Patterns of virtual reality and Fitbit wearable activity device use after skull base surgery.

KEY POINTS: Virtual reality (VR) and Fitbit devices are well tolerated by patients after skull base surgery. Postoperative recovery protocols may benefit from incorporation of these devices. However, challenges including patient compliance may impact optimal device utilization.

Molecular profile of head and neck rhabdomyosarcomas: A systematic review and meta-analysis.

OBJECTIVE: This systematic review aimed to identify the molecular alterations of head and neck rhabdomyosarcomas (HNRMS) and their prognostic values. STUDY DESIGN: An electronic search was performed using PubMed, Embase, Scopus, and Web of Science with a designed search strategy. Inclusion criteria comprised cases of primary HNRMS with an established histopathological diagnosis and molecular analysis. Forty-nine studies were included and were appraised for methodological quality using the Joanna Briggs Institute Critical Appraisal tools. Five studies were selected for meta-analysis. RESULTS: HNRMS predominantly affects pediatric patients (44.4%), and the parameningeal region (57.7%) is the most common location. The alveolar variant (43.2%) predominates over the embryonal and spindle cell/sclerosing types, followed by the epithelioid and pleomorphic variants. PAX-FOXO1 fusion was observed in 103 cases of alveolar RMS (79.8%). MYOD1 mutation was found in 39 cases of sclerosing/spindle cell RMS (53.4%). FUS/EWSR1-TFCP2 gene fusions were identified in 21 cases of RMS with epithelioid and spindle cell morphologies (95.5%). The 5-year overall survival rate of patients was 61.3%, and MYOD1 mutation correlated with significantly higher mortality. CONCLUSION: The genotypic profile of histologic variants of HNRMS is widely variable, and MYOD1 mutation could be a potential prognostic factor, but more studies are required to establish this.

Interconnections Between the Oral and Gut Microbiomes: Reversal of Microbial Dysbiosis and the Balance Between Systemic Health and Disease.

The human microbiota represents a complex array of microbial species that influence the balance between the health and pathology of their surrounding environment. These microorganisms impart important biological benefits to their host, such as immune regulation and resistance to pathogen colonization. Dysbiosis of microbial communities in the gut and mouth precede many oral and systemic diseases such as cancer, autoimmune-related conditions, and inflammatory states, and can involve the breakdown of innate barriers, immune dysregulation, pro-inflammatory signaling, and molecular mimicry. Emerging evidence suggests that periodontitis-associated pathogens can translocate to distant sites to elicit severe local and systemic pathologies, which necessitates research into future therapies. Fecal microbiota transplantation, probiotics, prebiotics, and synbiotics represent current modes of treatment to reverse microbial dysbiosis through the introduction of health-related bacterial species and substrates. Furthermore, the emerging field of precision medicine has been shown to be an effective method in modulating host immune response through targeting molecular biomarkers and inflammatory mediators. Although connections between the human microbiome, immune system, and systemic disease are becoming more apparent, the complex interplay and future innovations in treatment modalities will become elucidated through continued research and cross-disciplinary collaboration.

Reconstruction of the maxilla and mandible with particulate bone graft and titanium mesh for implant placement.

PURPOSE: The purpose of the study was to evaluate the magnitude of ridge augmentation with titanium mesh, overall graft success, anatomic location of ridge defects and their relationship to mesh exposure. MATERIALS AND METHODS: This retrospective study evaluated 44 patients who received mandibular or maxillary reconstruction with autogenous particulate bone graft and titanium mesh for the purpose of implant placement. Autogenous bone graft was harvested from the iliac crest, tibia, and mandibular symphysis. A total of 45 sites were included in the study. Average augmentation bone heights were measured and compared. Statistical analysis was done with ANOVA and Student's t test. Histomorphometric analysis was performed on the soft tissue specimen found between the mesh and the bone graft. RESULTS: Twenty-nine sites underwent mandibular reconstruction and 16 underwent maxillary reconstruction. The mean augmentation in partial maxillary defects was 11.33 +/- 1.56 mm, and in complete maxillary augmentation, the height achieved was 14.3 +/- 1.39 mm. In the mandible, mean increase in height for partial defects was 14 +/- 1.42 mm and for complete augmentation it was 13.71 +/- 1.14 mm. The mean augmentation for all sites was 13.7 mm (12.8 mm in the maxilla and 13.9 mm in the mandible). A total of 82 implants were placed in the maxilla and 92 implants were placed in the mandible. In the maxillary group, 7 sites had exposure of the titanium mesh and 16 sites were exposed in the mandible. The success of the bone grafting procedure was 97.72%. CONCLUSIONS: Porous titanium mesh is a reliable containment system used for reconstruction of the maxilla and the mandible. This material tolerates exposure very well and gives predictable results.

