Valerie A. Murrah

Distinctive Pattern of Glial Fibrillary Acidic Protein Immunoreactivity Useful in Distinguishing Fragmented Pleomorphic Adenoma, Canalicular Adenoma and Polymorphous Low Grade Adenocarcinoma of Minor Salivary Glands

Objectives Immunohistochemistry (IHC) can be helpful in the diagnosis of minor salivary gland neoplasms including those that have been incisionally biopsied or fragmented during surgery that do not contain key diagnostic features on hematoxylin and eosin sections. IHC has been used as an adjunct to distinguish among many salivary gland neoplasms using both qualitative and quantitative methods. The objective of this study was to determine whether a distinctive immunoreactivity staining pattern to GFAP can be consistently observed among three selected minor salivary gland neoplasms and thus serve as a diagnostic adjunctive procedure. Study Design Glial fibrillary acidic protein (GFAP) reactivity was examined among 78 minor salivary gland neoplasms: 27 canalicular adenomas (CAA), 21 pleomorphic adenomas (PA) and 30 polymorphous low grade adenocarcinomas (PLGA). Each case was evaluated by two oral and maxillofacial pathologists (OMP) blinded to the diagnosis. Consensus was reached on the pattern of GFAP reactivity among the neoplastic cells and on the similarities and differences among the cases. Results Ninety-six percent (96%) of CAAs demonstrated a distinctive linear immunoreactive pattern among cells in proximity to connective tissue interface. All (100%) PAs demonstrated diffuse immunopositivity within tumor cells. All (100%) PLGAs showed little or no intralesional reactivity and no peripheral linear immunoreactivity. Additional challenge cases were examined by outside OMPs to demonstrate the utility of these findings. Conclusions This study demonstrates that the pattern of GFAP immunoreactivity may be an adjunct to diagnosis among PA, CAA and PLGA. The pattern of distinctly linear GFAP immunoreactivity at the tumor/connective tissue interface in CAA has not been reported previously. This distinctive feature may permit the pathologist to differentiate among CAA, PA and PLGA when an incisional biopsy and/or fragmentation cause key diagnostic features to be absent. Because each of these neoplasms requires a different treatment approach, this can be of major significance.

Carcinoma cuniculatum of the oral mucosa: a potentially underdiagnosed entity in the absence of clinical correlation.

OBJECTIVE To delineate the features of carcinoma cuniculatum (CC), emphasizing potential management errors. STUDY DESIGN A retrospective study examined archival cases of CC. An analysis of clinical, microscopic, and management parameters was performed. RESULTS Ten cases were identified, and their clinical and microscopic features were summarized. CC exhibits a sessile pink/red mildly papillary surface. Histologically, CC presents a tortuous invasive component with a more subtle papillary appearance than verrucous carcinoma. CONCLUSIONS CC is an uncommon variant of squamous cell carcinoma distinct from verrucous carcinoma. Diagnostic delays result from misinterpretation of superficial samples or lack of awareness of the entity. Bland cytology and unusual architecture result in underdiagnosis of CC without clinicopathologic correlation. Clinicians should submit multiple deep samples of lesions displaying a cobblestone-like surface and provide a clinical photograph to the pathologist. Pathologists can avoid underdiagnosis by thorough sampling of biopsies and requesting additional tissue as needed.

Transcriptome Variability in Keratocystic Odontogenic Tumor Suggests Distinct Molecular Subtypes.

