Vascular Stroma Research Articles

Predictors of disease progression in ductal carcinoma in situ of the breast and vascular patterns

Breast carcinoma-induced angiogenesis helps meet growing metabolic needs of tumors and progressively increases with malignant transformation of benign ducts to ductal carcinoma in situ (DCIS) and ductal carcinoma in situ to invasive carcinoma. There are conflicting data regarding the difference in angiogenesis in low-, intermediate-, and high-grade ductal carcinoma in situ. If angiogenesis is related to ductal carcinoma in situ progression, the types of ductal carcinoma in situ with more aggressive biologic potential would have different vascular patterns than the less aggressive ones. In this study, we classified 51 cases of ductal carcinoma in situ as low (10-20 years to progression to invasive carcinoma), moderate, or high aggressive (2-5 years to progression to invasive carcinoma), based on criteria outlined by Tsikitis and Chung (Am J Clin Oncol 2006; 29:305), which takes into account nuclear grade, mitotic rate, Ki-67, Her2Neu, P53, estrogen, and progesterone receptor expression. We correlated these 3 groups of ductal carcinoma in situ with the extent of periductal and stromal vascularity and the presence and type of vascular breaks. No association of aggressive biologic behavior of ductal carcinoma in situ with any vascular pattern was found. Moreover, no correlation was found between vascular patterns and classifiers of aggressiveness, microvascular density, or outcome (local recurrence, invasive carcinoma, or metastatic disease). To validate our cohort, we confirmed expected correlations of all measured parameters of aggressiveness by correlating them with each other. In summary, vascular patterns in ductal carcinoma in situ do not correlate with the predictors of aggressive behavior, suggesting that the biologic potential of ductal carcinoma in situ is independent of angiogenesis.

OP19.02: Stromal ovarian vascularization assessed by spatial temporal image correlation (STIC)‐high definition flow (HDF) in women with PCOS

OP19.02: Stromal ovarian vascularization assessed by spatial temporal image correlation (STIC)‐high definition flow (HDF) in women with PCOS

The Nyhus–Wantz lectureship: etiology, herniosis, diverticulosis coli, and cancer

The Nyhus-Wantz Lectureship honors two giants who represent the few who formed a new surgical specialty: herniology. My topics are etiology, herniosis, diverticulosis coli, and cancer. Hippocrates blamed wear and tear for herniation. Russell's (Lancet 1:1519-1523, 1902) explanation was congenital peritoneal "buds" extending down to the pelvis. Harrison (Arch Surg 4:680-689, 1922) attributed herniae to transversalis fascial degradation. Keith (Lancet 2(17):1398-1399, 1906) concluded that pathology was involved, even though Russell (Lancet 1:1519-1523, 1902) had denied it. Nevertheless, the congenital theory prevailed. According to McVay (Christopher's textbook of surgery, W.B. Saunders, Philadelphia, 1960, p. 159), defects arise in normal musculo-aponeurotic structures. Research showed that atrophy was caused by damaged fibroblasts producing less collagen, which was abnormal (having a reduced I/III ratio). The disease was systemic, later named herniosis. Nicotine addiction increased the incidence of herniation by an inflammatory process named metastatic emphysema. In 1948, Saint's Triad, an aggregation of hiatus hernia (later, any primary hernia), gallstones, and diverticulosis coli, was introduced. This association occurred eight times more often than expected, with herniosis appearing to be its cause, abetted by high blood cholesterol causing gallstones. In 2006, Krones et al. (Int J Colorectal Dis 21:18-24, 2006) provided evidence that colon cancer is accompanied by a reduction in diverticula. Klinge et al. (Hernia 8(4):300-301, 2004) showed that these entities require different extracellular matrices (ECMs). Ghajar and Bissell (Histochem Cell Biol 130:1105-1118, 2008) pointed out that the ECM, which comprises 80% of the breast, influences its epithelial genetic expression, likewise with other organs (kidney, skin, lung, colon, and ovaries). Recently, a fundamental change in our understanding of cancer growth and metastasis has taken place. Whereas the degradation of connective tissue was thought to encourage invasion, eliciting concern for the herniated, now, investigators report the reverse, a reactive vascularized stroma resembling wound healing with an increase in fibroblasts and collagen I. Words such as desmoplasia, fibrosis, and stiffening abound. In conclusion, degradation of the ECM may be why herniosis appears to be hostile to the development of cancer throughout the body. Studies are needed of patients with and without a history of hernia to determine their incidence of cancer. Data from smokers should be separated, since they carry their own high risk of malignancy.

