Faizan Alawi

Solitary fibrous tumor of the oral soft tissues: a clinicopathologic and immunohistochemical study of 16 cases.

We describe the clinicopathologic and immunohistochemical features of 16 solitary fibrous tumors (SFTs) originating within the oral soft tissues. There were 10 women and six men with a mean age at diagnosis of 56 years. In all cases the tumors were slow-growing, asymptomatic, submucosal growths of variable size and duration. The buccal mucosa was involved in 12 cases, and the tongue and lower lip were affected in two cases, respectively. Thirteen tumors developed on the left side of the mouth. Follow-up information was available in 10 cases and averaged 44.7 months, with no evidence of recurrence or metastasis. All 16 tumors were well circumscribed and demonstrated histologic features that were invariably benign. In all cases they were composed of an admixture of alternating hypercellular and hypocellular, collagenous zones; haphazardly arranged, cytologically bland spindle and ovoid cells that in areas were intimately intermixed with collagen; a prominent vasculature; and perivascular hyalinization. Immunohistochemically, the tumors were consistently positive for CD34, bcl-2, factor XIIIa, and vimentin, whereas 75% of the tumors were reactive for CD99. To further define the clinicopathologic profile of intraoral SFT, we include a review of the previously reported cases. We also include a comparison and brief review of the clinicopathologic and immunohistochemical features of other spindle cell tumors of the oral cavity, from which SFTs must be differentiated.

Diabetes aggravates periodontitis by limiting repair through enhanced inflammation

Periodontitis is the most common lytic bone disease and one of the first clinical manifestations of diabetes. Diabetes increases the risk of periodontitis. The aim of the present study was to examine mechanisms by which diabetes aggravates periodontitis. Ligature‐induced periodontitis was examined in Goto‐Kakizaki rats with type 2 diabetes. A tumor necrosis factor (TNF)‐specific‐inhibitor, pegsunercept, was applied to diabetic rats after the onset of periodontal disease. Interferon‐γ (IFN‐γ), TNF‐α, interleukin‐1 β (IL‐1β), fibroblast growth factor‐2 (FGF‐2), transforming growth factor beta‐1 (TGFβ‐1), bone morphogenetic protein‐2 (BMP‐2), and BMP‐6 were measured by real‐time RT‐PCR, and histological sections were examined for leukocyte infiltration and several parameters related to bone resorption and formation. Inflammation was prolonged in diabetic rats and was reversed by the TNF inhibitor, which reduced cytokine mRNA levels, leukocyte infiltration, and osteoclasts. In contrast, new bone and osteoid formation and osteoblast numbers were increased significantly vs. untreated diabetic animals. TNF inhibition in diabetic animals also reduced apoptosis, increased proliferation of bone‐lining cells, and increased mRNA levels of FGF‐2, TGFβ‐1, BMP‐2, and BMP‐6. Thus, diabetes prolongs inflammation and osteoclastogenesis in periodontitis and through TNF limits the normal reparative process by negatively modulating factors that regulate bone.—Pacios, S., Kang, J., Galicia, J., Gluck, K., Patel, H., Ovaydi‐Mandel, A., Petrov, S., Alawi, F., Graves, D. T. Diabetes aggravates periodontitis by limiting repair through enhanced inflammation. FASEB J. 26, 1423‐1430 (2012). www.fasebj.org

Hamartomatous tongue lesions in children

The incidence and spectrum of tongue lesions in children, in particular tongue hamartomas, is relatively unknown. We report a retrospective review of all tongue lesions seen at a major tertiary care childrens hospital over an 18-year period with an emphasis on describing tongue hamartomas. A total of 135 tongue lesions were identified. Vascular/lymphatic lesions (36/135) were the most common followed by mucus extravasation phenomenon (22/135). Interestingly, hamartomatous lesions (18/135) were the third most common lesion category identified. Lingual hamartomas were predominantly submucosal in location and were classified histologically by tissue composition as follows: neurovascular (2/18), smooth muscle predominant (5/18), fat predominant (1/18), and smooth muscle and fat containing (10/18). All 5 smooth muscle predominant hamartomas also contained vasculature, and 1 case additionally contained salivary gland tissue. The single fat predominant hamartoma additionally contained vessels and salivary gland. The final 10 hamartomas contained varying amounts of both smooth muscle and fat, and also admixed combinations of vessels, nerves, and salivary glands. Two of these 10 cases additionally contained foci of choristomatous elements, including cutaneous adnexal structures and cartilage. Most patients with hamartomatous lesions were young, 2 years or less. Eight cases were congenital in origin. Females outnumbered males by 2:1. The majority of lesions (16/18) were dorsal in location, and 4 patients had a syndromic association, all oral-facial-digital syndrome.

