Endocrine Carcinoma Research Articles

Association between Thyroid Profile Levels and Lymph Node Metastasis in Papillary Thyroid Carcinoma: A Retrospective Study

Background: Thyroid cancer is the most common endocrine carcinoma, accounting for 3.26% of all cancers. The most histologically, well-differentiated thyroid cancer is papillary thyroid carcinoma (PTC). Although PTC is regarded as an indolent tumor, a portion of the cancer cells metastasize to lymph nodes around the thyroid gland. Lymph node metastasis (LNM) is a critical risk factor for tumor recurrence in PTC, which strongly affects disease prognosis and the quality of life. Methods: This study aims to examine how differences in the level of the thyroid profile and other risk factors may influence LNM incidence in patients with PTC in Taiwan. We carried out a single-center retrospective study. These PTC patients were retrospectively reviewed by the Department of Endocrinology from 2016 to 2019. A total of 165 patients were included in our research. Results: The findings revealed a close relationship with the level of free thyroxine (FT4), the level of the thyroid-stimulating hormone (TSH), and lymph node metastases. The correlation in terms of FT4 (p = 0.005) and TSH (p = 0.417) with LNM was found as a result of the univariate regression analysis. In the multiple regression analysis, the findings revealed a close relationship between LNM, FT4 (p < 0.001), and TSH (p = 0.008). Conclusions: Although the predictability of the TSH should be examined further, the association between LNM and FT4 or TSH should not be ignored. The results could help guide decision-making and patient counseling, using the level of serum FT4 or the TSH as a possible predictive factor of the LNM in PTC.

An Enlarging Painless Eyelid Nodule.

A 50-year-old Asian man with a history of a kidney transplant presented with a painless enlarging lesion on his right lower eyelid that had been growing for two years. Biopsy revealed a low-grade neoplasm with cribiform architecture and mucin production, and subsequent immunohistochemistry was suggestive of Endocrine Mucin-Producing Sweat Gland Carcinoma (EMPSGC). This case highlights the importance of a high index of suspicion for malignancy in immunocompromised patients with non-resolving lesions, and the need for regular skin checks.

Dihydrotanshinone I exhibits antitumor effects via β-catenin downregulation in papillary thyroid cancer cell lines

Thyroid cancer is the most common endocrine carcinoma and, among its different subtypes, the papillary subtype (PTC) is the most frequent. Generally, PTCs are well differentiated, but a minor percentage of PTCs are characterized by a worse prognosis and more aggressive behavior. Phytochemicals, naturally found in plant products, represent a heterogeneous group of bioactive compounds that can interfere with cell proliferation and the regulation of the cell cycle, taking part in multiple signaling pathways that are often disrupted in tumor initiation, proliferation, and progression. In this work, we focused on 15,16-dihydrotanshinone I (DHT), a tanshinone isolated from Salvia miltiorrhiza Bunge (Danshen). We first evaluated DHT biological effect on PTC cells regarding cell viability, colony formation ability, and migration capacity. All of these parameters were downregulated by DHT treatment. We then investigated gene expression changes after DHT treatment by performing RNA-seq. The analysis revealed that DHT significantly reduced the Wnt signaling pathway, which plays a role in various diseases, including cancer. Finally, we demonstrate that DHT treatment decreases protein levels of β-catenin, a final effector of canonical Wnt signaling pathway. Overall, our data suggest a possible use of this nutraceutical as an adjuvant in the treatment of aggressive papillary thyroid carcinoma.

TRPS1 expression in non-melanocytic cutaneous neoplasms: an immunohistochemical analysis of 200 cases.

