Feasibility of desorption electrospray ionization mass spectrometry for diagnosis of oral tongue squamous cell carcinoma.

RATIONALE: Desorption electrospray ionization mass spectrometry (DESI-MS) has demonstrated utility in differentiating tumor from adjacent normal tissue in both urologic and neurosurgical specimens. We sought to evaluate if this technique had similar accuracy in differentiating oral tongue squamous cell carcinoma (SCC) from adjacent normal epithelium due to current issues with late diagnosis of SCC in advanced stages. METHODS: Fresh frozen samples of SCC and adjacent normal tissue were obtained by surgical resection. Resections were analyzed using DESI-MS sometimes by a blinded technologist. Normative spectra were obtained for separate regions containing SCC or adjacent normal epithelium. Principal Component Analysis and Linear Discriminant Analysis (PCA-LDA) of spectra were used to predict SCC versus normal tongue epithelium. Predictions were compared with pathology to assess accuracy in differentiating oral SCC from adjacent normal tissue. RESULTS: Initial PCA score and loading plots showed clear separation of SCC and normal epithelial tissue using DESI-MS. PCA-LDA resulted in accuracy rates of 95% for SCC versus normal and 93% for SCC, adjacent normal and normal. Additional samples were blindly analyzed with PCA-LDA pixel-by-pixel predicted classifications as SCC or normal tongue epithelial tissue and compared against histopathology. The m/z 700-900 prediction model showed a 91% accuracy rate. CONCLUSIONS: DESI-MS accurately differentiated oral SCC from adjacent normal epithelium. Classification of all typical tissue types and pixel predictions with additional classifications should increase confidence in the validation model.

A systematic review including an additional pediatric case report: Pediatric cases of mammary analogue secretory carcinoma.

IMPORTANCE: Mammary Analogue Secretory Carcinoma (MASC) is a newly characterized salivary gland carcinoma resembling secretory carcinoma of the breast. Prior to being described, MASC was most commonly misdiagnosed as Acinic Cell Carcinoma. Though MASC is predominantly an adult neoplasm, cases have been reported in the pediatric population. Reporting and summarizing of known cases is imperative to understand the prognosis and clinical behavior of MASC. OBJECTIVE: EVIDENCE REVIEW: Web of Science, Medline, EMBASE, and The Cochrane Library were searched for studies that included pediatric cases of MASC. Data on clinical presentation, diagnosis and management, and pathology were collected from all pediatric cases. FINDINGS: CONCLUSIONS AND RELEVANCE: Since the first case of MASC in the pediatric population was described in 2011, only 12 cases, including this one, have been described in the literature. With this paucity of information, much remains unknown regarding this new pathologic diagnosis. The collection of clinical outcomes data of children with MASC is needed to better understand the behavior of this malignancy as well as determine optimal treatment regimens.

Proton therapy for head and neck adenoid cystic carcinoma: initial clinical outcomes.

BACKGROUND: The purpose of this study was to report outcomes of proton therapy in head and neck adenoid cystic carcinoma. METHODS: We conducted a retrospective analysis of 26 patients treated between 2004 and 2012. Twenty patients (77%) had base of skull involvement; 19 (73%) were treated for initial disease and 7 (27%) for recurrent disease. Twenty patients were treated postoperatively, 6 after biopsy alone and 24 had positive margins or gross residual disease.Median dose delivered was 72 Gy (relative biological effectiveness[RBE]). RESULTS: Median follow-up was 25 months (range, 7­50 months). The 2-year overall survival was 93% for initial disease course and 57% for recurrent disease (p5.19). The 2-year local control was 95% for initial disease and 86% for recurrent disease (p5.48). The 2-year distant metastatic rate was 25%. Late toxicity of grade 0 or 1 was seen in 17 patients, grade 2 in 5, grade 3 in 2, grade 4 in 1, and grade 5 in 1. CONCLUSION: Initial outcomes of proton therapy are encouraging. Longer follow-up is required.

Prognostic significance of basaloid squamous cell carcinoma in head and neck cancer.

