Aggressive Oral Carcinoma Cuniculatum in a Paediatric Patient: A Variant That Deserves Greater Attention

Oral squamous cell carcinoma (OSCC) is rare in paediatric patients and unrelated to risk factors, such as smoking or alcohol consumption 1. Instead, genetic instability or congenital syndromes have been implicated 2, 3. Among OSCC variants, oral carcinoma cuniculatum (OCC) is exceptionally uncommon in this age group. Defined as a well-differentiated OSCC variant, OCC clinically resembles verrucous carcinoma, presenting as an exophytic, keratinized papillomatous lesion 4, 5. Histopathology shows an endophytic, labyrinthine-growth pattern of squamous epithelium forming interconnecting keratin-filled crypts, with minimal atypia. Despite its locally aggressive behaviour, prognosis is favourable after complete excision, with rare recurrence and no reported metastasis 6. Only a few paediatric cases of OCC have been described 3, 7-9. We report a case of OCC with rapid growth in a 9-year-old boy, affecting the right retromolar region and the mandible, and raise the question of the need for greater discussion of oral cancer in paediatric patients. The lesion doubled in size within 1 month, revealing an 8 cm exophytic mass with ulceration, telangiectasia, and facial asymmetry (Figure 1A,B). The tumour involved teeth 46 and 85, and was associated with trismus and complaint during food intake. Initial radiographic evaluation was non-contributory, but preoperative CT revealed an aggressive-appearing lesion in the right mandibular ramus, with circumferential soft tissue extension into the buccal space, ipsilateral infraorbital fossa, and oral cavity, partially obstructing the airway (Figure 1C–E). Given the patient's age and rapid progression, malignant mesenchymal neoplasms such as pleomorphic sarcoma or Ewing sarcoma were initially suspected. Two incisional biopsies were performed. The first analysis revealed epithelial proliferation but insufficient content of lamina propria, with CD34 and D2-40 highlighting vascular and lymphatic vessels. A second biopsy collecting a larger amount of sample revealed well-differentiated squamous epithelium forming papillary and branching keratin-filled cystic structures, with both expansive and infiltrative growth. Detached and branching epithelial nests were frequent (Figure 1F–H). Moderate atypia, invasive growth, and strong AE1/AE3 positivity in the epithelial islands supported the diagnosis of OCC (Figure 1I,J). Following diagnosis, the patient underwent a hemimandibulectomy with fibula free flap reconstruction. No adjuvant radiotherapy was indicated, and imaging exams revealed no local or distant metastases. Postoperative follow-up showed graft dehiscence and failure of osseointegration, which led to subsequent removal of the bone graft, leaving only the fixation plate in place (Figure 1K). The patient was discharged from hospital care after 3 weeks and continued with home-based physiotherapy and speech therapy. At 7 months, neck fibrosis, limited tongue mobility, and trismus due to fibrotic tissue formation were observed, while intraoral healing was satisfactory (Figure 1L–N). At the 10-month follow-up, no recurrence was detected. This case highlights several key aspects for discussion: (1) OCC is extremely rare in children, although it can occur; (2) the disease may progress rapidly, with extensive mandibular infiltration that might not be easily detected on bidimensional radiographic examinations; and (3) initial biopsies may pose diagnostic challenges, as occurred in this case, which we discuss further below. OCC typically presents as a tumour mass or nonspecific ulcerated swelling, sometimes with keratin exudate resembling pus, often leading to misdiagnosis 4, 5, 10. Most cases occur in women in their seventh or eighth decades, mainly affecting the mandibular gingiva, followed by the maxilla 6, 11, making it rarely considered in the initial differential diagnosis. As OCC pathogenesis remains unclear 12, 13, its inclusion in paediatric diagnostic hypotheses is unusual. Certain genetic syndromes, including xeroderma pigmentosum, Fanconi anaemia, Li-Fraumeni, Bloom, and ataxia telangiectasia, predispose to early-onset malignancies through inherited mutations 2. In our case, no hereditary