Oral Squamous Cell Carcinoma in a 5-Year-Old Patient: A Rare Clinical Entity and Literature Review

Introduction

Oral Squamous Cell Carcinoma (OSCC) primarily affects people above 40 years of age and is extremely rare in pediatric patients (≤ 20 years) [1, 2]. Approximately 1 in 1000 cases of head and neck SCC will occur in patients 20 years or younger [3].

The risk factors and clinical behavior of this rare disease are poorly understood, due to limited number of reports of OSCC in pediatric patients [1]. Clinically, a growing swelling associated with teeth in a pediatric patient could mislead for a reactive lesion or an odontogenic tumor [1, 4]. This article presents a case of oral squamous cell carcinoma in a 5-year-old child.

Case Report

A 5-year-old male patient accompanied by his parents reported to the Oral and Maxillofacial Surgery department, MMCDSR, Mullana, with the chief complaint of swelling in his lower right back tooth region since 20 days. Being unaware of the disease, they visited local medical practitioner who had given the routine treatment for the swelling. Instead of responding to the respective treatment, the lesion progressed to the present status (Fig. 1). There was no associated significant medical or family history.

Fig. 1.

Clinical photograph showing lesion

Clinical Examination

The patient’s complete history was recorded, and clinical examination was carried out. No evident positive findings were seen extraorally. On intraoral examination, a diffuse and erythematous ulcerative lesion was seen, obliterating the vestibule and extending from distal to right side of deciduous canine to deciduous second molar with bucco-lingual extension measuring approximately 3 cm × 4 cm. Lesion was non-compressible, sessile and tender on palpation. Submandibular lymph nodes were palpable and non-tender. There were no neurosensory alterations on affected side. Mandibular deciduous second molars on both the sides were found grossly carious.

Radiographic Investigation

Orthopantomogram (OPG) revealed grossly carious 74 75 84 85 with root resorption seen in 84 85 and pathological migration with 46. No abnormal bony changes were seen in any part of the mandible on affected side (Fig. 2).

Fig. 2.

Panoramic radiographic image (OPG)

Treatment

The aggressive nature of the lesion and no evident bony changes derived us to go for excisional biopsy. Excisional biopsy was taken without damaging permanent tooth buds. Provisionally, the lesion was diagnosed as pyogenic granuloma; however, differential diagnosis was made for peripheral giant cell granuloma or lobular capillary hemangioma and rare suspicious squamous cell carcinoma. A complete specimen was sent for histopathological examination, on the basis of which it was diagnosed as “well-differentiated squamous cell carcinoma” (Figs. 3, 4). As the patient was very young, ablative surgery (radical neck dissection) for positive neck was the treatment of choice followed by either radiotherapy or chemotherapy. Considering the possible complications and age of the patient, he was referred to the higher center where surgical oncology is practiced routinely in pediatric age groups.

Fig. 3.

Excised lesion

Fig. 4.

×40, H&E-stained section showed hyper-chromatic malignant epithelial cells with large, centrally placed nucleus in an eosinophilic cytoplasm in the form of sheets and nests

Discussion

Oral squamous cell carcinoma in pediatric populations is rare, and this may present a diagnostic and therapeutic challenge [1]. The etiopathogenesis of OSCC in young individuals has long been debated. It has been proposed that tumorigenesis of OSCC is not dependent only on the type, duration and level of exposure to a specific carcinogen, but relatively on the genetic sensitivity of the individual. Genetic changes in a given individual are ascertained by two main parameters, the level of exposure to mutagenic factors and the inherent capability to efficiently repair DNA damage [5].

In contrast to the adult head and neck SCC (HNSCC) where the main etiologic/risk factors are smoking, alcohol consumption, use of tobacco, human papilloma virus (HPV), high risk factors in pediatric patients are seen in Fanconi’s anemia, Bloom’s syndrome, connexion mutations, xeroderma pigmentosa, dyskeratosis congenita, epidermolysis bullosa, Keratitis–ichthyosis–deafness (KID) syndrome, human papilloma virus infection and transplant recipient’s with chronic graft versus host reaction or unidentified genetic risk factor [2, 3].

OSCC among the patients who have systemic diseases/syndromes that predispose to cancer development is likely to be related to genetic instability. Tumor suppressor genes are now thought of as either gatekeepers or caretakers. The gatekeeper genes control cell growth by inhibiting cell proliferation or promoting apoptosis, and the caretaker genes maintain the integrity of the genome by DNA repair mechanisms. Inactivation of a caretaker gene is considered to promote neoplasia indirectly by facilitating genetic instability, which leads to increased mutations of all genes, including gatekeepers.

