|Year : 2018 | Volume
| Issue : 1 | Page : 3-9
Clinicopathological features of differentiated thyroid carcinoma referred to radioiodine therapy at Tripoli Medical Center
Hawa Juma El-Shareif
Department of Endocrine, Tripoli, Medical Center, Faculty of Medicine, Tripoli University for Medical Sciences, Tripoli, Libya
|Date of Web Publication||23-Mar-2018|
Dr. Hawa Juma El-Shareif
Department of Endocrine, Tripoli, Medical Center, Faculty of Medicine, Tripoli University for Medical Sciences, Tripoli
Source of Support: None, Conflict of Interest: None
Objectives: The objective of this study is to study the demographic, clinicopathological features, and geographical distribution of differentiated thyroid cancer (DTC) among Libyan patients referred from all parts of the country to the nuclear medicine department, for radioactive iodine (RAI) therapy.
Materials and Methods: Retrospective review of medical records of 265 patients with differentiated thyroid carcinoma (DTC) referred to RAI therapy in the Nuclear Medicine Branch-Tripoli Medical Center, in the period from May 2005 to October 2010. The data analyzed included sex, age at the time of diagnosis, the city of residence, pathological diagnosis, the extent of disease, and types of treatment.
Results: There were 225 (84.9%) females and 40 (15.1%) males giving a sex ratio of 5.6:1. The mean age of males at diagnosis was 51.2 ± 14.8 (range 24–78) years and the mean age of the females was 44.6 ± 15.6 (range 10–95) years. Two hundred and twenty-three (84.2%) had papillary thyroid cancer (PTC), 31 (11.7%) had follicular thyroid cancer, 3 (1.1%) had Hurthle cell thyroid cancer, and 2 (0.8%) had follicular-insular thyroid cancer. About 43 (16.2%) had a history of multinodular goiter, and 3 (1.1%) Hashimoto's thyroiditis. From data collected, cervical lymph node metastases were found in 45 (17.0%), and distal metastases in 27 (10.2%).
Conclusions: PTC was the most common type of DTC. DTC was more common among females. The current study showed that the disease tends to occur at an older age, and with less cervical lymph node metastases than previously reported.
Keywords: Differentiated thyroid cancers, follicular thyroid cancer, hurthle cell thyroid cancer, papillary thyroid cancer, radioactive iodine therapy
|How to cite this article:|
El-Shareif HJ. Clinicopathological features of differentiated thyroid carcinoma referred to radioiodine therapy at Tripoli Medical Center. Thyroid Res Pract 2018;15:3-9
|How to cite this URL:|
El-Shareif HJ. Clinicopathological features of differentiated thyroid carcinoma referred to radioiodine therapy at Tripoli Medical Center. Thyroid Res Pract [serial online] 2018 [cited 2018 Nov 22];15:3-9. Available from: http://www.thetrp.net/text.asp?2018/15/1/3/228374
| Introduction|| |
Thyroid cancer is the most common endocrine malignancy. Differentiated thyroid cancer (DTC) including papillary and follicular cancer, comprises the majority (>90%) of all thyroid cancers.
Thyroid cancer continues to be the most rapidly increasing cancer (>5%/year in both men and women). The rate of DTC is rising worldwide, with wide geographic, ethnic, and temporal variations in incidence rates.,
Genetic and environmental factors such as iodine status and radiation exposure play a key role in modulating thyroid cancer pathogenesis.,,,,
A fairly consistent female-to-male ratio of three-to-one has been observed in almost all geographic areas and ethnic groups.
The increased incidence has been attributed to more extensive screening and better detection of clinically occult papillary carcinomas as a result of improved diagnostic accuracy (neck ultrasound, and fine-needle aspiration cytology).,, The growing rate of the disease, which has been observed during several stages and tumorous sizes suggests that some factors may be environmental, such as obesity.,,,
Papillary thyroid cancer (PTC) is the most common type of thyroid cancer, accounting for 50%–90% of DTC worldwide. Most papillary cancers are identifiable in early stages and have excellent prognosis.,
Follicular thyroid cancer (FTC) is more common in iodine-deficient areas and associated with a less favorable prognosis than PTC, partly because a large proportion of patients suffer distant metastases.,
DTC is among the few easily cured cancers. When managed according to best practice, the vast majority of patients can expect a cure.
