Fatty acid synthase (FASN) is the biosynthetic enzyme responsible for the endogenous synthesis of fatty acids. It is downregulated in most normal cells, except in lipogenic tissues such as liver, lactating breast, fetal lung, and adipose tissue. Conversely, several human cancers, including head and neck squamous cell carcinomas (HNSCC), overexpress FASN, which has been associated with poor prognosis and recently suggested as a metabolic oncoprotein. Orlistat is an irreversible inhibitor of FASN activity with cytotoxic properties on several cancer cell lines that inhibits tumor progression and metastasis in prostate cancer xenografts and experimental melanomas, respectively. To explore whether the inhibition of FASN could impact oral tongue squamous cell carcinoma (OTSCC) metastatic spread, an orthotopic model was developed by the implantation of SCC-9 ZsGreen LN-1 cells into the tongue of BALB/c nude mice. These cells were isolated through in vivo selection, show a more invasive behavior in vitro than the parental cells, and generate orthotopic tumors that spontaneously metastasize to cervical lymph nodes in 10 to 15 days only. SCC-9 ZsGreen LN-1 cells also exhibit enhanced production of MMP-2, ERBB2, and CDH2. The treatment with orlistat reduced proliferation and migration, promoted apoptosis, and stimulated the secretion of VEGFA 165b by SCC-9 ZsGreen LN-1 cells. In vivo, the drug was able to decrease both the volume and proliferation indexes of the tongue orthotopic tumors and, importantly, reduced the number of metastatic cervical lymph nodes by 43%. These results suggest that FASN is a potential molecular target for the chemotherapy of patients with OTSCC. Mol Cancer Ther; 13(3); 585-95. Ó2013 AACR.
Tripe palms are characterized clinically by thickened velvety palms with pronounced dermatoglyphics. We describe two patients with triple palms and pulmonary tumors, and review the 77 patients with idiopathic- and malignancy-associated tripe palms reported in the world literature. The majority (94%) of published cases of tripe palms occurred in patients with cancer; only five patients showed no evidence of an associated malignancy. Tripe palms were frequently seen in conjunction with acanthosis nigricans (77% of cases), although they can occur alone (23% of cases). In cancer patients with tripe palms alone, the most common underlying neoplasm was pulmonary carcinoma (53% of cases), whereas patients with both tripe palms and acanthosis nigricans frequently had gastric (35% of cases) or pulmonary (11% of cases) carcinomas. A wide variety of other solid tumors have also been observed. Importantly, in over 40% of patients, tripe palms were the presenting feature of a previously undiagnosed malignancy. Therefore, all patients with tripe palms should be evaluated with a full diagnostic work-up for an associated malignancy, particularly lung or gastric carcinoma.
Osteomas are benign osteogenic lesions that result from the proliferation of mature bone. Three variants are known: central, peripheral, and extraskeletal. The peripheral variant is the most common and it most frequently affects the paranasal sinuses, rarely occurring in the jaws. This article describes the case of a 33-year-old white male patient who was referred complaining of facial asymmetry. Clinical examination revealed an increase in volume at the base of the right side of the mandible, hard bony consistency and well delimited, painless to the touch, without signs of infection or intraoral alterations. Radiographic examination revealed an oval lobulated, radiopaque sessile lesion adhered to the mandibular base near the insertion of the masseter muscle. The patient reported practicing martial arts many years ago. Owing to the limited access, it was decided to perform the complete lesion removal through an extraoral surgical approach, by using a skin crease in the upper neck region below the lesion. The patient recovered well and the histopathological analysis confirmed the diagnosis of osteoma. The etiopathogenesis of osteoma is not completely elucidated, and 3 theories are more accepted: developmental defect, neoplastic nature, and reactive lesion owing to trauma or local infection. The clinicopathological correlation in the present case supports a traumatic origin. Traumatic peripheral osteoma should be considered in the differential diagnosis of nodular bone-forming lesions affecting the mandible.
The low-fat and fat-free spindle cell lipomas (SCLs) are rare and often mistaken for other benign and malignant morphological mimics, because of the fact that the diagnosis relies on its non-lipogenic component analysis. Here, we report the clinicopathological features of two oral SCLs (low-fat and fat-free variants). Both lesions
M2 macrophages are often detected in oral squamous cell carcinoma (OSCC), which, influenced by hypoxic conditions, appear to have high angiogenesis‐inducing capacity. However, the effects of immunosenescence on tumor‐associated macrophages (TAMs) and angiogenesis in OSCC are unknown.
Fifty‐seven OSCCs were divided into 3 groups (I: <40 years [n = 17]; II: 40‐65 years [n = 20]; III: >65 years [n = 20]). Immunohistochemistry for CD68 and CD163 (TAMs), and CD34 and D2‐40 for microvessel density (MVD), microvessel area (MVA), and total vascular area (TVA) were performed.
All groups showed similar clinicopathological and immunohistochemical findings. Similar CD68 and CD163 expression, confirmed a M2 phenotype. MVD, MVA, and TVA were similar, however, with significant predominance of blood vessels. No significant correlation between macrophage and angiogenic markers was observed.
A similar TAM and angiogenesis profile suggests the participation of other mechanisms, instead immunosenescence, in young and elderly OSCC patients.
Cellular neurothekeomas (CNs) are distinctive benign tumors of uncertain histogenesis, with predilection for the skin of the head and neck region. We describe the first case of multiple desmoplastic CNs (DCNs) affecting the oral cavity in a 9-year-old girl. Histopathologic evaluation showed a proliferation of spindle and epithelioid cells, forming nests and bundles, supported by exuberant fibrous stroma, as well as scattered multinucleated floret-like giant cells. The tumor cells were immunopositive for vimentin, CD63, CD56, whereas AE1/AE3, S100, CD34, α-SMA, GFAP, EMA, CD57 and NSE were negative. Ki-67 was <2%. Multiple DCNs should be considered in the differential diagnosis of oral nodular lesions.
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