Mutations in linker histone genes HIST1H1 B, C, D, and E; OCT2 (POU2F2); IRF8; and ARID1A underlying the pathogenesis of follicular lymphoma.

Follicular lymphoma (FL) constitutes the second most common non-Hodgkin lymphoma in the western world. FL carries characteristic recurrent structural genomic aberrations. However, information regarding the coding genome in FL is still evolving. Here, we describe the results of massively parallel exome sequencing and single nucleotide polymorphism 6.0 array genomic profiling of 11 highly purified FL cases, and 1 transformed FL case and the validation of selected mutations in 102 FL cases. We report the identification of 15 novel recurrently mutated genes in FL. These include frequent mutations in the linker histone genes HIST1H1 B-E (27%) and mutations in OCT2 (also known as POU2F2; 8%), IRF8 (6%), and ARID1A (11%). A subset of the mutations in HIST1H1 B-E affected binding to DNMT3B, and mutations in HIST1H1 B-E and in EZH2 or ARID1A were largely mutually exclusive, implicating HIST1H1 B-E in epigenetic deregulation in FL. Mutations in OCT2 (POU2F2) affected its transcriptional and functional properties as measured through luciferase assays, the biological analysis of stably transduced cell lines, and global expression profiling. Finally, multiple novel mutated genes located within regions of acquired uniparental disomy in FL are identified. In aggregate, these data substantially broaden our understanding of the genomic pathogenesis of FL.

Esthesioneuroblastoma: updating histologic grading as it relates to prognosis.

OBJECTIVE: The Hyams grading system has been extensively used to predict prognosis in patients with esthesioneuroblastoma (ENB). However, most studies showing prognostic correlation group grading into I/II versus III/IV, essentially comparing low versus high grade. In addition, these studies include patients with variable treatment regimens, including some that were treated with chemoradiation alone. We aimed to determine whether additional histologic variables correlate with outcome with regard to disease free and overall survival in a series of patients universally treated with anterior skull base resection and +/- adjuvant chemoradiation. STUDY DESIGN: A retrospective review of 27 patients with ENB was performed. METHODS: The sections of tumor from these 27 patients were studied and reviewed with attention to percentage lobularity, degree of pleomorphism, degree of neurofibrillary matrix, and degree of apoptosis. In addition, the presence or absence of rosettes, necrosis, calcification, spindle cells, gland hyperplasia, and bone invasion were noted. Finally, the number of mitoses per high power field and the nature of chromatin (fine vs coarse) were recorded. The histopathologic features of these 27 ENBs were reviewed and correlated with clinical outcome. RESULTS: There were 11 patients with recurrence (40.7% recurrence). There were 5 deaths (81.5% survival). The study cohort's mean overall survival was 158 months and the mean disease-free survival was 70.6 months. In terms of overall survival, necrosis and mitosis (#/10hpf) were significant but not when multivariate analysis was performed, these were not individually significant. In terms of disease-free survival, mitosis (#/10hpf) was significant but not on multivariate analysis. Gland hyperplasia was found to be a positive prognostic variable, associated with longer overall and disease-free survival, but only in combination with no spindle features and without necrosis. CONCLUSIONS: An updated histologic grading system may provide more valuable prognostic information in patients with esthesioneuroblastoma treated with a standardized treatment paradigm.

Transcranial orbital decompression for progressive compressive optic neuropathy after 3-wall decompression in severe graves' orbitopathy.

PURPOSE: To determine surgical outcomes after transcranial decompression of the superior orbit in patients with progressive compressive optic neuropathy (CON) secondary to Graves' orbitopathy (GO) who had previously been treated with 3-wall decompression. METHODS: Approval from the West Virginia University Institution Review Board was obtained. A retrospective review of 4 patients with GO who received bilateral transcranial decompression of the orbits for progressive compressive optic neuropathy after bilateral maximal extracranial 3-wall decompression was performed. The patients were treated by the Multidisciplinary Orbit and Skull Base Services at West Virginia University and the University of Michigan. RESULTS: Bilateral transcranial decompression of the orbit for GO was performed on 8 orbits in 4 patients. All 8 orbits had radiographic evidence of compression of the orbital apex, and all patients had been treated with steroids, orbital radiation, and bilateral 3-wall decompression. Preoperative vision ranged from 20/25 to 20/100, which improved to 20/25 or better in all eyes. The visual field mean deviation improved from a mean of -13.05 to -1.67 dB. Hertel measurements improved from a mean of 19.25 to 15.25 mm. Extraocular motility was essentially unchanged. Two patients were noted to have asymptomatic ocular pulsations. There were no other complications, and all patients remained stable during a follow-up period of 5 years (range 2-8 years). CONCLUSIONS: Transcranial decompression is an effective and safe method of salvaging vision when standard treatments fail. This is only the second report of transcranial decompression for refractory compressive optic neuropathy after decompression from a standard approach.

