Dermatology Online Journal

Cheilitis glandularis and actinic cheilitis: Differential diagnoses - Report of three unusual cases
Emanuel Sávio Souza Andrade DDS MSc PhD¹, Ana Paula Veras Sobral DDS MSc PhD², José Rodrigues Laureano Filho DDS MSc PhD³, Marconi Eduardo Sousa Maciel Santos DDS MSc⁴, Igor Batista Camargo DDS⁵
Dermatology Online Journal 15 (1): 5

1. Senior Lecturer in Oral and Maxillofacial Pathology. Director of the Master and PhD Programs in Oral and Maxillofacial Surgery
2. Associate Professor of Oral Pathology
3. Senior Lecturer in Oral and Maxillofacial Surgery. Professor of the Master and PhD Programs in Oral and Maxillofacial Surgery
4. Student of PhD Degree - Post-Graduation Program of Oral and Maxillofacial Surgery
5. Student of Master Degree - Post-Graduation Program of Oral and Maxillofacial Surgery
School of Dentistry of Pernambuco (FOP/UPE), Recife, Brazil. igorbcamargo@bol.com.br, igorildo@hotmail.com

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Abstract

A variety of pathological conditions of diverse etiologies may involve the lips. Cheilitis glandularis (CGL) is a rare disorder of unknown etiology characterized by inflammation of the minor salivary glands of the lower lip. The aim of this paper is to compare the diagnosis and treatment of two cases of CGL at an early age (one in a child and the other in a young adult with mental retardation) with the diagnosis and treatment of actinic cheilitis, which is much more prevalent than CGL in tropical countries.

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Introduction

The vermilion is the most obvious element of the anatomy of the lips and represents the junction between the skin and the mucosa [11]. First conceptualized by the French dermatologist Jean Darier as the semimucosa, the vermilion is the external representation of the pars marginalis of the orbicularis ori muscle. The lips continue their course beyond the vermilion border through the pars peripheralis of the orbicularis delimited by the ala and the columella of the nose, superiorly, and the chin, inferiorly [11].

Inflammatory disorders of the lips of the oral cavity are commonly designated as cheilitis when affecting the vermilion of the lips [11]. Whether it is acute and symptomatic, chronic, or disabling, a thorough evaluation is required to determine the cause and rule out malignancy. A good history and clinical examination with careful attention paid to the oral cavity will often uncover the cause [2, 5, 11].

The clinical evaluation of and histopathology of the salivary glands is a complex and difficult area of diagnostic pathology [4, 13]. In the latest World Health Organization (WHO) classification there are 40 named neoplasms, many of which have variable histological features that can challenge even the most experienced pathologist [3]. Cheilitis glandularis (CGL) is a rare disorder originally described in the minor labial salivary glands and characterized clinically by edema and focal ulceration [3, 4, 5, 11, 13].

The present report details the diagnosis and treatment of one patient with an unusual pediatric presentation of cheilitis glandularis and another that developed cheilitis as a young adult. Because this condition presents many features in common with other lesions, a third case of actinic cheilitis in a child is described to reinforce the need for developing a thorough differential diagnosis.

Case reports

Case one

A 12-year-old boy, came to the Oral and Maxillofacial Surgery Outpatient Clinic of the Pernambuco School of Dentistry, University of Pernambuco (FOP/UPE) in September, 2003, with his mother, having been referred by the Dermatology Study Center of Recife (CEDER), so that an incisional biopsy could be performed on an ulcerated area of his lower lip. The vermilion exhibited an ulcer covering around 75 percent of the total lip area. The patient's lower lip was slightly everted due to the presence of edema and the patient complained of discomfort during palpation and while eating. He reported no previous surgical intervention in the area and no family history of similar cases was elicited. On intra-oral examination the patient was found to have mixed dentition with the presence of all the permanent anterior teeth, which were in a good state of cleanliness (Fig. 1a & Fig. 1b). An incisional biopsy was carried out and the material was sent to the Oral Pathology Laboratory of the Pernambuco School of Dentistry (LPBFOP/UPE) (Fig. 1c) and the histopathology showed extensive ulceration and an intense, lymphoplasmocytic inflammatory infiltrate in the glandular parenchyma, as well as dilated ducts (Fig. 2). The histological diagnosis was chronic mucositis with ulceration and chronic sialodentitis compatible with the clinical diagnosis of cheilitis glandularis.

