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Polycystic ovary syndrome (PCOS) is a common endocrine condition characterised by a range of reproductive, endocrine, metabolic and psychological abnormalities. Reports estimate that around 10% of women of reproductive age are affected by PCOS, representing a significant prevalence worldwide, which poses a high economic health burden. As the origin of PCOS remains largely unknown, there is neither a cure nor mechanism-based treatments leaving patient management suboptimal and focused solely on symptomatic treatment. However, if the underlying mechanisms underpinning the development of PCOS were uncovered then this would pave the way for the development of new interventions for PCOS. Recently, there have been significant advances in our understanding of the underlying pathways likely involved in PCOS pathogenesis. Key insights include the potential involvement of androgens, insulin, anti-Müllerian hormone and transforming growth factor beta in the development of PCOS. This review will summarise the significant scientific discoveries on these factors that have enhanced our knowledge of the mechanisms involved in the development of PCOS and discuss the impact these insights may have in shaping the future development of effective strategies for women with PCOS.

Orbilia xanthostigma, with golden yellow to yellow-orange apothecia and O. leucostigma, with white to very pale rose-lilaceous apothecia, were described by E.M. Fries over 200 years ago. Each of the two taxa, which are not easy to interpret because type material is lacking, was proposed in the past as lectotype of the genus Orbilia. In the here presented circumscription, which follows the current usage, O. xanthostigma is among the most frequently recorded species of the genus, whereas O. leucostigma appears to be much less common. Both grow gregariously on decorticated hygric gymno- and angiosperm wood or rarely bark and show a worldwide distribution. They are characterised by minute, strongly curved, warted ascospores and a dicranidion-like anamorph. Except for apothecial colour, there are no other notable morphological differences between them, either in the teleomorph (asci, ascospores, paraphyses) or anamorph (conidiophores, conidia). Because of their strong similarities, the two taxa have often been treated as infraspecific variants (subspecies, varieties) of a single species or even as synonyms. In order to overcome the ambiguities associated with the two names, O. delicatula, a name proposed by P.A. Karsten for a collection with golden yellow apothecia, was suggested by B. Spooner as a replacement name for them. The present study reveals unexpectedly high ITS and LSU variation within a morphologically extremely homogeneous group, representing over 16 more or less invariable genotypes whenever more than one sample with a sequence was available. ITS and LSU rDNA data from European (Luxembourg, Germany, Ukraine) and Macaronesian (Tenerife) collections suggest that the two colour variants represent two distinct species with a 16.5% ITS and 3.5% LSU D1–D2 distance, but very low infraspecific variation (0.2% ITS, 0% LSU). A sample with scattered yellow apothecia from Luxembourg on a xeric branch deviates from typical European-Macaronesian O. xanthostigma by 4% (ITS) and 0.7% (LSU). Further available sequences from samples from Asia, New Zealand and North America with mainly yellow apothecia clustered in various other clades that represent further distinct genotypes. In the absence of morphological characteristics, none of these genotypes are given names pending further investigation. Only two of these genotypes are sufficiently distinct to be recognised morphologically: O. aureocrenulata from tropical, Middle and South America, with golden yellow apothecia with a crenulate margin and prominent stipe, and O. xanthoflexa from temperate, northeastern North America with yellow sessile apothecia with a smooth margin and larger, less curved, smooth-walled ascospores.

Polycystic ovary syndrome (PCOS) is a common, multifactorial disorder characterized by endocrine, reproductive, and metabolic dysfunction. As the etiology of PCOS is unknown, there is no cure and symptom-oriented treatments are suboptimal. Hyperandrogenism is a key diagnostic trait, and evidence suggests that androgen receptor (AR)-mediated actions are critical to PCOS pathogenesis. However, the key AR target sites involved remain to be fully defined. Adipocyte and muscle dysfunction are proposed as important sites involved in the manifestation of PCOS traits. We investigated the role of AR signaling in white adipose tissue (WAT), brown adipose tissue (BAT), and skeletal muscle in the development of PCOS in a hyperandrogenic PCOS mouse model. As expected, dihydrotestosterone (DHT) exposure induced key reproductive and metabolic PCOS traits in wild-type (WT) females. Transplantation of AR-insensitive (

