[A case of rectal implantation cyst diagnosed by EUS and EUS-guided FNA].

A 73-year-old woman was referred to our hospital complaining of bloody stool. She had undergone high anterior resection with the double stapling technique for a sigmoid colon cancer 2 years prior to this admission. Colonoscopy revealed a soft submucosal tumor, 4cm in size, on the anal side of the previous anastomosis in the rectum. EUS revealed a cystic lesion located in the third and fourth layers of the rectal wall. EUS-FNA was performed, and the content of the cystic lesion was transparent mucinous liquid. Histologically, the specimen revealed PAS and Alcian blue-positive mucinous material and a small number of inflammatory cells such as foamy macrophages. Therefore, this cystic lesion was diagnosed as a rectal implantation cyst.

Abnormalities of the Wnt/ß-catenin signalling pathway induce tumour progression in sporadic desmoid tumours: correlation between ß-catenin widespread nuclear expression and VEGF overexpression.

AIMS: To analyse the correlation between ß-catenin and vascular endothelial growth factor (VEGF) in sporadic desmoid tumours. METHODS AND RESULTS: The correlation between ß-catenin aberrant expression and VEGF overexpression was examined and microvessel density (MVD) assessed by immunohistochemical expression of CD31 in 74 samples (63 primary and 11 recurrent samples, 63 patients) of sporadic desmoid tumours without familial adenomatous polyposis (FAP). ß-catenin gene mutation and mRNA expression of VEGF was then examined by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). There was a statistically significant correlation between widespread nuclear expression of ß-catenin and overexpression of VEGF in all desmoid tumours (P = 0.04, Fisher's exact test). MVD in recurrent tumours was significantly higher than that in primary tumours. CONCLUSIONS: Abnormalities of ß-catenin and VEGF overexpression play an important role in the neoplastic progression of sporadic desmoid tumours.

Reduced expression of SMARCB1/INI1 protein in synovial sarcoma.

Synovial sarcoma is classified as a tumor of uncertain differentiation, and some synovial sarcomas have rhabdoid cells. In previous studies, all malignant rhabdoid tumors and renal medullary carcinomas, some extraskeletal myxoid chondrosarcomas, almost all epithelioid sarcomas and half of epithelioid malignant peripheral nerve sheath tumors showed a loss of SMARCB1/INI1 protein expression in tumor cells and all of these tumors are also known to have rhabdoid cells. We analyzed the immunohistochemical and mRNA expression of SMARCB1/INI1 in 95 synovial sarcomas (73 monophasic fibrous type, 18 biphasic type and 4 poorly differentiated type) and 30 spindle cell sarcomas (3 adult fibrosarcomas, 7 fibrosarcomas arising in dermatofibrosarcoma protuberans, 10 leiomyosarcomas and 10 malignant peripheral nerve sheath tumors) resembling monophasic fibrous synovial sarcoma. The results have shown that 66 of the 95 synovial sarcoma cases (69%) had reduced SMARCB1/INI1 protein expression, whereas the remaining 29 cases (31%) and all 30 spindle cell sarcomas showed preserved this protein expression. No case with a complete loss of SMARCB1/INI1 protein expression was recognized. The median values of SMARCB1/INI1 mRNA expression in non-tumor skeletal muscle and synovial sarcoma with reduced protein expression were 12.86 and 134.01, respectively, and a statistically significant difference was detected between these two groups (P=0.0000004). However, there was no statistically significant difference of prognosis between the synovial sarcoma group with reduced and that with preserved SMARCB1/INI1 protein expression (P=0.46). Therefore, it was suggested that there is a post-transcriptional SMARCB1/INI1 regulatory mechanism in the tumor cells of synovial sarcoma.

Overexpression of A disintegrin and metalloproteinase 28 is correlated with high histologic grade in conventional chondrosarcoma.

Low-grade chondrosarcoma and enchondroma are occasionally difficult to differentiate solely by reference to clinicoradiologic and histologic findings. The A disintegrin and metalloproteinases are a new gene family of proteins having a metalloprotease domain with matrix metalloproteinases and play an important role in the chondrocyte development process. Therefore, we analyzed the expression of A disintegrin and metalloproteinases and matrix metalloproteinases in several kinds of cartilaginous bone tumors at the messenger RNA level and immunohistochemical protein level and ascertained their relationships to the histologic degree of malignancy. Reverse transciptase-polymerase chain reaction and real-time quantitative reverse transciptase-polymerase chain reaction of the expression of the A disintegrin and metalloproteinase family in cartilaginous bone tumors demonstrated that A disintegrin and metalloproteinase 28 messenger RNA levels in grade I chondrosarcoma were significantly higher than those in enchondroma (P = .009). Moreover, positive immunoreactivity of A disintegrin and metalloproteinase 28 was observed in 12 (59%) of 22 patients with grade I chondrosarcoma and in 21 (91%) of 23 patients with grade II chondrosarcoma, respectively. In contrast, only 2 (9%) of 21 cases of enchondromas demonstrated positive staining for A disintegrin and metalloproteinase 28. On the other hand, the immunohistochemical expressions of matrix metalloproteinase 9 and matrix metalloproteinase 13 were significantly higher in enchondromas than in normal cartilage tissue; however, there is no statistically different expression between enchondromas and grade I chondrosarcomas. We detected that overexpression of A disintegrin and metalloproteinase 28 was increased according to its histologic grade in conventional chondrosarcoma and could be one of the helpful tools in distinguishing between low-grade chondrosarcoma and enchondroma.

