Primary epithelioid angiosarcoma of endometrium.

Angiosarcoma is a poor prognostic tumor observed less than 1% in soft tissue, while it is rarely detected in the endometrium and has been described in few case reports. In this report, we present a case of primary epithelioid angiosarcoma of endometrium to raise awareness and emphasize for pathologists and clinicians.

A Novel PUS1 Mutation in 2 Siblings with MLASA Syndrome: A Review of the Literature.

ABSTRACT: Myopathy, lactic acidosis, and sideroblastic anemia (MLASA) is a rare mitochondrial disorder characterized by MLASA. Variable features of this condition include failure to thrive, and developmental delay or intellectual disability. Additional symptoms consist of cognitive impairment, skeletal and dental abnormalities, delayed motor milestones, cardiomyopathy, dysphagia, and respiratory insufficiency. MLASA has previously been associated with mutations in pseudouridylate synthase 1 (PUS1) and YARS2. PUS1 encodes the nuclear PUS1 enzyme, which is located in both the nucleus and the mitochondria. PUS1 converts uridine into pseudouridine in several cytosolic and mitochondrial transfer RNA positions and increases the efficiency of protein synthesis in both compartments.In the present report, we report on 2 Turkish sisters 4 and 11 of years with an MLASA plus phenotype. Both patients have sideroblastic anemia, lactic acidosis, failure to thrive, developmental delay, and chronic diarrhea; in addition, the older sister has strabismus and skeletal anomalies. The sequencing of the PUS1 gene revealed a novel homozygous p.Glu311* mutation. The phenotype of the older sibling is also unique because of the strabismus and skeletal anomalies, when compared with her sister and other previously reported patients with MLASA. The structural differences in the nuclear versus mitochondrial isoforms of PUS1 and modifier genes may be implicated in the variability of the clinical presentations in MLASA. CONCLUSION: This report adds to the growing number of mutations causing complex clinical manifestations of MLASA including lactic acidosis, sideroblastic anemia, chronic diarrhea, and myopathy.

The prognostic importance of TGF-ß, TGF-ß receptor, and fascin in childhood solid tumors.

Fascin plays a role in tumor metastasis under the influence of TGF-ß, each potentiating the effect of the other. We retrospectively investigated whether there was a prognostic relationship between TGF-ß and fascin, and disease stage, local recurrence, metastasis tendency, and response to treatment. Twelve neuroblastomas, 17 osteosarcomas, 14 Ewing's sarcomas, 15 rhabdomyosarcoma cases, and 8 rare solid tumors were included. Serum TGF-ß levels were high at the time of diagnosis in all groups (p = .015) and decreased significantly during remission (p = .008). Serum TGF-ß values in the relapse period rarely reached high levels at the time of diagnosis and even stayed under the control group values (p = .017). When TGF-ß receptor expression in tumor tissues was evaluated, the association of TGF-ß receptor positivity with metastatic disease and advanced stage was striking. We found that 88% of rhabdomyosarcoma cases with alveolar histopathology expressed the TGF-ß receptor, and the association between TGF-ß receptor positivity and alveolar histopathology seemed to be a negative prognostic marker. When fascin levels were evaluated in childhood solid tumor tissue, the risk of relapse increased when the fascin total score at diagnosis was >4. This is one of the few studies including prognostic markers such as serum TGF-ß, tissue TGF-ß, TGF-ß receptor, and fascin in pediatric solid tumors. Considering the poor prognosis of advanced stage pediatric solid tumors and the need for biomarkers to predict which patient might need more intensive therapy or warrant closer follow-up afterward, we think that TGF-ß, TGF-ß receptor, and fascin expression have an important prognostic role.

Myeloid sarcomas: a clinicopathologic study of 20 cases.

