Well-differentiated Carcinoma Research Articles

Does Locally Advanced Thyroid Cancer Have Different Features? Results from a Single Academic Center.

Background: Despite the fact that the majority of thyroid cancers are indolent, 15% of patients with well-differentiated carcinoma including papillary thyroid carcinoma (PTC) present with locally advanced thyroid cancer (LATC) at diagnosis. The current study analyzes a cohort of patients with LATC focusing on their risk for local recurrence, distant metastases, and overall survival. Materials and methods: From January 2010 to December 2020, 65 patients with LATC were retrieved, including 42 cases with preoperative cytological samples. BRAFV600E and TERT mutations were performed on both cytology and histopathology specimens in this cohort. Results: Among the 65 cases, 42 (65%) were women. The median age was 60.1 years. Histological diagnoses included 25 (38.4%) with classic PTC and 30 (46.1%) aggressive variants of PTC, mostly tall cell variant (17 cases, 26.1%). Multifocality was seen in 33 cases (50.8%). All patients had nodal metastases. The most common site of extrathyroidal extension was the recurrent laryngeal nerve (69.2%). Staging revealed 21 cases were stage I, none were stage II, 33 were stage III, and 7 were stage IVa and 4 stage IVb. No differences were found between well and poorly/undifferentiated thyroid cancers. Conclusion: These data suggest that locally advanced thyroid cancers, including variants of PTC, exhibit a more aggressive biological course and should accordingly be more assertively managed.

The IVF-generated human embryonic microenvironment reverses progestin resistance in endometrial cancer cells by inducing cancer stem cell differentiation.

Progestin resistance is a critical factor that prevents patients with endometrial cancer (EC) from receiving conservative therapy. However, the etiology remains elusive. Cancer stem cells (CSCs) may be a contributing factor to progestin resistance in EC. These cells share similar stemness properties with embryonic stem cells that have a multipotent but differential naïve phenotype. Embryonic stem cells are programed to self-renew, to differentiate and to show plasticity toward a normal cellular phenotype in their defined microenvironment. However, whether this microenvironment may promote CSC differentiation toward a better responsive phenotype and reverse progestin resistance has not yet been clarified. In the current study, we found that progestin resistance of endometrial CSCs can be improved or reversed by using in vitro fertilization (IVF)-generated embryonic sac-derived fluid containing the embryonic microenvironment. Furthermore, suppression or reversal of progestin resistance was mediated by placental alkaline phosphatase (ALPP), a factor secreted into the embryonic microenvironment by IVF-generated blastocysts. ALPP significantly reversed progestin resistance by facilitating endometrial CSC differentiation through downregulating the stemness genes NANOG, OCT4 and SOX2. We further showed that the downregulation of NANOG, OCT4 and SOX2 by ALPP was carried out by TET1/2-mediated epigenetic modulation of the promoter regions of these genes. Such changes at the molecular level initiated endometrial CSC differentiation and promoted a better responsive endometrial cancer phenotype. In fact, their response to progestin treatment was similar to that of well-differentiated endometrioid carcinoma cells without CSCs. ALPP could be a novel target in the process to overcome progestin resistance, and such findings may provide a new approach for the conservative treatment of endometrial cancer.

Genitourinary syndrome, local oestrogen therapy and endometrial pathology: a single-centre, randomised study

The objective of this study was to assess the endometrial pathology developed (EP) in postmenopausal women with genitourinary syndrome during and after vaginal oestrogen therapy. The 67 patients included were randomly grouped into group I underwent local oestrogen (oestriol) therapy and group II, underwent no therapy. Each patient’s medical history was taken and clinical and gynecological examination, with transvaginal ultrasound at the time of inclusion and during the control visits, was done. The study results show no statistically higher risk of EP for vaginal oestrogen therapy of genitourinary syndrome users compared to the non-users in menopause. No one atypical endometrial hyperplasia and endometrial intraepithelial neoplasia case during the study period was found. Impact statement What is already known on this subject? Treatment of genitourinary syndrome with oestrogens in menopausal women is the most commonly used and affordable method. Topical vaginal oestrogens do not have the same stimulating effect on the endometrium as oral ones, and therefore the association between them and endometrial hyperplasia or cancer has not been established categorically. What do the results of this study add? This single-center, randomised study found no statistically higher risk of endometrial pathology for vaginal oestrogen (oestriol) therapy of genitourinary syndrome users compared to the non-users in menopause. No one atypical endometrial hyperplasia and endometrial intraepithelial neoplasia case during the study period was found. What the implications are of these findings for clinical practice and/or further research? This study confirms the safety of local oestrogen (oestriol) therapy of genitourinary syndrome in menopausal women with regards to the development of endometrial pathology and especially atypical endometrial hyperplasia and endometrial intraepithelial neoplasia or well-differentiated carcinoma

