Masami Hosaka

Histogenesis-specific expression of fibroblast activation protein and dipeptidylpeptidase-IV in human bone and soft tissue tumours.

Aims:  Fibroblast activation protein (FAP)/seprase and dipeptidylpeptidase‐IV (DPP‐IV)/CD26 are serine integral membrane proteases. They are involved in tissue remodelling, cancer invasion and metastases, mechanisms that are controversial. The aim was to identify cell types that express FAP and DPP‐IV in human bone and soft tissue tumours, and to determine whether there are any correlations between the expression of FAP and DPP‐IV and the malignant potential of tumours.

Sex steroid receptors expression and hormone‐induced cell proliferation in human osteosarcoma

Sex steroid receptors including estrogen receptors (ER), progesterone receptors (PR), and androgen receptors (AR) have been sporadically reported in human osteosarcoma or its cell lines. Therefore, sex steroids have been considered to play some roles in human osteosarcoma, but no systematic and detailed studies regarding the correlation between the status of these receptors in sarcoma cells and clinicopathological parameters have been reported. We examined the existence of ER, PR and AR in 28 cases of osteosarcoma using immunohistochemistry. We then characterized the potential influence of sex steroids on cell proliferation of osteosarcoma cells using MG‐63 human osteosarcoma cell line, which expressed all of these receptors. ER‐β and PR were detected in the great majority of the cases (23 and 24 cases, respectively) but ER‐α and aromatase were not detected in all the cases, and AR was detected only in eight cases. There was a significant positive correlation between ER‐β and Ki‐67 (MIB1) labeling indexes. The absence of aromatase in tumors also suggests the relative importance of concentrations of circulating sex steroids. Proliferation of MG‐63 cells was significantly stimulated by estradiol, progesterone, and 5α‐dihydrotestosterone (DHT), and was significantly suppressed by the addition of fulvestrant (ICI), mifepristone (RU), and hydroxiflutamide, blockers for ER, PR and AR, respectively. Sex steroids, particularly estrogen and progesterone, are considered to play important roles in the regulation of cell proliferation in human osteosarcoma. In addition, these data suggest the potential for a novel endocrine therapy in osteosarcoma using clinically available inhibitors of progesterone and estrogen actions. (Cancer Sci 2008; 99: 518–523)

Sex steroid synthesis in human skin in situ: The roles of aromatase and steroidogenic acute regulatory protein in the homeostasis of human skin

Sex steroids have been known to play important roles in the homeostasis of human skin, but little is known about their biosyntheses in that tissue. In this study, we characterized the correlation between the concentrations of sex steroids and the expression levels of the factors involved in their synthesis or metabolism in human skin. The expression levels of aromatase (ARO) and steroidogenic acute regulatory protein (StAR) were positively correlated with estrogens and testosterone concentrations, respectively. We demonstrated that estrogen synthesis was markedly decreased by ARO inhibitor and that skins with higher ARO expression had thicker elastic fibers than those with lower ARO expression. While pregnenolone and testosterone concentrations were increased by cholesterol administration to epidermal keratinocytes. Scalp skin with higher StAR expression was cleared to have significantly fewer hair follicles than that with lower expression. Our results suggest that the status of ARO and StAR contribute to estrogen synthesis in situ, especially for the regulation of elastic fiber formation, and to testosterone synthesis, which may be associated with hair growth, respectively.

Effect of addition of hyaluronic acids on the osteoconductivity and biodegradability of synthetic octacalcium phosphate.

The present study was designed to investigate whether three sodium hyaluronic acid (HyA) medical products, Artz(®), Suvenyl(®) and a chemically modified derivative of sodium HyA Synvisc(®), can be used as suitable vehicles for an osteoconductive octacalcium phosphate (OCP). OCP granules (300-500 μm diameter) were mixed with these sodium HyAs with molecular weights of 90 × 10(4) (Artz(®)), 190 × 10(4) (Suvenyl(®)) and 600 × 10(4) (Synvisc(®)) (referred to as HyA90, HyA190 and HyA600, respectively). OCP-HyA composites were injected using a syringe into a polytetrafluoroethylene ring, placed on the subperiosteal region of mouse calvaria for 3 and 6 weeks, and then bone formation was assessed by histomorphometry. The capacity of the HyAs for osteoclast formation from RAW264 cells with RANKL was examined by TRAP staining in vitro. Bone formation was enhanced by the OCP composites with HyA90 and HyA600, compared to OCP alone, through enhanced osteoclastic resorption of OCP. HyA90 and HyA600 facilitated in vitro osteoclast formation. The results suggest that the osteoconductive property of OCP was accelerated by the HyAs-associated osteoclastic resorption of OCP, and therefore that HyA/OCP composites are attractive bone substitutes which are injectable and bioactive materials.

Imaging features of intraosseous lipomas of the calcaneus

Abstract We report two cases of intraosseous lipoma arising in the calcaneus of a 36-year-old and a 22-year-old women complaining of heel pain. Plain radiographs and computed tomography scans revealed cystic lesions in the calcaneus triangle. On magnetic resonance images, the lesions had high signal intensities on both T1-weighted and T2-weighted images, corresponding to adipose tissue. Histological examination revealed mature fat cells with small bone fragments. Curettage and bone grafting were performed. There was no recurrence identified on plain radiographs 2 years following the surgery.

