Verruciform Xanthoma : A Retrospective Clinical and Histopathologic Analysis of 90 Cases

Objective: This study retrospectively investigated the clinical and histopathological findings of lesions diagnosed as Verruciform Xanthoma (VX) by the Louisiana State University Oral Pathology Biopsy Service from 1970 to 2014. Study Design: A clinical and histopathologic evaluation was completed for 99 cases. A questionnaire was sent to surgeons who performed the biopsies from 1994 to 2014 to obtain further patient information regarding recurrence, tobacco use, oral health history, and history of oral trauma. Results: After histopathologic evaluation, 90 confirmed cases of VX were included in the study. Males made up 57.3% of the cases. The mean age was 56.6 and was most common in the 6  Postgraduate Resident, Department of Periodontics, Louisiana State University Health Science Center School of Dentistry, New Orleans, LA Associate Professor and Chair, Department of Diagnostic Sciences, Louisiana State University Health Science Center School of Dentistry, New Orleans, LA #Assistant Professor, Department of Diagnostic Sciences, Louisiana State University Health Science Center School of Dentistry, New Orleans, LA ║Assistant Professor, Department of Periodontics, Louisiana State University Health Science Center School of Dentistry, New Orleans, LA ¶ Corresponding author through 8 decades of life (57.8%). Most common location was the gingiva (47.8%) with 58.1% of the gingival lesions occurring in the mandible. Inflammation was present in 97.8% of the cases with varying severity. Foam cells were found below the rete ridges 23.3% of the time. There was one confirmed recurrence. Seventy percent of the time mitotic figures were detected. Only four clinicians reported any history of trauma in the area of the biopsy. Three patients admitted tobacco use. Conclusions: VX is a rare, benign, slow growing lesion with unknown etiology and low recurrence that commonly affects patients between the 6 and 8 decade of life. Histopathologically these lesions often present with varying degrees of inflammation, hyperparakeratosis, and foam cells between or below the rete ridges. The presence of mitotic figures may be an indication of the etiology or pathogenesis of these lesions. Introduction Verruciform xanthoma (VX) is a rare, benign lesion of the oral mucosa with unknown etiology which was first reported by Shafer in 1971 as a series of 15 cases [1]. Other extra oral sites of development include the vulva [2], penis [3,4], scrotum [5,6,7], and esophagus [8,9]. Current data regarding the prevalence of oral VX is minimal, with Buchner et al. reporting 6 cases out of 24,426 from Oral Pathology Diagnosis Services of University of California from 1968-1980. [14,21]. Clinically VX most commonly presents as a slightly elevated, slow growing, asymptomatic lesion with a rough surface architecture [10]. Lesions have been reported as pink, yellow, red, or gray in color and reportedly range from 1-25 mm [10,12]. VX most often develops on the gingiva and alveolar ridges, however lesions may develop at any intraoral location [11,12]. Given the clinical presentation, the differential diagnosis typically includes squamous papilloma, verruca vulgaris, condyloma acuminatum or possibly squamous cell carcinoma [13,28]. Gender predilection data has varied with some authors finding a slight male predominance and others reporting a slight female predilection [11,12,14]. Previous studies have found that VX can occur over a wide age range, however it is most commonly diagnosed in the fourth to sixth decades of life [12,14]. VX is treated with surgical excision [1] and a limited number of recurrences have been documented [11,12,15]. While the majority of VXs occur in patients who are otherwise healthy, cases have been reported in patients with various inflammatory disorders including discoid lupus erythematosus, pemphigus vulgaris, epidermal dysplasia, bone marrow transplantation, graft-versus-host disease and lichen planus [13,35,36]. Biopsy with histopathologic examination is required to establish a diagnosis of VX. Lesions generally exhibit papillary, hyperplastic stratified squamous epithelium surfaced by a prominent layer of parakeratin. Some have described the parakeratin as having an orange color on hematoxylin and eosin (H&E) staining [11]. The parakeratin may fill crypts between the papillary epithelial projections. Although most lesions exhibit a prominent papillary architecture, some may have a more flat surface. Nowparast et al classified VX into three morphologic subtypes: verrucous, papillary, and flat [12]. Another diagnostic feature is the presence of macrophages with foamy cytoplasm (foam cells or xanthoma cells) within the connective tissue papillae and occasional extension below the level of the rete ridges. [12]. The foam cells are believed to represent inflammatory macrophages based on positive staining with monocytemacrophage biomarkers including CD68 [18,19]. Additionally, these foam cells stain positively with Periodic Acid-Schiff (PAS) and are diastase resistant [16]. Although there have been many single case reports of VX, few large series have been published. The largest case series are Nowparast et al (54 cases), Ide et al (36 cases), and Neville and Weathers (21 cases) [12,31,11]. The purpose of this study was to examine 90 VX cases diagnosed at the Louisiana State University School of Dentistry (LSUSD) Oral Pathology Biopsy Service between January 1, 1970 to December 31, 2014. Available patient demographics were recorded and additional data received from a follow-up questionnaire to clinicians who submitted the biopsy was collected. A detailed histopathologic analysis of all specimens was performed. Materials and Methods: This project was approved by the Louisiana State University Health Sciences Center Institutional Review Board. Ninety-nine cases diagnosed as VX were identified through a search of the LSU Oral Pathology Biopsy Service database from January 1, 1970 to December 31, 2014. Pathology request forms submitted with the specimens, glass slides and pathology reports were collected and reviewed. Nine cases were excluded due to degraded slide quality or lack of definitive diagnostic features. The 90 remaining cases were included in the study. The following clinical and demographic features were collected: age, gender, race, location of lesion, size of specimen. A questionnaire was mailed to all clinicians who submitted biopsies between 1994 and 2014. Because records are not generally required by law to be kept for more than 7 years post treatment, the likelihood of record availability for cases submitted samples submitted prior to 1994 was presumed to be low. The purpose of the questionnaire was to gather more information regarding history of trauma at the site of the VX, recurrence, use of tobacco products, and presence of other mucosal lesions. All H&E-stained glass slides were initially reviewed by a third year periodontics resident and subsequently assessed by two board certified oral and maxillofacial pathologists. Each case was evaluated for the following features: papillary or flat architecture, presence of ulceration, parakeratosis, hyperkeratosis, location of foam cells (between rete ridges only or extension beyond rete ridges), location and intensity of inflammation, and quantity of epithelial mitotic figures per 5 high power fields (HPF, 40x). Frequency of mitoses was divided into three categories: absent (none observed per 5 HPF), less than 3 per 5 HPF, or 3 or more per 5 HPF.