Transgenic Mice that Express Normal and Mutated Amelogenins

Amelogenin proteins are secreted by ameloblasts within the enamel organ during tooth development. To better understand the function of the 180-amino-acid amelogenin (M180), and to test the hypothesis that a single proline-to-threonine (P70T) change would lead to an enamel defect similar to amelogenesis imperfecta (AI) in humans, we generated transgenic mice with expression of M180, or M180 with the proline-to-threonine (P70T) mutation, under control of the Amelx gene regulatory regions. M180 teeth had a relatively normal phenotype; however, P70T mineral was abnormally porous, with aprismatic regions similar to those in enamel of male amelogenesis imperfecta patients with an identical mutation. When Amelx null females were mated with P70T transgenic males, offspring developed structures similar to calcifying epithelial odontogenic tumors in humans. The phenotype argues for dominant-negative activity for the P70T amelogenin, and for the robust nature of the process of amelogenesis.

Pigmented Lesions of the Oral Cavity: An Update

Oral pigmentation may be focal, multifocal, or diffuse. The lesions may be blue, purple, brown, gray, or black. They may be macular or tumefactive. Some are localized harmless accumulations of melanin, hemosiderin, or exogenous metal; others are harbingers of systemic or genetic disease; and some can be associated with life-threatening medical conditions that require immediate intervention. The differential diagnosis for any pigmented lesion is extensive, and can include examples of endogenous and exogenous pigmentation. Although biopsy is a helpful and necessary aid in the diagnosis of focally pigmented lesions, with diffuse presentations lesions require a thorough history and laboratory studies to establish a definitive diagnosis.

Medical management update: Peutz Jeghers syndrome

Peutz Jeghers syndrome (PJS) is an autosomal dominant disease characterized by hamartomatous polyposis and distinct mucocutaneous pigmentation. PJS is associated with an increased risk for several cancers and other complications such as small intestine intussusception, short bowel syndrome, and anemia. Medical management mainly consists of treatment of the polyps and surveillance. This medical management update will review clinical concepts, therapeutic advances, and emphasize features of PJS important to the oral health care provider.

Dyskerin is required for tumor cell growth through mechanisms that are independent of its role in telomerase and only partially related to its function in precursor rRNA processing

Dyskerin is an essential nucleolar protein required for the biogenesis of ribonucleoproteins that incorporate H/ACA RNAs. Through binding to specific H/ACA RNAs, dyskerin exerts most of its influence in the cell. To that end, dyskerin is a core component of the telomerase complex and is required for normal telomere maintenance. Dyskerin is also required for post‐transcriptional processing of precursor rRNA. Germline dyskerin mutations increase cancer susceptibility. Conversely, wild‐type dyskerin is usually over‐expressed and not mutated in sporadic cancers. However, the contributions of dyskerin to sporadic tumorigenesis are unknown. Described herein, we demonstrate that acute loss of dyskerin function by RNA interference significantly reduced steady‐state levels of H/ACA RNAs, disrupted the morphology and inhibited anchorage‐independent growth of telomerase‐positive and telomerase‐negative human cell lines. Unexpectedly, dyskerin depletion only transiently delayed rRNA maturation but with no appreciable effect on the levels of total 18S or 28S rRNA. Instead, while rRNA processing defects typically trigger p53‐dependent G1 arrest, dyskerin‐depleted cells accumulated in G2/M by a p53‐independent mechanism, and this was associated with an accumulation of aberrant mitotic figures that were characterized by multi‐polar spindles. Telomerase activity and the rate of rRNA processing are typically increased during neoplasia. However, our cumulative findings indicate that dyskerin contributes to tumor cell growth through mechanisms which do not require the presence of cellular telomerase activity, and which may be only partially dependent upon the proteins role in rRNA processing. These data also reinforce the notion that loss and gain of dyskerin function may play important roles in tumorigenesis. Mol. Carcinog.

