseq analyses upon modulation of GRHL2 expression in mesenchymal and epithelial cell lines. Direct DNA binding by GRHL2 was enriched in proximity of genes positively regulated in mesenchymal cell lines, which include several epithelial TFs as well as an array of epithelial genes. Biotinylation and mass spectrometry analysis of membrane proteins confirmed surfaceome remodeling via induction of membrane proteins with roles in cell-cell contacts and adhesion. Repression of mesenchymal genes was mediated in part by direct induction of miRNAs targeting mesenchymal transcription factors. In addition, GRHL2 strongly induced expression of the cofactor VGLL1, whose expression is high in the triple-negative (TNBC) basal-like subtype. VGLL1 overexpression in mesenchymal cell lines and suppression in basal-like TNBC cells confirmed its role in mediating part of GRHL2 signaling, in particular via interaction with and modulation of TEAD transcription factors. In addition, GRHL2 also interacted with VGLL1 upon its induction in mesenchymal cells, recruiting it to some of its binding motifs, suggesting a multilayered cross-talk between GRHL2 and TEAD factors. Together, our results indicate that GRHL2 acts as a master regulator in the induction of TNBC epithelial differentiation via direct upregulation of epithelial transcription factors, miRNAs and TEAD cofactor VGLL1, resulting in both upregulation of epithelial genes and suppression of mesenchymal genes.(1) Cieply B. et al., Cancer Res. 2013 Oct. 1;73 (20): 6299-309
Presentation: Tuesday, June 14, 2022 10:15 a.m. - 10:30 a.m.
PSAT275 A Rare Case of Thyroid-Stimulating Immunoglobulin-Induced Thyrotoxicosis in Poorly Differentiated Metastatic Thyroid Cancer
Authors: Berardo Jeronimo , Fogelfeld Leon A , Mihailescu Dan V , Padilla Sorto Maria E , Trepashko Donald W 
Published: November 2022

Abstract
We report case of a rare of hyperthyroidism secondary to functional metastatic thyroid carcinoma, which is an infrequent phenomenon that can be challenging to diagnose and treat, as low thyroid-stimulating hormone (TSH) levels can suppress the development and growth of differentiated thyroid carcinoma cells. Previous studies have reported that hyperfunctioning thyroid carcinoma may present as autonomous functioning thyroid nodules (AFTN) within the thyroid gland, or as functioning lesions in metastatic foci, which is our case. Functional thyroid carcinomas are capable of absorbing iodine, as well as synthesizing and releasing thyroxine, are often associated with follicular thyroid carcinomas. Potential mechanisms for the thyrotoxicosis include a large aggregate tumor mass, as well as the presence of thyroid-stimulating immunoglobulins (TSIs) that are able to stimulate the thyroid-stimulating hormone (TSH) receptors of the thyroid carcinoma. In this clinical case, patient presented with high titers of TSIs, and metastatic thyroid carcinoma, with persistent hyperthyroidism after thyroidectomy and with a remarkable radioactive iodine treatment response.
Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT279 Thyroid Oncocytic tissue: Presenting as metastatic thyroid carcinoma
Authors: Gannamani Gowtham , Gibbs Otto , Milazzo Eliana , Harper Jennifer , Kaczmar John , Richardson Mary , Fernandes Jyotika 
Published: November 2022

Abstract

Case
A 76-year-old male with status post thyroidectomy in 2017 for compressive multi-nodular goiter. Pathology reported as benign thyroid tissue with follicular hyperplasia.
In 2020, he presented with incidental finding of left neck mass on MRI. Ultrasound neck confirmed two extra-thyroidal masses left neck largest dimension of 2.9 cm. FNA reported as benign follicular cells favoring benign thyroid tissue. Surgical resection of the neck masses revealed benign thyroid tissue with focal oncocytic features and two benign lymph nodes.
In 2021, he presented with left chest mass. Biopsy reported benign thyroid tissue, no evidence of papillary cancer. PET CT confirmed hypermetabolic chest mass, multiple lytic bone lesions and pulmonary nodules. Referred to Endocrinology for further evaluation, Thyroglobulin level elevated at &gt;4500 ng/mL (Tg Ab &lt;1.0 IU/mL). Molecular testing of chest wall mass was positive for TERT and HRAS mutations, loss of 22q and gain of 17q on microarray consistent with changes found in thyroid cancer.
Surgical resection of the chest wall mass not feasible due to size and location. External beam radiation for cytoreduction of the sternal mass planned and radioactive iodine therapy if tumor RAI (radioactive iodine) avid. He is currently not a candidate for tyrosine kinase inhibitor (TKI) as he recently had acute coronary event. Zoledronic acid infusions initiated for bone involvement.

