The relevance of miRNAs as promising biomarkers in lip cancer.

OBJECTIVES: This study aimed to analyze the expression of miR-181b, miR-21, miR-31, and miR-345 in actinic cheilitis with and without epithelial dysplasia and lower lip squamous cell carcinomas, and to verify if the deregulated expression of these miRNAs would be indicative of malignant transformation. MATERIALS AND METHODS: The sample was selected from formalin-fixed paraffin-embedded tissues of 19 actinic cheilitis without epithelial dysplasia, 32 actinic cheilitis with epithelial dysplasia, 42 lower lip squamous cell carcinomas, and 10 nonaltered oral mucosa of the lip. The microRNA (miR, miRNA) expression was quantified by real-time RT-PCR and the expression of the selected miRNAs among the groups of actinic cheilitis and lower lip cancer was compared by chi-square. RESULTS: A higher expression of miR-181b, miR-31, and miR-345 was found in actinic cheilitis without epithelial dysplasia in comparison to that in actinic cheilitis with epithelial dysplasia and with lower lip cancer. There were no differences in miR-21 expression between actinic cheilitis and lower lip cancer. Hierarchical clustering analysis showed a tendency for a downregulation of miR-181b, miR-21, miR-31, and miR-345 in most patients with lower lip cancers. CONCLUSIONS: The upregulation of miR-181b, miR-31, and miR-345 expression in actinic cheilitis without epithelial dysplasia and the decrease in the expression of these miRNAs in actinic cheilitis with epithelial dysplasia and in lower lip cancer are potential biomarkers of malignant progression. CLINICAL RELEVANCE: This miRNA signature can help to identify actinic cheilitis with potential to progress to lip cancer.

Osseous Flap of Galea and Periosteum Filled With Mesenchymal Stem Cells, Platelet-Rich Plasma, Bone Dust, and Hyaluronic Acid.

Reconstructive surgery to craniofacial deformities caused by tumor ressections, traumas or congenital malformation are frequent in medicine practice. It aims to provide the patients with better quality of life and functional improvement of speech, breathing, chewing, and swallowing. Many are the techniques described in the literature to recover bone defects. This study evaluated a vascularized galeal and periosteum flap in rabbits, which could possibly substitute the bone graft in reconstructive surgery, especially for facial defects. It involved rabbits, divided into 12 groups, submitted to a surgical procedure to construct the galea and periosteum cranial flap filled with fragments of cranial bone, platelet-rich plasma, mesenchimal stem cells, and hyaluronic acid. The evaluation methods included image examinations and histological analysis.The results demonstrated bone formation with the use of platelet-rich plasma, mesenchimal stem cells, and bone fragments. The use of several enrichment materials of osseous cellular stimulation improved the quality and bone tissue organization. The more enrichment factor used, the better the tissue quality result was.Much research should be done to improve the methods and to analyze if results in human have the same bone formation as it happened in rabbits.

Apoptotic index for prediction of postmolar gestational trophoblastic neoplasia.

