Immunotherapy and chemotherapy benefit few patients with metastatic melanoma, and even fewer experience durable survival benefit. These poor results come from treating melanoma as a single homogeneous disease. Recently, it has been shown that targeting activated tyrosine kinases (oncogenes) can mediate striking clinical benefits in several cancers. In 2002, a mutation at the V600E amino acid of the BRAF serine/threonine kinase was described as present in over 50% of melanomas. The mutation appeared to confer a dependency by the melanoma cancer cell on its activation of the MAP kinase pathway. The frequency and specificity of this mutation (95% at V600E of BRAF) suggests that it may be a potential target for therapy, and recent results with one inhibitor, PLX4032/RG7204, bare this out. This review updates the status of BRAF inhibitors in melanoma and what may be on the horizon.
Intravascular lymphoma (IVL) is an extremely rare subtype of diffuse large B-cell lymphoma, characterized by the occlusion of small blood vessels with clonal lymphoid cells [1]. Neoplastic cells are commonly of B-cell origin, although rare cases of T or NK-cells have been reported [2][3][4]. The mechanism for the peculiar blood vessel tropism of IVL is not known. Ponzoni et al. [5] demonstrated defects in the surface expression of adhesion molecules ( 1 integrin and I-CAM) responsible for intravascular migration of lymphocytes in IVL, which could be associated with this characteristic distribution pattern. Anthracycline-based chemotherapy is considered the standard front-line treatment, however, its utility is limited because of relatively short remission durations and poor performance status at presentation [1,2]. Rituximab (Rituxan, Genentech, San Francisco, CA) is an attractive treatment option in IVL because of the intravascular location of brightly CD20 positive lymphoid cells. We report here a case of IVL in a 63-year-old patient who had a dramatic sustained remission to planned treatment with single-agent rituximab without anthracycline-based chemotherapy.A 63-year-old white male presented with fevers (1038F) and a nonproductive cough. His past medical history was significant for diabetes, hypothyroidism, hyperlipidemia, and celiac disease with associated iron deficiency anemia. On two prior occasions, he had suffered similar symptoms but a thorough workup of his symptoms including blood cultures, hepatitis profile, HIV testing, radiographic imaging, bone marrow biopsy, and lumbar puncture etc., recovered only with a diagnosis of FUO. On the most recent occasion, his physical examination was unremarkable. Laboratory studies showed mild anemia, platelet count of 296 Â 10 9 /l, an erythrocyte sedimentation rate of >140 mm/hr, and lactate dehydrogenase (LDH) of 788 U/l (normal range 94-172 U/l). CT-scans of chest, abdomen, and pelvis were normal.
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