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.

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.

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.

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.

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.

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.

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.

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.

Bone- and cartilage-forming tumors and ewing sarcoma: an update with a gnathic emphasis.

Over the past decade, there have been remarkable advances in bone tumor pathology. Insights into the genetic basis and pathobiology of many tumor types have impacted diagnosis, classification, and treatment. However, because gnathic lesions may comprise only a small proportion of cases overall for many tumors, clinicopathologic features and management considerations specific to this subset may be overlooked. Here we provide a summary of recent developments in the following tumor types: osteosarcoma (OS), chondrosarcoma (CS), osteoid osteoma (OO), osteoblastoma (OB), and Ewing sarcoma (ES). In particular, we will give special consideration to cases arising in the jaws.

Sclerosing rhabdomyosarcoma: report of a case arising in the head and neck of an adult and review of the literature.

Sclerosing rhabdomyosarcoma is a unique rhabdomyosarcoma variant, characterized by a prominent hyalinizing matrix. A notable pitfall is the potential for the unusual matrix and often pseudovascular growth pattern of this lesion to lead to confusion with other sarcoma types, including osteosarcoma, chondrosarcoma, and angiosarcoma. Here we report a case of sclerosing rhabdomyosarcoma arising in a 40-year old male. The tumor was centered in the pterygomaxillary fossa with extensive infiltration into adjacent structures. Fine needle aspiration yielded a preliminary diagnosis of high-grade pleomorphic undifferentiated sarcoma, for which he received neoadjuvant chemotherapy and surgical resection. Microscopic examination showed a malignant spindled to round cell neoplasm with prominent osteoid-like, hyaline stroma. Focal rhabdomyoblastic differentiation and diffuse immunoreactivity for desmin and myogenin aided in diagnosis. Nineteen months status post primary resection, the patient expired with multiple lung and bony metastases. Among 39 cases reported thus far (including the present case), there is a broad age range (0.3-79 years), with an average age at presentation of 27 years. The most commonly involved sites are the extremities (n = 19) and head and neck (n = 15). Most cases have been treated by resection, often combined with radiation and/or chemotherapy. Out of 31 cases with follow-up information provided, 6 patients developed local recurrence, 7 patients developed regional or distant metastasis, and 5 patients died of disease. Herein we discuss the ongoing controversy regarding how sclerosing rhabdomyosarcoma might best fit into existing rhabdomyosarcoma classification schemes, based upon current clinicopathologic and molecular genetic evidence.

Intravascular fasciitis: report of an intraoral case and review of the literature.

Intravascular fasciitis (IF) is an unusual variant of nodular fasciitis. It is characterized by intraluminal, intramural, and extramural involvement of small to large arteries or veins. Only three cases involving the oral cavity have been reported previously in the literature. Here we present an additional case of oral IF arising in the submucosa of the upper lip of a 20-year old female. Microscopic examination showed a well-circumscribed, nodular proliferation of spindle cells arranged in intersecting fascicles. Occasional multinucleated giants cells also were noted. The tumor was present within the lumen of an intermediate-sized artery and extended into adjacent smaller vessels, thereby creating a multinodular appearance. Extramural extension into the surrounding connective tissue also was observed. Among the 31 cases of IF reported thus far (including the present case), the majority (n = 23) arose in individuals in the 1st through 3rd decades, with a 1.4:1 male:female ratio. The most common sites of involvement were the head and neck (n = 11) and upper extremity (n = 11), followed by the lower extremity (n = 6) and trunk (n = 3). Conservative excision is standard treatment, although local recurrence has been reported in three cases. It is important for the pathologist to be aware of this lesion in order to avoid misdiagnosis as a sarcoma with angioinvasion.

Implication of RNA-binding protein La in proliferation, migration and invasion of lymph node-metastasized hypopharyngeal SCC cells.

The 5-year survival rate for oral cavity cancer is poorer than for breast, colon or prostate cancer, and has improved only slightly in the last three decades. Hence, new therapeutic strategies are urgently needed. Here we demonstrate by tissue micro array analysis for the first time that RNA-binding protein La is significantly overexpressed in oral squamous cell carcinoma (SCC). Within this study we therefore addressed the question whether siRNA-mediated depletion of the La protein may interfere with known tumor-promoting characteristics of head and neck SCC cells. Our studies demonstrate that the La protein promotes cell proliferation, migration and invasion of lymph node-metastasized hypopharyngeal SCC cells. We also reveal that La is required for the expression of ß-catenin as well as matrix metalloproteinase type 2 (MMP-2) within these cells. Taken together these data suggest a so far unknown function of the RNA-binding protein La in promoting tumor progression of head and neck SCC.

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.

Odontogenic Cysts and Tumors.

This article presents various odontogenic cysts and tumors, including periapical cysts, dentigerous cysts, odontogenic keratocysts, orthokeratinized odontogenic cysts, lateral periodontal cysts, glandular odontogenic cysts, ameloblastomas, clear cell odontogenic carcinomas, adenomatoid odontogenic tumors, calcifying epithelial odontogenic tumors, squamous odontogenic tumors, ameloblastic fibromas, ameloblastic fibro-odontomas, odontomas, calcifying cystic odontogenic tumors, and odontogenic myxomas. The authors provide an overview of these cysts and tumors, with microsopic features, gross features, differential diagnosis, prognosis, and potential diagnostic pitfalls.

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.

Papillary synovial metaplasia-like change in oral mucoceles: a rare and previously undescribed histopathologic variant of a common oral lesion.

The development of synovial membrane-like structures has been described previously only in association with breast implants, the bone-cement interface of hip prostheses, tendon implants, testicular implants, and traumatized skin. Previous investigators have theorized that this phenomenon-referred to as "synovial metaplasia"-develops in response to gliding trauma. In some cases, these lesions can exhibit a papillary growth pattern. We report 2 unusual cases of oral mucoceles exhibiting papillary synovial metaplasia-like change: the first arising in the lower lip of an 11-year old African-American boy and the second in the lower lip of a 12-year-old European-American girl. We propose that these cases represent a rare and previously undescribed histopathologic variant of the oral mucocele. These lesions should be distinguished from other oral lesions that may exhibit a papillary cystic growth pattern.