Collision tumors: A review of their types, pathogenesis, and diagnostic challenges.

A collision tumor is a neoplastic lesion comprised of two or more distinct cell populations that maintain distinct borders. Collision tumors, which are rare but well documented, can be composed of two benign tumors, a benign and malignant tumor, and two malignant tumors. Although case reports and reviews on specific types of collision tumors exist, a cohesive source discussing these tumors is lacking. We critically reviewed the literature by analyzing case reports and retrospective studies in order to evaluate the following regarding collision tumors: definitions, types, pathogenesis, diagnosis, and management. Reports of these tumors are infrequent but not insignificant, and accurate classification and diagnosis will lead to better patient outcomes.

First-Onset Herpesviral Infection and Lung Injury in Allogeneic Hematopoietic Cell Transplantation.

Rationale: "Noninfectious" pulmonary complications are significant causes of morbidity and mortality after allogeneic hematopoietic cell transplant. Early-onset viral reactivations or infections are common after transplant. Whether the first-onset viral infection causes noninfectious pulmonary complications is unknown. Objectives: To determine whether the first-onset viral infection within 100 days after transplant predisposes to development of noninfectious pulmonary complications. Methods: We performed a retrospective review of 738 allogeneic hematopoietic cell transplant patients enrolled from 2005 to 2011. We also established a novel bone marrow transplantation mouse model to test whether herpesviral reactivation after transplant causes organ injury. Measurements and Main Results: First-onset viral infections with human herpesvirus 6 or Epstein-Barr virus within 100 days after transplant increase the risk of developing idiopathic pneumonia syndrome (adjusted hazard ratio [aHR], 5.52; 95% confidence interval [CI], 1.61-18.96; P = 0.007; and aHR, 9.21; 95% CI, 2.63-32.18; P = 0.001, respectively). First infection with human cytomegalovirus increases risk of bronchiolitis obliterans syndrome (aHR, 2.88; 95% CI, 1.50-5.55; P = 0.002) and grade II-IV acute graft-versus-host disease (aHR, 1.59; 95% CI, 1.06-2.39; P = 0.02). Murine roseolovirus, a homolog of human herpesvirus 6, can also be reactivated in the lung and other organs after bone marrow transplantation. Reactivation of murine roseolovirus induced an idiopathic pneumonia syndrome-like phenotype and aggravated acute graft-versus-host disease. Conclusions: First-onset herpesviral infection within 100 days after allogeneic hematopoietic cell transplant increases risk of pulmonary complications. Experimentally reactivating murine roseolovirus causes organ injury similar to phenotypes seen in human transplant recipients.

Hydroxyurea: a reappraisal of its cutaneous side effects and their management.

Hydroxyurea (HU) is known to cause a broad spectrum of cutaneous side effects, ranging from relatively benign to severe. Although dermatologists are often consulted for the treatment of these side effects, a comprehensive resource discussing the different types and their management is lacking. In this study, we conducted a literature search in order to critically evaluate the reported types and management of hydroxyurea's cutaneous side effects, as well as review its mechanism of action, dermatologic uses, and common systemic side effects. Relatively common and benign side effects include hyperpigmentation, xerosis, and skin atrophy. While serious cutaneous side effects such as leg ulcers or nonmelanoma skin cancers occur in a substantial proportion of patients, these may resolve with HU discontinuation and proper dermatologic management. Therefore, it is crucial for dermatologists to be aware of these various cutaneous side effects and their management as prompt diagnosis and proper treatment will improve patient outcomes.

Antipsychotic Medication-Induced Hyperthermia Leading to Cerebrovascular Accident: A Case Report.

Antipsychotic medications are used in the management of schizophrenia. Antipsychotic medications treat both positive and negative symptoms via the dopamine D2 receptor and serotonin 5-HT2A blockade pathway. Side effects include hyperprolactinemia, prolonged QTc, and neuroleptic malignant syndrome. However, antipsychotic medication-induced hyperthermia potentiating a cerebrovascular accident (CVA) is a rare side effect that is less well known. A 47-year-old male presented to the emergency department (ED) via emergency medical services for altered mental status. He was given naloxone without improvement in mental status. His glucose was 110 mg/dL. Upon presentation to the ED, he was hyperthermic (106.7 degrees Fahrenheit) and tachycardic (heart rate of 160's beats/minute). Home medications included risperidone and fluphenazine. After the resolution of his hyperthermia, he had a right-sided facial droop concerning a cerebrovascular accident. Magnetic resonance imaging (MRI) of the brain confirmed an early/acute subacute right cerebellar infarction. The patient received optimal treatment; his mental status returned to baseline, and he was discharged home without antipsychotic medications. Patients who are prescribed antipsychotics should be aware of the potentially fatal adverse events that can occur from these medications. Thermoregulation may be impaired in these patients, resulting in significant hyperthermia, in which case antipsychotic medications should be discontinued.

