Malignant Cell Tumors Research Articles

PNR-20PRIMARY METASTATIC LEIOMYOSARCOMA OF THE SKULL

PNR-20. PRIMARY METASTATIC LEIOMYOSARCOMA OF THE SKULL Alexandra Paul1, Olinda Rebelo2, and Alice Carvalho1; Pediatric Oncology Department, Centro Hospitalar e Universitario de Coimbra-EPE, Coimbra, Portugal; Neuropathology Department, CentroHospitalar e Universitario de Coimbra-EPE, Coimbra, Portugal We report the case of a previous healthy 11 yearold-boy, with a one month history of worsening headache which appeared apparently in the context of trauma. He had an x-ray of the skull that showed a right fronto-parietal lytic lesion with 10 cm in size and with ill-defined borders. CT scan and MRI of the skull revealed a soft tissue mass invading the cranial cavity just beyond the lytic lesion, compressing the brain parenchyma, the upper sagittal sinus and the right ventricle. Skeletal scintigraphy with technetium 99m showed a positive uptake of the proximal left femur and the distal right femur. Chest CT scan detected multiple bilateral lesions of the lung. Blood tests were normal, HIV 1 and 2 were negative. Histopathological results of the soft tissue biopsy were compatible with an unspecified high-grade sarcoma and a second opinion was requested to Prof. Christopher Fletcher Harvard Medical School, USA. His examination was compatible with a high-grade spindle cell malignant neoplasm with extensive necrosis. Immunohistochemistry showed multifocal positivity for smoth muscle actin, numerous scattered cells were positive fordesmin andalsowith quiteextensivekeratinpositivity,while caldesmon, CD34 and epithelial membrane antigen were negative, suggesting a high grade leiomyosarcoma. A high complex karyotype was detected by genetic analysis. Despite chemotherapy and radiotherapy, the disease progressed and he died five months after the diagnosis. Neuro-Oncology 18:iii7–iii15, 2016. doi:10.1093/neuonc/now067.17 #The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Clinicopathological features and response to platinum-based chemotherapy (PBC) in pancreatic neuroendocrine carcinoma (pNEC): Updated results of Japan pNEC study.

e15652 Background: The WHO classified pancreatic neuroendocrine Neoplasms (pNEN) in 2010 as G1, G2, and NEC. However, pNEC is suspected to include heterogeneous disease entities, but is still not fully studied. We aimed to clarify the clinicopathological/molecular characteristics of pNECs. Methods: A total of 100 cases clinical data and pathological slides originally diagnosed as pNEC by the WHO in 2010(WHO-NEC) were retrospectively collected from 31 institutes. Expert pathologists were reassessed all cases slide using the designed protocol and reclassified as well differentiated NET (NET-G3), small cell NEC (SCNEC), and large cell NEC (LCNEC) by morphological features. Results: Thirty cases were eliminated mostly because acinar cell carcinoma, NET-G2 and malignant tumor not otherwise specified, and were eliminated. Remained 70 cases were subclassified into NET-G3 (n = 21, 30%), SCNEC (n = 31, 44.3%), and LCNEC (n = 18, 25.7%). Comparisons of NET-G3 vs. SCNEC vs. LCNEC revealed the following traits: ENETS stage IV (%): 76, 81, 78; median Ki67 LI (%): 28.5 (15–53), 85 (50–100), 70.0 (22–90); abnormal Rb expression (%): 0, 59, 47; KRAS mutations (%): 0, 48, 50; response rate (RR) to PBC (%): 0, 60, 44.4; and overall survival (days): 1255, 196, 340, respectively. When KRAS divided mutation (n = 20) and wild type group (n = 42), RR to PBC as 1st line treatment was 77% vs. 23%. In the same manner, when Rb immune stain divided negative (n = 24) and positive (n = 41), RR to PBC as 1st line treatment was 80% vs. 23.8%. In terms of double abnormalities of Rb expression and KRAS mutation, positive and negative predictive values of response to PBC as 1st line treatment were 100% (7/7, 97.5%CI; 59.0–100) and 69.2% (26/18, 95%CI; 48.2–85.7), respectively. Conclusions: In this retrospective study, WHO-NEC include 30% NET-G3. NET-G3 is clinically and genetically different from SCNEC and LCNEC. As for chemotherapy, Mutated KRAS and/or Rb immunonegativity in tumors with pNEC is associated with response to PBC. Double abnormalities of KRAS mutation and Rb expression may be a strong predictor of PBC.