Context Exposure to endocrine disrupting chemicals (EDCs) are associated with underactive thyroid glands, and possibly autoimmunity. Firefighters are exposed to EDCs from flame retardants; however, the prevalence and risk factor associations of thyroid antibodies among firefighters are unknown. Context We aimed to determine the prevalence of thyroid peroxidase antibodies (TPOAb) and associated sociodemographic and occupational risk factors among firefighters. Methods Firefighters attending professional health and safety conferences between November 2018 and January 2020, and with no prior diagnosis of thyroid disease were invited (n = 278) to submit a health survey, blood samples, and complete a thyroid ultrasound. The survey assessed for sociodemographic and occupational characteristics, including a history of familial thyroid disease, smoking, firefighter tenure, and job rank, radiation exposure, and mitigation practices of occupational exposures. Serum thyroid peroxidase antibody (TPOAb) was also assessed. Results Approximately 39.9% of firefighters evaluated had a positive TPOAb test. The mean age for those TPOAb positive was lower than those who tested negative (41.4 ± 7.9 vs 43.1 ± 7.9 years, P = 0.07) but this difference was not significant. Firefighters with a family history of thyroid disease had a statistically significant higher prevalence of TPOAb compared with those without a family history (60.0% vs 37.5%, P = 0.02); this association remained significant after adjusting for sociodemographic and occupational factors (odds ratio 2.99; CI, 1.31-6.85). Conclusion The prevalence of TPOAb is high among firefighters in our study, and family history is a significant determinant of testing positive for TPOAb. Firefighters may benefit from TPOAb and thyroid stimulating hormone tests, and screening for family history of thyroid disease at baseline employee medical check-ups. This finding suggests the need for further studies.

Background Florida Firefighters experience a higher risk of thyroid cancer than non-firefighters. This study examines whether the histologic types and tumor stage of thyroid cancer is different among firefighters compared to other occupational groups. Methods Eligible cases were firefighters (n = 120) identified in a linkage of Florida Cancer Data System (FCDS) registry records (1981–2014) and Florida State Fire Marshal’s Office employment and certification records, and non-firefighters classified into: blue-collar (n = 655), service (n = 834), white-collar (n = 4,893), and other (n = 1,789). Differences in thyroid histologic type (papillary, follicular, and rare/other less common forms of thyroid cancer), tumor stage, and age at diagnosis were evaluated using multinomial logistic regression models comparing blue-collar, service, white-collar, and other occupational groups with firefighters. Univariate odds ratios as well as odds ratios adjusted for age, gender, race, tumor stage, and year of diagnosis (aOR) and 95% confidence intervals (95%CI) were reported. Results Service (aOR = 4.12; 95%CI: 1.25—13.65), white-collar (aOR = 3.51; 95%CI: 1.08—11.36), and blue-collar (aOR = 4.59; 95%CI: 1.40—15.07) workers had significantly higher odds of being diagnosed with rare histologic types of thyroid cancer vs papillary type compared to firefighters. Service (aOR = 0.42; 95%CI: 0.27—0.66), white-collar (aOR = 0.39; 95%CI: 0.26—0.59), blue-collar (aOR = 0.36; 95%CI: 0.23—0.56), and other (aOR = 0.34; 95%CI: 0.22—0.53) occupational groups have a significantly lower odds of being diagnosed with rare vs papillary type at a younger age (30—49 years) vs 50—69 years compared to firefighters. However, stage at diagnosis was not significantly different among occupational groups. Conclusion Firefighters diagnosed with thyroid cancer experience a higher odds of papillary compared to rare histologic types of thyroid cancer relative to other workers; there is no evidence of an increased odds of late-stage diagnosis in firefighters relative to other worker groups. Firefighters may benefit from routine screening and active surveillance of suspected thyroid tumors especially given the excellent treatment outcomes available for those diagnosed with early-stage papillary thyroid tumors.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder, defined by reproductive and endocrine abnormalities, with metabolic dysregulation including obesity, insulin resistance and hepatic steatosis. Recently, it was found that skeletal muscle insulin sensitivity could be improved in obese, post-menopausal, pre-diabetic women through treatment with nicotinamide mononucleotide (NMN), a precursor to the prominent redox cofactor nicotinamide adenine dinucleotide (NAD

