Clinical Pathologic Conference Case 1: A reddish nodule on the midline hard palate

Clinical Presentation

A 13-year-old boy was referred for evaluation of an asymptomatic lesion on the midline hard palate with a 3-month history of evolution. The patient denied any history of trauma or injury to the area. Intraoral examination revealed a reddish sessile nodule, with well-defined borders, fibroelastic consistency, and measuring approximately 5 mm. Telangiectasia was also noticed on the surface (Figure 1A). Panoramic radiography showed complete permanent dentition and no bone alterations were observed in the area corresponding to the lesion (Figure 1B).

Differential Diagnosis

Lesions on the hard palate in pediatric patients may represent a complex diagnostic challenge, encompassing a range of benign and malignant possibilities. Given the clinical and radiographic characteristics, several entities can be included in the differential diagnoses, such as cysts, benign mesenchymal neoplasms, salivary gland tumors, inflammatory processes of the salivary glands, and developmental entities such as choristomas, hamartomas, and vascular lesions.

Reactive and inflammatory processes represent a group of lesions that can be frequently observed in pediatric patients, such as pyogenic granuloma, follicular lymphoid hyperplasia, subacute sialadenitis, and atypical histiocytic granuloma. Pyogenic granuloma (PG) is a common benign lesion characterized by an overgrowth of granulation tissue that typically develops in response to chronic irritation or trauma.¹ PG occurs more frequently in the gingiva and tongue. On the other hand, it is unusual on the hard palate, particularly in the middle region.¹ Follicular lymphoid hyperplasia (FLH) is a non-neoplastic lymphoproliferative disease (also known as a nodular lymphoid lesion and pseudolymphoma) associated with persistent local irritation that commonly affects the hard palate. Notably, a third of palatal FLH cases are linked to denture wear, predominantly affecting elderly patients. The typical presentation is a painless, slowly growing, non-ulcerated nodule, measuring less than 3 cm, with a color ranging from normal mucosa to purple-reddish and a texture varying from soft to firm.^2,3 Subacute sialadenitis (SAS) is a rare inflammatory condition affecting minor salivary glands. It is an uncommon and self-limiting necrotizing condition that often affects the minor salivary glands of the palate.⁴ This condition typically occurs in men over 45 years of age but can also appear in teenagers and young adults. The most common clinical appearance is an ulcerative lesion, usually 1 to 3 cm in size, which can mimic a malignant growth. On the other hand, in some cases, the mucosal surface remains undamaged.⁴ However, because of the absence of salivary glands in the midline of the hard palate, this diagnosis is unlikely. Atypical histiocytic granuloma is rarely reported in the palate and typically occurs in elderly patients, affecting both sexes, with a mean age of 55 years.⁵ The lesion is usually ulcerated and frequently associated with chronic trauma or a hypersensitivity reaction. In the palate, the lesion often develops in association with a removable prosthesis, suggesting a reactive condition.⁵

Benign mesenchymal neoplasms (BMNs) are diverse with distinct clinical features.^6-11 Leiomyomas are benign tumors of smooth muscle origin that rarely occur in the oral cavity. They are classified into 3 groups: solid leiomyoma, epithelioid leiomyoma, and angioleiomyoma. Oral leiomyomas are most frequently identified in middle-aged adults, with a peak incidence in the fifth decade of life and a slightly higher prevalence in men. These lesions usually present as nonspecific masses with varying background vascularity, with the lip, palate, buccal mucosa, and tongue being the most common sites of occurrence.⁷ Oral angioleiomyoma is a rare variant of leiomyoma, usually asymptomatic, characterized by multiple tortuous blood vessels with a thickened smooth muscle layer and intervening smooth muscle stroma.^7,8 The lip is the most commonly affected site, followed by the palate (both hard and soft) and buccal mucosa.^7,8 Neurofibromas are common benign skin tumors originating from Schwann and mesenchymal cells constituting the nerve sheath.⁹ Because of this area's rich innervation, neurofibromas commonly involve the head and neck region. In the oral cavity, the tongue, buccal mucosa, gingiva, salivary glands, and, in some cases, palatal mucosa are frequently involved.⁹ Schwannomas are benign, slow-growing, and usually solitary tumors originating from the Schwann cells of the nerve sheath.¹⁰ They are typically diagnosed in children and young adults and manifest as slowly enlarging nodules, sometimes associated with pain.¹⁰ Although rare in the oral cavity (approximately 1%), when present, the most common location is the tongue; however, palatal schwannomas have been reported.¹⁰ Sialolipomas are growths consisting of fatty tissue within the salivary glands found on the tongue, lips, and hard palate.¹¹ They can occur at any age but are more common in people in their 40s.¹¹ Sialolipomas typically appear as well-defined masses enclosed in a fibrous capsule containing neoplastic mature fat tissue and non-neoplastic salivary gland elements.¹¹

Salivary gland tumors (SGTs), although rare in pediatric patients, could be a diagnostic possibility.¹² In pediatric patients, SGTs generally occur more frequently in the second decade of life, with a mean age of 14 years for benign tumors and 10 years for malignant ones.¹² Pleomorphic adenoma is the most common benign tumor, and, among the malignant ones, mucoepidermoid carcinoma is the most predominant and accounts for about 25% of SGTs in pediatric populations.¹² Although most SGTs develop in the posterior region of hard palate and soft palate, they rarely occur in the anterior midline area (anterior part of the palatine raphe) due to the absence of salivary glands in this location.¹²

