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World Journal of Surgery Feb 2023The basic nature of cancer includes unlimited growth, invasion, and metastasis. The TNM staging system is very simple and popular. It indicates the degree of the...
INTRODUCTION
The basic nature of cancer includes unlimited growth, invasion, and metastasis. The TNM staging system is very simple and popular. It indicates the degree of the anatomical spread of the disease but does not include tumor growth. Collins reported that human tumors grow exponentially, which can be expressed in doubling time.
PATIENTS AND METHODS
We found that in patients with medullary thyroid carcinoma (MTC) and papillary thyroid carcinoma (PTC) serum calcitonin and thyroglobulin levels changed exponentially over time, respectively, and that doubling times of these values were very strong prognostic factors. Doubling time has two major limitations. Doubling rate resolves these limitations. Using doubling rate, we performed kinetic analyses on tumor volume during active surveillance of micro-PTC.
RESULTS
Our kinetic studies on patients with biochemically persistent disease revealed that 17% of MTC and 51% of PTC showed decrease in serum tumor marker levels over time. During active surveillance of micro-PTC, 17% of the patients showed clear decrease in their tumor volume. The evidences currently available are limited. However, our data indicate the following: Growth slowdown and regression are very common phenomena in the natural history of micro-PTC, clinical PTC in young and middle-aged patients, and hereditary MTC. The biologic characteristics of cancers of the same name, such as PTC, are diverse and vary widely with age.
CONCLUSIONS
Doubling time and doubling rate are very powerful tools to provide the most appropriate management for the patients with thyroid cancers. Knowing the natural history of thyroid cancer is essential for the best disease management of thyroid cancer.
Topics: Middle Aged; Humans; Kinetics; Carcinoma, Papillary; Thyroid Neoplasms; Thyroid Cancer, Papillary; Retrospective Studies
PubMed: 36153411
DOI: 10.1007/s00268-022-06741-4 -
Current Oncology (Toronto, Ont.) Nov 2023Papillary thyroid carcinoma (PTC) is the most common type of differentiated TC, while medullary TC (MTC) accounts for 4%. The concomitant presence of PTC and MTC is rare. (Review)
Review
BACKGROUND
Papillary thyroid carcinoma (PTC) is the most common type of differentiated TC, while medullary TC (MTC) accounts for 4%. The concomitant presence of PTC and MTC is rare.
METHODS
This is a retrospective, single-center observational study conducted over 16 years (2001-2017). The data were collected from the clinical records of patients who underwent total thyroidectomy at the Endocrine Unit-Department of Medicine of the University Hospital of Pisa, Italy.
RESULTS
Over 690 analyzed cases, 650 (94.2%) were exclusive DTC, 19 exclusive MTC (2.75%) and 5 PTC/MTC (0.7%). No case of mixed medullary/follicular TC or hereditary MTC (familial MTC/multiple endocrine neoplasia type 2) was found. Among the five PTC/MTC cases, there was a male prevalence (M:F = 3:2), and all PTC components were at stage I, whereas 40% of MTC were at stage I and III and 20% of MTC were at stage II; microPTC (mPTC) was prevalent (80%) and also microMTCs were frequent (40%); 60% of MTC patients recovered, while 40% of patients developed metastatic disease. The search for germline mutations of the RET gene resulted in being negative in all cases.
CONCLUSIONS
The incidence of PTC/MTC has been increasing over the past 30 years. The etiology of PTC/MTC forms is still unknown, and although this simultaneous occurrence could be only a coincidence, we cannot exclude the hypothesis of a shared genetic origin.