Application of Time-Driven Activity-Based Costing for Head and Neck Microvascular Free Flap Reconstruction.

OBJECTIVE: Traditional hospital accounting fails to provide an accurate cost of complex surgical care. Here we describe the application of time-driven activity-based costing (TDABC) to characterize costs of head and neck oncologic procedures involving free tissue transfer. STUDY DESIGN: Retrospective cohort study. SETTING: Single tertiary academic medical center. METHODS: An analysis of head and neck oncologic procedures involving microvascular free flap reconstruction from 2018 to 2020 (n = 485) was performed using TDABC methodology to measure cost across operative case and postoperative admission, using quantity of time and cost per unit of each resource to characterize resource utilization. Univariate and generalized linear mixed models were used to examine associations between patient and hospital characteristics and cost of care delivery. RESULTS: The total cost of care delivery was $41,905.77 ± 21,870.27 with operating room (OR) supplies accounting for only 10% of the total cost. Multivariable analyses identified significant cost drivers including operative time, postoperative length of stay, number of return trips to the OR, postoperative complication, number of free flaps performed, and patient transfer from another hospital or via emergency department admission (P < .05). CONCLUSION: Operative time and postoperative length of stay, but not operative supplies, were primary drivers of cost of care for head and neck oncology cases involving free tissue transfer. TDABC offers granular cost characterization to inform cost optimization through unused capacity identification and postoperative admission efficiencies.

Orbitocranial approach for treatment of adenoid cystic carcinoma of the lacrimal gland.

OBJECTIVES: Multiple treatment options exist for management of adenoid cystic carcinoma of the lacrimal gland. Our objective was to perform an analysis of outcomes in a cohort of patients with adenoid cystic carcinoma of the lacrimal gland treated identically with an orbitocranial approach. METHODS: We performed a retrospective review of 7 consecutive patients who presented to a tertiary care academic medical center between 1995 and 2009 with adenoid cystic carcinoma of the lacrimal gland. RESULTS: All patients were treated with an orbitocranial approach to tumor resection followed by postoperative radiotherapy. The mean and median follow-up times were 39 and 19 months, respectively (range, 7 to 138 months). Six patients had orbital reconstruction using free tissue transfer, and 1 patient had a split-thickness skin graft to line the orbital cavity. Two patients developed distant metastases 18 months and 29 months after surgery and ultimately died with disease. Five patients are alive without disease. CONCLUSIONS: The orbitocranial approach followed by postoperative irradiation achieves excellent local and regional control rates for adenoid cystic carcinoma of the lacrimal gland, although patients remain at risk long-term for distant metastases. Orbital bone removal to obtain adequate margins should be a routine part of tumor resection for these malignancies.

Ossifying lipoma of c1-c2 in an adolescent.

BACKGROUND: Ossifying lipomas, characterized by their independence of bony connection to the skeleton, are extremely rare benign neoplasms. They have primarily been described in adults older than 50 years of age and occur in the head and neck region. The etiology is unknown. Excision is the preferred treatment. The objective of this study is to report the case of a rare ossifying lipoma immediately anterior to C1 to C2, requiring a transoral approach for excision. METHODS: The case of an adolescent with a retropharyngeal mass is described. RESULTS: A 15-year-old female patient presented with an asymptomatic parapharyngeal mass detected on routine physical examination. Computed tomography and magnetic resonance imaging noted a calcified, left-sided, parapharyngeal mass, approximately 3×2×2 cm, anterior to C1 and C2, most consistent with a benign osseous lesion. A transoral approach was used to excise the mass. Histologic examination demonstrated an ossifying lipoma. Postoperative imaging confirmed complete excision. The postoperative course was unremarkable, and the patient has had no recurrence at 6-month follow-up. CONCLUSIONS: This case demonstrates that a transoral approach to a lesion anterior to C1 to C2 in an adolescent can be safe, complete, and effective. LEVEL OF EVIDENCE: Case Report, level 5.

