scholarly journals Sporadic hypercalcitoninemia: clinical and therapeutic consequences

2009 ◽  
Vol 16 (1) ◽  
pp. 243-253 ◽  
Author(s):  
C Scheuba ◽  
K Kaserer ◽  
A Moritz ◽  
R Drosten ◽  
H Vierhapper ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Lymph Node ◽  
Lymph Node Metastases ◽  
Medullary Thyroid Cancer ◽  
Germ Line ◽  
Daily Practice ◽  
Cell Hyperplasia ◽  
Medullary Thyroid ◽  
Node Metastases ◽  
Calcitonin Screening

‘Calcitonin screening’ is not accepted as the standard of care in daily practice. The clinical and surgical consequences of ‘calcitonin screening’ in a series of patients with mildly elevated basal calcitonin and pentagastrin stimulated calcitonin levels are presented. 260 patients with elevated basal (>10 pg/ml) and stimulated calcitonin levels (>100 pg/ml) were enrolled in this prospective study. None of the patients was member of a known medullary thyroid carcinoma family. Thyroidectomy and bilateral central and lateral neck dissections were performed. Testing for the presence of germ-line mutations was performed in all patients. Histological and immunohistochemical findings were compared with basal and stimulated calcitonin levels. All patients were subsequently followed biochemically. C-cell hyperplasia (CCH) was found in 126 (49%) and medullary thyroid cancer was found in 134 (51%) patients. RET proto-oncogen mutations were documented in 22 (8%) patients (medullary thyroid cancer:18, CCH:4). In 56 (46%) of 122 patients, sporadic CCH was classified neoplastic (‘carcinoma in situ’). Of 97 (72%; 10 with hereditary medullary thyroid cancer) had pT1 (International Union against Cancer recommendations 2002) and 33 (25%) had pT2 or pT3 and 4 (3%) pT4 tumors. Of 39 (29.1%) had lymph node metastases. 106 (79.1%; 15 (38.5%) with lymph node metastases) patients were cured. Evaluation of basal and stimulated calcitonin levels enables the prediction of medullary thyroid cancer. All patients with basal calcitonin >64 pg/ml and stimulated calcitonin >560 pg/ml have medullary thyroid cancer. Medullary thyroid cancer was documented in 20% of patients with basal calcitonin >10 pg/ml but <64 pg/ml and stimulated calcitonin >100 pg/ml but <560 pg/ml.

Influence of lymph node metastases on survival in pediatric medullary thyroid cancer

2010 ◽  
Vol 45 (10) ◽  
pp. 1947-1954 ◽  
Author(s):  
Mehul V. Raval ◽  
Cord Sturgeon ◽  
David J. Bentrem ◽  
Dina M. Elaraj ◽  
Andrew K. Stewart ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Lymph Node ◽  
Lymph Node Metastases ◽  
Medullary Thyroid Cancer ◽  
Medullary Thyroid ◽  
Node Metastases

scholarly journals Biomarker-Based Risk Stratification for Previously Untreated Medullary Thyroid Cancer

2010 ◽  
Vol 95 (6) ◽  
pp. 2655-2663 ◽  
Author(s):  
Andreas Machens ◽  
Henning Dralle
Keyword(s):  
Thyroid Cancer ◽  
Lymph Node ◽  
Lymph Node Metastases ◽  
Medullary Thyroid Cancer ◽  
Serum Levels ◽  
Neck Surgery ◽  
Lateral Neck ◽  
Medullary Thyroid ◽  
Node Metastases ◽  
Extent Of Disease

Abstract Context: Preoperative neck ultrasonography may yield false-negative findings in more than one-third of medullary thyroid cancer (MTC) patients. If not cleared promptly, cervical lymph node metastases may emerge subsequently. Reoperations entail an excess risk of surgical morbidity and may be avoidable. Objective: This comprehensive investigation aimed to evaluate in a head-to-head comparison the clinical utility of pretherapeutic biomarker serum levels (basal calcitonin; stimulated calcitonin; carcinoembryonic antigen) for indicating extent of disease and providing biochemical stratification of pretherapeutic MTC risk. Design: This was a retrospective analysis. Setting: The setting was a tertiary referral center. Patients: Included were 300 consecutive patients with previously untreated MTC. Interventions: The intervention was compartment-oriented surgery. Main Outcome Measure: Stratified biomarker levels were correlated with histopathologic extent of disease. Results: Higher biomarker levels reflected larger primary tumors and more lymph node metastases. Stratified basal calcitonin serum levels correlated better (r = 0.59) with the number of lymph node metastases than carcinoembryonic antigen (r = 0.47) or pentagastrin-stimulated calcitonin (r = 0.40) levels. Lymph node metastases were present in the ipsilateral central and lateral neck, contralateral central neck, contralateral lateral neck, and upper mediastinum, respectively, beyond basal calcitonin thresholds of 20, 50, 200, and 500 pg/ml. Bilateral compartment-oriented neck surgery achieved biochemical cure in at least half the patients with pretherapeutic basal calcitonin levels of 1,000 pg/ml or less but not in patients with levels greater than 10,000 pg/ml. Conclusions: Most newly diagnosed MTC patients, i.e. those with pretherapeutic basal calcitonin levels greater than 200 pg/ml, may need bilateral compartment-oriented neck surgery to reduce the number of reoperations.

