Adult-Type Rhabdomyoma of the Larynx in Birt-Hogg-Dubé Syndrome: Evidence for a Real Association.

The autosomal dominant Birt-Hogg-Dubé syndrome is known to be associated with skin, lung and kidney lesions. It is caused by heterozygous germline mutations in the folliculin gene and has a high penetrance. We report the case of a 51 year old woman with Birt-Hogg-Dubé syndrome who presented with a laryngeal mass. Imaging confirmed a mass centered on the piriform sinus and following excision histological examination confirmed the lesion was composed of polygonal cells with abundant eosinophilic cytoplasm consistent with a rhabdomyoma. Laryngeal rhabdomyoma is rare condition and has not been previously described in association with Birt-Hogg-Dubé. In patients with Birt-Hogg-Dubé syndrome who develop upper aerodigestive tract symptoms secondary to mass lesion an adult-type rhabdomyoma might be considered as a differential, with endoscopic excision being the treatment of choice.

Use of a Rho kinase inhibitor to increase human tonsil keratinocyte longevity for three-dimensional, tissue engineered tonsil epithelium equivalents.

The generation of tissue-engineered epithelial models is often hampered by the limited proliferative capacity of primary epithelial cells. This study aimed to isolate normal tonsillar keratinocytes (NTK) from human tonsils, increase the lifespan of these cells using the Rho kinase inhibitor Y-27632 and to develop tissue-engineered equivalents of healthy and infected tonsil epithelium. The proliferation rate of isolated NTK and expression of c-MYC and p16INK4A were measured in the absence or presence of the inhibitor. Y-27632-treated NTK were used to generate tissue-engineered tonsil epithelium equivalents using de-epidermised dermis that were then incubated with Streptococcus pyogenes to model bacterial tonsillitis, and the expression of pro-inflammatory cytokines was measured by cytokine array and ELISA. NTK cultured in the absence of Y-27632 rapidly senesced whereas cells cultured in the presence of this inhibitor proliferated for over 30 population doublings without changing their phenotype. Y-27632-treated NTK produced a multi-layered differentiated epithelium that histologically resembled normal tonsillar surface epithelium and responded to S. pyogenes infection by increased expression of pro-inflammatory cytokines including CXCL5 and IL-6. NTK can be isolated and successfully cultured in vitro with Y-27632 leading to a markedly prolonged lifespan without any deleterious consequences to cell morphology. This functional tissue-engineered equivalent of tonsil epithelium will provide a valuable tool for studying tonsil biology and host-pathogen interactions in a more physiologically relevant manner.

Skull base infection presenting with multiple lower cranial nerve palsies.

Diseases of the temporal bone causing lower cranial nerve palsies are uncommon. In the presence of bony erosion, they are highly suggestive of a malignant process. However, when there is a clear history of otitis externa in an immunocompromised or diabetic patient, a diagnosis of osteomyelitis and secondary inflammatory mass should be considered. We report 4 separate cases of infective skull base lesions causing multiple lower cranial nerve palsies in elderly patients who were not immunocompromised or diabetic, highlighting that this condition is not exclusive to this population.

Vascular endothelial growth factor (VEGF), VEGF receptors expression and microvascular density in benign and malignant thyroid diseases.

Angiogenesis is critical for the growth and metastatic spread of tumours. Vascular endothelial growth factor (VEGF) is the most potent inducer of neovasculature, and its increased expression has been related to a worse clinical outcome in many diseases. The purpose of this study was to evaluate the relation between VEGF, its receptors (VEGFR-1 and VEGFR-2) and microvessel density (MVD) in thyroid diseases. Immunostaining for VEGF and VEGF receptors was performed in 66 specimens of thyroid tissue, comprising 17 multinodular goitre (MNG), 14 Graves' disease, 10 follicular adenoma, 8 Hashimoto's thyroiditis, 7 papillary carcinoma and 10 normal thyroid specimens. Thyrocyte positivity for VEGF and VEGF receptors was scored 0-3. Immunohistochemistry for CD31, and CD34 on the same sections was performed to evaluate MVD. Immunohistochemical staining of VEGF in thyrocytes was positive in 92% of all the thyroid tissues studied. Using an immunostaining intensity cut off of 2, increased thyrocyte staining was seen in follicular adenoma specimens, MNG and normal thyroids compared with Hashimoto's thyroiditis and Graves' disease (P < 0.05). Similarly, VEGF thyrocyte expression in Graves' disease was less than other pathologies (P < 0.05). VEGFR-1 expression and the average MVD score did not differ between the different thyroid pathologies. VEGF expression was lower in autoimmune pathologies compared to autonomous growth processes. Conversely, both VEGFR-1 and VEGFR-2 were widely expressed in benign and neoplastic thyroid disease, suggesting that the up-regulation of VEGF and not its receptors occurs as tissue becomes autonomous. There was no clear relationship between MVD measurement and thyroid pathology.