Sinonasal teratocarcinosarcoma: report of a case with review of literature and treatment outcome.

Sinonasal teratocarcinosarcoma is a highly malignant, polymorphous neoplasm that combines features of carcinosarcoma and teratoma. We describe the clinicopathologic features and management of a well-documented example of this unique entity that involved a 41-year-old Hispanic man. The patient presented with a history of multiple episodes of epistaxis, nasal obstruction and frontal headaches. Computerized tomography scans and magnetic resonance imaging revealed a large mass filling the left nasal cavity and extending to the cribriform plate with involvement of the ethmoid sinuses, lamina papyracea, and orbit. The patient underwent a complex procedure for a T3N0 tumor. Histologic examination revealed a heterogeneous admixture of epithelial, mesenchymal, and neuroepithelial elements. The mesenchymal components consist of fibrous stroma and myxomatous areas, labeled with calponin and smooth muscle actin. The epithelial components vary from clear cells, nonkeratinizing epithelium to glandular pattern, and keratin containing cysts. Immature neuroepithelium and olfactory neuroblastomalike tissue are highlighted with neuroendocrine markers. Postoperatively, the patient had a rapid local recurrence of the tumor and underwent reexcision, and was treated with radiotherapy and chemotherapy. Twelve months after his primary resection, computerized tomography scans revealed an intrathoracic tumor with dominant mass in the left hilum and metastases to the mediastinum, left pleural space, and both lungs. The histologic nature of his chest mass remains undetermined. Among 54 cases of reported sinonasal teratocarcinosarcoma, 67% of patients with initial single surgical resection and 80% of patients primarily treated with radiotherapy had recurrence, or metastatsis, or unresponsiveness to treatment. The high rate of local recurrence and metastasis is indicative of its highly aggressive biologic behavior. Almost half of the patients died of tumor within 3 years of diagnosis, despite aggressive therapy. Seventy percent of the patients who survived more than 1 year had the initial therapeutic regiments of combined surgery and adjuvant therapies, suggesting that aggressive therapeutic approaches may improve the treatment outcome.

Synovial sarcoma: clinicopathologic features, treatment, and prognosis.

Synovial sarcoma is a characteristic subtype of soft tissue sarcomas with a predilection for young people. There may be a long delay in diagnosis or misdiagnosis, because of its insidious growth, varied presentation on imaging studies and associated joint pain, which can be confused with trauma. Diagnosis requires a tissue sample in the form of a needle or open biopsy. The needle biopsy may not be representative of the tumor, particular if it is biphasic, and it may be necessary to proceed to open biopsy. Ideally, the biopsy should be performed by the surgeon who will be performing the definitive surgical resection. Although treatment is predicated on surgery, adjuvant radiation and/or chemotherapy may be beneficial, particularly in high risk patients. Significant prognostic factors include: size > 5 cm, deep-seated location, adequacy of surgical margins, and history of recurrence. In the future, multi-institutional prospectively randomized, controlled studies will be needed to better define the role of adjuvant chemotherapy. Currently, outcome may be optimized by early suspicion and detection with referral to an orthopedic oncology specialist prior to the biopsy.

Combined DOG1 and Mammaglobin Immunohistochemistry Is Comparable to ETV6-breakapart Analysis for Differentiating Between Papillary Cystic Variants of Acinic Cell Carcinoma and Mammary Analogue Secretory Carcinoma.

