Oral cavity and oropharyngeal squamous cell carcinoma--an update.

Oral cavity squamous cell carcinoma (OC-SCC) is the most common malignancy of the head and neck (excluding nonmelanoma skin cancer). Recent trends have shown a dramatic rise in the incidence of oropharyngeal squamous cell carcinoma (OP-SCC), with a marked increase in lesions related to human papillomavirus infection. This update presents the latest evidence regarding OC-SCC and OP-SCC. In particular, the authors compare and contrast tumors at these two sites with respect to epidemiology, etiopathogenesis, clinicopathologic presentation, clinical assessment, imaging, management, and prognosis. It is important for clinicians to be aware of differences between OC-SCC and OP-SCC so that appropriate patient education and multidisciplinary care can be provided to optimize outcomes.

Grading systems of oral cavity pre-malignancy: a systematic review and meta-analysis.

PURPOSE: Oral potentially malignant disorders (OPMDs) may have varying degrees of oral epithelial dysplasia (OED). Traditional grading schemes separate OED into three-tiers (mild, moderate, and severe). Alternatively, a binary grading system has been previously proposed that stratifies OED into low-risk and high-risk categories based on a quantitative threshold of dysplastic pathologic characteristics. This systematic review evaluates the predictive value of a binary OED grading system and examines agreement between pathologists. METHODS: This meta-analysis queried 4 databases (PubMed, Ovid-MEDLINE, Cochrane, and SCOPUS) and includes 4 studies evaluating binary OED grading systems. Meta-analysis of proportions and correlations was performed to pool malignant transformation rates (MTR), risk of malignant transformation between OED categories, and measures of interobserver agreement. RESULTS: Pooled analysis of 629 lesions from 4 different studies found a six-time increased odds of malignant transformation in high-risk lesions over low-risk lesions [odds ratio (OR) 6.14, 95% 1.18-15.38]. Reported ORs ranged from 2.8 to 22.4. The overall MTR was 26.8%, with the high-risk and low-risk lesions having MTRs of 57.9% (95% CI 0.386-0.723) and 12.7% (95% CI - 0.210 to 0.438), respectively. Pooled unweighted interobserver kappa values for the binary grading system and three-tiered system were 0.693 (95% CI 0.640-0.740) and 0.388 (95% CI 0.195-0.552), respectively. CONCLUSION: Binary grading of OED into low-risk and high-risk categories may effectively determine malignant potential, with improved interobserver agreement over three-tiered grading. Improved grading schemes of OED may help guide management (watchful waiting vs. excision) of these OPMDs.

Perineurioma of the Tongue: A Case Report and Review of the Literature.

A perineurioma (PN) is a rare benign peripheral nerve sheath tumor derived from perineurial cells. Based on clinical and pathologic features, PNs can be classified into 2 major subtypes: intraneural PN (IPN) and the more common extraneural PN (EPN). EPNs and IPNs are extremely rare in the oral cavity, and there have been only 38 reported cases (21 EPNs, 17 IPNs). In the present case, a 20-year-old man presented with a painless left dorsal tongue mass. Excisional biopsy examination indicated a diagnosis of EPN based on microscopic examination with immunohistochemical analysis. Twenty-eight months later the patient presented again with concern for a recurrent lesion. Intraoral examination showed a firm nonulcerated left dorsal tongue mass. Re-excision and microscopic examination with immunohistochemical analysis confirmed the diagnosis of an EPN. This report presents an unusual case of EPN that arose in the tongue and potentially recurred, although the possibility of persistence versus true recurrence exists. In addition, the clinicopathologic characteristics of previously reported cases of oral PN are reviewed.

Calcified chondroid mesenchymal neoplasm: report of a case involving the temporomandibular joint region and review of the literature.