OBJECTIVE: Myeloid sarcoma is a tumoral mass of mature or immature myeloid blasts in extramedullary anatomic locations. It can be seen de novo or in association with acute myeloid leukemia, myeloproliferative neoplasias, or myelodysplastic syndrome. Isolated myeloid sarcoma can be seen as a relapse in cases with allogenic bone marrow transplantation. Although it may involve any tissue in the body, the most common locations are skin, soft tissues, lymph nodes, and the gastrointestinal tract. Immunohistochemically, most cases show myelomonocytic or pure monoblastic differentiation. We reviewed the clinicopathological features of 20 cases of myeloid sarcoma diagnosed in our institute in view of the literature. MATERIALS AND METHODS: The cases diagnosed between 2005 and 2012 at the Ankara University Faculty of Medicine, Department of Pathology, were selected. Clinicopathological findings including the age and sex of the patients; symptoms; anatomic location; accompanying hematological disease; and the morphological, immunohistochemical, and cytogenetic features of the cases were noted. RESULTS: Sixteen of the patients were male and 4 were female. The median age at diagnosis was 47 years. The most commonly involved locations were the lymph nodes and skin. Immunohistochemically, eleven cases were of the myelomonocytic and 7 cases were of the myeloid phenotype, whereas 2 cases showed pure monoblastic differentiation. The median follow-up period for the 18 cases with known clinical data was 33 weeks. Five patients died of the disease in an average of 36 weeks. CONCLUSION: Myeloid sarcoma is a rare presentation of leukemias, myeloproliferative neoplasias, or myelodysplastic syndrome, composed of immature myelomonocytic cells in extramedullary tissues. It may present with variable morphological and phenotypic features, always creating a challenge in pathological diagnosis.

Epstein-barr virus-negative post-transplant lymphoproliferative diseases: three distinct cases from a single center.

Three cases of Epstein-Barr virus (EBV)-negative post-transplant lymphoproliferative disease that occurred 6 to 8 years after renal transplantation are reported. The patients respectively had gastric mucosa-associated lymphoid tissue lymphoma, gastric diffuse large B-cell lymphoma, and atypical Burkitt lymphoma. Absence of EBV in the tissue samples was demonstrated by both in situ hybridization for EBV early RNA and polymerase chain reaction for EBV DNA. Patients were treated with reduction in immunosuppression and combined chemotherapy plus an anti-CD20 monoclonal antibody, rituximab. Despite the reduction in immunosuppression, patients had stable renal functions without loss of graft functions. The patient with atypical Burkitt lymphoma had an abnormal karyotype, did not respond to treatment completely, and died due to disease progression. The other patients are still alive and in remission 5 and 3 years after diagnosis, respectively. EBV-negative post-transplant lymphoproliferative diseases are usually late-onset and are reported to have poor prognosis. Thus, reduction in immunosuppression is usually not sufficient for treatment and more aggressive approaches like rituximab with combined chemotherapy are required.

Relevance of Additional Immunohistochemical Markers in the Differential Diagnosis of Small B-Cell Lymphomas: A Case-Control Study

Objective: Clinical and pathological differential diagnosis of small B-cell lymphomas (SBCLs) is still controversial and may be difficult due to their overlapping morphology, phenotype, and differentiation to plasma cells. We aimed to examine the expression of the immune receptor translocation-associated protein 1 (IRTA1), myeloid cell nuclear differentiation antigen (MNDA), lymphoid enhancer-binding factor-1 (LEF1), and stathmin 1 (STMN1) markers in SBCL cases involving different sites that may have plasma cell differentiation. Materials and Methods: We studied 154 tissue samples with lymphoma involvement from 116 patients and evaluated the staining distribution of the markers. Expressions were evaluated in 21 chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), 7 follicular lymphoma (FL), 14 nodal marginal zone lymphoma, 17 extranodal marginal zone lymphoma, 55 splenic marginal zone lymphoma, 22 marginal zone lymphoma-not otherwise specified, and 18 lymphoplasmacytic lymphoma/Waldenström macroglobulinemia cases by immunohistochemistry. Results: The results confirmed that LEF1 was the most sensitive and specific marker for CLL/SLL and STMN1 was the most sensitive and specific marker for FL (p<0.001). MNDA and IRTA1 were useful markers to distinguish marginal zone lymphomas. Conclusion: Our results suggest that LEF1 for CLL/SLL and STMN1 for FL are reliable markers. LEF1, MNDA, STMN1, and IRTA1 are helpful with other routinely used immunohistochemical markers in a diagnostic algorithm considering their limitations.

Superficial Acral Fibromyxoma.

Superficial acral fibromyxoma is a rare, benign, slow-growing, soft-tissue tumor commonly located in the acral regions, with a predilection for the great toe, developing from the nail unit. Because of its nonspecific features and rarity, clinical diagnosis is difficult. In this article, we present a case of superficial acral fibromyxoma located in the nail unit with new dermatoscopic and radiologic findings that have not been previously reported in the literature.

Diagnostic importance of clinicopathologic features and p16, CD34, MDM2 expression in differential diagnosis of adipocytic tumors.

