Surgical removal of an isolated femoral metastasis of uterine cervical squamous cell carcinoma: a case report and review of the literature.

A bone metastasis from uterine cervical cancer normally indicates short life expectancy. Resection of the lesion is therefore palliative. The authors consider herein whether surgical resection can promote disease control while improving quality of life. A 33-year-old woman -presenting FIGO Stage IB 1 uterine cervical squamous cell carcinoma underwent a radical hysterectomy and pelvic irradiation. Twenty-two-months later, a solitary femoral metastasis was detected. Given the pain, imminent bone fracture, the patient's relative youth, absence of other metastases, and complete control of the primary lesion, wide excision of the lesion, and reconstruction were performed. Sixteen months later, she was disease-free and ambulatory using a cane. The findings of both the present case and the review showed that patients were disease-free for over one year after surgery, suggesting that resection may assist disease control as well as improve patients' quality of life.

Optimum interpolation analysis of basin-scale ¹³7Cs transport in surface seawater in the North Pacific Ocean.

¹³7Cs is one of the conservative tracers applied to the study of oceanic circulation processes on decadal time scales. To investigate the spatial distribution and the temporal variation of ¹³7Cs concentrations in surface seawater in the North Pacific Ocean after 1957, a technique for optimum interpolation (OI) was applied to understand the behaviour of ¹³7Cs that revealed the basin-scale circulation of Cs ¹³7Cs in surface seawater in the North Pacific Ocean: ¹³7Cs deposited in the western North Pacific Ocean from global fallout (late 1950s and early 1960s) and from local fallout (transported from the Bikini and Enewetak Atolls during the late 1950s) was further transported eastward with the Kuroshio and North Pacific Currents within several years of deposition and was accumulated in the eastern North Pacific Ocean until 1967. Subsequently, ¹³7Cs concentrations in the eastern North Pacific Ocean decreased due to southward transport. Less radioactively contaminated seawater was also transported northward, upstream of the North Equatorial Current in the western North Pacific Ocean in the 1970s, indicating seawater re-circulation in the North Pacific Gyre.

The EWSR1/NR4A3 fusion protein of extraskeletal myxoid chondrosarcoma activates the PPARG nuclear receptor gene.

The NR4A3 nuclear receptor is implicated in the development of extraskeletal myxoid chondrosarcoma (EMC), primitive sarcoma unrelated to conventional chondrosarcomas, through a specific fusion with EWSR1 resulting in an aberrant fusion protein that is thought to disrupt the transcriptional regulation of specific target genes. We performed an expression microarray analysis of EMC tumours expressing the EWSR1/NR4A3 fusion protein, comparing their expression profiles to those of other sarcoma types. We thereby identified a set of genes significantly overexpressed in EMC relative to other sarcomas, including PPARG and NDRG2. Western blot or immunohistochemical analyses confirm that PPARG and NDRG2 are expressed in tumours positive for EWSR1/NR4A3. Bioinformatic analysis identified a DNA response element for EWSR1/NR4A3 in the PPARG promoter, and band-shift experiments and transient transfections indicate that EWSR1/NR4A3 can activate transcription through this element. Western blots further show that an isoform of the native NR4A3 receptor lacking the C-terminal domain is very highly expressed in tumours positive for EWSR1/NR4A3, and co-transfections of this isoform along with EWSR1/NR4A3 indicate that it may negatively regulate the activity of the fusion protein on the PPARG promoter. These results suggest that the overall expression of PPARG in EMC may be regulated in part by the balance between EWSR1/NR4A3 and NR4A3, and that PPARG may play a crucial role in the development of these tumours. The specific up-regulation of PPARG by EWSR1/NR4A3 may also have potential therapeutic implications.

Histopathologic characteristics of gastric ulcers created by endoscopic submucosal dissection.

