Oral Mycosis Fungoides: A Report of Three Cases and Review of the Literature.

Mycosis fungoides (MF) and Sézary syndrome are clonal T-cell proliferations that exhibit skin homing and represent the majority of cutaneous T-cell lymphomas. Early MF is a diagnostic challenge as both the clinical and microscopic features often mimic benign inflammatory conditions. Oral MF is very rare and has been associated in the past with advanced disease and a poor prognosis. Skin lesions are present for an average of > 6 years before oral involvement occurs. The clinical appearance is highly variable with tongue, palate and gingiva most often affected. We report 3 additional cases of oral MF, including one in which oral lesions are the initial disease presentation. Survival in patients presenting with oral MF is improving and can be attributed to advances in therapy.

Opportunistic Oral Infections.

An opportunistic infection (OI) is a disease of microbial cause or pathogenesis generally thought to occur in hosts with weakened immunity. Oral OIs are associated with many risk factors and pathogens. Causative organisms for oral OIs have unique modes of transmission. The clinical presentation of oral OIs is heterogeneous and diagnosis can be challenging. Therefore, laboratory identification of causative pathogens is useful for definitive diagnosis and targeted therapeutics, and can be achieved by biological, serologic, histologic, and/or molecular methods. Clinical risk assessment and history with review of systems, and accurate diagnosis, treatment, and follow-up, are essential.

Hair Follicle Nevus With Features of Comedo Nevus: An Expanding Spectrum.

Hair follicle nevus (HFN) is a rare hamartomatous lesion of the folliculosebaceous unit, with or without admixed fibroadipose or muscular tissue. It typically has a congenital presentation in the preauricular area of infants and is frequently confused with an accessory tragus. Acquired tumors with similar histopathologic features have been described infrequently during adolescence and adult life. We report yet another unique presentation of this unusual lesion in a 4-year-old girl who had a long-standing tumor of the nasal columella that started growing rapidly after trauma. Histopathologic examination revealed increased numbers of hair follicles, some of which were associated with diminutive sebaceous glands, with no associated central cystic structure. In addition, the infundibula of the follicles were dilated and filled with keratinous debris. Although these hamartomas are common in the head and neck region, to our knowledge, this is the first report of a HFN at this anatomic location. In addition, this tumor has an overall architecture of a HFN but is accompanied by features of a comedo nevus. We also present a review of the literature and summarize the current diagnostic criteria for HFN.

Evaluating a Web-Based Educational Module on Oral Cancer Examination Based on a Behavioral Framework.

Patients at risk of developing oral and/or oropharyngeal cancer (OPC) are more likely to see primary care providers (PCPs) than a dentist. Many PCPs do not regularly perform oral cancer examination (OCE). The purpose of this study was to design a web-based educational program based on a behavioral framework to encourage PCPs to conduct OCE. PCPs were solicited to provide feedback on the program and to evaluate their short-term knowledge. The integrated behavioral model was used to design the program. Fifteen PCPs (five in each group: physicians, physician assistants, and nurse practitioners) reviewed the program and took a posttest: (1) index of knowledge of risk factors for oral cancer (RiskOC) and (2) index of knowledge of diagnostic procedures for oral cancer (DiagOC). Findings from the process evaluation were mainly positive, with comments on the length of the program comprising the ten negative comments. No significant difference among groups of PCPs (physicians, physician assistants, and nurse practitioners) was detected for DiagOC (p = 0.43) or RiskOC (p = 0.201). A program on OPC for PCPs should be less than 40 min. Postviewing knowledge outcomes were similar for all PCPs. The web-based program on OPC based on a behavioral framework could have similar short-term knowledge outcomes for all PCPs and may increase the number of PCPs performing OCEs.

The prevalence of pseudoxanthoma elasticum-like connective tissue changes in an oral biopsy service and review of the literature.

OBJECTIVE: The objective of this pilot study is to determine the prevalence of pseudoxanthoma elasticum (PXE)-like connective changes in an oral biopsy service and compare it with the estimated prevalence of PXE as well as to the prevalence of the mutated PXE gene ABCC6. STUDY DESIGN: This prevalence study utilized 500 oral mucosal biopsy specimens received from the biopsy service of the Oral Pathology Consultants at the Ohio State University. Each specimen was microscopically evaluated using hematoxylin and eosin, Verhoeff-van Gieson and von Kossa stains. RESULTS: A prevalence of 9.8% was identified for PXE-like changes in the connective tissue of oral biopsy specimens submitted to this service. CONCLUSIONS: The overall prevalence of PXE-like connective tissue changes found in routine oral mucosal biopsy specimens (9.8%) was much higher than either the suspected prevalence of PXE (0.001%-0.004%) or the estimated prevalence of the mutated gene ABCC6 (0.625%-1.25%).

