Successful Treatment with Denosumab of a Giant Cell Tumor of Bone in the Iliac Bone of an 84-Year-Old Man.

We report a case of GCTB in an 84-year-old Japanese man who had a tumor in his left iliac bone and was treated safely with denosumab. The patient noticed a painful mass, with gradual enlargement, in his left low back next to the iliac region. Magnetic resonance imaging revealed that the tumor measured 94 × 66 × 90 mm and was located in the left iliac bone. Histologically, the tumor was composed of proliferative oval-shaped mononuclear cells, admixed with large number of osteoclast-like giant cells. Immunohistochemically, a strong positivity for histone 3.3 G34W mutant protein was observed in the nuclei of the mononuclear cells, confirming the diagnosis of GCTB. Because it was considered as unresectable tumor, the patient was treated with denosumab without any side effects.

Considering the Better Donor-side in Reconstruction of Composite Radius After Resection of Spindle Cell Sarcoma Using Free Fibular Osteocutaneous Flap: A Case Report.

Reconstruction of bone and soft-tissue defects in the forearm is a surgery that often proves unsuccessful. Free fibular osteocutaneous flaps are a useful material for reconstruction that enable simultaneous reconstruction of bone, skin, and soft tissues. However, in free fibular osteocutaneous flaps, the fibula, skin, and vascular pedicle are tightly bound together by the posterior intermuscular septum and the perforators that pass through the septum, giving the disadvantage of a low degree of freedom when setting these structures in place. We take into account the 3-dimensional structure of the free skin flap when selecting which lower leg to use as the donor. We report here the case of a 61-year-old man with defects in the radius, skin, and soft tissues after resection of spindle cell carcinoma of the right forearm, which was reconstructed using a free fibular osteocutaneous flap harvested from the left lower leg. Two years postoperatively, recovery has been uneventful with no complications. Donor-side selection of free fibular osteocutaneous flap is an important factor for safely completing composite radius reconstruction.

Detailed analysis of a superficial CD34-positive fibroblastic tumor: A case report and review of the literature.

Superficial cluster of differentiation (CD)34-positive fibroblastic tumor (SCPFT) is a rare mesenchymal neoplasm of borderline malignancy. It is characterized by a superficial location, marked cellular pleomorphism, an extremely low incidence of mitotic figures, and strong CD34 immunohistochemical positivity. As SCPFT is a recently described neoplasm, its characteristics are yet to be fully elucidated. To the best of our knowledge, no detailed studies regarding the imaging findings and cytogenetic analyses of SCPFTs exist. The present study describes a typical case of an 18-year-old man who developed an SCPFT measuring 87×70×80 mm in the subcutaneous adipose tissue of his right thigh. Computed tomography (CT) revealed a well-marginated tumor without calcification, and the enhancement on CT was weak. The tumor demonstrated abnormal uptake on 2-(18F) fluoro-2-deoxy-D-glucose positron emission tomography (PET), with a maximum standardized uptake value of 2.57. Magnetic resonance imaging (MRI) revealed a clearly defined tumor that exhibited homogeneous low signal intensity on T1-weighted imaging and high signal intensity on T2-weighted imaging, with small lobulated structures. Histopathologically, the tumor was composed of irregular spindle-to-oval-shaped cells with eosinophilic glassy cytoplasm and hyperchromatic, bizarre and pleomorphic nuclei that frequently exhibited intranuclear pseudoinclusions. Immunohistochemically, the tumor cells were diffusely and strongly positive for CD34. The Mindbomb E3 ubiquitin protein ligase 1 labeling index was 8.6%. Ultrastructurally, the tumor cells exhibited irregular or convoluted nuclei with abundant euchromatin-prominent nucleoli. The cytoplasmic organelles consisted of scattered, abundant rough endoplasmic reticulum, mitochondria, lysosomes, ribosomal rosettes and aggregated lipid globules. Of 18 metaphase cells identified, 2 demonstrated translocation between chromosomes 2 and 5 in cytogenetic studies. To the best of our knowledge, this is the first study describing imaging data (CT, MRI and PET-CT) and chromosomal aberrations for SCPFT.

Pediatric myositis ossificans mimicking osteosarcoma.

