VHL c.505 T>C mutation confers a high age related penetrance but no increased overall mortality.

BACKGROUND: Germline mutations of the VHL gene cause von Hippel-Lindau syndrome (VHL). In southern Germany, a specific mutation in this gene, c.505 T>C, is one of the most frequent alterations owing to a founder effect. METHODS: This study was conducted to evaluate morbidity, specific clinical risk profile, and mortality among a series of VHL c.505 T/C mutation carriers. A total of 125 eligible subjects carrying VHL c.505 T/C underwent ophthalmoscopy and gadolinium enhanced magnetic resonance imaging of the brain, the spinal cord, and the abdomen. Age related penetrance, morbidity, and mortality were assessed. RESULTS: Frequently observed lesions were phaeochromocytoma (47%), retinal angiomas (36%), haemangioblastoma of the spine (36%), and haemangioblastoma of the brain (16%). Four patients developed renal cell carcinoma. VHL was symptomatic in 47% of subjects; 30% were asymptomatic despite the presence of at least one VHL related tumour and 23% of the carriers had no detectable VHL lesion. Of the 19 patients who had died (15%), 10 died of symptomatic VHL lesions. Overall penetrance by cumulative incidence functions is estimated at 48% by 35 years and 88% by 70 years. In contrast to the only existing published report based on patients with presumably unselected VHL germline mutations, the mortality rate for c.505 T/C mutation carriers is comparable to that of the general population of Germany. CONCLUSIONS: Our results are an important example that a specific genotype, at least in the case of VHL c.505 T/C, can favourably impact on mortality despite a high age related penetrance. Our study also indirectly provides objective data which might be useful to the life and health insurance industry; it would appear that c.505 T>C mutation positive subjects have similar disease specific mortality to that of the general population owing to a combination of phenotype and timely detection of mutation carrier status followed by aggressive clinical screening and, if necessary, treatment.

[Diagnosis of questionable mandibular infiltration by squamous epithelial carcinomas. 3-D 99mTc-DPD SPECT reconstruction and (18F) fluoride PET study: diagnostic advantages or unnecessary expense?]. / Diagnostik fraglicher Unterkieferinfiltrationen durch Plattenepithelkarzinome. 3-D-99mTc-DPD-SPECT-Rekonstruktion und [18F]-Fluorid-PET-Untersuchung: diagnostischer Vorteil oder übertriebener Aufwand?

OBJECTIVE: A prospective study was designed to compare computer-aided 3D 99mTc-DPD SPECT reconstruction, conventional 99mTc-DPD SPECT investigation (n = 88) and flurine-18 PET (n = 10) in the assessment of mandibular bone invasion by SCC. PATIENTS/METHODS: Between 10/97 and 03/00 88 patients with SCC of the mandibular region were enrolled in this study. In 50 cases mandibular resection (segmental or marginal) was performed basing on the pretherapeutic diagnostic results. RESULTS: No differences could be found between 3D 99mTc-DPD SPECT reconstruction and conventional 99mTc-DPD SPECT investigation. Both techniques revealed the same high sensitivity (100%) and the same specificity of 91.6 (efficiency 95.4%). Flurine-18 PET showed a sensitivity of 100%, but specificity only reached 50% (efficiency 60.0%). CONCLUSIONS: This investigation does not provide evidence that the financial and time consuming techniques of computer-aided 3D 99mTc-DPD SPECT reconstruction and flurine-18 PET show advantages compared to conventional 99mTc-DPD SPECT investigation in the assessment of mandibular invasion by SCC.

Computer-aided 3-D 99mTc-DPD-SPECT reconstruction to assess mandibular invasion by intraoral squamous cell carcinoma: diagnostic improvement or not?

OBJECTIVE: A prospective study was designed to compare computer-aided 3-D 99mTc-DPD-SPECT (Technetium-Dicarboxy propan-single photon emission CT) reconstruction with clinical examination, panoramic radiography, CT scan and conventional 99mTc-DPD-SPECT investigation in the assessment of mandibular bone invasion by squamous cell carcinoma. PATIENTS AND METHODS: Between October 1997 and December 1999, 88 patients with intraoral squamous cell carcinoma of the regions adjacent to the mandible were enrolled in this study. In 50 cases, mandibular resection (segmental or marginal) was performed based on the pre-treatment diagnostic results. Imaging studies were read independently by four experienced observers. RESULTS: No differences could be found between presurgical 3-D 99mTc-DPD-SPECT reconstruction and conventional 99mTc-DPD-SPECT investigation. Both techniques revealed a sensitivity of 100% whereas CT scan showed the greatest specificity (93.8%). SPECT investigation had a specificity of 91.6% and the greatest efficiency (95.4%). The greatest predictive positive value was found for CT scan (92.3%). Clinical examination and panoramic radiography displayed the lowest sensitivity, 82.5% vs. 85.0%, and specificity, 79.2% vs. 89.5% respectively. CONCLUSION: This investigation does not provide evidence that 3-D 99mTc-DPD-SPECT reconstruction has any advantages when compared to conventional 99mTc-DPD-ECT investigation in the assessment of mandibular invasion by squamous cell carcinoma. Despite a sensitivity of 100% the specificity is still in need of improvement. Until newer methods or techniques become available the combination of CT scanning and conventional 99mTc-DPD-SPECT investigation appears to be the best means of detecting tumour invasion preoperatively and is thus helpful in directing appropriate surgical procedure.

Functioning thoracic paraganglioma: association with Von Hippel-Lindau syndrome.

Functioning thoracic paraganglioma (pheochromocytoma) is unusual and therefore suggestive of a pathogenesis distinct from that of sporadic adrenal pheochromocytoma. To determine whether the pheochromocytoma-associated syndromes Von Hippel-Lindau disease (VHL) and multiple endocrine neoplasia type 2 (MEN 2) play a role in the development of thoracic functioning paragangliomas, germline DNA from five unselected patients with this rare tumor was analyzed for mutations in the genes that predispose to VHL and MEN 2. Genetic investigations and further clinical data revealed that three had VHL, with two different germline mutations of the vhl gene, but no individual was affected by MEN 2. Two of the three patients with VHL did not show any additional VHL-associated lesions. This result suggests that VHL should be considered in the differential diagnosis of thoracic pheochromocytoma, as such a diagnosis carries further important implications for the patient and family. Conversely, in patients suspected of a catecholamine-secreting tumor and known VHL, thoracic localization should be considered if an adrenal pheochromocytoma cannot be detected.