BACKGROUND: Although 85% of patients with a complete hydatidiform mole achieve spontaneous remission after a few months, 15% of them will experience gestational trophoblastic neoplasia, which requires chemotherapy. To date, there is no biomarker to predict post-molar gestational trophoblastic neoplasia before the initiation of human chorionic gonadotropin surveillance. OBJECTIVE: The purpose of this study was to assess the relationship between the expression of apoptosis markers in the molar villous trophoblasts and the subsequent development of gestational trophoblastic neoplasia after the evacuation of a complete hydatidiform mole. STUDY DESIGN: This was a retrospective cohort study of patients with complete hydatidiform mole who were diagnosed, treated, and followed at the Center of Trophoblastic Diseases (Botucatu/São Paulo State and Rio de Janeiro/Rio de Janeiro State, Brazil) from 1995-2014. Patients were divided temporally into derivation (1995-2004) and validation (2005-2014) cohorts. Immunohistochemistry was used to examine tissue expression of the apoptosis inhibitor survivin or the pro-apoptotic enzyme caspase-3. Survivin stains for cytoplasmic and nuclear expression were evaluated independently. Caspase-3 expression was measured as an apoptotic index of positive staining cells over negative staining cells multiplied by 100. Receiver operating characteristic curves were then constructed, and the area under the curve was calculated to test the performance characteristics of the staining to predict the subsequent development of gestational trophoblastic neoplasia. RESULTS: The final study population comprised 780 patients, with 390 patients in each temporal cohort: 590 patients entered spontaneous remission, and 190 patients experienced post-molar gestational trophoblastic neoplasia. Neither nuclear nor cytoplasmic survivin expression performed well as a predictor of subsequent gestational trophoblastic neoplasia. The caspase-3 apoptotic index was a strong risk factor for subsequent gestational trophoblastic neoplasia development. When the apoptotic index was <4%, the risk of gestational trophoblastic neoplasia had an odds ratio of 35.55 (95% confidence interval, 14.02-90.14; P < .0001) in the derivation cohort and an odds ratio of 25.71 (95% confidence interval, 10.13-65.29; P < .0001) in the validation cohort. However, in both cohorts, the positive predictive value for gestational trophoblastic neoplasia of an apoptotic index <4.0% was modest (49% in the derivation cohort and 41% in the validation cohort); the negative predictive value for gestational trophoblastic neoplasia of an apoptotic index ≥4.0% was high (97% in both cohorts). CONCLUSION: The subsequent development of gestational trophoblastic neoplasia after evacuation of complete hydatidiform mole is tied closely to the apoptotic index, which may be a useful biomarker for future prospective studies.

Loss of cytokeratin 10 indicates malignant transformation in actinic cheilitis.

OBJECTIVES: The aim of this study was to investigate the relationship the expression of cytokeratins (CK10 and CK13) and the cell proliferation index determined by Ki-67 of lip squamous cell carcinoma and actinic cheilitis with different degrees of dysplasia. MATERIALS AND METHODS: Forty-five paraffin-embedded actinic cheilitis with and without dysplasia and 20 lip squamous cell carcinoma were analyzed by immunohistochemistry using anti-human anti-CK10, anti-CK13, and anti-Ki-67 antibodies. RESULTS: The majority of actinic cheilitis showed immunopositivity for CK10 and CK13 with decrease or loss of expression in dysplastic areas. In lip squamous cell carcinoma of the lip, heterogeneous expression of CK13 and immunonegativity for CK10 were observed. There was a statistically significant difference between CK10 expression in lip squamous cell carcinoma and in actinic cheilitis with or without dysplasia (p < 0.001). The cell proliferation index was higher in actinic cheilitis with dysplasia and lip squamous cell carcinoma than in actinic cheilitis without epithelial dysplasia. A significant correlation was found between the intensity of the epithelial dysplasia and the cell proliferation index (p < 0.001). CONCLUSION: These results provide evidence that there is a downregulation of CK10 expression in dysplastic areas of patients with actinic cheilitis and in those with lip squamous cell carcinoma (LSCC) and that the index of cell proliferation, determined by Ki-67, is directly correlated with the intensity of the epithelial dysplasia. CLINICAL RELEVANCE: Altogether, these results suggest that CK10 expression and the epithelial cell proliferation index can help to identify malignant transformation in the lip region.

Paracoccidioidomycosis in patients with lymphoma and review of published literature.