Esthesioneuroblastoma: Results and Outcomes of a Single Institution's Experience.

OBJECTIVES: Analysis of outcomes of a cohort of patients with esthesioneuroblastoma. DESIGN: Retrospective cohort analysis. SETTING: PATIENTS presenting with esthesioneuroblastoma from 1994 to 2006 in a tertiary care academic medical center. PATIENTS: Fifteen consecutive patients diagnosed as having esthesioneuroblastoma were treated during this time period using a subcranial resection. The mean follow-up is 75 months (range, 2 to 240 mos). RESULTS: The overall survival was 100% and the overall disease-free survival was 49% and 24% at 5 and 15 years, respectively. PATIENTS treated with radiation therapy following surgical resection had a 5- and 15-year disease-free survival of 83.3% compared with a 5- and 15-year disease-free survival of 26.7% and 0%, respectively, for patients whose initial treatment was surgery alone. The mean time to recurrence was 82.1 months. None of the patients had a decrease in Karnofsky Performance Score following subcranial resection. CONCLUSIONS: PATIENTS with esthesioneuroblastoma whose initial treatment consists of surgical resection followed by radiation therapy have a longer disease-free survival than patients treated with surgery alone. However, initial treatment modality did not have an effect on survival. Long-term, close follow-up is necessary to identify recurrences, which can be treated with a high degree of success.

A Family With a Carotid Body Paraganglioma and Thyroid Neoplasias With a New SDHAF2 Germline Variant.

At least 30% of all pheochromocytomas (PCCs)/paragangliomas (PGLs) arise in patients with a germline predisposition syndrome. Variants in succinate dehydrogenase subunits A, B, C, and D (SDHA, SDHB, SDHC, and SDHD) are the most common pathogenic germline alterations. Few pathogenic variants have been reported in succinate dehydrogenase assembly factor 2 (SDHAF2). Here, we describe a 30-year-old female patient who presented with a left-sided neck mass, which was later characterized as a carotid body PGL. Genetic testing revealed a likely pathogenic SDHAF2 variant (c.347G>A;p.W116X). Two sisters carried the same pathologic variant, and screening protocols were recommended. Whole-body MRI revealed thyroid nodules; this testing was followed by fine-needle aspiration, which confirmed papillary thyroid carcinoma in one sister and a follicular adenoma in the other. The two sisters then underwent hemithyroidectomy and total thyroidectomy, respectively. Because evidence for pathogenic variants in SDHAF2 causing predisposition to PCC/PGL is limited, we discuss the challenges in mutational variant interpretation and decision making regarding screening for associated tumors.

Assessment of Intraoperative Nerve Monitoring Parameters Associated With Facial Nerve Outcome in Parotidectomy for Benign Disease.