Myositis ossificans (MO) is a rare benign cause of heterotopic bone formation in soft tissue that most commonly affects young adults, typically following trauma. We report the case of an 11-year-old girl who developed MO mimicking osteosarcoma in her right shoulder. Plain radiography and computed tomography showed poorly defined flocculated densities in the soft tissue and a periosteal reaction along the proximal humerus. On magnetic resonance imaging, the mass displayed an ill-defined margin and inhomogeneous signal change. Histologically, the mass had a pseudosarcomatous appearance. Based on these findings, the patient was initially misdiagnosed with osteosarcoma at another hospital. The diagnosis was difficult because the patient was 11 years old and had no trauma history, with atypical radiographic changes and a predilection for the site of origin for osteosarcomas. We finally made the correct diagnosis of MO by carefully reviewing and reflecting on the pathological differences between stages.

Proliferative fasciitis mimicking a sarcoma in a child: a case report.

Proliferative fasciitis (PF) is a benign, discrete proliferation of fibroblasts or myofibroblasts in soft tissue. Proliferative fasciitis mostly occurs in adults and is often confused with a sarcoma because of its rapid growth and peculiar histological features. We report a case of PF mimicking a sarcoma which developed in a 13-year-old boy, who noticed a painful tumor, with gradual enlargement, in his right lower leg. Magnetic resonance imaging revealed that the tumor measured 34 mm × 20 mm × 41 mm and was located in the subcutaneous tissue. The tumor was surgically resected. Pathologically, the tumor was composed of a proliferation of atypical spindle cells, admixed with larger ganglion-like cells. Immunohistochemically, the tumor cells were positive for vimentin, cytokeratin, smooth muscle actin, HHF-35 and Fli-1. The tumor was subsequently diagnosed as a PF, although it was difficult to differentiate from a sarcoma. Five years after surgery, the postoperative course has been uneventful with no recurrence or metastasis.

Expression of minichromosome maintenance 7 (MCM7) in small lung adenocarcinomas (pT1): Prognostic implication.

Minichromosome maintenance (MCM) proteins, essential molecules in the initiation and elongation of DNA replication, have been considered to be good indicators of cell proliferation. We examined the expressions of MCM7 and Ki-67 in lung adenocarcinomas (ACs) with a diameter less than 3cm (pT1), to clarify their pathobiological significance. Immunohistochemistry was conducted to obtain labeling indices (LIs%) for MCM7, MCM2 and Ki-67 in 100 surgically removed pT1 ACs. The LIs were compared with clinicopathological profiles and overall survival rates. The mean LIs of MCM7 and Ki-67 were 20.2+/-15.2% and 13.7+/-11.2%, the value being higher in the former than in the latter (P<0.01). MCM7 LIs were significantly correlated with sex, histological grade, histological subtype, tumor size, LIs of Ki-67, MCM2 and P53 (P<0.05). LIs of MCM7 and Ki-67 were significantly higher in the 84 non-bronchioloalveolar carcinomas than in the 16 bronchioloalveolar carcinomas (P<0.01). Kaplan-Meier survival curves showed that patients with higher MCM7 LIs had poorer prognosis in the 100 pT1 ACs as well as in the 73 stage I ACs. Multivariate Cox regression analysis confirmed that the LIs of MCM7, but not the LIs of MCM2 and Ki-67, was an independent prognostic marker in the 73 stage I ACs. These results suggest that MCM7 is an independent prognostic marker, being more reliable than MCM2 or Ki-67 in human pT1 ACs as well as in human stage I ACs.

High expression of EZH2 is associated with tumor proliferation and prognosis in human oral squamous cell carcinomas.

Enhancer of zeste homolog 2 (EZH2) is a member of the polycomb group of genes and is important in cell cycle regulation. Overexpression of EZH2 protein has been associated with biological malignancy of prostate cancer and several other cancers. The aim of the present study was to evaluate the expression of EZH2 protein in human oral normal mucosa, dysplasia and oral squamous cell carcinoma (OSCC) with clinicopathological profiles. EZH2 expression was assessed by Western blotting and immunohistochemistry in 3 OSCC cell lines, 10 normal mucosae, 50 dysplasias and 102 OSCCs. The labeling indices (LIs) of EZH2, Ki-67, P53, and the apoptotic index (AI) were evaluated by immunohistochemistry and the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxigenin nick-end labeling (TUNEL) method. Western blot analysis detected EZH2 protein as a single band at 91kDa in the 3 OSCC cell lines, but it was almost absent in non-tumoral oral mucosae. The LI of EZH2 was highest in the OSCCs, followed by the dysplasias (p<0.05) and normal mucosae (p<0.05) with significant difference. The LI of EZH2 correlated with the clinical stage, tumor size, lymph node metastasis and LIs of Ki-67 and P53, but not with the AI in OSCCs, and inversely correlated with the histological differentiation of OSCCs. The survival rate calculated by the Kaplan-Meier method revealed that OSCC patients with higher EZH2 expression showed poorer prognosis than those with a lower EZH2 expression (p<0.01). These results suggest that overexpression of EZH2 is correlated with malignant potential and poor prognosis in OSCCs. EZH2 might serve as a novel biomarker for predicting prognosis in patients with OSCCs.