The calcified chondroid mesenchymal neoplasm (CCMN) represents a recently recognized tumor type with only 50 well-documented cases in the English-language literature. Herein we report an additional case of CCMN presenting as a large mass in the temporomandibular joint region of a 41-year-old female. A review of previously reported cases and the current case of CCMN shows the following features: 1) average age 52 years (range 14-87 years) and an approximately even sex distribution; 2) most frequently involved sites: distal extremities (including foot, hand, wrist, forearm) (n=41) and temporomandibular joint/temporal/parotid region (n=9); 3) multilobular soft tissue tumor with chondroid to cartilaginous matrix, often grungy or lace-like calcifications, and variable cytologic atypia; 4) frequently detected FN1 rearrangement (n=15), including FN1 fusion with FGFR2 (n=7) or other receptor tyrosine kinases; 5) 2 reported local recurrences (after incomplete excision); 6) no reports of malignant biologic behavior.

Oral mucoceles: a clinicopathologic review of 1,824 cases, including unusual variants.

PURPOSE: To review the clinicopathologic features of oral mucoceles, with special consideration given to unusual variants and exclusion of salivary duct cysts. MATERIALS AND METHODS: This was a retrospective consecutive case review of all oral mucoceles diagnosed by the Medical University of South Carolina, Oral Pathology Biopsy Laboratory, from 1997 to 2006. The following data were recorded: patient demographics, clinical features (anatomic location, color, size, and consistency), clinical impression, history of trauma, history of periodic rupture, and occurrence of unusual mucocele variants. RESULTS: During the study period, 1,824 oral mucoceles were diagnosed. Of these cases, 1,715 represented histopathologically confirmed cases that were not recurrences. There was no significant gender predilection, and the average age was 24.9 years. The most common locations were the lower labial mucosa (81.9%), floor of mouth (5.8%), ventral tongue (5.0%), and buccal mucosa (4.8%); infrequent sites included the palate (1.3%) and retromolar area (0.5%). The lesions most often were described as blue/purple/gray or normal in color. The mean maximum diameter was 0.8 cm (range, 0.1 to 4.0 cm). In 456 cases, a history of trauma was reported, and in 366 cases a history of periodic rupture was reported. Unusual variants included superficial mucoceles (n = 3), mucoceles with myxoglobulosis (n = 6), and mucoceles with papillary synovial metaplasialike change (n = 2). CONCLUSIONS: Our results confirm the findings of previous investigators regarding the major clinicopathologic features of oral mucoceles. Special variants of oral mucoceles occur infrequently, although it is important to recognize these variants to avoid misdiagnosis.

Plexiform Schwannoma of the Oral Cavity: Report of Eight Cases and a Review of the Literature.

Plexiform schwannoma represents an unusual schwannoma variant, characterized by multinodular growth grossly and/or microscopically. A review of the English-language literature reveals only 28 previously reported cases involving the oral cavity, and herein we present 8 additional cases. Among these 36 patients, the average age at diagnosis was 28 years (range 5 to 62 years), with a female-to-male ratio of 1.4:1. The most frequently involved sites were the tongue (n = 13) and lip (n = 11). Lesion duration prior to presentation averaged 5.3 years (range, 6 weeks to 26 years). The average lesion size was 2.1 cm (range, 0.3 to 16 cm). The typical clinical presentation was a painless mass, although infrequent findings included pain/discomfort, paresthesia, difficulty chewing, and limited buccal mobility. All cases clinically appeared as a solitary mass or localized cluster of tumor nodules, with the exception of one patient who had neurofibromatosis 2 (NF2) and exhibited two distinct nodules on the tongue and buccal mucosa. In addition, extraoral neural neoplasms were evident in four patients, including three with NF2. Typical microscopic findings included multiple well-circumscribed tumor nodules, each surrounded by a perineurium-derived capsule with immunoreactivity for epithelial membrane antigen. The nodules contained characteristically bland and diffusely S-100-positive spindle cells arranged in Antoni A and B patterns; however, modest nuclear pleomorphism was evident in three cases. Most patients (n = 23) were treated by excision or enucleation and curettage, and three patients experienced recurrence. Unlike plexiform neurofibromas, plexiform schwannomas exhibit only a weak association with neurofibromatosis and have no known malignant potential.

Interobserver Variation in Evaluating Perineural Invasion for Oral Squamous Cell Carcinoma: Phase 2 Survey Study.

In a previous study, we found interobserver agreement among 88 board-certified pathologists evaluating perineural invasion (PNI) in oral squamous cell carcinoma (OSCC) was fair, and participants most often used the following criteria: (1) tumor invading the perineurium, (2) tumor surrounding a nerve. In this study, we aimed to determine whether application of these most commonly used criteria may improve interobserver agreement. 512 pathologists were invited to participate in a web-based survey. Participants were asked to assess the presence/absence of PNI in a set of OSCC photomicrographs by applying each of the two criteria above. The survey was completed by 84 board-certified pathologists [mean age: 52 years (range 31-81), mean years in practice: 19 (range 1-56)]. Interobserver agreement was moderate (k = 0.46, 95% CI 0.45-0.46) when using definition #1 (tumor invading the perineurium) and fair (k = 0.24, 95% CI 0.23-0.25) when using definition #2 (tumor surrounding a nerve). By comparison, interobserver agreement was fair (k = 0.36, 95% CI 0.35-0.37) among phase 1 participants asked to evaluate these photomicrographs as they would in their pathology practice. Differences in kappa between definition #1 and phase 1, definition #2 and phase 2, and definition #1 and #2 were statistically significant (p < 0.001). Compared to our prior study based on pathologists' personal views, the current study shows improved interobserver agreement with application of the criterion, "tumor invading the perineurium." However, further work is needed to delineate concise, objective, and more reproducible criteria for histopathologic assessment of PNI.

Oral manifestations of systemic disease.

Careful examination of the oral cavity may reveal findings indicative of an underlying systemic condition, and allow for early diagnosis and treatment. Examination should include evaluation for mucosal changes, periodontal inflammation and bleeding, and general condition of the teeth. Oral findings of anemia may include mucosal pallor, atrophic glossitis, and candidiasis. Oral ulceration may be found in patients with lupus erythematosus, pemphigus vulgaris, or Crohn disease. Additional oral manifestations of lupus erythematosus may include honeycomb plaques (silvery white, scarred plaques); raised keratotic plaques (verrucous lupus erythematosus); and nonspecific erythema, purpura, petechiae, and cheilitis. Additional oral findings in patients with Crohn disease may include diffuse mucosal swelling, cobblestone mucosa, and localized mucogingivitis. Diffuse melanin pigmentation may be an early manifestation of Addison disease. Severe periodontal inflammation or bleeding should prompt investigation of conditions such as diabetes mellitus, human immunodeficiency virus infection, thrombocytopenia, and leukemia. In patients with gastroesophageal reflux disease, bulimia, or anorexia, exposure of tooth enamel to acidic gastric contents may cause irreversible dental erosion. Severe erosion may require dental restorative treatment. In patients with pemphigus vulgaris, thrombocytopenia, or Crohn disease, oral changes may be the first sign of disease.

Pseudomembranous disease (ligneous inflammation) of the female genital tract, peritoneum, gingiva, and paranasal sinuses associated with plasminogen deficiency.

Pseudomembranous disease (or ligneous inflammation) is a rare condition characterized by accumulations of fibrin-rich eosinophilic material. Recent investigations have linked the etiology of this condition to plasminogen deficiency (hypoplasminogenemia). Although much of the literature concerning this disease has focused upon the often clinically striking ocular manifestations, it is important to note that pathologic changes may develop in a variety of anatomic locations, including the oral cavity, upper and lower respiratory tract, female genital tract, kidneys, and gastrointestinal tract. Here, we report an unusual case of a 33-year-old woman who initially presented with gingival inflammation. In subsequent years, she developed additional signs and symptoms related to sinonasal and genital tract involvement. Despite numerous clinical evaluations, biopsies, and laboratory tests, the patient's diagnosis remained elusive for 7 years. Ultimately, it was the distinctive appearance of the gingiva that led to a diagnosis of plasminogen deficiency. Unfortunately, the complicated clinical course and elapsed time between initial presentation and diagnosis illustrated by the present case are not uncommon among patients with this condition. Greater familiarity with the clinical and histopathologic features of this condition among pathologists and treating clinicians is essential for timely diagnosis and management.