BACKGROUND: We investigated the reliability of combined DOG1 and mammaglobin immunohistochemistry compared with ETV6 fluorescence in situ hybridization (FISH) in the assessment of salivary tumors previously diagnosed as acinic cell carcinoma (ACC). Ultrastructural features of cases reclassified as mammary analogue secretory carcinoma (MASC) were assessed by transmission electron microscopy (TEM). METHODS: Immunohistochemical (IHC) reactivity to DOG1 and mammaglobin was validated against FISH targeting the ETV6 gene in all 14 cases. RESULTS: Three cases with papillary cystic histomorphology previously diagnosed as ACC were revised to MASC. TEM features of the ETV6 rearrangement-positive MASC cases showed large numbers of secretory granules with extrusion into the intercellular spaces, well-developed endoplasmic reticulum, lipid-laden vacuoles, well-formed microvilli, and large lining cystic spaces. CONCLUSIONS: Combined DOG1 and mammaglobin immunohistochemistry is comparable to ETV6 -breakapart analysis for differentiating between papillary cystic variants of ACC and MASC.

Overexpression of the oncogenic kinase Pim-1 leads to genomic instability.

Aneuploidy and chromosomal aberrations are hallmarks of most human epithelial malignancies. Here we show that overexpression of the oncogenic kinase Pim-1 in human prostate epithelial cells induces genomic instability by subverting the mitotic spindle checkpoint. Cells overexpressing Pim-1 have a defect in the mitotic spindle checkpoint, abnormal mitotic spindles, centrosome amplification, and chromosome missegregation. Polyploidy and aneuploidy ensue due to a delay in completing cytokinesis. These results define a novel role for elevated Pim-1 expression in promoting genomic instability in human prostate tumors.

Osteoclastogenesis: the role of calcium and calmodulin.

Enhanced osteoclastogenesis is an important pathological feature in several aging-associated bone diseases. Thus, research activities on osteoclastogenesis have been intense during the last ten years. There has been great progress made in this field, however, and in this review, we will focus on current advances in understanding the role of Ca2+/calmodulin signaling in osteoclastogenesis. There are two major Ca2+/calmodulin signaling pathways emerging as important in osteoclastogenesis. The first is from our recent data, which has established a specific role for calmodulin in osteoclastogenesis and, more specifically, calmodulin-dependent kinase II (CaMKII). The other is that a pathway involving RANK-Ca2+-calmodulin-calcineurin-NFAT is critical for osteoclastogenesis. Collectively, these reports highlight the importance of Ca2+/calmodulin signaling in osteoclastogenesis, which may present novel targets for the new therapeutic agents to combat bone loss.

Craniofacial manifestations of ß-thalassemia major.

Hemoglobinopathies are by far the most common genetic diseases, affecting millions worldwide with a prevalence for natives of Iran, Southeast Asia, and the Caspian Sea, as part of the so-called Thalassemia Belt, and an overall incidence ranging approximately from 3 to 100 patients per 100,000 population. ß-Thalassemia major is of particular significance, providing bad outcomes despite aggressive therapeutic approaches. We report a case of ß-thalassemia in a 5-year-old Persian boy who presented with classical diagnostic features of the disease and who did not survive despite an aggressive management approach. A review of the clinical, radiographic, laboratory, and therapeutic characteristics as well as diagnostic tests of this disease is also presented. The multifactorial challenges that face clinicians in the management of this serious disease are also reviewed.

Clear cell odontogenic carcinoma: report of a case and analysis of the literature.

BACKGROUND: Clear cell odontogenic carcinoma (CCOC), which has been described within the past 2 decades, is a rare odontogenic tumor that tends to occur in the mandible of older adults, with a predilection for women. It is potentially aggressive and capable of multiple local recurrences and locoregional and distant metastases. OBJECTIVES: To report the clinicopathologic findings and follow-up of a case of CCOC and to review the literature. DESIGN: Case report and literature review. MAIN OUTCOME MEASUREMENTS: Findings from histologic analysis, immunohistochemistry, and electron microscopy. RESULTS: An 81-year-old woman experienced 3 locoregional recurrences within 21 months of initial therapy. She is presently disease free, 4.5 years after initial resection, having received multiple resections and adjuvant radiotherapy. CONCLUSIONS: The diagnosis of CCOC must be considered in the differential diagnosis of jaw tumors with a clear cell component. For these tumors, resection with negative margins is the treatment of choice because more conservative surgery (eg, curettage) inevitably results in recurrence and/or metastasis. Adjuvant radiotherapy is a rational option for tumors that have eroded cortex.

