PRAME and Historical Immunohistochemical Antibodies Ki-67, P16, and HMB-45 in Ambiguous Melanocytic Tumors.

ABSTRACT: Ambiguous melanocytic lesions/tumors (AMLs) can be simply described as melanocytic neoplasms that cannot be differentiated as either a melanoma or a nevus. Preferentially expressed antigen in melanoma (PRAME) is a novel antibody that can help differentiate between nevi and melanomas. However, its usefulness remains controversial in AMLs. The aim of this study was to demonstrate the importance of PRAME and diagnostic auxiliary antibodies (Ki-67, p16, HMB-45) in the diagnosis of melanocytic lesions, especially in AMLs. This study included 52 ambiguous melanocytic lesions, 40 nevi, and 40 melanomas. All immunohistochemical studies were performed automatically using the Universal Alkaline Phosphatase Red Detection Kit. Different analytic approaches were used for each antibody based on the literature. Statistically, the multinomial forward stepwise elimination logistic regression analysis was used to create a statistical model to predict the diagnosis of melanocytic lesions based on clinical, morphological, and immunohistochemical data. PRAME positivity was very strong and diffuse in the melanoma group and statistically significantly higher than that of the AML and nevus groups. There was no statistically significant difference between the nevus and AML groups. The Ki-67 proliferation index and HMB-45 staining pattern provided valuable indications for distinguishing between these 3 groups. The P16 antibody was limited in supporting the differential diagnosis. Our statistical model showed that a high mitosis count, central pagetoid spread, and PRAME positivity increased the probability of melanoma against an AML diagnosis. This study showed the advantages of evaluating the PRAME antibody together with morphological features and other immunohistochemical markers (Ki-67 and HMB-45) in the differential diagnosis of melanocytic lesions.

Endoscopic endonasal approach to the cavernous sinus Epstein-Barr virus-positive B cell non-Hodgkin lymphoma in a child: case report.

Cavernous sinus (CS) lymphoma without paranasal sinuses involvement is extremely rare in pediatric population and remains a diagnostic challenge due to its similarity to other tumors located in this area. An 8-year-old boy presented with a 6-day history of gradually developing ptosis in the right eyelid. After admission, his symptoms progressed within 24 h to include right-sided ophthalmoplegia consisting of oculomotor and abducens nerve palsies. Endoscopic endonasal approach (EEA) was performed urgently to decompress the CS and to obtain a diagnosis. The postoperative course was uneventful, and there was no complication related to the surgical approach. No immunodeficiency was identified. The histopathological diagnosis was an Epstein-Barr virus (EBV)-positive high-grade mature B cell non-Hodgkin lymphoma. He was initiated chemotherapy according to COG ANHL01P1 protocol. Two months after surgery, the third and sixth nerve palsies had resolved completely. Currently, he is well and has no clinical or radiological recurrence. This is the first pediatric case with EBV-positive CS lymphoma that underwent EEA for the diagnosis and decompression. In the pediatric population, EEA enables minimally invasive access to the CS and can play an alternative role in the management of CS lesions, either through biopsy or debulking.

Investigation of the effect of isolated mitochondria transplantation on renal ischemia-reperfusion injury in rats.

Ischemia/Reperfusion (I/R) injury is clinically important in many surgical practice including kidney transplantation. It is known that mitochondria have a key role in the intracellular and extracellular signaling pathways of ischemia and reperfusion injury. In this respect, we pointed to explore the probable effects of isolated mitochondria transplantation from MSCs (mesenchymal stem cells), to alleviate ischemia/reperfusion-induced renal injury. Experiments were held on the 48 male Sprague Dawley rats. Groups were divided as Control (C1), I/R-Control (C2), Vehicle-1 (V1), Vehicle-2 (V2), Transplantation-1 (T1) and Transplantation-2 (T2) group. Unilaterally nephrectomy was performed in all groups. In the groups except the control, the left kidneys ischemized for 45 min and then reperfusion was carried out. According to the study groups, isolated mitochondria or vehicle infused into the renal cortex and rats were monitored for 48 h. Following that mentioned procedure, animals were sacrificed and biological samples were taken for physiological, histological and biochemical examinations. The results of present study show that mitochondrial transplantation promoted proliferation and regeneration of tubular cells after renal injury. Moreover, mitochondrial transplantation reduced mitochondrial dynamics-DRP-1 fission protein of tubular cells and reversed renal deficits. Mitochondrial transplantation diminished apoptotic markers including TUNEL and Caspase-3 levels in injured renal cells. Our results provide a direct link between mitochondria dysfunction and ischemia/reperfusion-induced renal injury and suggest a therapeutic effect of transplanting isolated mitochondria obtained from MSCs against renal injury.

