Laboratory Studies
To rule out systemic granulomatous diseases (eg, sarcoidosis, Crohn disease), perform ACE levels, erythrocyte sedimentation rate, and CBC count and differential.
Imaging Studies
Reflectance confocal microscopy (RCM) was described by Laurenco et al. This is a noninvasive imaging technique that allows for in vivo en face visualization of tissues with resolution that approaches that of conventional microscopy. With RCM, the entire lip can be examined nonsurgically, from surface to deeper stromal structures. According to the investigators who applied RCM to patients with clinical features consistent with cheilitis glandularis, correlating the clinical, digital RCM images, and histopathology improved diagnostic skills in the evaluation of clinical findings suggestive of cheilitis glandularis. [20]
Other Tests
Microbial culture and sensitivity testing may be warranted. In cases with acute or chronic suppuration, bacterial culture and sensitivity testing is indicated for selection of appropriate antibiotic therapy.
Fungal culture or smear may be warranted. Chronic angular cheilitis or erosive surface changes may be indicative of chronic candidal infection. Confirmation is an indication for appropriate antifungal therapy.
Procedures
Lip biopsy is indicated to rule out specific granulomatous diseases that predispose to lip enlargement and to aid in establishing a definitive diagnosis. A representative incisional biopsy specimen should consist of a wedge (or punch) of lip tissue that includes surface epithelium and is of adequate depth to ensure inclusion of several submucosal salivary glands.
Labial minor salivary gland biopsy (ie, sampling 8-10 labial minor salivary glands obtained through an incision into the mucosa of the lower lip) should be performed if Sjögren syndrome is suspected.
Histologic Findings
The term cheilitis glandularis is a provisional clinically descriptive designation rather than a definitive diagnosis. It refers to a constellation of clinical findings that can reflect a broad scope of possible histologic changes; therefore, no consistent or pathognomonic features of this disorder are seen at the microscopic level. Instead, a diverse array of possible alterations can be seen in both the surface epithelium and the submucosal tissues. These findings best enable the clinician to presumptively determine the etiology and the nature of an individual case.
The maturational profile of the epithelium can be essentially normal or show evidence of disturbance that ranges from varying degrees of atypia or dysplasia to frank carcinoma. Epithelial alterations attended by basophilic collagen degeneration (solar elastosis) constitute a diagnosis of actinic cheilitis. The presence of epithelial maturational disturbance indicates risk for progression to carcinoma.
The minor salivary glands may appear normal under the microscope, or they may exhibit various changes indicative of nonspecific sialadenitis. These changes can include atrophy or distention of acini, ductal ectasia with or without squamous metaplasia, chronic inflammatory infiltration and replacement of glandular parenchyma, and interstitial fibrosis. Suppuration and sinus tracts may be present in cases that involve bacterial infection.
Reiter et al studied 77 cases drawn from a literature search from 1950-2010 and added four additional cases. The clinical criteria for cheilitis glandularis that they applied included the coexistence of multiple lesions (on the lower lip primarily) and mucoid/purulent discharge. Their histopathological criteria for cheilitis glandularis required two or more of the following findings: sialectasia, chronic inflammation, mucous/oncocytic metaplasia, and mucin in ducts. Of the 81 cases reviewed only 47 fulfilled the correlated clinicopathological criteria for cheilitis glandularis. In their study, squamous cell carcinoma of the lower lip was found in three cases in conjunction with the submucosal findings. These observations led the researchers to suggest that minor salivary gland findings associated with squamous cell carcinoma or actinic cheilitis are "secondary, reactive changes of the glands". [19]
Other possible histologic findings include stromal edema, hyperemia, surface hyperkeratosis, erosion, or ulceration.
Note the images below.
Medium-power photomicrograph. Note mildly atypical epithelial maturation, modest lymphocytic infiltrate within the lamina propria region, and the striking basophilic collagen degeneration within the superficial stroma plus telangiectasias. The composite features are consistent with a diagnosis of actinic cheilitis (hematoxylin and eosin, original magnification, X100).
Low-power photomicrograph. Deep submucosa of the lip. Several minor salivary glands demonstrate ductal ectasia, interstitial inflammation, atrophy, and fibrosis. No evidence of salivary gland hypertrophy is seen (hematoxylin and eosin, original magnification X40).
Lip biopsy specimen. Low-power photomicrograph reveals focal surface hyperkeratosis accompanied by vascular congestion and fibrosis of the underlying stroma (hematoxylin and eosin, original magnification X40).
High-power photomicrograph of the minor salivary glands. Note ductal ectasia, acinar atrophy, interstitial fibrosis, and inflammation (hematoxylin and eosin, original magnification X100).
-
A 56-year-old woman with an 18-month history of chronic swelling and a dry, burning sensation in her lower lip. She reports intermittent increases and decreases in size of the lip with painful episodes of erosion, crusting, and rare instances of drainage. History reveals medication-induced xerostomia plus a tendency to compulsively lick the lip to maintain hydration. Note eversion of the mucosal surface, which appears erythematous and dry, and narrowing of the vermilion border. The lower labial mucosa appears nodular; however, on palpation, it is diffusely soft. The composite features are consistent with a clinical impression of cheilitis glandularis. A lip biopsy sample was obtained.
-
Medium-power photomicrograph. Note mildly atypical epithelial maturation, modest lymphocytic infiltrate within the lamina propria region, and the striking basophilic collagen degeneration within the superficial stroma plus telangiectasias. The composite features are consistent with a diagnosis of actinic cheilitis (hematoxylin and eosin, original magnification, X100).
-
Low-power photomicrograph. Deep submucosa of the lip. Several minor salivary glands demonstrate ductal ectasia, interstitial inflammation, atrophy, and fibrosis. No evidence of salivary gland hypertrophy is seen (hematoxylin and eosin, original magnification X40).
-
Note the fullness of the lower portion of the lip and the indistinct junction between the vermilion border and the skin.
-
Lip biopsy specimen. Low-power photomicrograph reveals focal surface hyperkeratosis accompanied by vascular congestion and fibrosis of the underlying stroma (hematoxylin and eosin, original magnification X40).
-
High-power photomicrograph of the minor salivary glands. Note ductal ectasia, acinar atrophy, interstitial fibrosis, and inflammation (hematoxylin and eosin, original magnification X100).
