Clinicopathological profile of Papillary thyroid carcinoma in a tertiary cancer hospital in Nepal

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Introduction
The incidence of differentiated thyroid cancers (DTC) is steadily increasing, primarily comprised of papillary thyroid carcinomas (PTC), along with follicular and Hurthle variants. 1Thyroid cancers constitute around 10% of head and neck cancers in Nepal. 2 Despite salt iodization efforts, the Correspondence: Dr. Samyam Parajuli, Head and Neck Unit, Dept of Surgical Oncology, B.P. Koirala Memorial Cancer Hospital, Bharatpur, Nepal.E-mail: samparajuli34@gmail.com, Phone: +977-9808582076 surge in thyroid cancers remains partially unexplained, showing distinct patterns among genders, ages with higher rates among younger women. 3,4C are discovered on routine examination as a asymptomatic neck mass. 5A study in 2002 noted a 2.4-fold rise in thyroid cancer incidence from 1973 to 2002, mainly the tumors ≤1 cm, actually attributed to improved detection by imaging. 6Guidelines from the American Thyroid Association (ATA) suggest tailored surgeries, however depending on disease characteristics and patient preferences, the treatment team may opt for total thyroidectomy to facilitate Radio Iodine Ablation (RIA) therapy or to enhance follow-up. 7sed on the 2004 World Health Organization classification, aside from the most prevalent classic PTC type, there exist 15 other subtypes some of which are highly aggressive such as tall cell variant conferring risk of mortality. 8PTC generally shows a favorable prognosis, but specific factors like age, metastasis, and tumor size influence outcomes and disease severity assessment. 9,10,11The clinical difficulty lies in promptly distinguishing patients who require aggressive treatment from those with a slowdeveloping course. 12 conducting this study, we can identify any unique characteristics of PTC in the Nepalese population, such as age-specific incidence, gender distribution, stage at diagnosis, presence of metastasis which will enhance our understanding of the disease's characteristics and contribute to the advancement of clinical practice.

Methods
This study was a retrospective cross-sectional analysis held at the

Results
The study consisted of 105 patients diagnosed with Papillary thyroid carcinoma.Regarding patient demographics, the maleto-female ratio was found to be 1:5.2 in our study.Analysis of patient ethnicities revealed the majority of the patients (29) to be Chettri (27.6%).In order of decreasing frequencies other ethnicities included Brahmins (16.2%),Madhesis (14.3%) and Magars (12.4%).Newars, Dalits and Tharus were 7.6% each followed by Gurungs (6.7%).The majority of patients in our study were from Pradesh 5 (Lumbini Pradesh) which comprised 28.5%.
The mean age of patients was 40.78±13.04years (range: 9-72) and specifically the mean age of female patients was 40.22 years.There were 88 female and 17 male patients in our study.(Table 1) Histopathological variants of PTC showed the classical type to be most prevalent (78.1%).(Table 3) *Chi-square test The average tumor size was 2.74±1.39,with a range of 0.7 cm to 8 cm.There was a dominance of lesions falling within the T2 range (57.1%).(Table 5)  7).Among the overall patients, Radioactive iodine ablation was received by 32 (30.5%) patients.