Metabolic Syndrome is an Independent Risk Factor for Fuhrman Grade and TNM Stage of Renal Clear Cell Carcinoma.

BackgroundMore and more evidences show that metabolic syndrome (MS) is closely related to clear cell renal cell carcinoma (ccRCC), but the impact of MS on Fuhrman grade and TNM stage of ccRCC is rarely reported.PurposeTo explore the relationship between MS and its components of Fuhrman grade and TNM stage in ccRCC.ObjectiveThe clinical data of 247 patients with ccRCC diagnosed in our hospital from January 2016 to November 2020 were retrospectively collected and analyzed. Based on diagnostic criteria of MS, the patients were divided into MS and non-MS group. Logistic regression analysis was used to analyze the independent risk factors of ccRCC.ResultsThe incidence of MS was 32.79% (81/247). There was no significant difference in age, gender, smoking and drinking between MS group and non-MS group (P > 0.05). In MS group, BMI ≥25kg/m2, hypertension, diabetes, hyperlipidemia, tumor diameter, poorly differentiated renal cancer, high-stage renal cancer, triglyceride, fasting blood glucose, glycated hemoglobin, fasting insulin and homeostasis model assessment index were significantly higher than those in non-MS group (P < 0.001), while in high density lipoprotein cholesterol (p < 0.005), islet beta cell secretory index (P < 0.001), well-differentiated renal cell carcinoma (P= 0.009), and low-stage renal cell carcinoma (P = 0.019) were significantly lower than that of non-MS group. Logistic regression analysis showed that hypertension (P = 0.005), diabetes (P = 0.012), hyperlipidemia (P = 0.021) are independent risk factors for Fuhrman grade of ccRCC, while diabetes (P = 0.002), hyperlipidemia (P = 0.007) are independent risk factors for TNM staging of ccRCC.ConclusionThe patients with ccRCC and MS had higher Fuhrman grade and TNM stage. MS is an independent risk factor for Fuhrman grade and TNM stage of ccRCC.

Hysteroscopic Curettage Followed by Megestrol Acetate Plus Metformin as a Fertility-Sparing Treatment for Women with Atypical Endometrial Hyperplasia or Well-Differentiated Endometrioid Endometrial Carcinoma.

Background:In reproductive-aged women, the incidence of atypical endometrial hyperplasia (AEH) or endometrioid endometrial carcinoma (EEC) is rising globally. The study aimed to investigate the effectiveness of hysteroscopic curettage followed by megestrol acetate (MA) plus metformin as conservative treatment in AEH and early EEC.Methods:We retrospectively studied AEH and stage IA, grade 1 EEC patients treated with hysteroscopic curettage followed by MA (160 mg/d) plus metformin (1500 mg/d) from January 2010 to December 2020 at Fudan University Shanghai Cancer Center. Treatment outcomes were assessed by complete response (CR) rate, recurrence rate, and pregnancy outcomes. Univariate and multivariate analyses were performed via the logistic regression model.Results:The study included 79 patients, 31 (39.2%) with AEH and 48 (60.8%) with EEC. The medians of age (years) and follow-up time (months) were 30 and 39.5, respectively. Seventy-six patients (96.2%) finally achieved CR. The median time to CR was 3.6 (3.0-20.6) months. The CR rate after 3 months, 6 months, and 1 year was 55 (69.6%), 67 (84.8%), and 72 (91.1%), respectively. Recurrence occurred in 26 (34.2%) patients. Treatment duration ⩾9 months was associated with a lower recurrence rate after CR (P = .012). Fourteen (93.3%) of the 15 recurrent patients who received progestin re-treatment achieved CR again. Finally, 29 patients delivered live births.Conclusions:Hysteroscopy followed by MA plus metformin can achieve CR in short time and is overall safe. Consolidation treatment should be prolonged to decrease the recurrence rate, despite a shorter time to CR.

