Browsing by Author "Edwards, Paul C."

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    Assessment of p63 expression in the salivary gland neoplasms adenoid cystic carcinoma, polymorphous low-grade adenocarcinoma, and basal cell and canalicular adenomas
    (2004-05) Edwards, Paul C.; Bhuiya, Tawfiqul; Kelsch, Robert D
    Purpose The purpose of this study was to determine the extent of p63 immunoreactivity in the malignant salivary gland neoplasms adenoid cystic carcinoma (ACC) and polymorphous low-grade adenocarcinoma (PLGA) and to compare this to the expression of this marker in the benign salivary gland tumors canalicular adenoma and basal cell adenoma. Few studies on the expression of p63 in head and neck salivary gland tumors have been published to date. P63, a selective immunohistochemical marker of basal/stem cells of stratified epithelium and of myoepithelial cells, is a p53 homologue that plays an essential role in both morphogenesis of epidermis and limb development. P63 immunoreactivity has been demonstrated in squamous cell and urothelial carcinomas. It is generally absent in most nonsquamous cell carcinomas. Study design Formalin-fixed paraffin-embedded sections from 49 salivary gland neoplasms, representing 6 canalicular adenomas, 11 basal cell adenomas, 17 PLGA and 15 ACC accessioned from 1989 to 2002 by the Department of Pathology, Long Island Jewish Medical Center, New Hyde Park, NY, were stained with an anti-p63 monoclonal antibody. Results Nuclear p63 reactivity was uniformly positive in PLGA (17/17, 100%). Positive reactivity was also identified in the majority of cases of ACC (13/15, 87%), primarily in the nonluminal myoepithelial-like cells surrounding luminal cells. Canalicular adenoma did not exhibit any p63 immunoreactivity. All basal cell adenomas of parotid origin stained strongly for p63, with staining localized to the peripheral tumor cells situated adjacent to the connective tissue stroma. None of the basal cell adenomas originating in the upper lip stained with p63. In native adjacent salivary gland tissue, p63 reactivity was identified focally in the nuclei of myoepithelial and basal duct cells. Conclusions P63 is strongly expressed in basal cell adenoma of parotid origin, and in ACC and PLGA. Canalicular adenoma did not demonstrate p63 staining, consistent with this tumor's putative luminal ductal cell differentiation. Our results suggest that the neoplastic cells in PLGA may represent either a population of p63-positive epithelial stem/reserve cells similar to the basal cells of stratified epithelium, or modified myoepithelial cells. Given the staining pattern of the tumors examined, p63 does not appear to be an ideal marker for distinguishing between ACC, PLGA, and basal cell adenoma.
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    Bilateral Central Giant Cell Granulomas of the Mandible in An Eight Year-Old Girl with Noonan Syndrome (Noonan-Like/Multiple Giant Cell Lesions Syndrome)
    (2005-03) Edwards, Paul C.; Fox, Joyce; Fantasia, John E; Goldberg, Jeff; Kelsch, Robert D
    A number of conditions can present with lesions that histologically are indistinguishable from the central giant cell granuloma (CGCG) of bone, including brown tumors of hyperparathyroidism, cherubism, and, less commonly, a number of inherited syndromes. We report a case of an eight-year girl who presented with bilateral CGCGs of the posterior mandible. Characteristic facial features, reported increased post-operative bleeding and history of pulmonary stenosis led us to suspect a diagnosis of Noonan syndrome. A medical geneticist confirmed this on further evaluation. This case report will discuss the salient features of this diagnosis.
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    Bisphosphonates Inhibit Expression of p63 by Oral Keratinocytes
    (2011-07) Scheller, E L; Baldwin, C M; Kuo, S; D'Silva, N J; Feinberg, S E; Krebsbach, P H; Edwards, Paul C.
