Clinical Pathologic Conference Case 6: An ulcerated lesion on the gingiva of an adolescent female

Abstract

Clinical Presentation

A 12-year-old female patient presented with a chief complaint of a non-healing ulcer in the anterior maxilla. The lesion had been present for 3 months, and there was a history of a slowly growing mass. Clinical examination revealed an approximately 1.5 × 1 cm ulcerated mass involving the left maxillary canine-lateral incisor area (Figure 1). The surface appeared to be ulcerated, with an overall erythroleukoplakic appearance. The patient experienced variable sensitivity, and the medical history was unremarkable. Further palpation revealed a firm, ulcerated mass with rolled borders. An incisional biopsy was performed, and the tissue was sent for histopathological examination.

Differential Diagnosis

The clinical differential diagnosis for a gingival lesion in an adolescent is broad, encompassing a range of possibilities from reactive and benign to malignant lesions. The patient's age makes a malignant lesion unlikely. However, the clinical presentation of a speckled and granular erythro-leukoplakic appearance, along with visible dilated blood vessels (telangiectasias), raises suspicion for a malignancy. Despite the patient's age, the primary considerations include malignant entities such as squamous cell carcinoma and rhabdomyosarcoma, intermediate conditions like Langerhans cell histiocytosis, and benign conditions such as myofibroma, although the latter is less likely.

Squamous cell carcinoma (SCC) is highly suspected in this case, despite the patient's age. The clinical presentation of an exophytic lesion with a granular and erythro-leukoplakic appearance telangiectasias is concerning. The presentation of erythro-leukoplakia suggests an epithelial neoplastic origin. SCC is the most common malignancy of the oral cavity.¹ It typically exhibits a peak incidence in the elderly and is strongly associated with smoking and alcohol abuse.¹ Whereas oral SCC (OSCC) is rare in individuals under 50, recent global epidemiological studies have shown a rising incidence, particularly among young adults.^1-3 The etiopathogenesis of OSCC in younger patients remains unclear, and traditional risk factors like tobacco and alcohol use are thought to play a minimal role in these cases, since the duration of exposure to these factors is believed to be shorter in young individuals.^1,4

The gingival-alveolar ridge is a common site for OSCC in children without known genetic predisposition to cancer.⁴ However, the possibility of a genetic predisposition should be considered in such cases. Rare hereditary syndromes, such as Fanconi anemia, xeroderma pigmentosum, Bloom syndrome, Li-Fraumeni syndrome, and dyskeratosis congenita, have all been associated with an increased risk of developing OSCC, particularly in the tongue, as well as other head and neck neoplasms.⁴

Rhabdomyosarcoma (RMS) was considered because it is the most common soft tissue sarcoma in pediatric patients, although it is rare in the oral cavity.^5,6 RMS originates from skeletal muscle and often affects the head and neck region.⁵ More than 50% of RMS cases are diagnosed within the first decade of life.⁶ According to the World Health Organization classification, RMS is divided into 4 main subtypes: embryonal, alveolar, pleomorphic, and spindle/sclerosing. The most common subtypes are embryonal, followed by alveolar and pleomorphic.⁷

RMS is an aggressive tumor that typically grows rapidly in children.^6,7 In the oral cavity, RMS is more common in male patients and often occurs during the first 2 decades of life.⁷ Its clinical manifestations can vary and may be misleading. In the early stages, it usually presents as a painless swelling, but other symptoms such as tooth mobility, paresthesia, trismus, and cervical lymphadenopathy may also be present.^6,7 However, the clinical presentation in this case does not fully support a diagnosis of RMS.

Langerhans cell histiocytosis (LCH) can affect patients across a wide age range, with over 50% of cases occurring in those under 15 years.^8,9 The most common presentation involves bone lesions, which can affect almost any bone. The skull, ribs, pelvis, vertebrae, mandible, and extremities are commonly affected. These bone lesions are usually accompanied by dull pain and tenderness.⁸ In 10% to 20% of cases, the jaws are involved, with the lesions appearing as sharply punched out or ill-defined radiolucency.⁸ A characteristic “scooped out” appearance is seen when alveolar bone destruction occurs, which can cause teeth to loosen and give the clinical impression of severe periodontitis.^8,10 When extensive alveolar involvement is present, the teeth may exhibit a “floating in air” appearance on radiographs.^8,10 If lesions break out of the bone, ulcerative or proliferative mucosal lesions or gingival masses may develop, and, in some cases, only the oral soft tissues are affected.⁸ Oral soft tissue involvement can present as gingival ulcers or hyperplastic tissue.⁹ However, the clinical presentation helps exclude this entity from consideration, as LCH is a hematological disorder and the involved mucosa typically appears red or hemorrhagic in nature, unlike the present case.

Myofibroma is a rare myofibroblastic tumor that can affect individuals across a broad age range, with a mean age of 23 years.^11,12 It has a slight male predominance, with a male-to-female ratio of 1.2:1.^11,12 The head and neck region are the most commonly affected area, particularly the skin and subcutaneous tissues.¹² In the oral cavity, buccal mucosa, retromolar region, and tongue, are commonly involved, followed by the labial mucosa.^11,12 In patients under 20 years of age, 58% of myofibromas occur on the attached gingiva, whereas 38% are found on the movable mucosa.¹² Many myofibromas in the posterior alveolar mucosa may be associated with unerupted molars and tend to involve bone more frequently in pediatric patients than in adults.¹² Conversely, individuals over 40 years of age have a higher incidence (67.8%) of myofibromas on the movable mucosa.¹² Clinically, myofibroma in the oral cavity appears as an asymptomatic, slow-growing soft tissue mass. Most cases arise as a solitary lesion but multiple lesions (myofibromatosis) are sometimes seen commonly in infants.¹¹ The erythroleukoplakic appearance of the lesion in the present case may argue against this diagnosis.

Diagnosis and Management

The lesion was biopsied and sent for histopathological examination. Histopathology revealed a well-differentiated squamous cell carcinoma. The tumor exhibited large islands, nests, interconnecting sheets and strands of neoplastic cells (Figure 2A). The tumor cells were relatively bland with mild pleomorphism (Figure 2B). Some of the proliferation was reminiscent of pseudo-epitheliomatous hyperplasia like changes. The tumor cells exhibited features such as an increased nuclear-cytoplasmic ratio, glassy cytoplasm, occasional dyskeratotic cells, and low mitotic activity (Figure 2C). This lesion was diagnosed as a gingival carcinoma, of well-differentiated type. The patient was treated with local resection and follow-up showed no progression of the disease.

Discussion

Various case reports have described gingival carcinomas arising as masses or swellings of a few weeks’ duration, which may progress into ulcers in young individuals. Radiographic findings may be unremarkable, or cupping resorption and mild bone loss may be observed.^13,14 Common histopathologic features in these cases include bland cytology or minimal cytological atypia and superficially invading islands with keratin-filled crypts and invaginations, which have been described as “carcinoma cuniculatum” or “keratoacanthoma-like changes” of the gingiva.¹³ Although the exact pathogeneses have yet to be understood, these unique malignancies that present as ulcerated masses in the gingiva of adolescent patients, must be further studied through large clinicopathologic series. Understanding the molecular pathogenesis is equally important for establishing the treatment guidelines, especially in comparison to conventional oral carcinomas. This case underscores the importance of considering a provisional diagnosis of squamous cell carcinoma as a differential diagnosis in young and adolescent patients presenting with an erythroleukoplakic lesion.