Oral ulceration associated with concurrent herpes simplex virus, cytomegalovirus, and Epstein-Barr virus infection in an immunocompromised patient.

In immunocompromised patients, oral ulcerations are common and have a wide spectrum of causes, including herpesvirus infection. We report on a case in which an oral ulcer was simultaneously infected by herpes simplex (HSV), cytomegalovirus (CMV), and Epstein-Barr virus (EBV) in a kidney-pancreas transplant recipient. A 46-year-old woman presented with a clinically nonspecific dorsal tongue ulcer of 3 months duration. Histopathologic evaluation indicated keratinocytes exhibiting herpetic viral cytopathic effect. Nuclear and cytologic alterations suggestive of CMV infection were found in endothelial cells subjacent to the ulcer. Immunohistochemistry testing for HSV and CMV was positive in these cells. Large atypical mononuclear cells were also evident in the ulcer bed's inflammatory infiltrate, which had intense nuclear positivity for Epstein-Barr encoding region in situ hybridization. We believe this is the first well-documented report of the definitive concomitant presence of HSV, CMV, and EBV in an immunocompromised patient. Although the pathogenesis of coinfected ulcers remains unknown, a synergistic effect is possible.

A rapidly growing mandibular swelling.

The authors ask readers to diagnose a case of a patient who visited a dental clinic seeking evaluation and treatment of a rapidly growing swelling of the left mandible of approximately three months' duration.

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.

Lymphomatoid granulomatosis presenting with gingival involvement in an immune competent elderly male.

Lymphomatoid granulomatosis (LYG) represents a B cell lymphoproliferative disorder that appears to be driven by infection of the lesional cells by Epstein-Barr virus (EBV). Although not a common condition, the overwhelming majority of cases affect the lungs and mediastinal lymph nodes. Oral mucosal involvement has been documented in only one other report. We describe an 82-year-old man who developed a chronic oral ulcer following extraction of a mandibular molar tooth. Biopsy of the ulcer identified large atypical mononuclear cells that had a B cell immunophenotype and were associated with the walls of several arterioles in the sample. In situ probes for EBV-encoded small RNA showed prominent labeling of these large cells, suggesting the possibility of LYG. Imaging studies identified mediastinal and hilar lymphadenopathy on CT imaging, while PET scans showed hypermetabolic activity in the lymph nodes as well as the left mandible. Based on these findings, a diagnosis of LYG was made and the patient was treated with rituximab, an anti-CD20 monoclonal antibody, combined with a chemotherapeutic regimen consisting of etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin. After three cycles of therapy, the oral ulcer resolved significantly, as well as the areas of hypermetabolic nodal activity. Remission continued for 3 years, however the patient eventually developed non-small cell carcinoma of the lung and expired as a result of that tumor.

Human cytomegalovirus and mucoepidermoid carcinoma of salivary glands: cell-specific localization of active viral and oncogenic signaling proteins is confirmatory of a causal relationship.

Human cytomegalovirus (hCMV) infection is common. Although still controversial, there is growing evidence that active hCMV infection is associated with a variety of malignancies, including brain, breast, lung, colon, and prostate. Given that hCMV is frequently resident in salivary gland (SG) ductal epithelium, we hypothesized that hCMV would be important to the pathogenesis of SG mucoepidermoid carcinoma (MEC). This was initially supported by our finding that purified CMV induces malignant transformation in SG cells in an in vitro mouse model, and utilizes a pathogenic pathway previously reported for human MEC. Here we present the histologic and molecular characterizations of 39 human SG MECs selected randomly from a repository of cases spanning 2004-2011. Serial sections were obtained from formalin-fixed, paraffin embedded, tissue blocks from previous incisional or excisional biopsies. Immunohistochemical assays were performed for active hCMV proteins (IE1 and pp65) and the activated COX/AREG/EGFR/ERK signaling pathway. All four prospective causal criteria for viruses and cancer are fully satisfied: (1) protein markers for active hCMV are present in 97% of MECs; (2) markers of active hCMV are absent in non-neoplastic SG tissues; (3) hCMV-specific proteins (IE1, pp65) are in specific cell types and expression is positively correlated with severity; (4) hCMV correlates and colocalizes with an upregulation and activation of an established oncogenic signaling pathway (COX/AREG/EGFR/ERK). Thus, the evidential support reported here and previously in a mouse model is strongly confirmatory of a causal relationship between hCMV and SG mucoepidermoid carcinoma. To our knowledge, this is the first demonstration of hCMV's role in human oncogenesis that fully responds to all of Koch's Postulates as revised for viruses and cancer. In the absence of any contrary evidence, hCMV can reasonably be designated an "oncovirus."