Tophaceous pseudogout of the temporomandibular joint: a series of 3 cases.

OBJECTIVE: We report a series of 3 cases of tophaceous pseudogout of the temporomandibular joint (TMJ). STUDY DESIGN: Three patients, two men and one woman, ranging in age between 60 and 75 years, presented with unilateral painful swelling of the TMJ area associated with limitation of mouth opening. RESULTS: Radiographic and computed tomographic images showed opaque masses in the supracondylar region of the TMJ. The preoperative clinical impression was a "neoplastic lesion" in the 3 cases. Microscopic examination revealed numerous deeply basophilic masses of calcified deposits, exhibiting birefringence under polarized light and morphologically consistent with calcium pyrophosphate dihydrate deposition, referred to in these cases as "tophaceous pseudogout." CONCLUSION: Tophaceous pseudogout is a rare benign arthropathy that presents with clinical and radiographic features mimicking neoplastic conditions of the TMJ. Therefore, it is recommended that tophaceous pseudogout be considered in the differential diagnosis when a TMJ is involved with "neoplasm-like" lesions clinically and radiographically.

Moderately differentiated neuroendocrine carcinoma (atypical carcinoid) of the parotid gland: report of three cases with contemporary review of salivary neuroendocrine carcinomas.

Primary neuroendocrine carcinomas (NECs) of the salivary glands are rare. Most reported NECs in that region are small cell carcinomas with few cases of large cell undifferentiated carcinoma and typical carcinoid tumors. Only two moderately differentiated NECs (atypical carcinoid tumors) have been previously reported. In the current series, the authors report three additional moderately differentiated NECs (atypical carcinoid tumors) of the parotid gland; two occurred in women and one in a man. All patients were initially treated with parotidectomy, with selective lymph node excision in one, and radiation therapy in another. Follow-up was available for two cases (18 and 79 months). One patient had two local recurrences, developing lymph node and liver metastases requiring further surgery and chemotherapy. Currently, she is alive with disease, on supportive care. The second patient is alive with no signs of recurrence. Patients' work-up excluded the possibility of metastatic NECs to the salivary glands in all cases. Histologically, the tumors demonstrated infiltrating nests, cords and trabeculae of round, oval to spindle shaped cells with moderate to focally abundant eosinophilic cytoplasm, small to prominent nucleoli and chromatin stippling. Scattered rosette-like structures were prominent in one tumor. The highest mitotic counts for the three tumors ranged from 5 to 8 mitotic figures/10 hpfs. Necrosis, focal but distinct, was noted in two tumors, vascular invasion in two tumors and perineural invasion in one tumor. Immunohistochemical staining was diagnostic of neuroendocrine carcinoma, showing uniform positive labeling with broad-spectrum cytokeratin (with a paranuclear punctuate pattern in one case), chromogranin and synaptophysin antibodies. CK20 was negative in two tumors and stained rare cells (<1%) in the third.

Salivary mucoepidermoid carcinoma: demonstration of transcriptionally active human papillomavirus 16/18.