Figure 1	Figure 2
Figure 1a. View of the child's face demonstrating the asymmetry and eversion due to edema in the lower lip, 1b. Close-up view showing ulcer covering 75% of the extension of the vermilion of the lower lip, 1c. Cheiloplasty with a #5 scalpel, 1d. View of the lip during surgery showing the removal of the minor salivary glands. Figure 2. Demarcated areas of the periphery (#) showing ulceration and underlying areas of vascular neoformation and inflammation (>). In the deep portion of the specimen (*) minor salivary glands are observed exhibiting periacinal inflammatory infiltrate.

The patient was submitted to a topical and systemic treatment with corticosteroids. At three months the patient's condition had improved slightly, and he was then sent back to the FOP outpatient clinic with a request from the dermatology team that the lesion be treated by verminelectomy.

Labioplasty of the lower lip was planned and performed en bloc with removal (shaving) of the ulcer over the entire vermilion under local anesthesia, with demarcation on the midline to facilitate a wedge closure with no need to create pediculate flaps. In association with the removal of the lesion, the largest possible number of minor salivary glands in the area of the surgical bed were removed for the purpose of preventing relapse (Fig. 1d). The histological appearance of the excision specimen was the following: fragment of oral mucosa lined with stratified parakeratinized pavement epithelium displaying areas of ulceration and acanthosis. The connective tissue was fibrous and well vascularized, exhibiting an abundance of small salivary glands in which foci of mononuclear inflammatory infiltrate at periacinal and periductal locations were observed, in addition to dilated ducts. The final diagnosis was a chronic acute inflammatory process with ulceration matching a clinical picture of cheilitis glandularis.

Figure 3
Figure 3a. Close-up view of the lower lip with the cicatricial crust on the seventh postoperative day, 3b & 3c. View of the lower lip and of the child's face at 6 months with a faint scar line.

On the seventh postoperative day the patient presented with a cicatricial crust associated with the sutures. (Fig. 3a). The results were considered satisfactory over the 3-month period of follow-up when compared with possible alternative clinical treatments (Fig. 3b). The case has been under observation for five years with no clinical signs of relapse to date (Fig. 3c).

Case two

Figure 4
Figure 4a. View of the face of the young adult with mental retardation showing edema of the lower lip, as well as the absence of lip sealing due to presence of open bite of the anterior teeth, 4b. Close-up view showing undulations in the central portion of the vermilion of the lower lip, 4c. View of the size of the surgical specimen removed during the cheiloplasty.

A 23-year-old male with mental retardation came to the Oral and Maxillofacial Surgery Outpatient Clinic in September, 2007, with his mother, also having been referred by the Dermatology Study Center of Recife (CEDER) for vermelinectomy of his lower lip. The vermilion of the lower lip was found to be everted due to the presence of a large amount of edema with undulations and thinning of the skin covering around 60 percent of the total lip area (Fig. 4a). The patient complained of discomfort during palpation and while eating, despite his difficulty in communication. His mother reported no previous surgical intervention in the area and no family history of a similar condition was reported during the patient history. On intra-oral examination the patient was found to have an anterior open bite and the presence of all the permanent anterior teeth, which were not in a good state of cleanliness. The patient exhibited buccal respiration, which contributed to the difficulty in the sealing of the lips (Fig. 4b).