Toxicity and response in cats with neoplasia treated with toceranib phosphate.

Objectives Toceranib phosphate is a tyrosine kinase inhibitor licensed for the treatment of non-resectable Patnaik grade II/III recurrent cutaneous mast cell tumours in dogs. There is no information in cats regarding the tolerated dose, toxicity or tumour response of this drug. The aim of this study was to analyse retrospectively a cohort of cats with advanced neoplasia treated with toceranib to identify toxicity and response. Methods The medical records of the Small Animal Teaching Hospital were reviewed. Cats were included if they had received toceranib for at least 2 weeks for the treatment of histologically or cytologically confirmed neoplastic disease, and had at least one set of monitoring blood tests (haematology, biochemistry) performed after baseline tests. Toxicity was graded according to the Veterinary Comparative Oncology Group - common terminology criteria for adverse events(VCOG-CTCAE) and response was measured according to Response Evaluation In Solid Tumors (RECIST) criteria. Results Fourteen cats met the inclusion criteria, the majority of which (13/14) had received previous therapy (surgery, radiotherapy, chemotherapy). The most common tumour types were mast cell tumours or malignant epithelial tumours. Toxicity occurred in 10/14 cats - 10 cats had mild myelosuppression or gastrointestinal effects. Two cats developed severe hepatoxicity. One cat died from congestive heart failure, although whether this was related to toceranib therapy is unknown. Regarding response, one cat achieved complete response; two cats achieved partial response and five cats achieved stable disease: overall biological response rate was 57.1%. All of the cats that achieved either partial or complete response were treated for mast cell disease. Overall median duration of response was 90 days (range 14-570 days). None of the cats with squamous cell carcinoma achieved a response. Conclusions and relevance Toceranib phosphate is generally well tolerated in cats, with toxicity limited to mild gastrointestinal or myelosuppressive effects in the majority of cases (10/14) in this study; however, hepatotoxicity is a concern. Response to treatment in this small cohort was similar to that reported in dogs.

Evaluation of NKX2-2 expression in round cell sarcomas and other tumors with EWSR1 rearrangement: imperfect specificity for Ewing sarcoma

Ewing sarcoma shows considerable histologic overlap with other round cell tumors. NKX2-2, a homeodomain transcription factor involved in neuroendocrine/glial differentiation and a downstream target of EWSR1-FLI1, has been reported as an immunohistochemical marker for Ewing sarcoma. We assessed the specificity of NKX2-2 for Ewing sarcoma compared with other round cell malignant neoplasms and other soft tissue tumors with EWSR1 translocations. We evaluated whole-tissue sections from 270 cases: 40 Ewing sarcomas (4 with atypical/large cell features), 20 CIC-DUX4 sarcomas, 5 BCOR-CCNB3 sarcomas, 9 unclassified round cell sarcomas, 10 poorly differentiated synovial sarcomas, 10 lymphoblastic lymphomas, 10 alveolar rhabdomyosarcomas, 10 embryonal rhabdomyosarcomas, 10 Merkel cell carcinomas, 10 small cell carcinomas, 20 melanomas, 5 NUT midline carcinomas, 10 Wilms tumors, 10 neuroblastomas, 10 olfactory neuroblastomas, 12 mesenchymal chondrosarcomas, 10 angiomatoid fibrous histiocytomas, 10 clear cell sarcomas, 5 gastrointestinal clear cell sarcoma-like tumors, 5 desmoplastic small round cell tumors, 10 extraskeletal myxoid chondrosarcomas, 10 soft tissue and cutaneous myoepitheliomas, and 19 myoepithelial carcinomas. NKX2-2 positivity was defined as moderate-to-strong nuclear immunoreactivity in at least 5% of cells. NKX2-2 was positive in 37/40 (93%) Ewing sarcomas, including all atypical Ewing sarcomas and cases with known EWSR1-FLI1 or EWSR1-ERG fusion; 85% of Ewing sarcomas showed diffuse (>50%) staining. NKX2-2 was positive in 9 (75%) mesenchymal chondrosarcomas, 8 (80%) olfactory neuroblastomas, 1 CIC-DUX4 sarcoma, 1 poorly differentiated synovial sarcoma, 1 neuroblastoma, 2 unclassified round cell sarcomas, and 3 small cell carcinomas; all other EWSR1-associated tumors were negative for NKX2-2, apart from 1 desmoplastic small round cell tumor, 1 myoepithelioma, and 1 myoepithelial carcinoma. In summary, NKX2-2 is a sensitive but imperfectly specific marker for Ewing sarcoma. Nonetheless, NKX2-2 may be helpful to distinguish Ewing sarcoma from some histologic mimics including CIC-DUX4 and BCOR-CCNB3 sarcomas. Most other EWSR1-associated soft tissue tumors are negative for NKX2-2.

