An Unusual Case of Medullary Thyroid Carcinoma and A Revision of Current Literature

Author(s): Claudia Cipri*, Fabio Vescini, Francesca Torresan, Gianmaria Pennelli, Maria Rosa Pelizzo, Vincenzo Triggiani, Edoardo Guastamacchia, Franco Grimaldi

Journal Name: Endocrine, Metabolic & Immune Disorders - Drug Targets
Formerly Current Drug Targets - Immune, Endocrine & Metabolic Disorders

Volume 19 , Issue 2 , 2019

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Graphical Abstract:


Background: Medullary thyroid cancer (MTC) accounts for 5% of all thyroid cancers and occurs either sporadically or in a hereditary pattern. Routine calcitonin (CT) measurement is suggested for MTC screening in patients with nodular thyroid disease.

Patient Findings: A 45 years-old woman incidentally discovered, with neck ultrasound, the presence of thyroid micronodules. Fine-needle aspiration (FNA) on thyroid prevailing nodule did not demonstrate cellular atypia.

During follow-up, FNA was repeated on the previously analyzed nodule suspicious for Hürthle cell nodule suspicious for follicular neoplasm and on another hypoechoic right nodule which showed cellular atypia. CT was <2 pg/ml (normal values <18.2 pg/ml), anti-thyroid antibodies were positive and the patient showed a normal thyroid function.

The patient also was diagnosed with primary hyperparathyroidism with an enlarged parathyroid gland behind the right thyroid lobe. Therefore, she underwent total thyroidectomy and a selective parathyroidectomy was performed.

Histology showed an encapsulated microMTC (pT1aNxMx) associated with diffuse C-cell hyperplasia and lymphocytic thyroiditis. The neoplasm was positive for calcitonin and chromogranin A and negative for thyroglobulin. A right parathyroid adenoma was also diagnosed. One month after surgery basal and stimulated CT were <2 ng/ml. Genetic analysis did not reveal mutation of RET proto-oncogene. Twelve months after surgery, neck ultrasonography, chest and abdomen computed tomography did not demonstrated residual/recurrent disease with undetectable serum CT.

Conclusion: In the literature, few MTC cases with normal serum CT have been reported. Although MTC without elevated plasma CT is extremely rare, normal or low CT levels, do not entirely exclude this diagnosis.

Keywords: Thyroid, thyroid nodular disease, calcitonin, thyroid carcinoma, medullary thyroid carcinoma, thyroidectomy.

