Paragangliomas and paraganglioma syndromes.

Paragangliomas are rare tumors of neural crest origin. They are benign in the majority of cases and are characterized by a strong vascularisation.In the head and neck region they most commonly occur as carotid body tumors. Jugulotympanic and especially vagal paragangliomas are seen less frequently. Complete surgical resection represents the only curative treatment option even though resection of locally advanced tumors regularly results in lesions of the lower cranial nerves and major vessels. Appoximately 30% of all head and neck paragangliomas (HNPs) are hereditary and associated with different tumor syndromes. The paraganglioma syndromes 1, 3 and 4 (PGL 1, 3 and 4) make up the majority of those familial cases. PGL 1 is associated with mutations of the succinate dehydrogenase subunit D (SDHD) gene, PGL 3 is caused by SDHC and PGL 4 by SDHB gene mutations. Multiple HNPs and the occurance of HNPs together with pheochromocytomas are seen in SDHD as well as SDHB mutation carriers. In patients with SDHB mutations the risk for the development of malignant paraganglial tumors is significantly higher compared to SDHC and SDHD patients as well as patients with sporadic tumors. SDHC mutation carriers almost exclusively present with benign HNP that are unifocal in the majority of cases. The role of transmission is autosomal dominant for all three symptoms. Interestingly, there is a "parent-of-origin-dependent-inheritance" in subjects with SDHD gene mutations. This means that the disease phenotype may only become present if the mutation is inherited through the paternal line. We recommend screening for mutations of the genes SDHB, SDHC and SDHD in patients with HNPs. Certain clinical parameters can help to set up the order in which the three genes should be tested.

Clinical features of paraganglioma syndromes.

Head and neck paragangliomas (HNPs) and pheochromocytomas are rare tumors. Sporadic and hereditary forms are recognized. Four different paraganglioma syndromes (PGLs 1-4) have been described: PGL 1 is associated with mutations of the succinate dehydrogenase (SDH) subunit D (SDHD) gene; PGL 3 is caused by SDHC gene mutations; PGL 4 is caused by SDHB gene mutations; the susceptibility gene for PGL 2 is unknown. The objective of this study is to review distinct clinical features of the different PGLs. An international registry for HNPs was founded in Freiburg, Germany, in 2000. The data presented in this article have been acquired from registered HNP patients who have been screened for mutations of the genes SDHB, SDHC, and SDHD. Approximately 30% of apparent sporadic HNPs are caused by a germline mutation in one of these genes. Patients with PGL 1 or 4 have a very high lifetime risk of developing HNPs as well as thoracic and abdominal pheochromocytomas. Compared with sporadic HNPs, tumors developing in SDHB, SDHC, and SDHD mutation carriers arise at a significantly younger age. The SDHB mutations are associated with a high percentage of malignant paraganglionic tumors. We recommend molecular genetic screening of all HNP patients for SDHB, SDHC, and SDHD gene mutations. Mutation carriers must be screened for paraganglial tumors in the head, neck, thorax, and abdomen. Appropriately timed surgical intervention will minimize disease-specific morbidity and mortality. Lifelong follow-up is mandatory.

Juxtacondylar approach in temporal paraganglioma surgery: when and why?

As it became clear that patients with paraganglioma (PGL) syndromes had a higher risk of multifocal tumors, we changed our surgical strategy to avoid the possibility of bilateral cranial nerve paralysis. The juxtacondylar approach offers advantages for some jugular foramen tumors, including types C and D temporal PGLs. This approach allows exposure of the jugular foramen without skeletonizing or transposing the facial nerve. It improves the surgeon's ability to distinguish between the pars vascularis and the pars nervosa at the jugular foramen, and it helps to save functioning of the lower cranial nerves. There is already considerable experience using the juxtacondylar approach for patients suffering from schwannomas and meningiomas involving the jugular foramen. Some limitations have been noted for using the juxtacondylar approach with jugular PGLs that are related to their vascular nature. In this article we demonstrate its use for the management of eight patients with locally advanced temporal PGLs and how it can be combined with an infratemporal fossa approach.

Malignant head and neck paragangliomas in SDHB mutation carriers.