Ki-67 expression in human oral squamous cell carcinoma

Oral cancers are one of the 10 leading cancers in the world. However, in India, it is one of the most common cancers and constitutes a major public health problem. Oral squamous cell carcinoma is a well-known malignancy that accounts for more than 90% of all oral cancers. The study is carried out on 40 biopsy samples received on oral mucosa, in Department of Pathology of our institute. Maximum numbers of patients were from 3th to 6th decade in our study. 38 cases of oral squamous cell carcinoma were observed, out of which 31 (81.57%) were male, and 07 (18.42%) cases were female. The most common site was tongue (50%), followed by buccal mucosa (18.42%), 06 patients (15.78%) had lesion at palate. Thirty-five (92.10%) cases had a significant history of tobacco use/smoking, whereas 03 (7.89%) did not have any history of tobacco use. We observed Ki-67 LI for normal oral mucosa was 14 ± 5.6%. In well-differentiated carcinoma, the KI-67 LI was 28.52 ± 21.25%, which increased to 42.85 ± 18.2% in moderately differentiated carcinoma and 68.57 ± 17.6% in poorly differentiated carcinoma. Ki-67 acts as an excellent marker of cellular proliferation. There is a statistical difference in KI-67 overexpression between various grades of oral squamous cell carcinoma and normal oral mucosa (p value &amp;#60;0.05).

Poorly Differentiated Thyroid Carcinoma: Single Centre Experience and Review of the Literature.

There is controversy in the literature regarding a distinct subset of thyroid carcinoma whose histologically classification falls between well-differentiated and anaplastic carcinomas, previously identified as ‘poorly differentiated thyroid carcinoma’ (PDTC), or ‘insular carcinoma’, in view of the peculiar morphological characteristics of the cell groupings. The correct diagnosis and treatment of this entity have important prognostic and therapeutic significance. In this review, we describe the epidemiology, diagnosis, and management of PDTC and report our single centre experience to add to the limited evidence existing in the literature.

Hepatic Adenomatosis in a Young Asymptomatic but High-risk Patient: An Incidental Diagnosis with Potentially Severe Clinical Implications.

Hepatic adenomatosis (HA) is a very rare condition and defined as the presence of 10 or more adenomas in an otherwise normal liver. HA has an incidence of 10–24% in patient with hepatic adenoma and it is more common in women. Most patients with HA are asymptomatic with a normal liver function test and half of cases are detected incidentally on imaging. Although HA is considered a benign disease, some patients may develop potentially fatal complications, such as hypovolaemic shock due to rupture of the liver lesion or malignant transformation to hepatocellular carcinoma.We report the case of a 29-year-old woman who presented to the emergency room after a car accident. Whole-body computed tomography revealed multiple focal hepatic hypervascular lesions in the right lobe of the liver together with a fatty liver. Subsequent hepatic magnetic resonance imaging suggested the diagnosis of HA with a suspicion of focal nodular hyperplasia (FNH). The patient refused to undergo liver biopsy, so we instituted a 3-month surveillance program, which included clinical assessment, liver function tests, tumour marker assessment and blood tests as well as sonographic evaluation for follow-up of the liver lesions.LEARNING POINTSHepatic adenomatosis is an extremely rare disease which predominantly affects women and is associated with hormone consumption, liver steatosis, glycogen storage disease, obesity, metabolic syndrome, abnormalities of hepatic vasculature and maturity onset diabetes of the young (MODY).The two main differential diagnoses include focal nodular hyperplasia (FNH) and well-differentiated hepatocellular carcinoma. Histological confirmation is required when MRI findings are inconclusive or when a malignancy is suspected.In men, resection of adenomas is mandatory due to the high risk of malignant transformation. In woman, a conservative approach with contraceptive discontinuation and biannual follow-up with MRI and alpha-fetoprotein is recommended; resection is needed in case of positive immunohistochemical staining for β-catenin on biopsy, symptomatic adenomas, adenoma increasing in size, and when malignancy cannot be ruled out.

