Chen, Tiffany

AbstractBackgroundBuccal squamous cell carcinoma (SCC) is a locoregionally aggressive malignancy, representing a small subset of oral cancers in North America. We investigated the prognostic value of several clinicopathologic factors in a cohort of patients diagnosed with buccal SCC.MethodsBetween years 1992 and 2017, 52 patients were diagnosed with conventional buccal SCC. Archival surgical pathology material was retrospectively reviewed for reportable findings according to the latest reporting guidelines published by the College of American Pathologists. Clinical data were obtained through chart review.ResultsThe majority of patients were of older age, current or past smokers, and without specific gender predilection. Most presented at a clinically advanced stage and were treated with surgery alone, or surgery followed by adjuvant radiotherapy. The tumor recurred in about 40% of patients, and almost half of the patients died from the disease by the end of the follow‐up period. The worst pattern of invasion (WPOI) was associated with greater depth of invasion (DOI) (P = .031) and perineural invasion (P < .001). In univariate analyses, older age (P = .004), positive nodal status (P = .047), lymphovascular invasion (P = .012), perineural invasion (P = .05), and WPOI‐5 (P = .015) were adverse predictors of 5‐year overall survival (OS). In multivariate analysis, older age (P = .011), WPOI‐5 (P < .001), and perineural invasion (P = .001) remained statistically significant independent prognosticators of worse 5‐year OS.ConclusionsOlder age, WPOI‐5, and perineural invasion are significant prognosticators of worse OS. WPOI is associated with DOI, a finding which may have important implications for the pathogenesis and biologic behavior of the disease.

Background OnabotulinumtoxinA has been demonstrated to be effective for the preventive treatment of headache in individuals with chronic migraine and has been approved and recommended for this patient population. While the therapeutic effect of onabotulinumtoxinA on migraine headache is well documented, there is limited information on the effect of onabotulinumtoxinA on migraine aura. Objective Given the prolonged and often debilitating nature of aura in patients with hemiplegic migraine, our group sought to examine the effect of onabotulinumtoxinA on aura frequency and severity in this specific subset of migraine patients. Methods All clinical notes from July 1, 1994 to December 1, 2017 at our institution were retrospectively reviewed to identify patients diagnosed with hemiplegic migraine who received at least one set of onabotulinumtoxinA injections. Thirty‐four patients were identified; and of those, 23 were excluded due to incomplete documentation regarding aura symptoms at follow‐up visits. The clinical notes of the remaining 11 patients (4 with familial hemiplegic migraine [FHM] and 7 with sporadic hemiplegic migraine [SHM]) were reviewed, and the frequency and description of their headaches and aura before and after receiving onabotulinumtoxinA were recorded. Results Nine of the 11 patients in our series noted a decrease in the frequency, severity, and/or duration of their aura after receiving onabotulinumtoxinA. Of the 2 non‐responders, one was FHM and one was SHM. Of the 9 that noticed improved aura symptoms, 6 described a “wearing off” effect of onabotulinumtoxinA around week 9 or 10 of the 12‐week cycle, with subsequent improvement after the next round. Conclusion For 9 of 11 patients with hemiplegic migraine, onabotulinumtoxinA was helpful not only in reducing the frequency and severity of headaches but also in reducing the frequency and severity of the aura. In this manuscript, we speculate on potential pathophysiologic mechanisms that could have contributed to this effect.

AbstractBackgroundCalciphylaxis is a devastating multifactorial disorder of the subcutaneous fat that is known to be associated with hypercoagulability. Recent literature has proposed subclassifying patients with calciphylaxis as having warfarin‐associated or warfarin‐unassociated disease.AimWe aimed to determine whether patients with warfarin‐associated calciphylaxis differ clinically from patients with warfarin‐unassociated calciphylaxis.Materials and methodsWe performed a subgroup analysis of patients with nonuremic calciphylaxis from a previously studied cohort and compared clinical and outcomes features of patients who were taking warfarin at the time of disease onset to those of patients who were not.ResultsNineteen patients with nonuremic calciphylaxis were identified, including 10 (53%) who had been on warfarin at the time of disease onset and 9 (47%) who had not. Of all clinical and outcomes parameters tested, no significant differences were detected between the two groups.Discussion and ConclusionsThough this study is limited by its retrospective nature and the relatively small number of patients studied, available data do not support subclassifying patients with nonuremic calciphylaxis as having warfarin‐associated or warfarin‐unassociated disease. Rather, the body of literature would suggest that identification and correction of underlying disorders of hypercoagulability should be prioritized.

