Hypocellular Zone Research Articles

Effects of culturing temperature on extracellular matrix formation and redifferentiation of expanded human chondrocyte

s / Osteoarthritis and Cartilage 22 (2014) S57–S489 S170 using the Cre-loxP system (PiT1lox/lox; Acan-CreErt2). All pups were injected intraperitoneal with tamoxifen (0.2mg/g body weight) at postnatal day 3 (P3) and harvested at P6, P7 and P10. Histological analyses of long bones were performed by coloration and in situ hybridizations on paraffin section. Results: Histological analysis of humerus paraffin section at P6 reveals the formation of a hypocellular zone in the center of the growth plate. This hypocellular zone resulted from a massive cell death as shown by TUNEL analysis. The periphery of the neoplastic core was surrounded with smaller, round resting like-chondrocytes. This phenotype resembles to the one observed in mice lacking the hypoxia-inducible transcription factor HIF-1a in cartilage. We are currently investigating the involvement of HIF-1a in the setting up of this phenotype. A similar, but less severe phenotype was observed at P7. At P10 the neoplastic core was not present anymore. However, pronounced disorganization of the proliferative and hypertrophic layers was evident when compared to wild type littermates. Conclusions: Our findings are in line with our previous observations showing that PiT1-depleted cells are more sensitive to pro-apoptotic signals. Considering the specific chondrocyte microenvironment, PiT1 could represent a key player of the chondrocyte survival, therefore being essential to the growth plate maturation. 284 EFFECTS OF CULTURING TEMPERATURE ON EXTRACELLULAR MATRIX FORMATION AND REDIFFERENTIATION OF EXPANDED HUMAN CHONDROCYTE A. Ito yz, T. Aoyama x, J. Tajino y, M. Nagai y, S. Yamaguchi y, H. Iijima y, X. Zhang y, H. Akiyama k, H. Kuroki y. yDept. of Motor Function Analysis, Graduate Sch. of Med., Kyoto Univ., Kyoto, Japan; zRes. Fellow of Japan Society for the Promotion of Sci., Tokyo, Japan; xDept. of Dev. and Rehabilitation of Motor Function, Graduate Sch. of Med., Kyoto Univ., Kyoto, JAPAN; kDep. of Orthopaedic Surgery, Graduate Sch. of Med., Gifu

Invasive carcinoma of no special type, with central acellular zone/fibrotic focus

Clinical history A 83-year-old woman noticed a nodule in her left breast. On ultrasound, there was a 2.3 cm hypoechoic mass. Mammography showed an irregular mass. Needle biopsy was performed and a diagnosis of invasive carcinoma was made. Subsequently mastectomy was performed. Discussion points Triple negative carcinomas show heterogeneity. They include basal-like carcinomas indicating a worse prognosis, and adenoid cystic carcinomas and secretary carcinomas considered to be of a favorable prognosis. Invasive carcinoma of no special type, with central acellular zone/fibrotic focus, is one of the triple negative carcinomas with basal-like features. When a myxoedematous infarcted stroma and/or fibrotic focus with a high-grade cancer cells is seen in the biopsy or excision specimens, this diagnosis should be considered, as this may lead to differential managements. The morphologic characteristics of this tumor type include the presence of tumor cells at the periphery, with a central hypocellular zone. The tumor cells are high-grade, with basaloid features. Immunohistochemistry of the tumor cells demonstrates c-kit and CK14 positivity. In particular, this case shows partial morphologic overlap with adenoid cystic carcinoma, which shows generally favorable prognosis. The differentials of invasive carcinoma with central acellular zone/fibrotic focus and adenoid cystic carcinoma will be also discussed.

Epithelioid hemangioendothelioma with extensive cystic change and CAMTA1 rearrangement

Epithelioid hemangioendothelioma (EHE) is a rare vascular neoplasm that has the ability to recur locally and metastasize. Thus, it is important to distinguish this tumor from other epithelioid vascular neoplasms. A 47-year-old man presented to our hospital with a pelvic mass with severe ischialgia and weight loss. Surgical resection was performed, and the mass was found to have dark red multiloculated cysts with hemorrhage and calcification. The histopathologic examination showed a central sclerotic, hypocellular zone and a peripheral cellular zone. Only the peripheral portion of the wall revealed nested tumor cells in light blue myxoid stroma. These tumors are typically composed of short strands or cords of bland epithelioid cells with occasional intracytoplasmic lumens embedded in a myxohyalinized stroma. The tumor cells were positive for CD31 and CD34 and negative for factor VIII-related antigen, CK (AE1/AE3) and S-100. The tumor nuclei showed distinct break-apart signals with individual green and/or red signals, indicating the presence of CAMTA1 rearrangement. In this study, we report a case of EHE that was difficult to diagnose based on histology alone. Therefore, we also performed fluorescence in situ hybridization, and found that the tumor harbored a CAMTA1 gene rearrangement, which confirmed the diagnosis.