Although trichorhinophalangeal syndrome type 1 (TRPS1) was initially thought to be highly sensitive and specific for carcinomas and mesenchymal tumors of mammary origin, more recent data suggest its expression is not limited to breast neoplasms but also can be seen in other cutaneous neoplasms, such as extramammary Paget disease and squamous cell carcinoma (SCC) in situ. Two-hundred cases of non-melanocytic cutaneous neoplasm, including basal cell carcinomas (BCCs) (n = 41), SCCs (n = 35), Merkel cell carcinomas (MCCs) (n = 25), and adnexal neoplasms (n = 99), were tested for TRPS1 expression using a monoclonal anti- TRPS1 rabbit anti-human antibody. TRPS1 expression was present in almost all cases of SCC (94%), with a median H-score of 200, while it was either absent or only focally present in most BCCs (90%), with a median H-score of 5. The difference between BCCs and SCCs in H-score was significant (p < .001). All MCCs (100%) lacked TRPS1 expression. TRPS1 expression was frequently seen in most adnexal neoplasms, benign and malignant, in variable intensity and proportion but was consistently absent in apocrine carcinomas. All endocrine mucin-producing sweat gland carcinomas (EMPSGCs) (100%, 6/6) showed diffuse and strong TRPS1 immunoreactivity, with a median H-score of 300, which was significantly different (p < .001) than that of BCCs. Our study shows that TRPS1 may be an effective discriminatory marker for BCCs and SCCs. It also has a role in distinguishing BCCs from EMPSGCs.

Recurrent GATA3 P409Afs*99 Frameshift Extension Mutations in Sweat-gland Carcinoma With Neuroendocrine Differentiation.

Sweat-gland carcinoma with neuroendocrine differentiation (SCAND) was recently proposed as a new cutaneous adnexal neoplasm with neuroendocrine differentiation; however, its genetics are not well known. Herein, we performed clinicopathologic and genetic analyses of 13 SCAND cases and 5 control cases of endocrine mucin-producing sweat gland carcinoma (EMPSGC). The SCAND group included 11 males and 2 females with a median age of 68 years (range, 50 to 80y). All SCAND lesions occurred in the ventral trunk or genital area. Of the 13 SCAND cases, 9 and 5 exhibited lymph node and distant metastases, respectively. Three (23.1%) patients with SCAND died of the disease. In contrast, neither metastasis nor mortality was confirmed in the EMPSGC cases. Immunoexpression of the androgen receptor, c-Myb, and MUC2 was limited in SCAND, whereas EMPSGC frequently expressed these immunomarkers. GATA3 P409Afs*99 extension mutations were detected in 7 (53.8%) of the 13 SCAND cases, using Sanger or panel sequencing. All 7 SCAND cases with GATA3 mutations were located in the genital, inguinal, or lower abdominal regions, whereas 5 of the other 6 SCAND cases were located in the anterior upper to mid-trunk. No GATA3 mutations were detected in the EMPSGC cases (0/5, 0%). These clinicopathologic and genetic findings support SCAND as a tumor entity distinguishable from EMPSGC. In addition, the characteristic frameshift extension mutations in GATA3 contribute to the establishment of the tumor-type concept of SCAND.

AHNAK2 Promotes the Progression of Differentiated Thyroid Cancer through PI3K/AKT Signaling Pathway.