Abstract: Calciphylaxis is a rare, painful, and life-threatening condition with a high mortality rate. Although the etiology of calciphylaxis is not well understood, it has been proposed that calcium deposition within and around subcutaneous vessels restricts blood flow chronically, thereby predisposing the patient to acute pannicular and dermal thrombosis. Given increasing recognition of the role of hypercoagulability in calciphylaxis, this retrospective cohort study sought to evaluate the presence of thromboses and dermal angioplasia in calciphylaxis. Moreover, we aimed to validate previous observations about the histopathology of calciphylaxis compared with skin biopsies from patients with end-stage renal disease but without calciphylaxis. After a meticulous clinical chart review, we assessed the corresponding skin biopsies for the presence of vessel calcification, thromboses, and dermal angioplasia in skin biopsies from patients with calciphylaxis (n = 57) and compared with those from patients with end-stage renal disease but without calciphylaxis (n = 26). Histopathologic findings were correlated with clinical features such as chronic kidney disease, diabetes, or associated malignancy. Our results validated a prior observation that calciphylaxis was significantly more likely to show calcification of dermal vessels and diffuse dermal thrombi. This study reports the frequent finding of dermal angioplasia, a potential marker of chronic low-grade ischemia, as another frequent microscopic finding in calciphylaxis. Among cases of calciphylaxis, histopathologic changes in patients with chronic kidney disease were indistinguishable from those in patients without chronic kidney disease, thereby implying a final common pathogenic pathway in both uremic and nonuremic calciphylaxis. In future, larger, prospective studies may be useful in validating these findings.

Objectives/HypothesisDesign and test a novel biomaterial for injection laryngoplasty aimed to increase the duration of effectiveness of micronized acellular dermis.Study DesignAnimal model.MethodsInjection laryngoplasty was performed in three groups (n = 5) of New Zealand White rabbits. Acellular dermis was either used alone as a control (group 1), was combined with undifferentiated stem cells (group 2), or with predifferentiated chondrocytic cells (group 3). Groups 2 and 3 were supplemented with growth factors. Animals were sacrificed 4 and 12 weeks after laryngoplasty and histologic analysis was completed. The major outcome measure was volume of tissue remaining.ResultsAfter 4 weeks, the mean volume of tissue remaining was 341 ± 89 mm3, 295 ± 102 mm3, and 133 ± 15 mm3, for groups 1 to 3, respectively. At the 12‐week time point, volumes were 62 ± 62 mm3, 235 ± 35 mm3, and 107 ± 99 mm3. After 12 weeks, there was a significantly higher volume in group 2 compared to group 1 or 3 (P = .01, P = .04). Volumes between week 4 and week 12 were significantly lower in group 1 (P = .02), but not significantly different for groups 2 and 3 (P = .38, P = .74). Histologic evaluation revealed a robust lymphocytic infiltration in all cases as well as morphologic and immunophenotypic features suggestive of chondrogenic differentiation in a single animal.ConclusionsMicronized acellular dermis combined with stem cells and growth factors showed significantly less resorption 12 weeks after injection laryngoplasty compared to micronized acellular dermis alone. Groups using novel tissue‐engineered biomaterial showed a lower resorption rate over time compared with acellular dermis alone.Level of EvidenceNA. Laryngoscope, 128:160–167, 2018