The effects of mesenchymal stem cell mitochondrial transplantation on doxorubicin-mediated nephrotoxicity in rats.

The effect of dysfunctional mitochondria in several cell pathologies has been reported in renal diseases, including diabetic nephropathy and acute kidney injury. Previous studies have reported that mitochondrial transplantation provided surprising results in myocardial and liver ischemia, as well as in Parkinson's disease. We aimed to investigate the beneficial effects of isolated mitochondria transplantation from mesenchymal stem cells (MSCs) in vivo, to mitigate renal damage that arises from doxorubicin-mediated nephrotoxicity and its action mechanism. In this study, a kidney model of doxorubicin-mediated nephrotoxicity was used and isolated mitochondria from MSCs were transferred to the renal cortex of rats. The findings showed that the rate of isolated mitochondria from MSCs maintains sufficient membrane integrity, and was associated with a beneficial renal therapeutic effect. Following doxorubicin-mediated renal injury, isolated mitochondria or vehicle infused into the renal cortex and rats were monitored for five days. This study found that mitochondrial transplantation decreased cellular oxidative stress and promoted regeneration of tubular cells after renal injury (P < .001, P = .009). Moreover, mitochondrial transplantation reduced protein accumulation of tubular cells and reversed renal deficits (P = .01, P < .001). Mitochondrial transplantation increased Bcl-2 levels, and caspase-3 levels decreased in injured renal cells (P < .015, P < .001). Our results provide a direct link between mitochondria dysfunction and doxorubicin-mediated nephrotoxicity and suggest a therapeutic effect of transferring isolated mitochondria obtained from MSCs against renal injury. To our knowledge, this study is the first study in the literature that showed good therapeutic effects of mitochondrial transplantation in a nephrotoxicity model, which is under-researched.

Issues in diagnosis of small B cell lymphoid neoplasms involving the bone marrow and peripheral blood. Report on the Bone Marrow Workshop of the XVIIth meeting of the European Association for Haematopathology and the Society for Hematopathology.

Small B cell lymphoid neoplasms are the most common lymphoproliferative disorders involving peripheral blood (PB) and bone marrow (BM). The Bone Marrow Workshop (BMW) organized by the European Bone Marrow Working Group (EBMWG) of the European Association for Haematopathology (EAHP) during the XVIIth EAHP Meeting in Istanbul, October 2014, was dedicated to discussion of cases illustrating how the recent advances in immunophenotyping, molecular techniques and cytogenetics provide better understanding and classification of these entities. Submitted cases were grouped into following categories: (i) cases illustrating diagnostic difficulties in chronic lymphocytic leukaemia (CLL); (ii) cases of BM manifestations of small B cell lymphoid neoplasms other than CLL; (iii) transformation of small B cell lymphoid neoplasms in the BM; and (iv) multiclonality and composite lymphomas in the BM. This report summarizes presented cases and conclusions of the BMW and provides practical recommendations for classification of the BM manifestations of small B cell lymphoid neoplasms based on the current state of knowledge.

Solitary Supraclavicular Fossa Masses.