AHNAK2 may be used as a candidate marker for TC diagnosis and treatment. Thyroid cancer (TC) is the most frequent malignancy in endocrine carcinoma, and the incidence has been increasing for decades. To understand the molecular mechanism of DTC, we performed next-generation sequencing (NGS) on 79 paired DTC tissues and normal thyroid tissues. The RNA-sequencing (RNA-seq) data analysis results indicated that AHNAK nucleoprotein 2 (AHNAK2) was significantly upregulated in the thyroid cancer patient's tissue. We also analyzed AHNAK2 mRNA levels of DTC tissues and normal tissues from The Cancer Genome Atlas (TCGA). The association between the expression level of AHNAK2 and clinicopathological features was evaluated in the TCGA cohort. Furthermore, AHNAK2 gene expression was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) in 40 paired DTC tissues and adjacent normal thyroid tissues. The receiver operating characteristic (ROC) curve was performed to evaluate the diagnostic value of AHNAK2. For cell experiments in vitro, AHNAK2 was knocked down using small interfering RNA (siRNA), and the biological function of AHNAK2 in TC cell lines was investigated. The expression of AHNAK2 was significantly upregulated in both the TCGA cohort and the local cohort. The analysis results of the TCGA cohort indicated that the upregulation of AHNAK2 was associated with tumor size (P < 0.001), lymph node metastasis (P < 0.001), and disease stage (P < 0.001). The area under the curve (AUC, TCGA: P < 0.0001; local validated cohort: P < 0.0001) in the ROC curve revealed that AHNAK2 might be considered a diagnostic biomarker for TC. The knockdown of AHNAK2 reduced TC cell proliferation, colony formation, migration, invasion, cell cycle, and induced cell apoptosis. Furthermore, the protein levels of phospho-PI3 Kinase p85 and phospho-AKT were downregulated in the transfected TC cell. Our study results indicate that AHNAK2 may promote metastasis and proliferation of thyroid cancer through PI3K/AKT signaling pathway. Thus, AHNAK2 may be used as a candidate marker for TC diagnosis and treatment.

Misleading wheeze in a case of atypical large cell neuroendocrine carcinoma of lung - A deadly variety

Neuroendocrine tumors are neoplasms arising from cells of endocrine and nervous system containing special secretory granules with biogenic amines and polypeptide hormones. One of the varieties that occurs commonly in the lung is large cell neuro endocrine carcinoma. The replicative potential of these neuroendocrine malignancies is so rapid that the patients usually present with metastatic disease. We describe a case of 29-year-old-male presented with nocturnal wheeze which led on to a misdiagnosis of bronchial asthma and finally found to be LCNEC with endobronchial obstruction. They are usually peripherally located lesions, mostly in the upper lung zones of an elderly male smoker. But he had a hilar mass with right lower lobe collapse due to endobronchial obstruction. Hence careful examination of wheeze whether unilateral or bilateral, monophonic or polyphonic, random or fixed, inspiratory or expiratory or biphasic may help in early identification of the endobronchial lesions.

Pro-oncogene FBI-1 inhibits the ferroptosis of prostate carcinoma PC-3 cells via the microRNA-324-3p/GPX4 axis.

Ferroptosis has been characterized as non-apoptotic programmed cell death and is considered a novel strategy for antitumor treatment. The factor that binds to inducer of short transcripts-1 (FBI-1) is an important proto-oncogene playing multiple roles in human malignancies and the development of resistance to therapy. However, the roles of FBI-1 in ferroptosis of endocrine independent prostate carcinoma are still unknown. The results of this study showed that FBI-1 inhibited the ferroptosis of prostate carcinoma PC-3 cells (a typical endocrine-independent prostate carcinoma cell line) via the miR-324-3p/glutathione peroxidase 4 (miR-324-3p/GPX4) axis. Overexpression of FBI-1 enhanced the expression levels of GPX4. In contrast, knockdown of FBI-1 decreased the expression of GPX4 and induced the ferroptosis of PC-3 cells. The miR-324-3p decreased the expression of GPX4 by targeting the 3'-untranslated region of GPX4 to induce ferroptosis. Notably, FBI-1 increased the expression of GPX4 by repressing the levels of miR-324-3p. The transcription of miR-324-3p was mediated by specificity protein 1 (SP1), and FBI-1 repressed the expression of miR-324-3p by repressing the activation of SP1. In clinical specimens, the endogenous levels of FBI-1 were positively associated with Glutathione Peroxidase 4 (GPX4) and negatively related with the expression of miR-324-3p. Therefore, the results indicated that the miR-324-3p/GPX4 axis participates in the FBI-1-mediated ferroptosis of prostate carcinoma cells.

TRPS1 Expression in Endocrine Mucin-Producing Sweat Gland Carcinoma: Diagnostic Utility and Pitfalls.

TRPS1 Expression in Endocrine Mucin-Producing Sweat Gland Carcinoma: Diagnostic Utility and Pitfalls.