Introduction Checkpoint Inhibitor Immunotherapy (CII) has been linked to multiple endocrinopathies. Thyroid dysfunction is more frequently associated with anti-PD-1 and anti-PD-L1 monoclonal antibody use, yet there are no good predictors for the development of thyroid complications after immunotherapy treatment. Iodinated contrast studies have been related to the development of thyroid dysfunction, and are frequently used in the oncology patient population for surveillance of malignancy and response to treatment. Methodology and Results We conducted a retrospective observational study to identify any potential association between the development of thyroid dysfunction and exposure to iodinated contrast studies in patients receiving CII. A chart review was conducted from 2012-2020. Data analysis was performed using Chi-square. Using ICD codes, 236 patients with new thyroid dysfunction after initiation of CII, and no alternative etiology for the thyroid dysfunction, were included. Out of these, 162 (68.6%) patients developed hypothyroidism, 71 (30%) developed thyrotoxicosis initially and subsequently developed hypothyroidism, and 3 (1.27%) developed hyperthyroidism. Of the total patients who developed thyroid dysfunction following CII, 145 vs.91 patients received ≥3 contrast studies, (p. 0. 0004). Discussion These findings suggest that there is an association with the use of three or more iodinated contrast studies and the development of thyroid dysfunction in patients receiving CII. More research is needed to identify additional predictors that could be utilized in clinical practice for earlier detection of patients at risk of developing CII related thyroid dysfunction. Conclusion Thyroid dysfunction following the use of CII, namely anti-PD-1 and anti-PD-L1 therapies, remains prevalent; however, it has been difficult to identify who is most at risk for this complication. This is the first study examining exposure to iodinated contrast and its potential contribution to CII thyroid endocrinopathy, and it warrants further investigation. Presentation: No date and time listed

Polycystic ovary syndrome (PCOS) is a common and heterogeneous disorder; however, the etiology and pathogenesis of PCOS are poorly understood and current management is symptom-based. Defining the pathogenesis of PCOS traits is important for developing early PCOS detection markers and new treatment strategies. Hyperandrogenism is a defining characteristic of PCOS, and studies support a role for androgen-driven actions in the development of PCOS. Therefore, we aimed to determine the temporal pattern of development of PCOS features in a well-characterized dihydrotestosterone (DHT)-induced PCOS mouse model after 2, 4, and 8 weeks of DHT exposure. Following 2 weeks of treatment, DHT induced the key PCOS reproductive features of acyclicity, anovulation, and multifollicular ovaries as well as a decrease in large antral follicle health. DHT-treated mice displayed the metabolic PCOS characteristics of increased body weight and exhibited increased visceral adiposity after 8 weeks of DHT treatment. DHT treatment also led to an increase in circulating cholesterol after 2 weeks of exposure and had an overall effect on fasting glucose levels, but not triglycerides, aspartate transaminase (AST) and alanine transaminase (ALT) levels, or hepatic steatosis. These data reveal that in this experimental PCOS mouse model, acyclicity, anovulation, and increased body weight are early features of a developing PCOS phenotype whereas adiposity, impaired glucose tolerance, dyslipidemia, and hepatic steatosis are later developing features of PCOS. These findings provide insights into the likely sequence of PCOS trait development and support the addition of body weight criteria to the early diagnosis of PCOS.

Polycystic ovary syndrome (PCOS) is a prevalent endocrine condition characterized by a range of endocrine, reproductive, and metabolic abnormalities. At present, management of women with PCOS is suboptimal as treatment is only symptomatic. Clinical and experimental advances in our understanding of PCOS etiology support a pivotal role for androgen neuroendocrine actions in PCOS pathogenesis. Hyperandrogenism is a key PCOS trait and androgen actions play a role in regulating the kisspeptin-/neurokinin B-/dynorphin (KNDy) system. This study aimed to investigate if targeted antagonism of neurokinin B signaling through the neurokinin 3 receptor (NK3R) would reverse PCOS traits in a dihydrotestosterone (DHT)-induced mouse model of PCOS. After 3 months, DHT exposure induced key reproductive PCOS traits of cycle irregularity and ovulatory dysfunction, and PCOS-like metabolic traits including increased body weight; white and brown fat pad weights; fasting serum triglyceride and glucose levels, and blood glucose incremental area under the curve. Treatment with a NK3R antagonist (MLE4901) did not impact the observed reproductive defects. In contrast, following NK3R antagonist treatment, PCOS-like females displayed decreased total body weight, adiposity, and adipocyte hypertrophy, but increased respiratory exchange ratio, suggesting NK3R antagonism altered the metabolic status of the PCOS-like females. NK3R antagonism did not improve circulating serum triglyceride or fasted glucose levels. Collectively, these findings demonstrate that NK3R antagonism may be beneficial in the treatment of adverse metabolic features associated with PCOS and support neuroendocrine targeting in the development of novel therapeutic strategies for PCOS.