Burkitt lymphoma of the oral cavity: an atypical presentation

Burkitt lymphoma (BL) is an aggressive form of non-Hodgkin B-cell lymphoma with 3 variants: endemic, sporadic, and immunodeficiency-associated types. The sporadic form, most commonly involving the abdomen and ileocecal region, presents as an abdominal mass, rarely presenting in the orofacial region. A 36-year-old Indian female presented to the Hospital of the University of Pennsylvania for evaluation of a persistent intraoral swelling ulceration of the lower right mandibular alveolar ridge with minimal bony invasion. Progressive systemic symptoms of fatigue, weakness, and fever developed without resolution following treatment for a presumed odontogenic infection in the 4 weeks before presentation. An incisional biopsy revealed a diffuse proliferation of intermediate- to large-sized lymphocytes with multiple small peripheral nucleoli, scant cytoplasm, and nuclear pleomorphism. Nearly all cells displayed Ki67 expression. A final diagnosis of BL was rendered following confirmation of a cMYC translocation by fluorescence in situ hybridization. This article presents a case of the sporadic form of BL with atypical presentation clinically and morphologically, primarily involving the oral soft tissue.

Epithelioid blue nevus of the oral mucosa: a rare histologic variant.

Epithelioid blue nevus (EBN) is an extremely rare histologic variant of blue nevus that has only recently been identified. Unlike other variants of blue nevus, which primarily are composed of pigmented, spindle-shaped melanocytes, EBN is characterized by large, well-defined, heavily-pigmented polygonal or epithelioid-shaped melanocytes intermixed with less densely pigmented epithelioid- and fusiform-shaped melanocytes. Furthermore, in contrast to other benign melanocytic proliferations, the lesional cells in EBN exhibit little or no maturation as they extend deeper into the underlying tissue. Blue nevi are the second most common form of nevus in the oral cavity. However, to our knowledge, the epithelioid variant has not been previously identified in the mouth. Only 6 examples of EBN have been identified in the skin of the head and neck. We now report the first documented case of EBN involving the oral mucosa. A brief review of the clinical and histopathologic features of EBN is also presented.

Gene Expression Dynamics during Diabetic Periodontitis

Diabetes impairs the resolution of periodontal inflammation. We explored pathways altered by inflammation in the diabetic periodontium by using ligatures to induce periodontitis in type-2 diabetic Goto-Kakizaki rats. Ligatures were removed after 7 days, and rats were then treated with TNF inhibitor (pegsunercept) or vehicle alone and euthanized 4 days later. RNA was extracted from periodontal tissue, examined by mRNA profiling, and further analyzed by functional criteria. We found that 1,754 genes were significantly up-regulated and 1,243 were down-regulated by pegsunercept (p < 0.05). Functional analysis revealed up-regulation of neuron-associated and retina-associated gene clusters as well as those related to cell activity and signaling. Others were down-regulated by TNF inhibition and included genes associated with host defense, apoptosis, cell signaling and activity, and coagulation/hemostasis/complement. For selected genes, findings with microarray and rt-PCR agreed. PPAR-α was investigated further by immunohistochemistry due to its anti-inflammatory function and was found to be up-regulated in the gingiva during the resolution of periodontal inflammation and suppressed by diabetes. The results indicate that diabetes-enhanced inflammation both up- and down-regulates genes involved in cellular activity and cell signaling, while it predominantly up-regulates genes involved in the host response, apoptosis, and coagulation/homeostasis/complement and down-regulates mRNA levels of neuron, retina, and energy/metabolism-associated genes.