Total Superficial Parotidectomy: Pros and Cons

Background: Total superficial parotidectomy is the most commonly used approach in excising the tumors that affect the superficial lobe of the parotid gland, whether they're benign or malignant. The aim of the study is to evaluate the benefits and drawbacks of total superficial parotidectomy for parotid gland tumors within five years of follow-up. Patients and methods: Nineteen patients with lateral facial swelling affecting the parotid region were included in this study. All of them operated under general anesthesia with oral endotracheal intubation, where Modified Blair Incision (lazy S incision) was utilized in all cases. Anterograde dissection with facial nerve identification was accomplished with total superficial parotidectomy. Results: Fifteen patients had benign parotid tumors, and only four patients had well-differentiated mucoepidermoid carcinoma. Skin necrosis of the distal tip of the postauricular flap was the most commonly observed postoperative complication, it occurred in five patients; facial nerve weakness was observed in the another three patients. Conclusions: total superficial parotidectomy is an efficient, safe technique for benign and malignant tumors affecting the superficial lobe of the parotid gland with minimum postoperative complications.

Primary high-grade non-anaplastic thyroid carcinoma: a retrospective study of 364 cases.

We aimed to study the clinicopathological and molecular features of high-grade non-anaplastic thyroid carcinomas (HGTCs), a carcinoma with a prognosis intermediate between those of well-differentiated carcinoma and anaplastic carcinoma. This study included 364 HGTC patients: 200 patients (54.9%) were diagnosed with poorly differentiated thyroid carcinoma (PDTC), based on the Turin consensus (HGTC-PDTC), and 164 were diagnosed with high-grade features that did not meet the Turin criteria (HGTC-nonPDTC). HGTCs are aggressive: the 3-year, 5-year, 10-year and 20-year disease-specific survival (DSS) rates were 89%, 76%, 60%, and 35%, respectively. Although DSS was similar between HGTC-PDTC and HGTC-nonPDTC patients, HGTC-PDTC was associated with higher rate of radioactive iodine avidity, a higher frequency of RAS mutations, a lower frequency of BRAF V600E mutations and a higher propensity for distant metastasis (DM) than HGTC-nonPDTC. Independent clinicopathological markers of worse outcome were: older age, male sex, extensive necrosis and lack of encapsulation for DSS; older age, male sex and vascular invasion for DM-free survival; and older age, necrosis, positive margins and lymph node metastasis for locoregional recurrence-free survival. The frequencies of BRAF, RAS, TERT, TP53 and PTEN alterations were 28%, 40%, 55%, 11%, and 10%, respectively. TP53, PTEN and TERT were independent molecular markers associated with an unfavourable outcome, independently of clinicopathological parameters. The coexistence of BRAF V600E and TERT promoter mutation increased the risk of DM. The above data support the classification of HGTC as a single group with two distinct subtypes based on tumour differentiation: HGTC-PDTC and HGTC-nonPDTC.

Comparison of diagnostic efficacy of ultrasound, ultrasound elastography and magnetic resonance imaging for breast lesions