Importance: Prior studies suggest that the use of facial nerve monitoring decreases the rate of immediate postoperative facial nerve weakness in parotid surgery, but published data are lacking on normative values for these parameters or cutoff values to prognosticate facial nerve outcomes. Objective: To identify intraoperative facial nerve monitoring parameters associated with postoperative weakness and to evaluate cutoff values for these parameters under which normal nerve function is more likely. Design, Setting, and Participants: This retrospective case series of 222 adult patients undergoing parotid surgery for benign disease performed with intraoperative nerve monitoring was conducted at an academic medical institution from September 13, 2004, to October 30, 2014. The data analysis was conducted from May 2018 to January 2019. Main Outcomes and Measures: The main outcome measure was facial nerve weakness. Receiver operating characteristic curves were generated to define optimal cut point to maximize the sensitivity and specificity of the stimulation threshold, mechanical events, and spasm events associated with facial nerve weakness. Results: Of 222 participants, 121 were women and 101 were men, with a mean (SD) age of 51 (16) years. The rate of temporary facial nerve paresis of any nerve branch was 45%, and the rate of permanent paralysis was 1.3%. The mean predissection threshold was 0.22 milliamperes (mA) (range, 0.1-0.6 mA) and the mean postdissection threshold was 0.24 mA (range, 0.08-1.0 mA). The average number of mechanical events was 9 (range, 0-66), and mean number of spontaneous spasm events was 1 (range, 0-12). Both the postdissection threshold (area under the curve [AUC], 0.69; 95% CI, 0.62-0.77) and the number of mechanical events (AUC, 0.58; 95% CI, 0.50-0.66) were associated with early postoperative facial nerve outcome. The number of spasm events was not associated with facial nerve outcome. The optimal cutoff value for the threshold was 0.25 mA, and the optimal cutoff for number of mechanical events was 8. If a threshold of greater than 0.25 mA was paired with more than 8 mechanical events, there was a 77% chance of postoperative nerve weakness. Conversely, if a threshold was 0.25 mA or less and there were 8 mechanical events or less, there was 69% chance of normal postoperative nerve function. No parameters were associated with permanent facial nerve injury. Conclusions and Relevance: Postdissection threshold and the number of mechanical events are associated with immediate postoperative facial nerve function. Accurate prediction of facial nerve function may provide anticipatory guidance to patients and may provide surgeons with intraoperative feedback allowing adjustment in operative techniques and perioperative management.

The transglabellar/subcranial approach for surgical excision of periocular second tumors in retinoblastoma.

PURPOSE: To evaluate the use of transglabellar/subcranial approach for surgical resection of periocular second non-ocular tumors in retinoblastoma patients. METHODS: Seven retinoblastoma patients with periocular second tumor involving anterior skull base underwent surgical resection by transglabellar/subcranial approach in a single center. The medical records of these patients were retrospectively evaluated. RESULTS: The most common presenting symptom in retinoblastoma patients with periocular second tumor was difficulty in maintaining the prosthesis in three patients (43%), followed by epistaxis in one (14%), palpable orbital mass in one (14%), persistent periocular swelling in one (14%), and visual loss in one (14%) patient. Periocular second tumors were leiomyosarcoma in three (43%) patients, osteosarcoma in three (43%), and sphenoid wing meningioma in one (14%) patient. Surgical resection by the transglabellar/subcranial approach was the only treatment in one (14%) patient with sphenoid wing meningioma and was combined with chemotherapy in three (43%) patients, and with both external beam radiotherapy and chemotherapy in three (43%) patients. Surgical margins were negative in three (43%) patients and microscopically positive in four (57%) patients. Complications were minor, including cerebral spinal fluid (CSF) leak in one (14%) patient and CSF leak and subgaleal hematoma in one (14%) patient. After 31 months mean follow-up, three (43%) patients were alive and four patients (57%) were dead. CONCLUSIONS: Retinoblastoma patients with periocular second tumors have a poor prognosis. The transglabellar/subcranial approach can be used for surgical resection of periocular second tumor involving skull base with low morbidity.

Surgical Treatment of Olfactory Neuroblastoma: Major Complication Rates, Progression Free and Overall Survival.

Objective We aimed to compare major complication rates in patients undergoing open versus endoscopic resection of olfactory neuroblastoma (ONB) and to determine the prognostic utility of the Kadish staging and Hyams grading systems with respect to progression-free survival (PFS) and overall survival (OS). Methods It is a retrospective review of experience in treating ONB at a single tertiary care hospital from 1987 through 2015. Major complications were defined as cerebrospinal fluid (CSF) leak, meningitis, osteomyelitis, tracheostomy, and severe neurologic injury. Results Forty-one patients were included. An open approach was used in 34 (83%), endoscopic in 6 (15%), and combined in 1 (2%) case. Rates of major complications by surgical approach were 17% after endoscopic versus 31% after open ( p = 0.65). There was no significant difference in PFS or OS based on Kadish B versus C (PFS, p = 0.28; OS, p = 0.11) or Hyams grade 1 and 2 versus Hyams grade 3 and 4 (PFS, p = 0.53; OS, p = 0.38). Conclusions There was no significant difference in major complications between open and endoscopic approaches for the treatment of ONB. Patient stratification using the Kadish staging and Hyams grading systems did not show significant differences in PFS or OS. Further research is needed to determine if a different staging system would better predict patient outcomes.