The inferior medullary velum: anatomical study and neurosurgical relevance

Although it is often visualized surgically, details regarding the inferior medullary velum are lacking in the literature. The present study is intended to better elucidate this neuroanatomical structure using microsurgical and immunohistochemical analyses. To study the inferior medullary velum, the authors performed microdissection in 15 adult cadavers. Following gross study, specimens were examined histologically. The inferior medullary velum extended from the flocculus to the middle cerebellar peduncle and stretched between the inferior cerebellar peduncle and the nodule and pyramid. The average thickness of the velum was found to be 0.5 mm (range 0.35-0.8 mm) and the average length was found to be 6 mm (range 5.5-7.2 mm). Arterial branches were identified in all specimens that arose from medullary branches of the posterior inferior cerebellar artery and supplied the inferior medullary velum. Histologically and from internal to external, a choroid plexus epithelium as a single cell layer was adjacent to a cuboidal layer of ependymal cells with no visible cilia. The next layer contained scattered glia in single cells or small clusters. The most external layer was composed of flat spindle cells resembling fibroblasts. No neurons of any type were identified. Only rare axons traversed the thin hypocellular zone that disappeared toward the midline. Based on this cadaveric study, the authors conclude that division of the inferior medullary velum should be relatively harmless as no neuronal cells were identified in this structure, which appears to be a vestigial bridge of tissue between the left and right sides of the cerebellum.

Nodular/Keloidal Scleroderma: Acquired Collagenous Nodules in Systemic Sclerosis

To the Editor: Systemic sclerosis (SSc) is characterized by diffuse fibrosis of the skin and internal organs, whereas localized scleroderma is defined by discrete areas of cutaneous fibrosis without systemic involvement. There are also reports of patients developing exophytic collagenous nodules, which are considered to be a rare variant of localized scleroderma. As in the plaques of localized scleroderma, these collagenous nodules can occur as an isolated skin disease or they can appear in the setting of SSc1,2. Histologically, these nodules can resemble scleroderma: thickened sclerotic collagen bundles without increased spindled fibroblasts intercalating between the collagen, and are therefore termed nodular scleroderma3. In contrast, there have also been reports of patients with scleroderma who develop nodules that histologically have the features of keloid: hypocellular zones of thick glassy hyalinized collagen bundles, which have been referred to as keloidal scleroderma4. We describe 2 cases of SSc, 1 diffuse (dcSSc) and 1 limited (lcSSc), with dramatic eruptive collagenous nodules appearing at different stages of the disease course. A 70-year-old woman presented in June 2003 because of development of Raynaud’s phenomenon and fibrotic skin thickening involving her hands that rapidly progressed to her face, chest, abdomen, and upper and lower extremities [modified Rodnan skin score (mRSS) was 33 (on … Address correspondence to Dr. F.M. Wigley, Division of Rheumatology, Johns Hopkins University, 5200 Eastern Avenue, Suite 4100, Mason F. Lord Building, Center Tower, Baltimore, MD 21224, USA. E-mail: fwig{at}jhmi.edu

Clinicocytopathology of breast cancers with a ring‐like appearance on ultrasonography and/or magnetic resonance imaging