Outcomes and prognostic factors for parotid acinic cell Carcinoma: A National Cancer Database study of 2362 cases.

OBJECTIVES: To evaluate the demographics, clinical features, survival outcomes, and prognostic indicators of patients with acinic cell carcinoma (ACC) of the parotid gland with emphasis on the roles of grade, tumor size, and nodal status in survival. MATERIALS AND METHODS: A retrospective analysis of cases diagnosed between 2004 and 2012 from the National Cancer Database was performed. Multivariable logistic regression was used to determine factors associated with survival. RESULTS: 2362 cases were identified. Most patients were females (61.3%) and Caucasian (85.4%) with a median age of 54 years (range, 18-90 years). Most tumors were <3 cm in size (75.8%). Regional metastases and high-grade histology were rare (8.2%, 5.1%). All patients received surgery as primary treatment with 42.7% of patients receiving adjuvant radiation therapy or chemoradiotherapy. 5 year overall survival was 88.6%. On multivariable analysis, age >70 years (hazard ratio [HR]: 10.05, 95% confidence interval [CI]: 5.64-17.91), high-grade (HR: 5.30, 95% CI: 3.39-8.29), tumor size of 3 to 6 cm (HR: 1.53, 95% CI: 1.10-2.12), tumor size >6 cm (HR: 2.98, 95% CI: 1.681-5.289), pN2+ (HR: 3.14, 95% CI: 2.10-4.69), T4 (HR: 2.89, 95% CI: 1.74-4.80) were significant prognosticators. CONCLUSION: Although patients with ACC generally are considered to have a favorable prognosis, an aggressive subgroup with poor outcomes was identified. This group is characterized by high-grade, advanced T classification, tumors larger than 3 cm, with regional metastases and age greater than 70 years. Histologic grade is a substantially stronger predictor of survival than T and N classifications.

Autocrine motility-stimulatory pathways of oral premalignant lesion cells.

Patients with premalignant oral lesions have varying levels of risk of developing oral squamous cell carcinoma (OSCC), whose aggressiveness requires increased motility. Not known is if and how premalignant oral lesion cells acquire the increased motility characteristic of OSCC. This was addressed by immunohistochemical analysis of banked premalignant lesion tissues and by functional analyses using cultures established from premalignant oral lesions and OSCC. These studies showed premalignant oral lesion cells and OSCC to be more motile than normal keratinocytes. Concomitantly, levels of ceramide were reduced. The activity of the protein phosphatase PP-2A, which restricts motility and which can be activated by ceramide, was also diminished. This was due to IL-10 released from premalignant lesion cells. Treatment with a membrane-permeable ceramide restored PP-2A activity and blocked migration. These studies show an autocrine motility-stimulatory pathway that is mediated in premalignant lesion cells by IL-10 through its reduction of ceramide levels and inhibition of PP-2A activity.

Rhabdomyosarcoma of the maxillary gingiva.

