Abdelrahman Sherif Abdalla, Mobeen Rahman, Saad A Khan
Anaplastic thyroid cancer presents formidable challenges, particularly in cases of recurrence or metastasis. Timely BRAF V600E testing is imperative at diagnosis, initially through immunohistochemistry, followed by comprehensive genomic profiling encompassing genes such as NTRK, RET, ALK, and assessment of tumor mutation burden (TMB). FDA-approved treatment options include dabrafenib and trametinib for patients with BRAF mutations, while those exhibiting high TMB may benefit from pembrolizumab. Further therapeutic decisions hinge upon mutational profile, urgency of response required, airway integrity, and access to targeted therapies There is growing use of immunotherapy for ATC based on published reports of activity, but currently there is no FDA approved agent for ATC...
June 12, 2024: Current Treatment Options in Oncology
Daniel W Scholfield, Conall W R Fitzgerald, Lillian A Boe, Alana Eagan, Helena Levyn, Bin Xu, R Michael Tuttle, James A Fagin, Ashok R Shaha, Jatin P Shah, Richard J Wong, Snehal G Patel, Ronald Ghossein, Ian Ganly
BACKGROUND: Diffuse sclerosing papillary thyroid carcinoma (DSPTC) is an aggressive histopathologic subtype of papillary thyroid carcinoma. Correlation between genotype and phenotype has not been comprehensively described. This study aimed to describe the genomic landscape of DSPTC comprehensively using next-generation sequencing (NGS), analyze the prognostic implications of different mutations, and identify potential molecular treatment targets. METHODS: Tumor tissue was available for 41 DSPTC patients treated at Memorial Sloan Kettering Cancer Center between 2004 and 2021...
June 7, 2024: Annals of Surgical Oncology
Li-Hsin Pan, Jen-Fan Hang, Jui-Yu Chen, Po-Sheng Lee, Yun-Kai Yeh, Tai-Jung Huang, Chii-Min Hwu, Chin-Sung Kuo
BACKGROUND: Cribriform morular thyroid carcinoma has been recently renamed in the 2022 WHO classification as a thyroid tumor of uncertain histogenesis. The epidemiologic, pathological, and pathophysiological characteristics distinguish it from papillary thyroid carcinoma (PTC). Preoperative genetic testing plays a role in facilitating the differential diagnosis. METHODS: This report presents a confirmed case of cribriform morular thyroid carcinoma. Initially, fine-needle aspiration cytology suggested a diagnosis of PTC...
2024: Case Reports in Endocrinology
Simon Garinet, Audrey Lupo, Thomas Denize, Romain Loyaux, Sarah Timsit, Benoit Gazeau, Elizabeth Fabre, Zineb Maaradji, Laure Gibault, Etienne Giroux-Leprieur, Boris Duchemann, Isabelle Monnet, Stéphane Jouveshomme, Mihaela Aldea, Benjamin Besse, Françoise Le Pimpec-Barthes, Karen Leroy, Marie Wislez, Hélène Blons
Metastatic non-small-cell lung cancer (NSCLC) displays various molecular alterations in the RAS-MAPK pathway. In particular, NSCLCs show high rates of targetable gene fusion in ALK, RET, ROS1, NRG1 and NTRK, or MET exon 14 skipping. Rapid and accurate detection of gene fusion in EGFR/KRAS/BRAF mutations is important for treatment selection especially for first-line indications. RNA-based next-generation sequencing (NGS) panels appear to be the most appropriate as all targets are multiplexed in a single run...
May 18, 2024: Pathology
X L Ma, R N Jia, K Han, Y X Zhang
Objective: To correlate the common driver gene variations in primary lung adenocarcinoma with their clinical characteristics and histopathological subtypes. Methods: There were 4 995 cases of primary lung adenocarcinoma diagnosed at Weifang People's Hospital of Shandong Province from January 2015 to December 2021 which were retrospectively analyzed. Among them 1 983 cases were evaluated for their histopathological subtype; 3 012 were analyzed for the correlation of their histopathological subtypes and corresponding driver gene variations, including invasive non-mucinous adenocarcinoma (INMA) and invasive mucinous adenocarcinoma (IMA), and morphologically, poorly-differentiated, moderately-differentiated and well-differentiated adenocarcinomas...
