scholarly journals Risk Patterns of Distant Metastases in Follicular, Papillary and Medullary Thyroid Cancer

2021 ◽  
Author(s):  
Andreas Machens ◽  
Kerstin Lorenz ◽  
Frank Weber ◽  
Henning Dralle
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Distant Metastasis ◽  
Medullary Thyroid Cancer ◽  
Papillary Thyroid ◽  
Follicular Thyroid Cancer ◽  
Follicular Variant ◽  
Node Negative ◽  
Medullary Thyroid ◽  
Node Metastasis

AbstractThis study of 542 patients with follicular thyroid cancer, 366 patients with the follicular variant and 1452 patients with the classical variant of papillary thyroid cancer, and 819 patients with sporadic medullary thyroid cancer operated at a tertiary referral center aimed to determine risk patterns of distant metastasis for each tumor entity, which are ill-defined. On multivariable logistic regression analyses, lymph node metastasis consistently emerged as an independent risk factor of distant metastasis, yielding odds ratios (ORs) of 2.4 and 2.8 for follicular thyroid cancer and the follicular variant of papillary thyroid cancer, and ORs of 5.9 and 6.4 for the classical variant of papillary thyroid cancer and sporadic medullary thyroid cancer. Another independent risk factor consistently associated with distant metastasis, most strongly in follicular thyroid cancer and the follicular variant of papillary thyroid cancer (OR 3.5 and 4.0), was patient age >60 years. Altogether, 2 distinct risk patterns of distant metastasis were identified, which were modulated by other cancer type-dependent risk factors: one with lymph node metastasis as leading component (classical variant of papillary thyroid cancer and sporadic medullary thyroid cancer), and another one with age as leading component (follicular thyroid cancer and the follicular variant of papillary thyroid cancer). Distant metastasis was exceptional in node-negative patients with sporadic medullary thyroid cancer (1.7%) and the classical variant of papillary thyroid cancer (1.4%), and infrequent in node-negative patients with the follicular variant of papillary thyroid cancer (4.4%). These findings delineate windows of opportunity for early surgical intervention before distant metastasis has occurred.

scholarly journals Decreasing tumor size of thyroid cancer in Germany: institutional experience 1995–2009

2010 ◽  
Vol 163 (1) ◽  
pp. 111-119 ◽  
Author(s):  
Andreas Machens ◽  
Henning Dralle
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Tumor Size ◽  
Medullary Thyroid Cancer ◽  
Secular Trends ◽  
Papillary Thyroid ◽  
Follicular Thyroid Cancer ◽  
Thyroid Cancers ◽  
Medullary Thyroid ◽  
Screening Programs

ObjectiveDecreasing tumor size in a population over time is widely interpreted as a measure of effectiveness of cancer screening programs. Nonetheless, thyroid cancer size is rarely analyzed as a function of time. This study aimed to explore secular trends of thyroid cancer diameter in Germany.DesignRetrospective analysis of 1644 thyroid cancer patients from a large referral center for thyroid cancer (1995–2009).MethodsCalculation of largest tumor diameters for each type of cancer as a function of time periods and birth cohorts.ResultsOver the past 25 years, subdivided into 5-year periods by year of thyroidectomy (1985–1989; 1990–1994; 1995–1999; 2000–2004; 2005–2009), tumor diameters diminished from 25 to 16 mm (P=0.025) for medullary thyroid cancer and from 28 to 18 mm (P=0.017) for papillary thyroid cancer. This reduction was greater for hereditary medullary thyroid cancer (from 27 to 11 mm; P=0.088) than sporadic medullary thyroid cancer (from 23 to 19 mm; P=0.11). No decline was observed for follicular thyroid cancer (means of 45 to 42 mm; P=0.52). From the first (1921–1940) to the most recent birth cohort (1981–2000), tumor size fell from 22 to 10 mm (P<0.001) for medullary thyroid cancer, from 24 to 22 mm (P<0.001) for papillary thyroid cancer, and from 49 to 38 mm (P=0.011) for follicular thyroid cancer. The reduction of medullary thyroid cancers affected exclusively patients with hereditary disease (from 20 to 7 mm; P<0.001).ConclusionThe consistency and robustness of these data signify powerful secular trends toward smaller papillary, follicular, and medullary thyroid cancers. The causes and consequences of these trends warrant further investigation.

scholarly journals Should we use ultrasound features associated with papillary thyroid cancer in diagnosing medullary thyroid cancer?