OBJECTIVE: The aim of this study is to present the diagnostic spectrum of solitary supraclavicular fossa (SCF) masses in a Turkish context. The demographic data of the patients and the effectivity of the diagnostic tools are also discussed to improve current diagnostic strategies. PATIENTS AND METHODS: The charts of patients who underwent surgical intervention for solitary SCF mass of an unknown etiology between January 2005 and January 2015 were reviewed. Patients presenting evidences of synchronous cancers and patients with a history of previous cancers were excluded. The data encompassing the demographics of the patients, the discriminative specifications, the histopathological diagnosis of the masses, and the diagnostic tools used in the workup period were noted. The descriptive data are presented and statistical analyses were performed using the Mann-Whitney test, Fisher exact test, and Chi-squared tests. RESULTS: In total, 44 male (76%) and 14 (24%) female patients were enrolled in the study. Thirty-five masses (60%) were located in the left SCF and 23 masses (40%) in the right. The masses were categorized as neoplastic (n = 31, 53%), inflammatory (n = 18, 31%), and congenital (n = 9, 16%). The 44 (76%) masses in our series were lymph nodes (LNs), and 25 (57%) of them were malign, whereas 19 (43%) were either inflammatory or benign. Male sex (P = 0.027) and the size of the mass (P = 0.017) were significantly related to malign LNs. The patients' ages and sides of the masses were not significantly different between the malign and benign LN groups. CONCLUSIONS: Lymph nodes constitute the majority of solitary SCF masses. Although imaging techniques and fine needle aspirations are routinely applied, excisional biopsies are necessary in most cases to reach an exact diagnosis and to plan a definitive treatment regime in this presented series.

Immunosuppressive effects of multipotent mesenchymal stromal cells on graft-versus-host disease in rats following allogeneic bone marrow transplantation.

OBJECTIVE: Graft-versus-host disease (GVHD) is a major obstacle to successful allogeneic bone marrow transplantation (allo-BMT). While multipotent mesenchymal stromal cells (MSCs) demonstrate alloresponse in vitro and in vivo, they also have clinical applications toward prevention or treatment of GVHD. The aim of this study was to investigate the ability of MSCs to prevent or treat GVHD in a rat BMT model. MATERIALS AND METHODS: The GVHD model was established by transplantation of Sprague Dawley rats' bone marrow and spleen cells into lethally irradiated (950 cGy) SDxWistar rat recipients. A total of 49 rats were randomly assigned to 4 study and 3 control groups administered different GVHD prophylactic regimens including MSCs. After transplantation, clinical GVHD scores and survival status were monitored. RESULTS: All irradiated and untreated control mice with GVHD died. MSCs inhibited lethal GVHD as efficiently as the standard GVHD prophylactic regimen. The gross and histopathological findings of GVHD and the ratio of CD4/CD8 expression decreased. The subgroup given MSCs displayed higher in vivo proportions of CD25+ T cells and plasma interleukin-2 levels as compared to conventional GVHD treatment after allo-BMT. CONCLUSION: Our results suggest that clinical use of MSCs in both prophylaxis against and treatment of established GVHD is effective. This study supports the use of MSCs in the prophylaxis and treatment of GVHD after allo-BMT; however, large scale studies are needed. CONFLICT OF INTEREST: None declared.

Protein profiling of anastomosed facial nerve treated with mesenchymal stromal cells.

BACKGROUND AIMS: The types of proteins released from mesenchymal stromal cells (MSC) are still unclear. Our aim was to compare apoptosis scores and the expression of myelin-associated glycoprotein (MAG), myelin basic protein (MBP), neural cell adhesion molecule (NCAM)-1,matrix metalloproteinase (MMP)-1A, tissue inhibitor of metalloproteinase (TIMP)-1, TIMP-1/MMP-1A ratio, nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), neurotrophin (NT)-3, NT-4, glial cell-derived neurotropic factor (GDNF), leukemia inhibitory factor (LIF), basic fibroblast growth factor (FGF)-2, insulin-like growth factor (IGF)-1, platelet-derived growth factor (PDGF)-α and transforming growth factor (TGF)-ß1 in anastomosed facial nerves that had been treated with or without MSC. METHODS: In seven rats, the buccal branch of the right facial nerve was transected, anastomosed and treated with MSC (anastomosed + MSC group). The left buccal branch was anastomosed only (anastomosed-only group). The left mandibular branch served as an intact nerve group. On days 18-20, the distal segments of the branches were examined in terms of expression of the mentioned proteins and apoptosis scores using polymerase chain reaction (PCR) and terminal deoxynucleotidyl transferase-mediated digoxigenin-UTP nick end labeling (TUNEL) assays. RESULTS: MSC application significantly increased CNTF, PDGF-α, LIF, TGF-ß1, BDNF and NT-3 expression (P < 0.05). MAG expression slightly decreased whereas NCAM-1, MMP-1A and FGF-2 slightly increased(P > 0.05). Changes in other proteins and apoptosis scores were not significant. CONCLUSIONS: These results suggest that MSC increases expression of CNTF, PDGF-α, LIF,TGF-ß1, BDNF and NT-3. MAG, NCAM-1, MMP-1A and FGF-2 expressions were slightly changed in this stage of nerve regeneration. The comparison of apoptotic activity was not conclusive. Overall, it appears that MSC might have differential effects on the mentioned tissue-related proteins and trophic/growth factors.