Topics: Humans; Male; Carcinoma, Medullary; Carcinoma, Papillary; Observational Studies as Topic; Proto-Oncogene Proteins c-ret; Retrospective Studies; Thyroid Cancer, Papillary; Thyroid Neoplasms; Female
PubMed: 38132379
DOI: 10.3390/curroncol30120745 -
Therapeutic Advances in Endocrinology... 2021Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor that represents <5% of all thyroid malignancies and is generally more aggressive than differentiated thyroid... (Review)
Review
Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor that represents <5% of all thyroid malignancies and is generally more aggressive than differentiated thyroid cancer. The aim of this study is to provide an update, through review of clinical studies of patients with MTC published between January 1, 2016, and June 1, 2021, on recent advances in the diagnosis and treatment of MTC. This review focuses on updates in biochemical testing, imaging, hereditary disease, surgical management, adjuvant therapies, and prognosis. Recent advances reviewed herein have sought to diagnose MTC at earlier stages of disease, predict when patients with a hereditary syndrome may develop MTC, use functional imaging to assess for distant metastases, perform optimal initial surgery with appropriate lymphadenectomy, employ targeted systemic therapies for patients with progressive metastatic disease, and better predict patient-specific outcomes.
PubMed: 34659736
DOI: 10.1177/20420188211049611 -
Journal of Endocrinological... Dec 2023The determination of tumour biomarkers is paramount to advancing personalized medicine, more so in rare tumours like medullary thyroid carcinoma (MTC), whose diagnosis...
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.
Topics: Humans; MicroRNAs; Thyroid Neoplasms; Circulating MicroRNA; Biomarkers; Biomarkers, Tumor
PubMed: 37286863
DOI: 10.1007/s40618-023-02115-2 -
Frontiers in Endocrinology 2022Calcitonin (Ct)-negative medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor. This study aimed to clarify its incidence, clinicopathologic characteristics,...
OBJECTIVE
Calcitonin (Ct)-negative medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor. This study aimed to clarify its incidence, clinicopathologic characteristics, management, and treatment outcome.
METHODS
We retrospectively analyzed data of patients with primary MTC. Patients were divided into two groups according to the preoperative serum Ct level (Ct-negative and Ct-positive). The demographic, pathologic, and molecular characteristics, and treatment outcomes were compared between the two groups. In the Ct-negative group, we analyzed the association between the operation type and treatment outcome.
RESULTS
Of the total 312 patients, 24 were diagnosed with Ct-negative MTC. The rate of lymph node metastasis was significantly higher in the Ct-positive than in the Ct-negative group (47.9% vs. 0%, <0.001). The proportion of patients with Ki-67 ≤10% was significantly higher in the Ct-negative than in the Ct-positive group (87.5% vs. 38.2%, <0.001). Excellent response was achieved by 91.7% and 34.7% of patients in the Ct-negative and Ct-positive groups, respectively (<0.001). In the Ct-negative group, excellent response was achieved by all female patients, but only 50% of male patients.
CONCLUSIONS
Ct-negative MTC is rare and unlikely to develop lymph node metastasis. Unilateral lobectomy tends to provide a satisfactory chance of excellent response; however, this requires further validation.
Topics: Humans; Male; Female; Calcitonin; Carcinoma, Medullary; Lymphatic Metastasis; Retrospective Studies; Thyroid Neoplasms; Calcium-Regulating Hormones and Agents; Peptide Hormones; Neuropeptides
PubMed: 36506082
DOI: 10.3389/fendo.2022.1025629 -
Current Oncology (Toronto, Ont.) Dec 2019Medullary thyroid cancer is a rare type of neuroendocrine tumour that arises from the parafollicular cells (C cells) of the thyroid gland. It accounts for 3%-5% of... (Review)
Review
Medullary thyroid cancer is a rare type of neuroendocrine tumour that arises from the parafollicular cells (C cells) of the thyroid gland. It accounts for 3%-5% of thyroid cancer cases. Close to 25% of cases are familial, and 75% are considered sporadic. Familial cases are associated with a germline mutation; 43%-65% of sporadic cases harbour a somatic event in the gene. Germline mutations are associated with the autosomal-dominant inherited multiple endocrine neoplasia (men) 2a and 2b syndromes and the isolated familial medullary thyroid cancer syndrome. More than 100 codon mutations have been reported to date, with genotype-phenotype correlations that include the extent and aggressiveness of the medullary thyroid cancer and the presence of other features of the men2 syndromes. The latter include pheochromocytoma-paraganglioma, hyperparathyroidism, cutaneous lichen amyloidosis, and Hirschsprung disease. In this narrative review, we focus on proto-oncogene physiology and pathogenesis induced by germline and somatic mutations, the genotype-phenotype correlation, and the management and follow-up of patients with germline-mutated medullary thyroid cancer.