Data quality in rare cancers registration: the report of the RARECARE data quality study.

Rare cancers represent 22% of all tumors in Europe; however, the quality of the data of rare cancers may not be as good as the quality of data for common cancer. The project surveillance of rare cancers in Europe (RARECARE) had, among others, the objective of assessing rare cancer data quality in population-based cancer registries (CRs). Eight rare cancers were considered: mesothelioma, liver angiosarcoma, sarcomas, tumors of oral cavity, CNS tumors, germ cell tumors, leukemia, and malignant digestive endocrine tumors. We selected data on 18,000 diagnoses and revised, on the basis of the pathologic and clinical reports (but not on pathologic specimens), unspecified morphology and topography codes originally attributed by CR officers and checked the quality of follow-up of long-term survivors of poor prognosis cancers. A total of 38 CRs contributed from 13 European countries. The majority of unspecified morphology and topography cases were confirmed as unspecified. The few unspecified cases that, after the review, changed to a more specific diagnosis increased the incidence of the common cancer histotypes. For example, 11% of the oral cavity epithelial cancers were reclassified from unspecified to more specific diagnoses: 8% were reclassified as squamous cell carcinoma (commoner) and only 1% as adenocarcinoma (rarer). The revision confirmed the majority of long-term survivors revealing a relative high proportion of mesothelioma long-term survivors. The majority of appendix carcinoids changed behavior from malignant to borderline lesions. Our study suggests that the problem of poorly specified morphology and topography cases is mainly one of difficulty in reaching a precise diagnosis. The awareness of the importance of data quality for rare cancers should increase among registrars, pathologists, and clinicians.

Retinoblastoma in the adolescent. Unusual clinical and histopathology findings

Case reportA 17-year-old male with 2 years history of an intraocular mass and progressive visual loss of the left eye. Spontaneous sclera rupture occurred during enucleation. Microscopic evaluation with H–E, PAS and immunohistochemistry (NSE, GAFP, SYN, CD99) revealed a small blue round cell malignant neoplasm with extensive necrosis and apoptosis. The optic nerve, ciliary body, choroid, anterior chamber, and sclera were infiltrated. SYN was positive and CD99 was negative in neoplastic cells, consistent with a poorly differentiated retinoblastoma. DiscussionRetinoblastoma is the most frequent primary intraocular malignant tumor in childhood, but occasionally older patients can be affected. Immunohistochemistry is mandatory in poorly differentiated retinoblastomas.

Clinicopathological features and response to platinum-based chemotherapy in pancreatic neuroendocrine carcinoma: A retrospective multicenter study of 70 patients.

