scholarly journals Medullary thyroid carcinoma and duodenal calcitonin-secreting neuroendocrine tumour: more than coincidence?

2013 ◽  
Vol 2013 ◽  
Author(s):  
I Huguet ◽  
C Lamas ◽  
R Vera ◽  
A Lomas ◽  
R P Quilez ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
Metastatic Disease ◽  
Neuroendocrine Tumour ◽  
Heterogeneous Group ◽  
List Type ◽  
Medullary Thyroid ◽  
Her Family ◽  
Or Genes ◽  
Learning Points

Summary Neuroendocrine tumours (NETs) are a heterogeneous group of neoplasms whose management can be problematic. In many cases, multiple tumours may occur in the same patient or his or her family, and some of these have now been defined genetically, although in other cases the underlying gene or genes involved remain unclear. We describe a patient, a 63-year-old female, who was diagnosed with a medullary thyroid carcinoma (MTC), which was confirmed pathologically after thyroidectomy, but whose circulating calcitonin levels remained elevated after thyroidectomy with no evidence of metastatic disease. Subsequently, an entirely separate and discrete duodenal NET was identified; this was 2.8 cm in diameter and was removed at partial duodenectomy. The tumour stained immunohistochemically for calcitonin, and its removal led to persistent normalisation of the circulating calcitonin levels. There was no germline mutation of the RET oncogene. This is the first identification of a duodenal NET secreting calcitonin and also the first demonstration of a second tumour secreting calcitonin in a patient with MTC. We suggest that where calcitonin levels remain high after removal of a MTC a search for other NETs should be conducted. Learning points NETs are a complex and heterogeneous group of related neoplasms, and multiple tumours may occur in the same patient. Calcitonin can be produced ectopically by several tumours outside the thyroid. Persistently elevated calcitonin levels after removal of a MTC may not necessarily indicate persisting or metastatic disease from the tumour. The real prevalence of calcitonin-producing NETs may be underestimated, as serum determination is only recommended in the diagnosis of pancreatic NETs.

scholarly journals Metastatic medullary thyroid carcinoma presenting as ectopic Cushing’s syndrome

2021 ◽  
Vol 2021 ◽  
Author(s):  
Hannah E Forde ◽  
Niamh Mehigan-Farrelly ◽  
Katie Ryan ◽  
Tom Moran ◽  
Megan Greally ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
Recurrent Disease ◽  
Neuroendocrine Tumour ◽  
List Type ◽  
Acth Secretion ◽  
Ectopic Acth ◽  
Serum Calcitonin ◽  
Ectopic Acth Secretion ◽  
Medullary Thyroid

Summary A 41-year-old male presented to the Emergency Department with a 6-month history of back and hip pain. Skeletal survey revealed bilateral pubic rami fractures and MRI of the spine demonstrated multiple thoracic and lumbar fractures. Secondary work up for osteoporosis was undertaken. There was no evidence of hyperparathyroidism and the patient was vitamin D replete. Testosterone (T) was low at 1.7 nmol/L (8.6–29.0) and gonadotrophins were undetectable. The patient failed a 1 mg dexamethasone suppression test (DST) with a morning cortisol of 570 nmol/L (<50) and subsequently a low dose DST with a cortisol post 48 h of dexamethasone of 773 nmol/L (<50) and an elevated ACTH 98 ng/L. A corticotropin-releasing factor (CRF) test suggested ectopic ACTH secretion. The patient was commenced on teriparatide for osteoporosis and metyrapone to control the hypercortisolaemia. A positron emission tomography (PET) scan to look for the source of ACTH secretion demonstrated right neck adenopathy. Biopsy and subsequent lymph node dissection were performed and histology revealed a metastatic neuroendocrine tumour. Immunostaining was positive for calcitonin and thyroid transcription factor 1 (TTF1). Serum calcitonin was also significantly elevated at 45 264 ng/L (<10). The patient proceeded to a total thyroidectomy and left neck dissection. Histology confirmed a 7 mm medullary thyroid carcinoma (MTC). Post-operatively, the patient commenced vandetanib therapy and achieved a clinical and biochemical response. After approximately 18 months of vandetanib therapy, the patient developed recurrent disease in his neck. He is currently on LOXO-292 and is doing well 36 months post-diagnosis. Learning points Unexplained osteoporosis requires thorough investigation and the workup for secondary causes is not complete without excluding glucocorticoid excess. MTC should be considered when searching for sources of ectopic ACTH secretion. Resistance to tyrosine kinase inhibitors is well described with MTC and clinicians should have a low threshold for screening for recurrent disease.