OBJECTIVE: Three of four paraganglioma syndromes (PGLs) have been characterized on a molecular genetic basis. PGL 1 is associated with mutations of the succinate dehydrogenase subunit D (SDHD) gene, PGL 3 is caused by SDHC gene mutations, and PGL 4 is caused by SDHB gene mutations. The objective of this study was to investigate whether PGLs are associated with malignant head and neck paragangliomas (HNPs). STUDY DESIGN AND SETTING: Through November 2005, we screened 195 HNP patients for mutations of the genes SDHB, SDHC, and SDHD. RESULTS: We detected 5 SDHC, 13 SDHB, and 45 SDHD gene mutations. In seven SDHB mutation carriers, there were distant metastases. No signs of metastases were found in SDHC and SDHD patients. One patient with a sporadic HNP presented with locally metastatic disease. CONCLUSIONS: SDHB mutations are associated with a high rate of malignant HNPs. SIGNIFICANCE: In SDHB patients, a three-body region imaging and scintigraphy or DOPA-PET must be performed to exclude metastases.

Ultrasound-guided core-needle biopsy in the diagnosis of head and neck masses: indications, technique, and results.

BACKGROUND: Unclear cervicofacial masses are common presentations that often require tissue sampling to guide therapy. While open biopsy is invasive, fine-needle aspiration cytology includes a high rate of nondiagnostic samples. METHODS: A retrospective analysis on 181 core-needle biopsies in 88 patients was performed to determine the diagnostic efficacy of ultrasound-guided core-needle biopsies in the head and neck. RESULTS: We experienced 100% success in obtaining high-quality histopathologic specimens. The target tissue was correctly sampled in 80 of 88 patients. In these patients the sensitivity, specificity, and accuracy rate of core-needle biopsies in differentiating benign from malignant cervicofacial lesions was 98.1%, 100%, and 98.8%, respectively. CONCLUSIONS: Ultrasound-guided core-needle biopsies can be recommended as a safe and reliable technique in the diagnosis of cervicofacial masses with a high diagnostic yield. It obtains tissue samples of high quality and represents a sufficient alternative to open biopsy even in the diagnosis of lymphoma.

Radiation-induced leiomyosarcoma of the oropharynx.

Leiomyosarcoma is a malignant mesenchymal tumor originating from smooth muscle cells, which most frequently develops in the myometrium and in the gastro-intestinal tract. Reviewing the international literature, radiation-induced sarcoma arise in 0.035 to 0.2% of all irradiated patients. Especially in the head and neck region, radiation-induced leiomyosarcoma is an extremely rare lesion. The authors report a case of a radiation-induced leiomyosarcoma of the tonsillar region of the oropharynx in a 51-year-old male patient, who had undergone radiation therapy of this region 38 years before. The lesion was treated by radical surgery. Diagnostic steps, histological presentation and therapy are described in detail and the literature concerning radiation induced malignancies in general as well as radiation induced leiomyosarcoma in particular is reviewed. The highlights of this case are an extremely uncommon location and a rare pathological entity of radiation induced malignancies.

Primary Ewing sarcoma of the petrous temporal bone: an exceptional cause of facial palsy and deafness in a nursling.

BACKGROUND: Primary Ewing sarcoma affecting the skull base in general and the petrous bone in particular is extremely rare with only 4 reports of Ewing sarcoma arising in the petrous temporal bone in the international medical literature. METHODS: The authors report for the first time a case of a primary Ewing sarcoma of the petrous temporal bone in a 5-month-old nursling, which became apparent with a complete peripheral facial palsy and ipsilateral surdity. RESULTS: The neoformation was treated by systemic chemotherapy and radiation of the tumor region. The diagnostic steps, therapy, and development of the child are described in detail; the literature concerning Ewing sarcoma originating from the skull in general and from the petrous temporal bone in particular is reviewed. CONCLUSIONS: The highlights of this case are an extremely uncommon location, an unusual age of presentation, as well as a unique set of symptoms.

Endolymphatic sac tumours: surgical management.