IDH2 and TP53 mutations are correlated with gliomagenesis in a patient with Maffucci syndrome

We report on a 24‐year‐old woman who was diagnosed as having Maffucci syndrome with anaplastic astrocytoma. We analyzed the IDH1 and IDH2 mutations of enchondroma, hemangioma and anaplastic astrocytoma tissues and the same somatic mosaic mutation in IDH2 gene was identified in all these tissues. In addition, we identified additional mutation of the TP53 gene in anaplastic astrocytoma tissue but not in other benign tumors. This is the first report of the detection of an identical IDH2 mutation in multiple tissues and TP53 mutation in anaplastic astrocytoma in a patient with Maffucci syndrome. This case is unique and supports the IDH2‐dependent genetic pathway and second‐hit model for gliomagenesis.

Lipofibromatosis arising in a pediatric forearm : A case report

Lipofibromatosis is a rare pediatric tumour described by Fetsch et al. in 2000. There have been few reports about this tumour and few descriptions of its imaging features. We report a case of this tumour forming a slowly growing, painless mass arising in the forearm of a ten-month-old boy. This is the first report of lipofibromatosis to present the radiological findings before surgery. Plain radiography and computed tomography demonstrated a tumour located just beneath the fascia. Ultrasonic study showed a hyperechoic tumour of 33 x 30 x 7 mm in size. Magnetic resonance imaging demonstrated a multilobular mass with high signal intensities on both T1 / T2 weighted images. Macroscopically, the tumour was poorly marginated. Microscopically, the tumour was composed of abundant adipose tissues transversed by fibroblastic bands. The adipose tissue occupied over 70% of the tumour. Adipocytes and fibroblastic element infiltrated into the normal skeletal muscle tissues. Recognition of this clinical entity is needed, especially in cases of lipomatous tumours arising in pediatric hands and feet.

Eosinophilic granuloma arising from the pelvis in children: A report of three cases

Eosinophilic granuloma (EG) is a benign tumor-like condition which is characterized by a clonal proliferation of Langerhans-type histiocytes and defined as a local form of Langerhans cell histiocytosis (LCH). The radiographic appearances of EG are quite different depending on the phase of the disease and the site of involvement. A status of EG in the bone is divided into acute and chronic phases. Radiologically acute phase of EG is difficult to differentiate from a malignant bone tumor such as Ewings sarcoma or acute osteomyelitis. Chronic phase of EG may mimic a chronic osteomyelitis or a benign bone tumor. We report 3 childrens cases of EG in the pelvis which showed quite different radiological features and clinical courses. A 6-year-old boy (Case 1) had an osteolytic lesion with slightly defined margins in the right acetabulum. A 4-year-old boy (Case 2) had a radiologically similar-looking lesion in the left acetabulum. These lesions resembled radiologically chronic osteomyelitis (Brodies abscess) or a benign bone tumor and healed spontaneously after biopsy. A 2-year-old boy (Case 3) had an osteolytic lesion with ill-defined margin in the ilium. It was difficult to differentiate from a malignant tumor such as Ewings sarcoma, or acute osteomyelitis. The lesion became enlarged after needle biopsy. In spite of an additional curettage, the osteolytic lesion remained in the left pelvis in 1 year. Treatment for EG is controversial. Curettage of the affected site and bone grafting is usually accomplished. However, some EG heal spontaneously. It is of great importance to understand the natural course of EG and this knowledge will give us the opportunity to avoid unnecessary treatment. EG with poor osteolytic margins may progress further after biopsy. EG with well-defined margins may heal spontaneously after biopsy only.

The role of estrogen-metabolizing enzymes and estrogen receptors in human epidermis

Local estrogen metabolism and its sensitivities in the skin have been also suggested to contribute to skin homeostasis in addition to age- and/or gender-dependent circulating estrogen, even though their local mechanisms have been largely unknown. To characterize their potential correlations, age- and gender-dependencies were evaluated focusing on 5 pivotal estrogen-metabolizing enzymes including aromatase, estrogen sulfotransferase, steroid sulfatase, and 17β-hydroxysteroid dehydrogenases and estrogen receptors (ERα and ERβ) using immunohistochemistry of 100 human skin specimens. When their epidermal expression levels were compared among 7 age groups, ranging from the teens to the seventies, the highest expression in the teens group and the lowest expression in the seventies group were found in the expression of aromatase and ERβ, respectively, while no significant differences between the male and the female groups were found in the immunoreactivities of our interested proteins. Our results suggest that age-related differences in aromatase and ERβ expressions impact epidermal homeostasis.

Calcific myonecrosis and the role of imaging in the diagnosis: A case report

Calcific myonecrosis is a rare posttraumatic complication characterized by the replacement of muscles of one or more compartments with central liquefaction and peripheral calcification. We report magnetic resonance imaging (MRI) and CT imaging features of calcific myonecrosis arising 43 years after trauma. A 62-year-old man presented with a slowly enlarging mass in the left lower leg. Plain radiographs revealed a soft tissue mass with extensive amorphous calcification. The middle third of the tibia and fibula were eroded. MRI demonstrated peripheral ring enhancement on postcontrast fat-suppressed T1-weighted images. Volume-rendered images extracting only the images of bone and vessels also showed many branches from the tibialis posterior and peroneal arteries around the bone defect. During the operation, bleeding continued heavily from the vessels penetrating the cortical bone of the tibia, from the posterior compartment, and from the branches of tibialis posterior artery. The total blood loss was approximately 2,400 milliliters. There may be a causal relationship between massive bleeding and the hypervascularity of this tumor as evidenced by MRI and volume-rendering CT studies.