298 Background: The WHO classified pancreatic neuroendocrine Neoplasms (pNEN) in 2010 as G1, G2, and neuroendocrine carcinoma (NEC). However, pNEC is suspected to include heterogeneous disease entities, but is still not fully studied. We aimed to clarify the clinicopathological and molecular characteristics of NECs. Methods: A total of 100 cases clinical data and pathological slides originally diagnosed as NEC by the WHO in 2010(WHO-NEC) were retrospectively collected from 31 institutes. Expert pathologists were reassessed all cases slide using the designed protocol and reclassified as well differentiated NET (NET-G3), small cell NEC(SCNEC), and large cell NEC(LCNEC) by morphological features. Results: Thirty cases were eliminated mostly because acinar cell carcinoma, NET-G2 and malignant tumor not otherwise specified. Remaining 70 cases were subclassified into 21(30%) NET-G3, 31 (44.3%) SCNEC, 18(25.7%) LCNEC. Comparisons of NET-G3 vs. SCNEC vs. LCNEC revealed the following traits: ENETS stageⅣ: 76%, 81% and 78%; median Ki67 LI: 28.5% (15-53), 85 % (50-100) and 70.0 %(22-90); abnormal Rb expression: 0 %, 59% and 47%; KRAS mutations: 0 %, 48% and 50%; response rates to platinum-based chemotherapy: 0%, 60% and 44.4% ;and median survival(days): 1255, 340 and 196, respectively. When KRAS divided wild (n = 20) and KRAS mutation group (n = 42), response rate to platinum-based chemotherapy was 77% vs 23%.In the same manner, when Rb immune stain divided negative (n = 24) and positive (N = 41), response rate to platinum-based chemotherapy was 80% vs 23.8%. Besides response rate to platinum-based chemotherapy of KRAS mutation(+) and Rb immunopositivity(-) group (n = 7) were 100%, on the other hand, KRAS mutation(-) and Rb immunopositivity(+) group (n = 7) were 18.7%. Conclusions: In this retrospective study, WHO-NEC include 30% NET-G3. NET-G3 are genetically different from SCNEC and LCNEC. As for chemotherapy,Mutated KRAS and/or Rb immunonegativity in tumors with pNEC is associated with response to platinum-based chemotherapy.

Retinoblastoma en un adolescente. Hallazgos clinicopatológicos poco frecuentes

Case reportA 17-year- old male with 2years history of an intraocular mass and progressive visual loss of the left eye. Spontaneous sclera rupture occurred during enucleation. Microscopic evaluation with H-E, PAS and immunohistochemistry (NSE, GAFP, SYN, CD99) revealed a small blue round cell malignant neoplasm with extensive necrosis and apoptosis. The optic nerve, ciliary body, choroid, anterior chamber, and sclera were infiltrated. SYN was positive and CD99 was negative in neoplastic cells, consistent with a poorly differentiated retinoblastoma. DiscussionRetinoblastoma is the most frequent primary intraocular malignant tumour in childhood, but occasionally older patients can be affected. Immunohistochemistry is mandatory in poorly differentiated retinoblastomas.

Oral Non Squamous Cell Malignant Tumors in an Iranian Population: a 43 year Evaluation.

The prevalence of non-squamous cell malignant tumors of the oral cavity has not been evaluated in Iran extensively. The aim of this study was to evaluate epidemiological aspects of the oral malignancies with non-squamous cell origin during a 43-year period in the Faculty of Dentistry, Mashhad University of Medical Sciences, Iran. In this retrospective study, the records of all patients referred to dental school of Mashhad university of medical sciences in northeast of Iran, during the period 1971-2013 were evaluated. All confirmed samples of oral non squamous cell malignant tumors were included in this study. Demographic information including age, gender and location of the lesions were extracted from patient's records. Data were analyzed using SPSS statistical soft ware, Chi-square and Fisher's exact tests. Among 11,126 patients, 188 (1.68%) non squamous cell malignant tumors were found, with mean age of 39.9 years ranging from 2 to 92 years. The most common tumors were mucoepidermoid carcinoma (33 cases) and lymphoma (32 cases). Non squamous cell malignant tumors occurred almost equally in men (94 cases) and women (93 cases). Most (134 cases) of them were located peripherally with high frequency in salivary glands (89 cases) and 52 cases were centrally with high frequency in the mandible (38 cases). More findings in this survey were similar to those reported from other studies with differences in some cases; it may be due to variation in the sample size, geographic and racial differences in tumors.

Expression of G Protein-coupled Receptor 56 Is an Unfavorable Prognostic Factor in Osteosarcoma Patients.

