Plasma Cell Mucositis: A Clinical Conundrum.

Plasma cell mucositis (PCM) is an unusual disorder most evident in the accessible mucosa and usually reported in the upper aerodigestive tract, although it is named according to its specific anatomical site of involvement such as plasma cell cheilitis, plasma cell gingivitis, plasma cell vulvitis, and Zoon's balanitis. PCM reflects a dense polyclonal rather than a monoclonal plasma cell proliferation of unclear and unknown etiology. This perplexing disorder tends to be treated by avoiding possible triggers and intralesional and/or systemic steroids. In this work, we provide a review and update on PCM, which often represents a clinical conundrum.

Plasma Cell Mucositis: A Clinical Conundrum.

Plasma cell mucositis (PCM) is an unusual disorder most evident in the accessible mucosa and usually reported in the upper aerodigestive tract, although it is named according to its specific anatomical site of involvement, such as plasma cell cheilitis, plasma cell gingivitis, plasma cell vulvitis, and Zoon's balanitis. PCM reflects a dense polyclonal, rather than a monoclonal, plasma cell proliferation of unclear and unknown etiology. This perplexing disorder tends to be treated by avoiding possible triggers and intralesional and/or systemic steroids. Herein we review and provide an update on PCM, which often represents a clinical conundrum.

Examining the efficacy of intravenous administration of predatory bacteria in rats.

The proteobacteria Bdellovibrio bacteriovorus and Micavibrio aeruginosavorus are obligate predators of Gram-negative bacteria, and have been proposed to be used to treat multidrug-resistant bacterial infections. The ability of predatory bacteria to reduce bacterial burden in vivo within the lungs of rats has been demonstrated, but it was unknown if predatory bacteria can attenuate systemic bacterial burden administered intravenously. In this study, we first assessed the safety of intravenous inoculation of predatory bacteria in rats. No rat morbidity or adverse histopathology of various organs due to predatory bacteria administration was observed. An increase in proinflammatory cytokines (TNFα and KC/GRO) was observed at two hours post-inoculation; however, cytokines returned to baseline levels by 18 hours. Furthermore, bacterial dissemination analysis demonstrated that predatory bacteria were efficiently cleared from the host by 20 days post-injection. To determine whether predatory bacteria could reduce bacterial burden in vivo, Klebsiella pneumoniae was injected into the tail veins of rats and followed with multiple doses of predatory bacteria over 16 or 24 hours. Predatory bacteria were unable to significantly reduce K. pneumoniae burden in the blood or prevent dissemination to other organs. The results suggest that predatory bacteria may not be effective for treatment of acute blood infections.

Effect of predatory bacteria on the gut bacterial microbiota in rats.

Bdellovibrio bacteriovorus and Micavibrio aeruginosavorus are Gram-negative proteobacteria that are obligate predators of other Gram-negative bacteria and are considered potential alternatives to antibiotics. Most studies focusing on predatory bacteria have been performed in vitro, thus the effect of predatory bacteria on a live host, including the impact on the ecology of the native microbiota, has yet to be fully examined. In this study, intrarectal inoculations of Sprague-Dawley rats with predatory bacteria were performed. Additionally, feces were collected for seven days post-inoculation to determine the effect on gut bacterial diversity. Rat colonic tissue exhibited no abnormal histopathological effects due to predatory bacteria. A modest increase in pro-inflammatory cytokines was measured in the colons of rats inoculated with predatory bacteria by 24 and 48 hours, with all but IL-13 returning to baseline by seven days. V4 16S rRNA gene sequencing of fecal DNA demonstrated minimal shifts in taxonomic representation over the week due to predatory bacteria. Changes in bacterial populations due to exposure to B. bacteriovorus are predicted to contribute to health, however, an overgrowth of Prevotella was observed due to exposure to M. aeruginosavorus. This study further addresses safety concerns associated with the potential use of predatory bacteria to treat infections.

Predatory Bacteria Attenuate Klebsiella pneumoniae Burden in Rat Lungs.

