Challenging Management of Plexiform Schwannoma and Plexiform Neurofibroma.

ABSTRACT: Plexiform variants of neurofibromas and schwannomas are rare and typically arise in superficial soft tissues in the head and neck region. The treatment of these tumors is challenging and no generally accepted guidelines exist for their optimal management. The purpose of this study was to review the management and longterm prognosis of head and neck plexiform neurofibromas and schwannomas at 2 tertiary care academic hospitals in Finland over a 31-year period. The pathology files were searched for plexiform neurofibromas and schwannomas between the years 1990 and 2020. The case notes were reviewed for full management details. Two plexiform schwannomas and 6 plexiform neurofibromas were identified. Five of the 6 plexiform neurofibromas were managed operatively. All patients with a surgically managed plexiform neurofibroma underwent multiple operations. Sclerotherapy abolished 1 patient's cutaneous plexiform neurofibromas. The management of plexiform neurofibromas and plexiform schwannomas remains challenging. Sclerotherapy may offer a promising management option for cutaneous plexiform neurofibromas.

Submandibular gland cancer: Specific features and treatment considerations.

BACKGROUND: In the absence of unified treatment protocol, we evaluated the management and outcomes of submandibular gland cancers in an unselected patient series. METHODS: We included all patients with resected submandibular gland cancer treated at the Helsinki University Hospital from 2000 to 2010 with a 5-year minimum follow-up. RESULTS: Twenty-five patients with cancer represented 30% of submandibular gland neoplasms, and most were adenoid cystic carcinomas (ACCs; 56%). At presentation, 3 patients showed clinical signs of probable malignancy. Of 22 neck dissection specimens, 5 patients (20%) had metastases with an occult metastasis rate of 4%. Cancer recurred in 11 patients (44%), of which 7 (28%) were only at a distant site. The 5-year disease-specific survival (DSS) and overall survival (OS) rates were 76%, and disease-free survival (DFS) was 68%. CONCLUSION: Most tumors were ACCs differing from the histological pattern of parotid gland cancers. Occult metastases were rare. The rarity of submandibular gland cancer, its variable histological pattern, and varying biological behavior warrant centralized management.

Otogenic Intracranial Abscesses, Our Experience Over the Last Four Decades.

OBJECTIVE: To evaluate the predisposing factors for otogenic intracranial abscesses, assess their changes over time, and analyze how they differ from those due to other causes. MATERIALS AND METHODS: The medical records of all patients treated for otogenic intracranial abscesses, between 1970 and 2012 at a tertiary referral center, were retrospectively analyzed. The analysis included patient demographics, clinical characteristics, causative pathogens, treatments, outcomes, and comparisons of otogenic and non-otogenic intracranial abscesses. RESULTS: Of all intracranial abscesses, 11% (n=18) were otogenic. In the 1970s, otogenic infections were a common predisposing factor for intracranial abscess; but within our study period, the incidence of otogenic intracranial abscesses decreased. Most (94%) otogenic cases were due to chronic suppurative otitis media and 78% were associated with cholesteatoma. Most patients (94%) had ear symptoms. The most common presenting symptoms were discharge from the infected ear (50%), headache (39%), neurological symptoms (28%), and fever (17%). The most common pathogens belonged to Streptococcus spp. (33%), Gram-negative enteric bacteria (22%), and Bacteroides spp. (11%). Neurosurgery was performed on all patients, 69% of which were prior to a later ear surgery. Surgery of the affected ear was performed on 14 patients (78%). A favorable recovery was typical (78%); however, one patient died. CONCLUSION: Otogenic intracranial abscesses were most commonly due to a chronic ear infection with cholesteatoma. Ear symptoms and Gram-negative enteric bacteria were more common among patients with otogenic than non-otogenic intracranial abscesses.

Severe Acute Otitis Media and Acute Mastoiditis in Adults.