On breast cancer imaging some cancers have an anechoic or high-echoic zone in the tumor on ultrasonography and ring-shaped enhancement on contrast-enhanced magnetic resonance imaging (MRI) with high intensity in the central area of the tumor on T2-weighted imaging, necessitating their differentiation from benign disease. Thus, nine breast cancers with a ring-like appearance on imaging were analyzed on cytopathology. Histologically the cancer cells of these lesions showing a ring-like appearance were located in the periphery of the tumor, with a central hypocellular zone. Five such lesions with a thick, doughnut-like appearance were identified as cancers with acellular zones (CAC), and four lesions with a thinner, rim-like appearance as matrix-producing carcinomas (MPC). The percentage ratio of the cancer-zone width to the tumor diameter was 26.4 +/- 7.8 and 8.0 +/- 3.2 (mean +/- SD), respectively (P= 0.003). Cytologically, highly atypical, naked-nucleus cells were observed in eight of the nine cancers. In two MPC and three CAC, cartilage matrix and amorphous material, respectively, were observed in the background. In summary, the present series of breast cancers having a ring appearance on imaging did not have uniform cytopathological features. They were classified as MPC or CAC, and cytology was useful in their diagnosis and differentiation in some cases.

Basal Phenotype in Breast Carcinoma Occurring in Women Aged 35 or Younger

Breast cancer in the young is considered a special clinical presentation of the disease. Sixty-nine breast cancer cases diagnosed at or before the age of 35 were analyzed for common morphological and immunophenotypical features of basal-like carcinomas. Sixteen carcinomas displayed the immunophenotypical characteristics (estrogen receptor and HER2 negativity and positivity for at least one of the following basal markers: cytokeratin 5 or 14, epidermal growth factor receptor, p63) of basal-like carcinomas, and most of them demonstrated characteristic histological features (pushing borders, lymphocytic peritumoral infiltrate, central hypocellular zone or necrosis, high mitotic rate) too. These tumors were more likely to be high-molecular-weight cytokeratin: 34betaE12 and p53 positive by immunohistochemistry. The presence of a basal-like phenotype can be important as concerns systemic treatment issues and could theoretically be associated with a higher rate of BRCA1 mutations in the young, because of the overlap of BRCA1 mutation associated breast carcinomas and the basal-like phenotype.

Amide proton transfer imaging of 9L gliosarcoma and human glioblastoma xenografts

Amide proton transfer (APT) imaging is a variant of magnetization transfer (MT) imaging, in which the contrast is determined by a change in water intensity due to chemical exchange with saturated amide protons of endogenous mobile proteins and peptides. In this study, eight Fisher 344 rats implanted with 9L gliosarcoma cells and six nude rats implanted with human glioblastoma cells were imaged at 4.7 T. There were increased signal intensities in tumors in the APT-weighted images. The contrast of APT imaging between the tumor and contralateral brain tissue was about 3.9% in water intensity (1.49 +/- 0.66% vs -2.36 +/- 0.19%) for the more uniformly hypercellular 9L brain tumors, and it was reduced to 1.6% (-1.18 +/- 0.60% vs -2.77 +/- 0.42%) for the human glioblastoma xenografts that contained hypocellular zones of necrosis. The preliminary results show that the APT technique at the protein level may provide a unique MRI contrast for the characterization of brain tumors.

Development of arteries in embryonic chick bone marrow with special reference to the appearance of periarterial granulopoietic sheaths.

Arterial development was studied in embryonic chick bone marrow starting on day 11 of incubation and continuing until day 18. Arteries first appear on day 11 as vessels with two components to their wall structure, namely a thin, complete endothelium and a nearly complete pericyte layer. With advancing age, three distinct layers--an endothelium, a complete muscularis, and adventitia--appear. Long, narrow endothelial cells form cellular junctions at their basal surfaces. Smooth muscle cells remain relatively undifferentiated and do not consist of more than three layers even in the largest arteries. The adventitia consists of a hypocellular zone containing fibroblasts and a collagenous extracellular matrix. Unmyelinated nerves are located at the peripheral margin of the adventitia. All of the larger arteries are surrounded by a sheath of heterophilic granulopoietic cells. These cells do not intrude into the adventitia, but basophilic or mast cells often do intrude. The stromal cells of the periarterial granulopoietic sheaths remain as either fibroblastic cells or as multilocular preadipocytes. They, unlike those stromal cells beyond the sheath, never become unilocular adipocytes. By day 18, granulopoiesis is restricted to the periarterial sheaths and to the endosteal regions of the marrow. These studies indicate that fibroblastic stromal cells and preadipocytes, but not fully developed adipocytes, support granulopoiesis in the chick marrow. The stromal cells in the periarterial sheaths either represent a subpopulation of cells that do not develop into adipocytes or represent cells whose development into adipocytes is locally inhibited.