Evaluation of Biopsy Results, Consultations, and Follow-Ups in Pediatric Dermatopathology.

OBJECTIVE: Since skin diseases may show atypical presentation in children, histopathological evaluation plays a more critical role. The aim of this study is to determine the diagnoses that are finalized after the histopathological evaluation, which departments are frequently consulted, and the methods of follow-up in pediatric dermatology.
MATERIALS AND METHODS: This cross-sectional study was conducted on pediatric and adolescent patients whose biopsy was taken after evaluation in the pediatric dermatology outpatient clinic for 42 months.
RESULTS: Of the pediatric patients whose histopathological evaluation was made, 16.7% were consulted to other departments and 70.8% were followed up in the pediatric dermatology clinic with different methods. According to the histopathological evaluation results, 91.9% of the lesions were benign, 5.6% were premalignant, and only 1.5% were malignant. Three patients (1.5%) with malignant lesions in our pediatric dermatology clinic were followed up with pediatric dermatology and pediatric hematology. In comparison, premalignant lesions of 3 patients were excised in pediatric dermatology surgery; 6 patients were excised in plastic surgery, 1 patient in pediatric surgery, and 1 patient in ophthalmology.
CONCLUSION: Pediatric dermatology is a department that should have pediatric dermatopathology and pediatric dermatosurgery units in itself. It is crucial to be in the teamwork for consultations and follow-ups after histopathological examinations.

In previous studies, clinical correlation with histopathological evaluations was investigated.

How the histopathological evaluations performed on pediatric patients were concluded, how they were followed up, and which departments they were consulted frequently were evaluated, and the importance of multidisciplinary work was emphasized.

Introduction

Skin biopsy (SB) is planned by dermatologists when the clinical examination is insufficient to diagnose or when an adequate response to treatment is not considered. Skin biopsy is considered a reliable method because even the most classic skin disorders can be observed differently in childhood and adolescence by dietary habits, socioeconomic status, climatic exposure, and external environment.[1]

While evaluating the results of SBs taken from children and adolescents, consultations with patients who have difficulties in diagnosis continued to be a necessary tool for accurate diagnosis and appropriate further management among doctors. In addition, the results of SBs taken from the pediatric age group are frequently consulted with other departments to clarify the diagnosis, determine the treatment method, and follow-up of pediatric patients. Pediatric skin diseases are diseases with a broad spectrum that teamwork should evaluate.

Until today, prevalence studies of diseases frequently seen in children in pediatric dermatology (PD)[2] and clinical and pathological correlation studies of SB results in PD were conducted.[3] However, in practice that was seen the PD clinic is only performed with general pediatricians, pediatric dermatologists, pathologists.

Our primary aim in this study is to evaluate the SB results from PD patients, determine the departments that are frequently consulted in line with the SB results, determine the methods that are important for the follow-ups of PD patients, and emphasize the importance of teamwork in pediatric skin diseases. Our secondary aim is to evaluate all our data regarding both sex and age.

Materials and Methods

Study Design and Subjects

It is a cross-sectional study conducted on pediatric and adolescent patients aged 16 years and younger between January 2018 and June 2021. After 7725 pediatric patients were evaluated in the PD outpatient clinic, SBs were taken from 195 pediatric patients, and the histopathological and clinical diagnosis was clarified.

Ethics committee approval was received from Tertiary Hospital Scientific Research and Publication Ethics Board (diary number: 2758, date: March 05, 2021), and the study was carried out in accordance with the principles of the Declaration of Helsinki. Furthermore, the informed content form was obtained from patients or/and their parents who agreed to participate in the study.

Pediatric and adolescent patients whose biopsy results were evaluated both histopathologically and clinically, whose diagnosis was clarified, all necessary consultations were completed, and who were followed up regularly were included in the study.

Demographic and Clinical Data

Demographic data (patients age at biopsy, sex (girl and boy), age group (toddler, preschool, schoolgoing, adolescent), and clinical data (duration, localization, region (head, trunk, upper extremities, lower extremities, and genital)) and the number of skin lesions, treatment (topical, systemic, surgery, cryotherapy, phototherapy, and laser therapy), consultations (general pediatric, pediatric hematology, pediatric rheumatology, pediatric neurology, pediatric allergy, pediatric surgery, pediatric ophthalmology, pediatric otorhinolaryngology pediatric orthopedic surgery, and pediatric plastic surgery), and follow-ups (no follow-up, clinical follow-up, follow-up with dermoscopy, follow-up with laboratory, follow-up with re-histopathology, and follow-up with radiography) were collected in separate forms for all patients.

