Brian S. Shumway

Allelic imbalance in oral lichen planus and assessment of its classification as a premalignant condition

OLP is a relatively common immune-mediated mucosal condition with a predilection for middle-aged women. Although classified as a premalignant condition, this classification remains controversial. Using stringent diagnostic criteria, some authors have found that OLP patients are not at increased risk for oral SCC. Credible but limited genetic evidence also indicates that epithelial tissues from OLP patients diagnosed using stringent criteria differs from premalignant or malignant oral lesions but is similar to epithelium from benign oral lesions. To further investigate this genetic line of evidence, biopsy specimens diagnosed as fibroma, OLP, low-grade dysplasia, high-grade dysplasia, and SCC were retrieved from the archives of the Oral Pathology Consultants at the Ohio State University. Using laser capture microdissection, tissue of interest was captured from each case and DNA subsequently extracted. Fluorescently labeled PCR primers were used to amplify DNA at 3 tumor suppressor gene loci (3p14.2, 9p21, and 17p13) and evaluated for LOH or microsatellite instability (MSI). OLP was found to be significantly different from low-grade dysplasia, high-grade dysplasia, and SCC when LOH/MSI was found at more than 1 loci (P = .011, P = .032, P = .003), but not different from benign fibromas (P = .395). In agreement with previous studies, well-documented cases of OLP diagnosed using stringent criteria exhibit a genetic profile more similar to a benign or reactive process than a premalignant/malignant one. These findings do not support the classification of OLP as a premalignant condition.

Platelet-Rich Plasma–Assisted Guided Bone Regeneration for Ridge Augmentation: A Randomized, Controlled Clinical Trial

BACKGROUND Platelet-rich plasma (PRP) contains a number of biologically active growth factors, and previous studies have reported conflicting ridge augmentation results. The primary aim of this randomized, controlled, masked, clinical trial was to determine if PRP combined with a rapidly resorbing cancellous allograft would enhance the regenerative result compared with an allograft without PRP. METHODS Thirty-two patients with an edentulous ridge defect were sequentially entered into the study; four were excluded from data analysis. Fourteen patients received a cancellous allograft (CAN group) and the other 14 received a cancellous allograft mixed with PRP (PRP group). All 28 grafted sites were covered with a resorbable polylactide membrane. After elevation of a full-thickness flap, horizontal ridge dimensions were measured with a digital caliper at the crest and 5 mm apical to the crest. Vertical ridge dimensions were measured from a tooth-supported stent. All sites were reentered at 4 months, and a trephine core was obtained for histologic analysis before implant placement. RESULTS The crestal ridge width for the CAN group had a mean gain of 2.0 ± 1.2 mm, whereas the PRP group gained 2.9 ± 1.0, and the difference was statistically significant between groups (P <0.05). The percent vital bone was 36% ± 14% for the CAN group compared with 51% ± 15% for the PRP group and was statistically significant between groups (P <0.05). Loss of augmented ridge width was 34% ± 17% for the CAN group and 28% ± 17% for the PRP group (P >0.05). CONCLUSION These clinical and histologic findings suggest that PRP enhanced bone regeneration and resulted in increased horizontal bone gain and percentage vital bone.

Basal Cell Carcinoma of the Buccal Mucosa in a Patient with Nevoid Basal Cell Carcinoma Syndrome

Basal cell carcinoma (BCC) of the oral cavity is a controversial lesion with clinical and histopathologic features that overlap with those of peripheral ameloblastoma (PA). Ber-EP4, a cell surface glycoprotein preferentially expressed in BCC of the skin, has been suggested as a useful marker to support the diagnosis of oral BCC.This study presents a case of intraoral BCC arising in the anterior buccal mucosa of a patient with nevoid basal cell carcinoma syndrome (NBCCS), which represents a previously unreported clinical finding, to our knowledge. Histopathologic and immunohistochemical features of the case were compared to examples of PA, conventional intraosseous ameloblastoma, sporadic cutaneous BCC and cutaneous BCC from NBCCS patients. Ber-EP4 expression by the oral tumor was distinct from both peripheral and intraosseous forms of ameloblastoma and was identical to cutaneous BCC in both sporadic and syndromic settings.