This paper describes four new cases of lymphomas, two Hodgkin lymphomas and two non-Hodgkin lymphomas in patients with paracoccidioidomycosis. All had mycosis diagnosed before lymphomas with Paracoccidioides brasiliensis demonstrated in several lymph nodes, as seen in the disseminated form of the disease. When lymphoma was diagnosed, one patient was under regular paracoccidioidomycosis treatment and in clinic-serological remission for this disease, another was under regular treatment but with clinic-serological mycosis activity, one had abandoned paracoccidioidomycosis treatment 6 years earlier, and the other had not yet received any kind of antifungal drugs. Three patients received treatment for lymphomas with one remaining in remission until now, one achieving tumor remission which relapsed years later, and one having only residual lymphoma in bone marrow for a decade but clinically well. All three experienced paracoccidioidomycosis clinical remission, however, serology became negative just in one. Similar previously described cases were reviewed: five Hodgkin lymphomas, three non-Hodgkin lymphomas, and one described only as "lymphoma" without specifying type; a summary of their findings is presented. Finally, there is also a brief discussion on the possible pathophysiological mechanisms involved in the concomitance of these two disorders.

Tissue-engineered blood vessel substitute by reconstruction of endothelium using mesenchymal stem cells induced by platelet growth factors.

BACKGROUND: Cardiovascular diseases remain leaders as the major causes of mortality in Western society. Restoration of the circulation through construction of bypass surgical treatment is regarded as the gold standard treatment of peripheral vascular diseases, and grafts are necessary for this purpose. The great saphenous vein is often not available and synthetic grafts have their limitations. Therefore, new techniques to produce alternative grafts have been developed and, in this sense, tissue engineering is a promising alternative to provide biocompatible grafts. This study objective was to reconstruct the endothelium layer of decellularized vein scaffolds, using mesenchymal stem cells (MSCs) and growth factors obtained from platelets. METHODS: Fifteen nonpregnant female adult rabbits were used for all experiments. Adipose tissue and vena cava were obtained and subjected to MSCs isolation and tissue decellularization, respectively. MSCs were subjected to differentiation using endothelial inductor growth factor (EIGF) obtained from human platelet lysates. Immunofluorescence, histological and immunohistochemical analyses were employed for the final characterization of the obtained blood vessel substitute. RESULTS: The scaffolds were successfully decellularized with sodium dodecyl sulfate. MSCs actively adhered at the scaffolds, and through stimulation with EIGF were differentiated into functional endothelial cells, secreting significantly higher quantities of von Willebrand factor (0.85 µg/mL; P < .05) than cells cultivated under the same conditions, without EIGF (0.085 µg/mL). Cells with evident morphologic characteristics of endothelium were seen at the lumen of the scaffolds. These cells also stained positive for fascin protein, which is highly expressed by differentiated endothelial cells. CONCLUSIONS: Taken together, the use of decellularized bioscaffold and subcutaneous MSCs seems to be a potential approach to obtain bioengineered blood vessels, in the presence of EIGF supplementation.

Usefulness of clinical, ultrasonographic, hysteroscopic, and immunohistochemical parameters in differentiating endometrial polyps from endometrial cancer.

STUDY OBJECTIVE: To evaluate the usefulness of clinical, ultrasonographic, hysteroscopic, and immunohistochemical parameters in differentiating endometrial polyps from endometrial cancer. DESIGN: Cross-sectional study (Canadian Task Force classification II-2). SETTING: Tertiary public hospital, university teaching center. PATIENTS: Eighty-two women who underwent hysteroscopic polypectomy and 20 women who underwent surgery to treat endometrial cancer. INTERVENTIONS: Analysis of medical records and immunohistochemical assessment of estrogen receptors, progesterone receptors, and endothelial markers CD34 and CD105. MEASUREMENTS AND MAIN RESULTS: Among women with endometrial cancer and endometrial polyps, respectively, mean age was 63 and 57 years (p = .01), 89% and 67% were postmenopausal (p < .05), and 85% and 30.5% had postmenopausal bleeding (p < .01). No sonographic parameter enabled differentiation of endometrial polyp from cancer. Of patients with endometrial cancer, 72% exhibited signs suggestive of hyperplasia, and endometrial polyps were diagnosed during hysteroscopy. Estrogen receptors (≥ 2 vs ≥ 1; p < .001) and progesterone receptors (≥ 3 vs ≥ 2; p = .07) were greater in endometrial polyps. There was no significant difference in microvessel density (p > .05). CONCLUSIONS: Ultrasonographic parameters and endothelial markers did not enable differentiation of polyps from endometrial neoplasia. Postmenopausal bleeding and endometrial hypervascularization along with vascular atypia at diagnostic hysteroscopy showed a greater association with endometrial cancer.