Network medicine approaches for identification of novel prognostic systems biomarkers and drug candidates for papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) is one of the most common endocrine carcinomas worldwide and the aetiology of this cancer is still not well understood. Therefore, it remains important to understand the disease mechanism and find prognostic biomarkers and/or drug candidates for PTC. Compared with approaches based on single-gene assessment, network medicine analysis offers great promise to address this need. Accordingly, in the present study, we performed differential co-expressed network analysis using five transcriptome datasets in patients with PTC and healthy controls. Following meta-analysis of the transcriptome datasets, we uncovered common differentially expressed genes (DEGs) for PTC and, using these genes as proxies, found a highly clustered differentially expressed co-expressed module: a 'PTC-module'. Using independent data, we demonstrated the high prognostic capacity of the PTC-module and designated this module as a prognostic systems biomarker. In addition, using the nodes of the PTC-module, we performed drug repurposing and text mining analyzes to identify novel drug candidates for the disease. We performed molecular docking simulations, and identified: 4-demethoxydaunorubicin hydrochloride, AS605240, BRD-A60245366, ER 27319 maleate, sinensetin, and TWS119 as novel drug candidates whose efficacy was also confirmed by in silico analyzes. Consequently, we have highlighted here the need for differential co-expression analysis to gain a systems-level understanding of a complex disease, and we provide candidate prognostic systems biomarker and novel drugs for PTC.

Efficacy of olaparib in advanced cancers with germline or somatic mutations in BRCA1, BRCA2, CHEK2 and ATM, a Belgian Precision tumor-agnostic phase II study

The Belgian Precision initiative aims to maximize the implementation of tumor-agnostic next-generation sequencing in patients with advanced cancer and enhance access to molecularly guided treatment options. Academic tumor-agnostic basket phase II studies are part of this initiative. The current investigator-driven trial aimed to investigate the efficacy of olaparib in advanced cancers with a (likely) pathogenic mutation (germline or somatic) in a gene that plays a role in homologous recombination (HR). This open-label, multi-cohort, phase II study examines the efficacy of olaparib in patients with an HR gene mutation in their tumor and disease progression on standard of care. Patients with a somatic or germline mutation in the same gene define a cohort. For each cohort, a Simon minimax two-stage design was used. If a response was observed in the first 13 patients, 14 additional patients were included. Here, we report the results on four completed cohorts: patients with a BRCA1, BRCA2, CHEK2 or ATM mutation. The overall objective response rate across different tumor types was 11% in the BRCA1-mutated (n= 27) and 21% in the BRCA2-mutated (n= 27) cohorts. Partial responses were seen in pancreatic cancer, gallbladder cancer, endocrine carcinoma of the pancreas and parathyroid cancer. One patient with a BRCA2 germline-mutated colon cancer has an ongoing complete response with 19+ months on treatment. Median progression-free survival in responding patients was 14+ months (5-34+ months). The clinical benefit rate was 63% in the BRCA1-mutated and 46% in the BRCA2-mutated cohorts. No clinical activity was observed in the ATM (n= 13) and CHEK2 (n= 14) cohorts. Olaparib showed efficacy in different cancer types harboring somatic or germline mutations in the BRCA1/2 genes but not in ATM and CHEK2. Patients with any cancer type harboring BRCA1/2 mutations should have access to olaparib.

Comprehensive prognostic signatures in thyroid cancer: A summarized review for molecular signatures construction strategies

Thyroid carcinoma (TC) is one of the most common endocrine carcinomas with an increasing rate of morbidity in recent decades. With a high risk of relapse and metastasis occurring in TC patients, it is essential to identify potential prognostic signatures for TC patients. Here, through a comprehensive review, we summarized 45 prognostic signatures for TC patients and concluded three main strategies for signature establishment after an extensive investigation. In particular, these signatures were classified according to different construction strategies, and the verification methods were summarized. Besides, we found that 18 key genes were overrepresented in reported signatures. This review provides a comprehensive understanding, systematic summary, and integrated analysis of current prognostic signatures of TC, which may help researchers to further understand cancer progression, construct prognostic signatures of TC, and guide future clinical treatment.

