Trends in Thyroid Malignancies in Accra Ghana : A Retrospective Histopathological Review in the Department of Pathology ( 1994-2013 ) , Korle-Bu Teaching Hospital

Background: Malignancies of the thyroid gland are common in certain parts of the world. In Ghana there are no available data on the trends and gender characteristics of thyroid malignancies (TMs). The aim of this retrospective study was to determine the trends and gender characteristics of TMs in the Department of Pathology.


Introduction
Malignancies of the thyroid gland are relatively rare neoplasms worldwide, accounting for approximately 1-5% of all cancers in females and less than 2% in males [1].Emerging evidence across the globe have shown an association between iodine intake and thyroid malignancies [2,3].Ghana is among the world's top six countries with iodine deficiency [4,5] and hence the introduction of the national iodization program in 1996 [6][7][8][9].Similarly, ionizing radiation has historically been linked to thyroid cancer particularly papillary thyroid carcinoma [10,11].There is no published data implicating the atomic nuclear reactor in Ghana, nor any published literature reports that workers of the two radiotherapy centres in Ghana have developed thyroid cancers due to exposure to radiations.Published data on thyroid cancers in Ghana, particularly the incidence and trends, are limited compared to other African countries [12].The aim of this retrospective study was to determine the trends and gender characteristics of thyroid malignancies using data from the Department of Pathology, Korle-Bu Teaching Hospital (KBTH), Accra, Ghana.1994 to December 2013.This is the largest and oldest Pathology unit in the country which is also located in the biggest referral hospital in Ghana.
All the histologically confirmed thyroid malignancies from 1 st January 1994 to 31 st December 2013 in the department were reviewed.Congo red was employed to confirm three cases of medullary thyroid carcinomas that we had difficulty in arriving at the definitive diagnosis based of the H&E stains.Data were collected on: age at diagnosis, sex, nature and duration of the presenting complaint, type of surgical specimen and the histological subtypes of thyroid malignancies, as well as vascular invasion and lymph nodal involvement by malignant cells.Data were entered into a statistical data base (SPSS software version 23.0 Chicago).Descriptive statistics were computed for the ages (mean, range, standard deviation) of all patients included in the study.Results were presented as bar chart for all continuous variables, while pie charts were used for categorical variables.The proportions of thyroid specimens that contained malignancy and the spectrum were evaluated for each year.Annual trends in the relative proportions of thyroid malignancies over the period 1994-2013 was determined.Comparisons between the gender characteristics of thyroid malignancies were made using Fisher exact test.

Data Collection and Analysis
The eligibility criterion is thyroid malignancy only.

Inclusion Criteria Exclusion Criteria
All cases with incomplete records were excluded.

Figure 1: Types of surgical specimens in which thyroid malignancies were diagnosed
There was a gradual decline in the relative proportions of thyroid malignancies diagnosed in our institution over the 20-year period of study (Figure 2, and Table 1).For instance, within the first half (1994)(1995)(1996)(1997)(1998)(1999)(2000)(2001)(2002)(2003) of the review period, there was a relative rise of 0.22% in the relative proportions of TMs diagnosed in our institution, compared to a relative declined of 0.32% in the second part (2004-2013) of the study (Table 2).Papillary carcinomas (PTC) was the commonest TM 116 (52.7%) during the period of review (Table 3).Majority of the malignancies were commonly diagnosed in females 151 (68.6%;P<0.001), with female to male ratio of approximately 2:1.A total of 29 (13.2%) of the TMs showed vascular invasion.There were 36 (16.4%) patients who had positive lymph nodes at the time of histological diagnosis.The great majority had single nodal involvement (Figure 3).

Comparing the clinico-pathological characteristics of females and males with thyroid malignancies (TMs).
The ages of the 151 women diagnosed with TMs ranged from 10 to 88 years, with a mean age of 40.7 years (SD±16.7),compared to an age range of 11-78 years and a mean age of 43.0 years (SD±15.5)for the 69 males with the disease.The modal age group was 20-29 years for the females compared to 50-59 years for the males (Table 2).Approximately 51.0% of the females compared to 42.0% of the males were aged 40 years or younger (P=0.246)(Table 3).The common clinical presentation of TMs in both females and males was a palpable anterior neck swelling (96.1% versus 91.3%, P=0.200).Approximately 4.6% females and 8.7% males presented with metastatic disease at diagnosis (P=0.200)(Table 3).