Standard therapy of DTC includes surgery. Total or nearly total thyroidectomy with selective central compartment lymph node dissection is usually the appropriate initial surgical procedure, 11 often followed by radioiodine ablation of remnant thyroid tissue, and L-thyroxine replacement in sufficient dose to suppress thyroid-stimulating hormone.
This study is aimed at finding out the demographic, clinicopathological features, and geographical distribution of DTC among patients referred from all parts of the country to the Nuclear Medicine Department, in the Tripoli Medical Center (TMC), over the period from May 2005 to October 2010.
| Materials and Methods|| |
The data of our study were obtained from the archives of the Department of Nuclear Medicine of TMC, which is the only center in Libya that provides radioactive iodine (RAI) treatment.
DTC management protocol is multidisciplinary. All patients in this study received surgical treatment, an evaluation by an endocrinologist and a referral to radioiodine ablation of remnant thyroid tissue.
The study was retrospective. All patients with the diagnosis of DTC that were referred to the Nuclear Medicine Department, during the period between May 2005 and October 2010 regardless of age, were included in the present study.
The records of all the thyroid cancer patients of the study period were reviewed. Data were collected using a standardized data collection form, which included the patient's residence, age, sex, history of thyroid disease, type of thyroid surgery, final histopathological diagnosis, and the presence of nodal and distal metastases.
Detailed histological reports, tumor, nodes, metastasis staging, imaging reports, and thyroglobulin results are usually kept in patients' files at their endocrinology clinic and were missing in most files. Therefore, they were not included in the present study.
This study was carried out in accordance with the principles of the Helsinki Declaration. A formal approval was obtained from institutional authorities.
Data were analyzed using the Statistical Package for Social Science (SPSS Inc., IBM, Chicago, IL USA), 19th version. Continuous variables are expressed as mean ± standard deviation and range. Categorical data are expressed as numbers and percentages. Student's t-test was used to compare continuous variables and qualitative variables were analyzed with the Chi-square test or Fisher's exact test.
| Results|| |
The Nuclear Medicine Department at the TMC is the only center for treatment with RAI treatment in the country.
A total of 265 patients with thyroid cancer were registered and treated with RAI therapy at the center during the study period of May 2005–October 2010.
Of all the 265 patients with thyroid cancer, 223 (84.2%) had PTC, 31 (11.7%) had FTC, 3 (1.1%) had Hurthle cell tumor, and 2 (0.8%) had a follicular-insular type. In 6 (2.3%) patients, the histopathological type was not documented.
Two hundred and twenty-five patients (84.9%) were female and 40 (15.1%) were male, the female-to-male ratio was 5.6:1. The distribution of the cancer type according to gender was almost the same for those with papillary and follicular tumors with a female: male ratio of 5.6:1 and 5.2:1, respectively. All the three-Hurthle cell tumor patients, and the two patients with follicular-insular type were females [Figure 1].
The mean age was 45.5 ± 15.6 years, and the range was from 10 to 95 years.
The mean age of the female patients was 44.4 ± 15.6 (range 10–95) years and that of the male patients 51.2 ± 14.8 (range 24–78) years.
The difference between the average ages of male and female patients are statistically significant (P = 0.012).
Patients with FTC were older at diagnosis (P = 0.004) compared to the patients with PTC.
The mean age of PTC patients was 43.0 ± 15.3 (10–95) and 52.9 ± 15.2 (25–80), 47.0 ± 20.7 (25–66) years for follicular, and Hurthle cell tumor, respectively [Table 1].
Seventy-eight (29.4%) of cases were from Tripoli, and 93 (35.1%), 53 (20.0%), and 26 (9.8%), were from Western, Eastern, and Southern parts of the country. In 15 cases (5.7%), place of residence was not documented [Table 2].