Tuberculosis prevalence in forensic autopsies.

INTRODUCTION: According to the 2008 World Health Organization report, in 2006, 9.2 million new cases were determined, and 1.7 million people have lost their life due to tuberculosis (TB) in all around the world. In our country (Turkey), it is estimated that 35,000 to 40,000 people have TB disease annually. The Ministry of Health could just determine 18,500 of these cases, and only 6500 patient could be treated effectively. According to the Tuberculosis Dispensary records, the incidence for TB in Turkey is 28/100,000. MATERIALS AND METHODS: It is aimed to determine the infection with Mycobacterium tuberculosis using acidoresistant bacilli microscopy, TB culture, and histopathological methods in tissue samples that were obtained from lungs of forensic cases whose autopsies had been performed in Council of Forensic Medicine Ankara Department Morgue Specialized Committee. RESULTS: A total of 3 tissue samples that were obtained from lungs of randomized 302 cases, were positive for TB in Löwenstein-Jensen medium. Granuloma with caseating necrosis was found in histopathological examination and acidoresistant (+) bacilli (1+, 2+, and 2+, respectively) in microscopically analysis were also demonstrated in this 3 tissue samples. DISCUSSION: For this reason, we think that autopsy workers have to be careful about tuberculosis during their autopsy working.

Nuclear morphometry in epidermal changes due to electrical current and thermal energy: trial for usage of image analysis in histological sections.

Distinguishing between injuries resulted from electrical current versus thermal energy is not only a difficult, but also a controversial issue in forensic medicine practice.In this study, an electrical current and a cautery were applied to dorsal skins of 10 rats and biopsies were taken from the injured sites as well as normal skin. In the histologic sections; some planimetric variables such as the perimeter, area, diameter equivalent circle, minimum feret, maximum feret, and the circular form factor of the nuclei located in normal and injured epidermis were measured with the aid of the computer-assisted image analysis.When compared with normal skin, all of the variables -nuclear area, perimeter, diameter equivalent circle, minimum feret, maximum feret, and circular form factor seemed to be decreased both in the electrical current- and cautery-applied skin samples.The differences between the variables measured in normal skin and in electrical- or cautery-applied skin samples were statistically significant (P < 0.05). However none of the variables showed any meaningful differences between the electrical- and cautery-applied areas.It was concluded that the nuclear changes due to electrical current and thermal injury are identical and morphometric analysis seems not to make any further contributions in the differentiating from each other. Therefore, conventional and more established methods for detection of metallization would be more effective.

Primary gastric Burkitt lymphoma: a rare cause of intraabdominal mass in childhood.

Primary gastric lymphoma in the pediatric population is rare and the role of Helicobacter Pylori (H. Pylori) in its pathogenesis is unclear. In this report, we describe a case of non-Hodgkin's lymphoma (Burkitt's type) coexisting with H. pylori and discuss the potential relationship between H. Pylori and gastric Burkitt lymphoma.

The clinical significance of tumor cells in bone marrow or apheresis product and the efficacy of CD34+ selection and high-dose chemotherapy in patients with Stage III breast cancer.