2012 ◽  
Vol 59 (6) ◽  
pp. 503-508 ◽  
Author(s):  
Pierpaolo Trimboli ◽  
Naim Nasrollah ◽  
Stefano Amendola ◽  
Fabio Rossi ◽  
Giovanni Ramacciato ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Medullary Thyroid Cancer ◽  
Papillary Thyroid ◽  
Medullary Thyroid ◽  
Ultrasound Features

scholarly journals PROX1 Promotes Secretory Granule Formation in Medullary Thyroid Cancer Cells

Endocrinology ◽  
2016 ◽  
Vol 157 (3) ◽  
pp. 1289-1298 ◽  
Author(s):  
Jun Ishii ◽  
Takuya Yazawa ◽  
Tomohiro Chiba ◽  
Yukiko Shishido-Hara ◽  
Yuu Arimasu ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Cancer Cells ◽  
Papillary Thyroid Cancer ◽  
Secretory Granule ◽  
Chromogranin A ◽  
Medullary Thyroid Cancer ◽  
C Cells ◽  
Papillary Thyroid ◽  
Medullary Thyroid ◽  
Thyroid Cancer Cells

Abstract Mechanisms of endocrine secretory granule (SG) formation in thyroid C cells and medullary thyroid cancer (MTC) cells have not been fully elucidated. Here we directly demonstrated that PROX1, a developmental homeobox gene, is transcriptionally involved in SG formation in MTC, which is derived from C cells. Analyses using gene expression databases on web sites revealed that, among thyroid cancer cells, MTC cells specifically and highly express PROX1 as well as several SG-forming molecule genes. Immunohistochemical analyses showed that in vivo MTC and C cells expressed PROX1, although follicular thyroid cancer and papillary thyroid cancer cells, normal follicular cells did not. Knockdown of PROX1 in an MTC cells reduced SGs detected by electron microscopy, and decreased expression of SG-related genes (chromogranin A, chromogranin B, secretogranin II, secretogranin III, synaptophysin, and carboxypeptidase E). Conversely, the introduction of a PROX1 transgene into a papillary thyroid cancer and anaplastic thyroid cancer cells induced the expression of SG-related genes. Reporter assays using the promoter sequence of chromogranin A showed that PROX1 activates the chromogranin A gene in addition to the known regulatory mechanisms, which are mediated via the cAMP response element binding protein and the repressor element 1-silencing transcription factor. Furthermore, chromatin immunoprecipitation-PCR assays demonstrated that PROX1 binds to the transcriptional regulatory element of the chromogranin A gene. In conclusion, PROX1 is an important regulator of endocrine SG formation in MTC cells.

scholarly journals Presentation of Pheochromocytoma, Papillary Thyroid Cancer and Hyperparathyroidism in Three Family Members

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A1004-A1004
Author(s):  
Damilola Ashorobi ◽  
Kaushik Mandal ◽  
Huijuan Liao ◽  
Salini Chellappan Kumar
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Medullary Thyroid Cancer ◽  
Family Members ◽  
Papillary Thyroid ◽  
Urine Calcium ◽  
Medullary Thyroid ◽  
The Family ◽  
History Of ◽  
Men 2A

Abstract Introduction: Although rare, one of the most common inherited disorders is multiple endocrine neoplasia. It is an autosomal dominant disorder that predisposes individuals to certain endocrine abnormalities depending on which type. The type 2A is a combination of medullary thyroid cancer, hyperparathyroidism, and pheochromocytoma which have been explained to be due to a mutation in the RET proto-oncogene. This abstract present a case of a patient with hyperparathyroidism whom family members also have pheochromocytoma and papillary thyroid cancer. Case description: A 45 year-old Hispanic male came to the endocrinology clinic complaining of constipation and headache. He has a personal history of non-toxic multinodular goiter and underwent right sided thyroidectomy in 2015 with pathology report showing follicular adenoma. He is currently on thyroid replacement therapy. He is clinically and biochemically euthyroid with TSH of 2.29 IU/ml. Physical examination was unremarkable. His labs were pertinent for calcium 11.5mg/dl, parathyroid 245.7pg/ml, creatinine of 1.5mg/dl. Two years ago, parathyroid was 189.5pg/ml and calcium was 11mg/dl, 1.5 year ago parathyroid level was 235.5pg/ml, calcium was 11.4mg/dl, urine calcium 9.3mg/dl, 24hr urine calcium 286.4mg, calcitonin &lt;2pg/ml, vitamin D 23ng/ml, 1,25 vitamin D 53ng/ml. In 2017, Sestambi scan showed equivocal focus of faint parathyroid activity in the region of the mid to lower left thyroid lobe versus faint residual thyroid activity and in 2019, scan showed no definite parathyroid adenoma. Surgical intervention was recently recommended due to patient’s DEXA scan showing osteoporosis of the femoral neck. The family history of this patient is pertinent for two sisters; one with pheochromocytoma and the other with papillary thyroid cancer. One of the sisters is a 60 years old diagnosed with pheochromocytoma at 51. Her free normetanephrine level was 682pg/ml and total metanephrine was 727pg/ml at time of diagnosis. Her MRI report showed right adrenal mass measuring 3.5x2.8cm. Laparoscopic right adrenalectomy was done and pathology confirmed pheochromocytoma which was RET negative. She still follows up with endocrinology and calcitonin, chromogranin A and plasma metanephrines have been normal. The second sister is now 53 years old diagnosed with papillary thyroid cancer at age 27 and had total thyroidectomy with pathology confirming papillary thyroid cancer. Discussion: Based on the clinical presentation of these family members, the most likely explanation is familial inheritance. This pattern of inheritance cannot be explained by MEN 2A or 2B due to the absence of medullary thyroid cancer. It has also been reported that this unusual presentation could be a variant of MEN 2A.[i] Due to the family history, close follow up is required to monitor for the possible development of other endocrinopathies in the future.