scholarly journals Synchronous Lung and Liver Metastases from Medullary Thyroid Carcinoma

2003 ◽  
Vol 10 (1) ◽  
pp. 39-41 ◽  
Author(s):  
H Yanardag ◽  
C Tetikkurt ◽  
S Tetikkurt
Keyword(s):  
Thyroid Carcinoma ◽  
Liver Metastases ◽  
Medullary Thyroid Carcinoma ◽  
Metastatic Disease ◽  
Serum Markers ◽  
Initial Presentation ◽  
Medullary Thyroid ◽  
Common Causes ◽  
High Concentrations ◽  
First Time

Metastatic disease is one of the most common causes of calcified nodules in the lung or liver. The incidence of calcified metastasis mainly to the lung and liver is high at the initial presentation in patients with medullary thyriod carcinoma. Synchronous calcified metastasis in the lung and liver is reported for the first time. The diagnosis of medullary thyroid carcinoma may be evident from the synchronous presence of miliary calcified nodules in two different sites if they are associated with high concentrations of serum markers.

scholarly journals Animal models of medullary thyroid cancer: state of the art and view to the future

2017 ◽  
Vol 24 (1) ◽  
pp. R1-R12 ◽  
Author(s):  
Giovanni Vitale ◽  
Germano Gaudenzi ◽  
Luisa Circelli ◽  
Marco F Manzoni ◽  
Andrea Bassi ◽  
...  
Keyword(s):  
Animal Models ◽  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
State Of The Art ◽  
Neuroendocrine Tumour ◽  
Progression Free Survival ◽  
Therapeutic Approaches ◽  
Medullary Thyroid ◽  
New Therapeutic Approaches ◽  
Treatment Responses

Medullary thyroid carcinoma is a neuroendocrine tumour originating from parafollicular C cells accounting for 5–10% of thyroid cancers. Increased understanding of disease-specific molecular targets of therapy has led to the regulatory approval of two drugs (vandetanib and cabozantinib) for the treatment of medullary thyroid carcinoma. These drugs increase progression-free survival; however, they are often poorly tolerated and most treatment responses are transient. Animal models are indispensable tools for investigating the pathogenesis, mechanisms for tumour invasion and metastasis and new therapeutic approaches for cancer. Unfortunately, only few models are available for medullary thyroid carcinoma. This review provides an overview of the state of the art of animal models in medullary thyroid carcinoma and highlights future developments in this field, with the aim of addressing salient features and clinical relevance.

scholarly journals The RET polymorphic allele S836S is associated with early metastatic disease in patients with hereditary or sporadic medullary thyroid carcinoma

2010 ◽  
Vol 17 (4) ◽  
pp. 953-963 ◽  
Author(s):  
Débora R Siqueira ◽  
Mírian Romitti ◽  
Andreia P da Rocha ◽  
Lucieli Ceolin ◽  
Camila Meotti ◽  
...  
Keyword(s):  
Lymph Node ◽  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
Metastatic Disease ◽  
Cox Regression ◽  
Distant Metastases ◽  
Medullary Thyroid ◽  
Kaplan Meier ◽  
Increased Risk

The possible role of RET variants in modifying the natural course of medullary thyroid carcinoma (MTC) is still a matter of debate. Here, we investigate whether the RET variants L769L, S836S, and G691S/S904S influence disease presentation in hereditary or sporadic MTC patients. One hundred and two patients with hereditary MTC and 81 patients with sporadic MTC attending our institution were evaluated. The frequencies of RET polymorphisms in hereditary MTC were as follows: L769L, 17.3%; S836S, 7.95%; and S904S/G691S, 18.2%. No associations were observed between these polymorphisms and pheochromocytoma, hyperparathyroidism, lymph node, or distant metastasis. However, patients harboring the S836S variant were younger than those without this allele (17±8.2 vs 28.6±14.4 years, P=0.01), suggesting that these patients had metastases at a young age. Accordingly, the cumulative frequency of local and/or distant metastases as estimated by Kaplan–Meier curves showed that lymph node and distant metastases occurred earlier in patients harboring the S836S variant (P=0.003 and P=0.026 respectively). The S836S allele frequency was higher in sporadic MTC patients than in controls (10.5 vs 3.1%, P=0.01). Individuals harboring the S836S variant were younger (38.6±13.3 vs 48.5±16.7 years, P=0.02) and showed a higher percentage of lymph node and distant metastases (P=0.02 and P=0.04 respectively). Kaplan–Meier estimates of lymph node and distant metastases yielded distinct curves for patients with or without the S836S allele (P=0.002 and P=0.001 respectively). Additional analyses using a COX regression model showed that the S836S variant was independently associated with metastatic disease (hazard ratio 2.82 (95% confidence interval 1.51–5.26), P=0.001). In conclusion, the RET S836S variant is associated with early onset and increased risk for metastatic disease in patients with hereditary or sporadic MTC.