BACKGROUND: Rhabdomyosarcoma is a malignant neoplasm of primitive mesenchyme exhibiting skeletal muscle differentiation. Oral rhabdomyosarcoma is rare and accounts for only 0.04% of all head and neck malignancies. METHODS: A 33-year-old woman presented with an erythematous gingival mass involving the anterior maxillary gingiva. The lesion had been present for > or =13 months before presentation, and in recent months, it had become intermittently painful. RESULTS: Clinical examination exhibited erythema and enlargement of the interdental papillae between the left maxillary canine, lateral incisor, and central incisor. The tissue was boggy and tender on palpation. Incisional biopsies were performed, and microscopic examination showed a cellular proliferation of spindle-shaped to ovoid cells with hyperchromatic, enlarged, and pleomorphic nuclei. Many of the tumor cells exhibited abundant eosinophilic cytoplasm. Immunohistochemical stains showed the tumor cells to be positive for desmin, myogenin, and myogenic differentiation 1 (MyoD1). A diagnosis of embryonal rhabdomyosarcoma was made. The patient was treated by surgical resection with postoperative chemotherapy and radiation. The patient had no evidence of disease at a follow-up examination 1 month after completion of therapy. CONCLUSIONS: Oral rhabdomyosarcoma can develop insidiously. Pain is a variable presenting symptom, and early lesions may be mistaken for benign neoplastic, inflammatory, or infectious processes. Over several decades, a multidisciplinary treatment approach that includes surgical removal if resectable, in combination with multiagent chemotherapy and possibly radiation therapy, has improved survival rates.

Is alveolar ridge keratosis a true leukoplakia?: A clinicopathologic comparison of 2,153 lesions.

BACKGROUND: Alveolar ridge keratosis (ARK) is not widely recognized as a distinct clinicopathologic entity, and it often is included in studies of oral leukoplakia (OL), thereby implying premalignant potential. The authors' objectives were to characterize the clinicopathologic features of ARK and determine whether removing ARK from the OL category would significantly affect the prevalence of dysplasia or carcinoma in OL. METHODS: The authors conducted a retrospective consecutive case review of 477 ARK cases and 1,676 OL cases submitted to their biopsy service from 1995 through 2004. The authors defined ARK as a white plaque without erythema or ulceration and limited to the retromolar pad or edentulous ridge. RESULTS: Microscopically, most ARK cases (97.9 percent) exhibited hyperkeratosis without dysplasia. The few dysplastic cases (2.1 percent) were associated with one or more of the following: verrucous appearance, tobacco or alcohol use, multiple OL lesions and previous oral squamous cell carcinoma. Excluding ARK from OL increased the percentage of OL cases exhibiting dysplasia or carcinoma from 20.2 percent to 24.8 percent. Including versus excluding ARK resulted in good but less than excellent agreement in the OL case definition (kappa = 0.6128). CONCLUSIONS: ARK in patients without high-risk habits or other clinical warning signs appears to be a distinctly different lesion from OL, with a much smaller proportion of dysplasia or carcinoma evident among ARK versus OL cases. However, prospective studies are needed to confirm this hypothesis. CLINICAL IMPLICATIONS: Although most cases clinically consistent with ARK are benign hyperkeratoses, dysplasia or carcinoma can be excluded only by means of biopsy and histopathologic examination.

Interobserver Variation Among Pathologists in Evaluating Perineural Invasion for Oral Squamous Cell Carcinoma.

The aims of this study are as follows: (1) to assess variations among pathologists in evaluating perineural invasion (PNI) in oral squamous cell carcinoma (OSCC), (2) to survey PNI criteria used by pathologists and how they came to adopt those criteria. An electronic survey was sent to 363 oral and/or surgical pathologists. Eligibility criteria included pathology board certification. The survey participants were asked to rate whether PNI was present, absent, or uncertain for 15 provided photomicrographs, which depicted various types of tumor-nerve relationships without excessive desmoplasia or lymphocytic host response. The survey obtained information regarding demographics, whether PNI criteria were taught during residency, criteria used by participants to evaluate PNI, how the participants developed their criteria, and agreement with six proposed PNI definitions. 88 pathologists completed the survey. The participants included 47 males and 41 females, with average age = 49 years and average practice experience = 17 years. Practice settings included dental school (40 %), medical school (36 %), private pathology lab (13 %), and other (11 %). Agreement between participants in rating PNI status for the provided images was fair (κ = .38, 95 % CI .37-.39). 56 % of respondents indicated that they were taught PNI criteria during residency training. The basis for criteria currently used by participants included residency training (n = 42), published literature (n = 29), and own experience/views (n = 32). Agreement regarding six proposed PNI definitions was slight (κ = .10, 95 % CI .08-.11). In conclusion, interobserver agreement in assessing PNI status was fair. Our results suggest that more widely accepted, objective, and reproducible criteria are needed for evaluating PNI in OSCC.