Herein we test the following hypotheses: (1) High-risk Human Papillomavirus (HR-HPV) may be involved in the etiology of mucoepidermoid carcinoma (MEC), and (2) The detection rate of HR-HPV in MEC has been increasing over time. Ninety-eight archival MEC specimens from three institutions spanning three decades were studied for HPV16/18 E6/E7 transcripts. RNA was extracted from formalin-fixed paraffin embedded specimens and HPV16/18 E6/E7 expression assessed by nested reverse transcription polymerase chain reaction (RT-PCR). A subset of MEC were also studied for MECT1-MAML2 fusion transcripts by nested RT-PCR and amplicon sequencing. The HPV expression data was validated by immunofluorescence (IF) with monoclonal HPV16/18 E6 antibody, PCR with the GP5+/6+ consensus primers, and sequencing of RT-PCR amplicons. HPV genome was localized by in-situ hybridization with the Ventana Inform HPVIII Family 16 probe. P16(INK4a) overexpression and aberrant p53 expression were assessed by immunohistochemistry. HPV16 E6/E7 transcripts were demonstrated in (29/98) 30% of MEC by RT-PCR. HPV18 E6/E7 transcripts were demonstrated in 13/98 (13%) of MEC by RT-PCR. Seven of 98 tumors (7%) demonstrated both HPV16/18. No significant association was found between HPV status and gender, age, and tumor site. All 13 HPV18+ MEC were diagnosed between 2001 and 2010, whereas 45 MEC diagnosed from 1977 to 2000 were negative for HPV18 (p = 0.002). By contrast, there was no significant difference with respect to HPV16 detection and date of diagnosis. All MEC that were positive for E6 protein were also HPV16/18 positive by RT-PCR. Sequencing a subset of RT-PCR amplicons confirmed HPV type- and region-specific sequences. PCR using GP5+/6+ consensus primers demonstrated HPV status concordance in 9 of 10 cases. DNA degradation was present in the last case; the RT-PCR amplicons were sequenced from this case which confirmed the presence of HPV type- and region-specific sequences. Strong (+4/+4) and diffuse (>50%) nuclear and cytoplasmic p16 expression was seen in 64% of MEC in the glandular regions, and 18% of MEC in the solid, squamoid regions. No correlation was seen between p16 expression and HPV status. Twenty-nine MEC (22 HPV+ and 7 HPV-negative) were selected for further evaluation for p53 expression. Strong aberrant nuclear p53 expression was present in only 2/22 HPV + MEC (9%, both Grade 3); no HPV-negative MEC demonstrated aberrant p53 expression. MECT1-MAML2 fusion transcripts were demonstrated in 23/37 (62%) MEC. No significant association was found between the presence of the MECT1-MAML2 fusion transcripts and tumor grade, HPV status, gender, era of diagnosis (2000 and earlier vs. 2001-2010) or tumor site. We demonstrate for the first time that transcriptionally active HPV16/18 is common to MEC. These findings were validated by demonstrating concordant results by separate PCR with consensus primers, and/or confirming the presence of HPV type- and region-specific sequences in the RT-PCR amplicons. We also visualized E6 viral oncoprotein and HPV genome within tumor cells. HR-HPV is thus potentially implicated in the pathogenesis of MEC. The frequency of HPV18 detection is significantly increased in MEC diagnosed after 2001, whereas we found no differences in the HPV16 detection rates per era of diagnosis.

Head and neck mucosal malignant melanoma: clinicopathologic correlation with contemporary review of prognostic indicators.

Unlike their cutaneous counterparts, head and neck mucosal malignant melanomas (HNMM) behave much more aggressively and their prognostic markers have not been fully elucidated. Therefore, the aim of this study was to review the clinicopathologic features of a contemporary series of primary HNMM, retrieved from archival material of 2 large medical centers, and to explore the association, if any, between these variables, the clinical features, and outcomes. The clinicopathologic, radiographic, and follow-up information as well as the dominant histologic pattern, mitotic rate, presence/absence of pigmentation, necrosis, ulceration, vascular invasion, and host-associated lymphocytic response were retrieved and recorded. Twenty cases were identified including 1 melanoma in situ. Eight-five percent of tumors arose in the sinonasal tract and 3 (15%) in the oral cavity. After a median follow-up of 25 months, all patients with invasive melanoma developed recurrence and/or metastasis. Local recurrences occurred in 82% of the patients after a median of 12 months, and distant metastasis occurred in 71% of the patients after a median of 13 months. Of those with adequate follow-up, 82% died with disease, and the remaining 3 had recurrent or metastatic disease. Fourth-seven percent of tumors were pigmented, 89% showed at least focal necrosis, and 93% demonstrated ulceration. Sixth-eight percent showed vascular invasion and 63% had a brisk host lymphocytic response. Mitotic rates ranged from 2 to 60/10 high-power fields. The absence of an invasive component might be associated with a better prognosis but other clinical and pathological features that predict outcome, and/or could influence therapy, remain to be determined in HNMM.