Topics: Carcinoma, Neuroendocrine; Genetic Association Studies; Genetic Testing; Humans; Mutation; Proto-Oncogene Mas; Proto-Oncogene Proteins c-ret; Thyroid Neoplasms
PubMed: 31896937
DOI: 10.3747/co.26.5553 -
Journal of Endocrinological... May 2021Familial non-medullary thyroid carcinoma (FNMTC), mainly of papillary histotype (FPTC), is defined by the presence of the disease in two or more first-degree relatives... (Review)
Review
BACKGROUND
Familial non-medullary thyroid carcinoma (FNMTC), mainly of papillary histotype (FPTC), is defined by the presence of the disease in two or more first-degree relatives in the absence of other known familial syndromes. With the increasing incidence of PTC in the recent years, the familial form of the disease has also become more common than previously reported and constitutes nearly 10% of all thyroid cancers. Many aspects of FNMTC are debated, concerning both clinical and genetic aspects. Several studies reported that, in comparison with sporadic PTCs, FPTCs are more aggressive at disease presentation, while other authors reported no differences in the clinical behavior of sporadic and familial PTCs. For this reason, recent guidelines do not recommend screening of family members of patients with diagnosis of differentiated thyroid cancer (DTC). FNMTC is described as a polygenic disorder associated with multiple low- to moderate-penetrance susceptibility genes and incomplete penetrance. At the moment, the genetic factors contributing to the development of FNMTC remain poorly understood, though many putative genes have been proposed in the recent years.
PURPOSE
Based on current literature and our experience with FNMTC, in this review, we critically discussed the most relevant controversies, including its definition, the genetic background and some clinical aspects as screening and treatment.
Topics: Carcinoma, Papillary; Early Detection of Cancer; Genetic Predisposition to Disease; Humans; Patient Care Management; Thyroid Cancer, Papillary
PubMed: 33025555
DOI: 10.1007/s40618-020-01435-x -
Indian Journal of Cancer Oct 2023Concurrence of medullary and papillary thyroid carcinoma (MTC and PTC) represents less than 1% of all thyroid malignancies. We aimed to reveal the demographic and...
PURPOSE
Concurrence of medullary and papillary thyroid carcinoma (MTC and PTC) represents less than 1% of all thyroid malignancies. We aimed to reveal the demographic and clinical characteristics of this rare pathology and to evaluate the effect of the same or contralateral lobular localization of these two malignancies in clinical and laboratory features. Evaluation of progression-free survival (PFS) in current pathology is one of the important features of our study.
METHODS
All patients diagnosed with simultaneous MTC and PTC after thyroidectomy were evaluated retrospectively. Data on the following variables were recorded: age, gender, tumor localization (ipsilateral lobe located MTC and PTC-Group I, contralateral lobe located MTC and PTC-Group II), tumor size, cervical lymph node metastasis, distant metastasis, tumor stage, postoperative basal calcitonin, carcinoembryonic antigen, thyroglobulin (Tg), and anti-Tg values. In all our cases, since MTC progressed before PTC, progression was accepted as serum calcitonin values exceeded 150 pg/mL.
RESULTS
Groups were formed as follows: Group I, four cases where MTC and PTC were localized in different foci in the same lobe; Group II, nine cases where they were localized in different lobes. There was only one case in which two tumors were located in the same focus. The case with dual differentiation was included in Group I (35. 7%). When the PFS of the two groups were compared, no statistically significant difference was found ( P = 0.87).
CONCLUSIONS
As a result of this analysis, the location of the simultaneously detected PTC in the same or different lobes with the MTC does not make a significant difference in clinical and laboratory features.
Topics: Humans; Thyroid Cancer, Papillary; Calcitonin; Survival Rate; Retrospective Studies; Carcinoma, Papillary; Thyroid Neoplasms; Carcinoma, Neuroendocrine
PubMed: 38090963
DOI: 10.4103/ijc.IJC_9_21 -
Bosnian Journal of Basic Medical... Oct 2021Medullary thyroid carcinoma (MTC) is a relatively rare thyroid carcinoma of C-cell deviation and produces and secrete calcitonin (CT) and chromogranin A (CgA) into the...