OBJECTIVE: To evaluate and compare clinical and microbiological findings in adults hospitalized for acute otitis media (AOM) or mastoid infections (acute or latent). MATERIALS AND METHODS: We retrospectively reviewed the medical records of all adults (≥17 years old) hospitalized (between 2003 and 2012) at a tertiary referral center for acute mastoid infections or AOM not responding to outpatient medical treatment. RESULTS: Of the 160 patients in the study sample, 19% had an infection caused by S. pyogenes, 14% by S. pneumoniae, and 11% by P. aeruginosa. AOM was the most common infection (38%), whereas 33% had acute mastoiditis (AM), 18% had latent mastoiditis (LM), and 13% AM of a chronically infected ear (AMc). In contrast to the other infections, P. aeruginosa (30%) and S. aureus (25%) were most common in AMc. Otorrhea (83%), tympanic membrane perforation (57%), and hearing problems (83%) were common in S. pyogenes infections. Patients with S. pneumoniae had longer lengths of hospitalization than those with other bacterial infections (7 vs. 4 days). Otorrhea (94%) and retroauricular symptoms were more common in P. aeruginosa infections. Hearing symptoms were common (67%) but fever (32%) and retroauricular symptoms were uncommon in AOM. Fever (44%) and mastoid tenderness (65%) were common in AM. Patients with LM underwent the most mastoidectomies (54%). Prior medical conditions, retroauricular symptoms, otorrhea (90%), and post-infection problems were common in AMc. CONCLUSION: The bacteriological etiology of hospitalized AOM more closely resembled those of LM and AM than that of AMc. Adults hospitalized for AOM or AM required fewer mastoidectomies than those hospitalized for LM or AMc.

Boron Neutron Capture Therapy in the Treatment of Recurrent Laryngeal Cancer.

PURPOSE: To investigate the safety and efficacy of boron neutron capture therapy (BNCT) as a larynx-preserving treatment option for patients with recurrent laryngeal cancer. METHODS AND MATERIALS: Six patients with locally recurrent squamous cell laryngeal carcinoma and 3 patients with persistent laryngeal cancer after prior treatment were treated with BNCT at the FiR1 facility (Espoo, Finland) in 2006 to 2012. The patients had received prior radiation therapy with or without concomitant chemotherapy to a cumulative median dose of 66 Gy. The median tumor diameter was 2.9 cm (range, 1.4-10.9 cm) before BNCT. Boron neutron capture therapy was offered on a compassionate basis to patients who either refused laryngectomy (n=7) or had an inoperable tumor (n=2). Boronophenylalanine-fructose (400 mg/kg) was used as the boron carrier and was infused over 2 hours intravenously before neutron irradiation. RESULTS: Six patients received BNCT once and 3 twice. The estimated average gross tumor volume dose ranged from 22 to 38 Gy (W) (mean; 29 Gy [W]). Six of the 8 evaluable patients responded to BNCT; 2 achieved complete and 4 partial response. One patient died early and was not evaluable for response. Most common side effects were stomatitis, fatigue, and oral pain. No life-threatening or grade 4 toxicity was observed. The median time to progression within the target volume was 6.6 months, and the median overall survival time 13.3 months after BNCT. One patient with complete response is alive and disease-free with a functioning larynx 60 months after BNCT. CONCLUSIONS: Boron neutron capture therapy given after prior external beam radiation therapy is well tolerated. Most patients responded to BNCT, but long-term survival with larynx preservation was infrequent owing to cancer progression. Selected patients with recurrent laryngeal cancer may benefit from BNCT.

Multidisciplinary Approach to Management of Temporal Bone Giant Cell Tumor.

Background Giant cell tumors (GCTs) are rare osseous tumors that rarely appear in the skull. Methods We review the clinical course of a 28-year-old previously healthy woman with a complicated GCT. Results The reviewed patient presented with a middle cranial fossa tumor acutely complicated by reactive mastoiditis. Left tympanomastoidectomy was performed for drainage of the mastoiditis and for biopsies of the tumor. Due to the challenging tumor location, the patient was treated with denosumab, a fully humanized monoclonal antibody against receptor activator of nuclear factor kappa-B ligand, for 7 months, which resulted in significant preoperative tumor shrinkage. Extensive temporal craniotomy and resection of the tumor followed utilizing a temporomandibular joint total endoprosthesis for reconstruction. A recurrence of the tumor was detected on computed tomography at 19 months after surgery and treated with transtemporal tumor resection, parotidectomy, and mandible re-reconstruction. Conclusion A multidisciplinary approach resulted in a good functional result and, finally, an eradication of the challengingly located middle cranial fossa tumor.