Bdellovibrio bacteriovorus and Micavibrio aeruginosavorus are predatory bacteria that naturally-and obligately-prey on other Gram-negative bacteria, and their use has been proposed as a potential new approach to control microbial infection. The ability of predatory bacteria to prey on Gram-negative human pathogens in vitro is well documented; however, the in vivo safety and efficacy of predatory bacteria have yet to be fully assessed. In this study, we examined whether predatory bacteria can reduce bacterial burden in the lungs in an in vivo mammalian system. Initial safety studies were performed by intranasal inoculation of rats with predatory bacteria. No adverse effects or lung pathology were observed in rats exposed to high concentrations of predatory bacteria at up to 10 days postinoculation. Enzyme-linked immunosorbent assay (ELISA) of the immune response revealed a slight increase in inflammatory cytokine levels at 1 h postinoculation that was not sustained by 48 h. Additionally, dissemination experiments showed that predators were efficiently cleared from the host by 10 days postinoculation. To measure the ability of predatory bacteria to reduce microbial burden in vivo, we introduced sublethal concentrations of Klebsiella pneumoniae into the lungs of rats via intranasal inoculation and followed with multiple doses of predatory bacteria over 24 h. Predatory bacteria were able to reduce K. pneumoniae bacterial burden, on average, by more than 3.0 log10 in the lungs of most rats as measured by CFU plating. The work presented here provides further support for the idea of developing predatory bacteria as a novel biocontrol agent. IMPORTANCE: A widely held notion is that antibiotics are the greatest medical advance of the last 50 years. However, the rise of multidrug-resistant (MDR) bacterial infections has become a global health crisis over the last decade. As we enter the postantibiotic era, it is crucial that we begin to develop new strategies to combat bacterial infection. Here, we report one such new approach: the use of predatory bacteria (Bdellovibrio bacteriovorus and Micavibrio aeruginosavorus) that naturally-and obligately-prey on other Gram-negative bacteria. To our knowledge, this is the first study that demonstrated the ability of predatory bacteria to attenuate the bacterial burden of a key human pathogen in an in vivo mammalian system. As the prevalence of MDR infections continues to rise each year, our results may represent a shift in how we approach treating microbial infections in the future.

Large, expansile odontogenic cyst with bilateral maxillary sinus involvement.

Residual cysts are common odontogenic lesions of the tooth-bearing areas of the jaws. A case of an unusually large residual cyst that crosses the maxillary midline and occupies portions of the maxillary sinuses is being reported. Investigations included a panoramic radiograph, CT scan and a biopsy. The differential diagnoses were common odontogenic lesions, including cysts and benign tumors. The value of advanced imaging modalities is stressed when determining the presence and extent of lesions in complex structures such as the maxilla. The need to visualize the entire lesion beyond what may be seen on intraoral views, as well as panoramic radiographs, is discussed.

Large, expansile odontogenic cyst with bilateral maxillary sinus involvement.

Residual cysts are common odontogenic lesions of the tooth-bearing areas of the jaws. A case of an unusually large residual cyst that crosses the maxillary midline and occupies portions of the maxillary sinuses is being reported. Investigations included a panoramic radiograph, CT scan and a biopsy. The differential diagnoses were common odontogenic lesions, including cysts and benign tumors. The value of advanced imaging modalities is stressed when determining the presence and extent of lesions in complex structures such as the maxilla. The need to visualize the entire lesion beyond what may be seen on intraoral views, as well as panoramic radiographs, is discussed.

Proteomic identification of immunoproteasome accumulation in formalin-fixed rodent spinal cords with experimental autoimmune encephalomyelitis.