June 8, 2024: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
Jonathan P Rivera, Yi-Chen Yeh, Paul Chih-Hsueh Chen, Jen-Fan Hang
Multifocal papillary thyroid carcinomas (PTCs) are common and the majority of the tumors harbor mutual BRAF p.V600E mutation. This study aimed to investigate a contemporary series of multifocal PTCs with discordant molecular drivers. Consecutive thyroidectomies diagnosed with multifocal PTCs ≥0.5 cm between 2019 and 2023 were reviewed. Immunohistochemistry (IHC) for BRAF VE1 was performed for all tumors. Cases with discordant BRAF IHC results or morphologic discrepancy were identified, and BRAF IHC-negative tumors were subjected to RAS Q61R IHC and/or targeted RNA next-generation sequencing...
May 31, 2024: American Journal of Surgical Pathology
Bassam AlHamer, Ajit Singh, Carmen Patrascu, Mona Al Mukaddam
Tumor-induced osteomalacia (TIO) is an exceedingly rare paraneoplastic condition characterized by hypophosphatemia, osteomalacia, fragility fractures, and fatigue. A 39-year-old man was assessed for hemoptysis, pathological rib fractures, and fatigue, and was found to have a chest mass with lung metastasis. Biopsy of the mass suggested high-grade epithelioid and spindle cell neoplasm. He was initially treated for soft tissue sarcoma with an ifosfamide-based regimen and developed Fanconi syndrome that resolved on cessation of ifosfamide...
June 2024: JCEM Case Rep
Hui-Fen Zhang, Shu-Ling Huang, Wen-Li Wang, Yu-Qing Zhou, Jun Jiang, Zhuo-Jin Dai
BACKGROUND: Multiple endocrine neoplasia type 2 (MEN2) is a rare, autosomal dominant endocrine disease. Currently, the RET proto-oncogene is the only gene implicated in MEN2A pathogenesis. Once an RET carrier is detected, family members should be screened to enable early detection of medullary thyroid carcinoma, pheochromocytoma, and hyperparatitity. Among these, medullary thyroid carcinoma is the main factor responsible for patient mortality. Accordingly, delineating strategies to inform clinical follow-up and treatment plans based on genes is paramount for clinical practitioners...
May 26, 2024: World Journal of Clinical Cases
Yuki Nagakubo, Yosuke Hirotsu, Mona Yoshino, Kenji Amemiya, Ryota Saito, Yumiko Kakizaki, Toshiharu Tsutsui, Yoshihiro Miyashita, Taichiro Goto, Masao Omata
Companion diagnostic (CDx) tests play important roles in identifying oncogenic driver genes and tailoring effective molecularly targeted therapies for lung cancer patients. In Japan, the Oncomine Dx target test (ODxTT) and the AmoyDx pan lung cancer PCR panel (AmoyDx) are prominent CDx tests and only one of these tests is covered by the domestic insurance system. However, these CDx tests cover different target regions and apply different technologies (ODxTT is amplicon-based next-generation sequencing and AmoyDx is multiplex PCR-based assay), which may lead to missing of actionable mutations affecting patient prognosis...
May 30, 2024: Scientific Reports
Alexander Haragan, Robert Lee
OBJECTIVES: Comprehensive molecular analysis for patients with non-small-cell lung carcinoma (NSCLC) is essential for managing modern targeted therapies. This study sought to establish the feasibility of utilising real-time PCR to perform rapid and comprehensive profiling on minimal amounts of endobronchial ultrasound-guided (EBUS) aspirates as a fast, tissue-sparing route of predictive profiling. METHODS: A volume of 500 μL of EBUS aspirate and fixative from patients with NSCLC was decanted, and 80 μL (<1% of total specimen received) was utilised for analysis...