La presente cartilla, está dividida en tres secciones; la primera postula las generalidades sobre lo que es conocimiento y los enfoques de investigación, la segunda enfatiza en la metodología de la investigación cualitativa, su epistemología, métodos, diseños, ontología, y otros aspectos generales. La ultima parte enfatiza en el diseño narrativo, sus aplicaciones, estrategias definición, y propone un ejemplo de como se emplea este diseño cualitativo en la investigación científica. Tiene como finalidad exponer, aclarar y explicar conceptos básicos de la investigación cualitativa, pero en particular se busca conocimiento sobre el diseño narrativo, la importancia que este diseño representa para la expresión y visualización de movimientos sociales, minorías, entre otros. También se pretende exponer la concepción histórica de este diseño, sus características, objetos y procedimientos.

Lifestyle, mainly dietary, interventions are first-line treatment for women with polycystic ovary syndrome (PCOS), but the optimal diet remains undefined. We combined a hyperandrogenized PCOS mouse model with a systematic macronutrient approach, to elucidate the impact of dietary macronutrients on the development of PCOS. We identify that an optimum dietary macronutrient balance of a low protein, medium carbohydrate and fat diet can ameliorate key PCOS reproductive traits. However, PCOS mice display a hindered ability for their metabolic system to respond to diet variations, and varying macronutrient balance did not have a beneficial effect on the development of metabolic PCOS traits. We reveal that PCOS traits in a hyperandrogenic PCOS mouse model are ameliorated selectively by diet, with reproductive traits displaying greater sensitivity than metabolic traits to dietary macronutrient balance. Hence, providing evidence to support the development of evidence-based dietary interventions as a promising strategy for the treatment of PCOS, especially reproductive traits., Lifestyle interventions are first-line treatment for women with polycystic ovary syndrome (PCOS), but the optimal diet remains undefined. Here the authors identify an optimum dietary macronutrient balance that can rectify PCOS reproductive traits in a mouse model of PCOS, while metabolic features were less sensitive to diet changes.

Ovarian tissue cryopreservation and future transplantation is the only strategy to preserve the fertility of young female adolescent and prepubertal patients. The primary challenge to ovarian graft longevity is the substantial loss of primordial follicles during the period of ischaemia post-transplantation. Nicotinamide mononucleotide (NMN), a precursor of the essential metabolite NAD+, is known to reduce ischaemic damage. Therefore, the objective of the current study was to assess the impact of short- and long-term NMN administration on follicle number and health following ovarian tissue transplantation. Hemi-ovaries from C57Bl6 mice (n = 8–12/group) were transplanted under the kidney capsule of bilaterally ovariectomised severe combined immunodeficient (SCID) mice. Recipient mice were administered either normal drinking water or water supplemented with NMN (2 g/L) for either 14 or 56 days. At the end of each treatment period, ovarian transplants were collected. There was no effect of NMN on the resumption of oestrous or length of oestrous cycles. Transplantation significantly reduced the total number of follicles with the greatest impact observed at the primordial follicle stage. We report that NMN did not prevent this loss. While NMN did not significantly impact the proportion of apoptotic follicles, NMN normalised PCNA expression at the primordial and intermediate stages but not at later stages. In conclusion, NMN administration did not prevent ovarian follicle loss under the conditions of this study.

Polycystic ovary syndrome (PCOS) is a complex disorder characterised by endocrine, reproductive and metabolic abnormalities. Despite PCOS being the most common endocrinopathy affecting women of reproductive age, its etiology is poorly understood so there is no cure and symptom-oriented treatment is suboptimal. Elucidation of the underlying mechanisms involved in the pathogenesis of PCOS would pave the way for the development of new interventions for PCOS. Hyperandrogenism is the most consistent feature observed in PCOS patients, and recently aberrant neuroendocrine signalling and adipose tissue function have been proposed as playing a pathogenic role in the development of experimental PCOS. To investigate the role of adipose tissue and the brain as potential key sites for androgen receptor (AR)-mediated development of PCOS, we combined an adipocyte and brain-specific ARKO knockout (AdBARKO) mouse model with a dihydrotestosterone (DHT)-induced mouse model of PCOS. Wildtype (WT) and AdBARKO prepubertal mice were implanted with a blank or DHT implant and examined after 12 weeks. In WT control females, DHT exposure induced the PCOS reproductive traits of cycle irregularity, ovulatory dysfunction and reduced follicle health. In contrast, these reproductive features of PCOS were absent in DHT-treated AdBARKO females. The PCOS metabolic characteristics of increased adiposity, adipocyte hypertrophy and hepatic steatosis were induced by DHT in WT females. Despite DHT treatment, AdBARKO females displayed normal white adipose tissue weight, and adipocyte hypertrophy and hepatic steatosis were not evident. However, as with WT mice, DHT treatment induced increased fasting glucose levels in AdBARKO females. These results demonstrate that adipose tissue and the brain are key loci for androgen-mediated actions involved in the developmental origins of PCOS. These findings support targeting adipocyte and neuroendocrine AR-driven pathways in the future development of novel therapeutic strategies for PCOS.