Myxomas and angiomyxomas of the orbit: a clinicopathologic study of 6 cases.

PURPOSE: To report clinical and histopathologic features and biologic behavior of orbital myxomas and angiomyxomas. DESIGN: Noncomparative retrospective case series. PARTICIPANTS: Patients with histopathologic diagnoses of orbital myxoma or angiomyxoma. METHODS: Clinical metadata and features were obtained from the medical record. Neoplasms were studied by routine histopathology, special stains, and immunohistochemistry. MAIN OUTCOME MEASURES: Final diagnosis, based on histopathology, special stains, and immunohistochemistry, and clinical course from analysis of metadata and clinical features. RESULTS: Three myxomas and 3 angiomyxomas were identified in 5 males and 1 female. Median age at presentation was 56 years (range, 4-69), with a follow-up ranging from 6 months to 8 years. Two angiomyxomas occurred in children ages 4 and 7 years whose tumors were locally aggressive and recurred. Recurrence also complicated one case of myxoma after incomplete excision. Pathologically, the tumors were poorly circumscribed. Histopathology showed them to be hypocellular, containing stellate and spindled cells in an abundant, loose, myxoid stroma rich in hyaluronic acid. Small blood vessels were rare in myxomas but abundant in angiomyxomas. Tumor cells were frequently immunoreactive for vimentin, CD34, and factor XIIIa. CONCLUSIONS: Myxomas rarely involve orbital tissue, and no angiomyxomas of the region have been previously reported. Angiomyxomas in children may be aggressive. Vascularity and bone involvement appear to be important prognostic features for recurrence. Complete resection with a margin of healthy tissue appears to be the treatment of choice. Tumor cell immunopositivity for vimentin, CD34, and factor XIIIa may assist in the histopathologic diagnosis.

Nasopharyngeal airway to prevent tension pneumocephalus after open resection of anterior skull base tumors.

We conducted a retrospective study to assess the efficacy of using a nasopharyngeal airway in lieu of a tracheotomy or prolonged intubation for the diversion of airflow to prevent tension pneumocephalus after an open resection of anterior skull base tumors. Our study population was made up of 120 patients-74 males and 46 females, aged 12 to 84 years (mean: 48.7)-who had undergone an anterior skull base resection with documented nasopharyngeal airway placement from 1996 through 2009. Our main outcome measure was the presence of tension pneumocephalus while controlling for the placement of a lumbar drain, the development of a cerebrospinal fluid (CSF) leak, and the type of reconstruction. All patients had been extubated on the day of surgery, and their nasopharyngeal airway had remained in place for 3 days. No documented complications of nasopharyngeal airway placement (e.g., nasal septum pressure necrosis or the displacement of tubes) had been documented. Tension pneumocephalus occurred in 3 patients (2.5%). A total of 33 patients (27.5%) received a lumbar drain, 14 (11.7%) experienced a CSF leak, and 5 (4.2%) had both. There was a statistically significant difference in the rate of tension pneumocephalus between patients who did and did not receive a lumbar drain placement (p = 0.02), between those who did and did not experience a CSF leak (p = 0.04), and between those who did and did not meet both criteria (p = 0.004). We conclude that resection of anterior skull base tumors does not necessitate a prophylactic tracheotomy or prolonged intubation and that the use of a nasopharyngeal airway to divert airflow is well tolerated and highly successful. Lumbar drainage, the development of a CSF leak, or both may increase the risk of tension pneumocephalus.

Osseocutaneous radial forearm free tissue transfer for repair of complex midfacial defects.

