Adamantinoma-like Ewing Sarcoma (ALES) May Harbor FUS Rearrangements : A Potential Diagnostic Pitfall.

Adamantinoma-like Ewing sarcoma (ALES) is a rare malignancy currently considered a variant of Ewing sarcoma with most known cases harboring EWSR1 rearrangements. Herein we present a series of 6 cases of EWSR1 -negative ALES. The tumors arose in the sinonasal tract (n=3), major salivary glands (submandibular gland=1; parotid=1), and anterior mediastinum (n=1) in patients ranging from 25 to 79 years of age. Most tumors were basaloid in appearance, growing in large nests separated by interlobular fibrosis without overt squamous pearls. However, 1 case closely resembled a well-differentiated neuroendocrine tumor with uniformly round nuclei, eosinophilic cytoplasm, and trabecular architecture. All cases were diffusely positive for pan-cytokeratin, p40 or p63, and CD99. A subset of cases showed diffuse reactivity for synaptophysin, including 1 sinonasal tumor which also demonstrated sustentacular S100 protein expression. Molecular testing showed FUS rearrangements in all cases. Gene partners included known ETS family members FEV (n=2) and FLI1 (n=1). Our results expand the molecular diagnostic considerations for ALES to include FUS rearrangements. We also show that ALES may harbor FUS :: FLI1 fusion, which has not been previously reported in the Ewing family of tumors. Furthermore, ALES may show unusual histologic and immunophenotypic features that can overlap with olfactory carcinoma including S100-positive sustentacular cells. ALES should be considered in the diagnostic differential of small round cell tumors and tumors with neuroendocrine differentiation with immunohistochemical workup to include p40 and CD99/NKX2.2.

Benign fibrohistiocytic jaw lesions: a 48-year clinicopathologic analysis and review of the literature.

OBJECTIVE: Intra-osseous fibrohistiocytic lesions have long been reported in the literature; evidence suggests they represent a heterogeneous group of reactive and neoplastic processes. This study evaluated a series of gnathic fibrohistiocytic lesions to identify and categorize their clinical, radiographic and morphologic spectrum. STUDY DESIGN: A retrospective case search over 48 years was conducted for maxillary and mandibular intra-bony fibrohistiocytic lesions. Diagnoses were confirmed and demographic, radiographic, clinical and follow-up data was analyzed. RESULTS: Fifty cases met the inclusion criteria. Most cases (80%) were found in the second through fourth decades (mean, 29 years). The most common location (86%) was the posterior mandible. Radiographic presentations varied, but a few patterns emerged, including a distinctive mottled, honeycomb type with punctate lucencies. All cases demonstrated fibrous components admixed with variable histiocytes. Eight cases (16%) were histiocyte-rich with dominant sheets of xanthoma cells. Immunohistochemical staining revealed strong CD68 and CD163 expression, along with variable smooth muscle actin staining. The vast majority (92%) of cases were treated conservatively. Available follow-up showed lesional stability in 17 cases (average, 85 months) with 2 recurrences (24 months each) and no evidence of malignant transformation. CONCLUSIONS: This study is the largest to date of fibrohistiocytic gnathic lesions, revealing distinctive radiographic and histologic findings and characteristic clinical and immunophenotypic features. Available evidence suggests that most of these are indolent, slow-growing lesions amenable to conservative therapy.

Unlicensed driving among young drivers in North Carolina: a quasi-induced exposure analysis.

BACKGROUND: Little is known about the prevalence of driving among teenagers who have not yet obtained a license. The primary objective of the present study was to estimate the prevalence of unlicensed driving among young drivers using the quasi-induced exposure (QIE) approach and to determine whether unlicensed driving was more common among minority and lower-income teenagers. Additionally, we examined whether unlicensed driving among adolescents increased following the implementation of a graduated driver licensing (GDL) system and whether GDL differentially affected minority and low-income adolescents. METHODS: Using North Carolina crash and driver license data, we identified 90,267 two-vehicle crashes from 1991 through 2016 where only one driver was considered contributory and the non-contributory driver was a White or Black 16 or 17 years old. In the QIE approach, these non-contributory young drivers are assumed to be representative of all adolescents driving in the state during this time period. The prevalence of unlicensed driving among adolescents by age and year was estimated by identifying the proportion of non-contributory drivers who had never been licensed by the time of their involvement in these two-vehicle crashes. We further conducted logistic regression analyses to examine the likelihood of a non-contributory young driver being unlicensed as a function of race, neighborhood income level, and licensing era (prior to or after GDL was implemented). RESULTS: During the 26 years for which data were available, the mean annual prevalence of unlicensed driving was 1.2% for 16-year-olds and 1.7% among 17-year-olds. Young Black drivers and individuals living in lower-income neighborhoods were somewhat more likely to drive before obtaining a license, but the rates of unlicensed driving among these groups were also quite low. Unlicensed driving increased slightly for 17-year-olds following the implementation of GDL, but returned to previous levels after a few years. CONCLUSION: Unlicensed driving among adolescents in North Carolina is substantially less common than suggested by previous self-report studies and analyses of fatal crash data.