Endocrine Mucin-Producing Sweat Gland Carcinoma: Case Presentation with a Comprehensive Review of the Literature.

(1) Background: Endocrine Mucin-Producing Sweat Gland Carcinoma (EMPSGC) is a rare, low-grade, neuroendocrine-differentiated, cutaneous adnexal tumor, officially recognized by the World Health Organization (WHO) Skin Tumors Classification in 2018 as a separate entity and homologue of endocrine ductal carcinoma in situ (eDCIS)/solid papillary carcinoma of the breast. Although it is more frequent in the female sex, between 60 and 70 years old, in the peri-orbital region, EMPSGC has also been described in the male sex, in subjects under 60 and over 80, and in extra-eyelid localizations (cheek, temple, scalp), but also in extra-facial localizations (chest and scrotum). (2) Methods: We present the clinical case of a 71-year-old woman with an undated lesion of the scalp, which presented as a nodule, skin-colored, and 2.5 cm in maximum diameter. We also conduct a comprehensive literature review from 1997 to the end of 2022, consulting PubMed, Scopus, Web of Science (WoS), and Google Scholar using the following keywords: "Endocrine mucin-producing sweat gland carcinoma" and/or "EMPSGC" and/or "skin" and "cutaneous neoplasms". In addition, we followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A total of 253 patients were recorded; 146 were females (57.7%) and 107 were males (42.2%). The vast majority of the lesions were in the eyelids (peri-ocular region), and only a minority of cases involved the cheeks, supra-auricular, retro-auricular, and occipital region, with very rare cases in the scalp, to which the present is also added. (4) Conclusions: The morphological and immunophenotypical features are essential both for the correct diagnosis and to be able to classify this lesion among the corresponding eDCIS/solid papillary carcinoma of the breast, with neuroendocrine differentiation. Recent papers have attempted to shed light on the molecular features of EMPSGC, and much remains to be conducted in the attempt to subtype the molecular profiles of these entities. Future studies with large case series, and especially with molecular biology techniques, will be needed to further add information about EMPSGC and its relationship in the PCMC spectrum.

Endocrine Mucin-Producing Sweat Gland Carcinoma and Primary Cutaneous Mucinous Carcinoma: A Case Series.

Endocrine mucin-producing sweat gland carcinoma (EMPSGC) and primary cutaneous mucinous carcinoma (PCMC) are rare low-grade neoplasms thought to arise from apocrine glands that share many histological features and are proposed to be on a single histopathologic continuum, with EMPSGC as the in situ form that may progress to the invasive PCMC. Management involves a metastatic workup and either wide local excision (WLE) with greater than 5 mm margins or Mohs micrographic surgery (MMS) in anatomically sensitive areas. We present 2 cases of EMPSGC and 3 cases of PCMC and review their clinical and histopathologic features, differential diagnoses, and treatment.

239P Efficacy of single-agent chemotherapy in endocrine therapy-refractory metastatic invasive lobular carcinoma

239P Efficacy of single-agent chemotherapy in endocrine therapy-refractory metastatic invasive lobular carcinoma

A Case of Endocrine Mucin-Producing Sweat Gland Carcinoma of the Eyelid

Purpose: We report an endocrine mucin-producing sweat gland carcinoma diagnosed by biopsy in a patient who presented with an eyelid mass.Case summary: A 64-year-old male presented with a 3 × 3 mm solitary, painless pinkish mass on the right lower eyelid that had developed over the past year. The mass was excised and a biopsy was performed. The pathological findings included basaloid nodules composed of cells with eosinophilic cytoplasm, focal mucin production, and occasional glandular structures. Immunohistochemical examination was positive for cytokeratin 7 (CK-7), tumor protein 63 (P63), and the androgen receptor (AR). The patient was thus diagnosed with an endocrine mucin-producing sweat gland carcinoma. The lesion healed, and there has been no sign of recurrence over 6 months of follow-up.Conclusions: An endocrine mucin-producing sweat gland carcinoma is a very rare low-grade glandular malignancy that has not been reported in Korea previously. The prognosis is good (i.e., there is no recurrence) when the lesion is completely surgically excised. We thought it would be useful to report this very rare case.

