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Purpose The aim of this study was to analyze the expression of PLUNC proteins, putative host-defense proteins, in patients diagnosed with oral graft-versus-host-disease (GVHD). Material and methods Whole saliva from eight patients diagnosed with oral GVHD was collected. Western blotting was performed using a LPLUNC1 antibody and two SPLUNC 2 antibodies; one raised to an internal peptide (SPLUNC 2B) and another to an epitope at the c-terminus (SPLUNC 2A). Clinical data were collected from medical records. Results PLUNC expression was found in all patients, however, there was a statistical difference in expression levels when we compared LPLUNC with SPLUNC 2A ( p = 0,035) and LPLUNC with SPLUNC 2B ( p = 0,044). Conclusion PLUNC proteins are differentially expressed in the saliva of patients with oral GVHD. Further studies are needed to better understand the biological processes involved in PLUNC expression and the significance of the differential expression patterns.

Purpose SPLUNC1 is a protein that participates in the host innate immunity, mainly expressed in the respiratory tract epithelium, secretions, salivary glands and saliva. Its expression was also described in infections, inflammatory disorders, and malignancies. Patients who underwent chemotherapy (CT) or radiotherapy (RT) for head and neck tumors may suffer important oral side effects, such as mucositis, candidosis, taste alterations and hypossalivation, which can interfere with SPLUNC1 expression. Therefore, the purpose of this study was to analyze the saliva of patients who underwent CT and/or RT and describe the association of SPLUNC1 expression and collateral effects of the therapy. Material and methods A prospective randomized study was performed with two groups, chemotherapy patients ( n = 10) and head and neck radiotherapy patients ( n = 10). Unstimulated saliva for 5 min was collected before, during, and after the treatment. Clinical data and collateral effects were obtained from the patients’ charts. SPLUNC1 expression was analyzed by western blotting, and densitometry was performed. The results were statistically analyzed (ANOVA, Tukey’s, p Results Twenty patients were included in this study, (mean age of 51 years). It was observed that 60% of the patients who received RT presented hypossalivation after treatment ( p = 0.001). Higher level of SPLUNC1 occurred in RT patients who had mucositis and candidosis ( p = 0.037), in all the three collected samples. On the other hand, SPLUNC1 proteins decreased in patients submitted to chemotherapy without correlation with any side effect. Conclusions The present study describes recent findings about expression of SPLUNC1 in cancer patients who underwent chemotherapy and head and neck radiotherapy before and after the treatment. Despite the small sample, this study suggests that changes in the SPLUNC1 expression could be associated with oral side effects during radiotherapy and chemotherapy.