The role of inexperience in motorcycle crashes among novice and returning motorcycle riders.

OBJECTIVES: To examine the crash trends of younger novice and older novice/returning motorcycle riders. METHODS: We used a linked database of North Carolina crash and licensing data from 1991 through 2018 that included 103,142 younger novice and 98,540 older novice/returning motorcycle riders. We examined the percent of riders who crashed each month after obtaining a motorcycle license. RESULTS: Crash rates peak for both younger novice and older novice/returning motorcycle riders immediately after licensure. Crash rates decline rapidly, and the rate of decrease resembles a power function. The improvement rate (IR) for younger novice riders is 0.42; that is, the crash rate for younger novices declines by approximately 42% as experience doubles. CONCLUSION: The crash curve for novice motorcyclists is similar to that of novice car drivers and is consistent with a learning process. PRACTICAL APPLICATIONS: The crash trends of novice motorcycle riders indicate that current training, licensing, and educational efforts are not adequately preparing new riders. Additional efforts to develop more effective training, and research to inform a well-calibrated graduated licensing process for new riders are needed.

Sinonasal Tumors With Neuroepithelial Differentiation (Olfactory Carcinoma): Delineation of Their Pathologic and Clinical Features With Insights into Their Relationship to Olfactory Neuroblastoma and Sinonasal Carcinoma.

Olfactory carcinoma is one of many names applied to sinonasal malignancies with histologic similarity to olfactory neuroblastoma (ONB) but cytokeratin expression or gland formation. It is unclear whether these neuroepithelial tumors represent a unified category and if they are separate from ONB and currently-recognized sinonasal carcinomas. This study aims to explore their clinicopathologic characteristics based on a large collective experience. A total of 53 sinonasal tumors with neuroepithelial differentiation were identified affecting 41 men and 12 women, median age 47 years (range: 12 to 82 y). The vast majority arose in the superior nasal cavity and presented at the high Kadish-Morita stage. Frequent histologic findings included (1) lobulated and solid growth, (2) rosettes and/or neurofibrillary stroma, (3) high-grade cytology, (4) complex, often ciliated glands, (5) nonfocal pancytokeratin expression, (6) neuroendocrine pos+itivity, and (7) variable S100-positive sustentacular cells. Twelve patients with available follow-up (48%) developed progressive disease at a median 8 months (range: 0 to 114 mo to progression), and 7 (28%) died of disease. Despite disparate historical terminology, neuroepithelial differentiation is a recurrent and recognizable histologic pattern that is associated with aggressive behavior in sinonasal tumors. While tumors with this phenotype may originate from olfactory mucosa, well-developed epithelial features warrant separation from conventional ONB and neural elements distinguish them from most sinonasal carcinomas. Although their full histogenesis remains uncertain and some heterogeneity may exist, we propose that this pattern is sufficiently distinctive to merit separate recognition as olfactory carcinoma. Use of consistent nomenclature may facilitate greater recognition of tumors with this phenotype and understanding of their pathogenesis and classification.

Epithelioid and Spindle Cell Rhabdomyosarcoma of the Oral Mucosa with FUS Rearrangement.

The spectrum of rhabdomyosarcomas continues to expand beyond the more widely recognized embryonal and alveolar types as newer and novel subtypes are identified. These variants are typically classified on the basis of recurring mutations or translocations and frequently show distinctive clinical, morphologic and immunophenotypic features. A case of newly characterized FUS gene rearranged epithelioid and spindle cell rhabdomyosarcoma presenting as an intra-oral mucosal lesion without evidence of an osseous component is described. The characteristic features of an FET-TFCP2 fusion rhabdomyosarcoma were present, including strong pancytokeratin expression. This uncommon and aggressive entity displays a predilection for head and neck sites and familiarity may help avoid diagnostic pitfalls.