Primary cutaneous endocrine mucin-producing sweat gland carcinoma: a rare case report

Background: Endocrine mucin-producing carcinoma is a rare adnexal tumour of the skin with low-grade cytological features and neuroendocrine differentiation. It has a predilection for skin of the eyelid, but has also been reported in the face and rarely extra-facial locations. The tumour is seen more frequently in women affecting the elderly. It is histologically and immunohistochemically analogous to solid papillary carcinoma of breast/ductal carcinoma in situ with nodular, solid, papillary, and /or cribriform architecture, neuroendocrine differentiation and mucin production with preserved myoepithelial cell layer.

Multimodal Neural Network for Recurrence Prediction of Papillary Thyroid Carcinoma

Papillary thyroid carcinoma (PTC) is the most common endocrine carcinoma and has frequent recurrence instances. Although PTC recurrence has been predicted using predictors established using various features and techniques, its early detection is still challenging. To address this issue, it is aimed to develop a deep‐learning model that utilizes not only the initial medical records but also the thyroid function tests (TFTs) performed periodically post‐surgery. Herein, a novel multimodal prediction model, called the hybrid architecture for multimodal analysis (HAMA), that can analyze numeric and time‐series data simultaneously, is proposed. For quantitative evaluation, fourfold cross validation is conducted on data of 1613 PTC patients including 63 locoregional recurrence patients, and the HAMA is achieved the following performance: sensitivity (0.9688); specificity (0.9781); F1‐score (0.7943); and area under the receiver‐operating characteristic curve, AUROC (0.9863). Furthermore, a real‐time prediction simulation is conducted at 6‐month intervals by reconstructing the data of each patient into real‐time data. It is demonstrated in the real‐time simulation results that the HAMA predicts PTC recurrence at least 1.5 years in advance by recalculating the recurrence probability using the additional follow‐up data. To the best of the knowledge, the HAMA is the first deep‐learning model to reflect continuous change in the physical condition of a patient post‐surgery.

Health Belief Model among Patients with Thyroid Carcinoma

Thyroid Carcinoma (TC) is the most common endocrine carcinoma accounts for90% of all endocrine malignancies, awareness of health belief can help patients with TC to preventmost of complication.

Parathyroid Carcinoma: A Diagnostic Challenge – A Case Report

Introduction Parathyroid carcinoma is a rare endocrine carcinoma, presenting as hypercalcemia with elevated parathyroid hormone (PTH) levels, and with renal and bone involvement. It is often misdiagnosed as parathyroid adenoma, resulting in conservative resection of the parathyroid gland and recurrence or metastasis after a few years. Case Description A 52-year-old, morbidly obese woman presented with asymptomatic hypercalcemia and elevated PTH. Ultrasound of the neck showed a cystic lesion adjacent to the right thyroid lobe. Sestamibi (MIBI) parathyroid scintigraphy showed increased radiopharmaceutical uptake by the right superior parathyroid gland without any enlarged or suspicious lymph nodes. She was diagnosed with primary hyperparathyroidism. She underwent right superior parathyroidectomy and en bloc right thyroid lobectomy due to suspicion of parathyroid carcinoma. The histological examination was consistent with parathyroid carcinoma. Discussion Parathyroid carcinoma is a rare disease with no clear diagnostic criteria. The curative treatment for parathyroid carcinoma is the initial en bloc resection. Therefore, early diagnosis is important and high clinical suspicion is warranted in patients with severe hypercalcemia and markedly elevated PTH, with or without palpable neck mass, and renal or bone involvement.