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Calcitonin-secreting neuroendocrine neoplasms of the lung are rare, with few cases reported in the literature. Differentiating between medullary thyroid carcinoma and an ectopic source of calcitonin secretion can represent a complex diagnostic conundrum for managing physicians, with cases of unnecessary thyroidectomy reported in the literature. Thi...
Context in source publication
Context 1
... discussion in the thyroid cancer multidisciplinary team meeting, her left thyroid confluence was upgraded to U4 using British Thyroid Association (BTA) guidelines (Table 1) (12). Serum calcitonin was measured and fine-needle aspiration (FNA) of the thyroid confluence was performed to help rule out MTC. ...Citations
... The neuroendocrine cells of the stomach and lung, and the parafollicular cells (C cells) of the thyroid, secrete procalcitonin (PCT), a 116-amino acid peptide precursor of calcitonin. Pantzaris et al. [4], under the regulation of the CALC-1 gene [5]. In healthy individuals serum PCT levels stay below the detection limit of 0.01 microg/l [6]. ...
Aims: The goal of this study was to determine the diagnostic importance and cut-off value of serum PCT as a vital biomarker in differentiating bacterial and non-bacterial causes of exacerbation of COPD. Study Design: It was a comparative cross-sectional study. Place and Duration of Study: Study was conducted on 80 patients recruited from VMMC and Safdarjung Hospital, New- Delhi, India, for a period of 18 months. Forty patients has COPD and other 40 had acute exacerbation of COPD. Methodology: Every enrolled patient received a thorough history, a clinical assessment, and records of tests such as a venous blood sample, spirometry, and a chest X-ray. We excluded from our study patients with various respiratory conditions such as hydrothorax, pneumothorax, CHF, pleural effusion, and those outside the respiratory system, as well as those who started antibiotic medication earlier than 48 hours after enrollment. Venous samples were obtained from each participant in order to measure procalcitonin levels and blood counts. Serum PCT levels were assessed by ELISA kit. Gram stain and culture was done of sputum sample collected from the exacerbated group. Results: Patients with bacterial COPD exacerbations had significantly higher mean serum PCT levels compared to non-bacterial exacerbations (2.58±1.54 vs 0.45±0.51 ng/ml; P=0.0001) based on sputum culture results. PCT cutoff of 0.9 ng/ml differentiated bacterial exacerbations with 100% sensitivity and 76.9% specificity. Conclusion: The findings of the study indicate the serum PCT levels can be regarded as an appropriate biomarker to differentiate between the bacterial and non-bacterial cause of exacerbation in COPD.
... MTC diagnosis is performed by thyroid nodule biopsy and assessment of calcitonin (Ctn) is mandatory either through immunohistochemical positivity for Ctn or measurement of Ctn from fine needle aspiration biopsies and deregulated Ctn serum levels. Of note, elevated Ctn serum levels are not only associated to MTC but also to non-tumoral conditions such as C cell hyperplasia, goiter and renal insufficiency as well as in a few non-thyroid related tumours (neuroendocrine tumours of the lung or gastro intestinal tract) [6][7][8]. MTC patients follow-up is performed by assessment of serum Ctn and carcinoembryonic antigen (CEA) along with imaging evaluations [9], however MTC progression is not always accompanied by the increase of these serum biomarkers leading to MTC patients' progression remaining undetected until the presence of a new lesion. ...
Purpose/methods:
The determination of tumour biomarkers is paramount to advancing personalized medicine, more so in rare tumours like medullary thyroid carcinoma (MTC), whose diagnosis is still challenging. The aim of this study was to identify non-invasive circulating biomarkers in MTC. To achieve this goal, paired MTC tissue and plasma extracellular vesicle samples were collected from multiple centres and microRNA (miRNA) expression levels were evaluated.
Results:
The samples from a discovery cohort of 23 MTC patients were analysed using miRNA arrays. Lasso logistic regression analysis resulted in the identification of a set of circulating miRNAs as diagnostic biomarkers. Among them, miR-26b-5p and miR-451a, were highly expressed and their expression decreased during follow-up in disease-free patients in the discovery cohort. Circulating miR-26b-5p and miR-451a were validated using droplet digital PCR in a second independent cohort of 12 MTC patients.
Conclusion:
This study allowed the identification and validation of a signature of two circulating miRNAs, miR-26b-5p and miR-451a, in two independent cohorts reporting a significant diagnostic performance for MTC. The results of this study offer advancements in molecular diagnosis of MTC proposing a novel non-invasive tool to use in precision medicine.
... In blood tests, Pro-GRP, which is specific for SCLC, is reported to be high, especially in nongastrointestinal neuroendocrine carcinoma, and may also be elevated in LCNEC of the lung, as seen in this case (10). In addition, calcitonin, a hormone specific to the thyroid gland, may be elevated in lung neuroendocrine tumors, as seen in this case (11). ...