May 30, 2024: Cytopathology: Official Journal of the British Society for Clinical Cytology
Vivek Subbiah, Mohamed A Gouda, Bettina Ryll, Howard A Burris, Razelle Kurzrock
Tumor-agnostic therapies represent a paradigm shift in oncology by altering the traditional means of characterizing tumors based on their origin or location. Instead, they zero in on specific genetic anomalies responsible for fueling malignant growth. The watershed moment for tumor-agnostic therapies arrived in 2017, with the US Food and Drug Administration's historic approval of pembrolizumab, an immune checkpoint inhibitor. This milestone marked the marriage of genomics and immunology fields, as an immunotherapeutic agent gained approval based on genomic biomarkers, specifically, microsatellite instability-high or mismatch repair deficiency (dMMR)...
May 30, 2024: CA: a Cancer Journal for Clinicians
Alexandria T M Lee, Sai-Hong Ignatius Ou
Selpercatinib, a potent and highly selective RET kinase inhibitor with significant CNS activity, has recently gained US approval for the treatment of NSCLC harboring RET fusions ( RET +) based on a large-scale single-arm study. The LIBRETTO-431 trial was the global pivotal registration phase 3 trial comparing selpercatinib to platinum-based chemotherapy with or without pembrolizumab as the first-line treatment of patients with advanced RET + NSCLC. Never-smokers constituted 67.4% of the RET + NSCLC patients enrolled...
2024: Lung Cancer: Targets and Therapy
Henning Dralle, Frank Weber, Kerstin Lorenz, Andreas Machens
Medullary thyroid cancer (MTC) is the most frequent manifestation of multiple endocrine neoplasia type 2 (MEN2) that determines the oncological outcome. Germline mutations in the rearranged during transfection (RET) protooncogene, a tumor suppressor gene on chromosome 10q11.2, were identified 30 years ago as the genetic basis of MEN2 and published in 1993 and 1994. These seminal findings gave rise to the concept of prophylactic thyroidectomy for asymptomatic gene mutation carriers based on a positive RET gene test, which has become the standard of care ever since...
May 28, 2024: Chirurgie (Heidelb)
Rui Fu, Yuanyuan Xiong, Miao Cai, Fang Li, Rongrong Chen, Yilong Wu, Wenzhao Zhong
Gene fusions and MET alterations are rare and difficult to detect in plasma samples. The clinical detection efficacy of molecular residual disease (MRD) based on circulating tumor DNA (ctDNA) in patients with non-small cell lung cancer (NSCLC) with these mutations remains unknown. This prospective, non-intervention study recruited 49 patients with operable NSCLC with actionable gene fusions (ALK, ROS1, RET, and FGFR1), MET exon 14 skipping or de novo MET amplification. We analyzed 43 tumor tissues and 111 serial perioperative plasma samples using 1021- and 338-gene panels, respectively...
May 28, 2024: Frontiers of Medicine
Katherine Wu, Shejil Kumar, Ed Hsiao, Ian Kerridge, Min Ru Qiu, Rhonda Siddall, Roderick Clifton-Bligh, Anthony J Gill, Matti L Gild
SUMMARY: RET mutations are implicated in 60% of medullary thyroid cancer (MTC) cases. The RET-selective tyrosine kinase inhibitor selpercatinib is associated with unprecedented efficacy compared to previous multi-kinase treatments. Langerhans cell histiocytosis (LCH) is a clonal histiocytic neoplasm usually driven by somatic BRAF mutations, resulting in dysregulated MAPK signalling. We describe a 22-year-old woman with metastatic MTC to regional lymph nodes, lung and liver. Tumour tissue harboured a somatic pathogenic RET variant p...