Study aimed to evaluate and compare the performance of ultrasound, ultrasound elastography and magnetic resonance imaging in the diagnosis of breast cancer & its differentiation from benign lesions Material & Method: This cross-sectional observational study was conducted at department of Radiodiagnosis, Era’s Lucknow Medical college. The study was conducted for 18 month from January 2019 to june 2020. Patients detected with breast lesions and willing to be part of study were included in the study. The patients with cystic nodules and non-consenting patients were excluded from the present study. All the patients were subjected to B-mode USG assessment followed with Real Time ultrasound Elastography and 0.5 Tesla MRI scan. Fine needle aspiration cytology (FNAC) or biopsy was performed and the specimen were evaluated cytologically/histopathologically to confirm the diagnosis Result: Histopathologically, 18 (36%) cases were diagnosed as malignant and remaining 32 (64%) were diagnosed as benign. Among 18 malignant cases, maximum (n=11) were intraductal carcinoma (NOS), followed by well-differentiated intraductal carcinoma (n=6) and invasive lobular carcinoma (n=1) respectively. Among 32 benign cases, maximum (n=20) were fibroadenoma, followed by breast abscess (n=3), galactocele, intraductal papilloma and simple cyst (n=2 each). There was 1 case each diagnosed as fibroadenolipoma, fibrocystic and phyllode respectively. Diagnostic efficacy of USG in terms of sensitivity, specificity, positive and negative predictive value was 77.8%, 87.5%, 77.8% and 87.5% respectively. The accuracy of USG diagnosis was 84%. Diagnostic efficacy of USG elastography in terms of sensitivity, specificity, positive and negative predictive value was 83.3%, 96.9%, 93.8% and 91.2% respectively. The accuracy of elastography diagnosis was 92%. Diagnostic efficacy of MRI in terms of sensitivity, specificity, positive and negative predictive value was 94.4%, 90.6%, 85.0% and 96.7% respectively. The accuracy of MRI diagnosis was 92%. Conclusion: In low-resource settings, USG elastography can emerge as a suitable alternative to MRI in diagnosis of malignant breast masses with highly appreciable positive and negative predictive values. Study Design: Observational Study.

Carcinome épidermoïde de la tête du pancréas : une observation inhabituelle

Epidermoid carcinoma of the pancreas is an extremely rare histological type. We report the case of a 62-year-old patient who has had epigastric pain and posterior irradiation for 2 months. Thoracoabdomino-pelvic CT scan has showed tissue process on the pancreatic incus. Surgical specimens were submitted to a histopathological examination which revealed a well-differentiated and mature invasive epidermoid carcinoma of the pancreas tumor classified as stage pT3N1. After surgical procedure (cephalic duodenopancreatectomy), the evolution was favorable. Hereby, we review literature and discuss various aspects of epidermoid carcinoma of the pancreas including epidemiology, pathogeny, diagnosis, treatment and survival. Received: July 4th, 2020 Accepted: July 30th, 2021

Applying criteria for hepatocellular neoplasm of uncertain malignant potential reclassifies more than half of hepatocellular adenomas

ObjectivesHepatocellular adenoma (HCA) is a benign well-differentiated hepatocellular neoplasm that can be difficult to distinguish from well-differentiated hepatocellular carcinoma (HCC). The term “well-differentiated hepatocellular neoplasm of uncertain malignant potential” (HUMP) has been proposed for neoplasms resembling HCAs, but arising in atypical clinical situations (in females over 50 years old or under 15, in males, with anabolic steroid use, or in some congenital conditions), and/or with atypical pathological features (focal cytological/architectural atypia, β-catenin activation, or focal reticulin loss) insufficient for an unequivocal diagnosis of HCC. MethodsThis study evaluated HUMP criteria on 42 previously diagnosed HCAs from 33 patients. ResultsTwenty-six (62%) masses from 21 patients were classified as HUMPs. Eleven (42%) had focal cytological atypia, and two (8%) had focal architectural atypia. Four (15%) showed focal reticulin loss. Five (19%) showed evidence of β-catenin activation. Four (12%) HUMP patients were male. ConclusionsIn this series, HUMP did not correlate with an increased rate of synchronous or metachronous HCC compared to HCA. Clinical colleagues may not accept such a high rate of tumors placed in a category of “uncertain malignant potential”. Additional study is warranted to refine criteria for designating well-differentiated hepatocellular neoplasms as of uncertain malignant potential.

