scholarly journals What Lies Beneath? - Medullary Thyroid Cancer in Nodular Graves’ Disease

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A904-A904
Author(s):  
Rongzhi Wang ◽  
Shirisha R Vallepu ◽  
Herbert Chen ◽  
Rajasree Nambron
Keyword(s):  
Thyroid Carcinoma ◽  
Total Thyroidectomy ◽  
Medullary Thyroid Carcinoma ◽  
The United States ◽  
Endocrine Surgery ◽  
Graves Disease ◽  
Hormone Production ◽  
Thyroid Cancers ◽  
Medullary Thyroid ◽  
Central Lymph Node Dissection

Abstract Background: Medullary thyroid carcinoma (MTC) accounts for 1%-2% of thyroid cancers in the United States (US). MTC originates from thyroid parafollicular C-cells, occurring either sporadically or hereditarily as part of type 2 multiple endocrine neoplasia (MEN) or familial MTC (FMTC). Hyperthyroidism is prevalent in approximately 1.2%, and Graves’ Disease (GD) is the most common cause of hyperthyroidism in the US. GD is an autoimmune disorder that results in increased thyroid hormone production due to the stimulation of TSH receptor by thyrotropin receptor antibodies (TRAb). Thyroid carcinoma in general is uncommon in GD patients, while MTC is extraordinarily rare. We report a case of sporadic MTC in GD, which is extremely rare. A recent publication stated that there were only 15 reported cases of MTC coexisting in GD until 2019. Clinical Case: A 62-year-old male with hypertension, diabetes and obesity presented to the endocrine surgery clinic with symptoms of diaphoresis, chest pain and fullness, shortness of breath, and palpitations. The patient had a brother with a pancreatic mass of unknown pathology and multiple family members with thyroid disease. On physical exam, there was a palpable non-tender left-sided nodule with no lymphadenopathy. His FT4 was 8.5 (0.76-1.46 ng/dL), TSH was <0.006 (0.36-3.74 μIU/dL) and thyroid-stimulating antibody was 1.25 (<0.10 IU/L). Ultrasound showed a multinodular goitre with a dominant nodule in the left lower pole measuring 2.3x1.9x1.5 cm. He was diagnosed with GD, treated with methimazole, and his symptoms improved. Subsequent nuclear medicine uptake scan showed diffusely increased uptake and a cold nodule in the left thyroid lobe. Repeat labs showed low TSH (<0.01μIU/dL) and elevated FT4, CEA, calcitonin, PTH, metanephrine, and normetanephrine (1.04 ng/dl, 5.2 (3-5 ng/ml), 796 (<18 pg/ml), 58.10 (18.40-88.00 pg/mL), 90 (< OR = 57 pg/ml) and 222 (< OR = 148 pg/ml), respectively). A thyroid fine-needle aspiration (FNA) was suggestive of MTC (Bethesda Category VI). Total thyroidectomy with left central lymph node dissection revealed a 2.5cm MTC confined in the left lobe with focal lymphovascular invasion. His postoperative course was uneventful, and CEA and calcitonin levels trended down (1.1 ng/ml and <2 pg/mL, respectively). Conclusion: The coexistence of medullary thyroid carcinoma and Graves’ Disease is rare, incidental, with five-year survival rates lower than other thyroid cancers. A delayed diagnosis of MTC would be detrimental. Patients with thyroid nodules and GD are five times more likely to be diagnosed with thyroid carcinoma. Radiation, chemotherapy and thyroidectomy are standard treatment options for MTC, with total thyroidectomy being the preferred option. It is necessary to evaluate patients with GD for possible thyroid cancers, especially in the presence of nodules.

Disappearance Rate of Serum Calcitonin after Total Thyroidectomy for Medullary Thyroid Carcinoma

1994 ◽  
Vol 9 (1) ◽  
pp. 21-24 ◽  
Author(s):  
L. Fugazzola ◽  
A. Pinchera ◽  
F. Luchetti ◽  
P. Iacconi ◽  
P. Miccoli ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Total Thyroidectomy ◽  
Medullary Thyroid Carcinoma ◽  
Half Life ◽  
Slow Component ◽  
General Rule ◽  
Disappearance Rate ◽  
Serum Calcitonin ◽  
Medullary Thyroid ◽  
Undetectable Serum

We studied the half-life of serum calcitonin (CT) in patients subjected to total thyroidectomy for medullary thyroid carcinoma (MTC). One patient showed a rapid serum CT component with a half-life of 3 hours and a slow component with a half-life of 30 hours; in another case only the 30-hour component was found. By chromatography of tumor extracts, we found that all the immunoreactive CT had a molecular weight of 3,600. After surgery, normalization of serum CT was achieved within 15 days in 4 patients, at 3 months and at 6 months in 2 other patients, while 1 patient never normalized. Normalization of serum CT after surgery is not an index of definitive cure in MTC, as demonstrated by one patient who relapsed 3 months after normalization of serum CT. However, as a general rule, patients who reach undetectable serum CT levels soon after surgery, are those having the best prognosis.