The gut microbiome has been implicated in the development of metabolic disorders such as obesity and type-2 diabetes, and more recently polycystic ovary syndrome (PCOS). PCOS is a heterogeneous disorder with reproductive, endocrine and metabolic irregularities, and clinical and animal studies have reported that PCOS causes a decrease in microbial diversity and composition. Diet is an important regulator of the gut microbiome, and a recent study identified that alterations in macronutrient balance impact gut microbial communities which correlate with different metabolic health outcomes (1). We have identified that macronutrient balance impacts the development of PCOS traits. Therefore, to investigate the interplay between macronutrient balance and a PCOS environment on the gut microbiome, we analyzed the intestinal microbiome from fecal pellets of control and DHT-induced PCOS mice exposed to 10 different diets that varied systematically in protein (P), carbohydrate (C) and fat (F) content. The amount of dietary P, C and F consumed significantly altered alpha and beta diversity of the gut microbiota of pooled control and PCOS mice (P

Polycystic ovary syndrome (PCOS) is a complex disorder characterized by endocrine, reproductive, and metabolic abnormalities. Despite PCOS being the most common endocrinopathy affecting women of reproductive age, the etiology of PCOS is poorly understood, so there is no cure and symptomatic treatment is suboptimal. Hyperandrogenism is the most consistent feature observed in PCOS patients, and recently aberrant neuroendocrine signaling and adipose tissue function have been proposed as playing a role in the development of PCOS. To investigate the role of adipose tissue and the brain as key sites for androgen receptor (AR)-mediated development of PCOS, we combined a white and brown adipose and brain-specific AR knockout (AdBARKO) mouse model with a dihydrotestosterone (DHT)-induced mouse model of PCOS. As expected, in wildtype (WT) control females, DHT exposure induced the reproductive PCOS traits of cycle irregularity, ovulatory dysfunction, and reduced follicle health, whereas in AdBARKO females, DHT did not produce the reproductive features of PCOS. The metabolic PCOS characteristics of increased adiposity, adipocyte hypertrophy, and hepatic steatosis induced by DHT in WT females were not evident in DHT-treated AdBARKO females, which displayed normal white adipose tissue weight and no adipocyte hypertrophy or liver steatosis. Dihydrotestosterone treatment induced increased fasting glucose levels in both WT and AdBARKO females. These findings demonstrate that adipose tissue and the brain are key loci of androgen-mediated actions involved in the developmental origins of PCOS. These data support targeting adipocyte and neuroendocrine AR-driven pathways in the future development of novel therapeutic strategies for PCOS.