A 76-year-old woman was admitted to our hospital for refractory diarrhea with a poor antidiarrheal effect. Chest and abdominal computed tomography revealed a 24×22-mm mass in the left upper lobe of lung and multiple masses in the liver. Urine 5-Hydroxy indol acetic acid was markedly elevated. A liver biopsy revealed large-cell neuroendocrine carcinoma with serotonin production, suggestive of a lung origin, and a lung biopsy revealed combined large-cell neuroendocrine carcinoma and squamous cell carcinoma. Therefore, we made a definitive diagnosis of carcinoid syndrome caused by large-cell neuroendocrine carcinoma of the lung. Although chemotherapy was performed after diagnosis, the patient died 50 days postadmission.
... NEN-UPs derived from the bronchi or lungs are usually positive for classic neuroendocrine markers and often express TTF1 and bombesin/gastrin-releasing peptide (GRP) [30]. Subsets of cases may also express calcitonin or calcitonin-related peptide [46]. However, note that subsets of typical and atypical carcinoids may display aberrant expression of serotonin, while pulmonary NECs may upregulate PAX8 (Figure 4) [47,48]. ...
Simple Summary
While most neuroendocrine neoplasms are indolent and slow-growing tumors, subsets of cases will spread beyond the tissue of origin. Given the rather slow progress, some lesions are incidentally discovered as metastatic deposits rather than primary masses. In these cases, a biopsy is often taken to allow the pathologist to identify the tumor type and possibly the primary tumor site via microscopic examination. In this review, the authors present a simplified guide on how to approach metastatic neuroendocrine tumors from a pathologist’s perspective.
Abstract
Neuroendocrine neoplasms (NENs) are diverse tumors arising in various anatomical locations and may therefore cause a variety of symptoms leading to their discovery. However, there are instances in which a NEN first presents clinically as a metastatic deposit, while the associated primary tumor is not easily identified using conventional imaging techniques because of small primary tumor sizes. In this setting (which is referred to as a “NEN of unknown primary”; NEN-UP), a tissue biopsy is often procured to allow the surgical pathologist to diagnose the metastatic lesion. If indeed a metastatic NEN-UP is found, several clues can be obtained from morphological assessment and immunohistochemical staining patterns that individually or in concert may help identify the primary tumor site. Herein, histological and auxiliary analyses of value in this context are discussed in order to aid the pathologist when encountering these lesions in clinical practice.
Neuroendocrine neoplasms can produce multiple hormones that are released into the bloodstream, causing symptoms that vary depending on the type and quantity of hormones involved. We herein report a 63-year-old asymptomatic patient with pancreatic insulinoma who showed marked elevations in circulating calcitonin and procalcitonin levels that returned to normal following surgery. Immunohistochemical analyses confirmed the co-staining of calcitonin and insulin immunoreactivity in the tumor cells, suggesting a calcitonin-producing insulinoma. This insulinoma released calcitonin and a considerable amount of its precursor peptide, procalcitonin, resulting in both hyperprocalcitoninemia and hypercalcitoninemia.
Background:
Medullary thyroid cancer (MTC) is a rare malignancy originating from the calcitonin-producing C cells of the thyroid. Despite recent therapeutic advances, metastatic MTC remains incurable. Adoptive cell therapy (ACT) using genetically engineered T cells targeting either tissue-restricted, tumor-associated antigens or mutated neoantigens has led to durable remissions in other metastatic solid tumors. The majority of MTC express the tumor-associated antigens calcitonin and carcinoembryonic antigen (CEA), and approximately 40% of MTC harbor the RET M918T oncogenic driver mutation.
Methods:
We developed and characterized three immunoreceptors that recognize either extracellular CEA, a calcitonin epitope presented by HLA-A*24:02, or a RET M918T neoepitope restricted by HLA-DPB1*04:01/02. The chimeric antigen-receptor (CAR) targeting CEA was synthetically designed, while the T-cell receptors (TCR) targeting calcitonin and RET M918T were isolated from a transgenic mouse and patient with MTC, respectively. These immunoreceptors were genetically engineered into peripheral blood T cells and tested for antigen specificity and antitumor activity.
Results:
T cells expressing the anti-CEA CAR or the calcitonin-reactive TCR produced effector cytokines and displayed cytotoxicity against cell lines expressing their cognate antigen in vitro. In immunodeficient mice harboring a human MTC cell line, the adoptive transfer of T cells engineered to express the anti-CEA CAR or calcitonin-reactive TCR led to complete tumor regression. T cells expressing the HLA-DPB1*04:01/02-restricted TCR targeting RET M918T, which was cloned from peripheral blood CD4+ T cells of a patient with MTC, demonstrated specific reactivity against cells pulsed with the mutated peptide and MTC tumor cells that expressed HLA-DPB1*04:01 and RET M918T.
Conclusion:
The preclinical data presented herein demonstrate the potential of using genetically engineered T cells targeting CEA, calcitonin, and/or RET M918T to treat metastatic MTC.