G protein-coupled receptor 56 (GPR56) is an atypical G protein-coupled receptor, with the long extracellular N-terminus. GPR56 can trigger various downstream signaling responsible for cell survival, proliferation, adhesion, and migration. Expression of GPR56 is associated with cell malignant transformation and tumor cell metastasis in several carcinomas such as melanoma and glioma. Osteosarcoma is the most common malignant bone tumor in adolescents and young adults with high metastasis tendency. The overall survival of osteosarcoma is unsatisfied, partially due to the lacking of predictive markers for metastasis and overall prognosis. This study aimed at figuring out whether expression of the GPR56 was associated with clinicopathological features of osteosarcoma. Eighty-nine patients who received osteosarcoma operation between March 2004 and February 2011 in Linyi People's Hospital were recruited. Immunohistochemical staining (IHC) was carried out to identify the expression of GPR56 in those osteosarcoma tissues, and our cohort was divided into higher-expression group and lower-expression group according to the cut-off of IHC score. Expression of GPR56 in osteosarcoma tissues was correlated with the TNM stage and overall survival. Univariate and multivariate analysis showed that GPR56 could act as an independent prognosis factor for osteosarcoma. Western blot results demonstrated that GPR56-siRNA down-regulated the expression of GTP-RhoA and Ki67. GTP-RhoA participates in the cell migration process, while Ki67 plays important roles in cell proliferation, indicating GPR56 may function in tumor development. Correspondingly, we show that GPR56 regulates the proliferation and invasion capacity of osteosarcoma cells. Our study has revealed the prognostic value of GPR56 expression in osteosarcoma.

Primary malignant bone tumours: Epidemiological data from an Orthopaedic Oncology Unit in South Africa

INTRODUCTION: Limited data is available with regard to the epidemiology of primary malignant orthopaedic tumours in the South African clinical setting. As a result, orthopaedic surgeons have to rely on data from other countries when formulating differential diagnoses for malignant bone lesions. Existing data, however, demonstrates variance in the incidence between different geographic regions. By analysing the tumour epidemiology at our centre and comparing it to published data from other parts of the world, we aim to better define the local prevalence of primary malignant bone tumours. Materials and methods: A retrospective review of all patients with biopsy confirmed malignant primary bone tumours that presented between January 2008 and June 2015 were conducted. Patients with multiple myeloma and lymphoma were excluded. Epidemiological data pertaining to patient demographics, tumour location and histological diagnosis were recorded and analysed. RESULTS: Included for review were 117 patients with biopsy-confirmed primary malignant bone tumours. Tumours involving the proximal humerus, distal femur, proximal tibia and pelvis accounted for 80% of all tumours. Osteosarcoma was the most common histological diagnosis (72.6%) and higher than reported figures from any other country. It was followed by chondrosarcoma (11.4%), Ewing's sarcoma (9.4%), spindle cell sarcoma (4.2%) and malignant giant cell tumour (GCT) (1.7%). A single patient was diagnosed with adamantinoma. HIV infection had no significant association with primary bone tumour incidence. CONCLUSION: Epidemiological data from this review reflect small but significant differences compared to international literature. The incidence of osteosarcoma appeared to be higher than in previous reports from other regions. Future study in this area may identify a reason for this difference, socio-economic reasons may be responsible.

Gastrointestinal Leiomyosarcoma with Disease Progression to the Central Nervous System: Case Report