The effect of extending graduated driver licensing to older novice drivers in Indiana.

INTRODUCTION: Graduated driver licensing (GDL) systems have been shown to reduce rates of crashes, injuries, and deaths of young novice drivers. However, approximately one in three new drivers in the United States obtain their first driver's license at age 18 or older, and thus are exempt from most or all provisions of GDL in most states. METHOD: In July 2015, the state of Indiana updated its GDL program, extending its restrictions on driving at night and on carrying passengers during the first 6 months of independent driving, previously only applicable to new drivers younger than 18, to all newly-licensed drivers younger than 21 years of age. The current study examined monthly rates of crashes per licensed driver under the affected conditions (driving at night and driving with passengers) among Indiana drivers first licensed at ages 18, 19, and 20 under the updated GDL system compared with drivers licensed at the same ages under the previous GDL system. We used Poisson regression to estimate the association between the GDL system and crash rates, while attempting to control for other factors that might have also influenced crash rates. We used linear regression to estimate the association between the GDL system and the proportion of all crashes that occurred under conditions restricted by the GDL program. RESULTS: Results showed, contrary to expectations, that rates of crashes during restricted nighttime hours and with passengers were higher among drivers licensed under the updated GDL system. This mirrored a statewide increase in crash rates among drivers of all ages over the study period and likely reflected increased overall driving exposure. The proportions of all crashes that were at night or with passengers did not change. Practical Applications: More research is needed to understand how older novice drivers respond when GDL systems originally designed for younger novice drivers are applied to them.

Vehicle safety characteristics in vulnerable driver populations.

OBJECTIVE: National data suggest drivers who are younger, older, and have lower socioeconomic status (SES) have heightened crash-related injury rates. Ensuring vulnerable drivers are in the safest vehicles they can afford is a promising approach to reducing crash injuries in these groups. However, we do not know the extent to which these drivers are disproportionately driving less safe vehicles. Our objective was to obtain population-based estimates of the prevalence of important vehicle safety criteria among a statewide population of drivers. METHODS: We analyzed data from the NJ Safety and Health Outcomes warehouse, which includes all licensing and crash data from 2010-2017. We borrowed the quasi-induced exposure method's fundamental assumption-that non-responsible drivers in clean (i.e., only one responsible driver) multi-vehicle crashes are reasonably representative of drivers on the road-to estimate statewide prevalence of drivers' vehicle characteristics across four driver age groups (17-20; 21-24; 25-64, and ≥65) and quintiles of census tract median household income (n = 983,372). We used NHTSA's Product Information Catalog and Vehicle Listing platform (vPIC) to decode the VIN of each crash-involved vehicle to obtain model year, presence of electronic stability control (ESC), vehicle type, engine horsepower, and presence of front, side, and curtain air bags. RESULTS: The youngest and oldest drivers were more likely than middle-aged drivers to drive vehicles that were older, did not have ESC, and were not equipped with side airbags. Additionally, across all age groups drivers of higher SES were in newer and safer vehicles compared with those of lower SES. For example, young drivers living in lowest-income census tracts drove vehicles that were on average almost twice as old as young drivers living in highest-income tracts (median [IQR]: 11 years [6-14] vs. 6 years [3-11]). CONCLUSIONS: Vehicle safety is an important component of seminal road safety philosophies that aim to reduce crash fatalities. However, driver groups that are overrepresented in fatal crashes-young drivers, older drivers, and those of lower SES-are also driving the less safe vehicles. Ensuring drivers are in the safest car they can afford should be further explored as an approach to reduce crash-related injuries among vulnerable populations.

Sinonasal Myxoma: A Distinct Lesion of Infants.

An 11 month old Caucasian male presented with swelling of the right side of the nose and buccal vestibule of unknown duration. Radiographic images revealed a well-circumscribed, hypodense soft tissue mass with a peripheral hyperdense circumference involving the anterior aspect of the right maxilla. The lesion extended from the inferior aspect of the orbital rim superiorly to the maxillary bone inferiorly without invading any nearby structures. The lesion was completely resected via combined extraoral and intraoral approach. The clinical, radiographic, histologic and immunohistochemical features of a sinonasal myxoma in an infant are discussed.