BACKGROUND AND STUDY AIM: We have previously reported that gastric ulcers artificially created by endoscopic submucosal dissection (ESD) would heal within 8 weeks regardless of size and location. The details of the healing process remain unclear, and we aimed to clarify the mechanism by histopathological investigation. PATIENTS AND METHODS: 21 post-ESD ulcers were examined histopathologically, using surgically resected specimens from patients who had subsequently undergone gastrectomy due to submucosal invasion and/or lymphovascular infiltration by the tumor. The grade of ulcer, appearance of regenerative mucosa, scar formation, and extent of fibrosis were evaluated. RESULTS: Fibrosis and wall thickening were observed from 2 weeks after ESD, but regenerative mucosa was not observed until 5 weeks. Among 12 patients who underwent gastrectomy later than 8 weeks after ESD, a mucosal defect was still observed in two patients. In these two patients the lesion was associated with severe fibrosis due to previous peptic ulcer or submucosal invasion by the lesion. CONCLUSION: Size reduction in these ulcers occurs by contraction in the early phase, then regenerative mucosa covers the remaining mucosal defect within 8 weeks. If there is fibrosis under the lesion before ESD, there is a possibility that the artificially created ulcer will not heal within 8 weeks.

An obstructed venous aneurysm presenting as an abdominal mass: report of a case.

We report herein the case of a 32-year-old woman found to have a venous aneurysm originating from the ovarian vein. The patient presented with a 9-cm abdominal tumor, and surgery was performed under the preoperative diagnosis of a mesenteric cyst. The tumor was easily ablated from the mesentery and resected with the right ovarian artery and vein. Histologically, the wall of the cyst showed the structure of a vein, and the diagnosis of a venous aneurysm was made. This disease is difficult to diagnose preoperatively when a patient presents with no symptoms other than a palpable mass, or when the lumen is obstructed by thrombus. This report serves to demonstrate that a venous aneurysm should be considered in the differential diagnosis of an asymptomatic abdominal mass.

Role of ras mutation in the progression of thyroid carcinoma of follicular epithelial origin.

The histological differentiation of thyroid carcinoma is known to correlate with prognosis. Ras oncogene mutations, which have been identified in various human cancers, have been suspected playing an important role in carcinogenesis and tumor progression. The purpose of this study was to clarify the mechanism of thyroid tumor progression, focusing on ras oncogenes. We examined ras mutations using nested polymerase chain reaction (PCR) and direct sequencing methods. The ras oncogene product was also examined immunohistochemically. Our results indicated that the incidence of ras mutations correlated with the histological differentiation of thyroid cancer. Three poorly differentiated carcinomas showed a higher rate of ras mutations than did 17 well-differentiated counterparts. Hot spots were not identified except for a relative accumulation of the N-ras gene at codon 61. There was a correlation between the immunoreactivity of the ras oncogene product and ras mutation, although the immunoreactivity of ras-p21 did not correlate with the histological differentiation. Mutation of the ras gene seemed to be one of the important events in the progression from well-differentiated carcinoma to poorly differentiated thyroid carcinoma.

Retroperitoneal liposarcoma with combined well-differentiated and myxoid malignant fibrous histiocytoma-like myxoid areas.

