Hereditary paraganglioma (PGL) is characterized by the development of benign, vascularized tumors in the head and neck. The most common tumor site is the carotid body (CB), a chemoreceptive organ that senses oxygen levels in the blood. Analysis of families carrying the PGL1 gene, described here, revealed germ line mutations in the SDHD gene on chromosome 11q23. SDHD encodes a mitochondrial respiratory chain protein-the small subunit of cytochrome b in succinate-ubiquinone oxidoreductase (cybS). In contrast to expectations based on the inheritance pattern of PGL, the SDHD gene showed no evidence of imprinting. These findings indicate that mitochondria play an important role in the pathogenesis of certain tumors and that cybS plays a role in normal CB physiology.

Tumors originating in the parapharyngeal space are rare. During the period of January 1977 to July 1989, 51 patients underwent surgery for parapharyngeal space tumors at the University of Pittsburgh's Eye and Ear Hospital. Eighty percent of the parapharyngeal space neoplasms were benign; 20% were malignant. Fifty-seven percent (31/54) were of neurogenic origin, 30% (16/54) were of salivary origin, and 13% (7/54) were of miscellaneous origin. The use of computed tomography scan and magnetic resonance imaging, and selective use of angiography, allowed us to ascertain the location, size, vascularity, and relation of parapharyngeal space tumors to surrounding anatomical structures. Imaging techniques established the site of origin of these tumors with 96% accuracy. This information was essential in planning surgical approaches and predicting prognoses. Details of the surgery, morbidity, and outcome of these patients are presented.

Perineural invasion of small nerves is associated with an increased risk of local recurrence and cervical metastasis and is, independent of extracapsular spread, a predictor of survival for patients with SCC of the upper aerodigestive tract.

We have built a digital nuclear atlas of the newly hatched, first larval stage (L1) of the wild type hermaphrodite of C. elegans at single cell resolution from confocal image stacks of 15 individuals. The atlas quantifies the stereotypy of the locations and provides for other statistics on the spatial patterns of the 357 nuclei that could be faithfully segmented and annotated of the 558 present at this developmental stage. Given this atlas we then developed an automated approach to assign cell names to each nucleus in a 3D image of an L1 worm. We achieve 86% accuracy in identifying the 357 nuclei automatically. This computational method is essential for high-throughput single cell analyses of the worm at post-embryonic stages, such as determining the expression of every gene in every cell during development from the L1 onward, or ablating or stimulating cells under computer control in a high-throughput functional screen.

This paper updates a 1981 report on the management of inverted papilloma. In that report, routine lateral rhinotomy with en bloc resection of the lateral nasal wall, including the entire schneiderian membrane, was recommended. This report emphasizes the use of computed tomography scanning in management planning. Of 33 patients with inverted papilloma treated between 1969 and 1987, 7 had associated squamous cell carcinoma. Twenty-two patients with IP alone were treated with medial maxillectomy; however, 3 patients have been successfully treated with either a Caldwell-Luc/ethmoidectomy or an external ethmoidectomy for localized disease. The use of computed tomography capable of higher resolution allowed preoperative determination of the extent of disease, enabling the surgeon to plan the surgery more precisely. Patients were followed for an average of 9.6 years. Recurrent disease occurred in one patient (4%) following a lateral rhinotomy/medial maxillectomy approach. The principles set forth in this series of patients remain the same as those previously described due to the unique characteristics of this tumor: its ability to destroy bone, its tendency to recur, and its association with malignancy. The technique of lateral rhinotomy and en bloc excision of the lateral nasal wall, followed by meticulous removal of all mucosa in the ipsilateral paranasal sinuses, remains the standard therapy.

