1. 106年3月19日 蕭炳昆 張渭文 呂長運 余信賢 謝茂志 劉自嘉 台北醫學大學 萬芳醫院 外科部 一般外科
Medullary thyroid cancer a case with elevated serum CEA level as first clue
106年3月19日
蕭炳昆 張渭文 呂長運 余信賢 謝茂志 劉自嘉
台北醫學大學 萬芳醫院 外科部 一般外科

2. Introduction
Medullary thyroid cancer (MTC) is a neuroendocrine tumor of the parafollicular cells (C cells) of the thyroid gland.
approximately 3 to 5 percent of thyroid carcinomas.
A characteristic feature of this tumor is the production of calcitonin.

3. Patient information 82-year-old male patient
Past history: CAD, arrhythmia s/p ablation, old CVA
Family history: daughter has hypothyroidism, mother and brother had colon cancer
no associated family history of thyroid tumor

4. Clinical course
referred to GI for persisted high CEA level(13.3) chest CT scan : 3.4cm low density at Rt thyroid PET scan showed 1.6 cm nodule over right thyroid
Refer to metabolism(euthyroid state)

5. Clinical course
R‘t thyroid mass lesion noted for 3 years with progressive enlargement
99-11 thyroid sono: Rt 3.2cm nodule (hypoechoic)
=> FNA : benign
thyroid sono: Rt 3.0cm nodule (hypoechoic)
=> FNA: benign
Thyroid sono: Rt 4.1cm nodule
(hetero, coarse calcif) => FNA: benign

6. Clinical course(Lab.) 102-10 CEA 31.75 (0-5ng/ml) 104-03 CEA 33.48
Calcitonin 696 ( pg/ml)
CEA Calcitonin 1158
calcium 8.9 ( mg/dl)

7. Clinical course 104-06 Thyroid sono:
Right thyroid gland heterogenous lesion with microcalcifications and mild increased vascularity, 3.34x2.8cm, thyroid neoplasm can't be ruled out
No abnormal neck LN
=> Discussion with pathologist, the latest cytology showed suspicious feature for medullary thyroid cancer

10. Clinical course For rule out MEN II, also checked:
24hr urine catecholamine and VMA 1.2g/d (WNL)
Ca 8.9 P 3.1 Alb 4.7 iPTH 32.4
=> No biochemical evidence of pheochromocytoma or hyperparathyroidism

11. Operation
Bil. total thyroidectomy + central neck LNs dissection

12. OP findings
A 4cm hard tumor at the Rt thyroid, occupied nearly total left lobe, mainly at midportion that frozen section to be c/w medullary cancer.
Enlarged LNs over Rt. pretracheal region

13. Pathology
Thyroid, right lobe, lobectomy, Medullary carcinoma, pStage III; pT2N1a
Thyroid, left lobe, lobectomy, nodular hyperplasia
Lymph node, neck, central, dissection, carcinoma, metastatic (6/7)

14. a well-circumscribed, non-encapsulated tumor

15. tumor cells in insular-like and trabecular patterns, separated by hyalinized collagen.

16. The tumor cells reveal round to oval, polygonal nuclei with occasional plasmacytoid appearance.

18. Congo red
Amyloid deposition in the stroma is also seen, highlighted by Congo red stain.

19. Lab.
CEA Calcitonin
Pre-op
Post-op

20. Discussion

21. MTC
1/4 of medullary thyroid cancer is genetic in nature, caused by a mutation in the RET proto-oncogene; classified as familial MTC.
3/4 cases are sporadic.
When it coexists with tumors of the parathyroid gland and medullary component of the adrenal glands (pheochromocytoma) => called multiple endocrine neoplasia type 2 (MEN2).

22. Schematic representation of downstream pathways of the RET receptor and other tyrosine kinase receptors (e.g. EGFR) with possible targets for therapeutic interventions.

24. Sporadic MTC
The most common presentation of sporadic MTC (75~95%) is a solitary thyroid nodule.
The disease has already metastasized at the time of diagnosis in most cases.
Basal serum calcitonin concentrations correlate with tumor mass and tumor differentiation; almost always high in patients with a palpable tumor.

25. MTC
The diagnosis of sporadic MTC is usually made after fine needle aspiration (FNA) biopsy in a patient who has a solitary thyroid nodule, or a dominant nodule within a multinodular goiter.

27. MTC
For patients diagnosed with MTC on the basis of cytologic evaluation of a thyroid nodule, evaluation should include:
serum calcitonin  (>18.7 ng/L in females ,>68 ng/L in males)
carcinoembryonic antigen (CEA)
ultrasonography of the neck (and images include chest and upper abdomen)
genetic testing for germline RET mutations
evaluation for coexisting tumors, especially pheochromocytoma

28. CEA > 30 ng/ml: central neck LN(+) CEA > 100 ng/ml: lateral neck LN(+),distant mets.
Arch. Surg Mar;142(3):289-93; discussion 294.
Abnormal carcinoembryonic antigen levels and medullary thyroid cancer progression: a multivariate analysis.
Machens A1, Ukkat J, Hauptmann S, Dralle H.

29. Treatment
Thyroxine (T4) therapy should be started immediately after surgery. (to restore and maintain euthyroidism).
Adjuvant therapy with radioiodine is not appropriate, because the tumor cells do not concentrate iodine.

30. Treatment
Total thyroidectomy rather than lobectomy for initial therapy (Grade 1B).
Routine prophylactic or therapeutic dissection of the nodal tissue in the central compartment from the hyoid bone to the innominate veins and medial to the jugular veins
Consideration of prophylactic lateral neck dissection if gross disease is identified in the adjacent central compartment.

31. Treatment
Radiotherapy to the neck and upper mediastinum may be appropriate after primary surgery in patients with extrathyroidal disease or extensive nodal metastases who do not undergo curative dissection.
Patients with progressive metastatic disease who cannot be treated by surgery or radiotherapy should be considered candidates for systemic therapy.

32. Treatment
For patients with asymptomatic metastatic tumors generally less than 1 to 2 cm in diameter, growing in diameter less than 20 percent per year, we recommend not giving systemic therapy (Grade 1C).
Such patients should be monitored for disease progression. (CT or MRI every 6~12 months)

33. Treatment
For patients with metastatic tumors at least 1 to 2 cm in diameter, growing by at least 20 percent per year, or for patients with symptoms related to multiple metastatic foci that cannot be alleviated with surgery or external beam radiotherapy, we prefer to administer systemic treatment as part of a clinical trial

34. Treatment
For patients who cannot participate in a clinical trial, we suggest an oral tyrosine kinase inhibitor (TKI), rather than traditional cytotoxic chemotherapy (Grade 2C).
For initial TKI therapy, we suggest cabozantinib or vandetanib rather than sorafenib or sunitinib (Grade 2C).

35. Treatment
For patients who cannot tolerate or who fail multiple TKIs, cytotoxic chemotherapy, of which dacarbazine-based regimens such as cyclophosphamide-vincristine-dacarbazine are preferable as an alternative option.

36. Is There a Role for Peptide Receptor Radionuclide Therapy (PRRT) in Medullary Thyroid Cancer (MTC)?
Original article
Clin Nucl Med 2015;40:

37. PRRT
Medullary thyroid cancer (MTC) is a rare but potentially lifethreatening disease with limited therapeutic options.
As a neuroendocrine tumor, MTC expresses somatostatin receptors, and therefore, somatostatin- labeled radiopharmaceuticals could be used to treat patients with MTC.

38. Thanks for your attention!