Clinically relevant formalin-fixed and paraffin-embedded (FFPE) tissues have not been widely used in neuroproteomic studies because many proteins are presumed to be degraded during tissue preservation. Recent improvements in proteomics technologies, from the 2D gel analysis of intact proteins to the "shotgun" quantification of peptides and the use of isobaric tags for absolute and relative quantification (iTRAQ) method, have made the analysis of FFPE tissues possible. In recent years, iTRAQ has been one of the main methods of choice for high throughput quantitative proteomics analysis, which enables simultaneous comparison of up to eight samples in one experiment. Our objective was to assess the relative merits of iTRAQ analysis of fresh frozen versus FFPE nervous tissues by comparing experimental autoimmune encephalomyelitis (EAE)-induced proteomic changes in FFPE rat spinal cords and frozen tissues. EAE-induced proteomic changes in FFPE tissues were positively correlated with those found in the frozen tissues, albeit with ∼50% less proteome coverage. Subsequent validation of the enrichment of immunoproteasome (IP) activator 1 in EAE spinal cords led us to evaluate other proteasome and IP-specific proteins. We discovered that many IP-specific (as opposed to constitutive) proteasomal proteins were enriched in EAE rat spinal cords, and EAE-induced IP accumulation also occurred in the spinal cords of an independent mouse EAE model in a disability score-dependent manner. Therefore, we conclude that it is feasible to generate useful information from iTRAQ-based neuroproteomics analysis of archived FFPE tissues for studying neurological disease tissues.

Quantitative Proteomic Analysis of Formalin Fixed Paraffin Embedded Oral HPV Lesions from HIV Patients.

Human immunodeficiency virus (HIV) infection is associated with dysplastic changes in oral human papilloma virus (HPV) lesions, suggesting changes in keratinocytes. In the present study, we seek to identify proteomic changes in oral HPV lesions between HIV(+) and HIV(-) patients. While fresh tissues represent the most desirable samples for proteomic investigations, they are often difficult to obtain in large numbers under clinical settings. We therefore have developed a new method to identify protein changes in formalin fixed and paraffin-embedded (FFPE) oral HPV lesions utilizing iTRAQ™ technology in conjunction with Liquid Tissue® sample preparation method. Using this method, we identified nine proteins that were differentially expressed in oral HPV lesions as a result of HIV infection. The quantitative proteomic method presented here will be valuable for others who plan to analyze FFPE tissues.

Rare, simultaneous, multiple, and recurrent mandibular bone cysts.

Simple bone cysts, also referred to as traumatic bone cysts, are benign connective tissue-lined cavities occurring most commonly in young people. Most of the time, they occur as solitary radiolucencies. In the jaws, they also have been reported to occur concurrently with benign fibro-osseous lesions. The radiographic appearance of simple bone cysts could be confused with other jaw cysts and benign tumors. This case report presents a patient who had 3 separate lesions simultaneously within the mandible. The right mandibular lesion presented as a multilocular radiolucency. The 2 left mandibular lesions were periapical, with mixed radiodensities and radiographically mimicked lesions of focal or periapical cemento-osseous dysplasia. More aggressive benign lesions of the jaw were initially included in the differential diagnosis, as well. A biopsy revealed the diagnosis of simple bone cysts in all 3 locations. Minimal surgical management resulted in complete recovery of these osseous defects only to recur in 2 years on the mandibular left premolar-molar region. A new biopsy confirmed that the lesion was a recurrent simple bone cyst. Simultaneous presence of benign cemento-osseous dysplasia was also considered, as it is known to coexist with the simple bone cysts.

Melanoma with cartilaginous differentiation originating within the mucosa of the nasal cavity.

Mucosal melanomas are uncommon in comparison to their counterpart on the skin, accounting for approximately 1% of all such tumors. The majority of mucosal melanomas arise within the head and neck region. Osteocartilaginous differentiation in these tumors is a rare phenomenon and can pose diagnostic challenges. Herein we report a case of melanoma with cartilaginous differentiation originating in the nasal cavity of a 76-year-old male, presenting dramatically as a large mass projecting well beyond the vestibule of the right naris. To our knowledge, this case represents the fifth example of a melanoma with bone and/or cartilage differentiation to arise in the head and neck region, and the third to be reported in the nasal cavity.

A determination of the range of oral conditions submitted for microscopic and direct immunofluorescence analysis.