Diagnostic Procedures

Pediatric patients underwent 3 types of biopsy: punch biopsy, excisional biopsy, and incisional biopsy. In line with the 3 prediagnoses of possible pediatric skin disease, the most appropriate biopsy method was selected from the most appropriate lesions of the children that lead to the diagnosis. Local anesthesia was applied to all pediatric patients before the SB. A punch biopsy takes the entire thickness of a piece of skin and is used for smaller lesions. In extensive lesions and to detect malignancy, excisional biopsy, in which layers of skin and fat were taken, was preferred, and the wound area was closed with sutures.

An incisional biopsy was preferred in extensive lesions in case when punch biopsy would be insufficient for malignancy detection, and the wound area was closed with a suture.

Histopathological Data

To analyze the entities of malignancy (malign, premalignant, and benign), the histopathological diagnosis was noted. In addition; the diseases of the 195 patients whose histopathological and clinical diagnoses were clarified were further divided into 11 disease groups as follows: tumor, cysts, and nevi, papulosquamous disease, infections, eczematous dermatoses, vascular diseases, connective tissue diseases, benign pigmentary lesions and pigmentary disorders, skin appendageal diseases, non-infectious vesiculobullous and vesiculopustular diseases, genodermatoses, and metabolic diseases of the skin.

Statistical Analysis

Analyses were performed using the Statistical Package for Social Sciences version 22.0 software (IBM Corp.; Armonk, NY, USA). Continuous variables were expressed in median, minimum, and maximum values. Conformity of continuous variables to normal distribution was tested with histogram and Q-Q plot test, and Mann–Whitney U test was used for comparisons. Categorical variables were expressed as frequency (n) and percentage (%) and compared with the Pearson chi-square test. P < .05 was accepted as the significance level.

Results

Demographic and Clinical Results

Histopathological and clinical diagnoses were clarified from 195 (2.5%) of 7725 pediatric patients examined in the PD outpatient clinic, and 105 (53.8%) of the patients whose biopsy was evaluated were boys. The mean age at biopsy was 12.5 ± 4.5 (range, 1-16). The duration of the lesions was 31.2 ± 47.7 months. The most common age group for biopsy was the adolescent group (56.4%). The least biopsy was taken in the toddler age group (5.1%).

The distribution of SB results of 195 patients included in pediatric dermatopathology evaluation according to disease groups is shown in Table 1. The most common histopathologically confirmed diagnoses are shown in Figure 1.

Table 1.

Distribution of Pediatric Skin Disease Groups

Spectrum of Disease	n (%)
Tumors, cysts, and nevi	55 (28.2)
Papulosquamous disease	36 (18.5)
Infections	18 (9.2)
Eczematous dermatoses	18 (9.2)
Vascular diseases	10 (5.1)
Connective tissue diseases	9 (4.6)
Non-infectious granulomas	9 (4.6)
Benign pigmentary lesions and pigmentary disorders	8 (4.1)
Skin appendageal diseases	7 (3.6)
Non-infectious vesiculobullous and vesiculopustular diseases	5(2.6)
Genodermatoses	2(1.0)
Metabolic diseases of the skin	1 (0.5)
Others	11 (5.6)

Figure 1.

Most common histopathologically confirmed diagnoses. *Diseases with two or fewer pediatric patients are not shown in the graph. When the histopathological reports of pediatric patients are examined, the most common diagnoses are verruca vulgaris (5.6%), lichen striatus (5.1%), atopic dermatitis (5.1%), spitz nevus (4,1%), and lichen nitidus (3.6%).

Body regions from which SB was taken were trunk (28.2%), head (26.7%), upper extremites (25.1%), and lower extremites(18.5%).

The most common SB type was punch biopsy (90.3%), followed by excisional biopsy (9.2%), and incisional biopsy (0.5%).

The most common treatments after SB results are topical treatment (36.0%), surgery (20.3%), systemic treatment (7.6%), cryotheraphy (2.5%), phototheraphy(1.0%), and laser treatment (0.5%).

Evaluation According to Sex in Pediatric Dermatopathology

The mean age at which biopsy was taken in boys was 12.1 ± 4.9; in girls, it was 13.0 ± 4.0 (P = .347). While the mean duration of the lesion was 29.3 ± 46.7 in boys, it was 33.4 ± 49.1 months in girls (P = .797).

After the histopathological evaluation, when interpreted according to the disease groups, “tumors, cysts, and nevi” and “papulosquamous diseases” are the most common in both girls and boys and are the first 2 diseases. In the third rank, “connective tissue diseases” in girls and “eczematous diseases” in boys were determined.

