Istanbul Bakirköy Dr. Sadi Konuk Research and Training Hospital, Department of Otorhinolaryngology, Istanbul, TurkeyTurkey
Istanbul Bakirkoy Sadi Konuk Research and Education Hospital, Department of General Surgery, Division of Endocrine Surgery, Istanbul, TurkeyTurkey
Istanbul Bakirköy Dr. Sadi Konuk Research and Training Hospital, Department of Pathology, Istanbul, TurkeyTurkey
Istanbul Bakirköy Dr. Sadi Konuk Research and Training Hospital, Department of Endocrinology, Istanbul, TurkeyTurkey
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Medullary thyroid carcinoma (MTC) is a neuroendocrine (NE) tumor and is very rarely ob-served. MTC originates from the parafolliculer C cell and can show various histopathological patterns. Head and neck paragangliomas are seen rarely. Paragangliomas in the head and neck region are usually non-functional. MTC should be considered in the differential diagnosis of paragangliomas in the head and neck region. A high degree of clinical investigation is needed to determine the rare potential etiology underlying this condition. Because patients with MTC can present different clinical manifestations, otolaryngologist must be aware of MTC and its rare medical presentations. This case presented here highlights the importance of serum calcitonin levels in the differential diagnosis of paragangliomas in the head and neck region.
Keywords: Calcitonin; Medullary thyroid cancer; Glomus vagale
Medullary thyroid carcinoma (MTC) is a neuroendocrine (NE) tumor and comprises lesser than 1-3 10% of all thyroid malign tumors. So it is a very rarely occuring tumor in all malignancies.1-3 Due to recent Surveillance, Epidemiology, and End Results (SEER) data in the United States, 4,5 MTC accounts for 1% to 2% of all thyroid cancers.4,5 A large part of the medullary carcinomas 4-6 are sporadic, and familial form constitutes nearly 25%.4-6 The 10-year survival rate of MTC is approximately about 75% with respect to current literature. The study of Jung et al7 reported that the 5- and 10-year survival rates for MTC were 92% and 87%, respectively. The MTC spreads early to both paratracheal and lateral cervical lymph nodes, and distant spreading occurs in the liver, lungs, bones, and less frequently in brain and skin. All the patients undergoing a pre-operative diagnosis of MTC should be evaluated with a detailed neck ultrasonography (US) and measurement of serum calcitonin and carcinoembryonic antigen (CEA). Basal serum
8-10
MTC is a neuroendocrine cancer that originates from the parafollicular C cells and 9,11 can indicate various histopathological patterns. One of these is a paraganglioma-like pattern.
inate from the vagus nerve ganglion, carotid body, jugular bulb and tympanic plexus.12 The differential diagnosis of neuroendocrine tumors appear to be quite difficult in certain unusual clinical presentations. Preoperative fine needle aspiration biopsies provide the results for the early diagnosis of MTC. Biochemical and genetic screening would also help determine patients with early stage sporadic MTC. However, FNAB is never excluded from a malignancy and sometimes proves to be inadequate in the differential diagnosis of MTC. The reported case illustrates a valuable example of what needs to be done in a similar situation. MTC should be considered in the differential diagnosis of paragangliomas in the head and neck region. A high degree of clinical investigation is needed to determine the rare potential etiology underlying this condition. To the best of our knowledge, this is the first case reported in the literature to focus on the differential diagnosis of MTC with serum calcitonin levels.
A 25 year old female patient reported to our clinic with a 3 cm mass in level 4 of the left side of her neck. She noticed 3 months ago that the mass showed a tendency to grow. On performing clinical investigation, there was no medical evidence other than a mass in the neck. No pathological findings were observed following the pan endoscopic examination. A mass of About 3 cm size in the left side of the neck was revealed in the ultrasonography (USG) reports. A diffuse echo reduction and, pseudonodular image in the thyroid gland was observed in the USG report. On performing the MRI of the neck, a 40×23 mm sized, well-circumscribed mass was seen that displaced the left common carotid artery and jugular vein to the anterior and the right. This mass showed intense contrast enhancement and vascular structures were observed in the mass. This view was consistent with the observation of the glomus vagale radiologically. No pathological finding was observed in the thyroid gland and other neck structures (Figure 1). Because glomus tumors are generally seen at level 2-3, radiological diagnosis of glomus tumor was viewed with medical suspicion. For this reason,
a fine needle aspiration biopsy (FNAB) was performed. FNAB was also found to be compatible with the vagal glomus and the patient was referred to the endocrinology clinic. The 24-hour analysis of adrenaline, noradrenaline, vanilmandelic acid, metanephrine, normetanephrine, dopamine and, 5-hydroxyindolacetic acid levels in the urine were observed to be in the normal range, where upon the patient was operated with the diagnosis of the non-functioning of the glomus vagale tumor to the left. While performing the surgery, the mass in close relation with the vagina carotica was extended into the carotid sheath posterolaterally. When the mass was dissected, it was observed that there was no direct relation with any structure in the carotid sheath and, the mass could be easily stripped from the vagus. Thereupon, the mass was subjected to frozen examination with the consultation of the pathologist. In the opinion of the pathologist, the mass was a neuroendocrine tumor and a glomus tumor and thyroid medullary cancer was observed following differential diagnosis. Palpation of the thyroid gland, and assessment of level 6 and level 4 was performed intraoperatively. Because of the lack of any pathological symptom during the intraoperative assessment, it was decided that before undertaking any further action, a definitive pathological report had to be obtained. In the definitive pathological examination, with chromogranin, synaptophysin and calcitonin by immunohistochemical staining, the reports following diagnosis were indicative of medullary thyroid cancer metastases (Figure 2). After pathological examination, we assessed the level of serum calcitonin and this was recorded as 809 pg/ml (n:0-5). Total thyroidectomy, bilateral functional neck dissection and level six neck dissection were decided to be performed by the endocrine surgery council. The operation was completed without any complications. Once, three of the four parathyroid glands were observed and confirmed by frozen examination, which were replanted to the left sternocleidomastoid muscle 1/3 middle segment. Postoperatively, bilateral vocal cord movements were normal, but to address the cause of hypo- ® calcemia, calcium 2×1500 mg and 1×0.25 mcg calcitriol® had to be administered. In the post-operative pathological report; four focus micromedullary thyroid cancer, four metastasis in the
Figure 1. Neck Contrast Enhanced Magnetic Resonance Imaging.