Background: Some individuals with Hashimoto’s thyroiditis (HT), characterized by anti-TPO antibodies (Abs), can also have positive TSI Abs in up to 20% of cases, without necessarily having Graves disease (GD). Patients with signs of both hyper-and-hypothyroidism with positivity to these two Abs can pose a diagnostic and therapeutic dilemma, as their course is often unpredictable. Clinical Case: A 49-year-old woman was diagnosed with hypothyroidism and took levothyroxine (LT4) for about 1 year, after which she developed symptoms of hyperthyroidism and was switched to methimazole (MMI), which she only took for 1 year. At her initial visit at our clinic she had been off of MMI for 12 months and she was biochemically hyperthyroid (TSH of 0.01 mcIU/ml, f-T4 of 2.26 ng/dl). TSI Abs were positive at 461, but she also tested positive for anti-TPO at 673. Thyroid receptor Abs (TRAb) were also elevated at 54.8. Her vital signs were stable, but she had marked proptosis and complained of eye dryness, so MMI was restarted. A RAIU scan could not be obtained, but a thyroid US showed a heterogeneous and hypervascular gland. On MMI, her thyroid function tests normalized, and her eye disease vastly improved over 2 years. Her MMI dose was progressively decreased until it was stopped completely. On re-evaluation a few months later, she had newly elevated TSH of 8.7 mcIU/ml and low f-T4 of 0.87 ng/dl, with no symptoms of hypothyroidism, so we opted for management with active surveillance instead of starting her on LT4. Her TSI level improved to 240, but remains elevated. Discussion: It is unclear if our patient has a mixed condition with features of both GD and HT, or if she has HT with a very prolonged hyperthyroid phase (hashitoxicosis). Extended periods of hashitoxicosis have been described, the longest reported lasted for 2 years[1]. Simultaneous presentation of GD and HT is very rare, with only a few cases described in the literature. RAIU scan is often diagnostic, showing increased uptake as seen in GD, but patchy areas of decreased uptake can also be seen. In our case it is likely that HT and GD were coexisting, with GD masking the hypothyroidism, until the former remitted with MMI, and her HT took over. Though no RAIU scan was available, the TSI positivity, clinical response of her hyperthyroidism to MMI and the presence of orbitopathy rule in favor of co-existing GD. Decision to treat with LT4 should be weighed against the risk of causing recurrence of hyperthyroidism. Special considerations should be taken in women of childbearing age due to the difficult management that overlapping hyper/hypothyroidism would entail during pregnancy. References: 1. Shahbaz, A et al. Prolonged Duration of Hashitoxicosis in a Patient with Hashimoto’s Thyroiditis: A Case Report and Review of Literature. Cureus. 2018; 10(6):e2804

Background: Papillary thyroid carcinoma (PTC) is generally considered a relatively slow-growing, indolent cancer; however, an important subset of these cancers known as the tall cell variant (TCV), portend a more aggressive prognosis. TCV PTC is characterized by cells, which are at least twice as tall as they are wide. Patients diagnosed with TCV PTC fare worse than those with the classic variant. A less common thyroid cancer, spindle cell squamous cell carcinoma (SCSC), may arise as a primary tumor, but rarely also alongside or from a previous TCV PTC (1). It may also occur as a component of an anaplastic thyroid cancer, the most aggressive and rarest thyroid malignancy. There are three main types of anaplastic SCSC arising from TCV PTC based on histological characteristics: Type 1 is defined by the presence of both TCV and SCSC within the initial resection; type 2 refers to when the SCSC arises as a recurrence or metastasis in patients with a known history of TCV PTC; type 3 occurs when SCSC presents as a primary laryngeal SCC in patients with or without a known history of TCV. We report a case of type 2 anaplastic SCSC. Clinical Case: A 76 yr old man with hx of invasive TCV PTC (diagnosed 2011) s/p total thyroidectomy with b/l neck dissection and laryngectomy, as well as 200 mci of I-131 (in 2012), returns to clinic in 2019, with worsening unexplained weight loss (> 20 lbs). He had been lost to follow-up since 2015. Now, chest CT showed a new, necrotic, left lower lobe mass obstructing the bronchus, as well as bony erosion of the right clavicle and manubrium. Bronchoscopy of the mass was performed, and pathology was consistent with metastatic anaplastic thyroid cancer with squamous nests. Immunohistochemistry was positive for PAX-8, p40, p63 and negative for TTF-1, Napsin A, TG and PDL-1. The endobronchial tumor tissue was compared to the prior resection specimen from 2011, showing morphologic similarity to the squamoid nests. In retrospect, these nests likely represented small foci of anaplastic thyroid cancer arising in association with TCV PTC. The positive staining for PAX-8 and lack of expression for TTF-1 and Napsin A supports this interpretation and is evidence against a primary pulmonary squamous cell carcinoma. Next Gen Sequencing was positive for BRAF V600E mutation, which allowed us to offer BRAF inhibitor and MEK inhibitor therapy. Unfortunately, due to patient’s non-adherence to therapy and follow-up clinic visits, we are not able to assess his response. Conclusion: This is a case of the rarely described type 2 anaplastic SCSC and is an example of the very poor prognosis associated with TCV PTC. It is a reminder that this variant of PTC should be treated more aggressively from the time it is first identified on biopsy. Reference: (1) Gopal PP et al. The variable presentations of anaplastic spindle cell squamous carcinoma associated with tall cell variant of papillary thyroid carcinoma. Thyroid. 2011;21(5):493–499.