Malignant lymphoma presenting as bilateral sensorineural hearing loss-A case report

Bilateral Sensorineural Hearing Loss is a rare disease that is often associated with other complex medical conditions. Primary central nervous system lymphoma is an uncommon and aggressive variant of non-Hodgkin lymphoma that can mimic many other neurological diseases. Herein, we present a rare case of lymphoma of the CNS as the etiology for progressive SSNHL. We describe a 58-year-old male with previous IgG4-disease presentation who was diagnosed with progressive sensorineural hearing loss. The condition evolved rapidly despite proper, conventional therapy. The patient acquired vestibular symptoms and other cranial nerve deficiencies and he was diagnosed with intracranial lymphoma, mainly in the cerebellar region. This case demonstrates that rare intracranial lymphoma can present initially as sensorineural hearing loss. A higher suspicion for malignancy should be held in mind for patients with a history of IgG4-related diseases and for patients presenting with progressing bilateral SSNHL that is not responding to therapy.Peer reviewe

MMP-7, -8, -9, E-cadherin, and beta-catenin expression in 34 ameloblastoma cases

Objectives Ameloblastoma is a benign, locally aggressive odontogenic tumor with high recurrence rates. Matrix metalloproteinases (MMPs) mediate extracellular integrity in normal and pathological conditions, and exert multiple functions coordinating inflammation and tumor progression. E-cadherin and beta-catenin are adherence junction molecules in cell-to-cell connections. We investigated the involvement of MMP-7, -8, -9, E-cadherin, and beta-catenin in ameloblastoma and the surrounding extracellular matrix. Material and methods Our material consisted of 30-34 tissue samples from ameloblastoma patients of Helsinki University Hospital. We used immunohistochemistry to detect the expression of the biomarkers. Two oral pathologists independently scored the immunoexpression intensities and statistical calculations were made based on the results. Results E-cadherin expression was weaker in the maxillary than in mandibular ameloblastomas. Beta-catenin was expressed in the ameloblastoma cell membranes. We detected MMP-8 and -9 expression in polymorphonuclear neutrophils in the extracellular area and these MMPs correlated positively with each other. Osteoclasts lining bone margins and multinuclear giant cells expressed MMP-9. Neither MMP-8 nor MMP-9 immunoexpression could be detected in ameloblastoma cells. MMP-7 expression was seen in some apoptotic cells. Conclusion The fact that E-cadherin immunoexpression was weaker in maxillary compared to mandibular ameloblastomas might associate to earlier recurrences. It promotes the idea of mandibular and maxillary ameloblastoma exerting differences in their biologies. We detected MMP-8 and -9 in polymorphonuclear neutrophils which relates to these MMPs participating in extracellular remodeling through a mild inflammatory process. Bone degradation around ameloblastoma may be due to MMP-9 in osteoclasts but this phenomenon might be an independent process and needs further investigations.Peer reviewe

BRAF V600E expression in ameloblastomas-A 36-patient cohort from Helsinki University Hospital

Objectives We aimed to investigate BRAF V600E percentage immunohistochemically in ameloblastomas of a single institute cohort. We were interested if age, location, histological properties, or tumor recurrence depend on the BRAF status. Subjects, materials and methods We had 36 formalin-fixed, paraffin-embedded ameloblastoma tissue samples of patients treated at the Helsinki University Hospital between the years 1983-2016. Tissue sections underwent immunohistochemistry by Ventana BenchMark XT immunostainer using Ms Anti-Braf V600E (VE1) MAB. We used R 3.4.2 and RStudio 1.1.383 to conduct statistical analysis for BRAF positivity and earlier onset as well as tumor location. We used chi-squared tests and 2-by-2 table functions to determine connections between BRAF positivity and recurrence, growth pattern, and type. Results BRAF-positive tumors occurred in younger patients compared to BRAF-negative tumors (p = 0.015) and they located mostly to the mandible (p <0.001). Growth patterns were limited to two in BRAF-negative tumors when BRAF-positive tumors presented with one to four growth patterns (p = 0.02). None of the maxillary tumors showed BRAF positivity and of these, 72.2% recurred. Conclusions An immunohistochemical BRAF marker could be a beneficial tool to predict the outcome of patients with this aggressive, easily recurring tumor.Peer reviewe