scholarly journals Calcitonin-negative medullary thyroid carcinoma: the ‘triple-negative’ phenotype

2020 ◽  
Vol 102 (3) ◽  
pp. e63-e66
Author(s):  
DC Murphy ◽  
SJ Johnson ◽  
S Aspinall
Keyword(s):  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
Triple Negative ◽  
Histopathological Examination ◽  
In Situ Hybridisation ◽  
Serum Calcitonin ◽  
Medullary Thyroid ◽  
Central Lymph Node Dissection ◽  
Post Surgery ◽  
The Right

Calcitonin-negative medullary thyroid carcinoma is a rare, poorly understood primary neuroendocrine carcinoma of the thyroid characterised by classic medullary thyroid carcinoma morphology without raised serum calcitonin. A 24-year-old woman presented with a slow-growing, right-sided neck swelling. She underwent an ultrasound scan, cytopathological and histopathological examination, and tests for alternative diagnoses. The ultrasound showed a heterogeneous, hyperechoic nodule in the right thyroid lobe. Serum calcitonin was normal. Cytopathology and histopathology showed typical medullary thyroid carcinoma morphology but without calcitonin upon immunostaining and mRNA in situ hybridisation. A ‘triple-negative’ calcitonin-negative medullary thyroid carcinoma was diagnosed. A completion thyroidectomy with bilateral central lymph node dissection was performed. The patient remains well three-years post-surgery. When cytopathology suggests a medullary thyroid carcinoma, serum calcitonin, pro-calcitonin, carcinoembryonic antigen and calcitonin-gene-related peptide should be measured to identify cases of calcitonin-negative medullary thyroid carcinoma. They should also be measured post-treatment for monitoring purposes. This will aid future calcitonin-negative medullary thyroid carcinoma diagnoses and will inform prognostic stratification and influence treatment decisions.

scholarly journals The Importance of Lymph Node Dissection in Medullary Thyroid Carcinoma Management

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A901-A902
Author(s):  
Camila Alejandra Villavicencio ◽  
Alberto Franco-Akel ◽  
Regina Belokovskaya
Keyword(s):  
Thyroid Carcinoma ◽  
Total Thyroidectomy ◽  
Neck Dissection ◽  
Medullary Thyroid Carcinoma ◽  
Tumor Markers ◽  
Lateral Neck ◽  
Lateral Neck Dissection ◽  
Medullary Thyroid ◽  
Preoperative Ct

Abstract Medullary thyroid carcinoma (MTC) is a rare endocrine malignancy that arises from calcitonin (Ct) parafollicular C-cells. Most cases are sporadic with frequent presentation being a solitary thyroid nodule. Total thyroidectomy with central neck dissection of lymph nodes (LN) is the standard treatment for MTC. The need for lateral neck dissection is controversial, with poor efficacy of non-surgical treatments presenting a problem. We present a case of MTC with preoperative Ct >500 pg/mL and negative imaging for metastases who underwent total thyroidectomy without LN exploration with an excellent postoperative biochemical response. This is a case of a 52-year-old female with a three-year history of anterior neck growth. The repeat fine needle aspiration (FNA) of a, previously negative for malignancy, growing nodule was consistent with MTC. Preoperative Ct and CEA levels were significantly elevated, 834.0 pg/mL and 11.2 ng/dL, respectively; a preoperative pan- CT scan did not reveal any suspicious LN or metastatic lesions and a negative RET oncogene mutation with normal plasma normetanephrines and metanephrines suggested a spontaneous rather than familial MTC. Patient underwent total thyroidectomy without LN exploration. Pathology confirmed MTC stage T1b. The one and three months postoperative follow up showed a significant downtrend with no normalization of Ct and CEA levels, 9.1 – 9.2 and 11.1 – 1.2, respectively. Reoperation for central and lateral neck dissection was considered; however, given the excellent biochemical response as well as the lack of radiographic evidence of disease, it was decided to continue monitoring of Ct and CEA levels for now. MTC response is monitored by the postoperative serum Ct and CEA levels when compared to the preoperative values. Serum Ct serves as a sensitive tumor marker, which is thought to have correlation with malignancy mass size and its cellular differentiation. The term biochemically cured, refers to the postoperative normalization of CEA and undetectable levels of Ct which carries a 5-year recurrence of 5%. It is believed that the higher the levels and the faster doubling time of these tumor markers the worse is the prognosis. In addition, it is suggested that patient’s age and extent of disease at the time of surgery are proportionally correlated with disease recurrence. However, there are reports of large MTC metastatic deposits with low serum Ct and CEA, rising up the hypothesis that levels reflect cell production potential for tumor markers rather than the number of cells. Reoperation rarely results in biochemical cure, but it may slow disease progression. Normal postoperative Ct levels predict cure; however, the clinical course of those with upper normal limit levels postoperatively is markedly variable. Careful regular biochemical and imaging follow-up will be of the utmost importance for the patient presented in this case.