About 46 (17.4%) had a history of thyroid disease, which was a multinodular goiter (MNG) in 43 (16.2%) and Hashimoto's thyroiditis in 3 (1.1%).
Four (1.5%) patients had a history of hyperthyroidism and 1 (0.4%) patient had a history of hypothyroidism.
A presurgery thyroid scintigraphy with technetium-99 m pertechnetate was available for 9 (3.4%) patients with a history of MNG, in 8 (88.9%) of them; the scan demonstrated a hot nodule in the context of MNG.
All patients with hot nodules were female with a younger mean age at diagnosis 39.4 ± 16.6 years. All had PTC type, nodal metastasis reported in one patient (12.5%), and no one had distal metastasis.
The main surgical treatment of DTC was total or near-total thyroidectomy. One hundred and sixty (60.4%) patients had total thyroidectomy, 10 (3.8%) had near-total thyroidectomy, 15 (5.7%) had lobectomy followed by completion thyroidectomy, and 8 (3.0%) cases had subtotal thyroidectomy. In 72 (27.2%), the type of surgery was missing.
RAI was administered for patients with mean first RAI ablation dose of 95 ± 29 mCi (range 30–264) and mean cumulative RAI dose of 236 ± 190 mCi (range 1–1298). Patients with nodal and/or distal metastasis were treated with higher dosages of RAI.
The cervical lymph node is the most common site of metastasis and 45 (17.0%) cases had cervical lymph node metastasis. Distant metastases occurred in 27 (10.2%), and organs involved were the lungs: 12 (4.5%), bones: 8 (3.0%), and liver: 1 (0.4%).
1 case (0.4%) had both lung and bone metastases and another 1 (0.4%) had liver and bone metastases. Metastases in other sites occurred to 4 (1.5%).
Thirteen (28.9%), of patients with lymph node metastases, also had a distant metastasis.
Cervical lymph node metastases were present in 38 (17.0%), 6 (19.4%), and 1 (50.0%), in patients with papillary, follicular, and follicular - insular type, respectively.
Distal metastases were present in 20 (9.0%), 5 (16.1%), 1 (50.0%), in patients with papillary, follicular, and follicular - insular type respectively.
The mean initial RAI dose in patients with no nodal or distal metastasis was 95.3 ± 26.6 mci.
No, statistically significant differences were found between the mean first RAI dose in those with only nodal metastasis 90.1 ± 33.3 (P = 0.420) and those with distal metastasis 100.3 ± 47.7 (P = 0. 703) compared to patients with no nodal or distal metastasis.
Patients older than 45 years had a statistically significant higher rate of cervical nodal metastasis (P = 0.027), distant metastasis (P = 0.019), and higher cumulative RAI doses (P = 0.000) [Table 3].
|Table 3: Comparison of Clinical Data and Cumulative RAI Dose of Patients Aged Below 45 years and above 45 Years|
Click here to view
Whole-body scans were negative in 63%, 79%, and 91% following the first, second, and third therapeutic dose of RAI, respectively. In 8 (3%) patients, whole-body scan was still positive after the seventh RAI dose.
Higher cumulative doses were used in patients with lymph node metastases (P = 0.005), and distant metastases (P = 0.004) versus those with no nodal or distal metastases.
Higher cumulative RAI doses were used in follicular carcinomas versus PTC (P = 0.047).
| Discussion|| |
Thyroid cancer is the most common malignant endocrine tumor. DTC, which includes papillary and follicular cancer, comprises the vast majority of all thyroid cancers.
Thyroidectomy followed by RAI ablation of residual thyroid tissue (remnant ablation) is considered the ideal treatment for DTC.
The goals of RAI ablation are to destroy any residual thyroid tissue and facilitate the early detection of recurring or metastatic disease by measurement of serum thyroglobulin or RAI scanning.,
The Nuclear Medicine Department at TMC is the only referral center for RAI therapy in Libya. This increases the likelihood that the data obtained in the present study is quite representative of the DTC in the whole country since the majority of patients that were referred to the center either for remnant ablation or diagnostic scanning came from cities all over the country.