Intracranial abscesses over the last four decades; changes in aetiology, diagnostics, treatment and outcome.

Background The development of modern medicine has resulted in changes in the predisposing conditions, clinical picture, treatment and results of treatment of intracranial abscesses. This study sought to evaluate these changes in a hospital district. Methods A retrospective analysis of the clinical data of all patients treated due to intracranial abscesses at a tertiary referral centre, between 1970-2012. Results The total number of intracranial abscesses was 166. The incidence of intracranial abscesses was 0.33/100 000/year (2000-2012). The most common predisposing conditions were infection of the ear-, nose- and throat region (22%), odontogenic infection (15%) and cardiac anomaly (13%). Lately (2000-2012), infections of the ear-, nose- and throat region (15%) and cardiac anomalies (5%) have become less common, whereas odontogenic infections (32%) have become more common. The most common pathogens belong to Streptococcus spp (42%), Fusobacteriae (14%), Actinomycetales (8%) and Staphylococcus spp (8%). Most patients (66%) experienced a favourable recovery; the proportion of patients with favourable outcome enabling return to prior occupation rose over time, from 12% in 1970-1989 to 24% in 1990-2012. Conclusions The predisposing conditions for intracranial abscesses have changed markedly within the study period. Odontogenic infections have become a common predisposing condition, whereas infections of the ear-, nose- and throat region and cardiac malformations are nowadays less common as predisposing conditions compared to at the beginning of the study period. The proportion of patients with favourable outcome enabling return to prior occupation seems to have increased with time.

Children hospitalized due to acute otitis media: how does this condition differ from acute mastoiditis?

OBJECTIVES: To evaluate the clinical picture and microbiological findings of children hospitalized due to acute otitis media and to analyze how it differs from acute mastoiditis. METHODS: A retrospective review of the medical records of all children (0-16 years) hospitalized due to acute otitis media in the Department of Otorhinolaryngology at the Helsinki University Hospital, between 2003 and 2012. Comparison with previously published data of children with acute mastoiditis (n=56) from the same institute and period of time. RESULTS: The most common pathogens in the children hospitalized due to acute otitis media (n=44) were Streptococcus pneumoniae (18%), Pseudomonas aeruginosa (16%), Streptococcus pyogenes (14%), and Staphylococcus aureus (14%). One of the most common pathogens of out-patient acute otitis media, Haemophilus influenzae, was absent. Otorrhea was common in infections caused by S. pyogenes and otorrhea via tympanostomy tube in infections caused by P. aeruginosa. In children under 2 years-of-age, the most common pathogens were S. pneumoniae (43%), Moraxella catarrhalis (14%), and S. aureus (7%). S. pyogenes and P. aeruginosa were only found in children over 2 years-of-age. Previous health problems, bilateral infections, and facial nerve paresis were more common in children hospitalized due to acute otitis media, compared with acute mastoiditis, but they also demonstrated lower CRP values and shorter duration of hospital stay. The number of performed tympanostomies and mastoidectomies was also comparatively smaller in the children hospitalized due to acute otitis media. S. aureus was more common and S. pneumoniae, especially its resistant strains, was less common in the children hospitalized due to acute otitis media than acute mastoiditis. CONCLUSIONS: Acute otitis media requiring hospitalization and acute mastoiditis compose a continuum of complicated acute otitis media that differs from common out-patient acute otitis media. The bacteriology of children hospitalized due to acute otitis media resembled more the bacteriology of acute mastoiditis than that of out-patient acute otitis media. The children hospitalized due to acute otitis media needed less surgical treatment and a shorter hospitalization than those hospitalized due to acute mastoiditis.

