A rare case of extraluminally pedunculated gastrointestinal stromal tumor with postoperative metastasis to pancreas.

The gastrointestinal stromal tumor (GIST) is the most common type of sarcomatous tumor of the gastrointestinal tract. Many GISTs appear as submucosal tumors with intraluminal protrusion. GISTs with malignant features have a high risk of postoperative recurrence or metastasis, usually to the liver or peritoneum. We present a case of gastric GIST with double rarities: arising completely extraluminally with a pedicle and postoperative metastasis to the pancreas. A woman in her seventies diagnosed with a large extraluminal gastric GIST underwent complete removal of the tumor. Nine months later, a solitary metastatic tumor in the pancreas was detected. Imatinib controlled metastasis well for four years before the tumor became resistant. The patient then had a partial pancreatectomy with splenectomy. She is currently free from recurrence. We genetically analyzed the primary and metastatic GISTs and found known mutations related to poor prognosis and imatinib resistance.

Extranodal lymphoma originating in the gluteal muscle with adjacent bone involvement and mimicking a soft tissue sarcoma.

INTRODUCTION: Extranodal lymphoma (ENL) in the muscles is a rare manifestation of non-Hodgkin lymphoma (NHL). The aim of this case report is to describe and evaluate the clinical presentation and important radiologic features of ENL affecting the musculoskeletal system. PRESENTATION OF CASE: We present a 52-year-old female with a 3-week history of left gluteal pain. Computed tomography (CT) showed a non-uniformly early enhancing mass in the left gluteal muscle, the tumor demonstrating central necrosis and adjacent bone involvement. Fluorine-18 fluorodeoxyglucose positron emission tomography ((18)F-FDG PET)/CT showed areas of increased (18)F-FDG uptake in the left gluteal musculature, pelvic bones, para-aortic and mediastinal lymph nodes and both lungs. Histopathological examination showed a diffuse large B cell lymphoma (DLBCL). After 8 cycles of R-CHOP chemotherapy, the mass in the left gluteal muscle has completely disappeared DISCUSSION: Although destructive tumor originating in the gluteal muscle with adjacent bone involvement is more common in soft tissue sarcoma, lymphoma should be regularly included in the differential diagnosis. While CT is a useful modality for assessing soft tissue masses, disruption and injury of the surrounding tissues, PET/CT fusion is superior for the detection of unexpected extranodal sites of disease, or for exclusion of disease in the presence of nonspecific extranodal CT findings. CONCLUSION: A rapid growth pattern and destructive masses that invade adjacent structures on CT are key findings of DLBCL, and (18)F-FDG PET/CT is a useful imaging modality to accurately determine the disease stage and disease aggressiveness of NHL.

Vascular smooth muscle cells isolated from adipose triglyceride lipase-deficient mice exhibit distinct phenotype and phenotypic plasticity.

The alteration of triglyceride (TG) metabolism in vascular smooth muscle cells (SMC) is likely to be correlated with certain phenotype, though this has not been elucidated. Adipose triglyceride lipase (ATGL) exerts major TG catalytic activity in both adipotic and non-adipotic cells. In the present study, we isolated SMC from ATGL-deficient mice (ATGL(-/-)mSMC). ATGL(-/-)mSMC showed spontaneous TG accumulation with lower mitogenic response and smooth muscle actin (SMA) expression compared to ATGL (+/+)mSMC. Percentage of senescence-associated ß-galactosidase positive cells was also increased in ATGL(-/-)mSMC. Real-time PCR followed by screening with focused DNA array analysis revealed up-regulated expression of glucokinase (1.7-fold), lipoprotein lipase (3.8-fold) and interleukin-6 (3.7-fold) and down-regulated expression of vascular endothelial growth factor-A (0.2-fold), type I collagen (0.5-fold), and transforming growth factor-ß (0.4-fold) in ATGL(-/-)mSMC compared to ATGL(+/+)mSMC. Next, ectopic gene transfer of human ATGL was attempted using doxycycline (Dox)-regulatable myc-DDK-tagged adenovirus vector (AdvATGL). AdvATGL infection resulted in a reduction of TG accumulation with elevated mitogenic response and SMA expression, and decreased in senescent cell numbers in ATGL(-/-)mSMC. Moreover, deviated gene expression pattern in ATGL(-/-)mSMC was potentially corrected. Our data suggest that ATGL(-/-)mSMC have a distinct phenotype that may be related to vascular pathogenesis. Plasticity of SMC phenotypes correlated to lipid metabolism could be a therapeutic target.

Lysophosphatidic acid receptor 4 signaling potentially modulates malignant behavior in human head and neck squamous cell carcinoma cells.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common non-skin cancer worldwide. Despite improvement in therapeutic strategies, the prognosis of advanced HNSCC remains poor. The extacellular lipid mediators known as lysophosphatidic acids (LPAs) have been implicated in tumorigenesis of HNSCC. LPAs activate G-protein-coupled receptors not only in the endothelial differentiation gene (Edg) family (LPA1, LPA2, LPA3) but also in the phylogenetically distant non-Edg family (LPA4, LPA5, LPA6). The distinct roles of these receptor isoforms in HNSCC tumorigenesis have not been clarified. In the present study, we investigated the effect of ectopic expression of LPA4 in SQ-20B, an HNSCC cell line, expressing a trivial level of endogenous LPA4. LPA (18:1) stimulated proliferation of SQ-20B cells, but did not affect proliferation of HEp-2, an SCC cell line expressing higher levels of LPA4, comparable to those of with LPA1. LPA-stimulated proliferation of SQ-20B cells was attenuated by Ki16425 and Rac1 inhibitor, but not by Y-27632. Infection with doxycycline-regulatable adenovirus vector expressing green fluorescent protein-tagged LPA4 (AdvLPA4G) abolished LPA-stimulated proliferation in SQ-20B cells with the accumulation of G2/M-phasic cells. Ectopic LPA4 induction further downregulated proliferation of Ki16425-treated SQ-20B cells, of which downregulation was partially recovered by LPA. Ectopic LPA4 induction also downregulated proliferation of Rac1 inhibitor-treated SQ-20B cells, however, LPA no longer recovered it. Finally, LPA-induced cell motility was suppressed by ectopic LPA4 expression as well as by Ki16425, Rac1 inhibitor or Y-27632. Our data suggest that LPA4 signaling potentially modulates malignant behavior of SQ-20B cells. LPA signaling, which is mediated by both Edg and non-Edg receptors, may be a determinant of malignant behavior of HNSCC and could therefore be a promising therapeutic target.