OBJECTIVE: The aim of this study was to investigate the immunohistochemical stain profiling of adipocytic tumors. METHODS: From our archive files between the years of 2012-2018, excised, formalin-fixed and paraffin-embedded adipocytic tumors were retrospectively screened and 61 subjects were selected. The gender, age, tumor location and tumor diameter were evaluated. The cases were investigated in terms of p16, CD34, MDM2 expression and clinicopathological information. RESULTS: Of the 61 patients included in the study, we found that 2 had hibernoma, 4 had lipoblastoma, 14 had spindle cell lipoma (SCL), 10 had lipoma, 20 had atypical lipomatous tumor/well differentiated liposarcoma (ALT/WDL), and 11 had dedifferentiated liposarcoma (DDL). In terms of diameter, ALT/WDL and DDL were significantly different from the others (p=0.001, p=0.001, respectively). There was a significant difference between the groups according to the location (p=0.001). 35% (7/20) of ALT/WDLs were in the lower extremities (thighs) and 35% (7/20) were located in the retroperitoneal region. 70% of DDLs (7/11) were located in the retroperitoneum. When CD34 expression was evaluated among the groups, a significant difference was observed (p=0.001). CD34 was positive in 92.9% of SCL cases. p16 immunoreactivity was significantly different between the groups (p=0.001). p16 expression was observed in 50.5% of ALT / WDL cases and 79% of DDL cases. CONCLUSION: p16 and CD34 expression are valuable in the differential diagnosis of lipomatous tumors when radiological and clinical considerations do not help to differential diagnosis of adipocytic tumors. LEVEL OF EVIDENCE: Level IV, Therapeutic Study.

A new location for pediatric immunoglobulin G4 related disease: the biceps muscle.

BACKGROUND: Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is a systemic disorder of unknown etiology characterized by elevated serum IgG4 and tissue infiltration of IgG4-positive plasma cells. The disease was described in the pancreas, aorta, thyroid, salivary glands, periorbital tissues, kidneys, pericardium and lymph nodes. CASE: Here in, we report a first pediatric case report of IgG4-related disease who presented with a mass in skeletal muscle i.e., biceps muscle. CONCLUSION: To the best of our knowledge, the involvement in skeletal muscle has previously not been reported in children.

Regulation of chondrocyte hypertrophy in an osteochondral interface mimicking gel matrix.

Calcified cartilage extracellular matrix (ECM) is a critical interface at the osteochondral junction which plays an important role in maintaining the structural continuity between articular cartilage and subchondral bone. This mineralized network is primarily composed of glycosaminoglycans (GAGs) and collagen type II (col II) and hosts hypertrophic chondrocytes. This work aimed to investigate the effect of gel composition and collagen II content on the behavior and hypertrophic differentiation of ATDC5 cells for regeneration of calcified cartilage tissue. For this purpose, chitosan/collagen type II/nanohydroxyapatite (chi/col II/nHA) composite hydrogels were prepared to mimic the calcified cartilage ECM. ATDC5 cells were encapsulated within the composite gels and the viability, ECM production and hypertrophic gene expression were assessed during culture. All composites were favorable for ATDC5 viability and proliferation, whereas specific ECM production and hypertrophic differentiation were dependent on gel composition. Chitosan: collagen II ratio had an impact on ATDC5 cell fate. Hypertrophic differentiation was best pronounced in chi/col II/nHA 70:30 composition. The results obtained from this study offers a scaffold-based approach for calcified cartilage regeneration and provide an insight for biomimetic design and preparation of more complicated gradient osteochondral units.

Chitosan/collagen based biomimetic osteochondral tissue constructs: A growth factor-free approach.

Tissue engineering approach offers alternative strategies to develop multi-layered/multi-component osteochondral mimetic constructs to meet the requirements of the heterogeneous and layered structure of native osteochondral tissue. Herein, an iterative overlaying process to fabricate a multi-layered scaffold with a gradient composition and layer specific structure have been developed by combining the natural extracellular matrix (ECM) components-chitosan, type I collagen, type II collagen, nanohydroxyapatite- of the osteochondral tissue in biomimetic compositions. Subchondral bone layer was prepared by using freeze-drying method to obtain 3D porous scaffolds. The calcified cartilage and cartilage layers were prepared by thermal gelation method in the hydrogel form. Osteochondral scaffolds fabricated by iterative overlaying of each distinct layer exhibited a porous, continuous gradient structure and supported cell proliferation in a co-culture of MC3T3-E1 preosteoblasts and ATDC5 chondrocytes. Histology and biochemical analysis showed enhanced extracellular matrix production and demonstrated collagen and glycosaminoglycan deposition. Expression of genes specific for bone, calcified cartilage and cartilage were improved in the osteochondral scaffold. Overall, these findings suggest that iterative overlaying of freeze-dried scaffolds and hydrogel matrices prepared by using ECM components in biomimetic ratios to fabricate gradient, multi-layered structures can be a promising strategy without the need for growth factors.