Bacteriology in relation to clinical findings and treatment of acute mastoiditis in children.

OBJECTIVE: We assessed clinical, radiological, laboratory and microbiological findings in children with acute mastoiditis in order to improve the diagnostics and treatment of these patients. We also investigated whether different pathogens cause different clinical findings of mastoiditis. METHODS: A retrospective review of the medical records of all children aged 0-16 years treated as in-ward patients for acute mastoiditis at Helsinki University Central Hospital, Department of Otorhinolaryngology, between 2003 and 2012. RESULTS: Fifty-six patients met the inclusion criteria. The incidence of mastoiditis was 1.88/100000/year. The most common pathogens were Streptococcus pneumoniae (38%), Streptococcus pyogenes (11%) and Pseudomonas aeruginosa (11%). Of S. pneumoniae, 48% had reduced susceptibility (intermediate or resistant) for the common antimicrobials; this was clearly overrepresented relative to the background population (p<0.001). Otalgia and retroauricular symptoms were common in the patients with S. pneumoniae. Otorrhoea was less common (p=0.03) in these patients relative to the other pathogens. Patients with S. pneumoniae had more destruction of the mastoid septa (p=0.05) than patients with any of the other pathogens. Mastoidectomy was performed in 34% of all cases, it was most common (60%) in the patients with S. pneumoniae with reduced susceptibility. The patients with S. pyogenes had less otalgia and seemed to have less retroauricular symptoms relative to other pathogens. P. aeruginosa especially affected children with tympanostomy tubes, caused otorrhoea in all patients and caused a milder form of disease with less retroauricular swelling (p=0.04) than the other pathogens, and there was no need for mastoidectomies. The younger children (<2 years) had less otorrhoea and more retroauricular symptoms of infection than the older patients. No significant differences emerged in outcome of the patient groups. CONCLUSIONS: The clinical findings of acute mastoiditis differ according to the causative pathogen. S. pneumoniae, especially strains with reduced susceptibility, causes severe symptoms and leads to mastoidectomy more often than the other pathogens. S. pyogenes causes less otalgia than the other pathogens. P. aeruginosa particularly affects children with tympanostomy tubes and causes a less aggressive form of disease.

Retropharyngeal involvement in Kawasaki disease--a report of four patients with retropharyngeal edema verified by magnetic resonance imaging.

Kawasaki disease is an acute systemic vasculitis of childhood. The diagnosis is based on clinical criteria. Prognosis with adequate treatment is favorable. Untreated patients, however, may develop coronary manifestations predisposing to acute myocardial infarction. Retropharyngeal edema is a rare but known manifestation of Kawasaki disease. We present a case series of four Kawasaki patients presenting with clinical findings for retropharyngeal abscess and the magnetic resonance imaging findings of these patients, diagnosed during a six week period. To our knowledge, this is the first systematic report of cervical MRI findings of Kawasaki patients.

The developing management of esthesioneuroblastoma: a single institution experience.

Esthesioneuroblastoma remains a challenging disease because of its rarity, the complexity of surrounding structures, missing opinions of optimal treatment protocol, and complications associated with necessary surgery. Our objective was to analyse the management and outcome of a cohort of patients with esthesioneuroblastoma from 1990 to 2009 in a tertiary medical centre. There were 17 eligible patients (8 males and 9 females) with the median age of 53 years (range 20-75 years). An obvious inconsistency was noted in the management of the various tumours of the present series during the two decades due to a lack of a uniform treatment protocol. The median follow-up time was 57.5 months (range 3-158 months). Nine patients (seven with curative treatment intent) died of the disease with the median time from diagnosis to death of 60 months (range 3-161 months). Eight patients had no evidence of the disease at last follow-up visit (median 76 months, range 24-119 months). Recurrences were documented in seven of the patients. The median time from end of primary treatment to a recurrence was 57 months (range 6-110 months). The 5-year overall survival and disease-free survival was 68 and 62%, respectively. The management of ENB should be planned by an experienced head and neck surgeon as part of a multidisciplinary team in a tertiary referral setting. Multimodality therapy with long-term follow-up is preferable and should be set based on the available disease-specific classifications for clinical staging and histopathological grading.