Age Characteristics
Ninety-four (62.3%) females compared to 45 (65.2%) males had stated the duration of their symptoms at presentation (P=0.763).Approximately, 61 (64.9%) of the female and 23 (51.1%) of the males presented to a health facility with symptoms of thyroid malignancies several years after the onset of the disease (P=0.140)(Table 3).

Discussion
The current study found that 6.8% of all thyroid specimens received during the 20-year period of review were malignant.The incidence of TMs vary globally, according to the method of evaluation, the population studied, dietary iodine (iodine content) in the population studied and the effects of ionizing radiation on the thyroid (including side effects of radiotherapy) [10][11][12][13][14][15][16].For instance, clinically, the prevalence of thyroid malignancies is estimated to be approximately 2.5 cases per 1,000 patients [15].Similarly, the incidence of occult thyroid cancer (TC) reported in previous autopsy studies across the world [13,14] ranged from 0.01% in USA [11] to 35.6% in Finland [17].Again in surgically excised cold nodules, the frequency of TMs has been reported to range from 1.5-38%, much higher than those reported in clinical studies [15].The low incidence of thyroid malignancies in this current study however supports a previous study by Vanderlaan that reported that the low incidence rates of thyroid cancers in Africa [13].
There was a gradual decline in the relative proportions of TMs over the 20-year period of review.This differs from studies over the past 4 decades that reported a rising trend of the disease in both females and males [19,20].There are reports of a rapid rise between 1973-2002 in some European countries, the United States of America and some parts of China [18][19][20][21][22][23].However, the trend in the current study conducted in Accra, Ghana, is in keeping with studies in Sweden and Midwest of the United States of America that reported a decrease in the incidence rates of TMs in both males and females [20,24].
The commonest histological subtype of TM in this study was PTC.There is endemicity of iodine deficiency in Ghana, and the expectation was that FTC which is historically linked to iodine deficiency would have been the predominance TM in Ghana.It is difficult to attribute the predominant of PTC in this study to any known cause, but the fact that this study was conducted in the southern part of the country located along the coast where there is high intake of iodine rich sea foods may be suggestive.However, the current finding supports previous histological and clinical studies in Ghana [25,26] Nigeria [27] and other parts of Africa [28] that found PTC to be the predominant type of TM, but differs from some studies in other parts of West Africa [29][30][31][32] South Africa [33,34] and North Africa [35] that reported the commonest TM as FTC in iodine deficient regions of the world.
The majority of the malignancies were diagnosed in young females than their male counterparts with significant positive association (P<0.004).For an unknown reason, thyroid malignancies are commoner in females [32][33][34].The predominance of TMs in relatively younger females in this current study is thus in accordance with reports of previous reports on the gender characteristic of TMs in Africa [32][33][34][35][36][37].
In this current study, patients with TMs commonly presented with palpable neck swellings of long duration associated with distant spread, suggestive of a neglected disease.For instance 4.6% females and 8.7% males presented with metastatic disease such as bone pain, pathological fractures and brain involvements.The clinicopathological features of patients with confirmed diagnosis of TMs in this review study are similar to those of studies that found patients with TCs to present with nodular neck swelling [38][39][40].The duration at diagnosis of thyroid malignancies in this study ranged from months to more than 20-years.However, many of the patients presented within 1 year of noticing the swelling (22.3%).There are no documented reasons for the late presentation of thyroid cancer in Ghana.This may be related to ignorance, but also the relatively expensive cost of medical care, which in most instances is borne directly by the patient, and thus thyroid nodules and goiters are often left uninvestigated until they become symptomatic (i.e., patients either develop obstructive symptoms, or develop hyperfunction ), enlarge rapidly, or cause considerable cosmetic disfigurement.This is compounded by the misconception among some health care professionals that multinodular goiters are caused by iodine insufficiency and usually remain benign, and are therefore incapable of neoplastic transformation.

Conclusion
The current study found a decline in the relative proportions of TMs over the period of review.TMs were common in young females compared to their male counterparts.A significant number of the study population had metastatic disease at diagnosis.

Ethical Clearance
We had permission to gather and publish (participate) by the Head of Department of pathology, School of Biomedical Sciences, College of Health Sciences, University of Ghana, Legon.This is so for it was retrospective study.

Table 1 :
Thyroid malignancies diagnosed during the period 1994-2013 in the department Figure 2: Trends in relative proportions of thyroid malignancies diagnosed from 1994-2013

Table 3 :
Clinicopathological features of thyroid malignancies diagnosed in males and females