Human papillomavirus (HPV)–related multiphenotypic sinonasal carcinoma (HMSC), originally known as HPV-related carcinoma with adenoid cystic carcinoma-like features, is a peculiar neoplasm that is restricted to the sinonasal tract, exhibits features of both a surface-derived and salivary gland carcinoma (particularly adenoid cystic carcinoma), and is associated with high-risk HPV. Given the limited number of published cases, the full clinicopathologic spectrum of this neoplasm is unclear. Here, we present an updated experience of 49 cases. All cases of HMSC were obtained from the authors’ files. Immunohistochemistry for p16, c-kit, and myoepithelial cell markers (S100, actin, calponin, p63, and/or p40) was performed along with RNA in situ hybridization for HPV (type 33-specific as well as a high-risk cocktail). Fluorescence in situ hybridization studies for fusions ofMYB,NFIB, andMYBL1was performed on a subset of cases. Clinical follow-up was obtained from medical records. A total of 49 cases of HMSC were collected. Twenty-eight (57%) were from women and 18 (43%) from men, ranging in age from 28 to 90 years (mean, 54 y). Of 40 cases with detailed staging information, 43% of HMSCs presented with a high T-stage (T3 or T4). Histologically, most grew predominantly as solid nests of basaloid cells exhibiting high mitotic rates and frequent necrosis, with histologic and immunohistochemical evidence of myoepithelial differentiation. Most cases also demonstrated foci of cribriform and/or tubular growth, along with an inconspicuous population of ducts. Thirty-four (69%) cases demonstrated an unusual pattern of surface involvement where markedly atypical squamous cells colonized tracts of the sinonasal mucosa. Less consistent histologic features included squamous differentiation within the invasive tumor (n=6), sarcomatoid transformation (n=5) including overt chondroid differentiation (n=3), and prominent epithelial-myoepithelial carcinoma-like growth (n=3). All cases were positive for p16 by immunostaining and HPV by RNA in situ hybridization. Thirty-three (67%) were positive for HPV 33. No cases tested forMYB,MYBL1, orNFIBgene fusions were positive. In the 38 cases with follow-up data, (mean follow-up, 42 mo) 14 recurred locally and 2 metastasized (lung, finger). There were no regional lymph node metastases, and no tumor-related deaths. HMSC is a distinct sinonasal neoplasm characterized by myoepithelial differentiation, frequent surface epithelial involvement, and the presence of high-risk HPV (especially type 33). Although it classically exhibits a cribriforming pattern that closely resembles adenoid cystic carcinoma, our expanded series highlights a histologic spectrum that is much broader than previously recognized, warranting a change in terminology. HMSC usually presents as a large and destructive sinonasal mass with high-grade histologic features, but it paradoxically behaves in a relatively indolent manner, underscoring the importance of distinguishing HMSC from true adenoid cystic carcinoma, squamous cell carcinoma, and other histologic mimickers.

Objectives/HypothesisMicronized AlloDerm is a commonly used injectable material for injection laryngoplasty; however, the histologic response to laryngeal implantation and resorption rate over time have not been elucidated. This study aimed to evaluate the in vivo response of micronized AlloDerm over time after laryngeal implantation using a rabbit model.Study DesignAnimal model.MethodsThe left recurrent laryngeal nerve was sectioned in five New Zealand White rabbits to create a vocal cord paralysis. Two weeks later, injection laryngoplasty was performed with 100 μL of micronized AlloDerm. Animals were sacrificed 4 (two rabbits) and 12 (three rabbits) weeks after injection. Histologic sections were stained and evaluated by a single pathologist. Volume estimates were made by assuming the implant took an ellipsoid shape using dimensions calculated from histologic slides.ResultsIn all cases, histological analysis revealed a lymphocytic inflammatory response infiltrating the peripheral margins of injection. After 4 weeks, the volume of injected material remaining in two rabbits was 404 and 278 mm3 (average 341 mm3). After 12 weeks, the volume of injected material remaining in three rabbits was 0, 61, and 124 mm3 (average 62 mm3), an 82% difference in volume of material between animals sacrificed at 4 weeks versus 12 weeks.ConclusionsInjection laryngoplasty using micronized AlloDerm induces a lymphocytic inflammatory response after injection in a rabbit model. Though a significant amount of material remains after 4 weeks, by 12 weeks the majority has been reabsorbed.Level of EvidenceNA Laryngoscope, 127:E166–E169, 2017