The purpose of this study is to determine the presence of disseminated tumor cells in bone marrow or apheresis product, and also to evaluate the clinical significance of contaminated products and the efficacy of CD34(+) selection and high-dose chemotherapy in patients with Stage III breast cancer. Fifty-five patients were enrolled in this prospective cohort study. Whereas CD34(+) positive selection was not carried out in the first group (unselected group, n:31), CD34(+) positive selection was performed in the second group (CD34 selected group, n:24). Tumor cells were detected with anticytokeratin monoclonal antibody in the bone marrow, apheresis product and positive fraction. Tumor cells were found in six (19.3%) patients in unselected group and four patients (16.6%) in CD34 selected group (P = 0.76). The percentages of distant metastases were found higher in unselected group (51.6% vs. 25%, P < 0.01). Although there were no differences between the two groups for disease free survival (DFS; 44% vs. 74%, P = 0.24) or overall survival (54% vs. 68%, P = 0.84), DFS was significantly lower in patients with tumor cells than in patients without tumor cells (21% vs. 62%, P = 0.02). In conclusion, the presence of tumor cells in bone marrow or apheresis product decreases DFS in patients with Stage III breast cancer who underwent high-dose chemotherapy. CD34(+) selection does not change survivals, but it may decrease the distant metastases.

Comparison of sequential and standard triple-drug regimen for Helicobacter pylori eradication: a 14-day, open-label, randomized, prospective, parallel-arm study in adult patients with nonulcer dyspepsia.

BACKGROUND: The eradication rates of Helicobacter pylori with standard treatments are decreasing worldwide. OBJECTIVES: The primary aim of this study was to compare the eradication success of a 14-day sequential regimen with proton pump inhibitor (PPI)-based triple treatment. The secondary objectives of the study were to evaluate the effect of gastritis score and smoking on eradication rates as well as evaluation of compliance and tolerability of both regimens. METHODS: Consecutive H pylori-positive patients with nonulcer dyspepsia were randomized into 1 of 2 groups in this 14-day, open-label, randomized, prospective, parallel-arm study. An upper endoscopy with biopsy and (14)C-urea breath test ((14)C-UBT) were performed before enrollment. The first group was administered a sequential regimen consisting of pantoprazole 40 mg and amoxicillin 1 g for 7 days, followed by pantoprazole 40 mg, tetracycline 500 mg, and metronidazole 500 mg for the next 7 days. The second group was administered pantoprazole 40 mg, amoxicillin 1 g, and clarithromycin 500 mg (PAC group) for 14 days. All drugs were administered BID, with the exception of tetracycline, which was administered QID. Eradication was confirmed by (14)C-UBT 6 weeks after the end of the treatment. Histologic examination and (14)C-UBT were conducted by investigators blinded to the protocols. Patients were asked to report any adverse events (AEs) during the treatment period. RESULTS: Three hundred white patients were enrolled in the study and evenly randomized into the sequential treatment group (98 males and 52 females; mean age, 40.2 years) and the PAC group (86 males and 64 females; mean age, 41.2 years). A total of 274 patients completed the study per protocol (PP). Twenty-six patients discontinued: lost to follow-up (16), withdrawn due to AEs (9); and noncompliance (1). The intent-to-treat (ITT) and PP H pylori eradication rates were 72.6% and 80.1% in the sequential group, and 58% and 63% in the PAC group, respectively. The eradication rate was significantly higher in the sequential group compared with the PAC group in both the ITT and PP populations (P=0.01 and P=0.002, respectively). The eradication rates were higher in nonsmoking patients compared with smoking patients both in the sequential group (85.8% vs 70.5%) and the PAC group (67.7% vs 53.3%), but the results were not statistically significant when the groups were analyzed separately. Overall, 32 patients (10.7%) reported an AE. Treatment was discontinued in 9 patients because of serious AEs (sequential group--abdominal pain [2 patients], diarrhea [1], chest pain [1], and vaginal pruritus [1]; PAC group--nausea/vomiting [2], chest pain [1], and numbness [1]). There were no significant between-group differences in regard to compliance or AEs. Univariate analyses found no significant effect of sex, age, alcohol consumption, antacid usage, or gastritis score on the eradication rates. CONCLUSIONS: A 14-day sequential treatment regimen achieved a significantly higher eradication rate of H pylori compared with standard PPI-based triple regimen in this small selected population. Large, double-blind, controlled studies are needed to confirm these results.

Lamellation in fibrous dysplasia: A clinicopathologic study.

