Spectrum of pediatric tumors diagnosed by fine-needle aspiration cytology

Abstract

Pediatric tumors differ markedly from adult tumors in their nature, distribution, and prognosis. In this 10-year retrospective study, we present our experience with fine-needle aspiration (FNA) in pediatric patients 18 years of age and younger and correlate relationship between gender with organ, diagnosis, malignancy, and age. In our study, FNA material of pediatric tumors or masses with 18 years aged and younger were analyzed retrospectively.

All FNAs in pediatric patients during this time period were identified and analyzed for age, gender, cytologic diagnosis, and site of aspiration. A total 1000 FNAs were performed from January 2007 to October 2015 in 499 children. Regardless the gender, the most frequently aspirated organ was lymph node, comprising 129 of the 499 cases followed by thyroid (112), neck cyst (79), and parotid (35) cases. The majority of the cases were diagnosed as benign lesions (436 of 499 cases). Other 63 cases comprising 40 female and 23 male cases had malignant lesions. There was significant age difference between people with or without malignancy. In malignant cases, there was a significant difference between the age on males and females. In regard to gender and diagnosis, cytologic diagnosis was stratified into 9 broad diagnostic categories: lymphadenitis, benign and malignant thyroid, cyst contents, benign breast, benign and malignant salivary, and negative for malignancy.

In conclusion, our study supports the use of FNA cytology (FNAC) in lesions of various anatomic sites in the children less than 18 years old. As a simple, minimally invasive, and rapid procedure, cytopathologists can reliably utilize FNAC in children. The mean age of children receiving a malignant diagnosis was significantly higher than that of benign lesions. The mean age of malignancy in boys is significantly lower than that of girls with malignancy.

1. Introduction

Pediatric tumors differ markedly from adult tumors in their nature, distribution, and prognosis.^[1] Pediatric patients represent a unique study population with regard to spectrum and frequency of disease. Although only 2% of all malignant tumors occur in infancy and childhood, cancer is the leading disease related cause of death among children in the world.^[2] Fine-needle aspiration cytology (FNAC) of the tumors is well accepted as a diagnostic procedure in the adult population. FNAC has been recently recommended as a technique for accurate evaluation and diagnosis of childhood.^[3–6] It has been shown to be a safe, with minimal trauma, and cost-effective diagnostic method that notably typically lacks the need for sedation or general anesthesia in compared to surgical biopsy.^[1] Despite these reported benefits, FNA as a diagnostic tool is still far less universally accepted in pediatric patients than in adults.^[7] To our knowledge there is only 1 report analyzing all FNAs, both benign and malignant, performed at a large medical center in children 12 years of age and younger.^[7]

Previous publications have more narrowly focused on FNA of specific anatomic sites or of particular disease entities. In this 10-year retrospective study, we present our experience with FNA in pediatric patients 18 years of age and younger and correlate relationship between gender with organ, diagnosis, malignancy, and age. Additionally, the diversity of lesions that can occur in the pediatric patients was investigated.

2. Materials and methods

Computer-generated searches were performed in the archives of the Pathology Departments of Dr Daneshbod Lab during the period January 2007 to October 2015. In our study, FNA material of pediatric tumors or masses with 18 years aged and younger were analyzed retrospectively.

All FNAs in pediatric patients during this time period were identified and analyzed for age, gender, cytologic diagnosis, and site of aspiration.

Aspirations were performed by cytopathologists using 25- or 27-gauge needles. The aspirated material was expelled onto glass slides and smeared. The smears were fixed immediately in 95% ethanol and stained by the Papanicolaou method or air-dried and stained with modified Giemsa. Cytologic diagnosis was classified into different diagnostic categories.

Nondiagnostic specimens were considered technically unfeasible (i.e., technical failures), the patients with recurrent lesions, and they were lost to follow-up were excluded from the study.

2.1. Statistical analysis

Data management was done by using the Statistical Package for Social Sciences (SPSS version 22). Descriptive statistics were used to gender, organ, diagnosis, and malignancy frequencies, age histogram and analysis of these frequencies with gender. Age difference between malignant/benign cases and sex difference between malignant/benign cases were analyzed by using t tests, and Chi-square, respectively.