scholarly journals Testicular and inguinal lymph node metastases of medullary thyroid cancer: a case report and review of the literature

2014 ◽  
Vol 14 (1) ◽  
Author(s):  
Marialuisa Appetecchia ◽  
Agnese Barnabei ◽  
Vincenzo Pompeo ◽  
Steno Sentinelli ◽  
Roberto Baldelli ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Case Report ◽  
Lymph Node ◽  
Lymph Node Metastases ◽  
Medullary Thyroid Cancer ◽  
Inguinal Lymph Node ◽  
Review Of The Literature ◽  
Medullary Thyroid ◽  
Node Metastases

scholarly journals Medullary Thyroid Cancer Responsiveness to Pentagastrin Stimulation: An Early Surrogate Parameter of Tumor Dissemination?

2008 ◽  
Vol 93 (6) ◽  
pp. 2234-2238 ◽  
Author(s):  
Andreas Machens ◽  
Steffen Hauptmann ◽  
Henning Dralle
Keyword(s):  
Thyroid Cancer ◽  
Lymph Node ◽  
Lymph Node Metastases ◽  
Medullary Thyroid Cancer ◽  
Fold Increase ◽  
Extrathyroidal Extension ◽  
Tumor Diameter ◽  
Medullary Thyroid ◽  
Tumor Dissemination ◽  
Node Metastases

Abstract Context: Because of its outstanding sensitivity, stimulation of calcitonin secretion with iv injection of pentagastrin is widely used for biochemical diagnosis of medullary thyroid cancer. Objective: The objective of this study was to explore the relationship between the results of the pentagastrin stimulation test and extent of disease in patients with previously untreated medullary thyroid cancer. Design: This was a retrospective study. Setting: The investigation took place at a tertiary referral center. Patients: Included were 89 patients with increased basal calcitonin levels who had a pentagastrin test at this institution before initial neck surgery for medullary thyroid cancer. Main Outcome Measure: Measurements included basal and stimulated calcitonin levels, carcinoembryonic antigen levels, primary tumor diameter, extrathyroidal extension, lymph node metastases, and distant metastases. Results: There was a strong dose-dependent relationship between a less than 10-fold increase in preoperative calcitonin levels after iv stimulation with pentagastrin and both the frequency (41–54 vs. 4–27%; P = 0.001) and number (means of 3.0–10.8 vs. 0–1.1 positive nodes, P &lt; 0.001) of lymph node metastases. Weaker associations were identified with the respective frequency of extrathyroidal extension (14–27 vs. 0–7%; P = 0.027), distant metastasis (9–23 vs. 0%; P = 0.017), and postoperative normalization of calcitonin (40–55 vs. 53–82%; P = 0.029). On multivariate analysis, only lymph node metastases were associated with a less than 10-fold increase in preoperative calcitonin levels. Conclusions: Based on these clinical data and preclinical literature, reduced responsiveness to stimulation with pentagastrin may reflect early dedifferentiation. Evidence of this condition may enable early risk stratification in patients with medullary thyroid cancer.

scholarly journals A Co-Occurrence of Familial Non-Medullary Thyroid Cancer and Lynch Syndrome

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A855-A855
Author(s):  
Kshama Aswath ◽  
James Welch ◽  
Sriram Gubbi ◽  
Mohammad Al Jundi ◽  
Padmasree Veeraraghavan ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Lymph Node ◽  
Medullary Thyroid Cancer ◽  
Family Members ◽  
Rare Event ◽  
Neck Lymph Node ◽  
Medullary Thyroid ◽  
Whole Exome ◽  
Node Metastases ◽  
Neck Lymph Node Metastases