Basement membrane collagen type IV expression by human mesenchymal stem cells during adipogenic differentiation.

During adipogenic differentiation human mesenchymal stem cells (hMSC) produce collagen type IV. In immunofluorescence staining differentiating hMSCs started to express collagen type IV when Oil Red O-positive fat droplets appeared intracellularly. Quantitative real time-polymerase chain reaction confirmed progressive increase of collagen type IV α1 and α2 mRNA levels over time, 18.6- and 12.2-fold by day 28, respectively, whereas the copy numbers of α3-α6 mRNAs remained rather stable and low. Type IV collagen was in confocal laser scanning microscopy seen around adipocytes, where also laminins and nidogen were found, suggesting pericellular deposition of all key components of the fully developed basement membrane. Immunofluorescence staining of matrix metalloproteinase-2 (MMP-2, 72 kD type IV collagenase, gelatinase A) and MMP-9 (92 kD type IV collagenase, gelatinase B) disclosed only faint staining of MSCs, but MMP-9 was strongly induced during adipogenesis, whereas MSC supernatants disclosed in zymography pro-MMP-2 and faint pro-MMP-9 bands, which increased over time, with partial conversion of pro-MMP-2 to its active 62 kD form. Differentiation was associated with increasing membrane type 1-MMP/MMP-14 and tissue inhibitor of metalloproteinase-2 (TIMP-2) staining, which may enable participation of type IV collagenases in basement membrane remodelling via ternary MT1-MMP/TIMP-2/MMP-2 or -9 complexes, focalizing the fully active enzyme to the cell surface. MMP-9, which increased more in immunofluorescence staining, was perhaps preferentially bound to cell surface and/or remodelling adipocyte basement membrane. These results suggest that upon MSC-adipocyte differentiation collagen type IV synthesis and remodelling become necessary when intracellular accumulation of fat necessitates a dynamically supporting and instructive, partly denatured adipogenic pericellular type IV collagen scaffold.

Mandibular osteomyelitis in children mimicking juvenile recurrent parotitis.

OBJECTIVE: To describe pediatric cases with mandibular osteomyelitis initially diagnosed and treated as juvenile recurrent parotitis. METHODS: We reviewed the patient data of all our pediatric patients treated at Helsinki University Central Hospital, a tertiary care hospital, between 1998 and 2010 who had the initial diagnosis of recurrent parotitis which in fact was osteomyelitis. RESULTS: Over a period of 12 years, six children (aged 5-17 years, five girls) presented with mandibular osteomyelitis primarily diagnosed as recurrent parotitis. Diagnostic delay ranged from 1.5 months to 6.0 years before the final diagnosis of mandibular osteomyelitis confirmed in MRI. Of the six cases undergoing biopsies, bacterial culture showed Actinomyces or Streptococcus viridans in four cases. All patients received antimicrobial treatment. Two received hyperbaric oxygen therapy with no resolution of symptoms. Debridement was performed in these two cases as well, and in the second case persistent symptoms led to bisphosphonate treatment. CONCLUSIONS: Juvenile parotitis is in most cases a clinical diagnosis, and treatment is symptomatic. In contrast, mandibular osteomyelitis is a severe disease requiring lengthy treatment. Because symptoms of these two entities may mimic each other, unclear cases require MRI.

Management of facial nerve schwannoma: A single institution experience.