2.2. Ethics statement

The Ethics Committee and the authors’ institutional review board of Shiraz Molecular Pathology Research Center (Shiraz, Iran) approved the study. The author group collected written informed consent from all the patients.

3. Results

A total 1000 FNAs were performed from January 2007 to October 2015 in 499 children who ranged in age from 4 months to 18 years (mean, 11.51 ± 5.41 years). Out of the patients 268 (53.7%) cases were female and 231 (46.3%) were male. The mean age of male and female patients was 9.72 ± 5.47 and 13.06 ± 4.86 years (Fig. 1A and B). The patients were classified in 4 age groups; 0 to 5 (76 cases, 15.2%), 5 to 10 (102 cases, 20.4%), 10 to 15 (129 cases, 25.9%), and 15 to 18 (192 cases, 38.5%) years old (Table 1).

Figure 1.

(A and B) Age histogram in male and female patients, (C) age histogram in malignant diagnoses.

Table 1.

Incidence rates for cancers and benign lesions in regard to age and cytologic diagnosis.

Regardless the gender, the most frequently aspirated organ was lymph node, comprising 129 of the 499 cases (25.9%) followed by thyroid including 112 cases (22.4%), neck cyst including 79 cases (15.8%) and parotid including 35 cases (7.0%) (Fig. 2A). Lymph nodes and thyroid were most frequently aspirated organs in male and female patients, respectively.

Figure 2.

(A) Organ frequency regardless to the gender. The most frequently aspirated organ was lymph node followed by thyroid including neck cyst and parotid cases. (B) Organ frequency in male and female patients.

Cytologic diagnosis was stratified into 9 broad diagnostic categories: lymphadenitis, benign and malignant thyroid, cyst contents, benign breast, benign and malignant salivary, and negative for malignancy (Table 2 ) (Fig. 3A). Lymphadenitis and benign thyroid were frequently detected in male and female patients, respectively (Fig. 3B).

Table 2.

Nine broad diagnostic categories was made by FNAC diagnosis.

Figure 3.

(A) Cytologic diagnosis was stratified into 9 broad diagnostic categories regardless to gender. (B) Lymphadenitis and benign thyroid were frequently detected in male and female patients, respectively.

Table 2 (Continued).

Nine broad diagnostic categories was made by FNAC diagnosis.

The majority of the cases were diagnosed as benign lesions (436 of 499 cases, 87.37%). Other 63 cases comprising 40 female and 23 male cases had malignant lesions. There was no significant sex difference between people with or without malignancy (P > 0.05). Organ frequency in malignant cases is shown in Fig. 4.

Figure 4.

Site or location frequency in malignant cases. Thyroid and lymph node were dominant malignant organ in girls and boys, respectively.

Regardless the gender, the mean age of children receiving a benign diagnosis was 11.26 ± 5.41 years, while the mean age for malignant diagnoses was 13.20 ± 5.14 years. There was significant age difference between people with or without malignancy (P < 0.01). The highest malignant cases were found in children with over 15 years old (Fig. 1C).

In regard to gender, the mean age of malignancy in male and female patients was 10.81 ± 5.60 and 14.56 ± 4.37 years, respectively. In malignant cases, there was a significant difference between the age on males and females (P < 0.01).

4. Discussion

The primarily aim of this study was to consider our experience with FNA in pediatric patients 18 years of age and younger and correlate relationship between gender with organ, diagnosis, malignancy, and age. The utility of FNA in children has been illustrated in numerous studies.^[8–10] However, to our knowledge, there is no report detailing the application of FNA cytology to lesions of several anatomic sites in the pediatric population. The majority of our cases, children presented with persistently enlarged lymph nodes followed by thyroid and neck lesions. Since lymph nodes and thyroid were most frequently aspirated organs in male and female patients in this study, lymphadenitis and benign thyroid were frequently detected in male and female patients, respectively. Pediatric head and neck lesions are common, and as illustrated in this series most represent reactive lymphoid proliferations. In the most of cases, children present with persistently enlarged lymph nodes after a trial course of antibiotics.^[11] Thyroid nodules < 1 cm are rarely biopsied unless or more suspicious ultrasound criteria are found, or if there is a concerning clinical history, including previous neck irradiation, previously diagnosed thyroid cancer or an increased calcitonin level.^[12]