Abstract 5067 Introduction Myelofibrosis (MF) is a myeloproliferative neoplasm (MPN) that is characterized by ineffective hematopoiesis and symptomatic burden such as cytopenias, and splenomegaly. The prevalence of MF symptoms is relatively uniform across the 3 main subtypes: primary MF (PMF), post – polycythemia vera MF (PPV MF), and post – essential thrombocythemia MF (PET MF). Available therapies (AT) in Mexico, includes hydroxyurea (HU), interferon (IFN), for ET, besides phlebotomy for PV, as well as androgens, steroids, chemotherapy, IFN, thalidomide, EPO and radiotherapy for PMF. The only potentially curative therapy is allogeneic hematopoietic stem cell transplantation (HSCT) but treatment-related mortality remains high. Recently ruxolitinib an oral Janus kinase–2 inhibitor (JAK-2) has been approved to treat patients with MF. The safety and efficacy of Ruxolitinib has been evaluated 528 patients from COMFORT I and COMFORT II trials. Objective To report the first clinical experience in a CUP with an oral JAK–2 Inhibitor (ruxolitinib) in 40 MF patients refractory to AT in Mexico. Patients and Methods PMF patients and PPV/PET MF eligible for the ruxolitinib CUP, were diagnosed according to the 2008 WHO criteria, irrespective of JAK2 mutation status; classified as high risk; intermediate risk level 2; or, intermediate risk level 1 with an enlarged spleen; with a peripheral blood blast count of < 10%; adequate renal and liver function, platelet count >100×109/L, all of them were treated with best available therapies in Mexico. Therapy with ruxolitinib was administered to all patients. Doses were adjusted according to the platelet counts. Clinical and demographic characteristics were assessed at baseline and during the follow-up. The analyzed characteristics were: Demographic: age, gender; Clinical: Risk group, Bone marrow fibrosis grade, spleen size, ECOG, MPN subtype, JAK mutation, CBC counts;Spleen size at baseline and at week 20 of treatment. Results The median age was 64. 2 (Interval 41 – 75). Gender distribution was 46% female and 54% male. Patients according to the International Prognostic Scoring System (IPSS) were distributed in the following risk category: 10% low risk; 53. 3% intermediate – 1 risk; 26. 7 % intermediate – 2 risk; and 20% high risk. Bone marrow fibrosis grade distribution was: Grade I 46. 15%; Grade II 23. 07%; Grade III 30. 76%. Spleen length below costal margin: 20 cm, 7. 7% of patients. Spleen Average size was 9. 58 cm below costal margin at the beginning of treatment. ECOG 0 was present in 15% of patients; ECOG 1, 73%; and ECOG 2, 12% of patients. The disease subtype distribution was: PMF 45%; PPV-MF 36% and PET-MF 46%. JAK mutation was positive for 19% of patients, 46% were negative, and 35% did not have mutation analysis. The findings from the baseline to week 20 were: Splenomegaly decreased from 9. 58 cm (avg) to 4. 5 cm (avg) (53. 02% of reduction); Median Hemoglobin level was 13. 2 gr/dL at baseline versus 10. 24 gr/dL (22. 42% of decrease). Median Platelet count was 437, 000/mm3 at baseline versus 341, 503/mm3 at week 20 of treatment (21. 85% of decrease). Median time of treatment is 20. 1 weeks. Hematologic adverse events presented: Hemoglobin level decrease events (CTCAE grade 2 and 3) resolved with transfusion support. Platelet count decreases (CTCAE grade 2) were transitory and resolved after two weeks of treatment interruption. Conclusion Data showed demonstrate principal characteristics of this MF cohort. Until recently, most treatments provided only palliative care with no single treatment addressing all of the complications and symptoms of the MF. Ruxolitinib showed a primary therapeutic benefit as reduction in splenomegaly and significant improvement in MF-related symptoms in this cohort of Mexican patients with myelofibrosis. Disclosures: No relevant conflicts of interest to declare.

The interrelationship of the odontogenic lesions consisting of odontogenic epithelium with odontogenic ectomesenchyme has not been established. To give further insight into the molecular pathogenesis of these odontogenic tumors, the present study investigated allelic loss of a panel of tumor suppressor genes. Six samples of ameloblastic fibroma (AF), 3 cases of ameloblastic fibro-odontoma (AFO) and 3 ameloblastic fibrosarcomas (AFS) were included in the study. We observed loss of heterozygosity (LOH) in 2/6 samples of AF in at least one of the analyzed markers and loss in all the three samples of AFO and AFS in more than one marker. Results are shown in table 1. For the markers AFM238WF2(CHRNB1) and P53, LOH was found all the three types of lesion studied. However, the markers D3S1293, D9S157 and D9S171 showed LOH only in AFS and none of the samples included in the study showed LOH of D11S1369 and D3S1029 markers. LOH was observed for the marker D9S162 in only one sample of AFO. Our data show that AFS have distinct patterns of LOH in tumor suppressor genes compared to their benign counterparts and allelic loss of some markers may be related to tumor behavior, as AFS is a malignant odontogenic tumor and the others are benign entities. This study was supported by FAPEMIG and CAPES, Brazil. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2204. doi:10.1158/1538-7445.AM2011-2204

Ck 1* 4 (44.4%) 5 (55.6%) 1 (9.1%) 10 (90.9%) Ck 10* 6 (66.7%) 3 (33.3%) 3 (27.3%) 8 (72.7%) Ck 5 0 (0%) 9 (100%) 0 (0%) 11 (100%) Ck 14† 0 (0%) 9 (100%) 0 (0%) 11 (100%) Ck 7 9 (100%) 0 (0%) 11 (100%) 0 (0%) Ck 8 9 (100%) 0 (0%) 11 (100%) 0 (0%) Ck 16* 5 (55.55%) 4 (44.4%) 4 (36.3%) 7 (63.7%) Ck 13 0 (0%) 9 (100%) 0 (0%) 11 (100%) Ck 6* 7 (77.77%) 2 (22.2%) 2 (18.1%) 9 (81.9%) Ck 18 9 (100%) 0 (0%) 11 (100%) 0 (0%) Ck 19 7 (77.77%) 2 (0%) 10 (90.9%) 1 (9.1%)