Figure 5	Figure 6
Figure 5a. Photomicrograph with 40x magnification showing increase in the thickness of the epithelium and underlying connective tissue with multiple acini and gland ducts permeated by inflammatory tissue, 5b. Photomicrograph with 100x magnification showing minor salivary glands and periacinal inflammatory infiltrate, 5c. Photomicrograph with 100x magnification showing disorganization of the epithelial tissue close to the basal lamina, 5d. Photomicrograph with 400x magnification showing epithelial cells illustrating loss of the cell arrangement and multiple mitoses, both characteristic of intense atypical epithelium. Figure 6a. Close-up view of the vermilion of the lower lip in the immediate postoperative period sutured with nylon 5-0. It can be seen that the patient presents sialorrhea due to inability to swallow correctly, 6b & 6c. View of the lower lip and the patient's face at 6 months showing a cosmetically acceptable scar.

Labioplasty of the lower lip was planned and performed en bloc with removal (shaving) of the entire area of edema in the vermilion under local anesthesia (Fig. 4c). The vermillionectomy was carried out and the material sent to the Oral Pathology Laboratory of the Pernambuco School of Dentistry (LPBFOP/UPE). The histological sections displayed extensive ulceration and an intense lymphoplasmocytic inflammatory infiltrate in the glandular parenchyma, as well as dilated ducts. In addition, the presence of many atypical epithelial cells was noted; there were some mitoses. The histological diagnosis was chronic mucositis with ulceration and chronic sialodentitis compatible with the clinical diagnosis of cheilitis glandularis with atypical epithelial cells (Fig. 5). In both cases 5-0 nylon suture was employed to prevent possible formation of excessive scar tissue (Fig. 6a). The results were considered satisfactory over the 6-month period of follow-up. The case has been under observation for one year with no clinical signs of relapse to date (Figs. 6b & 6c).

Case three

Figure 7
Figure 7a. Initial clinical appearance with areas of ulceration of the mucous membrane of the lower lip, 7b. After cheiloplasty, 7c. Histological appearance (H.E. 100x): parakinatinized stratified pavement epithelium. The underlying connective tissue exhibits solar elastosis (arrows) and slight inflammation as typical characteristics of the lesion.

An 11-year-old boy, came to the Oral and Maxillofacial Surgery Outpatient Clinic in July 2007 with his mother, having, like the other two patients, been referred by the Dermatology Study Center of Recife (CEDER) for vermelinectomy of his lower lip. The vermilion of the lower lip exhibited a deep ulcer covering around 35 percent of the total lip area near the midline (Fig. 7a). His sister reported no previous surgical intervention in the area and no family history of similar cases was elicited. On intraoral examination the patient was found to have all the permanent anterior teeth, which were in a good state of cleanliness. The patient complained that the ulcer became bigger whenever he engaged in school activities that exposed him to sunlight. This happened despite his use of lip protection products with sunblock prescribed by a dermatologist.

Labioplasty of the lower lip was planned and performed en bloc with removal (shaving) of the entire area of ulceration in the vermilion under local anesthesia. The vermillionectomy was carried out and the material sent to the Oral Pathology Laboratory of the Pernambuco School of Dentistry (LPBFOP/UPE). The histological sections displayed an extensive formation of elastosis in the underlying connective tissue (solar elastosis) (Fig. 7c). The epithelium exhibited areas of hypertrophy alternating with thinning of the skin. The histological diagnosis was cheilitis actinica.

The results were considered satisfactory over the 6-month period of follow-up. The case has been under observation for more than one year with no clinical signs of relapse to date (Fig. 7b).

Discussion

Cheilitis glandularis is a rare inflammatory disease affecting the minor salivary glands, predominantly those of the lower lip, although there have been occasional reports of CGL affecting the upper lips and palate [14]. Historically, CGL has been subclassified in three clinical types according to the spectrum of progression characteristics: simple, superficial suppurative, and deep suppurative [3, 4, 5, 13]. Similar lesions have occasionally been described elsewhere in the oral cavity with the alternative name of suppurative stomatitis glandularis [5]. This term is not applicable to our cases because the histological features were of the deep suppurative type and only the lower lip was affected.