Extra Nodal Rosai-Dorfman Disease Originating in the Nasal and Paranasal Complex and Gnathic Bones: A Systematic Analysis of Seven Cases and Review of Literature.

Rosai-Dorfman disease (RDD) is a benign, self-limiting histiocytosis of unknown etiology. The classic form of the condition includes a painless cervical lymphaenopathy accompanied by fever, weight loss and an elevated ESR. Extra nodal RDD (ENRDD) is most frequent in the head and neck. Thirty-eight cases of ENRDD have been described. Seven cases of ENRDD were identified in our pathology biopsy services. The demographic and clinical information was tabulated logically on the basis of age, gender, location and presence or absence of symptoms, treatment and follow-up. Radiographic and histopathological features were also examined. The findings in these cases were correlated with those available from the previously reported cases. Six cases affected women and one case was diagnosed in a male. The age ranged from 22-55 years. Three cases presented as a nasal mass. One of these lesions extended into the paranasal sinuses. One case was located in the maxilla and extended to involve the maxillary sinus. Three cases were diagnosed in the mandible. The maxillary and one mandibular lesion (Case 2) resulted in significant painful irregular bone destruction with a non-healing socket and tooth mobility respectively. One mandibular lesion was asymptomatic (Case 6). The third case affecting the mandible presented as a rapidly expansile mass following a tooth extraction (Case 7). Nasal masses presented with symptoms of obstruction. Nasal masses were excised with no recurrence from up to 2-3 years of follow-up. The mandibular lesions were curetted aggressively. The oral mass in Case 7 was excised synchronously. No recurrence up to 2 years was recorded in Case 2. Follow-up information is not available for Cases 6 and 7. The maxillary lesion was not intervened surgically. The patient has persistent but stable disease for a follow-up period of 2 years. ENRDD is rarely considered in the differential diagnosis in the absence of lymph node involvement. Lesions of ENRDD resemble many other histiocytic and histiocyte-rich lesions of the head and neck. This makes the diagnosis of ENRDD challenging with the potential for under diagnosis or misdiagnosis and delay in treatment.

Calcifying Fibrous Tumor of the Neck.

A 19 year old otherwise healthy male presented with a history of acute onset left neck pain with subsequent swelling and development of a left neck mass that progressively enlarged over a two month period. Imaging studies revealed a solid heterogeneous mass with prominent calcifications displacing normal structures. The lesion was resected via transcervical approach and a diagnosis of calcifying fibrous tumor (CFT) was rendered. The clinical, radiographic, histologic and immunophenotypic features of CFT are discussed. CFT is a rare benign soft tissue tumor with distinctive histologic findings. They present as well-circumscribed but unencapsulated, paucicellular lesions consisting of hyalinized fibrous tissue with chronic lymphoplasmacytic inflammation and variable amounts of both psammomatous and dystrophic calcifications distributed throughout. They are found in numerous locations throughout the body, most often in the gastrointestinal tract or subcutaneous soft tissue, but are relatively uncommon in the neck. This article describes a case of CFT which presented as an enlarging neck mass in a young male.

School start times and teenage driver motor vehicle crashes.

INTRODUCTION: Shifting school start times to 8:30 am or later has been found to improve academic performance and reduce behavior problems. Limited research suggests this may also reduce adolescent driver motor vehicle crashes. A change in the school start time from 7:30 am to 8:45 am for all public high schools in one North Carolina county presented the opportunity to address this question with greater methodologic rigor. METHOD: We conducted ARIMA interrupted time-series analyses to examine motor vehicle crash rates of high school age drivers in the intervention county and 3 similar comparison counties with comparable urban-rural population distribution. To focus on crashes most likely to be affected, we limited analysis to crashes involving 16- & 17-year-old drivers occurring on days when school was in session. RESULTS: In the intervention county, there was a 14% downward shift in the time-series following the 75 min delay in school start times (p = .076). There was no change approaching statistical significance in any of the other three counties. Further analysis indicated marked, statistically significant shifts in hourly crash rates in the intervention county, reflecting effects of the change in school start time on young driver exposure. Crashes from 7 to 7:59 am decreased sharply (-25%, p = .008), but increased similarly from 8 to 8:59 am (21%, p = .004). Crashes from 2 to 2:59 pm declined dramatically (-48%, p = .000), then increased to a lesser degree from 3 to 3:59 pm (32%, p = .024) and non-significantly from 4 to 4:59 (19%, p = .102). There was no meaningful change in early morning or nighttime crashes, when drowsiness-induced crashes might have been expected to be most common. DISCUSSION: The small decrease in crashes among high school age drivers following the shift in school start time is consistent with the findings of other studies of teen driver crashes and school start times. All these studies, including the present one, have limitations, but the similar findings suggest that crashes and school start times are indeed related, with earlier start times equating to more crashes. CONCLUSION: Later high school start times (>8:30 am) appear to be associated with lower adolescent driver crash rates, but additional research is needed to confirm this and to identify the mechanism by which this occurs (reduced drowsiness or reduced exposure).