To broaden the knowledge of myxoid morphology in liposarcoma, eight cases of unusual liposarcoma with combined well-differentiated and myxoid malignant fibrous histiocytoma (MFH)-like myxoid areas are reported. The tumors arose as huge retroperitoneal masses in elderly patients, except for one that occurred in the spermatic cord. Three cases had local recurrences, and one of the seven patients who were followed up had died of the tumor. Grossly, the tumors were mostly confluent and multinodular and showed a glistening myxoid appearance in variable proportions, which merged gradually into or were juxtaposed to yellow fatty or sclerotic whitish areas. Microscopically, in addition to areas of well-differentiated lipoma-like or sclerosing liposarcoma, all the tumors contained myxoid portions characterized by scattered multinucleated or bizarre giant cells and a prominent plexiform vascular pattern that resembled myxoid MFH or myxofibrosarcoma. The myxoid areas were associated with discernible lipogenesis. High-grade dedifferentiation was present in one tumor. Cytogenetically, in one case, the myxoid lesion had nonrandom chromosomal aberrations, such as ring and marker chromosomes, characteristic of a well-differentiated variant of liposarcoma. In a nested reverse transcription-polymerase chain reaction analysis using archival paraffin-embedded tissue, it was seen that none of the eight tumors with myxoid MFH-like features had TLS/FUS-CHOP fusion transcripts characteristic of myxoid and round cell liposarcomas. These clinicopathologic and molecular features suggest that the current myxoid tumors are more closely related to well-differentiated liposarcoma rather than to ordinary myxoid liposarcoma despite their unequivocal myxoid morphology. Missense point mutations of the p53 gene were detected in two (25%) cases by single-strand conformation polymorphism and sequence analyses. Immunohistochemical expressions of p53 and mdm2 were observed in 75% of the cases, in which immunoreactive tumor cells were seen more often in the myxoid MFH-like areas. Thus, altered p53 pathways, such as p53 gene mutation and mdm2-mediated inactivation of p53, may play a pathogenetic role in this form of tumor progression showing myxoid MFH-like morphology in liposarcoma, as has been suggested in dedifferentiated liposarcoma.

Coexpression of hepatocyte growth factor and c-Met proto-oncogene product in synovial sarcoma.

Hepatocyte growth factor (HGF) is a heterodimeric polypeptide growth factor that has pleiotropic roles, including those of mitogen, motogen and morphogen. The HGF receptor is characterized as a c-Met proto-oncogene product (c-Met), which is a heterodimeric tyrosine kinase receptor. Hepatocyte growth factor acts as a mediator between the mesenchymal and epithelial tissues because HGF is produced by mesenchymal cells and c-Met is mainly expressed on various epithelial cells. Furthermore, the HGF/c-Met system plays an important role in embryogenesis and the regeneration of various organs. Synovial sarcoma (SS) are unique sarcoma that show epithelial differentiation, but little is known about their histogenesis. The expression of HGF and c-Met was examined by immunohistochemistry in SS specimens from 12 patients (six each of biphasic and monophasic fibrous types). Immunohistochemical coexpression of HGF and c-Met was demonstrated in the epithelial component of five biphasic SS, while only c-Met was expressed in the epithelioid nests of three monophasic fibrous SS. The spindle cell component was negative for HGF and c-Met. In SS, positivity for epithelial markers, such as cytokeratins and epithelial membrane antigen, was diffusely observed in the epithelial component and was focally observed in spindle cells, while vimentin was positive predominantly in the spindle cell component. The areas expressing HGF and c-Met corresponded to distinct epithelial structures; however, HGF and c-Met expression were not found in any other tumor cells expressing epithelial markers in the spindle cell component of SS. Considering the morphogenic effect of HGF, which has been known to be one of its most important roles, the unique immunohistochemical localization of HGF and c-Met in SS suggests that the HGF/c-Met system may be closely related to the formation of epithelial (glandular) structures in biphasic SS.

Phenotypic diversity of neurofibromatosis 2: association with plexiform schwannoma.

AIMS: Plexiform schwannoma (PS) is a rare variant of benign schwannoma characterized by a multinodular and plexiform growth pattern. In contrast to plexiform neurofibroma. PS is not associated with neurofibromatosis 1 (NF-1; von Recklinghausen's disease) and has no propensity for malignant transformation. The purpose of this study was to clarify the relationship between PS and the entities of neurofibromatosis 2 (NF-2; bilateral acoustic neurofibromatosis) and schwannomatosis. METHODS AND RESULTS: Six cases of PS associated with NF-2 or meningioma were retrospectively studied clinicopathologically and immunohistochemically. Four cases of PS were found among the patients with NF-2, and all of these had multiple PSs; three cases also had multiple schwannomas of the spinal nerve roots and two of these had meningioma. Two other patients had meningioma, but not NF-2. Four patients were male and two were female. The ages ranged from 18 to 52 years (mean 29.6 years). Histologically, PS showed the histological features that have been previously described, i.e. schwannoma composed of a predominant Antoni A-type component with a plexiform growth pattern. Immunohistochemically, the tumour cells were positive for S100 protein. Each nodule was surrounded by perineural cells which were positive for epithelial membrane antigen. CONCLUSIONS: It is important to recognize that PS could be associated with NF-2 or meningioma. The combination of PS and meningioma may be a 'formes frustes' of NF-2, and is clinically overlapped with schwannomatosis.