Chemokine receptor CXCR4 expression is correlated with VEGF expression and poor survival in soft-tissue sarcoma.

The expression of chemokine receptor CXCR4 has been associated with poor prognosis and VEGF expression in several kinds of human malignancy. We measured CXCR4 expression levels in soft-tissue sarcoma and compared them with VEGF expression or microvessel density (MVD). We used real-time quantitative PCR to examine the CXCR4 and VEGF expression levels in a total 176 tumors, including 24 intermediate tumors, 24 malignant round-cell tumors (MRCTs) and 128 malignant non-round-cell tumors (MNRCTs). We also assessed their immunohistochemical expression of CXCR4 and VEGF, MVD and proliferative activities, as measured by the MIB-1-labeling index (LI). Furthermore, we evaluated their significance with respect to patient survival rates in MNRCTs, using the Cox regression model. Within the different types of tumor tissue, the expression levels of CXCR4 (p < 0.0001) and VEGF (p < 0.0001) in MNRCTs were significantly higher than those in intermediate tumors or MRCTs. Immunohistochemical expression levels of CXCR4 and VEGF were significantly correlated with their mRNA expression levels (p < 0.0001). Significant positive correlation was found between CXCR4 and VEGF expression in 112 primary MNRCTs (r = 0.434, p < 0.0001). Moreover, both univariate (p < 0.0001) and Cox multivariate analysis (p = 0.0001) revealed that overexpression of CXCR4 was an independent adverse prognostic factor, in addition to high stage according to the American Joint Committee on Cancer and a high MIB-1-LI. Determination of the CXCR4 expression level as a novel marker can provide useful prognostic information for patients and it could be a candidate for molecular targeting therapy in MNRCTs of soft-tissue sarcomas.

Correlation between beta-catenin widespread nuclear expression and matrix metalloproteinase-7 overexpression in sporadic desmoid tumors.

Desmoid tumors (desmoid-type fibromatoses) are locally aggressive soft tissue tumors associated with the Wnt/beta-catenin signaling pathway (APC-beta-catenin-Tcf pathway). Matrix metalloproteinase-7, which is one of the target genes of the Wnt/beta-catenin signaling pathway, has been reported to play an important role in tumor progression. We examined the immunohistochemical expression of beta-catenin and matrix metalloproteinase-7 in 72 samples (63 primary and 9 recurrent samples, 63 patients) of sporadic desmoid tumors without familial adenomatous polyposis, and the genetic alteration of the beta-catenin gene in 33 frozen materials (22 primary and 11 recurrent samples, 22 patients). We further examined messenger RNA expression of matrix metalloproteinase 7 by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and compared the results with those of normal skeletal muscles. Immunohistochemically, there was a statistically significant correlation between widespread nuclear expression of beta-catenin and overexpression of matrix metalloproteinase-7 (P < .01 in extra-abdominal desmoid, Fisher test). There were 7 missense point mutations in the 22 primary frozen samples (32%). In the beta-catenin mutated group, matrix metalloproteinase-7 messenger RNA expression was significantly higher than that of the beta-catenin wild-type group (P = .0018, Mann-Whitney U test). Our results suggest that the matrix metalloproteinase-7 gene may be up-regulated by mutated or continuously elevated beta-catenin protein and that the matrix metalloproteinase-7 gene may also be targeted in the Wnt/beta-catenin signaling pathway in sporadic desmoid tumors.

Dedifferentiated liposarcoma with leukocytosis. A case report of G-CSF-producing soft-tissue tumors, possible association with undifferentiated liposarcoma lineage.

BACKGROUND: Granulocyte-colony-stimulating factor (G-CSF) functions as a hematopoietic growth factor and it is responsible for leukocytosis. G-CSF-producing tumors associated with leukocytosis include various types of malignancies. CASE PRESENTATION: We report the case of a 72-year-old man with dedifferentiated liposarcoma characterized by dedifferentiated components of malignant fibrous histiocytoma (MFH)-like features in addition to well-differentiated lipoma-like liposarcoma, arising from his upper arm. Preoperative laboratory data showed leukocytosis (103,700/mul). The serum level of G-CSF was also elevated (620 pg/ml [normal, <8 pg/ml]). Nine days after the surgery, the leukocytosis was relieved (WBC; 6,920/mul) and the elevated serum G-CSF level was significantly decreased (G-CSF; 12 pg/ml). One month after the surgery, leukocytosis gradually began to appear again. Three months after the surgery metastatic lung lesions were confirmed, and the patient subsequently died of respiratory problems. In the English literature regarding soft-tissue tumors with leukocytosis, including the current case, we could review a total of 6 cases of liposarcoma with leukocytosis. The subtype of these 6 liposarcoma cases was undifferentiated liposarcoma, comprising dedifferentiated liposarcoma in 4 cases and pleomorphic liposarcoma in 2 cases. CONCLUSION: Since the only other soft-tissue tumor that was associated with leukocytosis was MFH, and since MFH is characterized by the absence of any specific differentiation, we would like to propose a possible association between G-CSF-producing soft-tissue tumors and an undifferentiated liposarcoma lineage, such as dedifferentiated liposarcoma or pleomorphic liposarcoma.