Blastic Plasmacytoid Dendritic Cell Neoplasm: A Case Series and Review.

ABSTRACT: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic malignancy that frequently has cutaneous manifestations. The diagnosis can be a challenge because of its heterogenous clinical presentation, ranging from a brown or violaceous solitary nodule or patch to mixed, disseminated lesions. Furthermore, BPDCN tumor cells express immunohistochemical markers in common with acute myeloid leukemia, which can lead to misdiagnosis. Timely diagnosis requires awareness of its cutaneous manifestations and unique histopathology and immunophenotype. We present a case series of patients diagnosed with BPDCN and review the cutaneous and histopathologic characteristics of this uncommon entity.

Melanoma patient notification and treatment timelines.

Melanoma is an extremely aggressive cancer for which the American Academy of Dermatology currently does not have formal recommendations outlining a timeline from biopsy to definitive treatment. Our dermatology department investigated our treatment timeline for melanoma. Using the database from our electronic medical record, Epic, we evaluated patients over a one-year period; in total we identified 109 melanomas. We evaluated patient demographics, tumor characteristics, and timelines regarding diagnosis and treatments. There was a statistically significant difference in patient notification of diagnosis and treatment times between stage 1 and stages 2-4 combined (based on the American Joint Committee on Cancer staging system). We found that 84% of melanomas were treated within 4 weeks of diagnosis and 96% within 6 weeks. The lower the stage, the earlier the melanoma was definitively treated; higher stage melanomas had a longer delay to definitive treatment. Herein, we have presented our single institutional experience of the melanoma timeline from diagnosis to definitive treatment and have identified factors that impact timely definitive treatment.

Diagnosing an ulcerated gouty tophus.

We present the case of a 44-year-old man with a complicated past medical history who presented with presumed sepsis secondary to pneumonia and severe joint pain secondary to gout. Despite an entirely negative infectious workup during his lengthy hospitalization, he developed ulcerated, draining wounds on his hands and feet that were also initially presumed to be infectious. The chalky substance draining from the wounds was eventually evaluated with potassium hydroxide under polarized microscopy and found to have the characteristic negative birefringence of sodium urate crystals. He was treated with steroids after an infectious etiology had been ruled out, and he improved clinically once his uric acid levels began to fall.

A novel bone morphogenetic protein 2 mutant mouse, nBmp2NLS(tm), displays impaired intracellular Ca2+ handling in skeletal muscle.

We recently reported a novel form of BMP2, designated nBMP2, which is translated from an alternative downstream start codon and is localized to the nucleus rather than secreted from the cell. To examine the function of nBMP2 in the nucleus, we engineered a gene-targeted mutant mouse model (nBmp2NLS(tm)) in which nBMP2 cannot be translocated to the nucleus. Immunohistochemistry demonstrated the presence of nBMP2 staining in the myonuclei of wild type but not mutant skeletal muscle. The nBmp2NLS(tm) mouse exhibits altered function of skeletal muscle as demonstrated by a significant increase in the time required for relaxation following a stimulated twitch contraction. Force frequency analysis showed elevated force production in mutant muscles compared to controls from 10 to 60 Hz stimulation frequency, consistent with the mutant muscle's reduced ability to relax between rapidly stimulated contractions. Muscle relaxation after contraction is mediated by the active transport of Ca(2+) from the cytoplasm to the sarcoplasmic reticulum by sarco/endoplasmic reticulum Ca(2+) ATPase (SERCA), and enzyme activity assays revealed that SERCA activity in skeletal muscle from nBmp2NLS(tm) mice was reduced to approximately 80% of wild type. These results suggest that nBMP2 plays a role in the establishment or maintenance of intracellular Ca(2+) transport pathways in skeletal muscle.

Is magnetic resonance imaging in addition to a computed tomographic scan necessary to identify clinically significant cervical spine injuries in obtunded blunt trauma patients?

BACKGROUND: Guidelines are in place directing the clearance of the cervical spine in patients who are awake, alert, and oriented, but a gold standard has not been recognized for patients who are obtunded. Our study is designed to determine if magnetic resonance imaging (MRI) detects clinically significant injuries not seen on computed tomographic (CT) scans. METHODS: The trauma registry was used to identify and retrospectively review medical records of blunt trauma patients from January 1, 2005, to March 30, 2012. Only obtunded patients with a CT scan and MRI of the cervical spine were included. RESULTS: The study cohort consisted of 277 patients. In 13 (5%) patients, MRI detected clinically significant cervical spine injuries that were missed by CT scans, and in 7 (3%) these injuries required intervention. The number needed to screen with MRI to prevent 1 missed injury was 21. CONCLUSIONS: The findings suggest that the routine use of MRI in clearing the cervical spine in the obtunded blunt trauma patient.

Skeletal muscle dysfunction in muscle-specific LKB1 knockout mice.

Liver kinase B1 (LKB1) is a tumor-suppressing protein that is involved in the regulation of muscle metabolism and growth by phosphorylating and activating AMP-activated protein kinase (AMPK) family members. Here we report the development of a myopathic phenotype in skeletal and cardiac muscle-specific LKB1 knockout (mLKB1-KO) mice. The myopathic phenotype becomes overtly apparent at 30-50 wk of age and is characterized by decreased body weight and a proportional reduction in fast-twitch skeletal muscle weight. The ability to ambulate is compromised with an often complete loss of hindlimb function. Skeletal muscle atrophy is associated with a 50-75% reduction in mammalian target of rapamycin pathway phosphorylation, as well as lower peroxisome proliferator-activated receptor-alpha coactivator-1 content and cAMP response element binding protein phosphorylation (43 and 40% lower in mLKB1-KO mice, respectively). Maximum in situ specific force production is not affected, but fatigue is exaggerated, and relaxation kinetics are slowed in the myopathic mice. The increased fatigue is associated with a 30-78% decrease in mitochondrial protein content, a shift away from type IIA/D toward type IIB muscle fibers, and a tendency (P=0.07) for decreased capillarity in mLKB1-KO muscles. Hearts from myopathic mLKB1-KO mice exhibit grossly dilated atria, suggesting cardiac insufficiency and heart failure, which likely contributes to the phenotype. These findings indicate that LKB1 plays a critical role in the maintenance of both skeletal and cardiac function.