syndrome, familial history, or harmful habits were identified, emphasizing the need to explore other potential etiological factors. A recent review of paediatric OSCC, including a 5-year-old with OCC, identified 24 English-language case reports since 1970 involving non-syndromic patients aged ≤ 16 years with tumours of the gingiva, alveolus, or palate. Of 11 cases with histopathology, nine showed features consistent with OCC, similar to the 5-year-old case 3. These findings suggest that OCC may be more frequent than recognised, with variants likely underdiagnosed or misclassified. OCC is a rare locally invasive but without metastatic potential 6. In our case, however, a markedly aggressive pattern was observed within 1 month, characterised by extensive soft tissue infiltration and bone destruction, showing that OCC may exhibit aggressive local behaviour despite its non-metastatic nature. A systematic review including 43 adult cases reported variable imaging findings, predominantly bone destruction, with 32% showing poorly defined margins, extensive bone loss and erosion in tumours involving soft tissue. Treatment most often comprises complete surgical resection with safety margins (97.7%), including subtotal maxillectomy or mandibulectomy when bone is invaded, and neck dissection for nodal involvement 11. In a review of 24 paediatric OSCC cases, radiographic findings generally revealed poorly defined bone erosion at advanced lesions. Of 15 cases with available imaging, 12 showed radiolucent areas with irregular borders or osteolysis, while three displayed nonspecific or unremarkable findings 3. The initial incisional biopsy revealed “mucosa with marked epithelial proliferation,” without dysplasia or malignancy. Such nonspecific findings may mimic benign processes, including pseudoepitheliomatous hyperplasia, a known diagnostic pitfall in paediatric cases 9. However, the rapid and aggressive clinical progression in our patient contradicted a benign interpretation. In this sense, this diagnostic challenge aligns with reports indicating that OCC may be mistaken for benign or reactive lesions, especially when biopsy specimens are limited 3-5. OCC typically shows an endophytic, labyrinthine growth of well-differentiated squamous epithelium interconnecting keratin-filled crypts 6, which was found on the second specimen. These hallmark features may be absent in small samples, underscoring the importance of biopsy size, depth, and site selection for accurate diagnosis 6, 13. In conclusion, OCC is a rare OSCC variant in children, often misdiagnosed due to its benign-like features and rarity. Despite its locally aggressive and rapid growth, prognosis is favorable after complete excision, with rare recurrence and no metastatic potential. Clinician and pathologist awareness is crucial for timely diagnosis and optimal outcomes. Study concepts: G.D.R. Study design: G.D.R. Data acquisition: H.M.C., R.E.S., C.A.-S. Quality control of data and algorithms: H.M.C., R.E.S., G.D.R. Data analysis and interpretation: H.M.C., R.E.S., C.A.-S., G.D.R. Manuscript preparation: H.M.C., R.E.S., C.A.-S. Manuscript editing: H.M.C., R.E.S., C.A.-S., R.L.C.A.J., F.M., G.D.R. Manuscript review: R.L.C.A.J., F.M., G.D.R. The authors thank Dr. José Narciso Rosa Assunção Júnior, Dr. Carla Miranda Santana, and Dr. Fernanda Cecconello for their support during medical and dental care, as well as for their scientific contributions. During the preparation of this work, the authors used ChatGPT by OpenAI to correct and improve English grammar for enhanced textual flow. After using this tool, the authors reviewed and edited the content as needed and took full responsibility for the final content of the published article. The authors Helena Miguel Cotter, Riéli Elis Schulz, and Caroline Alfaia Silva thank the Fundação de Amparo à Pesquisa e Inovação do Estado de Santa Catarina (FAPESC) for providing scholarship support. Written informed consent for the publication of clinical details and images was obtained from the patient's legal guardian and from the patient himself. The study was approved by the local ethics committee (registration no. 92176525.2.0000.0121; approval no. 7.922.202). The authors declare no conflicts of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request.