    Osteonecrosis of the jaw (ONJ), a side-effect of bisphosphonate therapy, is characterized by exposed bone that fails to heal within eight weeks. Healing time of oral epithelial wounds is decreased in the presence of amino-bisphosphonates; however, the mechanism remains unknown. We examined human tissue from individuals with ONJ and non-bisphosphonate-treated controlindividuals to identify changes in oral epithelium and connective tissue. Oral and intravenous bisphosphonate-treated ONJ sites had reduced numbers of basal epithelial progenitor cells, as demonstrated by a 13.8 ± 1.1% and 31.9 ± 5.8% reduction of p63 expression, respectively. No significant differences in proliferation rates, vessel density, or macrophage number were noted. In vitro treatment of clonal and primary oral keratinocytes with zoledronic acid (ZA) inhibited p63, and expression was rescued by the addition of mevalonate pathway intermediates. In addition, both ZA treatment and p63 shRNA knock-down impaired formation of 3D Ex Vivo Produced Oral Mucosa Equivalents (EVPOME) and closure of an in vitro scratch assay. Analysis of our data suggests that bisphosphonate treatment may delay oral epithelial healing by interfering with p63-positive progenitor cells in the basal layer of the oral epithelium in a mevalonate-pathway-dependent manner. This delay in healing may increase the likelihood of osteonecrosis developing in already-compromised bone.
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    C-kit expression in the salivary gland neoplasms adenoid cystic carcinoma, polymorphous low-grade adenocarcinoma, and monomorphic adenoma
    (2003-05) Edwards, Paul C.; Bhuiya, Tawfigul; Kelsch, Robert D
    Objective. Differentiating between adenoid cystic carcinomas (ACCs), polymorphous low-grade adenocarcinomas (PLGAs), and the monomorphic adenomas (including canalicular adenomas, trabecular adenomas, and basal cell adenomas) can present a diagnostic challenge, especially when examining tissue obtained from small incisional or fragmented biopsies. Recent studies have revealed that overexpression of the tyrosine kinase receptor protein c-kit occurs in a narrow subset of malignant neoplasms, including gastrointestinal stromal tumors, myeloid leukemias, seminomas, and ACCs. C-kit reportedly is not expressed in PLGAs. We compared the expression of the c-kit antigen in the malignant salivary gland neoplasms ACC and PLGA with its expression in salivary gland monomorphic adenoma (including canalicular adenoma and basal cell adenoma). Study design. Formalin-fixed paraffin-embedded sections of 49 salivary gland neoplasms (17 monomorphic adenomas, 17 PLGAs, and 15 ACCs) accessioned between 1989 and 2002 were retrieved from the files of the Department of Pathology, Long Island Jewish Medical Center, and were stained with an anti-c-kit polyclonal antibody. Results. C-kit reactivity was uniformly positive in the cytoplasm of luminal neoplastic cells in ACCs (15/15, 100%). Positive reactivity was also identified in the majority of PLGAs (16/17, 94%), with at least 25% of the tumor cells being positive. Similar reactivity was seen in monomorphic adenomas (16/17, 94%). Conclusions. In contrast to previous reports, we find that c-kit expression was not restricted to ACC but was expressed in all 3 tumor types evaluated (ACC, PLGA, and monomorphic adenoma). Therefore, c-kit does not appear to be a useful marker for distinguishing between either ACC and PLGA in equivocal cases, or in benign and malignant salivary gland neoplasms.
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    CERE-120 Prevents Irradiation-Induced Hypofunction and Restores Immune Homeostasis in Porcine Salivary Glands
    (Elsevier, 2020-09-11) Lombaert, Isabelle M. A.; Patel, Vaishali N.; Jones, Christina E.; Villier, Derrick C.; Canada, Ashley E.; Moore, Matthew R.; Berenstein, Elsa; Zheng, Changyu; Goldsmith, Corinne M.; Chorini, John A.; Martin, Daniel; Zourelias, Lee; Trombetta, Mark G.; Edwards, Paul C.; Meyer, Kathleen; Ando, Dale; Passineau, Michael J.; Hoffman, Matthew P.; Oral Pathology, Medicine and Radiology, School of Dentistry
    Salivary gland hypofunction causes significant morbidity and loss of quality of life for head and neck cancer patients treated with radiotherapy. Preventing hypofunction is an unmet therapeutic need. We used an adeno-associated virus serotype 2 (AAV2) vector expressing the human neurotrophic factor neurturin (CERE-120) to treat murine submandibular glands either pre- or post-irradiation (IR). Treatment with CERE-120 pre-IR, not post-IR, prevented hypofunction. RNA sequencing (RNA-seq) analysis showed reduced gene expression associated with fibrosis and the innate and humoral immune responses. We then used a minipig model with CERE-120 treatment pre-IR and also compared outcomes of the contralateral non-IR gland. Analysis of gene expression, morphology, and immunostaining showed reduced IR-related immune responses and improved secretory mechanisms. CERE-120 prevented IR-induced hypofunction and restored immune homeostasis, and there was a coordinated contralateral gland response to either damage or treatment. CERE-120 gene therapy is a potential treatment for head and neck cancer patients to influence communication among neuronal, immune, and epithelial cells to prevent IR-induced salivary hypofunction and restore immune homeostasis.