Introduction: Leiomyosarcomas (LMS) are rare malignant neoplasms with smooth muscle differentiation, which occur more commonly in the uterus, digestive tract or retroperitoneum. Before 2000, the mesenchymal gastric tumors were divided in leiomyomas, leiomyoblastomas and leiomyosarcomas. After discovery of the role of KIT oncogene, a distinct entity in the mesenchymal gastrointestinal tumors line has surfaced: GIST (Gastrointestinal Stomal Tumors). The true gastric leiomyosarcoma has become a rare entity. The presentation with brain metastasis had only been reported in the pre-GIST era. Case report: A female, 57 years old, admitted in October 2013, for investigation of abdominal pain, finding a lesion in the left illiac fossa continuing with the terminal ileum. She was submitted to the resection of the lesion with histopathological result showing leiomyosarcoma (6 mitotic figures/10 high power field; IHQ: vimentin positive, S-100 negative, desmin positive). Started chemotherapy. However, presented progression of the disease for subcutaneous tissue, liver (submitted to radiotherapy) and nervous system (only one lesion in the posterior fossa). The patient was submitted in March 7th 2016 to suboccipital craniotomy and en-block resection of the lesion. The microscopic examination revealed a fasicular spindle cell malignant neoplasm, with necrotic areas, with intense and diffuse desmin and smooth muscle actin-positivity in immunohistochemical study, which confirmed the leiomyosarcoma metastatic lesion hypothesis. The patient evolved well during the postoperative period, it was peformed the postoperative MRI, that showed a satisfactory resection. She remained hospitalized until the fourth postoperative day, with no complications, and was then discharged for outpatient follow-up. Conclusion: We have described a case of gastric leiomyosarcoma, emphasizing that even in front of the rarity of leiomyosarcoma itself as a primary lesion (especially after the discovery of GIST as an independent mesenchymal line tumor), this lesion may progress and present central nervous system metastasis, a fact not before reported in literature.

L-type amino acid transporter-1 and CD98 expression in bone and soft tissue tumors.

L-type amino acid transporter-1 (LAT1) is expressed in many cancers. We examined LAT1 and CD98 expression immunohistochemically in surgically resected specimens of various bone and soft tissue tumors. Out of 226 cases, 79 (35%) were LAT1(+) and 95 (42%) were CD98(+) . In bone tumors, LAT1 was highly expressed in osteoblastoma (89%), chondrosarcoma (50%), and osteosarcoma (60%); in soft tissue tumors, LAT1 was highly expressed in rhabdomyosarcoma (80%), synovial sarcoma (63%), Ewing's sarcoma (60%), epithelioid sarcoma (100%) and angiosarcoma (100%). In malignant soft tissue tumors, LAT1 expression was associated with higher histological grade. High CD98 expression was seen in many bone tumors of intermediate and high malignancy. Among soft tissue tumors, CD98 was expressed in tendon sheath giant cell tumor and malignant peripheral nerve sheath tumor (57%), Ewing's sarcoma (50%) and undifferentiated sarcoma (64%). Some of the malignant soft tissue tumors expressed both LAT1 and CD98. This study showed that LAT1 and CD98 was expressed in many malignant and intermediate bone tumors, and some malignant soft tissue tumors.

Autophagy in tumorigenesis and cancer treatment.

Autophagy is a self-digestion process, wrapping cytoplasmic proteins or organelles to form vesicles for degradation in lysosomes. The process plays an important role in the maintenance of intracellular homostasis. Here we overview articles on autophagy and cancer/tumors in Pubmed and found 327 articles. Autophagy exists in many tumors and is involved in cell malignant transformation and tumor cell growth. In early phases of tumorigenesis, autophagy clears the abnormally folded proteins and dysfunctional organelles such as mitochondria. Autophagy can also inhibit cell stress responses and prevent genetic damage. When a tumor develops, autophagy helps tumor cells survive nutritional deficiencies and hypoxic conditions. Studies of autophagy in the occurrence and progression of tumors should provide new therapeutic strategies for tumors.

Utility of transmission electron microscopy in small round cell tumors.

Small round cell tumors (SRCTs) are a heterogeneous group of neoplasms composed of small, primitive, and undifferentiated cells sharing similar histology under light microscopy. SRCTs include Ewing sarcoma/peripheral neuroectodermal tumor family tumors, neuroblastoma, desmoplastic SRCT, rhabdomyosarcoma, poorly differentiated round cell synovial sarcoma, mesenchymal chondrosarcoma, small cell osteosarcoma, small cell malignant peripheral nerve sheath tumor, and small cell schwannoma. Non-Hodgkin’s malignant lymphoma, myeloid sarcoma, malignant melanoma, and gastrointestinal stromal tumor may also present as SRCT. The current shift towards immunohistochemistry and cytogenetic molecular techniques for SRCT may be inappropriate because of antigenic overlapping or inconclusive molecular results due to the lack of differentiation of primitive cells and unavailable genetic service or limited moleculocytogenetic experience. Although usage has declined, electron microscopy (EM) remains very useful and shows salient features for the diagnosis of SRCTs. Although EM is not always required, it provides reliability and validity in the diagnosis of SRCT. Here, the ultrastructural characteristics of SRCTs are reviewed and we suggest that EM would be utilized as one of the reliable modalities for the diagnosis of undifferentiated and poorly differentiated SRCTs.