Developing entities (DEs), such as choristomas and hamartomas, are malformations involving the overgrowth of mature and normal tissues. These lesions, commonly found in children and adolescents, may resemble tumors due to their vascular richness.^13,14 A hamartoma is a mass of varying proportions of typically mature tissue native to the area, appearing as hard, firm, pedicle-like masses without invading neighboring anatomic structures.¹³ On the other hand, choristomas consist of tissue types that are not typically found in the oral cavity.¹⁴ Although these entities rarely affect the palate, this anatomic site may be susceptible to developing hamartomas and choristomas due to its complex embryological processes.^13,14

Among vascular lesions (VLs), oral hemangioma (OH) is the most common type of vascular tumor in the head and neck region, affecting around 5% of newborns, with a reported incidence ranging from 2% to 10%.¹⁵ Hemangiomas encompass various vascular disorders, such as hamartomas, benign neoplasms, or malformations.^15-17 Clinically, OH appears as a painless, soft tissue reddish mass of variable size, with a smooth or lobulated surface, that may be lobulated, sessile or pedunculated with a slight preference for female patients.¹⁶ Histologically, hemangiomas are categorized into capillary, cavernous, mixed, and sclerosing types, based on the size of the blood vessels blood vessels they contain.¹⁸ Capillary OHs consist of small, thin-walled vessels lined with endothelial cells, rarely seen in adults and mainly appearing on the lips, buccal mucosa, and tongue.^16-18 Lesions on the palate and uvula are rare.¹⁸

Although hemangiomas in the head and neck are relatively common, OHs are less frequent and occur more commonly on the lips, tongue, buccal mucosa, and palate.¹⁸ They are typically diagnosed in children and often regress over time.¹⁸ Primary clinicians are crucial in reassuring patients and parents about the benign nature of OHs and should schedule regular follow-up appointments for monitoring.¹⁸

Management

The patient was referred for treatment. The cone-beam computed tomography revealed bone involvement and the magnetic resonance imaging (T2) showed hypersignal compatible with vascular lesion (Figure 2A, 2B). Complete surgical removal was performed under local anesthesia and a removable acrylic prosthesis was immediately placed to improve the healing process (Figure 3A-E). The patient recovered well and no signs of recurrence were observed after 10 months of treatment (Figure 4F).

Diagnosis

The microscopic evaluation of the excised specimen revealed a fragment of palatal mucosa lined by surface epithelium. In the connective tissue, there was a proliferation of blood vessels suggesting a vascular origin. The lesion was positive for CD34 and CD31 in immunohistochemical analysis, confirming the presence of endothelial cells. The cell proliferation index measured by Ki-67 was of approximately 10%. Considering these data, the diagnosis of cellular hemangioma was established (Figure 4A-F).

Discussion

OHs are benign tumors characterized by a proliferation of endothelial cells and are considered the most common neoplasm of childhood.¹⁶ Whereas most hemangiomas occur in the head and neck region, OHs are relatively uncommon and usually involve the lips, tongue, buccal mucosa, and palate, as well as the mandible and maxilla (central hemangiomas).¹⁶

According to the International Society for the Study of Vascular Anomalies (ISSVA),¹⁷ clinically OHs are categorized as infantile hemangiomas (IHs) and congenital hemangiomas. IHs develop during the first months of life (6 to 12 months of age) with a rapid proliferation, followed by a period of slow growth and spontaneous involution between 6 and 9 years of age. In contrast, congenital hemangiomas are present at birth and can be categorized as rapidly involuting congenital hemangiomas, non-involuting congenital hemangiomas, or partially involuting congenital hemangiomas, depending on their clinical behavior.^16,17

OHs can appear as a red and purplish macule, papule or nodule, depending particularly on the depth of the lesion.¹⁸ The superficial lesions are reddish and present as lobulated masses, either sessile or pedunculated. While deeper lesions are more difficult to visualize clinically. They may appear purplish (violet) or bluish, distinct from the surrounding mucosa, and can mimic other lesions affecting the oral cavity.¹⁶

Most OHs are asymptomatic and diagnosed during routine physical examinations.¹⁶ In the current case, the patient and his parents did not notice any alteration over time. Therefore, it was not possible to classify exactly for how long the lesion had been present. In addition, according to the patient's report, the lesion was painless, and there were no bleeding episodes.

Generally, a biopsy in OHs is avoided due to the risk of bleeding and most lesions can be diagnosed clinically.¹⁶ However, in the current case, the biopsy was initially performed to establish the proper diagnosis because other clinical diagnostic hypotheses were considered. In addition, concern arose because the reported evolution time was particularly short and the presence of telangiectasia on the surface.

Most OHs do not require treatment and intervention will depend on a number of factors.¹⁶ However, the cases that require treatment are particularly because of the size, depth, location, stage of growth, behavior, functional impairment, and patient complaint.^16-19 The range of treatments includes surgical excision, cryotherapy, surgical lasers, laser photocoagulation, intense pulsed light, infrared coagulation, and sclerotherapy.^18,19 In the current case, the lesion was surgically removed without complications.

This case demonstrates the importance of the dental surgeon being aware of the uncommon characteristics of OHs and the importance of effective communication between clinicians, pathologists, and surgeons for accurate diagnosis and treatment.