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    Clinically aggressive central giant cell granulomas in two patients with neurofibromatosis 1
    (2006-12) Edwards, Paul C.; Fantasia, John E; Saini, Tamjit; Rosenberg, Tracey J; Sachs, Stephen A; Ruggiero, Salvatore
    Background Neurofibromatosis 1 (NF1) is an autosomal dominantly inherited disorder caused by a spectrum of mutations affecting the Nf1 gene. Affected patients develop benign and malignant tumors at an increased frequency. Clinical findings include multiple cutaneous café-au-lait pigmentations, neurofibromas, axillary freckling, optic gliomas, benign iris hamartomas (Lisch nodules), scoliosis, and poorly defined soft tissue lesions of the skeleton. Kerl first reported an association of NF1 with multiple central giant cell granulomas (CGCGs) of the jaws. There have since been 4 additional published cases of NF1 patients with CGCGs of the jaws. Clinical cases We report on 2 patients who presented with NF1 and aggressive CGCGs of the jaws. In both cases, the clinical course was characterized by numerous recurrences despite mechanical curettage and surgical resection. Conclusions We review proposed mechanisms to explain the apparent association between NF1 and an increased incidence of CGCGs of the jaws. While the presence of CGCGs of the jaws in patients with NF1 could represent either a coincidental association or a true genetic linkage, we propose that this phenomenon is most likely related to NF1-mediated osseous dysplasia. Compared to normal bone, the Nf1-haploinsufficient bone in a patient with NF1 may be less able to remodel in response to as of yet unidentified stimuli (e.g. excessive mechanical stress and/or vascular fragility), and consequently may be more susceptible to developing CGCG-like lesions. Alternatively, the CGCG in NF1 patients could represent a true neoplasm, resulting from additional, as of yet unidentified, genetic alterations to Nf1-haploinsufficient bone.
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    Cone beam CT evaluation of the presence of anatomic accessory canals in the jaws
    (2014-05) Eshak, M; Brooks, S; Abdel-Wahed, N; Edwards, Paul C.
    Objectives: To assess the prevalence, location and anatomical course of accessory canals of the jaws using cone beam CT. Methods: A retrospective analysis of 4200 successive cone beam CT scans, for patients of both genders and ages ranging from 7 to 88 years, was performed. They were exposed at the School of Dentistry, University of Michigan, Ann Arbor, MI. After applying the exclusion criteria (the presence of severe ridge resorption, pre-existing implants, a previously reported history of craniofacial malformations or syndromes, a previous history of trauma or surgery, inadequate image quality and subsequent scans from the same individuals), 4051 scans were ultimately included in this study. Results: Of the 4051 scans (2306 females and 1745 males) that qualified for inclusion in this study, accessory canals were identified in 1737 cases (42.9%; 1004 females and 733 males). 532 scans were in the maxilla (13.1%; 296 females and 236 males) and 1205 in the mandible (29.8%; 708 females and 497 males). Conclusions: A network of accessory canals bringing into communication the inner and outer cortical plates of the jaws was identified. In light of these findings, clinicians should carefully assess for the presence of accessory canals prior to any surgical intervention to decrease the risk for complications.
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    Contemporary Issues in Head and Neck Pathology and Radiology
    (2010-03-02) Edwards, Paul C.; Kanjirath, Preetha P.; Saini, Tarnjit; Norton, Neil S.
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    Dermoid cysts of the tongue: report of five cases and review of the literature
    (2003-11) Edwards, Paul C.; Lustrin, Liz; Valderrama, Elsa
    Dermoid cysts of the tongue are uncommon. To date, there have been nine reported cases in the English language literature. In this article, we describe five cases accessioned at our institution over a 12-year period, two of which have previously been reported. The prevalence of dermoid cysts at our institution over this period was quite low. Of 324,042 surgical cases, 0.24% (765 cases) were dermoid cysts. Of these, five were from the tongue, representing only 0.7% of the dermoid cysts accessioned and 0.0015% of the total surgical specimens. The literature is reviewed and the possible origin of these lesions is discussed.