scholarly journals Diagnosis and pathologic characteristics of medullary thyroid carcinoma—review of current guidelines

2019 ◽  
Vol 26 (5) ◽  
Author(s):  
C. M. Thomas ◽  
S. L. Asa ◽  
S. Ezzat ◽  
A. M. Sawka ◽  
D. Goldstein
Keyword(s):  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
Dna Analysis ◽  
Neuroendocrine Tumour ◽  
Needle Aspiration ◽  
Differentiated Thyroid Carcinoma ◽  
Serum Calcitonin ◽  
Medullary Thyroid ◽  
Fibrous Stroma

Background Medullary thyroid carcinoma (mtc) is a rare malignancy of the thyroid gland, and raising awareness of the recommended diagnostic workup and pathologic characteristics of this malignancy is therefore important.Methods We reviewed the current clinical practice guidelines and recent literature on mtc, and here, we summarize the recommendations for its diagnosis and workup. We also provide an overview of the pathology of mtc.Results A neuroendocrine tumour, mtc arises from parafollicular cells (“C cells”), which secrete calcitonin. As part of the multiple endocrine neoplasia (men) type 2 syndromes, mtc can occur sporadically or in a hereditary form. This usually poorly delineated and infiltrative tumour is composed of solid nests of discohesive cells within a fibrous stroma that might also contain amyloid. Suspicious nodules on thyroid ultrasonography should be assessed with fine-needle aspiration (fna). If a diagnosis of mtc is made on fna, patients require baseline measurements of serum calcitonin and carcinoembryonic antigen. Calcitonin levels greater than 500 pg/mL or clinical suspicion for metastatic disease dictate the need for further imaging studies. All patients should undergo dna analysis for RET mutations to diagnose men type 2 syndromes, and if positive, they should be assessed for possible pheochromocytoma and hyperparathyroidism.Summary Although the initial diagnosis of a suspicious thyroid nodule is the same for differentiated thyroid carcinoma and mtc, the remainder of the workup and diagnosis for mtc is distinct.

scholarly journals Concomitant medullary thyroid carcinoma with paraganglioma-like pattern and papillary thyroid carcinoma

2019 ◽  
Vol 2019 ◽  
Author(s):  
C Greco ◽  
G Brigante ◽  
E Taliani ◽  
S Corrado ◽  
M Simoni ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
Fine Needle Aspiration ◽  
Needle Aspiration ◽  
List Type ◽  
Serum Calcitonin ◽  
Medullary Thyroid ◽  
Fine Needle ◽  
Additional Tool ◽  
Post Surgery

Summary A 74-year-old man was referred to the Endocrinology Unit because of multinodular goiter. The dominant nodule (1.7 × 1.9 × 2.4 cm), at the medium-superior third of the left lobe, was inhomogeneously hypoechoic, with irregular margins, macrocalcifications and intranodular vascularization. Fine-needle aspiration biopsy (FNAB) was performed. The cytological diagnosis was TIR 2, benign, according to the 2013 Italian thyroid cytology classification system. Moderately high serum calcitonin (s-Ct) (61.5 pg/mL, n.r. 0–7.5) and normal CEA were detected. The Ct level in FNAB wash-out fluid (Ct-FNAB) was 1450 pg/mL. Based on s-Ct and Ct-FNAB levels, patient underwent total thyroidectomy. Macroscopically, a dominant circumscribed nodule of 2 ecm was described; the histological and immunohistochemical features identified medullary thyroid carcinoma (MTC) with paraganglioma (PG)-like pattern positive for Ct, CEA and chromogranin and negative for S-100 sustentacular cells (SC). Moreover, papillary carcinoma of 3 mm in the right lobe was also associated. No areas of hyperaccumulation of the tracer were documented at Ga68 PET/CT. No RET-proto-oncogene mutations were found. Post-surgery s-Ct levels were within normal range (4 pg/mL). Two years after thyroidectomy, the patient is still disease-free. We reported a case of sporadic and rare variant of MTC: this is the ninth described case of PG-like MTC. In this case, cytologically benign, the clinical suspicion arose from high Ct values at FNAB wash-out fluid. Even if clinical behavior of this variant seems indolent, additional studies are necessary to understand prognoses and predictive factors. Learning points: Several unusual histological variants of medullary thyroid carcinoma (MTC) have been described such as spindle cell, giant cell, clear cell, melanotic, squamous, angiosarcoma-like variants; even rarer is the paraganglioma (PG)-like pattern. We here describe a case of medullary PG-like thyroid carcinoma in a 74-year-old man. This is a rare histological variant of MTC hardly diagnosed by cytology, since immunohistochemical investigations are necessary. Measurement of calcitonin both in serum and in wash-out fluid from fine-needle aspiration could be an additional tool for an early and non-invasive identification of these variants.