DeLellis, R.A. The pathology of medullary thyroid carcinoma and its precursors. Monogr. Pathol., 1993, 35, 72-102.
Kloos, R.T.; Eng, C.; Evans, D.B.; Francis, G.L.; Gagel, R.F.; Gharib, H.; Moley, J.F.; Pacini, F.; Ringel, M.D.; Schlumberger, M.; Wells, S.A., Jr America thyroid association guidelines task force: Medullary thyroid cancer: Management guidelines of the america thyroid association. Thyroid, 2009, 19(6), 565-612.
Wolfe, H.J.; Melvin, K.E.; Cervi-Skinner, S.J.; Saadi, A.A.; Juliar, J.F.; Jackson, C.E.; Tashjian, A.H., Jr C-cell hyperplasia preceding medullary thyroid carcinoma. N. Engl. J. Med., 1973, 289, 437-441.
Papi, G.; Corsello, S.M.; Cioni, K.; Pizzini, A.M.; Corrado, S.; Carapezzi, C.; Fadda, G.; Baldini, A.; Carani, C.; Pontecorvi, A.; Roti, E. Value of routine measurement of serum calcitonin concentrations in patients with nodular thyroid disease: A multicenter study. J. Endocrinol. Invest., 2006, 29, 427-437.
Niccoli, P.; Wion-Barbot, N.; Caron, P.; Henry, J.F.; de Micco, C.; Saint Andre, J.P.; Bigorgne, J.C.; Modigliani, E.; Conte-Devolx, B. Interest of routine measurement of serum calcitonin: Study in a large series of thyroidectomized patients. The french medullary study group. J. Clin. Endocrinol. Metab., 1997, 82, 338-341.
Elisei, R.; Bottici, V.; Luchetti, F.; Di Coscio, G.; Romei, C.; Grasso, L.; Miccoli, P.; Iacconi, P.; Basolo, F.; Pinchera, A.; Pacini, F. Impact of routine measurement of serum calcitonin on the diagnosis and outcome of medullary thyroid cancer: Experience in 10,864 patients with nodular thyroid disorders. J. Clin. Endocrinol. Metab., 2004, 89, 163-168.
Vierhapper, H.; Raber, W.; Bieglmayer, C.; Kaserer, K.; Weinhausl, A.; Niederle, B. Routine measurement of plasma calcitonin in nodular thyroid disease. J. Clin. Endocrinol. Metab., 1997, 82, 1589-1593.
Cohen, R.; Campos, J.M.; Salaun, C.; Heshmati, H.M.; Kraimps, J.L.; Proye, C.; Sarfati, E.; Henry, J.F.; Niccoli-Sire, P.; Modigliani, E. Preoperative calcitonin levels are predictive of tumor size and postoperative calcitonin normalization in medullary thyroid carcinoma. Groupe d’Etudes des Tumeurs a Calcitonine (GETC). J. Clin. Endocrinol. Metab., 2000, 85, 919-922.
Iacobone, M.; Niccoli-Sire, P.; Sebag, F.; de Micco, C.; Henry, J.F. Can sporadic medullary thyroid carcinoma be biochemically predicted? Prospective analysis of 66 operated patients with elevated serum calcitonin levels. World J. Surg., 2002, 26, 886-890.
Machens, A.; Schneyer, U.; Holzhausen, H.J.; Dralle, H. Prospects of remission in medullary thyroid carcinoma according to basal calcitonin level. J. Clin. Endocrinol. Metab., 2005, 90, 2029-2034.
Jo, V.Y.; Stelow, E.B.; Dustin, S.M.; Hanley, K.Z. Malignancy risk for fine-needle aspiration of thyroid lesions according to the bethesda system for reporting thyroid cytopathology. Am. J. Clin. Pathol., 2010, 134, 450-456.
Roman, S.; Lin, R.; Sosa, J.A. Prognosis of medullary thyroid carcinoma: Demographic, clinical, and pathologic predictors of survival in 1252 cases. Cancer, 2006, 107, 2134-2142.
Ahmed, S.R.; Ball, D.W. Incidentally discovered medullary thyroid cancer: Diagnostic strategies and treatment. J. Clin. Endocrinol. Metab., 2011, 96(5), 1237-1245.
Boschin, I.M.; Torresan, F.; Toniato, A.; Zane, M.; Ide, E.C.; Pennelli, G.; Rampin, L.; Colletti, P.M.; Rubello, D.; Pelizzo, M.R. Incidental medullary thyroid microcarcinoma revealed by mild increase of preoperative serum calcitonin levels: Therapeutic implications. Endocrine, 2014, 45(3), 448-453.
Sand, M.; Gelos, M.; Sand, D.; Bechara, F.G.; Bonhag, G.; Welsing, E.; Mann, B. Serum calcitonin negative medullary thyroid carcinoma. World J. Surg. Oncol., 2006, 4, 97-100.
Iglesias, P.; Vicandi, B.; Ortega, P.; Diez, P.P. Anaplastic variant of thyroid medullar carcinoma. Med. Clin. (Barc.), 1997, 109, 276-277.
Bockhorn, M.; Frilling, A.; Rewerk, S.; Liedke, M.; Dirsch, O.; Schmid, K.W.; Broelsch, C.E. Lack of elevated serum carcinoembryonic antigen and calcitonin in medullary thyroid carcinoma. Thyroid, 2004, 14(6), 468-470.
Letelier, C.; Pineda, P.; Rodriguez, F.; Carreno, L.; Jaimovich, L.; Massardo, T. Cancer medular de tiroides metastatico con niveles plasmaticos de calcitonina indetectables, caso clinico. Abstract. Book. Of. The. Latin. American. Thyroid. Society. XII. Congress., 2007, 162 (abstract).
Redding, A.H.; Levine, S.N.; Fowler, M.R. Normal preoperative calcitonin levels do not always exclude medullary thyroid carcinoma in patients with large palpable thyroid masses. Thyroid, 2000, 10, 919-922.
Dora, J.M.; Busi da Silva Canalli, M.H.; Capp, C.; Pun˜ales, M.K.; Gilberto Vieira, J.H.; Maia, A.L. Normal perioperative serum calcitonin levels in patients with advanced medullary thyroid carcinoma: Case report and review of the literature. Thyroid, 2008, 18(8), 895-899.
Alapat, D.V.; Ain, K.B.; Sloan, D.A.; Monaghan, K.G.; Karabakhtsian, R.G. Disparity between tissue and serum calcitonin and carcinoembryonic antigen in a patient with medullary thyroid carcinoma. Endocrinology, 2011, 39, 148-152.
Brutsaert, E.F.; Gersten, A.J.; Tassler, A.B.; Surks, M.I. Medullary thyroid cancer with undetectable serum calcitonin. J. Clin. Endocrinol. Metab., 2015, 100, 337-341.
Giovanella, L.; Crippa, S.; Cariani, L. Serum calcitonin-negative medullary thyroid carcinoma: Role of CgA and CEA as complementary markers. Int. J. Biol. Markers, 2008, 23, 129-131.
Chambon, G.; Alovisetti, C.; Idoux-Louche, C.; Reynaud, C.; Rodier, M.; Guedj, A.M. The use of preoperative routine measurement of basal serum thyrocalcitonin in candidates for thyroidectomy due to nodular thyroid disorders: Results from 2733 consecutive patients. J. Clin. Endocrinol. Metab., 2011, 96, 75-81.
Frank-Raue, K.; Machens, A.; Leidig-Bruckner, G.; Rondot, S.; Haag, C.; Schulze, E. Prevalence and clinical spectrum of nonsecretory medullary thyroid carcinoma in a series of 839 patients with sporadic medullary thyroid carcinoma. Thyroid, 2013, 23, 294-300.
Trimboli, P.; Giovanella, L. Serum calcitonin negative medullary thyroid carcinoma: A systematic review of the literature. Clin. Chem. Lab. Med., 2015, 53(10), 1507-1514.
Fangous, M.S.; Kerspern, H.; Moineau, M.P.; Kerlan, V.; Alavi, Z.; Carre’, J.L. The hook effect in calcitonin immunoradiometric assay: A case report. Ann. Endocrinol. (Paris), 2012, 73(6), 552-555.

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Article Details

Year: 2019
Published on: 20 December, 2018
Page: [226 - 229]
Pages: 4
DOI: 10.2174/1871530319666181220165350

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