central neck dissection specimen and, pericapsular invasion in one of these four metastasis and, one metastasis with pericapsular invasion in the right neck dissection specimen was revealed (Figure 3A-3B). When the calcium and rocaltrol® treatment was terminated in the first month following the surgery, the serum calcium level remained stable at 8.25 mg/dL. In the early followup period, pregnancy occurred. Thus, adjuvant therapy was not administered. The patient is still followed up regularly without any sign of distant metastasis and local recurrence as has been observed in the imaging findings but the serum calcitonin level has been recorded at 66.20 pg/mL (n:0-5)
An elevated serum calcitonin level is a highly sensitive and specific tumor marker for postsurgical follow-up of patients with MTC following total thyroidectomy. However, relative to more advanced tumors, which may be dedifferentiated by decreased
calcitonin production, CEA may be a more worthy tumor marker.13 Other important prognostic factors for adverse outcome include advanced age at diagnosis, extent of primary tumor, and ® 14 nodal metastasis and distant metastases.14 Standard treatment for patients with MTC is total thyroidectomy and dissection of cervical lymph node (LN) compartments, depending on serum calcitonin levels and neck US findings. Usually in sporadic MTC, the tumor is unifocal and defined in the fifth or sixth decade of life. In the hereditary MTC, a vast majority of patients are asymptomatic initially and diagnosed by genetic or biochemical screening tests during the early stages of the disease. The clinical symptoms of sporadic MTC contain a thyroid nodule or mass, cervical lymphadenopathy or other cervical symptoms, metastatic disease, and seldom diarrhea, flushing, or Cushing’s syndrome due to chronic ectopic adrenocorticotropic hormone 15-18 production.
Histopathological differential diagnosis of MTC in-
cludes paraganglioma and other NE tumors.10 To distinguish NE tumors on the basis of cytomorphology is difficult. Owing to this reason, clinicians must keep the pathologist informed and immunohistochemistry must be performed.11 In the diagnosis of MTC, calcitonin, chromogranin A, or CEA immunostaining can be used.8 Calcitonin is an important molecule because it has a very significant role in the diagnosis and clinical followup of patients with MTC.6 If immunohistochemistry cannot be performed and there is a confusion regarding the diagnosis, the serum calcitonin level can help clarify the diagnostic reports.7 In particular, the glomus vagale has an origin in the neuroendocrine tumor and can be located anywhere in the vagus ganglia. Other neuroendocrine tumors and metastases of these tumors are observed by differential diagnosis. Especially in the evaluation of the head and neck region glomus tumors, medullary thyroid cancer metastasis is clinical relevant. As has been indicated in this case, such that FNAB and imaging cannot provide relevant information based on the differential diagnosis. Therefore, monitoring the role of calcitonin in preoperative evaluation will be very helpful in the planning of operations, thus preventing from possible secondary operations and eliminating additional risks of morbidity and mortality.
The main causes of death of patients with MTC are distant metastases. Survival after the discovery of distant metastases is 51% in 1 year, 26% in 5 years, and 10% in 10 years according to the existing research literature. Long-term survival of the two types of MTC patients was not significantly different. Various factors have been proposed as prognostic factors for the outcome for patients with MTC. Age at diagnosis, TNM stage and completeness of initial surgery are significant factors affect- 22,23 ing the outcome. Therefore, patients with MTC should be closely followed-up and recommended about related endocrine pathologies and the risk of the disease for other family members.
MTC should be considered for the differential diagnosis of paragangliomas in the head and neck region. A high degree of clinical suspicion needs to be observed to determine this rare potential etiology. Because patients with MTC can present with different clinical manifestations, the otolaryngologist must be aware of MTC and its rare presentations.
The authors declare that they have no conflicts of interest.
Written informed consent was obtained from the patient who participated in this case.