BACKGROUND: Endolymphatic sac tumours (ELSTs) have been known as an individual tumour entity only since 1984. ELSTs may occur either solitarily and sporadically or as a hereditary manifestation associated with von Hippel-Lindau (VHL) disease. The latter association was first observed in 1992 and confirmed by molecular genetic analysis of the VHL gene. No consensual diagnostic and treatment strategy of ELST exists at present. METHODS: Based on imaging criteria in computed tomography, magnetic resonance imaging (MRI), and magnetic resonance angiography, we developed a staging system to classify ELST in a series of seven consecutive patients in an attempt to custom-tailor the surgical approach. Type A referred to tumours that were locally confined without temporal bone erosion or infiltration of the dura (n = 2); type B tumours showed evidence of bone infiltration of the osseous labyrinth and sensorineural hearing loss (n = 2); and in type C, the tumour further invaded the sigmoid sinus and jugular bulb (n = 3). Two patients suffered from VHL disease. RESULTS: In all patients, the tumour was completely removed. Stage-adapted surgical approaches included various transpetrosal procedures, from the translabyrinthine to the infratemporal approaches. The functional integrity of the facial nerve was maintained in all tumour stages, whereas the vestibulocochlear nerve could be preserved only in patients with type A tumours. Follow-up MRI demonstrated no local tumour recurrence during a postoperative observation period ranging from 4 to 38 months. CONCLUSION: Stage-based surgical strategy enables the complete removal of ELST with minor morbidity. Transmastoid approaches are most efficient for resection of the tumour matrix to prevent local recurrence.

Spectrum and management of deep neck space infections: an 8-year experience of 234 cases.

OBJECTIVE: To study the clinical course and outcome of deep neck infections (DNI), with special emphasis on microbiology and histopathology. STUDY DESIGN: Two hundred thirty-four patients with DNIs were included in this study. Patients with peritonsillar or dental infections, infections arising from salivary glands, as well as subjects with abscesses caused by neck trauma were excluded. METHODS: Clinical analysis of all patients with DNIs who were treated between January 1, 1997 and May 31, 2005 in a single center. RESULTS: In 13 patients, the DNI was the first manifestation of a malignant tumor. In 17 cases, the DNI was associated with cat-scratch disease (CSD). Six patients suffered from tuberculosis, and in another 7, an infected lateral cleft cyst was found. In 176 patients, the origin of DNI remained unclear. CONCLUSIONS: Our results demonstrate that CSD, tuberculosis, and malignant tumors must be considered as possible causes of DNIs. The current study represents one of the largest series of DNIs in the modern medical literature. EBM RATING: C.

Cat-scratch disease: Otolaryngologic manifestations and management.

OBJECTIVE: The bacteria Bartonella henselae has been known as the principal causative agent of cat-scratch disease (CSD) since 1992. It is an important cause of infectious lymphadenopathies in the head and neck. Nevertheless, CSD often remains unrecognized in cases of cervicofacial lymph node enlargement. STUDY DESIGN: Between January 1997 and May 2003, we conducted a prospective clinical study including 721 patients with primarily unclear masses in the head and neck. RESULTS: CSD was diagnosed by serology and molecular investigations in 99 patients (13.7%; median age 33 years). Cervicofacial lymphadenopathy was the most common manifestation. Atypical manifestation of CSD including Parinaud's oculoglandular syndrome, swelling of the parotid gland and erythema nodosum were diagnosed in 8.1%, 8.1%, and 2.0% of cases, respectively. CONCLUSIONS: Our results demonstrate that CSD is a major cause of enlarged cervicofacial lymph nodes and should therefore be included in the differential diagnosis of lymphadenopathy in the head and neck region.

Paragangliomas in patients with mutations of the SDHD gene.

OBJECTIVE: Paragangliomas represent neoplasms of neural crest origin that arise from paraganglia. Mutations in the gene encoding succinate dehydrogenase subunit D (SDHD) are responsible for a percentage of hereditary paragangliomas. We previously described a group of 271 pheochromocytoma patients, 11 of whom had mutations of the SDHD gene. The objective of this study was to find out whether those 11 patients had additional paragangliomas. STUDY DESIGN: Ten patients participated in our clinical screening program that included MRI of the skull base and neck, thorax, and abdomen, as well as an 18 Fluoro-DOPA positron emission tomography (DOPA-PET). RESULTS: Five patients presented with head and neck paragangliomas, 1 patient with a thoracic paraganglioma, and 2 patients with intraabdominal paragangliomas. CONCLUSIONS: The screening for paragangliomas in patients with mutations of the SDHD gene offers the chance to diagnose those tumors in an early stage. SIGNIFICANCE: Because morbidity after surgical resection increases with tumor size, early surgery will minimize the potential risks.

Moyamoya disease complicated by life-threatening epistaxis: first report of a case.