Abstract Background: Lynch syndrome (LS) is an autosomal dominant disease caused by germline mutations in mismatch repair genes (MMR), leading to the early manifestation of tumors characterized by microsatellite instability (MSI) in &gt;3 family members across at least 2 generations. MSI is a rare event in thyroid cancer (TC), occurring in up to 2.5% of sporadic cases. There is limited data on germline MMR variants’ role in familial non-medullary thyroid cancer (FNMTC). The goal of this study was to analyze the potential clinical and molecular association between LS and FNMTC. Material and Methods: We performed a cohort study analyzing the demographic, clinical, and pathologic data of 43 kindreds with FNMTC. We performed a high-throughput whole exome sequencing (WES) of peripheral-blood DNA samples of 168 participants (54 affected by FNMTC and 140 unaffected). The GATK pipeline was used in variant analysis. The NIH Institutional Review Board approved the study. Results: The study included 383 family members (104 affected, 279 unaffected) aged 43.5 [7-99] years, with 2-9 members per family affected by FNMTC. FNMTC was more prevalent in women (68.3%) and characterized by a median tumor size of 1 [0.2-5] cm, multifocal growth in 44%, gross extrathyroidal extension in 11.3%, central neck lymph node metastases in 40.3%, lateral neck lymph node metastases in 12.9% of patients, and no distant metastases. Family history screening revealed one family of Caucasian descent meeting the clinical criteria for FNMTC and LS diagnosis with 5 members affected by FNMTC and 8 individuals by Lynch-like tumors (3 with colorectal cancer/colon polyps, 2 with endometrial or ovarian tumors, 1 with kidney cancer, 1 with keratoacanthoma and 1 with unspecified Lynch-like tumors with detailed pathology report unavailable). We performed whole exome sequencing of 10 members from this family (3 affected and 7 unaffected) and remaining 158 study participants and detected exclusively in this family, a heterozygous missense variant rs373226409, in MSH2 gene c2120G&gt;A (pCys707Tyr) in three adults affected by LS-like manifestations and two unaffected children under the age of 18 with clear segregation across three generations. This variant appears to be relatively rare with a minor allele frequency (MAF) of 0.0006 in Caucasians; however, it is more common in the South Asian population at 0.003 MAF. Immunostaining performed on the TC tumor tissue of one of the affected family members revealed intact nuclear expression of MSH2, suggestive of no major effect of the variant on MSH2 expression. Five out of seven in-silico models predicted the variant to be functionally deleterious. Conclusion: The co-occurrence of LS and FNMTC is a rare event, presenting in 2% (1/43) of families in our cohort. A common genetic association between LS and FNMTC has not been identified, and the MSH2 variant observed in this family is unlikely to be an etiologic factor.

scholarly journals Lymph Node Metastases of Medullary Thyroid Cancer: Role of Calcitonin in the Washout Fluid of Fine-Needle Aspiration

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Bernardo Marques ◽  
Nuno Cunha ◽  
Raquel G. Martins ◽  
Ana Rita Elvas ◽  
Joana Couto ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Lymph Node ◽  
Medullary Thyroid Cancer ◽  
Diagnostic Value ◽  
Needle Aspiration ◽  
Medullary Thyroid ◽  
Fine Needle ◽  
History Of ◽  
Node Metastases ◽  
Ct Measurement

Introduction. The diagnostic value of calcitonin (CT) measurement in fine-needle aspirate washout (FNA-CT) for medullary thyroid cancer (MTC) lymph node (LN) metastases remains to be determined. It may increase the diagnostic sensitivity, but data on this subject is sparse. Objective. Our study aimed to evaluate the utility of FNA-CT in the diagnosis of LN metastases of MTC. Methods. We retrospectively investigated, in our institutional database, 69 consecutive FNA LN cytology from 42 patients who underwent FNA cytology and CT measurement in needle washout for suspicious LN between 2012 and 2017. Results. From the total of 69 FNA, 30 (43.4%) were performed in patients with personal history of MTC. MTC was detected in 19 FNA cytology (27.5%), and CT was detectable in needle washout in 23 cases (median = 2014 pg/mL; interquartile range = 490–15111 pg/mL). Based on the combined results of FNA-CT and FNA cytology, LN surgical resection was performed in 33 cases (47.8%). Histology reported MTC LN metastases in 21 lesions (63.6%). Regarding the diagnosis of MTC LN metastases, FNA cytology showed sensitivity of 81.8% and specificity of 97.9%, and FNA-CT demonstrated sensitivity of 100% and specificity of 97.9%. We determined through ROC analysis an optimal FNA-CT cut-off value of 23 pg/mL for the diagnosis of LN metastases (sensitivity 100%; specificity 100%). Conclusions. FNA-CT may be a valuable diagnostic tool for detection of MTC LN metastases, along with FNA cytology, and it should be included in the clinical workup of neck adenopathies in patients with MTC or with thyroid nodules.

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