Cerebral Liposarcoma Embolus From Heart Metastasis Successfully Treated by Endovascular Extraction Followed by Cardiac Surgery.

The current case presents a patient with a tumor emboli stroke as a presenting symptom of a liposarcoma metastasis to the heart that was treated successfully with endovascular mechanical retrieval, followed by subsequent cardiac surgery. The patient is still alive, under chemotherapy treatment, 3 years following the interventions. This scenario should be considered as a part of the differential diagnosis of oncology patients presenting with new central neurological symptoms. This active approach can be an effective treatment if the patient is fit and there is no evidence of widespread disease.

Fortuitous administration of denosumab in breast carcinoma with osteoclastic giant cells.

Breast carcinoma with osteoclastic giant cells (OGCs) is a rare entity characterized by an admixture of giant cells and malignant epithelial cells within an inflammatory and vascular stroma. Denosumab is a monoclonal antibody that targets the pathway for osteoclast formation and activation, indicated for the prevention of skeletal-related events in patients with bone metastases, as well as for the treatment of giant cell tumor of bone. We report a patient who presented with aggressive bone recurrence of breast cancer 12 years after her original diagnosis, showing a transformed histology that included multinucleated OGCs, and that was refractory to traditional therapy. Misdiagnosed with a tumor-to-tumor metastasis of breast cancer to a giant cell tumor of bone, she was treated with denosumab for her presumed primary bone disease and had a remarkable clinical and radiological response. To the best of our knowledge, this is the first report of breast cancer with OGCs occurring initially in a metastasis while absent in the original tumor and the first description of its successful treatment with denosumab. This case sheds light on the development of giant cells in the tumor microenvironment and suggests the potential use of denosumab in the management of cancers with giant cell elements.

An 8-Year-Old Child with Malignant Deciduoid Mesothelioma of the Abdomen: Report of a Case and Review of the Literature.

Malignant mesothelioma is an uncommon tumor that usually arises in the pleural cavity of adults with a history of asbestos exposure. Less frequently, it appears in the peritoneum or other mesothelial surfaces. Deciduoid mesothelioma is a rare subtype that has been found at both sites. Of the 3 reported cases in children, 2 originated in the mesenterium and 1 in the pleura. We describe a 4th case of pediatric, malignant, deciduoid mesothelioma and a third case in the mesenteric cavity. The patient was an 8-year-old girl who presented with abdominal pain and fullness. Workup revealed extensive involvement of the abdomen by a serosa-based tumor. The clinical and pathologic findings are described, and the pertinent literature is reviewed.

Metastatic rhabdoid meningioma with BRAF V600E mutation and good response to personalized therapy: case report and review of the literature.

Rhabdoid meningioma is an aggressive phenotype of meningioma, associated with a poor prognosis. We present a very rare case of high-grade meningioma with rhabdoid features that eventually expressed in a coma state. Comprehensive genomic profiling using a Next Generation Sequencing (NGS) assay revealed three genomic alterations: activating BRAF mutation (V600E), loss of CDKN2A/2B, and APC I1307K. After treatment with BRAF inhibitor (dabrafenib), the child's clinical condition improved progressively. After seven months, an MEK inhibitor was added (trametinib).

Alkaline phosphatase level change in patients with osteosarcoma: its role as a predictive factor of tumor necrosis and clinical outcome.

BACKGROUND: In osteosarcoma the histological response, measured by the percentage of tumor necrosis, constitutes one of the most significant predictive factors, with better survival in patients whose tumor necrosis is > or = 90%. OBJECTIVES: To determine if the decrease rate of serum alkaline phosphatase (SAP) levels during the first month of neoadjuvant chemotherapy could serve as a predictive indicator of tumor necrosis and clinical outcome. METHODS: We analyzed the medical files of 53 osteosarcoma patients (19 females, 34 males) (median age 16 years, range 8-24); the disease was metastatic in 12 and localized in the other 41. RESULTS: The histological responses were good in 38 patients (71.7%) and poor in 15 (28.3%). At a median follow-up of 50 months, 34 patients (64.2%) had no evidence of disease and 19 (35.8%) had died from the disease. High levels of SAP at diagnosis correlated with worse survival (P = 0.002). There was no difference in overall survival between patients whose SAP decrease rate was > 25% and those with a rate < 25% (P = 0.14). Among female patients, "rapid" SAP responders had better survival than "slow" responders (P= 0.026). In patients with metastases the SAP decrease rate was positively correlated with survival (P = 0.042). CONCLUSIONS: There was no evidence that "rapid" SAP responders had a higher percentage of tumor necrosis than "slow" responders, although female "rapid" SAP responders had a better prognosis than "slow" responders. Patients with metastases at presentation and "rapid" SAP response had better prognoses.

