Citations

Objectives/HypothesisTo evaluate outcomes of salvage surgery for vestibular schwannoma (VS) that failed primary stereotactic radiosurgery (SRS).MethodsCase‐control study of 37 patients who underwent surgical resection of sporadic VS following prior SRS at two tertiary academic referral centers between 2003 and 2015. A cohort of nonirradiated control subjects, matched according to tumor size, age, and treatment center, were used as comparison.ResultsThirty‐seven patients were included. The median time from radiation to surgical salvage was 36 months (range 9.6–153 months). Following tumor progression after SRS, 18 (49%) patients underwent gross total resection, 10 (27%) underwent near‐total resection, and nine (24%) underwent subtotal resection. Postoperative complications following salvage surgery included one (3%) case of stroke, four (11%) cases of cerebrospinal fluid leak, and two (5%) cases of meningitis. Twenty‐seven (73%) patients had good postoperative facial nerve outcome (House‐Brackmann Score I–II) at long‐term follow‐up. There were no cases of tumor recurrence or regrowth after a median length of 26 months following microsurgical salvage (range 3–114 months). The rate of satisfactory postoperative facial nerve function was not different between study and control subjects (73% vs. 76%; P = 0.8); however, less‐than‐complete resection was utilized more frequently among previously radiated patients (P = 0.01).ConclusionMicrosurgical salvage of VS following primary radiation therapy is challenging. Less‐than‐complete resection is required in a greater percentage of patients to preserve facial nerve integrity and prevent neurological complications. Long‐term follow‐up is needed to determine the risk of delayed progression following incomplete tumor removal.Level of Evidence3b. Laryngoscope, 126:2580–2586, 2016

Abstract Identifying genetic variants with pleiotropic associations can uncover common pathways influencing multiple cancers. We took a two-stage approach to conduct genome-wide association studies for lung, ovary, breast, prostate, and colorectal cancer from the GAME-ON/GECCO Network (61,851 cases, 61,820 controls) to identify pleiotropic loci. Findings were replicated in independent association studies (55,789 cases, 330,490 controls). We identified a novel pleiotropic association at 1q22 involving breast and lung squamous cell carcinoma, with eQTL analysis showing an association with ADAM15/THBS3 gene expression in lung. We also identified a known breast cancer locus CASP8/ALS2CR12 associated with prostate cancer, a known cancer locus at CDKN2B-AS1 with different variants associated with lung adenocarcinoma and prostate cancer, and confirmed the associations of a breast BRCA2 locus with lung and serous ovarian cancer. This is the largest study to date examining pleiotropy across multiple cancer-associated loci, identifying common mechanisms of cancer development and progression. Cancer Res; 76(17); 5103–14. ©2016 AACR.

Abstract BACKGROUND: Studies examining patient-reported outcomes in subjects with vestibular schwannoma (VS) and “excellent” hearing are lacking. OBJECTIVE: To assess patient-reported audiovestibular handicap and overall quality of life (QoL) in VS patients with class A hearing in both ears. METHODS: Among 539 VS patients treated during 1998 to 2008, we identified 296 patients with either bilateral class A (AA) hearing or 1 good ear and 1 deaf ear (AD) according to the American Academy of Otolaryngology–Head and Neck Surgery classification. Patients responded to validated hearing, tinnitus, and dizziness handicap inventories and 2 QoL questionnaires, and the 2 groups were compared. A reference group of 103 adults filled out the same questionnaires. RESULTS: Forty-nine patients (16.6%) had class AA and 247 patients (83.4%) had class AD hearing. AA patients scored poorer than control subjects without tumor on all handicap questionnaires ( P < .001) and a VS-specific QoL instrument ( P = .006). Con-versely, AA patients scored significantly better than patients with AD on the hearing inventory and the disease-specific QoL instrument ( P < .001), but no difference was found between these groups with regard to tinnitus and dizziness. The hearing disability score was approximately 3 times poorer for AA patients compared with control subjects without tumor; a third of AA patients reported a hearing handicap. CONCLUSION: Patients with VS and bilateral class A hearing report significantly poorer hearing handicap than control subjects without tumor but better hearing than those with unilateral deafness. When patients with bilateral class A hearing are counseled, it should be noted that one-third of patients experience self-perceived hearing handicap.