Keratocystic Odontogenic Tumor (KCOT) is a locally aggressive developmental cystic neoplasm thought to arise from the odontogenic epithelium. A high recurrence rate of up to 30% has been found following conservative treatment. Aggressive tumor resection can lead to the need for extensive reconstructive surgery, resulting in significant morbidity and impacting quality of life. Most research has focused on candidate-genes with a handful of studies employing whole transcriptome approaches. There is also the question of which reference tissue is most biologically-relevant. This study characterizes the transcriptome of KCOT using whole genome microarray and compare it with gene expression of different odontogenic tissues (“dentome”). Laser capture microdissection was used to isolate the neoplastic epithelial tissue in 20 cases. KCOT gene expression was compared with the “dentome” and relevant pathways were examined. Cluster analysis revealed 2 distinct molecular subtypes of KCOT. Several inflammatory pathways were activated in both subtypes. The AKT pathway was activated in one subtype while MAP kinase pathway was activated in the other. Additionally, PTCH1 expression was downregulated in both clusters suggesting involvement in KCOT tumorigenesis. In conclusion, this study provides new insights into the transcriptome of KCOT and highlights pathways that could be of diagnostic and prognostic value.

Considerations in the diagnosis of oral hairy leukoplakia—an institutional experience

OBJECTIVE We report here the 10-year experience with oral hairy leukoplakia (OHL) at the Division of Oral and Maxillofacial Pathology at the University of North Carolina at Chapel Hill, NC, USA. STUDY DESIGN All the associated hematoxylin and eosin and Epstein-Barr virus encoding region in situ hybridization slides of OHL cases between January 1, 2008, and February 1, 2017, were retrieved and reviewed. Collected demographic characteristics, clinical presentation, medical and social histories were reviewed and reported. RESULTS Six OHL cases with confirmed in situ hybridization showed predilection for the lateral tongue. The study included 3 females and 3 males (mean age 50.5 years; age range 29-70 years). One patient had known HIV-positive status before biopsy was performed. Three patients had reported a history of heavy smoking. Other medical conditions reported were history of breast cancer, a long history of corticosteroid inhaler use for asthma treatment, high cholesterol, diabetes, and hypertension. CONCLUSIONS The findings of this study indicate the need to include OHL as a potential entity in the differential diagnosis of leukoplakic tongue lesions, regardless of the patients HIV status. In addition, the presence of OHL in the patient requires investigation of various explanations for EBV infection, including immunosuppression caused by HIV infection or chronic steroid use.

Ameloblastoma Phenotypes Reflected in Distinct Transcriptome Profiles

Ameloblastoma is a locally invasive benign neoplasm derived from odontogenic epithelium and presents with diverse phenotypes yet to be characterized molecularly. High recurrence rates of 50–80% with conservative treatment in some sub-types warrants radical surgical resections resulting in high morbidity. The objective of the study was to characterize the transcriptome of ameloblastoma and identify relevant genes and molecular pathways using normal odontogenic tissue (human “dentome”) for comparison. Laser capture microdissection was used to obtain neoplastic epithelial tissue from 17 tumors which were examined using the Agilent 44 k whole genome microarray. Ameloblastoma separated into 2 distinct molecular clusters that were associated with pre-secretory ameloblast and odontoblast. Within the pre-secretory cluster, 9/10 of samples were of the follicular type while 6/7 of the samples in the odontoblast cluster were of the plexiform type (p < 0.05). Common pathways altered in both clusters included cell-cycle regulation, inflammatory and MAPkinase pathways, specifically known cancer-driving genes such as TP53 and members of the MAPkinase pathways. The pre-secretory ameloblast cluster exhibited higher activation of inflammatory pathways while the odontoblast cluster showed greater disturbances in transcription regulators. Our results are suggestive of underlying inter-tumor molecular heterogeneity of ameloblastoma sub-types and have implications for the use of tailored treatment.

The future of oral and maxillofacial pathology.

The future of oral and maxillofacial pathology* John M. Wright, DDS, MS, Steven D. Vincent, DDS, MS, Susan Muller, DMD, MS, Kenneth D. McClatchey, DDS, MD, Steven D. Budnick, DDS, and Valerie A. Murrah, DDS, MS, Dallas, Tex; Iowa City, Iowa; Atlanta, Ga; Maywood, Ill; and Chapel Hill, NC BAYLOR COLLEGE OF DENTISTRY, UNIVERSITY OF IOWA, EMORY UNIVERSITY, LOYOLA UNIVERSITY, AND UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL