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Background: Though rare, pathologic extramedullary hematopoiesis (EMH) can occur in response to myeloproliferative disorders and may present as paravertebral masses. Case Description: We describe a 63-year-old female with unspecified thalassemia, hemochromatosis, and known asymptomatic extramedullary hematopoiesis of the thoracic spine who acutely developed severe spinal cord compression and a T9 vacuum phenomenon fracture 7 months after her initial diagnosis. Outcome: The patient was treated with urgent decompression and T9 kyphoplasty, which resulted in complete resolution of her neurological deficits. Conclusions: The timeline of symptomatology in the case suggests that asymptomatic patients with T-spine extramedullary hematopoiesis can develop progressive neurologic deterioration and atraumatic compression fractures culminating in acute spinal cord injury. While it may be appropriate to treat asymptomatic patients conservatively, surgical decompression must always remain a consideration.

Summary: Although combination BRAF/MEK inhibition has produced significant survival benefits for BRAF p.V600 mutant melanomas, targeted therapies approved for BRAF non-p.V600 mutant melanomas remain limited. Through the analysis of 772 cutaneous melanoma exomes, we reveal that BRAF non-p.V600 mutations co-occurs more frequently with NF1 loss, but not with oncogenic NRAS mutations, than expected by chance. We present cell signaling data, which demonstrate that BRAF non-p.V600 mutants can signal as monomers and dimers within an NF1 loss context. Concordantly, BRAF inhibitors that inhibit both monomeric and dimeric BRAF synergize with MEK inhibition to significantly reduce cell viability in vitro and tumor growth in vivo in BRAF non-p.V600 mutant melanomas with co-occurring NF1 loss-of-function mutations. Our data suggest that patients harboring BRAF non-p.V600 mutant melanomas may benefit from current FDA-approved BRAF/MEK inhibitor combination therapy currently reserved for BRAF p.V600 mutant patients.