Cheilitis glandularis presents a diagnostic challenge to clinicians because the etiologic factors are uncommon and not well understood. Its clinical differential diagnosis includes orofacial (cheilitis) granulomatosis, multiple mucoceles, actinic cheilitis, cystic fibrosis, cystadenoma, cystadenocarcinoma, mucoepidermoid carcinoma [5, 13]. In addition, the microscopic features may show a variety of histopathologic features encountered in the various types of CGL [13]. Examples of the difficulty in the diagnosis of CGL have been previously reported [5, 13].

Microscopically, CGL shows variably dilated and tortuous minor salivary gland ducts, together with interstitial acute and chronic inflammation. The ducts are frequently lined with oncocytic cells with foci of hyperplasia and there may be blunt intraluminal papillary projections [3, 11]. One of the cases of CGL described here was initially diagnosed as a chronic inflammatory mucositis and chronic sialodenitis, on the basis of a small incisional biopsy of the prominent suppurative edema of the lower lip. The initial histopathologic diagnosis in this pediatric case does not differ from the excisional biopsy and is in agreement with Stoopler et al. [13], who state that CG is defined histopathologically and clinically as ductal ectasia better observed in the entire specimen than in a small single specimen obtained during an incision biopsy [7].

Most cases of CGL have been reported in middle-aged and elderly men [1, 4], but a few cases have been reported in women [5, 13] and children [15]. Although the etiology of CGL is still unknown, the involvement of children reinforces the importance of familial history and suggests that this disease may be hereditary with an autosomal dominant pattern of inheritance [15]. Emotional disturbance, poor oral hygiene, smoking, chronic exposure to sunlight and wind, and a compromised immune system have been suggested as predisposing factors [3, 5]. However, one unusual case of CGL in a patient with HIV infection has been reported, but the association was considered coincidental because cell-mediated immunosupression is unlikely to be of significance in the etiology of CGL [4]. In the present report, Case one was a 12-year-old boy with no familial history of the disorder and good oral hygiene, whereas Case two was a young adult with child-like behavior owing to his mental retardation; both are at variance with the literature reviewed.

The treatment of CGL ranges from conservative treatment with topical and systemic steroids [10] to more extensive treatment, such as resection [8, 12, 13]. The reduction or elimination of predisposing factors is the first step in treatment [8]. Lip balms, emollients, and sunscreens have been advocated for patients with excessive exposure to the sun and wind [11]. If predisposing factors cannot be identified or eliminated, conservative treatment should ensue, including the use of topical steroids, intralesional steroids, systemic anticholinergics, systemic antihistamines, and/or antibiotics [15]. If conservative therapy fails, as in our clinical cases, surgical intervention is often required to reverse lip eversion and remove the sources of inflammation of the minor salivary glands [9, 12]. Surgical options include cryosurgery, vermillionectomy, and/or labial mucosal stripping, as advocated by Stoopler et al. [13] We therefore also agree with Nico et al. [6] that in cases of lip diseases, a single punch biopsy may not be a suitable method for accurately diagnosing this subset of patients and that, if vermilionectomy is performed, careful histological examination of the entire excised specimen (serial sections) is mandatory.

Patients with CGL, especially of the deep suppurative type, should be considered for surgical excision and must be closely monitored because of the risk of developing squamous cell carcinoma [11]. In addition, these patients should be placed on a regular follow-up schedule to monitor for any suspicious clinical changes, particularly when any cell atypia is observed on microscopy (Case two). For this reason our cases have been followed up for more than one year (Cases two and three) and up to five years (Case one) with no signs of clinical alterations to date.

In conclusion, the present reports represent unusual presentations of CGL presenting a diagnostic challenge to clinicians. The etiologic factors in both of these cases are unclear, but have been compared to an additional childhood case of actinic cheilitis.

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