The most common SB result in girls was lichen striatus and atopic dermatitis in boys (P = .001). The most common localization in SB was the right arm in girls and scalp in boys (P = .015). The upper extremities were the most frequently biopsied body regions in girls and head in boys (P = .455).

Distribution of Entities of Malignancy in Lesions

According to the results of the histopathological evaluation, 91.9% of the lesions were benign, 5.6% were premalignant, and only 1.5% were malignant. Lesions evaluated as premalignant were distributed as spitz nevus (8 patients), reed nevus (1 patient), dysplastic nevus (1 patient), and bowenoid papulosis (1 patient), while lesions evaluated as malignant were mastocytosis (1 patient) and mycosis fungoides (2 patients). Although all 3 malignant lesions were seen in boys, there was no statistically significant difference between the groups (P = .227). While malignant lesions showed an equal distribution except for the schoolgoing age group, premalignant lesions mainly were observed in adolescents (7 patients) and schoolgoing (4 patients) age groups (P = .055)

Consultations and Follow-ups

Based on SB results, only 33 (16.9%) of 195 pediatric patients required consultation. The distribution of consultations after histopathologic evaluations is shown in Figure 2. Consultation with child and adolescent psychiatrists in girls and pediatric ophthalmologists in boys was statistically significant (P = .013). In addition, pediatric plastic surgery consultations and adolescent psychiatry consultations requested by a pediatric dermatologist in adolescents were statistically significantly higher than in other age groups (P = .028) (Figure 3).

Figure 2.

Distribution of consultations after histopathological evaluations. The most frequently consulted departments were plastic surgery (40.0%), pediatric rheumatology (13.3%), and child and adolescent psychiatry (10.0%), pediatric hematology (6.6%), and general pediatrics (6.6%).

Figure 3.

Distribution of consultations by age groups.

Among 195 patients, 57 patients (29.2%) were evaluated as need not to be treated and followed up after the biopsy result. Follow-up of 15 (7.7%) patients was terminated within 1 year, follow-up of 83 patients (42.6%) was between 1 and 3 years, while 40 (20.5%) patients had follow-up longer than 3 years.

In pediatric patients, follow-up was continued with clinical follow-up (42.6%), follow-up with laboratory (9.1%), and follow-up with dermoscopy (8.6%) (Table 2). Follow-ups according to age groups are shown in Figure 4.

Table 2.

Distribution of Follow-Ups

	Number of Pediatric Patients, n(%)
Clinical follow-up	84 (42.6)
Follow-up with dermoscopy	17(8.6)
Follow-up with rebiopsy	3 (1.5)
Follow-up with laboratory	18 (9.1)
Follow-up with radiography	1(0.5)

Figure 4.

Follow-ups according to age groups. In older age groups, follow-up with different methods was increasing, but no statistically significant difference was found between the groups (P = .841).

Consultations and Follow-Ups of Lesions According to the Presence of Malignancy

Three patients (1.5%) with malignant lesions were followed up in our PD clinic together with pediatric hematology. While our pediatric dermatosurgery unit excised the premalignant lesions of 3 patients, 6 patients were consulted to plastic surgery, 1 patient to pediatric surgery, and 1 patient to ophthalmology to evaluate the residual tissues and preserve the surgical margin after histopathological evaluation. While 156 patients (80.0%) with benign lesions are followed in our PD clinic, 6 patients (3.0%) to pediatric plastic surgery, 4 patients (2.0%) to pediatric rheumatology, 3 (patients 1.5%) to general pediatrics, 3 patients (1.5%) to child and adolescent psychiatry, 3 patients 1.5%) to pediatric hematology, 1 (0.5%) patient to pediatric allergy, 1 patient (0.5%) to pediatric otorhinolaryngosurgery, and 1(0.5%) patient to pediatric orthopedic surgery were consulted.

While 2(1.1%) of the pediatric patients with malignant lesions were followed with laboratory, 1 (0.5%) of them was followed for re-biopsy and 4 (2.2%) of the pediatric patients with premalignant lesions were followed up for dermoscopy.

While 54 (30.0%) patients with benign lesions did not need follow-up, 83(46.1%) patients were clinically followed up, 16 (8.8%) followed up with laboratory, 13 (7.2%) followed up with dermoscopy, 2 (1.1%) followed up with re-biopsy, and 1(0.5%) followed up with radiography (Table 3).

Table 3.