Objective The purpose of this study was to evaluate the presence of myofibroblasts, frequently associated with a more aggressive neoplastic behavior, in oral tongue squamous cell carcinoma (TSCC) of young patients and to compare with the distribution observed in older patients. Study Design Tumor samples from 29 patients younger than 40 years old affected by TSCC were retrieved and investigated for the presence of stromal myofibroblasts by immunohistochemical reactions against α smooth muscle actin, and the results obtained were compared to TSCC cases affecting older patients. Results No positive reaction could be found in the stromal areas devoid of neoplastic tissue, whereas myofibroblasts were present in 58.6% of the lesions in young patients and in 75.9% of the older ones. No significant difference was found when comparing the invasive front and the overall stroma of both groups, and no correlation could be obtained with stromal α smooth muscle actin expression, higher tumor grades or clinical stage ( P > .05). Conclusion There was no significant difference between the presence of stromal myofibroblasts of TSCC affecting young and old individuals.

Tumores de glândulas salivares apresentam caracteristicas histopatologicas altamente heterogeneas. Existem poucos estudos epidemiologicos analisando um numero elevado de tumores de glândulas salivares benignos e malignos no Brasil. MATERIAL E METODOS: Revisamos os prontuarios hospitalares de 124 pacientes com tumores de glândulas salivares durante o periodo de Janeiro de 1993 ate Dezembro de 1999. Os pacientes foram analisados de acordo com o sexo, idade, tamanho do tumor, localizacao e tipo histopatologico. RESULTADOS E CONCLUSOES: Pacientes com tumores benignos e malignos apresentaram uma media de idade de 47,7 e 48,8 anos, respectivamente. A frequencia de ocorrencia dos tumores benignos foi de 80% (n=99) e dos tumores malignos de 20% (n=25). Tumores foram localizados na parotida em 71% (n=88) dos casos, na glândula submandibular em 24% (n=30), e glândulas salivares menores em 5% (n=6). Os principais tumores benignos foram o Adenoma Pleomorfico que representou 84% (n=84) dos casos e o Tumor de Warthin com 13% (n=13) dos casos. Entre os tumores malignos, o Carcinoma Mucoepidermoide foi o mais comum correspondendo a 52% dos casos (n=13), seguido pelo Carcinoma Adenoide Cistico em 20% (n=5) e Carcinoma ex Adenoma Pleomorfico que foi detectado em 12% dos casos (n=3).

Pigmented villonodular synovitis (PVNS) is an aggressive proliferative lesion that usually involves the synovial tissues of big joints. To date, there are ∼52 cases of PVNS affecting the temporomandibular joint reported in the English-language literature, about one-third of them exhibiting intracranial involvement. We herein describe an additional case of PVNS of the temporomandibular joint with skull base invasion affecting a 26-year-old male patient and discuss its clinicopathologic features considering previously published cases. Histopathology and imaging evaluation are important for the diagnosis of PVNS, which should be included in the differential diagnosis of preauricular aggressive swellings.

Linear verrucous epidermal nevi (LVEN) are characterized by verrucous papules often coalescing into well-demarcated skin-colored or brown plaques following the lines of Blaschko. We present two new cases of LVEN with oral mucosa involvement and briefly discuss this very rare finding. In both cases, oral biopsies showed hyperkeratosis, acanthosis, and papillomatosis. Although several treatment modalities have been reported for the cutaneous lesions, there is no consensus for the management of oral lesions so far.

Oncocytic metaplasia (OM) is not a well-known feature in inflammatory fibrous hyperplasia (IFH) lesions, although it may be common, as proposed in our previous study about this lesion. In the present paper, we assessed the histopathological and immunohistochemical features of 18 cases of IFH containing OM areas. All the samples were examined on haematoxylin and eosin stained sections and cytokeratins (AE1/AE3, 34betaE12, CK5, CK7, CK8, CK13, CK14 and CK19), CD15, CD20, CD68, CD45Ro, and LCA primary antibodies were used. The vast majority of IFH occurred in women (n=14) and the most common site of presentation was the buccal vestibule. Oncocytic and salivary duct cells showed uniform immunoreactivity for AE1/AE3, CK7, CK8 and CK19. CD45Ro+ T-lymphocytes were the most common inflammatory cells surrounding the OM areas followed by CD20+ B-lymphocytes. These findings suggest that oncocytic cells present in IFH might develop from salivary duct epithelium, and T-lymphocytes might play an important role in its etiopathogenesis.