OBJECTIVE: To evaluate the resulting aesthetics, function, and donor site morbidity of the osseocutaneous radial forearm free flap (OCRFFF) used for midface reconstruction. DESIGN: Prospective case series and a retrospective review of results. PATIENTS: Ten patients from an academic practice who underwent reconstruction at the University of Michigan Hospitals between 1995 and 2001. INTERVENTIONS: All patients had maxillectomy defects in which the entire infraorbital rim was reconstructed with an OCRFFF. Of the 10 patients included in the study, 3 underwent a total maxillectomy with orbital exenteration, 4 had a total maxillectomy without orbital exenteration, and 3 had a limited maxillectomy that did not involve the palate. Patients with palatal defects underwent reconstruction with a prosthetic palatal obturator. MAIN OUTCOME MEASURES: Facial contour and aesthetic results, speech understandability, ability to eat solid foods, oronasal separation, socializing outside the home, and return-to-work status. Flap success, donor site morbidity, and orbital complications were also studied. RESULTS: Mean +/- SEM follow-up was 23.2 +/- 5.0 months. A modified Funk facial deformity scale was used, and 7 of the 10 patients had either no deformity or minimal deformity. The mean aesthetic score for these reconstructions was 2.1 +/- 0.3 on a scale of 1 to 4, with 1 representing no deformity and 4 representing a severe deformity. All patients returned to a solid diet and had understandable speech, although patients who had an orbital exenteration trended to poorer scores. All patients socialized either frequently or occasionally outside the home, and all patients not retired or disabled prior to surgery returned to work. CONCLUSION: The OCRFFF reconstruction of the infraorbital rim in patients with total maxillectomy defects and obturator of the palatal defect controls orbital complications and optimizes aesthetic outcome while achieving nearly normal palatal function.

Reconstruction after resection of sphenoid wing meningiomas.

OBJECTIVE: To review our experience of reconstructing the lateral and superior orbital walls after resection of sphenoid wing meningiomas. We will review the presentation and complications, examine the aesthetic results postoperatively, and compare preoperative and postoperative computed tomographic scans. To our knowledge, a comparative analysis of preoperative defect and postoperative reconstruction has not been performed. METHODS: We conducted a retrospective analysis, with a minimum of 5 months and a maximum of 9 years of follow-up in an academic multidisciplinary skull base center. Twenty-two patients were treated for sphenoid wing meningiomas by resection and reconstruction with split calvarial bone graft and, for more than half of the patients, also with free abdominal fat graft. The main outcome measures were aesthetic evaluation of patients and analysis of tumor control using computed tomographic scans, survival, and complications. RESULTS: A total of 24 resections were performed on 22 patients. The average follow-up was 14.6 months. All patients had meningiomas with similar preoperative presentations, and for 21 of the 22 patients aesthetic reconstruction resulted in the near symmetry of the 2 sides. All patients are currently alive, those who underwent complete resection are without recurrence, and 15 (68.2%) did not incur complications. One patient experienced a worsening of temporal wasting following radiation therapy. CONCLUSION: Reconstruction of the defect with split calvarial bone and free abdominal fat grafts affords the patient excellent aesthetic results as well as good symmetry, as demonstrated by a postoperative computed tomographic scan.

High-Frequency Targetable EGFR Mutations in Sinonasal Squamous Cell Carcinomas Arising from Inverted Sinonasal Papilloma.

Inverted sinonasal papilloma (ISP) is a locally aggressive neoplasm associated with sinonasal squamous cell carcinoma (SNSCC) in 10% to 25% of cases. To date, no recurrent mutations have been identified in ISP or SNSCC. Using targeted next-generation sequencing and Sanger sequencing, we identified activating EGFR mutations in 88% of ISP and 77% of ISP-associated SNSCC. Identical EGFR genotypes were found in matched pairs of ISP and associated SNSCC, providing the first genetic evidence of a biologic link between these tumors. EGFR mutations were not identified in exophytic or oncocytic papillomas or non-ISP-associated SNSCC, suggesting that the ISP/SNSCC spectrum is biologically distinct among sinonasal squamous tumors. Patients with ISP harboring EGFR mutations also exhibited an increased progression-free survival compared with those with wild-type EGFR. Finally, treatment of ISP-associated carcinoma cells with irreversible EGFR inhibitors resulted in inactivation of EGFR signaling and growth inhibition. These findings implicate a prominent role for activating EGFR mutations in the pathogenesis of ISP and associated SNSCC and rationalize consideration of irreversible EGFR inhibitors in the therapy of these tumors.

Restoration of the orbital aesthetic subunit in complex midface defects.