Previously unrecognized pattern of central nervous system hemangiopericytoma with pseudoglandular spaces.

Central nervous system hemangiopericytoma (HPC) is an uncommon extraaxial tumor with controversial terminology, histogenesis, and grading. Herein, we report a unique example in a 64-year-old woman with a 3.2 cm extra-axial right frontal lobe mass. Histologic sections showed an HPC with increased mitotic activity and elevated proliferation index, interspersed with gland-like spaces lined by epithelioid cells with apical blebs and filled with proteinaceous material. Both spindled and epithelioid cells expressed BCL-2, CD99, and nuclear STAT6, but were negative for CD34, AE1/AE3, CAM5.2, and epithelial membrane antigen. A diagnosis of anaplastic HPC with pseudoglandular spaces was rendered. To our knowledge, this is the first pathologically and molecularly well-documented example in the literature. This pattern has only been reported once in 1983 and is not widely known. Differential diagnosis included synovial sarcoma, anaplastic meningioma with epithelial metaplasia, malignant peripheral nerve sheath tumor, and metastatic carcinosarcoma. Accurate diagnosis depends on recognition of this pattern, along with appropriate immunohistochemical and molecular work-up.

Association between esophageal leiomyomatosis and p53 mutation.

Li-Fraumeni syndrome is a cancer predisposition syndrome associated with a variety of neoplasms, mainly soft tissue sarcoma, premenopausal breast cancer, brain tumors, adrenocortical carcinoma, and leukemia. Esophageal leiomyomatosis involves the presence of several rare benign neoplastic lesions composed of proliferating smooth muscle cells in the esophageal wall. The current case report presents a patient with recurrent diffuse leiomyomas of the esophagus and confirmed p53 mutation with clinical criteria of Li-Fraumenilike syndrome.

Anaplastic ganglioglioma in the spinal cord: case report and literature review.

Anaplastic ganglioglioma (AGG) is a rare tumor. A PubMed database search yielded only a few case reports and fewer case series. An even rarer entity is AGG arising in the spinal cord. We present a case of a pediatric patient with a pathological diagnosis of spinal AGG.

Primary cardiac chondrosarcoma with rapid MFH-like recurrence: case report and review of tumor type.

We present a case report of a patient with a rare primary cardiac tumor, chondrosarcoma. After initial excision, a locally advanced recurrence appeared within six weeks at a different site in the heart with the histological features of a high-grade sarcoma. We discuss the background, management and prognosis of these rare tumors.

Undifferentiated sarcoma of the thyroid in a child.

The most common malignant tumor of the thyroid is papillary carcinoma. Sarcoma of the thyroid is encountered very rarely; its therapy is complex and poses significant problems due to the problematic location of the tumor. A 14-year-old female was diagnosed with undifferentiated sarcoma of the thyroid and received combined therapy comprising surgery, chemo- and radiotherapy without significant side effects. This case underlines the fact that undifferentiated thyroid sarcoma may be a diagnostic possibility in children with malignant masses of the neck and may be successfully treated with modern therapeutic strategies.

Osteogenic sarcoma in a child with familial expansile osteolysis syndrome: an accidental association?

We present the first reported case of a child with familial expansile osteolysis syndrome (FEO) who developed osteogenic sarcoma (OS) of the iliac bone. A 17-year-old adolescent presented with pain and a mass on the left pelvis. He was from a family with several members who had been diagnosed with FEO, from which he also suffered. The median life expectancy of affected members of the family was reported as 25 to 30 years, with death ensuing as a result of various respiratory and cardiac complications of severe skeletal deformations, characteristic of increased bone turnover as seen in FEO. Biopsy of the patient's mass revealed chondroblastic OS. He was treated according to the P9754 protocol for patients with newly diagnosed nonmetastatic OS. Chemotherapy consisted of HD-MTX, ifosfomide, doxorubicin, and cisplatin. Complete resection of the tumor was carried out, but the patient subsequently developed metastatic disease and died (histologic response to neoadjuvant chemotherapy-85%). The patient's alkaline phosphatase level that was highly elevated before the start of chemotherapy, dropped significantly during treatment, with repeated elevation soon after definitive surgery, while he was recuperating and not on treatment. We speculate that chemotherapy affected not only the malignant cells of OS but normal osteoblasts as well, with a decreasing level of alkaline phosphatase even in the absence of any clinical and radiographic signs of OS. We also think that increased bone turnover, characteristic of a condition such as FEO, may facilitate de novo development of OS.