Correlation Study on Expression of PD-1 and PD-L1 in Non-small Cell Lung Cancer and Epidermal Growth Factor Receptor Mutations

背景与目的肺癌的治疗模式以表皮生长因子受体酪氨酸激酶抑制剂（epidermal growth factor receptor-tyrosine kinase inhibitors, EGFR-TKIs）作为EGFR突变的非小细胞肺癌（non-small cell lung cancer, NSCLC）患者一线治疗；同时以程序性死亡受体1（programmed death receptor 1, PD-1）及其配体（programmed death receptor ligand 1, PD-L1）抑制剂为代表的免疫检查点抑制剂（immune checkpoint inhibitors, ICIs）的免疫治疗在肺癌治疗中疗效显著。本研究旨在探讨PD-1和PD-L1在NSCLC中的表达及其与临床病理特征、EGFR突变之间的关系。方法采用免疫组化方法检测127例NSCLC PD-1和PD-L1蛋白表达，同时用定量聚合酶链反应（quantitative polymerase chain reaction, qPCR）检测EGFR基因突变，分析其与临床病理特征之间的关系，研究PD-1、PD-L1表达之间以及其与EGFR突变的关系。结果NSCLC肿瘤细胞及肿瘤浸润免疫细胞PD-1阳性表达53.5%（68/127），肿瘤细胞PD-L1表达57.5%（73/127），PD-1和PD-L1的表达在低分化癌、临床分期Ⅰ期+Ⅱ期明显高于高中分化癌、Ⅲ期+Ⅳ期（均P < 0.05）；EGFR突变率为46.5%（59/127），EGFR突变的患者中女性、无吸烟史、腺癌、高中分化组分别高于男性、吸烟史、鳞癌、低分化组患者（均P < 0.05）；NSCLC患者PD-L1与PD-1蛋白表达存在一致性（kappa=0.107, 5, P=0.487），EGFR突变与PD-1、PD-L1表达存在负相关关系（Φ=-0.209，Φ=-0.221，均P < 0.05）；对NSCLC患者随访，在 < 65岁、腺癌、高中分化癌、PD-L1表达的患者中位总生存期分别高于≥65岁、鳞癌、低分化癌、PD-L1不表达患者（均P < 0.05）。PD-L1低表达患者中位生存期明显高于高表达患者（P=0.04）。结论参照《非小细胞肺癌PD-L1免疫组织化学检测规范中国专家共识》检测非小细胞肺癌PD-L1表达，筛选出抗PD-1/PD-L1治疗的优势人群；同时检测出EGFR突变的患者，并且EGFR突变与PD-1、PD-L1表达存在负相关关系，依据PD-L1表达和EGFR突变状态，可能使NSCLC患者在的个体化治疗中获益，同时65岁以下、腺癌、高中分化、PD-L1低表达的患者有相对好的预后，为NSCLC预后评估提供参考。

Significance of hepatocyte atypia in liver fine needle aspiration.

Fine needle aspiration (FNA) of the liver is frequently the diagnostic procedure of choice for sampling hepatic lesions. One of the main diagnostic challenges in the interpretation of liver FNA is distinguishing dysplastic lesions and well-differentiated hepatocellular carcinoma (WD-HCC) from benign processes, as they share significant cytomorphologic overlap. Furthermore, the diagnosis of HCC often requires evaluation of stroma for invasion, which may not be present on cytology and small needle biopsy specimens. A reporting system for liver cytopathology has yet to be instituted. Without standardized and well-defined criteria for hepatocyte atypia, we recommend limiting the use of atypia in evaluation of liver FNA specimens to describe a diagnosis of exclusion, in which all known benign and neoplastic processes have been ruled out. The cytologic findings on the FNA of a liver nodule may be best reported as atypical hepatocytes in the absence of a core needle biopsy or cell block sufficient to render a definitive diagnosis of HCC.

Thyroid cancer surgery during the coronavirus disease 2019 pandemic: perioperative management and oncological and anatomical considerations.

The coronavirus disease 2019 (COVID-19) pandemic has changed many aspects of our everyday lives and medical practice, including oncology treatment; thyroid cancer surgery is not an exception. The reported number of fine-needle aspirations performed during the first semester of 2020 was significantly reduced. Poorly differentiated, medullary and anaplastic thyroid tumors are considered important indications for immediate surgical intervention. By contrast, most well-differentiated carcinomas present slow growth, and thus surgery can be deferred for a short period of time during which patients are under active surveillance. Thyroid surgeries have decreased during the COVID-19 pandemic. Furthermore, prior to any intervention, negative COVID-19 status – with the use of a nasopharyngeal swab and reverse transcription PCR assay as the gold standard and chest CT scan as a complementary modality in some cases – must be confirmed to achieve a COVID-free pathway. Thorough preoperative assessment regarding both oncological and anatomical aspects should be performed to identify optimal timing for safe management.