Minichromosome maintenance 2 (MCM2) immunoreactivity in stage III human gastric carcinoma: clinicopathological significance.

BACKGROUND: The origin licensing factor minichromosome maintenance 2 (MCM2) has recently been identified as a critical regulator of proliferation in both normal and neoplastic cells. This study examined whether MCM2 expression was of prognostic relevance in patients with stage III gastric carcinoma and whether the expression of this marker showed any correlation with clinicopathological characteristics. In addition, we evaluated whether the expression of this proliferation marker was correlated with that of another marker, Ki-67, in gastric carcinoma. METHODS: We examined the immunohistochemical expression of MCM2, Ki-67, and p53 in 103 surgically removed stage III gastric carcinomas, which consisted of 60 intestinal-type and 43 diffuse-type carcinomas. The labeling indices (LIs) of MCM2 and Ki-67 in cancer cells were compared with clinicopathological characteristics, p53 expression, and overall survival rates. RESULTS: The mean MCM2 and Ki-67 LIs were 69.1 +/- 11.8% and 48.2 +/- 14.5%, respectively, in the intestinal carcinomas, and 43.7 +/- 9.9% and 24.9 +/- 11.0%, respectively, in the diffuse carcinomas. The LIs of these proteins revealed no significant association with clinicopathological characteristics or with p53 expression in the carcinomas. Kaplan-Meier survival curves showed that, in the patients with diffuse carcinoma, those with higher MCM2 LIs had a poorer prognosis (P < 0.05), but the MCM2 LI was not correlated with prognosis for those with intestinal carcinoma (P = 0.25). Ki-67 expression had no significant correlation with prognosis in either intestinal-type or diffuse-type carcinomas. Multivariate Cox regression analysis confirmed that MCM2 was an independent prognostic factor in patients with diffuse carcinoma. CONCLUSION: Our data suggest that MCM2 is a useful prognostic marker in patients stage III diffuse-type gastric carcinoma.

Down-regulation of cobalt-induced HIF-1alpha expression correlates with cell proliferation and apoptosis in human gastric carcinoma cells.

Previously we reported that the hypoxia-inducible factor-1alpha (HIF-1alpha) expression correlated with cell proliferation and apoptosis under 500 mM of CoCl2 treatment in a human gastric carcinoma cell line, MKN-1. Herein we report a similar correlation in other cell lines, MKN-45 and TMK-1. The dual-phase expression of HIF-1alpha was highest at 6 and 8 h of treatment in MKN-45 and TMK-1, respectively, while the peak in MKN-1 occurred at 4 h. The cell viability indices showed a similar dual phase to the HIF-1alpha expression, while the apoptotic indices started to increase as the level of the HIF-1alpha expression decreased. In our previous study, the FACS analysis showed a marked G2/M arrest and an increase of the pre-G1 area in MKN-1 after 36 h of treatment, whereas the G2/M arrest was not observed in MKN-45 and TMK-1. The expression of cell cycle and apoptosis-related proteins showed a correlation with the HIF-1alpha expression and the FACS results, which suggested that the level of HIF-1alpha correlated with proliferation and apoptosis in human gastric carcinoma cell lines with a possible cell-type specific pattern.

High expression of enhancer of zeste homologue 2 indicates poor prognosis in patients with soft tissue sarcomas.

Enhancer of zeste homologue 2 (EZH2), a member of the polycomb group of genes, is associated with malignancy in several human cancers. The purpose of this study was to examine the association between EZH2 expression and clinicopathological factors as compared to Ki-67 expression in human soft tissue sarcomas. Expression of EZH2 and Ki-67 was immunohistochemically determined in paraffin-embedded sections from 104 soft tissue sarcomas. High expression of both EZH2 and Ki-67 was significantly correlated with distant metastasis (P<0.01), histologic grade (P<0.01) and poor prognosis (P<0.01), but not with clinicopathological factors such as age, sex, and tumor location and size. Although EZH2 expression was significantly correlated with Ki-67 expression (rs=0.65, P<0.01), multivariate analysis showed that high expression of EZH2, but not of Ki-67, was an independent factor of poor prognosis (relative risk = 2.79; P=0.02). These data suggest that expression of EZH2 is a novel and reliable prognostic marker of human soft tissue sarcomas.