STEAP1 protein overexpression is an independent marker for biochemical recurrence in prostate carcinoma.

AIMS: To investigate the prognostic value of expression levels of the genes STEAP1 and STEAP2, and of STEAP1 protein, in prostate carcinomas (PCa). METHODS AND RESULTS: STEAP1 and STEAP2 transcript levels were evaluated by RT-qPCR in samples from 35 PCa, 24 adjacent non-neoplastic prostate (AdjP) tissues, five cases of benign prostatic hyperplasia (BPH), and two histologically normal prostates (N). STEAP1 expression was assessed by immunohistochemistry in samples from 198 PCa, 76 AdjP, 22 BPH, and two N. The findings were compared with clinical and pathological parameters and patient outcome. STEAP1 and STEAP2 transcript analysis showed no differences between the groups tested. Although not significant, higher STEAP1 mRNA levels were detected in tumours with high Gleason scores and in patients who presented with biochemical recurrence (BCR). STEAP1 overexpression was detected in PCa, and was significantly associated with high-grade Gleason scores, seminal vesicle invasion, BCR, and worse outcome (metastasis or PCa-specific death). STEAP1 overexpression was significantly associated with shorter BCR-free survival. Multivariate analysis revealed that STEAP1 is an independent marker for BCR. CONCLUSIONS: These findings provide evidence that STEAP1 is a biomarker of worse prognosis in PCa patients.

Chromosomal imbalances exclusively detected in invasive front area are associated with poor outcome in laryngeal carcinomas from different anatomical sites.

Laryngeal squamous cell carcinoma (LSCC) is a malignant neoplasm exhibiting aggressive phenotype, high recurrence rate, and risk of developing second primary tumors. Current evidence suggests that cells in the invasive front of carcinomas have different molecular profiles compared to those in superficial areas. This study aimed to identify candidate genes in the invasive front and superficial cells from laryngeal carcinomas that would be useful as molecular markers. Invasive front and tumor surface cells of 32 LSCC were evaluated by high-resolution comparative genomic hybridization. Both CCND1 copy number gains and cyclin D1 protein expression were evaluated to confirm gains of 11q13.3. Losses of 3q26.2-q29 and 18q23 were confirmed by loss of heterozygosity analysis. The most frequent chromosomal alterations observed only in invasive front cells involved gains of 1p, 4q, and 9p and losses of 3p, 11p, 12p, 13q, 17q, 18p, 19q, 20q, 21q, and Xp. Gains of 11q13 were detected in both components from glottis and supraglottis but only in invasive front cells from transglottic tumors. Fluorescence in situ hybridization confirmed gains of CCND1/CPE11 in a subset of cases. In supraglottic tumors, cyclin D1 positivity was associated with distant metastasis (P = 0.0018) and with decreased disease-free survival (P = 0.042). Loss of heterozygosity at 3q26.2 and 18q23 were associated with lymph node involvement (P = 0.055) and worsened prognosis, respectively. In conclusion, this study revealed regions that could be targeted in the search for molecular markers in LSCC. Cyclin D1 may be useful as a prognostic marker in supraglottic tumors.

Comparative study of the behavior of p53 immunoexpression in smoking associated lesions: Reinke's edema and laryngeal carcinoma.

