Ectodermal Wnt controls nasal pit morphogenesis through modulation of the BMP/FGF/JNK signaling axis.

BACKGROUND: Mutations of WNT3, WNT5A, WNT9B, and WNT11 genes are associated with orofacial birth defects, including nonsyndromic cleft lip with cleft palate in humans. However, the source of Wnt ligands and their signaling effects on the orofacial morphogenetic process remain elusive. RESULTS: Using Foxg1-Cre to impair Wnt secretion through the inactivation of Gpr177/mWls, we investigate the relevant regulation of Wnt production and signaling in nasal-facial development. Ectodermal ablation of Gpr177 leads to severe facial deformities resulting from dramatically reduced cell proliferation and increased cell death due to a combined loss of WNT, FGF and BMP signaling in the developing facial prominence. In the invaginating nasal pit, the Gpr177 disruption also causes a detrimental effect on migration of the olfactory epithelial cells into the mesenchymal region. The blockage of Wnt secretion apparently impairs the olfactory epithelial cells through modulation of JNK signaling. CONCLUSIONS: Our study thus suggests the head ectoderm, including the facial ectoderm and the neuroectoderm, as the source of canonical as well as noncanonical Wnt ligands during early development of the nasal-facial prominence. Both ß-catenin-dependent and -independent signaling pathways are required for proper development of these morphogenetic processes.

Disseminated and late metastatic disease from nasal pit leiomyosarcoma after radical surgical resection. Case report of a singular presentation of a rare disease.

BACKGROUND: Leiomyosarcoma of the head and neck is a rare cancer with high local aggressiveness. Radical surgery and adjuvant treatment offer the best chance for cure, nonetheless 5-years recurrence rate remains high. Despite international guidelines are available for soft tissue sarcomas, no recommendations are specifically endorsed for leiomyosarcoma of the head and neck, due to the rarity of its presentation and consequently scarcity of data on long-term outcome. CASE PRESENTATION: A 50-year old woman, operated 10 years before for leiomyosarcoma of the nasal pit and with negative 5-years follow-up, was admitted to our ward for impairment of the hepatic function. Total-body CT scan detected multiple localizations at lungs, kidneys, pancreas, bones, muscles, lymph nodes and thyroid. The pathologic report after lung biopsy confirmed the diagnosis of metastasis from leiomyosarcoma and the patients was scheduled for first line chemo-radiotherapy. CONCLUSIONS: Despite adequate primary treatment, distant and disseminated metastatic disease may be not excluded in leiomyosarcoma of the head and neck.