Bilateral testicular germ cell tumors.

392 Background: Germ cell tumors (GCTs), both seminomatous and non-seminomatous, account for greater than 90% of testicular cancers. While bilateral testicular GCTs are rare, the incidence of bilateral tumors has increased over time. Methods: 668 cases of bilateral and 38,593 cases of unilateral testicular GCTs were reported between 1973 and 2011 by the SEER database. Patient characteristics and tumor features were analyzed. Results: The incidence of bilateral GCTs among men with testicular GCTs was 1.7% (668 of 39,261 total cases). Among the 668 men with bilateral GCTs, 53% (n=353) of second GCTs occurred within three years after the first cancer. 29% (n=196) of bilateral tumors occurred synchronously. Among patients with bilateral GCTs, 378 first GCTs and 466 second GCTs were seminomatous. 43% of bilateral cases were concordant seminomatous GCTs, 16% were concordant non-seminomas, and 41% were discordant histologies. 68% of unilateral GCTs, 70% of first GCTs, and 82% of second GCTs were staged as Localized disease. Testicular cancer was the cause of death for 4% (n=1,630) of men with a unilateral GCT and 1% (n=8) of men with bilateral GCTs. A second malignant neoplasm (SMN) was the cause of death for 2% (n=736) of men with a unilateral GCT and 2% (n=16) of men with bilateral GCTs. Conclusions: Among men with bilateral testicular GCTs, 59% had concordant histological diagnoses between their first and second tumor. Most (53%) second cancers among men with bilateral tumors occurred within three years after diagnosis of first cancers. Men who experience bilateral testicular GCTs do not appear to have an increased risk of death due to testicular cancer or a subsequent non-germ cell malignant neoplasm compared to men with a unilateral testicular GCT. [Table: see text]

The Rare Presentation of Extraskeletal Ewing's Sarcoma on the Forehead.

The Rare Presentation of Extraskeletal Ewing's Sarcoma on the Forehead.

Molecular methods in diagnosis of poorly differentiated malignant brain tumors in children

The histological diagnosis of malignant brain tumors in children is a complex process. In some cases, glioblastoma, primitive neuroectodermal tumor of the central nervous system, and atypical teratoid/rhabdoid tumor have a histological type similar to that of small blue round cell malignant tumor. Despite the similar histology, biological properties and approaches to treatment, these neoplasms are completely different and require their own treatment protocols. We retrospectively reviewed the most malignant types of childhood tumors and analyzed our own experience to propose a diagnostic algorithm for intracerebral small blue round cell malignant tumors in children based on the use of immunohistochemistry and fluorescence in situ hybridization.

A Rare Case of Metastatic Bilateral Ovarian Dysgerminoma With Elevated CA-125 Levels

Ovarian dysgerminomas although rare are the most common malignant germ cell tumors of the ovary and comprise 2% of all ovarian malignancies. These tumors are most commonly seen in young girls and young women. Once diagnosed accurately, chemotherapy following post-op has excellent prognosis. We present a rare case of bilateral ovarian dysgerminoma in a 25 year old female patient with metastases and elevated CA-125 levels, with transvaginal ultrasound and CT correlation.

Solitomab, an EpCAM/CD3 bispecific antibody (BiTE®), is highly active against primary chemotherapy-resistant ovarian cancer cell lines in vitro and fresh tumor cells ex vivo

Objectives: Chemotherapy-resistant ovarian cancer remains an incurable disease. Solitomab is a novel bispecific single-chain antibody that targets the epithelial antigen EpCAM on tumor cells and also contains a CD3-binding region. We evaluated the in vitro activity of solitomab against multiple primary chemotherapy-resistant epithelial ovarian carcinoma cell lines and malignant tumor cells in ascitic fluid.