Neuroendocrine tumors of the liver and pancreas associated with elevated serum prostatic acid phosphatase.

A 58-year-old man was revealed to have multiple liver tumors with elevated prostatic acid phosphatase (PAP) during a medical examination. The tumors were of neuroendocrine nature, but no abnormal findings were obtained in other organs in which neuroendocrine tumors develop frequently. Repeated transarterial embolization was partially effective. However, the tumors became resistant to the therapy three years later, continued growing and ruptured. Autopsy disclosed neuroendocrine tumors in the pancreas, which were immunohistologically positive for PAP. Neuroendocrine tumors of the pancreas and liver producing PAP are rare; this case is reported with a review of literature.

Elevated serum-soluble interleukin-2 receptor (Tac antigen) levels in chronic myelogenous leukemia patients with blastic crisis.

We examined the expression of cell-surface interleukin-2 (IL-2) receptor (Tac antigen) on peripheral blood leukemic cells and measured soluble IL-2 receptor p55(alpha) chain (sIL-2R) levels in sera from chronic myelogenous leukemia (CML) patients with blastic crisis. Flow cytofluorometric analysis performed by dual immunofluorescence in three cases demonstrated coexpression of Tac antigen with myeloid (CD13, CD14, or CD33) or lymphoid (CD10) antigen on significant proportions of peripheral blood leukemic cells. Radiolabeled IL-2-binding assay demonstrated the specific IL-2 binding sites in three cases examined. The exogenous IL-2, however, failed to induce proliferative response. A myeloid cell line, Yut-K3, established from peripheral blood leukemic cells from a CML patient with blastic crisis, also expressed cell-surface Tac antigen and CD13 concurrently. SIL-2R assay showed that Yut-K3 released a detectable amount of sIL-2R in its culture supernatant. The serum sIL-2R levels were significantly elevated (range: 2,580 to 172,000 U/mL) in 12 CML patients with blastic crisis and were slightly elevated in ten patients in chronic phase (range: 250 to 820 U/mL) and in three in accelerated phase (range: 790 to 1,305 U/mL) compared with those in 24 normal controls (range: 70 to 695 U/mL, P less than .01). These results indicated that the leukemic cells from CML patients with blastic crisis expressed and released IL-2 receptor (Tac antigen). Longitudinal studies performed in three cases of CML with blastic crisis showed that the change of serum sIL-2R level was closely associated with that of the number of peripheral blood leukocytes and blasts, the percentage of blasts and serum LDH levels, also suggesting that the serum sIL-2R level is a useful clinical indicator of the leukemic cell burden in vivo.

Characteristics of the IL-2 receptor expressed on large granular lymphocytes from patients with abnormally expanded large granular lymphocytes. Implication of a non-Tac IL-2-binding peptide.

Large granular lymphocytes (LGL) from four patients with abnormally expanded LGL in the peripheral blood were studied regarding their receptor for IL-2. LGL from none of the cases examined expressed Tac Ag, an Il-2R glycoprotein recognized by anti-Tac mAb. However, 125I-labeled IL-2 binding experiments demonstrated that 1400 to 2800/cell IL-2 binding sites with a single affinity (K: 0.46-1.4 nM) were expressed on LGL from the four patients. The affinity was not high but about 10-fold higher than that of the low affinity IL-2R expressed on activated normal T lymphocytes. Furthermore, LGL from the four patients proliferated in response to higher concentrations of IL-2 and these responses were not inhibited by an excess amount of anti-Tac antibody. 125I-Labeled IL-2 cross-linking studies performed in two cases revealed the predominant expression of an IL-2 binding molecule with an estimated Mr of 70,000 to 75,000. After the culture with IL-2 for 48 h, expression of a small amount of Tac Ag (p55) was induced on LGL in at least three cases. These data strongly suggested that the IL-2R expressed on LGL is functional and identical to the p70, a novel IL-2 binding peptide that has been recently identified and speculated to form the high affinity IL-2R in association with the p55.