IMPORTANCE: Head and neck basaloid squamous cell carcinoma (BSCC) has been considered a more aggressive variant of squamous cell carcinoma (SCC) with a poorer prognosis, although case-control studies have reached conflicting conclusions. OBJECTIVE: To examine the prognostic significance of head and neck BSCC on overall survival in a large population-based registry. DESIGN AND SETTING: Retrospective data review of a population-based registry from the Surveillance, Epidemiology, and End Results database. PARTICIPANTS: Individual case data for 34,196 patients treated between January 2004 and December 2009 with head and neck primary SCC (n = 33,554) and BSCC (n = 642) of the oral cavity, oropharyx, larynx, or hypopharynx. Patients with metastatic disease, incomplete staging information, and those who did not receive surgery or radiation were excluded. INTERVENTIONS: Patients had been treated with surgery, radiation, or both. MAIN OUTCOMES AND MEASURES: Distribution of patient characteristics between patients of each histology. Hazard ratios, 3-year overall survival, subgroup, and multivariate analysis of patient and treatment characteristics were investigated. RESULTS: Across each cohort, patients with BSCC more often had high-grade tumors and treatment with lymph node dissection. Multivariate analysis found that group stage, T stage, N stage, size, lymph node dissection, and age statistically significantly influenced overall survival. In multivariate analysis, the hazard ratio for death for patients with BSCC in the oral cavity and larynx and hypopharynx was not statistically significantly different from that for SCC. In the oropharynx, the hazard ratio for death for BSCC histology compared with SCC histology was 0.73 (P = .03). CONCLUSIONS AND RELEVANCE: Compared with SCC, BSCC is not an independent adverse prognostic factor for patients with head and neck cancer. The Surveillance, Epidemiology, and End Results analysis has limits, including lack of information regarding chemotherapy, but after controlling for disease and treatment variables, including neck dissection and radiotherapy, BSCC histology did not have an independent adverse prognostic effect on overall survival. The reported association between human papillomavirus and BSCC histology may explain the lower hazard ratio for death in patients with oropharynx BSCC.

Parathyroid carcinosarcoma: a rare form of parathyroid carcinoma with normal parathyroid hormone levels.

Parathyroid carcinosarcoma was first described by Nacamuli et al in 2002. We present the second case of this rare disease. This rare carcinosarmoca presented as a parathyroid carcinoma with uncharacteristically normal parathyroid hormone levels. The patient is a 57-year-old woman with long-standing right-sided vocal cord paralysis presented with a progressive 3 × 2 × 3 cm mass in the right neck. She had previously undergone a total thyroidectomy revealing benign pathology. Parathyroid hormone and calcium blood levels were within normal limits. The mass was removed with negative surgical margins. Histopathology and immunohistochemical analysis showed a biphasic pattern, with positive for chromogranin and vimentin, consistent with carcinoma and sarcoma. The disease in our patient, as in the previously reported case, has shown systemic progression despite aggressive surgical resection and adjuvant therapy.

Multiple phosphaturic mesenchymal tumors associated with oncogenic osteomalacia: case report and review of the literature.

Oncogenic osteomalacia is a rare paraneoplastic syndrome that occurs secondary to tumor development in a variety of locations. Only about 140 cases have been reported in the literature. The most common causal tumor is phosphaturic mesenchymal tumor (PMT), a histologically benign lesion. The two most common sites of PMT are the lower extremities and the head/neck. We report the case of a 33-year-old woman with oncogenic osteomalacia who was diagnosed with two PMTs; the first arose in the tibia, and the second occurred 2 years later in the maxillary sinus. To the best of our knowledge, this is the first reported case of multiple PMTs. Despite resection of both tumors, the patient's signs and symptoms did not resolve, suggesting either incomplete tumor removal or the presence of another undetected tumor. We discuss the diagnosis of oncogenic osteomalacia, its associated biochemical abnormalities, and its histopathology.

Suppression of colon inflammation by CD80 blockade: evaluation in two murine models of inflammatory bowel disease.

BACKGROUND: Human inflammatory bowel disease (IBD) is a chronic condition mediated by aberrant immune responses to the luminal antigens by activated CD4+ T cells. The CD80/CD86:CD28/CD152 costimulatory pathways transmit signals critical for T cell activation and suppression. Macrophages and epithelial cells are the chief antigen-presenting cells in the gut. Macrophages from the IBD colon express significantly elevated levels of CD80 and CD86 costimulatory molecules. The CD28-CD80 interaction primarily participates in breaking the tolerance and inducing the immune response in murine models of colitis. Blockade of CD80-costimulatory axis is an attractive strategy in the treatment of IBD. METHODS: Incorporating the structural information of the CD80:CD152 complex together with the preferences of interface residues to form polyproline type II helix, we designed novel peptide agents that selectively blocked CD80 receptor interactions. RESULTS: Administration of CD80 blocking agent at the time of adoptive transfer prevented the SCID mice from CD4+CD45Rb(high) T-cell mediated colitis. Significantly, CD80-CAP (competitive antagonist peptide) treatment suppressed established inflammation in TNBS-induced colitis, a model for Th1-mediated Crohn's disease. The colons of the mice receiving the CD80 blocking agent appeared unaffected macroscopically and exhibited negligible microscopic inflammation. The CD80-CAP treatment was associated with significantly reduced Th1 cytokines in the colon. CONCLUSIONS: The CD80 blocking peptide appeared to mediate protection against colitis by inducing Th2 skewing of the cytokine response.