OBJECTIVE: To assess the behavior of the immunoexpression of protein p53 in Reinke's edema and laryngeal squamous cell carcinoma. STUDY DESIGN: retrospective. METHODS: we recovered the histological paraffin blocks of patients who were subjected to Reinke's edema and laryngeal squamous cell carcinoma surgery in 2000-2011. The paraffin blocks were cut into 3-µm sections; the specimens were prepared in silanized slides (one slide for each paraffin block) and subjected to immunohistochemical reaction according to the Avidin Biotin Peroxidase method. Monoclonal primary anti-p53 antibodies were used at 1:50 dilution. Slides were examined under a light microscope at different magnitudes and results were interpreted based on the degree of brown staining in the nuclei of epithelial cells and in the extent of the fragment by using a semi-quantitative score from 0 to 3. RESULTS: 67 slides of Reinke's edema and 60 slides of laryngeal squamous cell carcinoma were included. Scores 2 and 3 for staining of the nuclei of epithelial cells were recorded for 46 slides of Reinke's edema (68.65%) and for 57 slides of laryngeal squamous cell carcinoma (95%). As to the extent of the fragment, scores 2 and 3 were recorded for 74% slides of Reinke's edema and for 95% slides of carcinomas. CONCLUSION: the positive immunoexpression for protein p53, positive in 95% carcinomas and 74% Reinke's edemas, makes us aware of the possible preneoplastic condition of the latter lesion. Further studies are needed to identify and reveal the genetic changes that lead to these results.

Master Regulators of Epithelial-Mesenchymal Transition and WNT Signaling Pathways in Juvenile Nasopharyngeal Angiofibromas.

Juvenile nasopharyngeal angiofibroma (JNA) is a rare fibrovascular benign tumor showing an invasive growth pattern and affecting mainly male adolescents. We investigated the role of epithelial-mesenchymal transition (EMT) and WNT signaling pathways in JNA. Gene expression profiles using nine JNA paired with four inferior nasal turbinate samples were interrogated using a customized 2.3K microarray platform containing genes mainly involved in EMT and WNT/PI3K pathways. The expression of selected genes (BCL2, CAV1, CD74, COL4A2, FZD7, ING1, LAMB1, and RAC2) and proteins (BCL2, CAV1, CD74, FZD7, RAF1, WNT5A, and WNT5B) was investigated by RT-qPCR (28 cases) and immunohistochemistry (40 cases), respectively. Among 104 differentially expressed genes, we found a significantly increased expression of COL4A2 and LAMB1 and a decreased expression of BCL2 and RAC2 by RT-qPCR. The immunohistochemistry analysis revealed a low expression of BCL2 and a negative to moderate expression of FZD7 in most samples, while increased CAV1 and RAF1 expression were detected. Moderate to strong CD74 protein expression was observed in endothelial and inflammatory cells. A significant number of JNAs (78%) presented reduced WNT5A and increased WNT5B expression. Overall, the transcript and protein profile indicated the involvement of EMT and WNT pathways in JNA. These candidates are promising druggable targets for treating JNA.

p53 and p21 expression in bone marrow clots of megaloblastic anemia patients.

The pathogenesis of megaloblastic hemopathies (MH) is centered on the deficiency of vitamin B12 and folic acid with interruption of erythrocyte maturation. This study researched the participation of p53 and p21 in the pathophysiology of the disease. A retrospective study enrolled 95 patients with histopathologic diagnosis by biopsy or bone marrow clot (BMB/BMC), with clinical review and immunohistochemical study in tissue microarray (TMA) for p53 and p21, detailing their marking location. All patients had BMC and only 11 had BMB. The CMO was a differential of this study and it allowed an expanded sample. In the TMA, 63.7% (58/91) of the samples were immunopositive for p53; and 35.2% (31/88) were immunopositive for p21. Nuclear staining, divergent from the literature, was observed in 17.3% (10/58) among those p53+ and in 38.7% (12/31) among those p21+. The pattern of immunostaining showed non-significant differences (P=0.474) regarding morphologic and clinical aspects. The positivity for both may indicate an effective balance between apoptosis and anti-apoptotic action. Excessive inhibition of apoptosis would contribute to high global cellularity, but without functional maturation effectiveness. In conclusion, there is p21 and/or p53 immunoexpression in most cases of this study and there is no clear association between immunoexpression pattern and patient outcome. Unlike the literature, we also found a percentage of nuclear immunostaining, but the finding was not statistically significant. Combination of p21 and p53 results created different possibilities of pathologic interpretation for MH, reinforcing the importance of studies similar to this one.