Ameloblastoma: a multicentric study.

OBJECTIVE: The objective of this study was to supplement the current ameloblastoma database by reporting the clinicopathologic features of ameloblastoma from Asia and North America. MATERIALS AND METHODS: Biopsy records of the participating institutes were reviewed for lesions diagnosed as ameloblastoma during the years 1993 to 2009. Slides were reclassified according to the World Health Organization Classification of Odontogenic Tumors in 2005. Clinical information and radiographic features were collected and analyzed. RESULTS: The mean age of the patients ± SD was 38.27 ± 17.78 years; 662 patients (51.36%) were men. Mandible (84.26%) outnumbered maxilla and other locations combined in all countries. The number of multilocular radiolucencies (43.40%) was comparable with that of unilocular radiolucencies (42.04%). Follicular pattern was the most common histopathologic pattern (27.70%), followed by plexiform (21.10%) and unicystic pattern (20.71%), respectively. CONCLUSIONS: The clinicopathologic features of ameloblastomas in the present study show some similarities with previous studies; however, minor differences exist.

Lack of correlation between microvascular density and pathological features and outcomes in sinonasal and oral mucosal melanomas.

Unlike its cutaneous counterpart, prognostic markers for primary mucosal malignant melanoma have not been well elucidated. It has been recently demonstrated that microvascular density (MVD) in cutaneous malignant melanoma has a significant negative correlation with survival; however, this has not been well-studied in mucosal malignant melanoma of the head and neck. This study explores the potential association between MVD, various histological parameters, and the outcome of a series of sinonasal and oral mucosal melanomas. Nineteen such cases were immunostained with CD31 and the MVD was calculated by using Bioquant Image Analysis Software (R and M Biometrics, Nashville, TN). These cases included 16 sinonasal and 3 oral cavity tumors. The 1, 2, 3, 4 and 5 years overall survival rates were 75, 57, 61, 46 and 46%, respectively. The MVD of the tumors ranged from 25.7 to 732 vessels/mm(2) (mean 142.8 vessels/mm(2); median 84.7 vessels/mm(2)). There was no significant correlation between the MVD and the different clinicopathological features seen within the tumors. There was also no correlation between the MVD and relapse free and overall survival. The results of this study suggest that MVD does not correlate with outcome in mucosal melanoma of the head and neck as seen in cutaneous melanomas. Further larger studies are needed to identify predictive and prognostic markers in such melanomas.

Estrogen and progesterone receptor expression is not always specific for mammary and gynecologic carcinomas: a tissue microarray and pooled literature review study.

Given their frequent expression in breast and gynecologic carcinomas, the National Comprehensive Cancer Network has recommended that the immunohistochemical expression of estrogen (ER) and/or progesterone (PR) receptors in a carcinoma of unknown primary can be used to support a breast or gynecologic origin. Several reports in the literature, however, have described such expression in a variable proportion of nonmammary and nongynecologic carcinomas. The aim of this study was to systematically evaluate the immunohistochemical expression of ER and PR on tissue microarray sections representing 348 nonbreast or gynecologic and nongynecologic tumors of lung, esophageal, gastric, pancreatic, colonic, renal, or bladder origin. We also performed a pooled analysis of the published literature in this regard. Except for 1 (2.5%) out of 40 pancreatic adenocarcinomas that expressed PR, there was no ER or PR expression in any of the other tumors evaluated by immunohistochemistry. A pooled literature review demonstrated that most of the evaluated tumors express ER and/or PR in up to 3% of cases, whereas some lung and bladder carcinomas showed such expression in around 10% of cases. This literature review also demonstrated that the frequency of ER and PR expression was dependent on the antibody clone used. Given that ER and PR expression can occasionally be seen in carcinomas of nonmammary/nongynecologic origin, we conclude that the diagnosis of metastatic breast, ovarian or endometrial carcinoma in a carcinoma of unknown primary should not be based solely on such expression.