MDM2 Amplification and PI3KCA Mutation in a Case of Sclerosing Rhabdomyosarcoma.

A rare sclerosing variant of rhabdomyosarcoma characterized by prominent hyalinization and pseudovascular pattern has recently been described as a subtype biologically distinct from embryonal, alveolar, and pleomorphic forms. We present cytogenetic and molecular findings as well as experimental studies of an unusual case of sclerosing rhabdomyosarcoma. The primary lesion arose within the plantar subcutaneous tissue of the left foot of an otherwise healthy 23-year-old male who eventually developed pulmonary nodules despite systemic chemotherapy. Two genetic abnormalities identified in surgical and/or autopsy samples of the tumor were introduced into 10T1/2 murine fibroblasts to determine whether these genetic changes cooperatively facilitated transformation and growth. Cytogenetic analysis revealed a complex abnormal hyperdiploid clone, and MDM2 gene amplification was confirmed by fluorescence in situ hybridization. Cancer gene mutation screening using a combination of multiplexed PCR and mass spectroscopy revealed a PIK3CA exon 20 H1047R mutation in the primary tumor, lung metastasis, and liver metastasis. However, this mutation was not cooperative with MDM2 overexpression in experimental assays for transformation or growth. Nevertheless, MDM2 and PIK3CA are genes worthy of further investigation in patients with sclerosing rhabdomyosarcoma and might be considered in the enrollment of these patients into clinical trials of targeted therapeutics.

Cytogenetic analysis of a hemosiderotic fibrolipomatous tumor.

Hemosiderotic fibrolipomatous tumor is an extremely rare, nonencapsulated, fatty lesion with a consistent histologic appearance that was originally considered reactive in nature. To our knowledge, there are no previous reports on the cytogenetics of this lesion. Reported here is a case of hemosiderotic fibrolipomatous tumor arising within the subcutaneous tissue of the right foot, dorsal aspect, of an otherwise healthy 35-year-old woman. Subsequent cytogenetic analysis revealed a clonal reciprocal translocation between chromosomes 1 and 10, with a further rearrangement involving this derivative chromosome 1 and chromosome 3. This, in addition to its characteristic morphology and immunophenotype, supports the neoplastic nature of this tumor and may aid in its diagnosis.

Effects of larval density and predation by Toxorhynchites amboinensis on Aedes polynesiensis (Diptera: Culicidae) developing in coconuts.

Organisms manipulated as biological control agents of disease vectors should tolerate ranges of developmental conditions exploited by their target species. Furthermore, they should reduce numbers of host-seeking vector adults without providing fitness benefits to larval survivors developing among fewer competitors. We studied electrochemistry in rat-chewed coconuts, an important developmental habitat used by Aedes polynesiensis, a vector of lymphatic filariasis. We also studied the effects of larval density and predation by the mosquito Toxorhynchites amboinensis as predators of Ae. polynesiensis. The predators significantly reduced survival rates of Ae. polynesiensis and numbers of males and females developing in coconut husks. Adults from cohorts of Ae. polynesiensis exposed to predators emerged at the same time and were equal in size to adults emerging from predator-free cohorts. No differences were detected in the numbers or sizes of Ae. polynesiensis reaching adulthood among the densities tested. At least for this common natural habitat, Tx. amboinensis gave a good level of biological control of the vector Ae. polynesiensis.

Cardiac changes noted within 4 years of transplant in postmortem evaluation of a patient with untreated obstructive sleep apnea.

In this case report, the authors discuss the autopsy findings of biventricular cardiomegaly 4 years after transplantation of an otherwise normal heart in a patient who did not accept treatment for documented severe obstructive sleep apnea.

A standardized patient enrolled in medical school considers the national clinical skills examination.

The National Board of Medical Examiners' recent decision to include a clinical skills examination as part of the licensing requirements for U.S. medical graduates has generated widespread discussion about the role of standardized patients in medical education. The author demonstrates that while specific clinical skills can and should be integrated into the medical school curriculum, any assessment of these skills using interactions with standardized patients must allow for a fuller range of responses and immediate, multifaceted feedback (content, process, and patient satisfaction) than would be allowed in the proposed Step 2 Clinical Skills. The presence of a national examination would pressure medical schools to adopt the very limited model of patient-physician interaction favored by the National Board of Medical Examiners. In addition, the author argues that the cost of registering for the examination and traveling to one of the few test sites on borrowed money is not justified to verify skills that may be reliably assessed locally.