Increased DSG2 plasmatic levels identified by transcriptomic-based secretome analysis is a potential prognostic biomarker in laryngeal carcinoma.

OBJECTIVES: The tumor secretome deconvolution is a promising strategy to identify diagnostic and prognostic biomarkers. Here, transcriptomic-based secretome analysis was performed aiming to discover laryngeal squamous cell carcinomas (LSCC) biomarkers from potentially secreted proteins (PSPs). MATERIAL AND METHODS: The tumor expression profile (35 LSCC biopsies compared with surrounding normal tissues - SN) revealed 589 overexpressed genes. This gene list was used for secretome analysis based on laryngeal tumors and related secretome databases. RESULTS: Forty-nine (Laryngeal tumor secretome database) and 50 (Human Protein Atlas and Cancer Secretome Database) PSPs presented an association with worse overall survival. Specifically, DSG2 overexpression was strongly correlated with poor survival and distant metastasis. DSG2 increased expression was confirmed in the LSCC dataset (LSCC = 111; SN = 12) from TCGA. A significant association between shorter survival and DSG2 overexpression was also detected. In an independent cohort of cases, we analyzed and confirmed high protein levels of DSG2 in plasma from LSCC patients. CONCLUSION: A set of PSPs including the circulating DSG2, were associated with shorter overall survival in LSCC. DSG2 overexpression was also correlated with distant metastasis. The high plasmatic protein levels of DSG2 suggest its potential to be tested in liquid biopsies and applied as prognostic biomarker of LSCC.

Effects of cyclosporine on ischemia-reperfusion injuries in rat kidneys. An experimental model.

PURPOSE: To assess Cyclosporine A (CsA) therapy at an intraperitoneal dose of 15 mg.kg -1 in a rodent model of non-septic renal ischemia. METHODS: Twenty male Wistar rats were randomized to receive CsA therapy or none therapy before undergoing 30 minutes of renal ischemia followed by reperfusion. Additionally, 10 rats were randomized to undergo the same surgical procedure of the aforementioned animals with neither ischemia nor CsA therapy. Twelve hours after kidney ischemia, the left kidneys were evaluated for histological injury according to Park's criteria. Serum creatinine (Cr), urea nitrogen (Ur) and sodium levels were obtained at different times of the experimental protocol. RESULTS: Rodents in the CsA group showed negative results (p<0.05) in serum variables (Cr: 0.41±0.05mg/dL vs . 4.17±1.25mg/dL; Ur: 40.90±3.98mg/dL vs . 187.70±22.93mg/dL) even the non CsA or control group (Cr: 0.35±0.07mg/dL vs . 3.80±1.20mg/dL; Ur: 40.10±4.70mg/dL vs . 184.50±49.80mg/dL). The negative results were also verified in histological evaluation, CsA group had 50% in the very severe grade of lesion, 10% in the severe and 40% in the moderate to severe whereas the control group had 90% in the very severe grade. CONCLUSION: CsA was incapable of preventing the deleterious effects of ischemia-reperfusion injury in rat kidneys.

Integrated miRNA and mRNA expression analysis uncovers drug targets in laryngeal squamous cell carcinoma patients.