OBJECTIVES/HYPOTHESIS: Although various options exist for restoration of the orbital defect in complex craniofacial resections, the aesthetic appearance and functional result of the orbit are optimized when the bony orbital architecture, orbital volume, and facial contour are specifically addressed. The study describes an approach using free tissue transfer for restoration of the native orbital aesthetic subunit. STUDY DESIGN: Retrospective case series. METHODS: Nineteen patients (male-to-female ratio, 14:5; mean age, 52 y [age range, 8-79 y]) in the study period between 1997 and 2001 had orbital defects that could be classified into one of the following categories: 1) orbital exenteration cavities only, 2) orbital exenteration cavities with resection of less than 30% of the bony orbital rim, or 3) radical orbital exenteration cavities with resection of overlying skin and bony malar eminence. Group 1 had reconstructions with fasciocutaneous forearm flaps; group 2, with osseocutaneous forearm flaps; and group 3, with osseocutaneous scapula flaps. RESULTS: Eighteen of 19 patients achieved a closed orbital reconstruction with restoration of the orbital aesthetic subunit. Among 16 patients with more than 4 months of follow-up, 10 patients had minimal or no resulting facial contour deformity and 8 patients engaged in social activities outside the home on a frequent basis. Five of the nine patients who were working before their surgery were able to return to work. CONCLUSION: Patients with complex midface defects involving the orbit can undergo free tissue transfer and have successful restoration of the native orbital aesthetic subunit without an orbital prosthesis.

Urokinase-type plasminogen activator receptor expression in adenoid cystic carcinoma of the skull base.

BACKGROUND: Head and neck adenoid cystic carcinoma (ACC) is a malignancy of the salivary and lacrimal glands with a variable growth pattern and propensity for perineural spread. Involvement of the skull base indicates a poor prognosis. Despite surgical resection and adjuvant radiotherapy, tumor recurrence and metastases are common. The urokinase-type plasminogen activator and its receptor (uPAR) have an important role in tumor invasion and metastasis. The expression of uPAR is predictive of poor outcomes in many tumors. This study examines the expression of human uPAR in ACCs involving the skull base. OBJECTIVES: To determine uPAR expression in ACCs of the skull base by immunohistochemical analysis and compare expression with tumor histologic findings and clinical outcomes. STUDY DESIGN: Analysis of uPAR in archival ACC specimens and a retrospective medical chart review. SETTING: Multidisciplinary cranial base program at a university medical center with tertiary referral pattern. RESULTS: Ten (83%) of 12 tumors stained positive for uPAR. Three of 3 patients who died of ACC and 6 of 6 patients alive with disease expressed uPAR. Only 1 of 3 patients free of disease was uPAR positive. CONCLUSIONS: In most patients with ACC of the skull base, uPAR was expressed. Its expression seems to be a negative prognostic factor. However, the small study sample limits our observations. Additional study of uPAR expression in ACC at other anatomic sites is required.

Radial forearm free tissue transfer reduces complications in salvage skull base surgery.

OBJECTIVE: Patients who undergo skull base resection after prior surgery or radiation may be at high risk for complications when local flaps alone are used for reconstruction. To determine whether the complication rate could be reduced, fasciocutaneous free tissue transfer was used to reinforce the dural closure in patients who had prior skull base surgery or radiation. METHODS: This study is a case series of 20 patients (14 males, 6 females, aged 8-79 years of age with a mean of 47.7 years) from 1997 to 2001 who had prior skull base surgery or radiation, and underwent salvage skull base resection without large volume defects. All patients had a radial forearm free tissue transfer to reinforce the dural closure. Six patients had an osseous component to the forearm flap to provide vascularized bone to the orbital rim. RESULTS: The overall local complication rate was 35%. Three patients (15%) had major complications including 1 case of meningitis, 1 case of cerebrospinal fluid leak, and 1 case of a flap requiring venous salvage. There were no flap failures, 1 idiopathic median nerve palsy, and no pathologic radius bone fractures. CONCLUSION: Reconstruction with fasciocutaneous free tissue transfer for high-risk patients with low-volume dural defects following skull base resection can minimize the risk of major postoperative complications. EBM RATING: C.