Follow-ups of Lesions According to the Presence of Malignancy

	Number of Lesions, n(%)
Malignant	Premalignant	Benign
No follow-up	-	-	54 (30.0)
Clinical follow-up	-	-	83 (46.1)
Follow-up with laboratory	2(1.1)	-	16 (8.8)
Follow-up with dermoscopy	-	4 (2.2)	13 (7.2)
Follow-up with rebiopsy	1 (0.5)	-	2 (1.1)
Follow-up with radiography	-	-	1 (0.5)

Discussion

Pediatric dermatology is a subspecialty where specific points must be known to evaluate and manage skin disorders in children.[4] In PD, histopathological evaluation is often preferred because of the atypical presentation of skin diseases. With an experienced pediatric pathologist and pediatric dermatologist, definitive diagnoses can be made in the PD sub-unit, and follow-up and consultations can be made according to the biopsy results.

While the incidence of pediatric SB was 1.7%-3.7% in the literatüre[4], we found it to be 2.5% in our study. While tumor, cyst, and nevus were the most common biopsy diagnoses in our study, papulosquamous diseases were observed most frequently in pediatric SB studies conducted in India and Turkey.[5,6] Our histopathological diagnosis was almost similar to the study in Switzerland,[7] but according to the study conducted in our country, our pediatric SB incidence is higher, and our most common diseases are different. In our PD unit, dermoscopy and follow-ups are performed separately. Therefore, our pediatric patients with tumors, cysts, and nevi are more frequently biopsied to confirm our dermoscopic evaluation results.

Both clinically suspected and histopathologically clarified malignant lesions are rare in childhood. However, early diagnosis is much more critical. In their 24-month retrospective study, Theiler et al[7] reported that 2% of malignancies and spitz nevi were only 2% of premalignant lesions. This study found 1.5% malignancy and 5.6% premalignant lesions in a retrospective histopathological evaluation of 42 months.

In the pediatric age group, histopathological examination is performed to confirm the diagnosis of non-pigmented lesions and pigmented lesions. It is recommended to perform a biopsy from non-pigmented skin tumors to clarify the diagnosis and provide the most accurate treatment approach.[8] Nevus sebaceous, pilomatrixoma, and pyogenic granuloma were the most frequently detected benign skin tumors. Our results are consistent with the literature and incredibly similar to the study of Tükenmez et al.[8,9]

To our knowledge, this is the first study to explore the spectrum of pediatric skin conditions from which biopsy was taken. Afterward the pediatric cases were consulted in multiple pediatric-specific departments and being long-term follows-up in at tertiary hospital.

However, in the study by Akin et al.[10] the number of pediatric patients consulted after the clinical examination was 21.3%. However, in our study, the number of pediatric patients consulted according to the biopsy results obtained after the clinical evaluation was 16.9%.[10]

Consulting a plastic or pediatric surgeon to re-excise a biopsied lesion and consulting pediatric subspecialties when a chronic disease emerged as a biopsy were almost the results we expected. However, the fact that both plastic surgery and psychiatry were significantly higher in adolescents was one of the impressive results of our study.

The literature stated that psychiatry consultation was most frequently requested from adolescents, especially girls,[11-13] and in the study by Yılmaz et al.[12] dermatology was among the departments’ most frequently requested consultation. As stated in that study, psychiatric consultations may have been requested in adolescents after histopathological evaluation to detect chronic disease adjustment processes or possible psychiatric problems.

The literature published in 2017 is examined as long-term follow-up studies on pityriasis lichenoides,[14] alopecia areata,[15] infantile hemangiomas,[16,17] atopic dermatitis,[17] and congenital melanocytic nevus,[18] autoimmune blistering disease[19] in children. However, the method and duration of follow-up of children after the histopathological examination have not been investigated generally until now. It is also seen in our study that a more conservative approach was shown in children, and clinical follow-up was frequently performed.

Conclusion

Pediatric dermatology is a subfield that requires teamwork. In diagnoses that are clarified as a result of pediatric dermatopathological evaluations, many departments should be consulted for surgical procedures, multidisciplinary follow-up of chronic diseases, and the control of malignant or premalignant diseases. Therefore, it is necessary to use various follow-up methods skillfully and consciously for follow-ups in the PD unit.

Take-Home Messages

Pediatric skin diseases are among the skin disease groups that can be difficult to diagnose. Even a biopsy may not always provide a definitive diagnosis and the results may need to be consulted and evaluated as teamwork, and long-term follow-ups may be required.

Although we try to clarify our diagnoses clinically and histopathologically, pediatric skin lesions can change a lot over time. Therefore, studies designed this way should be presented with a follow-up period of much longer than 3 years with repeat biopsy results of pediatric patients during long-term follow-up.