The patients were classified in 4 age groups and the average age-specific incidence rates for each of the 4 calendar periods of observation show dissimilar and much higher cancer rates for the oldest (15–19 years of age) age groups than the youngest (0–5) and 2 intermediary age (5–10 and 10–15) groups. Regardless the gender, the mean age of children receiving a benign and malignant diagnosis was 11.26 ± 5.41 and 13.20 ± 5.14 years, respectively. There was significant age difference between people with or without malignancy. The highest malignant cases were found in children with over 15 years old. The most malignant cases of our patients were lymphoma and thyroid cancer. The most common cancer in children ages 0 to 14 are acute lymphocytic leukemia, brain and central nervous system, neuroblastoma, and non-Hodgkin lymphoma, hence, the most common cancers among adolescents ages 15 to 19 are Hodgkin lymphoma, thyroid carcinoma, and lymphoma.^[13] Since most of our patients were diagnosed as thyroid cancer (Table 1), the highest malignancies were detected in children over 15 years old. In regard to gender, the mean age of malignancy in male was lower than that of female patients (10.81 ± 5.60 years vs 14.56 ± 4.37 years). There was a significant difference between the age on boys and girls with malignancies. Some of these differences may reflect the different types of cancers that occur in male compared to female in this age group.^[14] For example, boys have somewhat higher rates of Hodgkin lymphoma for children younger than 15 years of age, but girls have higher rates for adolescents, 15 to 19 years of age.^[15]

In the present study the majority of cases were identified with benign lesions. The male-to-female ratio was 1:1 in patients with benign nodule versus 1:1.7 among those with malignancies. Although, for all sites combined, malignancy rate was generally higher for females (40 cases) than male (23 cases) during the 10-year period, there was no significant sex difference between people with or without malignancy.

Both thyroid nodules and cancer were detected in 19 (95 of 499) and 28.5 (18 of 63) percent of our patients. We found higher incidence of thyroid cancer than that of benign thyroid lesions by using FNA and all thyroid cancer were detected in girls. Unlike our results, it has been shown that odds of malignancy is 4.2 times higher for men versus women.^[16] Both thyroid nodules and cancer are less common in children than adults, but the risk of malignancy in thyroid nodules is much higher in children.^[17] It has been demonstrated that FNA cytology valuable tool to discriminate benign from malignant nodules in pediatric patients.^[18]

Hypocellularity, degenerated tumor cells, necrosis, and epithelial hyperplasia are some of the factors that may be encountered in evaluating a difficult smear, mimicking atypical or malignant lesions. The false-negative cases in FNAC, although few, are commonly due to poor tumor localization, poor sampling technique, and the presence of a well-differentiated histology of the tumor. Small tumor size and nonpalpable masses lesions are also commonly associated with false-negative and aspirate inadequacy. FNA for head and neck masses has also several limitations. Failure to establish an accurate diagnosis may be because of sampling error. In these circumstances, repeat aspiration is suggested, and excisional biopsy may be considered.^[19] This study has focused on spectrum of FNA in pediatrics. There are many papers on accuracy, sensitivity, and specificity which already confirmed FNA as useful.^[20–23]

In conclusion, our study supports the use of FNAC in lesions of various anatomic sites in the children less than 18 years old. As a simple, minimally invasive, and rapid procedure, cytopathologists can reliably utilize FNAC in children. Regardless the gender, the mean age of children receiving a malignant diagnosis was significantly higher than that of benign lesions.

The mean age of children receiving a malignant diagnosis was significantly higher than that of benign lesions. The mean age of malignancy in boys is significantly lower than that of girls with malignancy and the malignancy mostly occurs in the children over 15 years old.

Acknowledgment

The authors would like also to thank Dr K. Daneshbod and Shahrekord University for their help.