Plasma heparanase as a significant marker of treatment response in children with Hodgkin lymphoma: pilot study.

INTRODUCTION: The aim of this pilot study was to determine heparanase plasma levels (HP) at diagnosis and at restaging in children diagnosed with Hodgkin lymphoma and to investigate whether this parameter provides prognostic information for response to treatment after induction therapy. PATIENTS AND METHODS: HP levels of 19 pediatric patients (mean age: 10.3 years (y) (range, 4-18 y), 9 girls, 10 boys) with Hodgkin lymphoma were assayed at diagnosis and at restaging. HP levels were determined using an ELISA anti-human heparanase immunoassay kit. According to diagnosis, CAT scan and/or FDG/ PET-CT fusion were performed to assess response to treatment after 2-3 courses of chemotherapy. Two patients received VAMP protocol (1 stage IA, 1 stage IIA), 1 received AV-PC (nonbulky stage IIA), 4 received COPP/ABV (3 stage IIA bulky, 1 stage IIIA nonbulky), 4 received ABVE-PC (2 stage IIB, 1 stage IIA bulky, 1 stage IIIA bulky), 2 received ABVD (1 stage IIA bulky, 1 stage IIIA), and 6 received escalated BEACOPP (1 stage IIIB, 3 stage IVA, 2 stage IVB). RESULTS: Changes in HP levels were found to correlate with response to treatment for most of the children. At diagnosis, average HP level was 1019 pg/mL (range, 141-5733 pg/mL), decreasing at restaging to 588 pg/mL (range, 62-3267 pg/mL) (p = .034). At diagnosis, the average HP of the 16 patients in CR or VGPR was 1104 pg/mL; it had decreased at restaging to 586 pg/mL (p = .032). At diagnosis, the average HP level for the 3 patients with TP or PR was 1704 pg/mL; it had increased to 1938 pg/mL at restaging (p = .166). Due to the small number of patients, no correlation was observed between HP levels at diagnosis, staging, or any other clinical prognostic factor. CONCLUSIONS: Changes in plasma HP levels correlated with response to treatment for children diagnosed with Hodgkin lymphoma. This provides a rationale for exploring clinical interest in plasma heparanase measurements of a larger group, using the test for clinical trials of antiangiogenic therapies.

Accelerated pulmonary nodulosis and sterile pleural effusion in a patient with psoriatic arthropathy during methotrexate therapy: a case report.

Pulmonary nodulosis and sterile pleural exudates are well-known extra-articular manifestations in rheumatoid arthritis patients with a positive rheumatoid factor. In some patients, treatment with methotrexate has been postulated as the trigger of these complications. We report a patient with psoriatic arthropathy, negative RF, negative anticyclic citrulinated peptide antibodies but positive antibodies to cardiolipin who developed massive sterile pleural empyema and multiple cavitary pulmonary nodules during methotrexate treatment. We suggest that awareness of methotrexate-induced lung and pleural complications should be extended to other than rheumatoid arthritis diseases, not necessarily accompanied by rheumatoid factor or anticyclic citrulinated peptide antibodies.

Neuroprotective effect of Ro5-4864 following brain injury.

The 18 kDa translocator protein (TSPO) is a protein complex located at the outer mitochondrial membrane and interacting with the mitochondrial permeability transition pore (mPTP), indicating its involvement in the control of mPTP opening. We intended to explore the effect of TSPO ligands, PK 11195 and Ro5-4864 on apoptosis in a rat model of cortical injury. Sprague-Dawley rats received a daily intraperitoneal injection of dimethylsulfoxide (vehicle), PK 11195, or Ro5-4864, starting 2 days prior the injury and a third injection after the injury. At 6 weeks, immunohistochemistry analysis showed that Ro5-4864 resulted in a significant increase in the number of surviving neurons and in the density of the neurofilament network in the perilesional cortex in comparison with animals of the vehicle and PK 11195 groups. In tissue samples dissected from the injured area, Ro5-4864 caused a significant reduction in activation of caspases 3 and 9 but not of caspase 8 in comparison with the vehicle and PK 11195 groups. In addition, measurements of transmembrane mitochondrial potential of mitochondria (Deltapsi(M)) isolated from normal rat brain showed that loss of Deltapsi(M) induced by recombinant Bax could be significantly reduced by Ro5-4864 in a concentration-dependent manner. Our findings indicate that the neuroprotective effect shown by Ro5-4864 in the present model of brain injury involves the mitochondrial pathway of apoptosis modulation of mPTP.