MMP-7, -8, -9, E-cadherin, and beta-catenin expression in 34 ameloblastoma cases

Objectives Ameloblastoma is a benign, locally aggressive odontogenic tumor with high recurrence rates. Matrix metalloproteinases (MMPs) mediate extracellular integrity in normal and pathological conditions, and exert multiple functions coordinating inflammation and tumor progression. E-cadherin and beta-catenin are adherence junction molecules in cell-to-cell connections. We investigated the involvement of MMP-7, -8, -9, E-cadherin, and beta-catenin in ameloblastoma and the surrounding extracellular matrix.Material and methods Our material consisted of 30-34 tissue samples from ameloblastoma patients of Helsinki University Hospital. We used immunohistochemistry to detect the expression of the biomarkers. Two oral pathologists independently scored the immunoexpression intensities and statistical calculations were made based on the results.Results E-cadherin expression was weaker in the maxillary than in mandibular ameloblastomas. Beta-catenin was expressed in the ameloblastoma cell membranes. We detected MMP-8 and -9 expression in polymorphonuclear neutrophils in the extracellular area and these MMPs correlated positively with each other. Osteoclasts lining bone margins and multinuclear giant cells expressed MMP-9. Neither MMP-8 nor MMP-9 immunoexpression could be detected in ameloblastoma cells. MMP-7 expression was seen in some apoptotic cells.Conclusion The fact that E-cadherin immunoexpression was weaker in maxillary compared to mandibular ameloblastomas might associate to earlier recurrences. It promotes the idea of mandibular and maxillary ameloblastoma exerting differences in their biologies. We detected MMP-8 and -9 in polymorphonuclear neutrophils which relates to these MMPs participating in extracellular remodeling through a mild inflammatory process. Bone degradation around ameloblastoma may be due to MMP-9 in osteoclasts but this phenomenon might be an independent process and needs further investigations.</p

BRAF V600E expression in ameloblastomas-A 36-patient cohort from Helsinki University Hospital

Objectives: We aimed to investigate BRAF V600E percentage immunohistochemically in ameloblastomas of a single institute cohort. We were interested if age, location, histological properties, or tumor recurrence depend on the BRAF status. Subjects, materials and methods: We had 36 formalin-fixed, paraffin-embedded ameloblastoma tissue samples of patients treated at the Helsinki University Hospital between the years 1983-2016. Tissue sections underwent immunohistochemistry by Ventana BenchMark XT immunostainer using Ms Anti-Braf V600E (VE1) MAB. We used R 3.4.2 and RStudio 1.1.383 to conduct statistical analysis for BRAF positivity and earlier onset as well as tumor location. We used chi-squared tests and 2-by-2 table functions to determine connections between BRAF positivity and recurrence, growth pattern, and type. Results: BRAF-positive tumors occurred in younger patients compared to BRAF-negative tumors (p = 0.015) and they located mostly to the mandible (p Conclusions: An immunohistochemical BRAF marker could be a beneficial tool to predict the outcome of patients with this aggressive, easily recurring tumor.</div

Ameloblastoma: a retrospective single institute study of 34 subjects

Objective: This study aims to clarify demographic and clinical aspects of patients with ameloblastoma treated at a single Finnish institute during 1985–2016. Associations between predictor variables (gender and age) and outcome variables (location, tumour type, growth patterns and average tumour size) were sought.Materials and methods: A retrospective cohort study was designed and implemented including 34 patients diagnosed with primary ameloblastoma and treated at the Helsinki University Central Hospital. Patient records were investigated, and tissue samples re-evaluated. The chi-square test was used on all categorized variables and t-test for continuous ones. A p value equal to or under .05 was considered significant.Results: Males were slightly more predominant among the Finnish patients with ameloblastoma. Maxillary tumours were seen exclusively in male patients (p = .034). Additionally, these patients were older than patients with mandibular tumours (p = .007). A mixture in histological growth patterns was more common than originally anticipated. The study revealed a wide range of clinical signs and subjective symptoms, of which pain or other sensations were experienced most often.Conclusions: This study of 34 subjects shows that southern Finnish patients with ameloblastoma do not substantially differ from patients in similar study designs.</p