Spindle cell hemangioma: report of a case presenting in the oral cavity.

BACKGROUND: Spindle cell hemangioma, formerly termed spindle cell hemangioendothelioma, is an uncommon benign vascular tumor. Presentation in the oral cavity is rare with only two previously reported cases. METHODS: We report a case of spindle cell hemangioma that presented as an asymptomatic mass of the buccal mucosa in a 44-year-old man. RESULTS: The tumor was a well-circumscribed vascular proliferation of spindled to epithelioid endothelial cells. Tumor cells with intracytoplasmic vascular lumens were present in several areas. Larger, ectatic, thin-walled vessels lined by a single layer of flattened endothelial cells were evident at the periphery and focally in more cellular areas. The tumor was positive for CD31 and CD34. CONCLUSIONS: Spindle cell hemangioma rarely presents in the oral cavity and needs to be considered in the differential diagnosis of oral cavity vascular tumors to avoid misdiagnosis as a more aggressive vascular tumor.

The use of biopsy in dental practice. The position of the American Academy of Oral and Maxillofacial Pathology.

Biopsy is the gold standard of diagnostic procedures. The American Academy of Oral and Maxillofacial Pathology has stated its position concerning biopsy use in dental practice, believing that using the procedure more frequently will enhance diagnosis and contribute substantially to the quest for more evidence-based practice. Biopsy is a technique within the scope of practice of general dentists. It is vital to understand that biopsy is a tool for the diagnosis of myriad benign and malignant oral conditions. More frequent use of biopsy in dental practice will likely reduce the number of successful lawsuits brought for delay or failure to diagnose. This article offers 10 guidelines to dentists to help assure the success of the procedure.

Suppression of immune responses in collagen-induced arthritis by a rationally designed CD80-binding peptide agent.

OBJECTIVE: The CD80/CD86-CD28/CD152 costimulatory pathways transmit signals for CD4+ T cell activation and suppression and are critically involved in the pathogenesis of rheumatoid arthritis (RA). A significant number of CD4+ T cells and macrophages in the rheumatoid synovium express elevated levels of CD80, increasing the potential for costimulation in trans of naive T cells. To determine the effect of blockade of this costimulatory axis in RA, we designed novel CD80-binding peptides and evaluated their therapeutic potential in collagen-induced arthritis (CIA), an animal model of RA. METHODS: The conserved MYPPPY motif of CD152 adopts a polyproline type II (PPII) helical conformation in the CD80-CD152 complex. The pairing preferences of the critical residues at the CD80-CD152 interface and their propensity to form PPII helices were integrated to design peptides with optimum PPII helical content that selectively block CD80-receptor interactions. The clinical efficacy was tested in DBA/1LacJ mice that were administered the CD80 blocking agents, called CD80-binding competitive antagonist peptides (CD80-CAPs), at the time of immunization with bovine type II collagen or 3 weeks after immunization. RESULTS: A single administration of select CD80-CAPs significantly reduced the clinical, radiologic, and histologic disease severity in CIA. Importantly, administration of CD80-CAPs during activated immune response significantly suppressed disease development by reducing mononuclear cell infiltration in the joints and mediating peripheral deletion of activated CD4+ T cells. CONCLUSION: A rationally designed CD80-binding peptide both prevents and suppresses CIA, suggesting a potential application in RA. Apoptosis of activated CD4+ T cells following in vivo blockade suggests that the effects of CD80-CAPs may be long-lasting.

Metastatic tumors in the jaws: a retrospective study of 114 cases.

BACKGROUND: Malignancies involving the bones are metastatic tumors more commonly than primary tumors. In this retrospective study, the authors review metastatic disease in the jaws. METHODS: The authors retrieved cases of metastatic disease in the jaws over a 45-year period from the pathology archives at the University of Michigan School of Dentistry, Ann Arbor, and Indiana University School of Dentistry, Indianapolis. RESULTS: The authors conducted a retrospective analysis of 114 cases of metastatic disease in the jaws and found that approximately 60 percent of subjects had no history of malignancy. The sex distribution was equivalent. Mandibular predilection was more prominent in females than in males. Metastases from the breast were significantly greater than those from the lung and prostate (P < or = .05), the second and third most frequent sites, respectively. Women exhibited twice as many jaw metastases as did men 31 to 40 years of age and significantly fewer metastases than did men 71 to 80 years of age (P < or = .05). CONCLUSION: In the majority of cases, subjects had an undiagnosed primary cancer at the time the metastatic jaw disease presented. The most common site of origin of the primary cancer was the breast, when primary sites were considered independent of sex. CLINICAL IMPLICATIONS: Patients with metastatic disease in the jaws may have innocuous dental symptoms, such as pulpal or periodontal pain; therefore, clinicians will play a significant role in diagnosing the life-threatening disease.