Prevalence of incidentally finding of papillary thyroid cancer among patients with sporadic medullary thyroid cancer

2020 ◽  
Author(s):  
Georgios Boutzios ◽  
Nefeli Tomara ◽  
Evgenia Kotsifa ◽  
Eleni Koukoulioti ◽  
Alexis Terra ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Medullary Thyroid Cancer ◽  
Papillary Thyroid ◽  
Medullary Thyroid

Exceptionality of Distant Metastases in Node-Negative Hereditary and Sporadic Medullary Thyroid Cancer: Lessons Learned

2021 ◽  
Author(s):  
Andreas Machens ◽  
Kerstin Lorenz ◽  
Frank Weber ◽  
Henning Dralle
Keyword(s):  
Risk Factors ◽  
Thyroid Cancer ◽  
Lymph Node ◽  
Medullary Thyroid Cancer ◽  
Distant Metastases ◽  
Node Negative ◽  
Medullary Thyroid ◽  
Primary Tumor Size ◽  
Node Metastasis ◽  
Node Positive

Abstract Context Risk factors of lymph node and distant metastases have rarely been analyzed in hereditary and sporadic medullary thyroid cancer (MTC) using large genetic-clinical data sets. Objective This comprehensive investigation aimed to explore risk factors of lymph node and distant metastases and interdependencies between age at thyroidectomy, primary tumor size, lymph node metastasis and distant metastasis in patients with hereditary and sporadic MTC. Methods Comparative analyses of risk factors of metastasis, stratified by hereditary MTC (four mutational risk categories) and sporadic MTC. Results There were 1115 patients with hereditary MTC (307 patients) or sporadic MTC (808 patients). Age at thyroidectomy increased proportionately from 12.2, 22.7, 34.3, and 49.8 years for patients with decreasing mutational risk, as compared to 52.1 years for patients with sporadic MTC. Metastatic primary tumors overall were 10.7–19.4 mm larger in node-positive patients and 15.9–19.3 mm larger in distant metastatic patients at thyroidectomy than nonmetastatic tumors. Distant metastases were noted in 13–50% of node-positive vs. 0% of node-negative hereditary MTC, and in 23.5% of node-positive vs. 1.7% of node-negative sporadic MTC. In multivariable logistic regression analysis for sporadic MTC, lymph node metastasis contributed to distant metastasis (odds ratio 12.4) more than primary tumor size (odds ratios of 7.8, 5.5 and 2.4 for tumors measuring &gt;60, 41–60 and 21–40 mm). Conclusions When thyroidectomy is performed before lymph node metastases have developed, distant metastases are exceptional, both in patients with hereditary MTC, irrespective of the level of mutational risk, and patients with sporadic MTC.

Clinical Significance of Coexistence of Hashimoto Thyroiditis and Graves’ Disease with Differentiated and Medullary Thyroid Cancer

2021 ◽  
Author(s):  
Andreas Machens ◽  
Kerstin Lorenz ◽  
Frank Weber ◽  
Henning Dralle
Keyword(s):  
Thyroid Cancer ◽  
Medullary Thyroid Cancer ◽  
Hashimoto Thyroiditis ◽  
Graves Disease ◽  
Papillary Thyroid ◽  
Follicular Thyroid Cancer ◽  
Medullary Thyroid ◽  
Chronic Autoimmune Thyroiditis ◽  
Clinicopathological Study ◽  
Tumor Types

AbstractThe association of Hashimoto thyroiditis and Graves’ disease with papillary, follicular, and medullary thyroid cancer has not been comprehensively investigated until now. This comparative clinicopathological study of consecutive patients thyroidectomized at a surgical referral center aimed to explore interdependencies between chronic autoimmune thyroiditis and thyroid cancer. Altogether, there were 852 (58.4%) patients with papillary thyroid cancer, 181 (12.4%) patients with follicular thyroid cancer, and 426 (29.2%) patients with sporadic medullary thyroid cancer, of whom 75 (5.1%) patients also had Hashimoto thyroiditis and 40 (2.7%) patients also had Graves’ disease. Patients with papillary (medians of 42 vs. 48 years; P =0.008) and follicular (medians of 33 vs. 63 years; P=0.022) thyroid cancer, unlike patients with medullary thyroid cancer (medians of 57.5 vs. 57 years; P=0.989), were younger at thyroidectomy when they had Hashimoto thyroiditis concomitantly. No such associations were seen with Graves’ disease. Primary thyroid cancers tended to be more localized in conjunction with Hashimoto thyroiditis, and less so with Graves’ disease, although patterns were not consistent across tumor types. In conclusion, Hashimoto thyroiditis, but not Graves’ disease, may be associated with differentiated (papillary and follicular) thyroid cancer but not with medullary thyroid cancer.

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