In general, aberration of gatekeeper genes does not influence oral cancer, except Li-Fraumeni syndrome in which second primary malignancies including oral cancer are seen. The syndromes like Fanconi’s anemia, xeroderma pigmentosum, Bloom’s syndrome, ataxia telangiectasia, colorectal cancer and Werner syndrome are associated with caretaker genes. Genetic instability may certainly be fundamentally important in the pathogenesis of oral cancer [5–7].

In the pediatric age group, the most common sites for SCC in oral cavity are tongue and lip [1, 2]. Table 1 shows list of studies/case reports with tongue and gingiva as the most frequently involved sites followed by other regions of the oral cavity in a group of 20 patients of pediatric head and neck squamous cell carcinoma [2, 4, 8–13]. In another case review study done by Armed Forces Institute of Pathology, 20 cases of pediatric oral SCC were found; 9 of them involved the tongue [13]. Similarly, in another retrospective study conducted in Memorial Sloan-Kettering Cancer Center, New York, 10 pediatric patients of squamous cell carcinoma (< 20 years) were reported from the duration of 1983–2009 [12].

Table 1.

Studies/case reports showing the summary of reported cases of oral squamous cell carcinoma in pediatric age group (< 20 years)

S. No	Study	Year	Number of cases	Gender	Age (years)	Site involved	Histologic grading
1.	Bhanuprasad et al. [2]	2015	10	M-9 F-1	10–20	Tongue—3 cases, Palate—3 cases, Mandible, gingiva, floor of mouth, buccal mucosa—1 case each	Well-differentiated SCC—4 Moderately—5 Poor—1
2.	Harirchi et al. [5]	2012	1	F	15	Tongue	Well-differentiated
3.	Ribeiro et al. [6]	2011	1	M	7	Gingiva	Well-differentiated
4.	Woo et al. [4]	2009	4	M-1 F-3	11–18	Gingiva	Well-differentiated
5.	Sidell et al. [7]	2009	1	M	6	Gingiva	Well-differentiated
6.	Mahanna et al. [8]	2009	1	M	10	Mandible alveolar region	Well-differentiated
7.	Stolk-Liefferink et al. [9]	2008	1	M	11	Gingiva	Well-differentiated
8.	Binahmed et al. [10]	2007	1	F	10	Maxillary gingiva and alveolus	Well-differentiated

SCC squamous cell carcinoma

The diagnosis of squamous cell carcinoma in the pediatric age group is done in the same way as in adults. It is based on the histologic criteria. At a time, distinguishing squamous cell carcinoma from reactive or inflammatory lesions becomes a challenge in both the pediatric and adult patients [10, 12].

Management protocols for pediatric patients with HNSCC are similar to adult patients. Specific emphasis should be given to adopt an ablative surgery which can eradicate the disease with the least amount of morbidity, e.g., facial asymmetry, growth defects, secondary malignancies, cosmetic outcomes and quality of life. However, surgery remains the cornerstone of treatment with an adjuvant radiotherapy and chemotherapy based on indication. Sometimes, neo-adjuvant chemotherapy remains an effective option in surgically inoperable lesions [2].

With the potential for a composite defect, reconstruction may be necessary. Though there are pedicled flap options for reconstruction (e.g., pedicled pectoralis major myoosseous flap), they should not be considered the first choice, with an immediate preference given to microvascular reconstruction.

The free tissue transfer in mandibular reconstruction is more significant due to the growing facial skeleton. Thus, a multidisciplinary approach was adopted to construct an appropriate treatment strategy [14]. In a systematic review, Zhang et al. concluded that condylar preservation and reconstruction during the rapid growth period showed a trend toward an influence on the growth potential. Reconstruction after benign lesion resection, reconstruction between 8 and 12 years of age, and condylar preservation facilitate postoperative mandibular growth, whereas postoperative radiotherapy inhibits the same [15].

The pediatric mandible needs to develop synchronously with the rest of the craniofacial skeletal, e.g., maxilla and basicranium. Discrepancy in craniofacial growth following fibular free flap may require further surgical procedures, including orthognathic surgery, as the facial skeleton matures.

In extremely young (e.g., < 2 years) pediatric patients, prosthetic-only reconstruction (e.g., reconstruction plate, alloplastic stainless steel mandible prosthesis) are viable options, considering a future plan for bone grafting [14].

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.