Peripheral odontogenic keratocyst: report of two cases and review of the literature.

The odontogenic keratocyst is a developmental odontogenic cyst most commonly occurring in the jaws. In rare instances, however, this lesion has been reported to occur in the gingival soft tissues. Although most authors have regarded these soft tissue lesions to be peripheral odontogenic keratocysts, others have preferred to regard them as histopathologic variants of the gingival cyst of the adult. We document 2 additional cases occurring in the gingival soft tissues, and we review the existing literature concerning this unusual lesion. Given the distinct microscopic features and possible association with nevoid basal cell carcinoma syndrome, we favor the view that this lesion represents the soft tissue counterpart of the intraosseous odontogenic keratocyst.

AAOMP case challenge: painful oral ulcers.

This 33-year old Caucasian female presents complaining of a history of recurrent oral ulcers since childhood. In the past these ulcers typically lasted approximately 7-10 days and recurred every few months. However, more recently she has developed more persistent areas of irritation and ulceration, which tend to come and go. The patient reports the most severe areas of involvement to be the buccal mucosa bilaterally and the lateral tongue. Although in the past her braces seemed to exacerbate her condition, she has not noted significant improvement despite recent removal of her braces by her orthodontist.

Surface Papillary Epithelial Hyperplasia (Rough Mucosa) is a Helpful Clue for Identification of Polymorphous Low-Grade Adenocarcinoma.

The purpose of this study is to evaluate surface papillary epithelial hyperplasia, a microscopic finding that corresponds to the clinical finding of rough or stippled mucosa, as a predictor of polymorphous low-grade adenocarcinoma (PLGA). We conducted a retrospective review of minor salivary gland neoplasms submitted to our biopsy service from 1991 to 2013. Our review was limited to lesions involving the oral cavity/soft palate with the following diagnoses: PLGA, pleomorphic adenoma (PA), mucoepidermoid carcinoma (MEC), and adenoid cystic carcinoma (ACC). A total of 202 minor salivary gland neoplasms were included in the study. Among cases in which surface epithelium was present for evaluation (n = 112), surface papillary epithelial hyperplasia was evident in 30 % of PLGA and 1 % of non-PLGA (i.e., MEC, ACC, PA). The greater frequency of surface papillary epithelial hyperplasia in the PLGA versus non-PLGA cases and in the benign versus malignant cases was significant (p = .0001 and p = .041, respectively). The sensitivity and specificity of papillary epithelial hyperplasia for PLGA were 30 % (95 % confidence interval (CI) 11.97-54.27 %) and 99 % (95 % CI 94-99.82 %), respectively. The clinical presentation of PLGA appeared relatively nonspecific, with all analyzed tumor types exhibiting a predilection for females, middle-aged to older adults, palatal location, pink/tan/normal color, and firm consistency. In conclusion, papillary epithelial hyperplasia was evident in only a minority of PLGA. However, when present within the context of a palatal salivary gland neoplasm, it appears to indicate a high probability of PLGA. Accordingly, rough mucosa may be a useful clinical pearl for identification of PLGA.

Intraosseous schwannoma of the mandible: a case report and review of the literature.

Schwannomas are benign neoplasms originating from the neural sheath and occurring most often in the soft tissues of the head and neck. Intraosseous schwannomas, however, are rare. The most common site of occurrence for these unusual lesions is the mandible. This article documents a case of an intramandibular schwannoma and provides a review of the literature on intraosseous schwannomas, with special attention to cases arising in the mandible and the maxilla.