Ultrasound imaging of fasciitis due to body-building supplement.

BACKGROUND: Fascia and soft tissues, rich in collagen, receptors of pain and capable of significant distention, may be targets of autoimmune inflammatory diseases. We observed fasciitis due to the protein supplement Pure Whey, which has not been reported previously. METHODS: Sonography (Sonosite-Titan, 5 to 10 MHz, L-38) was performed on a patient (age, 26 years; body mass index, 38 kg/m2) with protein fasciitis. He had developed compact swelling of his forearms, hands, and legs, with skin irregularity and severe disability (without peripheral eosinophilia, normal Ig and ESR 18/hr) after taking Pure Whey, containing L-tryptophan (1.4 g per 100 g of protein). A deep skin biopsy was performed. The thickness of the brachioradial fascia (BRF) was measured and compared with 10 healthy control subjects (men ages 36.7 +/- 8.3 years; body mass index, 26.4 +/- 6.5 kg/m2). RESULTS: The deep skin biopsy showed severe fat interlobular and fascial thickening with mononuclear (noneosinophilic) infiltrate and fibrosis associated with fasciitis. BRF of the 10 healthy men had a thickness of 0.75 +/- 0.19 mm, compared with the patient's 2.4 mm thickened and cleaved BRF. After 2.5 months of corticosteroid therapy (30 mg/d with tapering) and discontinuation of the protein supplement, the patient's BRF returned to a monolayer appearance. Its thickness reduced to normal (0.8 mm), with significant clinical improvement. CONCLUSIONS: This case of noneosinophilic fasciitis associated with ingestion of L-tryptophan-containing protein supplement responded favorably to corticosteroid therapy. Sonography proved to be an effective method to visualize and confirm the fasciitis and to follow the course and therapy.

Secondary glioblastoma multiforme after treatment for primary choroid plexus carcinoma in childhood.

A 15-year-old boy was diagnosed with choroid plexus carcinoma (CPC) of the right lateral ventricle. His metastatic work-up was negative. After complete macroscopic resection of the tumor, the patient was treated with chemotherapy consisting of vincristine, cisplatin, etoposide, and carboplatin, followed by radiotherapy for a total dose of 34.2 Gy on the whole craniospinal axis plus a boost of 19.8 Gy at the tumor region. The patient remained in complete clinical and radiologic remission over the next 5 years when a secondary malignant tumor, glioblastoma multiforme, a rare complication of the treatment of CPC, was diagnosed. This case reflects the necessity of thorough follow-up in long-term survivors of CPC.

Imaging features of posterior mediastinal chordoma in a child.

A 5 1/2-year-old boy presented with repeated episodes of stridor and cough. Chest radiography demonstrated a widened mediastinum. Evaluation by CT revealed a low-density posterior mediastinal mass initially diagnosed as benign tumor. Histopathological analysis of the resected mass disclosed a malignant chordoma. Our radiological results are described with an analysis of the imaging findings in the medical literature. We present our suggestions for preoperative evaluation of posterior mediastinal tumors.

Immunohistochemical expression of peripheral benzodiazepine receptors in human astrocytomas and its correlation with grade of malignancy, proliferation, apoptosis and survival.

Peripheral benzodiazepine receptors (PBR) are widely distributed in peripheral tissues, astrocytes, and microglia of the brain. They are involved in apoptosis, proliferation, and many other processes, such as steroidogenesis in adrenal glands, male and female gonads, biological adaptation to stress, etc. It has been established that the expression of PBR in astrocytomas is higher than in the normal brain. The goal of this study was to explore the correlation of the immunohistochemical expression of PBR in astrocytomas with the grade of malignancy and rates of apoptosis, proliferation and survival. In 130 cases of astrocytomas (25 grade I, 25 grade II, 20 grade III, 60 grade IV), paraffin sections were stained immunohistochemically for PBR and MIB-1(Ki-67). TUNEL assay was used for evaluation of apoptosis. It was found that the intensity and extent of staining for PBR had a strong direct correlation with the grade of malignancy of the tumor, along with proliferative and apoptotic indices. The highest expression of PBR was in glioblastomas grade IV, especially around areas of necrosis. There was a strong negative correlation between PBR expression and survival. The results of this study may be applied in the pathological diagnosis of astrocytomas as an additional clue in establishing tumor grade; they may be used in the imaging of astrocytomas, both for diagnosis and follow-up, by the application of positron emission tomography scanning with PBR specific ligands. Targeting of PBR in high-grade gliomas may be a promising approach, achieving more specific anti-tumor effect.