Pseudomyogenic hemangioendothelioma (PMH) is a well-recognized neoplasm that usually arises in the soft tissue; concurrent bone involvement occurs in 24% of cases. PMH of bone without soft tissue involvement is rare. We describe the clinicopathologic findings of 10 such cases, the largest series reported to date. The study included 9 male and 1 female patient; their ages ranged from 12 to 74 years (mean 36.7 y). All patients had multiple tumors with a distinct regional distribution: 45% restricted to the lower extremity; 25% to the spine and pelvis; and 15% to the upper extremity. On imaging studies the tumors were well circumscribed and lytic. The neoplasms were composed of spindled cells arranged in intersecting fascicles with scattered epithelioid cells; epithelioid cells predominated in 3 cases. The neoplastic cells contained abundant densely eosinophilic cytoplasm and vesicular nuclei. There was limited cytologic atypia and necrosis, few mitoses (0 to 2/10 high-power fields), and inconspicuous stroma. Unique findings included abundant intratumoral reactive woven bone and hemorrhage with numerous osteoclast-like giant cells. Immunohistochemically, most tumors were positive for keratin, ERG, and CD31; CD34 was negative. The balanced t(7:19)(q22;13) translocation was documented in 3 cases. Follow-up is limited, but no patient developed documented visceral dissemination, and all have stable or progressive osseous disease. PMH exclusively involving bone is rare. It is multicentric, often involves the lower extremity, and has unusual morphology. The differential diagnosis includes epithelioid vascular neoplasms, giant cell tumor, bone forming neoplasms, and metastatic carcinoma. Because of its rarity, unusual presentation, and morphology, accurate diagnosis can be challenging.

Nasal secretory activity was measured in seven dogs in response to topical stimulation by histamine and methacholine. The methacholine response was blocked by atropine but not by chlorpheniramine. The histamine response was blocked by chlorpheniramine but not by atropine. These results suggest that there are two independent mechanisms of nasal secretion in the dog.

Giant cell granuloma is a benign lesion that generally involves the mandible and maxilla. It may be locally aggressive and result in extensive tissue destruction in advanced cases. A retrospective analysis of giant cell granuloma during the Interval 1970 to 1990 revealed 18 cases of advanced disease, as defined by bone destruction and a greatest dimension of 2.0 cm or more. Epidemiologic factors, physical findings, Imaging studies, pathologic specimens, treatment modalities, and outcome were reviewed for each case. Eight lesions were treated by local excision and curettage, and 10 were treated by partial mandibulectomy. Five mandibular defects were reconstructed with lilac bone grafts and one with a free flap. Only one patient with maxillary giant cell granuloma who underwent curettage had regrowth of what is suspected to have been residual disease. Individualized treatment, tailoring the extent of resection to the extent of disease, provided excellent results.

BackgroundRecently, a novel mutation in exon 24 of DNAJC13 gene (p.Asn855Ser, rs387907571) has been reported to cause autosomal dominant Parkinson's disease (PD) in a multi‐incident Mennonite family.MethodsIn the present study the mutation containing exon of the DNAJC13 gene has been sequenced in a Caucasian series consisting of 1938 patients with clinical PD and 838 with pathologically diagnosed Lewy body disease (LBD).ResultsOur sequence analysis did not identify any coding variants in exon 24 of DNAJC13. Two previously described variants in intron 23 (rs200204728 and rs2369796) were observed.ConclusionOur results indicate that the region surrounding the DNAJC13 p.Asn855Ser substitution is highly conserved and mutations in this exon are not a common cause of PD or LBD among Caucasian populations.