BACKGROUNDRetrospective studies to assess the distribution of oral diseases (ODs) are helpful in estimating the prevalence of oral diagnoses in the population, and thus help in preventive and curative services. Prevalence and frequency data for ODs are available from many countries, but information from Chile is scarce.METHODSThis study investigated the frequency of ODs in a Chilean population. For this, we included all patients treated at the University of Talca (UTALCA, Chile) between 2001 and 2014. Patient characteristics were retrieved from medical files. To contextualize our results, we conducted a systematic review (SystRev) using Publish or Perish software (PoP), Google Scholar and MEDLINE/PubMed.RESULTSOne hundred sixty-six ODs were diagnosed, and the most prevalent groups were soft tissue tumours, epithelial pathology and salivary gland pathology. Individually, irritation fibroma, oral lichen planus (OLP) and mucocele were the most common diagnoses. ODs frequently affected unspecified parts of the mouth (including cheek, vestibule and retromolar area), gum, lips, tongue and palate. In the SystRev, the more studied diagnoses were leukoplakia, OLP and recurrent aphthous stomatitis; prevalent lesions included Fordyce’s spots, recurrent aphthous stomatitis and fissured tongue. Chilean patients and SistRev shared almost all ODs.CONCLUSIONThe results reflect ODs diagnosed in a specialized service of oral pathology and medicine in Chile and will allow the establishment of preventive/curative policies, adequate health services and dentistry curriculum.

The aim of this study was to determine expression, not previously described, of PLUNC (palate, lung, and nasal epithelium clone) (BPI-fold containing) proteins in major and minor salivary glands from very early fetal tissue to the end of the second trimester and thus gain further insight into the function of these proteins. Early fetal heads, and major and minor salivary glands were collected retrospectively and glands were classified according to morphodifferentiation stage. Expression of BPI-fold containing proteins was localized through immunohistochemistry. BPIFA2, the major BPI-fold containing protein in adult salivary glands, was detected only in the laryngeal pharynx; the lack of staining in salivary glands suggested salivary expression is either very late in development or is only in adult tissues. Early expression of BPIFA1 was seen in the trachea and nasal cavity with salivary gland expression only seen in late morphodifferentiation stages. BPIFB1 was seen in early neural tissue and at later stages in submandibular and sublingual glands. BPIFA1 is significantly expressed in early fetal oral tissue but BPIFB1 has extremely limited expression and the major salivary BPIF protein (BPIFA2) is not produced in fetal development. Further studies, with more sensitive techniques, will confirm the expression pattern and enable a better understanding of embryonic BPIF protein function.

Adenoid cystic carcinoma (ACC) has a significant patient-population in need of effective systemic therapy, as no drug is currently approved by the FDA for its management. We critically reviewed ACC-clinical trials (CT) registered on the ClinicalTrials.gov website using "ACC" under condition or disease. Trials specifically designed to test a drug-based therapy for ACC (n = 33) were analyzed with most being one-arm phase II trials enrolling advanced, recurrent/metastatic, incurable ACC cases. Site restriction, maximum ECOG status, and period of disease progression varied as inclusion criteria. Small-molecule inhibitors were those most commonly investigated with Apatinib, Axitinib and Lenvatinib showing the best results in association with rigid enrollment criteria. The overall median time to progression remains modest and more efforts are urgently needed in this field. CTs designed to test drugs that act on key pathways associated with ACC aggressiveness are being conducted and represent a promising pathway if efficacy is proved.

O presente estudo teve como objetivos avaliar a sensibilidade, a especificidade e a acurácia da Punção Aspirativa por Agulha Fina (PAAF) em nódulos submucosos da cavidade bucal e da região de cabeça e pescoço como ferramenta auxiliar de diagnóstico. Foram selecionados 50 pacientes consecutivamente que procuraram a Clínica da Disciplina de Estomatologia Clínica da FOUSP, portadores de lesões em boca e em região de cabeça e pescoço. O material obtido pela PAAF foi enviado a um mesmo patologista apenas com o diagnóstico clínico e após a emissão do laudo da PAAF o laudo do anátomo patológico era emitido servindo como padrão ouro. Após os cálculos, o resultado da sensibilidade foi de 75%, a especificidade foi de 96%, a acurácia foi de 58,8%, o valor preditivo positivo foi de 86% e o valor preditivo negativo foi de 93%. A significância foi estabelecida para 5% e o teste usado foi o teste de Kappa com valor de P