OBJECTIVE: Subacute haemorrhage is a common emergency in otorhinolaryngology. Rapid evaluation of the aetiology and localization is a precondition for suitable treatment. We demonstrate a rare case of primarily intractable epistaxis associated with occlusion of the circle of Willis (moyamoya disease). PATIENT: A 38-year-old man presented with a 24-h history of recurrent epistaxis. Anamnesis revealed long-term anticoagulation after heart valve transplantation and arterial hypertension. RESULTS: As a result of several re-bleedings after anterior nasal packing, a re-packing was followed by surgical treatment under general anaesthesia. Four days after discharge the patient presented to the intensive care unit with severe re-bleeding. After removal of a temporary Bellocq packing, interdisciplinary treatment was necessary. Emergency angiography revealed advanced moyamoya disease, with occlusion of both internal carotid arteries. The cerebral blood supply was sustained by an excessive collateral network originating from external carotid anastomoses. This complicated the endovascular treatment, which consisted of embolization of the infraorbital and maxillar arteries with liquid material and coils flanked by Bellocq packing. The patient was doing well at follow-up after 12 months. CONCLUSION: Epistaxis complicating moyamoya disease is rare, and endovascular treatment is difficult due to the high risk of cerebral embolism. Malformations of the cerebral arteries should be considered in the differential diagnosis of intractable epistaxis.

Lateral upper arm free flap for primary reconstruction of pharyngeal defects in ablative oncological surgery. Report of six consecutive cases.

Free microvascular flaps are an established method for soft tissue reconstruction following ablative oncological surgery in the head and neck. Functional reconstructions of the hypopharynx and the pharyngoesophageal segment (PES) are of particular relevance, as they are highly demanding surgical procedures. So far, the radial forearm free flap (RFFF) and the free jejunal transfer have been the transplants predominantly used for this purpose. The lateral upper arm free flap (LUFF) presents an alternative method for the fasciocutaneous tissue transfer. We report on our experience with the LUFF in a 56-year-old male patient with a pT3pN0M0 squamous cell carcinoma of the hypopharynx. A pharyngocutaneous fistula developed 5 days after pharyngolaryngectomy with bilateral neck dissection. The fistula was localized between the pharyngeal constrictor muscle and the esophagus and was closed with an LUFF from the left arm. Excellent flap adaptation to the remaining pharyngeal mucosa was observed. Although the length of the vascular pedicle and the diameter of the vessels in the LUFF are smaller than those in the RFFF, neither pedicle length nor vessel diameter proved to be a problem. The LUFF can be recommended as a well-vascularized, relatively safe and reliable flap for reconstruction of tubular structures such as the hypopharynx and the PES after tumor ablation and as an alternative to the RFFF. The flexibility of the LUFF allows surgeons to reconstruct the anatomy of the lost soft tissues as adequately as possible.

Multilocular cervical thymic cysts in adults. A report of two cases and review of the literature.

Cervical thymic cysts are rare benign lesions that are hardly ever considered in the differential diagnosis of cystic neck masses. In the vast majority of cases, thymic cysts are found in infants and children. This article illustrates two cases of multilocular cervical thymic cysts in adults presenting as asymptomatic swellings in the neck. The clinical presentation, evaluation, surgical management and pathological findings are described. The possible pathogenesis as an acquired disease is reviewed and discussed. The authors recommend that, despite its rare occurrence, multilocular cervical thymic cysts should be considered in the differential diagnosis of all equivocal cases of unilateral cystic neck masses in adults.

Cicatricial pemphigoid in the upper aerodigestive tract: diagnosis and management in severe laryngeal stenosis.

Pemphigoid is a group of rare, acquired, autoimmune subepithelial blistering diseases. The condition has been subclassified into bullous pemphigoid and cicatricial pemphigoid (CP). Diagnosis is based on clinical presentation, evidence of subepithelialvesicles or bullae on routine histologic analysis, and direct and indirect immunofluorescence studies. Cicatricial pemphigoid is characterized by linear deposition of immunoreactants, principally IgG and complement factor 3, along epithelial basement membranes. Cicatricial pemphigoid usually leads to mucosal scarring. We present a case of severe CP that led to laryngeal and subglottic stenosis and involvement of both eyes and the oral, nasal, and nasopharyngeal mucosae. Treatment with dapsone, corticosteroids, azathioprine sodium, cyclosporine A, cyclophosphamide, methotrexate sodium, and mycophenolate mofetil between 1997 and 2001 only resulted in temporary disease control. The patient has been treated with leflunomide for the past 8 months, and there have been no relapses. Treatment of CP with leflunomide has not been described in the literature until now.