Neuroendocrine Neoplasms of the Larynx: A Clinicopathologic Analysis of 27 Neuroendocrine Tumors and Neuroendocrine Carcinomas.

Laryngeal neuroendocrine neoplasms (NENs) are rare and heterogeneous, encompassing well-differentiated neuroendocrine tumors (NETs; grade 1, 2, and 3), neuroendocrine carcinomas (NECs, small cell and large cell types), and mixed neuroendocrine non-neuroendocrine neoplasms (MiNEN). We aimed to study the clinicopathologic spectrum of these neoplasms. A retrospective review of all primary laryngeal NENs diagnosed from 2005 to 2017 was undertaken. Mitotic index was divided into < 2, ≥ 2-10, and > 10 mitoses/2 mm2, with a Ki-67 labelling index of < 2%, ≥ 2-20%, and > 20% for the NET grade 1, 2 and 3 categories, respectively. A total of 27 patients were included. The median age at presentation was 60years; the male-to-female ratio was 8:1. Supraglottis (n = 22) was the most frequently affected subsite. There were 9 NETs grade 2 (G2), and 18 NECs cases. There were no NET grade 1 or 3 cases in our cohort. Among the NETs G2, the morphology was epithelioid (2), plasmacytoid (3), clear (2), oncocytic (1), and rhabdoid (1). Unique 'glomeruloid structures' (n = 5), calcification (n = 3), lymphoid aggregates (n = 5), intranuclear inclusions (n = 2), hyaline globules (n = 3), and Leisegang rings (n = 2) were identified. NECs comprised 16 small cell neuroendocrine carcinoma and 2 large cell neuroendocrine carcinoma. On immunohistochemistry, tumor cells expressed AE1/AE3 (86%), synaptophysin (100%), chromogranin (100%), INSM1 (100%), calcitonin (33.3%). In the NEC group, p53 aberrant expression (87.5%), Retinoblastoma (Rb) loss (88.2%), and diffuse p16 immunoreactivity (66.7%) were additionally observed. Lymph-node metastasis was detected in 62.5% and 85.7%, while distant metastasis in 55.6% and 76.9%, respectively in NET G2 and NEC. Laryngeal NENs are aggressive neoplasms with a high rate of nodal and distant metastasis. Awareness of the wide pathologic spectrum of laryngeal NENs and appropriate use of IHC is needed to render an accurate diagnosis. Ki67 assessment is strongly recommended for laryngeal NEN prognostication.

Radical surgical treatment of neuroendocrine tumors of the appendix in children - a Polish multicenter study.

IntroductionThe aim of the study was to examine management of pediatric appendiceal neuroendocrine tumors (ANETs) in Poland.MethodsRecords of 27 patients with ANET diagnosed incidentally after appendectomy in the last decade.ResultsWell-differentiated NET G1/G2 was diagnosed in 25 and well-differentiated neuroendocrine carcinoma G3 in 2 patients. Extended surgery was performed primarily in one instance and secondarily in 10 patients (right hemicolectomy in 9, ileocecal resection in 1) without adjuvant chemotherapy. Follow-up range was 1–121 months. Recurrence after secondary surgery was observed in 1 (3.7%) patient.ConclusionsApplying ENETS guidelines resulted in 100% overall survival of patients with NET.