Seromucinous Hamartoma of the Nasal Cavity.

Seromucinous hamartoma (SMH) is a rare benign epithelial proliferation occurring in the sinonasal tract. The clinical, radiographic, and histologic appearance of SMH may mimic several benign and malignant entities. Presented is a novel case, with a review of the literature focused on potential histologic diagnostic pitfalls.

Exceptional responses to pertuzumab, trastuzumab, and docetaxel in human epidermal growth factor receptor-2 high expressing salivary duct carcinomas.

BACKGROUND: Alterations in the human epidermal growth factor receptor-2 (HER2) pathway have been identified in a subset of salivary duct carcinomas. Dual HER2 inhibition with trastuzumab and pertuzumab has superior antitumor efficacy to trastuzumab monotherapy in HER2-positive breast cancer, yet its efficacy in HER2-positive salivary duct carcinoma is unknown. METHODS: We report 2 cases of exceptional responses of HER2-positive salivary duct carcinomas to dual HER2 blockade and docetaxel combination and their molecular characteristics. RESULTS: A 54-year-old man with recurrent metastatic HER2 expressing salivary duct carcinoma of the parotid gland after definitive concurrent chemoradiation achieved a complete response (CR) after 6 cycles of trastuzumab, pertuzumab, and docetaxel (TPH). A 42-year-old woman with HER2-positive salivary duct carcinoma of the parotid gland with bone and liver metastases had CR with TPH and remains in remission on maintenance trastuzumab and pertuzumab. CONCLUSION: Dual HER2 blockage resulted in CR in patients with HER expressing salivary duct carcinoma and warrants further evaluation in this patient population.

Juvenile Trabecular Ossifying Fibroma.

Benign fibro-osseous lesions within the maxillofacial region represent a heterogeneous group of benign entities with overlapping histologic features. Ossifying fibroma, the rarest of these entities, represents a true neoplasm. Juvenile ossifying fibroma (JOF) is considered an aggressive rapidly growing sub-type. It tends to occur in the first or second decades of life. Based on histological and clinical features it can further be classified into two variants, namely juvenile trabecular ossifying fibroma (JTOF) and juvenile psammomatoid ossifying fibroma (JPOF). JTOF features a proliferation of cellular fibroblastic tissue admixed with woven bone trabeculae with varying histologic presentations. Correlation with clinical and radiographic features is essential to differentiate it from other fibro-osseous lesions. A case of JTOF of the mandible is exemplified in this Sine Qua Non Radiology-Pathology article.

NUT Midline Carcinoma of the Nasal Cavity.

Nuclear protein in testis (NUT) midline carcinoma (NMC) is a rare, aggressive, poorly differentiated form of squamous cell carcinoma caused by a chromosomal rearrangement of the NUT gene on chromosome 15. These tumors have a predilection for midline and paramidline structures of the upper aerodigestive tract and mediastinum and can affect patients across a broad age range, including children. In the current example, a 53 year old male presented with a mass originating in the left nasal cavity. The clinical, radiographic, and morphologic features of NMC are discussed.

Olfactory Neuroblastoma: A Case Report.

A 43-year-old female presented with persistent nasal congestion with intermittent epistaxis without resolution for the preceding 5 years. Clinical examination revealed a large pink rubbery mass, medial to the middle turbinate in the right nasal cavity extending to the choana. Radiographic images demonstrated a heterogeneously enhancing lobular soft tissue mass filling the right nasal cavity, causing lateral bowing of the right medial orbital wall and extending posteriorly to the right anterior ethmoid sinus. The clinical, radiographic, histologic, and immunohistochemical features of olfactory neuroblastoma are discussed.