Primary chondromesenchymal hamartoma of the orbit.

A 14-year-old girl presented with a 3-month history of proptosis of the left eye. Orbital MRI revealed a superiorly located, well-defined, large mass that was hyperintense on T1-weighted and T2-weighted images with heterogenous internal structure and contrast enhancement. The patient underwent superolateral orbitotomy with bone removal. The tumor was excised totally in a piecemeal fashion. Microscopic examination revealed hyaline cartilaginous nodules admixed with spindle cell stroma and bone formation. Immunohistochemically, the mesenchymal component was diffusely positive for vimentin, smooth muscle actin, and CD34. The cartilaginous nodules and stroma stained with S-100. Based on the histopathologic and immunohistochemical findings, a diagnosis of orbital chondromesenchymal hamartoma was made. The patient has been followed for 6 years with no sign of recurrence. A literature search from 1966 to present using the PubMed database yielded no prior reports of primary orbital chondromesenchymal hamartoma. This case demonstrates that chondromesenchymal hamartoma can occur as a primary orbital tumor in children. Awareness of the presence of this tumor is essential for correct diagnosis.

Simultaneous occurrence of Kaposi's sarcoma and nodular lymphocyte predominant subtype of Hodgkin's lymphoma in the same lymph node.

Many cases have been established with coexisting Kaposi's sarcoma (KS) and classical Hodgkin's Lymphoma (C-HL) in the same lymph node. But composite presentation of KS and Nodular Lymphocyte Predominant subtype of Hodgkin's lymphoma (NLPHL) in the same lymph node has not been described yet. KS is related to immunodeficiency most frequently due to human immunodeficiency virus (HIV) infection or immunosupression by other reasons. Our case presented here was not related to any immunodeficiency status. Besides of being the first case of composite KS and NLPHL in the same lymph node, it was also unusual with the indolent behaviour of the NLPHL without any therapy for 8 years follow up and primary lymph node presentation of KS without cutaneous involvement.

Antibacterial effects of electrically activated vertebral implants.

Bio-implants in the human body act as passive surfaces that are prone to bacterial adhesion potentially leading to deep body infections. Pedicle screws made of uncoated or silver-coated titanium alloy were used both in vitro and in vivo to determine whether silver-coated materials have antimicrobial properties when they are anodized. Twenty-four New Zealand Albino rabbits were divided into four groups with six in each. In Group 1, the rabbits were exposed to 8 muA direct current (DC) via silver-coated screws. In Group 2, the rabbits were not exposed to any electrical current, but silver-coated screws were used. In Group 3, the rabbits were exposed to 8 muA DC using uncoated screws. In Group 4, the rabbits were not exposed to any electrical current, but uncoated screws were used. Staphylococcus aureus (106 cfu) was inoculated into the rabbits before any electrical current was applied. All the animals were killed, and the areas surrounding the screws were histologically and microbiologically examined. Silver-coated titanium screws prevented implant-associated deep bone infections when they were polarized anodically. The antibacterial effects of the same screws with the same bacterium were confirmed in in vitro experiments on agar plates. When the screws were anodized with the same electrical parameters in vitro, a marked inhibition zone was detected around the silver-coated screws but not around the uncoated screws. Our findings suggest that silver-coated titanium implants can be used to prevent implant-associated deep bone infections when they are polarized anodically.

Placental S100 (S100P) and GATA3: markers for transitional epithelium and urothelial carcinoma discovered by complementary DNA microarray.

The morphologic distinction between prostate and urothelial carcinoma can be difficult. To identify novel diagnostic markers that may aid in the differential diagnosis of prostate versus urothelial carcinoma, we analyzed expression patterns in prostate and bladder cancer tissues using complementary DNA microarrays. Together with our prior studies on renal neoplasms and normal kidney, these studies suggested that the gene for placental S100 (S100P) is specifically expressed in benign and malignant urothelial cells. Using tissue microarrays, a polyclonal antiserum against S100P protein stained 86% of 295 urothelial carcinomas while only 3% of 260 prostatic adenocarcinomas and 1% of 133 renal cell carcinomas stained. A commercially available monoclonal antibody against S100P stained 78% of 300 urothelial carcinomas while only 2% of 256 prostatic adenocarcinomas and none of 137 renal cell carcinomas stained. A second gene, GATA3, also showed high level expression in urothelial tumors by cDNA array. A commercially available monoclonal antibody against GATA3 stained 67% of 308 urothelial carcinomas, but none of the prostate or renal carcinomas. For comparison, staining was also performed for p63 and cytokeratin 5/6. p63 stained 87% of urothelial carcinomas whereas CK5/6 stained 54%. Importantly, when S100P and p63 were combined 95% of urothelial carcinomas were labeled by one or both markers. We conclude that the detection of S100P and GATA3 protein expression may help distinguish urothelial carcinomas from other genitourinary neoplasms that enter into the differential diagnosis.