The histopathologic distribution of DTC is comparable to international literature. The majority of cases were papillary carcinomas (84.2%). This is higher than the reported rates in Algeria 62.5% and Pakistan 64.7–73.7%.,,
Even higher rates of papillary carcinomas were reported in Yemen 95.8%–96.5%, Tunis 91.3%, Saudi Arabia 89%–93%, and Jordan 88.8%.,,,,,,,
A previous retrospective study from the endocrine department of TMC, including 143 patients with thyroid cancer, registered since 1985 till August-2003. Of the 131 patients with DTC, 93 (71.0%) had papillary, 35 (26.7%) had follicular, and 3 (2.3%) had Hurthle cell carcinoma. The ratio of papillary to follicular carcinoma was 2:7.
Another older study by Elhamel et al. reported a ratio of 1:1.
The ratio of papillary to follicular carcinoma in the present study is 7.2; this is much higher than what previously reported.
This observation is going with the changing pattern of thyroid cancer worldwide, where the overall incidence is reported to be increasing with changing characteristics. Papillary forms are on the rise whereas follicular and anaplastic tumors are becoming less frequent.,
This might be attributed to the correction of the iodine deficiency status with the initiation of salt iodization program as well as increased awareness of risks associated with red meat consumption and the trend to substitute it with seafood.
In general, chronic iodine deficiency and residence in areas where goiter are endemic are associated with an increased incidence of FTC whereas chronically high iodine intake is associated with an increase in the incidence of PTC.
Papillary carcinoma is the predominant histological type, followed by follicular carcinoma in both genders.
The majority of DTC cases were female 84.9%; the female-to-male ratio was 5.6:1, This is higher than what previously reported of 3.9:1.
There was a female predominance in almost all age groups as stated by many other studies. Dietary and environmental factors do not appear to have a role in thyroid cancer gender disparity. It has been hypothesized that menstrual and reproductive factors may account for this disparity. However, based on clinical and epidemiological studies, there is no conclusive association between menstrual, reproductive, or hormonal history with thyroid cancer risk. Recent studies suggest estrogen and estrogen hormone receptors' status in thyroid cancer cells may have a role in the thyroid cancer progression.
The average age of our patients was (45.5 ± 15.6 years). Younger patients were reported in Yemen and Saudi Arabia.,,
The occurrence of thyroid cancer increases with age, plateauing after about age 50.
The mean ages for both genders are higher than those reported in the previous study; (51.2 vs. 40.8) for males and (44.6 vs. 42.6) for females.
A study from Saudi Arabia noticed a decrease of age at presentation compared to the previous reports and attributed that to an early detection of cases, better health awareness, or true change in the pattern of the disease with a younger age of onset compared to the past.
History of MNG in our study was documented in 43 (16.2%); studies have demonstrated the incidence of thyroid cancer varies from 7% to 17% in MNG.,
Papillary carcinoma is the predominant malignancy in MNG goiter. In this study, papillary carcinoma was the most common thyroid malignancy, seen in (88.3%) of those with MNG; this is consistent with data from various studies.,,,
Three (1.1%) patients had a history of Hashimoto's thyroiditis; all were PTC, with no nodal or distal metastasis.
The association between Hashimoto's thyroiditis and PTC has been reported by many studies.
Patients with PTC and Hashimoto's thyroiditis undergo a better prognosis, with a tendency toward a smaller sized tumor, less lymph node involvement, and longer survival rates, which might be explained by an early discovery since most Hashimoto's thyroiditis' patients receive frequent medical checkups for their hypothyroidism.
The prevalence of cervical lymph node metastasis in the present study was 17.0%, this is lower than the 24.5% reported rate in the previous study.
The frequency of individuals diagnosed with DTC presenting initially with distant metastatic disease ranges from 1% to 9%.,
The prevalence of distant metastases in the present study was 10.2%; this is almost similar to the previously reported rate of 9.1%.
As reported elsewhere, our study showed that patients 45 years and older had significantly higher rates of cervical and distal metastasis.,, The age cutoff of 45 years is traditionally used in the current DTC staging guideline.