April 1, 2024: Endocrinology, Diabetes & Metabolism Case Reports
Katarzyna Stawarz, Monika Durzynska, Adam Galazka, Monika Paszkowska, Karolina Bienkowska-Pluta, Jakub Zwolinski, Andrzej Tysarowski, Ewa Kwiatkowska, Agnieszka Podgorska
BACKGROUND: In clinical practice, genetic testing has become standard for many cancerous diseases. While a diagnosis of a single hereditary syndrome is not uncommon, the coexistence of two genetic diseases, even with partially common symptoms, remains unusual. Therefore, targeted next-generation sequencing (NGS), along with genetic consultation and imaging studies, is essential for every patient with confirmed paraganglioma. In this report, we present two sisters diagnosed with multiple endocrine neoplasia type 2 (MEN2A) and familial paraganglioma syndrome type 1 (FPGL1)...
May 27, 2024: World Journal of Surgical Oncology
Fabian Pitoia, Pierpaolo Trimboli, Erika Abelleira
Selpercatinib, a selective RET kinase inhibitor, has demonstrated remarkable efficacy in treating patients with advanced medullary (MTC) and differentiated thyroid cancer with RET alterations. Primary resistance to selpercatinib is a very uncommon situation, and its underlying mechanisms are poorly understood. We report the case of a 42-year-old female with advanced MTC harboring a somatic M918T RET mutation who exhibited a primary resistance to selpercatinib. Despite prompt treatment initiation after the diagnosis of progressive disease, the patient continued experiencing rapid spread of disease, characterized by the appearance of new metastatic lesions and increased tumor burden...
May 27, 2024: Endocrine
Xiaofang Zhang, Yixian Liu, Xiaoxuan Liu, Hua Shu, Zuoliang Dong
BACKGROUND: Calcitonin (CT) is a sensitive serum marker of medullary thyroid carcinoma usually detected via immunoassays; however, its levels are easily disturbed by several endogenous factors. OBJECTIVE: The study aimed to discuss a case of suspected interference resulting in aberrant CT values and review previous reports of CT interference. METHODS: A female patient visited our clinic with a physical ultrasound examination showing a slightly enlarged thyroid gland with small nodules...
May 24, 2024: Endocrine, Metabolic & Immune Disorders Drug Targets
A Y Lugovskaya, T A Britvin, L E Gurevich, I S Rog, L N Nefedova, I A Ilovayskaya
We presented the clinical case of neurofibromatosis type 1 (NF-1) associated with pheochromocytoma (PHEO) in a man under 40 years old without family history. The diagnosis of NF-1 was established based on 4 signs of the disease (multiple café au lait macules, scoliotic changes in posture, the presence of multiple neurofibromas, Lisch nodules). The diagnosis of PHEO was determined by a significant increase of free metanephrin/normethanephrin levels in daily urine, a malignant CT phenotype of the right adrenal tumor, and confirmed by pathomorphological study...
September 11, 2023: Problemy E̊ndokrinologii
Kalliopi Andrikou, Paola Ulivi, Elisabetta Petracci, Irene Azzali, Federica Bertolini, Giulia Alberti, Stefania Bettelli, Daniele Calistri, Elisa Chiadini, Laura Capelli, Paola Cravero, Giorgia Guaitoli, Francesca Zanelli, Marco Angelo Burgio, Maria Pagano, Alberto Verlicchi, Enrica Martinelli, Katia Di Emidio, Massimo Dominici, Carmine Pinto, Angelo Delmonte
The real-world, retrospective, NEROnE registry investigated the impact of next-generation sequencing (NGS) in advanced non-small-cell lung cancer (NSCLC) patients (pts) at three oncology units in the north of Italy between January 2020 and December 2022. We focused on the clinical characterization and outcomes of NSCLC with rare molecular alterations: EGFR exon 20 insertion, non-activating EGFR mutations, BRAF V600E and non-V600, ROS1 and RET rearrangements, MET , ErbB2, and FGFR mutations. Overall, these represented 6...
May 15, 2024: Diagnostics
Fetch more papers »
Fetching more papers... Fetching...
Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"

We want to hear from doctors like you!

Take a second to answer a survey question.