Leukemia cutis and facial nerve palsy as presenting symptoms of acute lymphoblastic leukemia.

Leukemia cutis and facial nerve palsy are rare presenting symptoms of leukemia. This report describes a case of acute T-cell lymphoblastic leukemia (ALL) presenting with only these two symptoms, a presentation of ALL that, to our knowledge, has not been previously described. It serves to alert physicians to look for underlying malignancy in the setting of cutaneous findings associated with facial nerve palsy.

Gluteal silicone injections leading to extensive filler migration with induration and arthralgia.

Silicone injections have been used for cosmetic soft tissue augmentation for over five decades with documented consequences both systemic and dermatologic. We present a case of extensive filler migration causing bilateral lower extremity woody induration in a 53 year old Hispanic woman. She presented with a multi-year history of progressive joint stiffening at the knees, accompanied by induration and pain of the bilateral lower extremities. The patient had received two injections of an unknown substance placed into her bilateral gluteals 11 years prior. MRI indicated an infiltrative process of both lower extremities and pathology was consistent with migration of injected tissue augmentation material, most likely silicone. Due to the extent of involvement the patient was started on a trial of doxycycline 100 mg PO BID.

PP6C hotspot mutations in melanoma display sensitivity to Aurora kinase inhibition.

UNLABELLED: Recent whole genome melanoma sequencing studies have identified recurrent mutations in the gene encoding the catalytic subunit of serine/threonine phosphatase 6 (PPP6C/PP6C). However, the biochemical, functional, and clinical ramifications of these mutations are unknown. Sequencing PP6C from patients with melanoma (233 primary and 77 metastatic specimens) with extended prospective clinical outcome revealed a large number of hotspot mutations in patients with both primary and metastatic melanoma. Despite minimal association between stage and presence of PP6C mutations in patients with primary melanoma, a subpopulation of cells within each tumor did contain PP6C mutations, suggesting PP6C mutation is an early, but non-tumor-initiating event in melanoma. Among patients with primary melanoma with PP6C mutations, patients with stop mutations had significantly shorter recurrence-free survival compared with patients without stop mutations. In addition, PP6C mutations were independent of commonly observed BRAF and NRAS mutations. Biochemically, PP6C mutations could be classified as those that interact with PP6C regulatory subunits and those that do not. Mutations that did not bind to PP6C regulatory subunits were associated with increased phosphorylation of Aurora kinase, a PP6C substrate, and mitotic defects. However, both classes of PP6C mutations led to increased sensitivity to Aurora kinase inhibition. Together, these data support for the first time that PP6C mutations are molecularly, biochemically, and clinically heterogeneous. IMPLICATIONS: PP6C mutations have distinct functional and clinical consequences in melanoma, and confer sensitivity to Aurora A kinase inhibitors.