Serum soluble interleukin-2 receptor levels in patients with adult T-cell leukemia and human T-cell leukemia/lymphoma virus type-I seropositive healthy carriers.

Using an enzyme-linked immunosorbent assay (ELISA) technique, we measured the soluble interleukin 2 receptor (s-IL-2R) levels in the sera of patients with adult T-cell leukemia (ATL) in Japan. The s-IL-2R levels in the sera of the ATL patients were markedly higher (range 540-310, 400 U/ml, mean +/- SD = 62,800 +/- 81,000 U/ml, n = 42) than those in normal individuals (range 42-950 U/ml, mean +/- SD = 322 +/- 198 U/ml, n = 35, P less than 0.01). The patients with acute-type or lymphoma-type ATL had high s-IL-2R levels (range 11,900-310,400 U/ml, mean +/- SD = 110,340 +/- 370 U/ml, n = 15; range 26,400-214,400 U/ml, mean +/- SD = 90,170 +/- 59,040 U/ml, n = 7, respectively). All of the patients with hypercalcemia (Ca greater than 10 mg/dl) or elevated serum LDH levels (LDH greater than 500 IU/liter) also had s-IL-2R levels above 10,000 U/ml. The high s-IL-2R levels in the sera of ATL patients indicate abnormal IL-2 receptor production and its release from the leukemic cells in vivo. Thus, the serum s-IL-2R level may be a sensitive and useful marker to monitor the total amount of tumor cells in ATL, especially in the lymphoma type. We next examined the serum s-IL-2R levels in human T-cell leukemia/lymphoma virus type-I (HTLV-I) seropositive healthy carriers to investigate whether there might be abnormal IL-2 receptor expression in such individuals. However, there was no statistically significant difference between the s-IL-2R level of 71 HTLV-I seropositive healthy carriers (range 65-880 U/ml, mean +/- SD = 394 +/- 212 U/ml) and that of 71 age- and sex-matched normal individuals (range 33-950 U/ml, mean +/- SD = 357 +/- 224 U/ml) who lived in Okinawa Prefecture.

Close association between interleukin 2 receptor mRNA expression and human T cell leukemia/lymphoma virus type I viral RNA expression in short-term cultured leukemic cells from adult T cell leukemia patients.

Human T cell leukemia/lymphoma (T-lymphotropic) virus type I (HTLV-I) infection has been considered to be closely associated with the leukemogenesis of adult T cell leukemia (ATL), in which interleukin 2 (IL-2) receptors are abnormally expressed. In this study, however, Southern blot analysis revealed no gross rearrangement or obvious amplification of the IL-2 receptor gene in ATL leukemic cells, indicating that abnormal IL-2 receptor expression in ATL is not due to the structural change of its gene. Hence, we studied the expression of the IL-2 receptor and HTLV-I at the RNA level during short-term cultures of leukemic cells from 9 ATL patients. Cytoplasmic dot hybridization and Northern hybridization revealed that fresh leukemic cells from seven of nine patients expressed a small amount of IL-2 receptor mRNA but HTLV-I RNA was undetectable in all cases. After cultures for up to 7 d, both IL-2 receptor mRNA and HTLV-I RNA (including pX message) expression concomitantly increased, whereas the amounts of other cellular genes, except for beta-actin, did not. The increases in their RNA expression were inhibited by early addition (within 12 h after the beginning of the culture) of cycloheximide, indicating that these increases are mediated by newly synthesized protein(s). These results strongly suggested that IL-2 receptor expression is closely associated with HTLV-I expression in leukemic cells from ATL patients.