OBJECTIVES: The current treatment of laryngeal squamous cell carcinoma (LSCC) is based on radical surgery and radiotherapy resulting in high morbidity. Chemoradiotherapy has been used as alternative to organ sparing; however, several advanced cases presented resistance to treatment, which contributes to a high risk of recurrence and mortality. Coding RNAs and miRNAs have potential to be used as biomarkers or targets for cancer therapy. MATERIALS AND METHODS: In this study, 36 LSCC and 5 non-neoplastic control samples were investigated using miRNA and mRNA large-scale expression analysis and a cross-validation was performed using the TCGA database (116 LSCC and 12 surrounding normal tissues). RESULTS: The large-scale profiling revealed the involvement of 28 miRNAs and 817 genes differentially expressed in LSCC. An integrative analysis comprising predicted and experimentally validated miRNA/mRNA interactions (negatively correlated), resulted in 28 miRNAs and 543 mRNAs. Decreased expression of miR-199b was significantly associated with shorter disease-free survival in LSCC (internal and TCGA datasets). The expression levels of selected miRNAs (miR-199b-5p, miR-29c-3p, miR-204-5p, miR-125b-5p and miR-92a-3p) and genes (COL3A1, COL10A1, ERBB4, HMGA2, HLF, TOP2A, MMP3, MMP13, MMP10 and PPP1R3) were confirmed as altered in LSCC by RT-qPCR. Additionally, a drug target prediction analysis revealed drug combinations based on miRNA and mRNA expression, pointing out novel alternatives to optimize the LSCC treatment. CONCLUSION: Collectively, these findings provide new insights in the LSCC transcriptional deregulation and potential drug targets.

Is there a role for fibronectin upon true histiocytic lymphoma progression?

Cell interaction with extracellular matrix is a crucial event for various biological processes, including tumor progression. Although not exclusively, these interactions are frequently mediated by bidirectional signaling receptors known as integrins. Using a human histiocytic lymphoma-derived cell line (U-937), we evaluated the effects of ECM proteins and their integrin-type receptors in the regulation of cell attachment, proliferation, migration and survival. Fibronectin induces higher cell attachment in vitro when compared to laminin. Fibronectin also promotes a decrease in cell migration but do not modulate cell proliferation and death. Pre-incubation of U-937 cells with VLA-5 antagonistic peptides inhibited attachment of the cells to fibronectin-coated substrates. In a second vein, we observed that lymph node specimens obtained from diagnosed patient for true histiocytic lymphoma had greater deposition of fibronectin (but not laminin) around malignant clones. These results suggest that fibronectins play a relevant role in the establishment and progression of true histiocytic lymphoma cells.

Perivascular epithelioid cell tumor of the liver coexisting with a gastrointestinal stromal tumor.

Approximately 10% of patients with gastrointestinal stromal tumors (GIST) develop other neoplasms, either synchronously or metachronously. In this report we describe coexistence of a gastrointestinal stromal tumor and a hepatic perivascular epithelioid cell tumor (PEComa) in a 51-year-old woman with no evidence of tuberous sclerosis. A subcapsular hepatic nodule (0.8 cm in diameter) was found during surgery for symptomatic gastric neoplasm (15 cm in diameter) arising from the lesser curvature. Both tumors revealed histomorphological and immunohistochemical features confirming a diagnosis of a small incidental hepatic PEComa and a high risky extramural gastric GIST, respectively. The patient remained disease-free 25 mo after surgery with no evidence of tumor recurrence or new neoplasms. To our knowledge, this is the first report of PEComa in a patient with GIST. Hepatic lesions detected synchronously or metachronously in patients with GISTs may represent histogenetically distinct lesions and should be sampled to confirm or exclude metastatic GISTs.

[Non-Hodgkin orbital lymphoma: case report]. / Linfoma não-Hodgkin de órbita: relato de caso.

The purpose is to report an unusual case of orbital non-Hodgkin lymphoma. A 75-year-old man presented with bilateral chronic epiphora complaint and inferior eyelid tumors, axial proptosis, without previous systemic manifestation. The patient was submitted to bilateral endonasal dacryocystorhinostomy twice and the epiphora complaint persisted. The inferior eyelid and bone marrow biopsy revealed non-Hodgkin lymphoma. The patient was treated with systemic chemotherapy and dacryocystorhinostomy with good resolution. The precise diagnosis and the treatment were very important to reach a good resolution of the bilateral epiphora complaint.