Strengths and limitations of this study
The enrolled patients were referred from all over the country. Our data, therefore, is likely to be reflective of the overall general population. The limitations of our study include its retrospective nature, and not all data were available for all patients. Data on tumor stage, the risk factor profile of patients, and thyroglobulin and anti-thyroglobulin antibody values were missing in most files. The development of multidisciplinary team meetings can improve the quality of care of DTC patients.
| Conclusions|| |
Our study has presented an overview of the clinicopathological features of DTC at the Nuclear Medicine Department-TMC, which is the only referral center for RAI therapy in Libya. PTC was the most common type of DTC. There was a female predominance in various types of DTC. This pattern is consistent with the results of other studies.
Compared with previous data, the current study showed an increase in the ratio of papillary DTC to follicular DTC and an increase in female-to-male ratio.
The disease tends to appear at an older age and with less cervical lymph node metastases than previously reported.
A national tumor registry is required to assess the epidemiological feature on a national level and identify trends in its incidence at different geographic locations.
The authors would like to thank Dr. Ebtisam abukra and Dr. Swhare El-quide for their help in collecting the data.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Katoh H, Yamashita K, Enomoto T, Watanabe M. Classification and general considerations of thyroid cancer. Ann Clin Pathol 2015;3:1045.
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin 2016;66:7-30.
Curado MP, Edwards B, Shin HR, Storm H, Ferlay J, Heanue M, et al
. IARC Scientifi c Publications: Cancer Incidence in Five Continents. IARC Publication No. 160. Lyon:IARC; 2007.
Bard D, Verger P, Hubert P. Chernobyl, 10 years after: Health consequences. Epidemiol Rev 1997;19:187-204.
Choi WJ, Kim J. Dietary factors and the risk of thyroid cancer: A review. Clin Nutr Res 2014;3:75-88.
Lee JH, Lee ES, Kim YS. Clinicopathologic significance of BRAF V600E mutation in papillary carcinomas of the thyroid: A meta-analysis. Cancer 2007;110:38-46.
Leenhardt L, Bernier MO, Boin-Pineau MH, Conte Devolx B, Maréchaud R, Niccoli-Sire P, et al.
Advances in diagnostic practices affect thyroid cancer incidence in France. Eur J Endocrinol 2004;150:133-9.
Chen AY, Jemal A, Ward EM. Increasing incidence of differentiated thyroid cancer in the United States, 1988-2005. Cancer 2009;115:3801-7.
Marcello MA, Cunha LL, Batista FA, Ward LS. Obesity and thyroid cancer. Endocr Relat Cancer 2014;21:T255-71.
Gonzalez-Gonzalez R, Bologna-Molina R, Carreon-Burciaga RG, Gómezpalacio-Gastelum M, Molina-Frechero N, Salazar-Rodríguez S, et al.
Papillary thyroid carcinoma: Differential diagnosis and prognostic values of its different variants: Review of the literature. ISRN Oncol 2011;2011:915925.
Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, et al.
2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: The American Thyroid Association guidelines task force on thyroid nodules and differentiated thyroid cancer. Thyroid 2016;26:1-33.
Sawka AM, Thephamongkhol K, Brouwers M, Thabane L, Browman G, Gerstein HC, et al.
Clinical review 170: A systematic review and metaanalysis of the effectiveness of radioactive iodine remnant ablation for well-differentiated thyroid cancer. J Clin Endocrinol Metab 2004;89:3668-76.
Rebai A, Rebaï M, Kallel I, Hamza F, Charfeddine S, Kaffel R, et al
. Retrospective study of a cohort of Tunisian patients with thyroid cancer. Int J Transl Community Dis 2016;4:79-84.
Zuberi LM, Yawar A, Islam N, Jabbar A. Clinical presentation of thyroid cancer patients in Pakistan – AKUH experience. J Pak Med Assoc 2004;54:526-8.
Khan MA, Khan KH, Shah SA, Mir KA, Khattak M, Shahzad MF, et al.
Risk factors associated with thyroid carcinoma in North Pakistan. Asian Pac J Cancer Prev 2016;17:377-80.