Central nervous system lymphoma in a patient with Sjogren's syndrome and autoimmune thyroiditis (Hashimoto's thyroiditis).

We present a case of central nervous system (CNS) lymphoma in a patient with Sjogren's syndrome (SS) and autoimmune thyroiditis (Hashimoto's thyroiditis) overlap. A 60-year-old woman, who had the diagnosis of SS for 16 years, had been admitted for visual loss, fever, weight and appetite loss for 3 months. Cranial magnetic resonance imaging was in accordance with CNS lymphoma, and biopsy from right parietal region showed diffuse large B-cell lymphoma of the CNS. This is the first report of diffuse large B-cell lymphoma of the CNS in SS and autoimmune thyroiditis (Hashimoto's thyroiditis) overlap.

Vitiligo associated with malignant melanoma and lupus erythematosus.

There exists several reports where malignant melanoma is associated with vitiligo, vitiligo with discoid lupus erythematosus and lupus erythematosus with urticaria. However, there are no reports in which vitiligo, malignant melanoma, lupus erythematosus and urticaria coexist in the same case. Herein, we report a case of a patient who developed lupus erythematosus, malignant melanoma, vitiligo and urticaria simultaneously.

Microvessel density and regulators of angiogenesis in malignant and nonmalignant prostate tissue.

The aim of this study was to investigate the relationship between microvessel density (MVD), positive and negative angiogenic factors, and established prognostic factors in prostate cancer (PC), and, to clarify the effect of angiogenic factors to angiogenesis. The vascularization of neoplastic, non-neoplastic prostate tissue was determined by CD34 immunostaining. Angiogenetic mediators VEGF, bFGF, TSP-1, and p53 were studied by immunohistochemistry. Neovascularization and p53, VEGF, and TSP-1 expressions of tumorous tissue were higher than non-tumorous tissue. The bFGF expression in these tissues was not different. The p53 expression was not correlated with the expressions of VEGF, bFGF, and TSP-1 in PC. Our results demonstrate a significant increase in MVD, VEGF, TSP-1, and p53 expressions in prostate tumorigenesis. The pretreatment sPSA was the only parameter demonstrating significant correlation with tumor grade and may have a value in the prediction of aggressive tumor behavior in PC.

The retinoic acid synthesis gene ALDH1a2 is a candidate tumor suppressor in prostate cancer.

Prostate cancer is the most common cancer among men in the United States, and aberrant DNA methylation is known to be an early molecular event in its development. Here, we have used expression profiling to identify novel hypermethylated genes whose expression is induced by treatment of prostate cancer cell lines with the DNA methyltransferase inhibitor 5-Aza-2'-deoxycytidine (5-aza-dC). Of the 271 genes that were induced by 5-aza-dC treatment, 25 also displayed reduced expression in primary prostate tumors compared with normal prostate tissue, and the decreased expression of only one gene, aldehyde dehydrogenase 1 family, member A2 (ALDH1a2), was also associated with shorter recurrence-free survival. ALDH1a2 encodes an enzyme responsible for synthesis of retinoic acid (RA), a compound with prodifferentiation properties. By immunohistochemistry, we observed that ALDH1a2 was expressed in epithelia from normal prostate but not prostate cancer. Using bisulfite sequencing, we determined that the ALDH1a2 promoter region was significantly hypermethylated in primary prostate tumors compared with normal prostate specimens (P = 0.01). Finally, transfection-mediated reexpression of wild-type ALDH1a2 (but not a presumptive catalytically dead mutant) in the prostate cancer cell line DU145 resulted in decreased colony growth (P < 0.0001), comparable with treatment with either 5-aza-dC or RA. Taken together, our findings implicate ALDH1a2 as a candidate tumor suppressor gene in prostate cancer and further support a role of retinoids in the prevention or treatment of prostate cancer.