BACKGROUND: Fibrous dysplasia (FD) is a maturation defect characterized by immature woven bones and stroma. However, especially in craniofacial bones, lamellation can be seen and this is associated with the maturation. AIM: To show maturation in FD and discuss the factors that may affect the maturation. MATERIALS AND METHODS: Ninety-five FD cases were divided into three subgroups according to the lamellation percentage as Groups 1, 2 and 3 (low, moderate and high lamellation, respectively). Each group was compared in terms of the peritrabecular clefting (PTC), stromal cellularity and the age. The lesions under pressure and the ones that are not were compared in terms of lamellation percentage. RESULTS: A significant statistical difference was found between Groups 1 and 3 in terms of PTC, stromal cellularity, histologic pattern suggesting maturation (p<0.001, p<0.001, p=0.002, respectively). CONCLUSION: The findings suggested a strong relation between lamellation and maturation. Lamellation was more prominent in the bones under pressure than the others. Considering lamellation as a finding of maturation, it is possible to establish a relation between maturation and pressure. Therefore, future studies should focus on the question if the pressure could be a factor for maturation and it could be used for treating FD.

Poor efficacy of ranitidine bismuth citrate-based triple therapies for Helicobacter pylori eradication.

BACKGROUND: Helicobacter pylori eradication rates have tended to decrease recently possibly related with increasing antibiotic resistance. The present study investigated the efficacy of three different ranitidine bismuth citrate (RBC) based triple regimens in a population with high prevalence of H. pylori. METHODS: 300 consecutive H. pylori positive patients with non-ulcer dyspepsia were randomized into three regimens: (1) RBC 400 mg, amoxicillin 1000 mg and tetracycline 500 mg [RBC-AT], (2) RBC 400 mg, amoxicillin 1000 mg and clarithromycin 500 mg [RBC-AC], (3) RBC 400 mg, metronidazole 500 mg and tetracycline 500 mg [RBC-MT]. Tetracycline was given q.i.d, all other drugs were given b.i.d. for 14 days. Gastroscopy and (14)C-Urea breath test (UBT) were performed before enrollment and UBT only was repeated 6 weeks after the end of treatment. RESULTS: 274 patients completed the protocols. The overall 'intention to treat' and 'per protocol' H. pylori eradication rates in all subjects were 57.6% (95% CI: 52-63) and 63.1% (95% CI: 57-68), respectively. The eradication rates achieved in the groups (RBC-AT, RBC-AC and RBC-MT) were 64.4% (95% CI: 54-74), 66.2% (95% CI: 56-76), and 58.9% (95% CI: 49-68) on 'per protocol' analyses, respectively. There was no difference in eradication rates, compliance and major side effects between the groups. CONCLUSION: The current RBC-based H. pylori eradication therapy is not adequately effective.

Endoscopic Removal of Suprasellar Colloid Cyst with Interpeduncular and Prepontine Cisterns Extension.

BACKGROUND: Colloid cysts (CCs) are rarely found in the sellar-suprasellar region. Differential diagnosis of CCs is more challenging in this region because many other cystic lesions may locate or invade sellar or suprasellar structures. We present a large and unusual case of sellar-suprasellar CC with extension into the suprasellar, interpeduncular, and prepontine cisterns. This is the first case of sellar-suprasellar CC treated with an endoscopic transsphenoidal approach. CASE DESCRIPTION: A 33-year-old woman presented with a 1-year history of recurrent headaches. Her headaches had been unresponsive to medical treatment for the last 2 weeks. She had normal neurologic and ophthalmologic examinations. Neuroradiologic studies showed a large cystic sellar lesion with extension into the suprasellar, interpeduncular, and prepontine cisterns. The lesion did not show any enhancement, not even in the cyst wall. Her hormonal status was also normal. The cystic lesion was totally resected via a purely endoscopic endonasal approach. There were no complications, and the patient was recovered completely with improvement of her headache. Pathology was consistent with a CC. At 6-month follow-up, magnetic resonance imaging did not show any evidence of the residual or recurrent lesion. CONCLUSIONS: Although rarely found in this location, CC should be considered in the differential diagnosis in patients who present with a sellar-suprasellar cystic lesion. Additionally, sellar-suprasellar CC would be a good candidate for the endoscopic endonasal approach.