Medullary thyroid carcinoma (MTC) is a relatively rare thyroid carcinoma of C-cell deviation and produces and secrete calcitonin (CT) and chromogranin A (CgA) into the blood. Thus, both CT and CgA are immunohistochemical and serum markers for MTCs. MTC occurs in both sporadic and inheritable cases and the hallmark of inheritable cases in multiple endocrine neoplasm 2 (NEN2) is MTC. MEN2 cases represent 30% of MTCs through germline RET protooncogene mutation and occur in younger ages involving bilateral thyroid lobes. Sporadic cases are 70% of cases of solitary tumor and occur in older ages. CgA and synaptophysin (SPY) are the two, most widely used and reliable immunohistochemical markers for neuroendocrine tumors including MTCs. This study aimed to detect different immunohistochemical staining patterns for CgA and SPY between non-symptomatic small, microscopic lesions and invading larger aggressive tumors in both MEA2 cases and sporadic cases. There was different CgA and SPY immunostaining in MEA2 cases where small tumors (≤ 0.3 cm) were lesser immunostained for CgA and SPY, despite strong staining for CT, compared to the larger (≥ 0.5cm) tumors, stronger immunostained for CgA. There was also different CgA and SPY immunohistochemical staining in sporadic cases between small lesion (≤ 0.5 cm) and larger tumors (≥ 1.0cm). One small sporadic tumor (0.5 x 0.3 cm) was strongly and weakly, patchy (about 10% of tumor tissue) stained for CgA and SPY, respectively, while larger sporadic tumors were diffusely, stronger stained for CgA and SPY. Therefore, stronger CgA and SPY immunostaining for larger tumors in both MEA2 and sporadic cases may be used as independent aggressive immunohistochemical markers for MTCs.
Topics: Adolescent; Adult; Aged; Calcitonin; Carcinoma, Neuroendocrine; Chromogranin A; Female; Humans; Immunohistochemistry; Male; Middle Aged; Multiple Endocrine Neoplasia; Synaptophysin; Thyroid Gland; Thyroid Neoplasms; Young Adult
PubMed: 33485291
DOI: 10.17305/bjbms.2020.5407 -
World Journal of Gastrointestinal... May 2021Several benign conditions such as chronic pancreatitis, autoimmune pancreatitis, and paraduodenal pancreatitis can present as mass lesions and may mimic pancreatic... (Review)
Review
Several benign conditions such as chronic pancreatitis, autoimmune pancreatitis, and paraduodenal pancreatitis can present as mass lesions and may mimic pancreatic ductal adenocarcinoma (PDAC) clinically and radiologically. Thorough histologic examination with attention to certain morphologic features can assist in deciphering neoplastic from reactive, however small biopsies often remain a challenge. Variable histologic patterns in conventional PDAC may also confound the diagnosis of PDAC. Uncommon subtypes of pancreatic carcinoma such as adenosquamous and squamous cell carcinoma, colloid carcinoma, medullary carcinoma, hepatoid carcinoma and signet ring cell carcinoma necessitate excluding metastasis from other sites prior to rendering the diagnosis of pancreatic carcinoma. The use of immunohistochemical staining and molecular markers can aid in separating benign from malignant and PDAC from metastasis. PDAC expresses a few non-specific epithelial and mucin immunomarkers such as CK7, CK19, MUC1, MUC4 and MUC5AC. However, the only immunohistochemical marker that is specific for PDAC in the right clinical context is SMAD4. Loss of SMAD4 within atypical glands and ducts supports the diagnosis of PDAC in a limited sample. Unfortunately, this finding is seen only in 50% of PDAC cases. The identification of certain mutations can help support a diagnosis of PDAC when benign conditions are in the differential. At the molecular level, oncogene mutations are seen in approximately 93% of PDACs. Subsequent neoplastic progression is driven by additional mutations of tumor suppressor genes, such as , , and . Molecular markers can also provide an insight to the prognosis. For instance, the loss of is associated with a poor outcome whereas mutations in , , , and are associated with improved survival.
PubMed: 34122731
DOI: 10.4240/wjgs.v13.i5.406