Abstract 2708: Dedifferentiated thyroid cancers have unique expression profiles of stromal cell markers and TIMER predicted immune cell infiltrate

Abstract While thyroid cancer is primarily indolent, forming well-differentiated carcinomas (DTCs), a subset of patients develop dedifferentiated tumors that are aggressive. The evolution of dedifferentiated carcinomas is complex, producing two subtypes: poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma (ATC). ATCs lack markers of differentiated thyroid tissue and have a median survival of 5 months. In contrast, PDTCs retain follicular cell differentiation and have 5-year disease-specific survival of 66%. It's possible that PDTCs and ATCs arise de novo; however, co-occurrences within DTCs have been observed. Consequently, it has been proposed that PDTCs are a transitional stage in the DTC dedifferentiation process, eventually leading to ATC. Dedifferentiation of many cancer types is associated with the accumulation of second hit driver mutations. However, despite large sequencing endeavors, few additional mutations between PDTCs and ATCs have been identified. It is likely that the drivers of dedifferentiation to ATC may be extrinsic to the mutational landscape. Thus, we hypothesize that the tumor microenvironment plays a central role in driving dedifferentiation of DTCs. We performed RNA sequencing on a cohort of 262 thyroid resection specimens encompassing a broad range of thyroid cancers and used DESeq2 to generate fold-change gene expression estimates for poor outcome samples (defined by transformation to PDTC or ATC, recurrence, distant metastasis, or death from disease). Functional enrichment analysis (WebGestalt) identified extracellular matrix (ECM) and regulation of leukocyte activation gene sets as enriched in poor outcome. In the ECM gene set, FAP, PDPN, TGFB1, FN1, COL11A1, LAMB3, POSTN, VCAN, and WNT2, amongst others, were significantly enriched. The neutrophil activating chemokine CXCL5 showed a striking 43-fold increase in poor outcome cases. Interestingly, segregating by histology shows that these stromal markers are upregulated in ATCs but not PDTCs, suggesting that distinct populations of fibroblasts may be present in ATCs. Similarly, the tumor immune cell prediction algorithm TIMER (Tumor Immune Estimation Resource) predicts increased macrophage and neutrophil infiltrate within ATCs relative to PDTCs. Together, these results support a model in which a heterogenous population of fibroblasts drive tumor aggression and granulocyte infiltrate in ATCs but not PDTCs. Single cell resolution will be instrumental to further clarify this model and elucidate the signals that support ATC aggression. Importantly, the distinct differences in stromal markers between PDTCs and ATCs in our cohort suggest that these may be pathologically distinct outcomes rather than existing on a spectrum of dedifferentiation with PDTCs eventually fated to become ATCs. Citation Format: Matthew A. Loberg, George Xu, Thomas P. Stricker, Quanhu Sheng, Barbara A. Murphy, Vivian L. Weiss. Dedifferentiated thyroid cancers have unique expression profiles of stromal cell markers and TIMER predicted immune cell infiltrate [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2708.

First case of huge classic papillary thyroid cancer rupturing spontaneously leading to ischemic necrosis, perforation and inflammation of overlying skin: Case report and review of the literature.

IntroductionPapillary thyroid cancer (PTC) is the commonest form of well-differentiated endocrine carcinoma. It is categorized into indolent and aggressive, where the indolent subtypes (classic, follicular) rarely demonstrate aggressive behavior. We present a classic PTC presenting with a rapidly growing huge anterior neck mass that subsequently spontaneously ruptured subcutaneously resulting in ischemia, necrosis, and perforation of overlying skin leading to inflammation.Presentation of caseA 37-year-old female with no comorbidities presented to our emergency department with a neck swelling of 2 years duration that rapidly enlarged one week prior to presentation. Though the mass initially appeared of inflammatory nature, the tumor was a PTC, and she underwent total thyroidectomy with selective right side neck dissection and debridement of necrotic skin. The gross specimen revealed a fragmented non-intact right thyroid lobe mass causing pressure ischemia, necrosis and perforation of the skin. Histopathology showed a 9 × 9 × 5 cm classic PTC staged as pT3b N1b. Postoperative course was uneventful, she was discharged by the eighth postoperative day, and then she received a high dose of radioactive iodine ablation (RAI).DiscussionClassic PTC is usually of a smaller size and a relatively benign course compared to other PTC subtypes and thyroid cancers. It is indolent with favorable prognosis. Although it is associated with increased risk of lymph node metastases at the time of diagnosis, it is slow growing with high survival rates approaching 95%.ConclusionDespite that classic PTC progresses slowly, it should still be suspected in neck swellings presenting with rapid and aggressive behavior. Prompt and systematic assessment is required with surgical intervention and radioactive iodine ablation therapy.