BACKGROUND: Direct immunofluorescence (DIF) testing is a useful adjunct for the diagnosis of immune-mediated oral vesiculobullous diseases, helping to identify separate, histologically similar, but prognostically different, conditions. It is unknown how often biopsy of these lesions yields positive DIF results. METHODS: A total of 270 consecutive archival cases submitted to a reference laboratory in Buffalo, New York, over a 2-year span were examined. These specimens were submitted to establish or rule out a diagnosis of a DIF-positive oral vesiculobullous disease. Demographic, clinical, and diagnostic information, based on conventional microscopic and DIF analysis, was tabulated. To assess the contribution of DIF to successful diagnosis, three pathologists examined the hematoxylin and eosin-stained slides of the known DIF-positive specimens without knowledge of the DIF results. RESULTS: Approximately 48% of the specimens demonstrated positive DIF findings and consisted of pemphigus vulgaris, mucous membrane pemphigoid, lichen planus, linear immunoglobulin A disease, and chronic ulcerative stomatitis. The remaining specimens had negative DIF findings and consisted of numerous non-specific inflammatory conditions. Of particular interest were several cases of epithelial dysplasia and squamous cell carcinoma. Of the DIF-positive cases, only pemphigus vulgaris could be diagnosed reliably by conventional microscopy alone. CONCLUSIONS: Approximately half of biopsies of oral conditions that clinically resembled typically DIF-positive vesiculobullous diseases did not yield positive findings on DIF testing. Instead, a wide range of oral diseases can mimic these lesions clinically. With the exception of pemphigus vulgaris, DIF is essential for establishing a definitive diagnosis for known DIF-positive diseases.

Unusually large complex odontoma in maxillary sinus associated with unerupted tooth. Report of case and review of literature.

An unusual case of a large complex odontoma with an associated impacted tooth is presented. Odontomas are hamartomatous growths of enamel, dentin, cementum and pulp tissue. Although they are usually tooth-sized or smaller, occasionally, the complex variant can exhibit considerable growth, as was seen in the case presented here. It occupied most of the maxillary sinus and displaced the floor of the orbit and the medial and posterior walls of the left maxillary sinus. Panoramic radiographs, as well as axial and coronal CT studies, showed the extent of the lesion in various dimensions. A differential diagnosis of various calcifying tumors was formulated on the basis of these findings. The lesion was surgically excised, and histologic analysis confirmed the radiographic impression. Although odontomas of this magnitude are rare, this case demonstrates the value of imaging, radiographic histopathologic diagnosis and surgical treatment planning prior to any definitive treatment.

Peripheral granular cell odontogenic fibroma.

Peripheral odontogenic fibroma is a rare lesion that arises on the gingiva and can clinically mimic a variety of reactive lesions, benign neoplasms, and metastases. We describe a symptomatic lesion arising on the mandibular gingiva of a 58-year-old female with no history of trauma or dental disease in the area. An excisional biopsy showed the lesional stroma to contain numerous polyhedral granular cells with occasional interspersed islands of inactive odontogenic epithelium. We believe this to represent the fourth case of peripheral granular cell odontogenic fibroma to be reported in detail in the literature.

Epithelioid osteosarcoma presenting as a rapidly expanding maxillary mass.

BACKGROUND: Osteosarcomas of the jaws account for less than 10% of reported neoplasms of this type. Patients with osteosarcoma in this region tend to be in the late-third to mid-fourth decades of life. The osteoblastic, chondroblastic, and fibroblastic variants constitute the majority of lesions. METHODS: A mass was observed in the maxilla of a 50-year-old male who presented for a complete odontectomy. Over the ensuing weeks, the mass substantially increased in size, despite multimodality treatment efforts. RESULTS: Radiographic findings revealed a mixed density mass of the left maxilla. Histologic, immunohistochemical, and electron microscopy examination of the tumor showed a malignant mesenchymal neoplasm consisting of sheets of epithelioid and spindle cells exhibiting focal osteoid formation. CONCLUSIONS: We report a rare and aggressive case of epithelioid osteosarcoma arising in the maxillofacial complex.