Human papillomavirus detection in histologic samples of multifocal epithelial hyperplasia: a novel demographic presentation

OBJECTIVE Human papillomavirus (HPV) typing of oral lesions microscopically consistent with multifocal epithelial hyperplasia (MEH) was performed to identify potential novel clinical presentations. STUDY DESIGN MEH (N = 22 lesions, 17 patients) and squamous papilloma control samples (N = 9 lesions, 9 patients) were compared by using polymerase chain reaction-based HPV genotyping. Students t tests were used to compare continuous characteristics. RESULTS Of the study cases, 86.4% of MEH and only 11% of controls were positive for HPV (P = .0002). In MEH lesions, 45.5% contained HPV32, 36.4% HPV6, and 4.5% HPV40. MEH lesions were mostly multifocal (50%) and occurred in HIV-negative patients (81.3%). They predominated on the labial/buccal mucosa (63.3%), and there were significant differences between groups by anatomic site (P < .0001). HPV32, but not HPV6, was detected in known HIV-positive patients. CONCLUSIONS A novel clinical presentation of MEH associated with HPV32 in HIV-negative, middle-aged to older adults is reported here. One case with HPV40 is the first to be reported. Future detection protocols should include HPV32, as it may be currently overlooked.

Ridge Preservation Comparing a Nonresorbable PTFE Membrane to a Resorbable Collagen Membrane: A Clinical and Histologic Study in Humans.

Purpose:The primary aim of this randomized, controlled, blinded clinical trial was to compare the effect of a resorbable collagen membrane (CM group) versus a nonresorbable high-density polytetrafluoroethylene membrane (PTFE group) on the clinical and histologic outcomes of a ridge preservation procedure. Materials and Methods:All 24 sites received an intrasocket cancellous allograft and a buccal overlay bovine derived xenograft. Results:The change in horizontal crestal ridge width was −1.4 ± 1.2 mm for the CM group, whereas the PTFE group lost −2.2 ± 1.5 mm, which was not statistically significant between groups (P > 0.05). Vertical ridge height change was −1.2 ± 1.5 for the CM group, whereas the PTFE group lost −0.5 ± 1.6, which was not significantly different between groups (P > 0.05). The percent vital bone was similar and not significantly different between groups. Primary closure was not obtained and the exposed membrane portion over the socket opening healed with keratinized tissue. Conclusion:The choice of a resorbable versus a nonresorbable barrier membrane did not affect the clinical or the histologic outcome of ridge preservation treatment.

Clinico-Pathologic Conference: Case 3

Clinical PresentationA 52-year old, HIV? homosexual male presented to adental specialist’s office with a 3 week history of painful‘‘gum sores’’ and a white lesion of the right lateral tongue,which appeared 2 weeks after a vacation to the southernUnited States. General physical exam was unremarkablewith vital signs as follows: temperature, 37.1 C; bloodpressure, 116/74 mm Hg; pulse rate, 88 beats/min; andrespiratory rate, 12 breaths/min. Appropriate medical care,including highly active antiretroviral therapy, had beenadministered since his diagnosis with HIV 10 years pre-viously. His current regimen included abacavir/lamivudine,ritonavir and atazanavir. During this period, annual rapidplasma reagin (RPR) titers were non-reactive, including thelatest testing 8 months prior to lesion onset. The patientindicated that he had been diagnosed and treated forsyphilis in 1975, 33 years previously. Recent laboratoryreports indicated an undetectable viral load with a CD4count of 624 cells/mm

Viral DNA integration and methylation of human papillomavirus type 16 in high-grade oral epithelial dysplasia and head and neck squamous cell carcinoma