scholarly journals Medullary thyroid carcinoma (MTC): unusual metastatic sites

2021 ◽  
Vol 2021 ◽  
Author(s):  
Paraskevi Kazakou ◽  
George Simeakis ◽  
Maria Alevizaki ◽  
Katerina Saltiki
Keyword(s):  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
Kinase Inhibitors ◽  
Distant Metastases ◽  
List Type ◽  
Medullary Thyroid ◽  
First Case ◽  
Disease Stabilization ◽  
Metastatic Sites ◽  
Unusual Metastases

Summary Medullary thyroid carcinoma (MTC) has a varying clinical course; distant metastases are frequently present even at diagnosis. We present two MTC cases with unusual metastatic sites. Two female patients are presented with slow progressive MTC. The first case developed distant metastases 23 years after diagnosis and underwent locoregional therapies. At the same time a breast mass developed representing MTC metastasis. Treatment with vandetanib led to long-term disease stabilization. The second patient is presented with metastases in the pancreas 13 years after diagnosis. Shortly, a painful mass developed in the mandible and metastasis of MTC was diagnosed. Disease progression was recorded 20 months after the initiation of local and systemic therapy. Such cases have only rarely been reported in the literature and highlight the need for prompt recognition of unexpected MTC metastases. Learning points Unusual sites of metastasis may appear in patients with medullary thyroid carcinoma (MTC) years after the initial diagnosis. Although rare, unexpected MTC metastases highlight the need for prompt recognition and appropriate treatment. Local recurrences accompanied by inappropriately low calcitonin levels should prompt further investigation for possible distant metastatic disease. Systemic treatment with tyrosine kinase inhibitors may be effective even in patients with unusual metastases from MTC.

Procalcitonin measured by three different assays is an excellent tumor marker for the follow-up of patients with medullary thyroid carcinoma

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Jürgen Kratzsch ◽  
Anja Willenberg ◽  
Karin Frank-Raue ◽  
Uwe Kempin ◽  
Jörg Rocktäschel ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Tumor Marker ◽  
Medullary Thyroid Carcinoma ◽  
Minimal Residual Disease ◽  
Metastatic Disease ◽  
Residual Disease ◽  
Clinical State ◽  
Medullary Thyroid ◽  
Minimal Residual

Abstract Objectives Procalcitonin (PCT) has been suggested as a tumor marker in patients with medullary thyroid carcinoma (MTC). Clinical application data in long term follow-up are missing. Methods 210 serum samples of 169 consecutive patients with MTC (92 sporadic, 77 hereditary, 158 postoperative follow-up, 11 preoperative) were collected between 2018 and 2020. Postoperative patients were stratified into three groups according to their disease status at the end of follow-up: cured (n=51, calcitonin (CT) levels < limit of quantitation), minimal residual disease (n=55, detectable CT and no metastases provable by imaging methods), metastatic disease (n=52). In five patients CT and PCT were measured while on therapy with tyrosine kinase inhibitors (TKI). CT was analyzed by the Roche ECLIA, PCT by three assays from Roche, PES, Abbott. Results The mean ± SD values seen with the three PCT assays in the MTC response groups, cured: <0.06, 0.016 ± 0.007, 0.014 ± 0.007 ng/mL, minimal residual disease: 0.511 ± 0.800, 0.389 ± 0.687, 0.341 ± 0.614 ng/mL, metastatic disease 109 ± 202, 60.4 ± 110, 63.3 ± 115 ng/mL correlate well with the CT results in these groups: cured <1.0 pg/mL, minimal residual disease 91.3 ± 121.5 pg/mL, metastatic disease 14,489 ± 30,772 pg/mL. There was a significant correlation (p<0.001) between the three PCT assays (Roche/PES r=0.970, Roche/Abbott r=0.976, Abbott/PES r=0.995). In the course of treatment with TKI both CT and PCT reflected clinical state. Preoperative PCT in hereditary MTC has the same diagnostic validity than CT. Conclusions PCT measured with three different immunoassays is as good as the standard tumor marker CT in the follow-up of MTC but has a superior analytical stability.

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