Granular cell leiomyoma of the oral cavity.

Granular cytoplasmic change is a reported but uncommon finding in leiomyoma. Leiomyoma in the oral cavity is also uncommon, and granular cell change in oral leiomyomas, to the best of our knowledge, has not been previously reported in the English literature. Two cases of oral leiomyomas with significant granular cell change are presented. These tumors may be confused with the more common granular cell tumor, however, routine histology and immunohistochemistry aided in establishing the diagnosis. Ultrastructural studies were done for one case. Both tumors were immunoreactive for muscle markers, namely, smooth muscle actin and desmin. One of the tumors (case 2) reacted postiviely for HHF-35 and alpha-1 antitrypsin. The tumors were unreactive for S-100 protein, pancytokeratin, myoglobin, and factor VIII related antigen (case 2).

Osteonecrosis of the mandible or maxilla associated with the use of new generation bisphosphonates.

OBJECTIVE: The use of bisphosphonates is well established for the treatment of patients with metastatic bone disease, osteoporosis, and Paget's disease. Osteonecrosis of the mandible or maxilla associated with the use of bisphosphonates is a newly described entity never before discussed in the otolaryngology literature. In this paper, we review a series of patients diagnosed with osteonecrosis, all treated with new generation bisphosphonates. Our objective is to inform and educate others, particularly otolaryngologists/head and neck surgeons, about this drug induced entity, a condition that should be recognized early to avoid potential devastating consequences. STUDY DESIGN: Retrospective chart review of a series of patients from a tertiary referral center. METHODS: Pathology reports of specimens submitted from either the mandible or maxilla were reviewed from the previous 12 months. Any patient diagnosed with osteonecrosis without evidence of metastatic disease at that site was included; those with a previous history of radiation therapy were excluded. Each patient's medical history and profile were reviewed. RESULTS: Twenty-three patients were identified with osteonecrosis of the mandible or maxilla. All of these were associated with the use of new generation bisphosphonates: zolendronate (Zometa, Novartis), pamidronate (Aredia, Novartis), and alendronate (Fosamax, Merck). Eighteen patients with known bone metastases had been treated with the intravenous form, whereas five patients with either osteoporosis or Paget's disease were using oral therapy. Patients typically presented with a nonhealing lesion, often times the result of previous dental intervention. Although the majority of these patients were treated with conservative surgical debridement, we present a case requiring a near total maxillectomy. CONCLUSIONS: Drug induced osteonecrosis of the mandible or maxilla has been recently recognized as a sequelae of treatment with the new generation of bisphosphonates. Most patients can be treated with conservative surgical debridement and cessation of bisphosphonate therapy, whereas a few may require radical surgical intervention. Other recommendations include regimented prophylactic care with an assessment of dental status before the administration of bisphosphonates, avoidance of dental procedures, and close monitoring of oral hygiene.

Spindle cell lipoma of the oral cavity.

Spindle cell lipoma is typically seen in the neck/trunk region of middle-aged and older men. Rare cases of oral spindle cell lipoma have been reported. An entity described as myxoid lipoma of the oral cavity has rarely been reported but appears to be more properly classified as spindle cell lipoma. We describe the largest series yet of oral spindle cell lipoma involving the tongue (4), buccal mucosa (1), floor of mouth (1), and lip (1). The patients (3M; 4F) ranged from 31 to 88 years old. All presented with mass lesions. All were circumscribed and composed of mature adipocytes admixed with bland spindled cells. In two cases the adipocytes appeared atrophic, imparting a pseudo-lipoblastic appearance. No true lipoblasts were seen and none had the characteristic vasculature of a myxoid liposarcoma or the characteristic hyperchromatic cells of well-differentiated liposarcoma. The stromal background of all cases contained characteristic wiry collagen and myxoid ground substance. The myxoid ground substance was prominent in four cases. Immunohistochemical stains for CD34 highlighted the bland spindle cells in all cases. The combination of the histologic features and the immunoreactivity for CD34 confirmed the diagnosis. Spindle cell lipoma should be considered in the differential diagnosis of oral cavity mesenchymal tumors.