Bilateral cervical chondrocutaneous remnants: a case report and review of the literature.

Cervical chondrocutaneous remnants are less common lesions, which are encountered at the lateral neck. They are similar in appearance to preauricular tags, which are more frequent. Bilateral appearance of this pathology is quite uncommon. The lesions always present at birth, and are located in the middle or lower third of the lateral neck with a significant prevalence of location anterior to the sternocleidomastoid muscle. The overlying skin is similar to the surrounding neck skin and the lesion is painless, lacking any inflammation or discharge. Surgically there is no connection with deep underlying structures. The therapy of choice should be complete surgical removal. Several associated anomalies may accompany cervical chondrocutaneous remnants. Thus these patients must be evaluated carefully in order to detect any additional anomaly. We herein report a four-year-old patient with bilateral cervical chondrocutaneous remnant located at the inferior third of the lateral neck anterior to the sternocleidomastoid muscle. We also review the literature for patients with bilateral cervical chondrocutaneous remnants and discuss embryologic and diagnostic aspects.

A case of neurofibromatosis and breast cancer: loss of heterozygosity of NF1 in breast cancer.

Only a few cases with breast cancer and neurofibromatosis type 1 (NF1) have been reported in the literature. Here, we present a family with a history of neurofibromatosis and breast cancer. No hereditary NF1 mutation was observed in this case. Loss of heterozygosity (LOH) analyses of the breast tumor revealed LOH in the NF1 region. In this family, the proband and her mother had breast cancer. The proband was diagnosed with breast cancer at the age of 23 years. No BRCA1 or BRCA2 mutations were observed in the proband's peripheral blood DNA nor were such mutations observed in the immunohistochemically analyzed paraffin block of the tumor DNA. Neurofibromin, encoded by the NF1 gene region, was reported as nearly absent in human breast cancer-MDA-MP-231 cells. Neurofibromin is similar in function to the GTPase activating protein (GAP), p120 GAP. It also accelerates the inactivation of the RAS oncogene. Molecular alterations in NF1 gene region cause neurofibromatosis. LOH in the tumor tissue of our case supports the role of the NF1 gene in the etiology of some cases of breast cancer.

Osteoma of the mandibular condyle: report of a case with 5-year follow-up.

Osteomas of the mandibular condyle are rare. An unusual case of an osteoma occurring in the mandibular condyle of a 22-year-old man with mandibular deviation and malocclusion is reported; this represents the 14th documented case in the English language literature. The tumor was resected with condylectomy. Postoperatively, mandibular deviation was minimized.

Effect of octreotide in the prevention of doxorubicin cardiotoxicity.

OBJECTIVE: A precise method for prevention from doxorubicin cardiotoxicity is not known. We examined whether octreotide has a protective effect against doxorubicin cardiotoxicity. METHODS: New Zealand rabbits (n=44) were divided into 4 groups according to drugs given: Group A (n=12) doxorubicin and octreotide, Group B (n=12) only doxorubicin, Group C (n=10) only octreotide and Group D (n=10) only saline. Effects of the drugs were evaluated in terms of histopathological score, fractional shortening (FS) and prolongation of the QTc interval. RESULTS: Mean pathological score for cardiotoxicity (Group A: 3.7+/-0.5, Group B: 3.9+/-0.3), prolongation of QTc (Group A: from 244.5+/-21.2 ms to 282.9+/-25.9 ms, p<0.0001; Group B: from 248.5+/-17.7 ms to 298.3+/-13.7 ms, p<0.00001) and the rate of decrease in FS (Group A: from 34.4+/-2.0 to 28.0+/-2.0, p<0.05; Group B: from 35.1+/-1.9 to 24.8+/-1.3, p<0.05) were higher in Group B when compared to Group A, but only difference in the rate of decrease in FS was statistically significant (p<0.001). None of these variables changed significantly in groups C and D. CONCLUSION: In this preliminary study, octreotide seems not to reduce doxorubicin cardiotoxicity. On the other hand, a consistent tendency of decreased cardiotoxicity in octreotide+doxorubicin group was observed, although only the difference in FS decrease was significant. Further investigations are needed to address the issue of the extent and the mechanisms of this effect.