International Medullary Thyroid Carcinoma Grading System: A Validated Grading System for Medullary Thyroid Carcinoma

2021 ◽  
Author(s):  
Bin Xu ◽  
Talia L. Fuchs ◽  
Sara Ahmadi ◽  
Mohammed Alghamdi ◽  
Bayan Alzumaili ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
Mitotic Index ◽  
Tumor Necrosis ◽  
The United States ◽  
Grading System ◽  
Routine Practice ◽  
High Grade ◽  
Proliferative Index ◽  
Medullary Thyroid

PURPOSE Medullary thyroid carcinoma (MTC) is an aggressive neuroendocrine tumor (NET) arising from the calcitonin-producing C cells. Unlike other NETs, there is no widely accepted pathologic grading scheme. In 2020, two groups separately developed slightly different schemes (the Memorial Sloan Kettering Cancer Center and Sydney grade) on the basis of proliferative activity (mitotic index and/or Ki67 proliferative index) and tumor necrosis. Building on this work, we sought to unify and validate an internationally accepted grading scheme for MTC. PATIENTS AND METHODS Tumor tissue from 327 patients with MTC from five centers across the United States, Europe, and Australia were reviewed for mitotic activity, Ki67 proliferative index, and necrosis using uniform criteria and blinded to other clinicopathologic features. After reviewing different cutoffs, a two-tiered consensus grading system was developed. High-grade MTCs were defined as tumors with at least one of the following features: mitotic index ≥ 5 per 2 mm2, Ki67 proliferative index ≥ 5%, or tumor necrosis. RESULTS Eighty-one (24.8%) MTCs were high-grade using this scheme. In multivariate analysis, these patients demonstrated decreased overall (hazard ratio [HR] = 11.490; 95% CI, 3.118 to 32.333; P < .001), disease-specific (HR = 8.491; 95% CI, 1.461 to 49.327; P = .017), distant metastasis-free (HR = 2.489; 95% CI, 1.178 to 5.261; P = .017), and locoregional recurrence-free (HR = 2.114; 95% CI, 1.065 to 4.193; P = .032) survivals. This prognostic power was maintained in subgroup analyses of cohorts from each of the five centers. CONCLUSION This simple two-tiered international grading system is a powerful predictor of adverse outcomes in MTC. As it is based solely on morphologic assessment in conjunction with Ki67 immunohistochemistry, it brings the grading of MTCs in line with other NETs and can be readily applied in routine practice. We therefore recommend grading of MTCs on the basis of mitotic count, Ki67 proliferative index, and tumor necrosis.

scholarly journals Replication of newly proposed TNM staging system for medullary thyroid carcinoma: a nationwide study

2019 ◽  
Vol 8 (1) ◽  
pp. 1-7 ◽  
Author(s):  
Jes Sloth Mathiesen ◽  
Jens Peter Kroustrup ◽  
Peter Vestergaard ◽  
Per Løgstrup Poulsen ◽  
Åse Krogh Rasmussen ◽  
...  
Keyword(s):  
United States ◽  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
Stage Iv ◽  
Staging System ◽  
The United States ◽  
Population Based ◽  
Tnm Staging ◽  
Medullary Thyroid ◽  
Tnm Staging System

A recent study proposed new TNM groupings for better survival discrimination among stage groups for medullary thyroid carcinoma (MTC) and validated these groupings in a population-based cohort in the United States. However, it is unknown how well the groupings perform in populations outside the United States. Consequently, we conducted the first population-based study aiming to evaluate if the recently proposed TNM groupings provide better survival discrimination than the current American Joint Committee on Cancer (AJCC) TNM staging system (seventh and eighth edition) in a nationwide MTC cohort outside the United States. This retrospective cohort study included 191 patients identified from the nationwide Danish MTC cohort between 1997 and 2014. In multivariate analysis, hazard ratios for overall survival under the current AJCC TNM staging system vs the proposed TNM groupings with stage I as reference were 1.32 (95% CI: 0.38–4.57) vs 3.04 (95% CI: 1.38–6.67) for stage II, 2.06 (95% CI: 0.45–9.39) vs 3.59 (95% CI: 1.61–8.03) for stage III and 5.87 (95% CI: 2.02–17.01) vs 59.26 (20.53–171.02) for stage IV. The newly proposed TNM groupings appear to provide better survival discrimination in the nationwide Danish MTC cohort than the current AJCC TNM staging. Adaption of the proposed TNM groupings by the current AJCC TNM staging system may potentially improve accurateness in survival discrimination. However, before such an adaption further population-based studies securing external validity are needed.

Sign in / Sign up

Export Citation Format

Share Document