Background: Paragangliomas are rare and highly heritable tumours of neuroectodermal origin that often develop in the head and neck region. Germline mutations in the mitochondrial complex II genes, SDHB, SDHC, and SDHD, cause hereditary paraganglioma (PGL). Methods: We assessed the frequency of SDHB, SDHC, and SDHD gene mutations by PCR amplification and sequencing in a set of head and neck paraganglioma patients who were previously managed in two otolaryngology clinics in the USA. Results: Fifty-five subjects were grouped into 10 families and 37 non-familial cases. Five of the nonfamilial cases had multiple tumours. Germline SDHD mutations were identified in five of 10 (50%) familial and two of 37 (∼5%) non-familial cases. R38X, P81L, H102L, Q109X, and L128fsX134 mutations were identified in the familial cases and P81L was identified in the non-familial cases. Both nonfamilial cases had multiple tumours. P81L and R38X mutations have previously been reported in other PGL families and P81L was suggested as a founder mutation. Allelic analyses of different chromosomes carrying these mutations did not show common disease haplotypes, strongly suggesting that R38X and P81L are potentially recurrent mutations. Germline SDHB mutations were identified in two of 10 (20%) familial and one of 33 (∼3%) non-familial cases. P131R and M71fsX80 were identified in the familial cases and Q59X was identified in the one non-familial case. The non-familial case had a solitary tumour. No mutations could be identified in the SDHC gene in the remaining four families and 20 sporadic cases. Conclusions: Mutations in SDHD are the leading cause of head and neck paragangliomas in this clinic patient series. SDHD and SDHB mutations account for 70% of familial cases and ∼8% of non-familial cases. These results also suggest that the commonness of the SDHD P81L mutation in North America is the result of both a founder effect and recurrent mutations.

BACKGROUND: Extracapsular spread (ECS) in cervical lymph node metastases from head and neck squamous cell carcinoma (SCC) is regarded as an adverse prognostic factor and is often used to select patients who may benefit from adjuvant therapy. The prognostic value of ECS was evaluated for patients with oropharyngeal SCC (OPC; with known p16/human papillomavirus [HPV] status) and for patients with SCC of the oral cavity (OCC). METHODS: Disease-specific survival (DSS) was assessed among SCC patients with cervical lymph node metastases (n 5 347, including 133 patients with OPC and 214 patients with OCC). All patients were treated surgically between 1983 and 2009. ECS status was determined by pathologists at the time of initial pathologic evaluation and confirmed for this study. HPV status of patients with OPC was determined via immunohistochemistry for p16 and in situ hybridization. RESULTS: Among OCC patients, ECS was a significant, independent factor influencing DSS. For OCC patients with ECS, 3-year DSS was 45% (95% confidence interval [CI], 36%-56%); for those without ECS, 3-year DSS was 71% (95% CI, 62%-81%; P 5.0018). The effect of ECS was independent of the number of positive lymph nodes as well as other clinical, pathologic, and treatment variables. Of the 133 OPC patients, 76 (57%) were p16-positive and 57 (43%) were p16-negative. ECS status did not correlate with DSS among p16-positive or p16-negative OPC patients. CONCLUSION: ECS was not associated with worse DSS in p16-positive or p16-negative OPC patients.

BACKGROUND Histopathologic grade of mucoepidermoid carcinoma (MEC) is an established predictor of prognosis and affects treatment protocol. Tumor behavior is more aggressive in high-grade than in low-grade MEC, leading to a more intensive treatment protocol. Outcomes for patients with intermediate-grade MEC are less clear; therefore, the optimal treatment protocol for this group is not well defined. The treatment protocol and survival outcomes of patients treated for MEC of the head and neck was investigated. METHODS A retrospective clinical review and prospective review of histopathologic grading were undertaken using the most recently established grading system of 50 patients with MEC of the head and neck from 1983 through 2004. RESULTS As histologic grade increased from low to intermediate to high, overall survival (P <.0001) and disease-free survival (P <.001) were significantly decreased. Overall and disease-free survival were significantly better for patients with intermediate-grade MEC than those with high-grade disease. Overall and disease-free survival were similar for patients with low-grade and intermediate-grade MEC. There was a low rate of disease recurrence in patients with intermediate-grade MEC, but this did not lead to death from disease. Although no patients with low-grade or intermediate-grade MEC died of disease, 52% of patients with high-grade MEC died of disease. Multivariate analysis revealed that histologic grade, age, and surgical margin status significantly predicted prognosis. CONCLUSIONS These findings suggest that, under the current histopathologic classification system, the behavior of intermediate-grade MEC is comparable to that of low-grade MEC and different from high-grade MEC, allowing for the establishment of an evidence-based treatment protocol.