Abdulmughni YA, Al-Hureibi MA, Al-Hureibi KA, Ghafoor MA, Al-Wadan AH, Al-Hureibi YA, et al.
Thyroid cancer in Yemen. Saudi Med J 2004;25:55-9.
Al-Jaradi M, Sallam A, Jabr H, Borda A, Decaussin-Petrucci M, Berger N, et al.
Prevalence of differentiated thyroid cancer in 810 cases of surgically treated goiter in Yemen. Ann Saudi Med 2005;25:394-7.
] [Full text]
Al-Amri A. Pattern of thyroid cancer in the eastern province of Saudi Arabia: University hospital experience. J Cancer Ther 2012;3:187-91.
Al-Qahtani KH, Tunio MA, Asiri MA, Bayoumi Y, Balbaid A, Aljohani NJ, et al.
Comparative clinicopathological and outcome analysis of differentiated thyroid cancer in Saudi patients aged below 60 years and above 60 years. Clin Interv Aging 2016;11:1169-74.
Shomaf MS, Younes NA, Albsoul NM, Musmar AA, Al-Zaheri MM, Tarawneh MS, et al.
New trends in the clinicopathological features of differentiated thyroid cancer in central Jordan. Saudi Med J 2006;27:185-90.
El-Shareif HJ. Thyroid cancer at Tripoli medical center. JMJ 2003;2:51-4.
Elhamel A, Sherif IH, Wassef SA. The pattern of thyroid disease in a closed community of 1-1/2 million people. Saudi Med J 1988;9:481-4.
Deandrea M, Gallone G, Veglio M, Balsamo A, Grassi A, Sapelli S, et al.
Thyroid cancer histotype changes as observed in a major general hospital in a 21-year period. J Endocrinol Invest 1997;20:52-8.
Bacher-Stier C, Riccabona G, Tötsch M, Kemmler G, Oberaigner W, Moncayo R, et al.
Incidence and clinical characteristics of thyroid carcinoma after iodine prophylaxis in an endemic goiter country. Thyroid 1997;7:733-41.
Frich L, Akslen LA, Glattre E. Increased risk of thyroid cancer among Norwegian women married to fishery workers – A retrospective cohort study. Br J Cancer 1997;76:385-9.
Rahbari R, Zhang L, Kebebew E. Thyroid cancer gender disparity. Future Oncol 2010;6:1771-9.
Alzahrani AS, Alomar H, Alzahrani N. Thyroid cancer in Saudi Arabia: A histopathological and outcome study. Int J Endocrinol 2017;2017:8423147.
Gandolfi PP, Frisina A, Raffa M, Renda F, Rocchetti O, Ruggeri C, et al.
The incidence of thyroid carcinoma in multinodular goiter: Retrospective analysis. Acta Biomed 2004;75:114-7.
Cole WH. Incidence of carcinoma of the thyroid in nodular goiter. Semin Surg Oncol 1991;7:61-3.
Benzarti S, Miled L, Bassoumi T, Ben Mrad B, Akkari K, Bacha O, et al
. Thyroid surgery (365 cases): The risks and complication. Rev Laryngol Otol Rhinol (Board) 2002;123:33-7.
Nadeem K, Akhtar N, Tarar JM. Thyroid malignancy in multi nodular goiter; incidence, a retrospective study in Southern Punjab. Prof Med J 2013;20:587-90.
Resende de Paiva C, Grønhøj C, Feldt-Rasmussen U, von Buchwald C. Association between Hashimoto's thyroiditis and thyroid cancer in 64,628 patients. Front Oncol 2017;7:53.
Huang BY, Hseuh C, Chao TC, Lin KJ, Lin JD. Well-differentiated thyroid carcinoma with concomitant Hashimoto's thyroiditis present with less aggressive clinical stage and low recurrence. Endocr Pathol 2011;22:144-9.
Sampson E, Brierley JD, Le LW, Rotstein L, Tsang RW. Clinical management and outcome of papillary and follicular (differentiated) thyroid cancer presenting with distant metastasis at diagnosis. Cancer 2007;110:1451-6.
[Table 1], [Table 2], [Table 3]