Ameloblastoma

Ameloblastoma is a benign albeit locally aggressive odontogenic tumor originating from remnants of the dental lamina, primarily affecting the mandible, and potentially mutilating if is left untreated. Ameloblastomas are classified as ameloblastoma (conventional), unicystic ameloblastoma, and peripheral ameloblastoma. Annual incidence is estimated to be 0.5/1 million population. In the Helsinki University Hospital (HUS) district, approximately five ameloblastoma patients are treated each year. Etiology has yet to be elucidated, although new genetic findings have emerged relating to the mitogen-activated protein kinase (MAPK) pathway. We surveyed the Q-pati system to identify all ameloblastoma patients (n = 64) treated at the Head and Neck Surgery Unit of HUS. A total of 30 to 36 patient records and the formalin-fixed paraffin-embedded tumor tissue samples were suitable for use from the Department of Pathology at HUS (HUSLAB) from 1985 through 2016. All patient reports were studied, and the parameters were collected using clinical data, Q-pati records, and imaging reports. A total of 26 ameloblastoma patients’ radiological findings were re-evaluated and studied. All tissue samples were revised microscopically, and representative paraffin blocks were chosen for immunohistochemistry with tested dilutions and protocol methods including positive and negative controls. BRAF, MMP-7, MMP-8, MMP-9, E-cadherin, and beta-catenin were of interest. For statistics, we used R studio, seeking correlations between parameters using the Fisher’s exact test, z-test, t-test, χ², and logistic regression to determine statistical significance. We considered p < 0.05 significant. Our results mostly coincide with previous knowledge with minor deviations and some notable differences to consider in future studies. Specifically, maxillary tumors occurred mostly in older, male patients. BRAF-positive tumors seemed to recur more often than BRAF-negative tumors in the mandible area. In addition, all maxillary tumors were BRAF-negative. Maxillary tumors are likely to recur easily, presumably along complex anatomical structures. Unlike previous studies, ameloblastoma cells did not express MMP-7, MMP-8, or MMP-9. MMP-9 positivity, however, was observed in inflammatory cells, macrophages, and osteoclasts. Beta-catenin expression appeared on the cell membranes. E-cadherin expression varied, although maxillary tumors presented with a weak E-cadherin expression. Radiologic re-evaluation revealed that ameloblastomas eradicate cortical bone already during the early stages of tumor growth. Ultimately, we found that CT and MRI imaging remain essential in differential diagnostics, serving to protect the patient from radical surgery. In conclusion, maxillary tumors might be reasonable to study separately from mandibular tumors because of their different protein properties. Our investigations among this Finnish ameloblastoma patient cohort have expanded our knowledge of a rare odontogenic tumor and further substantiated previous findings.Ameloblastoma on hyvänlaatuinen, mutta paikallisesti aggressiivinen, epiteeliaalinen hammasperäinen kasvain. Ameloblastooma kehittyy useimmin alaleuan luuhun ja hoitamattomana se voi johtaa kuolemaan. WHO luokittelee ameloblastoomat tavanomaiseen, unikystiseen ja periferiseen ameloblastoomaan. Vuotuisen esiintyvyyden arvioidaan olevan 0,5 tapausta/miljoona. Helsingin ja Uudenmaan sairaalanhoitopiirissä (HUS) hoidetaan vuosittain yhdestä viiteen ameloblastoomapotilasta. Etiologia ei ole vielä selvä, vaikka mitogeeniaktivoituneen proteiinikinaasi (MAPK) -reittiin liittyy uusia geneettisiä löydöksiä. Haimme Q-pati -järjestelmän kautta HUS:ssa vuosina 1985—2016 hoidetut ameloblastoomatapaukset (n = 64), joista 30-36:n potilastiedot ja formaliinifiksoidut kudosnäytteet olivat käytettävissämme. Kaikki potilasraportit tutkittiin ja suunnitellut parametrit kliinisistä tiedoista ja kuvantamisraporteista kerättiin. Yhteensä 26:n ameloblastoomapotilaan radiologiset löydökset tutkittiin ja arvioitiin uudelleen. Kaikki 36 histologista näytettä uudelleenarvioitiin. BRAF, MMP-7, MMP-8, MMP-9, E-kadheriini ja beetakateniini -immunohistokemiallisia värjäyksiä varten valitsimme edustavat näytteet. Kaikkiin värjäyssarjoihin liitettiin positiiviset ja negatiiviset kontrolloit. Tutkimukselle myönnettiin eettisen toimikunnan ja Valviran luvat. Tuloksistamme seuraavat asiat ovat huomionarvoisia. Erityisesti yläleuan kasvaimia esiintyi enimmäkseen vanhemmilla miespotilailla. BRAF-positiiviset kasvaimet alaleuassa näyttivät uusiutuvan useammin kuin BRAF-negatiiviset kasvaimet alaleuassa. Kaikki yläleuan kasvaimet olivat BRAF-negatiivisia. Toisin kuin aikaisemmissa vastaavissa tutkimuksissa, ameloblastoomasolut eivät tutkimuksissamme ilmentäneet MMP-7: ää, MMP-8: aa tai MMP-9: ää. MMP-9-positiivisuutta havaittiin kuitenkin tulehdussoluissa, makrofageissa ja osteoklasteissa viitaten tulehduksen osuuteen tuumoriympäristön muokkaajana. Beetakateeniinipositiivisuutta nähtiiin vain solukalvoilla. E-kadheriinin ekspressio vaihteli. Yläleuan ameloblastoomissa E-kadheriinin ekspressio oli heikompaa herättäen kysymyksen sen vaikutuksesta tuumorin uusimisriskiin. Yläleuan kasvaimet olisi hyvä tutkia omana ryhmänään alaleuan kasvaimista niiden erilaisten geneettisten ominaisuuksien vuoksi. Radiologinen uudelleenarviointi osoitti, että ameloblastooma tuhoaa kortikaalista luuta jo kasvaimen alkuvaiheessa, mikä on erotusdiagnostisesti huomionarvoista. Viime kädessä toteamme, että TT- ja MRI-kuvantaminen ovat välttämättömiä ameloblastoomadiagnostiikassa ja riittävän tarkka kuvantaiminen suojaa potilasta turhan laajoilta leikkauksilta. Nämä suomalaisen ameloblastooma-aineistoon kohdistuneet tutkimukset ovat laajentaneet tietämystämme ameloblastooman oireista, kliinisestä kuvasta, kuvantamislöydöksistä sekä parantaneet käsitystämme immunohistokemiallisten menetelmien hyödyistä diagnostiikassa