CONCLUSION: Difficulties in diagnosis, conservative initial steps in the management algorithm and intraoperative risks for facial nerve (FN) injury are divisive features for this tumour entity. OBJECTIVE: The aim of the present study was to investigate the management and outcome of FN schwannomas (FNSs) at a tertiary referral centre and academic institution in a 30-year material. METHODS: Data on age, sex, symptoms, tumour location, histopathological characteristics, imaging, management and outcome were retrospectively recorded. RESULTS: Ten cases (six males, 60%), with a median age of 34.5 years (range 19-75 years) were identified. Five of the patients had intact FN function at the time of diagnosis. Five of the tumours were intraparotid and five were located in the temporal bone. Preoperative fine needle aspirations were non-diagnostic in all of the four patients presenting with a parotid mass. Nine patients were managed surgically. One patient is currently under conservative follow-up for a parotid schwannoma (diagnosed with magnetic resonance imaging) with intact FN function. No malignant schwannomas were encountered. The clinical outcome and histology will be discussed.

Screening for celiac disease in Down's syndrome patients revealed cases of subtotal villous atrophy without typical for celiac disease HLA-DQ and tissue transglutaminase antibodies.

AIM: To investigate the prevalence of celiac disease (CD) as well as CD marker antibodies and susceptibility HLA-DQ haplotypes in 134 karyotyped Down's syndrome (DS) patients. METHODS: Immunoglobulin A (IgA) and G (IgG) type anti-gliadin antibodies (AGA), IgA type anti-tissue transglutaminase (tTG) antibodies (anti-tTG) with antigen of guinea pig and human source were determined by enzyme-linked immunosorbent assay and endomysium antibodies (EMA) by indirect immunofluorescence test. HLA-DQA1*0501/DQB1*0201 (DQ2) was revealed by polymerase chain reaction. Celiac disease was diagnosed by revised ESPGHAN criteria. RESULTS: 41% of DS patients had AGA, 6.0% IgA anti-tTG with guinea pig antigen, and 3.0% IgA EMA (all positive for anti-tTG with human tTG). Subtotal villous atrophy was found in 5 out of 9 DS patients who had agreed to small bowel biopsy. One of them had DQA1*0501/DQB1*0201 and anti-tTG and EMA i.e. typical for CD markers (this case also fulfilled the ESPGHAN diagnostic criteria),but other four lacked these markers. Three non-biopsied DS patients had also most probably CD because DQA1*0501/DQB1*0201 and IgA anti-tTG (EMA) were detected. Thus, the prevalence of CD among our DS patients population is 3.0% (95 % of confidence interval [CI]: 0.1-5.9%). CONCLUSION: We confirm the increased frequency of CD among DS patients. In addition, we have revealed a subgroup of patients with subtotal villous atrophy but without characteristic for CD immunological and genetic markers. Whether these cases represent CD (with atypical immunopathogenesis) or some other immune enteropathy, requires further investigations.

A novel metalloprotease from Vipera lebetina venom induces human endothelial cell apoptosis.

A novel endothelial cell apoptosis inducing metalloprotease (VLAIP) was found in the snake venom of Vipera lebetina. This metalloprotease is a heterodimeric glycoprotein with molecular mass of about 106 kDa. The protease hydrolyzes azocasein, fibrinogen and oxidized insulin B-chain. The enzyme readily hydrolyzes the Aalpha-chain and more slowly Bbeta-chain of fibrinogen. VLAIP does not cleave fibrin. The complete amino acid sequences of the two different monomers of VLAIP are deduced from the nucleotide sequences of cDNAs encoding these proteins. The full-length cDNA sequences of the VLAIP-A and VLAIP-B encode open reading frames of 616 and 614 amino acids that include signal peptide, propeptide and mature metalloproteinase with disintegrin-like and cysteine-rich domains. VLAIP belongs to the metalloprotease/disintegrin family of reprolysins and has high identity with the proteins that induce apoptosis of endothelial cells. Treatment of HUVEC cells with VLAIP induces changes in the attachment of cells to the substrate and causes cell death. We demonstrated that VLAIP inhibits endothelial cell adhesion to extracellular matrix proteins: fibrinogen, fibronectin, vitronectin, collagen I, and collagen IV. The induction of apoptosis by VLAIP was shown by means of a typical DNA fragmentation pattern of apoptotic cells as well as by monitoring phosphatidylserine externalization using annexin V-FITC staining and flow cytometric analysis.