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.

Angiopoietin-like 4: a novel molecular hallmark in oral Kaposi's sarcoma.

Kaposi's sarcoma (KS) remains among the most common causes of oral cancer in HIV-infected individuals. Infection with the KS-associated herpesvirus (KSHV/HHV8) is a necessary event for disease development. Emerging evidence suggests that KSHV infects vascular endothelial (or endothelial progenitor) cells promoting the formation of the KS tumor (or spindle) cell. These cells elaborate angiogenic growth factors and cytokines that promote the dysregulated angiogenesis and profuse edema that characterizes this unusual vascular tumor. Central among these secreted factors is the potent endothelial cell mitogen, vascular endothelial growth factor (VEGF). Indeed, VEGF has proven to be a key player in KSHV pathogenesis and is a molecular hallmark of KS lesions. We have recently shown that a second angiogenic factor, Angiopoietin-like 4 (ANGPTL4), may also play a critical role in KS development. Here we demonstrate that ANGPTL4 is upregulated both directly and indirectly by the KSHV oncogene, vGPCR. We further show that ANGPTL4 is a molecular hallmark of oral KS lesions. Indeed, expression of this protein was observed in more tumor cells and in more biopsies specimens than expression of VEGF (23/25 or 92% vs. 19/25 or 76%, respectively) in oral KS. These surprising results support a key role for ANGPTL4 in Kaposi's sarcomagenesis and further suggest that this angiogenic factor may provide a novel diagnostic and therapeutic marker for oral KS patients.

Multifocal lateral periodontal cysts: a report of 4 cases and review of the literature.

Lateral periodontal cyst (LPC) is a developmental jaw cyst of odontogenic origin. It has characteristic histopathologic features that are identical to those seen in the peripherally occurring gingival cyst of adults (GCA). The polycystic variant of LPC is termed the botryoid odontogenic cyst (BOC). The histogenetic origin of LPC is probably the rests of dental lamina in the alveolar bone. In the case of BOC, it might be that several adjacent epithelial rests simultaneously undergo cystic change and eventually form a polycystic lesion. Few previous examples of multifocal occurrence of LPC can be found in the literature. We report an additional 4 patients with this rare presentation of multiple, separate LPCs, and review the literature on this topic.

Aggressive osteoblastoma of the maxilla: a case report and review of the literature.

Aggressive osteoblastoma is a rare primary bone neoplasm with the potential for local invasion and recurrence. While the vertebrae or long bones are most commonly affected, few well-documented cases have been reported in the jaws. A 25-year-old man presented with a palatal mass of several months' duration. He reported the lesion had undergone gradual enlargement and, while generally asymptomatic, had recently become increasingly painful. An incisional biopsy was interpreted as "osteoblastic neoplasm" most suggestive of osteoblastoma. However, final diagnosis was deferred until the resection specimen could be evaluated. Following partial maxillectomy, histopathologic examination revealed a proliferation of large epithelioid cells with eccentric nuclei and prominent nucleoli associated with broad, irregular deposits of osteoid and trabeculae of bone. The lesional cells exhibited minimal pleomorphism with infrequent, normal-appearing mitotic figures and numerous osteoclast-like giant cells were observed within an associated loose fibrovascular stroma. Transformation of "blue bone" to more organized eosinophilic trabeculae of woven bone was noted at the periphery of the lesion and there was no evidence of invasion. A diagnosis of aggressive osteoblastoma was made. Previous reports of gnathic aggressive osteoblastoma are reviewed and the features that distinguish this process from conventional osteoblastoma or osteoblastoma-like osteosarcoma are presented.

Trabecular and psammomatoid juvenile ossifying fibroma of the skull base mimicking psammomatoid meningioma.

Ossifying fibroma (OF) is a fibro-osseous tumor that usually occurs in young people and arises in the craniofacial bones. We report a case of a 15-year-old boy who developed progressive proptosis and hypertelorism and was found to have a mid-face and skull base tumor, initially diagnosed as psammomatoid meningioma. The tumor recurred and the resected specimen revealed a unique OF having trabecular and psammomatoid features. The clinical, radiographic, histopathologic findings and differential diagnoses of the case are presented.

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.