This study evaluated the integration and methlyation of human papillomavirus type 16 (HPV16) in head and neck squamous cell carcinoma (HNSCC) and its oral precursor, high-grade oral epithelial dysplasia (hgOED). Archival samples of HPV16-positive hgOED (N = 19) and HNSCC (N = 15) were evaluated, along with three HNSCC (UMSCC-1, -47 and -104) and two cervical cancer (SiHa and CaSki) cell lines. HgOED cases were stratified into three groups with increasing degrees of cytologic changes (mitosis, karyorrhexis and apoptosis). The viral load was higher and the E2/E6 ratio lower (indicating a greater tendency toward viral integration) in group 3 than in groups 1 or 2 (p = 0.002, 0.03). Methylation was not observed in hgOED cases and occurred variably in only three HNSCC cases (26.67%, 60.0% and 93.3%). In HNSCC cell lines, lower E7 expression correlated with higher levels of methylation. HgOED with increased cytologic change, now termed HPV-associated oral epithelial dysplasia (HPV-OED), exhibited an increased viral load and a tendency toward DNA integration, suggesting a potentially increased risk for malignant transformation. More detailed characterization and clinical follow-up of HPV-OED patients is needed to determine whether HPV-OED is a true precursor to HPV-associated HNSCC and to clarify the involvement of HPV in HNSCC carcinogenesis.

Oral Atypical Cellular Blue Nevus: An Infiltrative Melanocytic Proliferation

The atypical cellular blue nevus is an extremely rare nevomelanocytic lesion which lacks precise histologic characterization in the current literature. Given the potential for significant architectural and cytologic overlap with melanoma, further study, including molecular analysis, is needed. This is the first description of an atypical cellular blue nevus of the oral cavity.

Clinical-Pathological Conference: Case 6

Clinical PresentationA 47-year-old male presented with a 5 cm, firm, painfulswelling over the left mandibular ramus that had progres-sively enlarged and was associated with limitation ofmandibular opening and trismus. He related that he firstnoted symptoms from the area shortly after dental treat-ment involving a tooth in his left lower jaw 2 monthspreviously. He indicated a 72 pack-year history of cigarettesmoking and currently smoked two packs of cigarettes perday. He reported minimal alcohol consumption.Since the swelling was initially believed to represent alesion of the soft tissues, a fine needle aspiration biopsywas performed. When this did not yield diagnostic infor-mation, a computed tomographic (CT) scan was obtained.At the time of the scan, paresthesia of the left lower lip wasobserved.The CT scan revealed an expansile, aggressive-appear-ing process with a sunburst-type periosteal reaction sur-rounding the angle and ramus of the left mandible withextension into the infratemporal fossa just below themandibular condyle (Figs. 1, 2) and overlying soft tissueinvolvement. Neoplastic growth was highly suspect.Differential DiagnosisBased on the clinical history, particularly the presence ofpain, swelling and paresthesia, along with available imag-ing, the differential diagnosis is heavily swayed towards amalignancy capable of inducing calcified matrix produc-tion. The most likely considerations include osteosarcoma,chondrosarcoma, and metastatic disease.Osteosarcoma of the jaws typically presents in the 4thdecade as a bony swelling that may also elicit pain andoccasionally causes a neurologic deficit [1, 2]. Mandibularlesions most often affect the posterior body and ramus andoften show extension into soft tissues [2]. Radiographi-cally, lytic lesions are most often observed [1] followed bya sclerotic or mixed appearance. The classic ‘‘sunburst’’pattern noted in lesions of the long bones is uncommon inthe jaws [1]. While this patient is a little older than thetypical average age at presentation, the signs, symptoms,location and radiographic features all support a clinicaldiagnosis of osteosarcoma.Chondrosarcoma of the jaw is a rare tumor which mostoften affects the maxilla and is most often reported in the5th decade with a wide age range [3]. Clinically, the tumoris characterized by swelling; pain is an unusual complaint[3]. Radiographs often show an ill-defined radiolucentmass exhibiting bone destruction, with variable calcifica-tion and soft tissue extension [3]. The age of the patientand location in this case could be consistent with a diag-nosis of chondrosarcoma but the presence of pain andparticularly paresthesia would generally be less likely forthis tumor.