A Malignant Granular Cell Tumor Excised with Mohs Micrographic Surgery

Malignant granular cell tumors are extremely rare, aggressive neoplasms displaying rapid growth and frequent associated metastatic disease. Excision and evaluation for metastatic disease are mandatory. We present a 54-year-old patient with a malignant granular cell tumor, treated with Mohs micrographic surgery. Cutaneous granular cell tumors are uncommon neoplasms, likely of perineural origin. Most follow a benign and uneventful course, with wide local excision being the treatment of choice (Enzinger, 1988). The malignant granular cell tumor is an extremely rare, aggressive variant, which provides a diagnostic challenge and management dilemma, especially with early presentation when it may be mistaken for other entities. There is also controversy regarding surgical management and follow-up of both benign and malignant granular cell tumors

Curcuminoids activate p38 MAP kinases and promote UVB-dependent signalling in keratinocytes.

Curcuminoids exhibit anti-proliferative properties in many cell lines by modulating signalling pathways to inhibit cell growth. However, the specific effects of curcuminoids on human keratinocytes are not well defined, and this situation impairs mechanistic thinking regarding potential therapeutic uses. We hypothesized that curcuminoids would modulate key growth regulatory pathways in keratinocytes to inhibit cell proliferation. To test this hypothesis, the effects of curcumin and tetrahydrocurcumin (THC) on mitogen-activated protein (MAP) kinase signalling in keratinoctyes were determined. Primary human keratinocytes treated with curcumin or THC demonstrated decreased activation of p44/42 MAP kinases but increased levels of activated p38 MAP kinases. These data suggest that curcuminoids specifically activate stress-induced MAP kinases while inhibiting mitogen-induced MAP kinases. Curcuminoids also promote the phosphorylation of p53 on serine 15 in a dose-dependent and p38-dependent manner, suggesting that these compounds may activate p53. The effects of curcuminoids on keratinocytes mirrored some aspects of UVB and could be inhibited by N-acetylcysteine, suggesting that these compounds activate p38 through a mechanism that involves glutathione depletion. Both curcuminoids induced G2/M block and inhibited keratinocyte growth, and THC increased cellular levels of p21, a known p53 transcriptional target. These data demonstrate that curcuminoids can differentially regulate MAP kinases to inhibit keratinocyte growth while inducing p21. Curcuminoids also synergize with UVB to enhance p53 phosphorylation. The findings provide a rationale for testing curcuminoids in disorders associated with impaired p53 function or in which UVB-treatment is efficacious