Discussion
This study gives insight into various aspects of patient demographics, tumor characteristics, treatment modalities, and prognostic markers, contributing to a deeper understanding of PTC within our patient population.In our study, the gender distribution revealed a male-to-female ratio of 1:5.17, which closely resembled the findings of Rao et al, who reported a ratio of 1:5. 13 Correspondingly, other studies conducted by Carcangiu et al and Heitz et al unveiled ratios of 1:2.6 and 1:3.1, respectively. 14,15on categorizing patients based on their ethnic backgrounds, the majority belonged to the Chettri community (27.6%), followed by Brahmins (16.2%),Madhesis (14.3%) and Magars (12.4%) respectively.Geographical diversity seemed to play a role, with a concentration of patients hailing from the western region of Nepal, particularly Lumbini Pradesh (Pradesh 5) which constituted 28.6%.This phenomenon might be correlated with inadequate iodine consumption, a known factor linked to an increased risk of thyroid cancer. 16e mean age of our patient cohort stood at 40.78 years (range: 9-72), closely paralleling the Italian study's mean age of 41.3 14 .Among female patients, the mean age was 40.22 years, akin to the findings by Joshi et al 17 , whereas another study by Dorairajan reported a lower mean age of 32 years among females. 18The potential contribution of hormonal and reproductive factors in females to the development of this malignancy, as indicated by previous research, might offer insights into the higher prevalence of thyroid carcinoma in females. 19,20,21The peak incidence of PTC was observed in the 4th to 6th decade of life, mirroring the findings of Catana et al 22  The diagnostic role of fine-needle aspiration cytology (FNAC) in precise and timely management strategies for thyroid cancers was underscored.Most tumors were classified as Bethesda VI (61%), followed by types V (26.6%) and IV (12.5%), aligning well with the study by Sarita et al, where Bethesda VI accounted for 57.6% of cases. 23 the context of treatment, our study revealed that 76.25% of patients underwent total thyroidectomy with or without neck dissection, whereas 14.28% underwent hemithyroidectomy.This trend deviated from the study by Joshi et al, where 64.29% of patients underwent total thyroidectomy. 17he study conducted by Doraijan et al had more patients in the TT group that is 82.24%, however hemithyroidectomy (17.75%) was similar to our study. 18The preference for total thyroidectomy in this study potentially stems from its association with improved outcomes since conservative surgery gave rise to a high rate of recurrence which adversely affectes survival.
Numerous histopathological variants of PTC with distinct prognostic significance were identified.The classical variant (CVPTC) was the most prevalent (78%), followed by the follicular variant (14.3%) and the micropapillary variant (PMC) (7.6%).These prevalence proportions mirrored those of the study by Karkuzhali et al, where CVPTC accounted for 68.7%. 24The study also had one case of tall cell variant which was absent in ours however, a unique instance of PTC and minimally invasive follicular carcinoma coexistence was noted in our study, which was seen in a 72 years female with multifocal T2 lesion echoing a similar finding by Plauche et al. 25 Incidence of PMC in our research was higher compared to an Indian study 13 , yet notably lower than the study conducted by Roti et al., which reported an incidence of 28.8%. 26This variance could potentially be explained by the broader recognition of PMCs, facilitated by enhanced diagnosis through highresolution ultrasounds.
Concerning tumor localization, most tumors were situated in the right lobe (55.25%), followed by the left lobe (35.25%), and a smaller proportion in bilateral locations (9.5%).This was similar to the study conducted by Joshi et al wherein 52.85% had disease in the right lobe. 17ltifocality was noted in 25.72% of tumors, in par to Feng's study in which multifocality was seen in 24.7%. 27Multicentricity is a marker of worse prognosis and a study showed that it had higher propensity for nodal and distant metastasis. 14In our study multifocality was seen in 11 male patients that was significantly high in comparison to the females (p<0.0001).(Table4) This was in par with the study by Karkuzhali et al 24 , which showed that there was association between centricity of tumors and gender, however study by Kawaura M et al showed that there was no correlation. 28There was also a significant relation between multifocality and central node metastasis in our study as in a study by Al Atif et al. 29 (Table 6) Histopathologically, the average tumor size was 2.74±1.39,ranging from 0.7 cm to 8 cm, like a study in India wherein majority of tumours fell in the T2 category. 30C demonstrate a tendency for lymphatic spread and the occurrence of nodal metastasis in patients with PTC ranges from approximately 20 to 50 %.31 32,33 Risk stratification revealed the majority of patients falling into the intermediate-risk category (53.5%), followed by low-risk (40%) and high-risk (6.5%).This distribution diverged from a Nepalese study, where lowrisk patients dominated at 62.85%, potentially accounting for the greater proportion of total thyroidectomy and radioiodine therapy in our study (30.5%) compared to that study.17 Risk stratification's role in treatment planning and management strategy was underscored, emphasizing the potential need for adjuvant therapy.
The study bears several limitations, primarily stemming from its retrospective nature, potentially introducing biases due to data availability and collection.Being conducted at a single center, the findings might not be universally applicable.The sample size is relatively small, which could limit the representation of broader trends.Long-term impacts and extended follow-up data aren't explored.Lastly, the absence of a control group limits the ability to make comparative assessments.

Conclusion
In conclusion, our study provides a detailed insight into the characteristics and trends of PTC within Nepal's tertiary cancer hospital.Females were predominantly affected, and the Chettri and Brahmin communities were prominently represented.FNAC emerged as a vital diagnostic tool, and total thyroidectomy was the preferred treatment.
Classical PTC was the most common histopathological variant.Tumor features like laterality, size, and multifocality were assessed, revealing noteworthy correlations.The intermediate-risk group dominated risk stratification.These findings offer crucial guidance for tailored patient care, leading to improved treatment strategies and better outcomes.

Table 6 )
As per the American Joint Commission of Cancer, Tumor Node Metastasis (AJCC TNM) Staging, majority of patients that is 93, were Stage I (88.5%).Stage II had 7.5% followed by Stage III (3%) and Stage IVB (1%) which was the least and consisted of a patient with bilateral lung metastasis.

Table 6 :
Tumour Focality and Central node status *Chi-square test On risk stratification, the majority of the patients fell in the Intermediate risk group (53.5%) (Table

Table 7 . Risk stratification in PTC (n=105)
, substantiating the significance of patient age in prognosis.