Discussion
Thyroid carcinomas that exhibit vascular invasion, or anaplastic dedifferentiation are readily and consistently diagnosed. However, the morphology of primary oncocytic thyroid tumors is similar to their non-oncocytic counterparts posing a huge challenge for the pathologist. This controversial and often confusing area of thyroid pathology requires careful evaluation for accurate diagnosis and management for patients with oncocytic thyroid lesions. Molecular and microarray testing should be considered when in doubt.
Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT374 Prognostic Utility of BRAF V600E Mutation as a Risk Factor for Tumor Recurrence among Filipino Patients with Papillary Thyroid Cancer
Authors: Chiu Harold Henrison , Corpuz Dianne Grace , Tonga Angelo Dela , Galarion Ma Jowina , Hernandez-Diwa Michele , Macalalad-Josue Anna Angelica , Maningat Patricia , Paragas Sahra May , Pintor Oliver 
Published: November 2022

Abstract

Background
Epidemiological studies have shown that Filipinos have a higher prevalence of well-differentiated thyroid cancer and a higher rate of recurrence amongst the different ethnicities. The BRAF V600E mutation has long been proposed as a potential prognostic marker in aggressive papillary thyroid cancers. In this study, we determined whether BRAF V600E mutation can be a novel risk factor for tumor recurrence in papillary thyroid cancer.

Methodology
We conducted an age and sex-matched case-control study of 14 patients for each arm using the histopathologic diagnosis of papillary thyroid cancer and with an available paraffin block as sample source. Pertinent demographic, clinical and histopathologic data were collected. The BRAF V600E mutation was detected using polymerase chain reaction following DNA extraction from the paraffin-embedded tissue blocks. Multivariate logistic regression was performed to determine the association between presence of BRAF V600E mutation with tumor recurrence at 95% confidence interval.

Results
The BRAF V600E mutation prevalence was at 32.14% (95% CI: 15.88-52.35%) for all cases; 21.43% (95% CI: 4.66-50.80%) among those with recurrence and 42.86% (95% CI: 17.66-71.14%) among those without recurrence. There was insufficient evidence to prove a significant association between BRAF V600E mutation and recurrence, OR 0.50 (95% CI: 0.08-2.34, p = 0.327).

Conclusion
Our study showed that there was a trend towards no association between BRAF V600E mutation and recurrence. However, due to the small sample size, we cannot accurately establish an association between the presence of the BRAF V600E mutation and increased recurrence rates among Filipinos diagnosed with papillary thyroid cancer. Despite the dismal results, we still opted to present the results of our study as there were many challenges encountered in the molecular diagnosis of thyroid cancer in developing countries like the Philippines. This opens the many possibilities for future studies and collaborations amongst different institutions to firmly establish the role of BRAF V600E in Filipinos with papillary thyroid cancer tumor recurrence.
Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSUN375 What Blindness and Paraganglioma Have in Common? A Rare Case of Paraganglioma Syndrome
Authors: Esaki Yumiko , Harbuz-Miller Inga 
Published: November 2022

Abstract

Background
Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors with an annual incidence in the U.S. of 500-1600 cases per year. Approximately 30-35% of PPGLs harbor germline mutations, while 35-40% are due to somatic mutations. Recent studies have identified the association between somatic mutations of the hypoxia-inducible factor 2 alpha (HIF2A) gene and a new syndrome of PPGLs associated with congenital polycythemia. Patients present with recurrent PPGLs, congenital malformation of intracranial veins, malformation of macula and retina, and type I Chiari malformations.

Case
A 44-year-old man with history of in-utero stroke, congenital blindness, polycythemia and spinal stenosis had an incidental para-aortic lesion found during workup of back pain. He experienced episodic palpitations associated with diaphoresis, headache and uncontrolled hypertension for the past eight year. There was no family history of neuroendocrine tumors. Dedicated abdominal computer tomography with contrast showed a right adrenal enhancing lesion measuring 1.4×1.2 cm and a conglomerate of heterogenous enhancing periaortic lesions measuring up to 5 cm in the mid-abdomen. Biochemical work up revealed plasma free normetanephrine of 27.5 nmol/L (0.00-0.89) and plasma free metanephrines of 0.49 nmol/L (0.00-0.49). Gallium 68 DOTATATE scan showed multiple avid retroperitoneal lesions measuring up to 4.4 cm and an avid right adrenal nodule. He underwent right adrenalectomy and para-aortic lesion resection with perio-operative alpha blockade. Pathology confirmed synchronous pheochromocytoma (1.5 cm, Ki-67&lt; 1%, with capsular and periadrenal fat invasion) and paraganglioma (9.3 cm, Ki-67 &lt; 1%, with lymphovascular invasion and one out of nine lymph nodes positive for metastatic disease). Post-operatively, his metanephrines normalized and a six-months positron emission tomography scan showed no evidence of disease. Genetic testing has been delayed.

Discussion
This case illustrates a rare syndrome of PPGLs, congenital blindness, and polycythemia, likely due to somatic mutations of HIF2a. HIF is an alpha/beta heterodimer. HIF2a becomes a transcription factor after dimerization with HIF2b. Any mutations that stabilize HIF protein leads to transcription of hypoxia inducible genes resulting in angiogenesis, polycythemia, and tumorigenesis. In our patient, we suspect the stroke in-utero may have been related to abnormal intracranial angiogenesis and/or polycythemia. Recognition of this syndrome and lifelong surveillance is imperative due to risk of recurrence of PPGL. Targeted therapies such as a HIF2a inhibitor have been proposed and trials are ongoing. Our patient remains disease free on radiographic and biochemical surveillance.
Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.