Serial in vivo imaging of transplanted allogeneic neural stem cell survival in a mouse model of amyotrophic lateral sclerosis.

Neural stem cells (NSCs) are being investigated as a possible treatment for amyotrophic lateral sclerosis (ALS) through intraspinal transplantation, but no longitudinal imaging studies exist that describe the survival of engrafted cells over time. Allogeneic firefly luciferase-expressing murine NSCs (Luc+-NSCs) were transplanted bilaterally (100,000 cells/2µl) into the cervical spinal cord (C5) parenchyma of pre-symptomatic (63day-old) SOD1G93A ALS mice (n=14) and wild-type age-matched littermates (n=14). Six control SOD1G93A ALS mice were injected with saline. Mice were immunosuppressed using a combination of tacrolimus+sirolimus (1mg/kg each, i.p.) daily. Compared to saline-injected SOD1G93A ALS control mice, a transient improvement (p<0.05) in motor performance (rotarod test) was observed after NSC transplantation only at the early disease stage (weeks 2 and 3 post-transplantation). Compared to day one post-transplantation, there was a significant decline in bioluminescent imaging (BLI) signal in SOD1G93A ALS mice at the time of disease onset (71.7±17.9% at 4weeks post-transplantation, p<0.05), with a complete loss of BLI signal at endpoint (120day-old mice). In contrast, BLI signal intensity was observed in wild-type littermates throughout the entire study period, with only a 41.4±8.7% decline at the endpoint. In SOD1G93A ALS mice, poor cell survival was accompanied by accumulation of mature macrophages and the presence of astrogliosis and microgliosis. We conclude that the disease progression adversely affects the survival of engrafted murine Luc+-NSCs in SOD1G93A ALS mice as a result of the hostile ALS spinal cord microenvironment, further emphasizing the challenges that face successful cell therapy of ALS.

Co-transplantation of syngeneic mesenchymal stem cells improves survival of allogeneic glial-restricted precursors in mouse brain.

Loss of functional cells from immunorejection during the early post-transplantation period is an important factor that reduces the efficacy of stem cell-based therapies. Recent studies have shown that transplanted mesenchymal stem cells (MSCs) can exert therapeutic effects by secreting anti-inflammatory and pro-survival trophic factors. We investigated whether co-transplantation of MSCs could improve the survival of other transplanted therapeutic cells. Allogeneic glial-restricted precursors (GRPs) were isolated from the brain of a firefly luciferase transgenic FVB mouse (at E13.5 stage) and intracerebrally transplanted, either alone, or together with syngeneic MSCs in immunocompetent BALB/c mice (n=20) or immunodeficient Rag2(-/-) mice as survival control (n=8). No immunosuppressive drug was given to any animal. Using bioluminescence imaging (BLI) as a non-invasive readout of cell survival, we found that co-transplantation of MSCs significantly improved (p<0.05) engrafted GRP survival. No significant change in signal intensities was observed in immunodeficient Rag2(-/-) mice, with transplanted cells surviving in both the GRP only and the GRP+MSC group. In contrast, on day 21 post-transplantation, we observed a 94.2% decrease in BLI signal intensity in immunocompetent mice transplanted with GRPs alone versus 68.1% in immunocompetent mice co-transplanted with MSCs and GRPs (p<0.05). Immunohistochemical analysis demonstrated a lower number of infiltrating CD45, CD11b(+) and CD8(+) cells, reduced astrogliosis, and a higher number of FoxP3(+) cells at the site of transplantation for the immunocompetent mice receiving MSCs. The present study demonstrates that co-transplantation of MSCs can be used to create a microenvironment that is more conducive to the survival of allogeneic GRPs.

Metastatic breast cancer cells in lymph nodes increase nodal collagen density.

The most life-threatening aspect of breast cancer is the occurrence of metastatic disease. The tumor draining lymph nodes typically are the first sites of metastasis in breast cancer. Collagen I fibers and the extracellular matrix have been implicated in breast cancer to form avenues for metastasis. In this study, we have investigated extracellular matrix molecules such as collagen I fibers in the lymph nodes of mice bearing orthotopic human breast cancer xenografts. The lymph nodes in mice with metastatic MDA-MB-231 and SUM159 tumor xenografts and tumor xenografts grown from circulating tumor cell lines displayed an increased collagen I density compared to mice with no tumor and mice with non-metastatic T-47D and MCF-7 tumor xenografts. These results suggest that cancer cells that have metastasized to the lymph nodes can modify the extracellular matrix components of these lymph nodes. Clinically, collagen density in the lymph nodes may be a good marker for identifying lymph nodes that have been invaded by breast cancer cells.