Histopathological findings of oral epithelial dysplasias and their relation to malignant transformation

Objectives: Oral squamous cell carcinomas (OSCCs) are often diagnosed late. This study aimed to determine how frequently oral epithelial dysplasia (OED) transforms to OSCC and to identify histological features that could influence the rate of malignant transformation.Materials and methods: The study was a retrospective analysis of OED over 29 years at the Institute of Dentistry, University of Turku, Finland. OEDs with co-existing carcinomas were excluded from the data (5.8%). OED patients who developed carcinoma were identified from the Finnish Cancer Registry database.Results: Altogether 681 OED patients had a mean age of 59.0 years, and the male:female ratio was 0.67. Of all OED samples, 21.8% were on the tongue, followed by lining mucosa (21.3%), lip (5.3%), and masticatory mucosa (4.85%). In addition, 46.7% had no location cited. The prevalence of mild dysplasia was 62.4%, moderate dysplasia 29.1%, and severe dysplasia 3.2%. Of the patients, 94.7% had an additional histological diagnosis alongside OED. Candidiasis, lichenoid inflammation, and ulcer were found in 18.2%, 0.0%, and 22.7% of severe dysplasias, in 12.1%, 12.2%, and 22.7% of moderate dysplasias, and in 6.6%, 12.2%, and 15.8% of mild dysplasias, respectively. An additional histopathological diagnosis did not increase the risk for OED to transform to OSCC. In a mean time of 5.2 (range 0.7-29.0) years, 7.5% of OED patients developed OSCC.Conclusions: Location on the tongue and the more severe OED grades increased the risk of malignant transformation of OED. These patients may benefit from an intensified follow-up schedule to ensure early diagnosis of OSCC