Adipokines and Redox Signaling: Impact on Fatty Liver Disease

Adipokines (adipose tissue cytokines) are polypeptide factors secreted by adipose tissue in a highly regulated manner. The 'classical' adipokines (leptin, adiponectin, and resistin) are expressed only by adipocytes, but other adipokines have been shown to be released by resident and infiltrating macrophages, as well as by components of the vascular stroma. Indeed, adipose tissue inflammation is known to be associated with a modification in the pattern of adipokine secretion. Several studies indicate that adipokines can interfere with hepatic injury associated with fatty infiltration, differentially modulating steatosis, inflammation, and fibrosis. Moreover, plasma levels of adipokines have been investigated in patients with nonalcoholic fatty liver disease in order to establish correlations with the underlying state of insulin resistance and with the type and severity of hepatic damage. In this Forum article, we provide a review of recent data that suggest a significant role for oxidative stress, reactive oxygen species, and redox signaling in mediating actions of adipokines that are relevant in the pathogenesis of nonalcoholic fatty liver disease, including hepatic insulin resistance, inflammation, and fibrosis.

Angiomatoid giant cellular blue nevus of vaginal wall associated with pregnancy

BackgroundBlue nevi that arise from the Müllerian tract are rare melanocytic lesions. Several histopathologic variants of cellular blue nevi have been described. The angiomatoid variant is characterized by a vascular component, and is considered to be a rare variant. Few studies have explored the influence of pregnancy on melanocytic lesions.CaseA 29-year-old woman was presented with a pigmented vaginal lesion that increased gradually during pregnancy. A full term gynecologic examination showed a tumor mass protruding into the vaginal canal. The mass was resected during cesarean-section under the clinical impression of vaginal hemangioma.ResultGross examination revealed a cystic mass measuring 6.0 × 4.3 × 3.5 cm, which was filled with dark friable material. Histologically, the mass showed a subepithelial cellular proliferation of heavily pigmented dendritic melanocytes with prominent vascular stroma. Cytologic pleomorphism, junctional activity, atypical mitosis, and necrosis were not found. The proliferation was immunoreactive for HMB-45, S-100 and melan-A, and non-immunoreactive for CD34, smooth muscle actin, and AE1/AE3. The MIB-1 proliferative index was less than 1%. The patient had a postoperative course without complication.ConclusionsAngiomatoid giant cellular blue nevus arising from the vagina during pregnancy is extremely rare. The low proliferative index and absence of cytologic pleomorphism, or necrosis, supports a benign biological behavior. Clinical follow-up showed no evidence of recurrence at one year after the resection of the mass.

Morphological Studies on the Choroid Plexus in Balady Goat (Capra hircus)

The lateral ventricle choroid plexus could be subdivided according to its vascular pattern into caudal part, middle part and rostral part (villus fringes), The two narrow bands which arose from the choroid plexuses of the lateral ventricles passed in the interventricular foramen, forming the choroid plexus of the third ventricle, each band appeared under stereomicroscope as down folding liner tufts reaching the level of pineal body. The third and fourth ventricles choroid plexuses consisted of a large number of leaveslike processes connected to a more basal core of the stromal tissue by a stem. Secondary leaf-like elevations might arise from primary leaves. The stromal tissue extended into the leaves accompanied by vessels which brake up into capillary plexuses in the body of the leaves. The highly vascular stroma of the choroid plexus covered with a single layer of cuboidal epithelium almost ciliated, with an average height 9.55 µm. The covering epithelium constitutes about 19.5 %, 31.9 % and 31.8% of the total bulk of the choroid plexuses of the lateral, third and fourth ventricles respectively. Relatively large amount of connective tissue separated the blood vessels from the epithelium representing about 30.1% of the total bulk of the

Osteoblastoma in the Nasal Cavity

A benign osteoblastoma of the nasal cavity is very rare. A 57-year-old woman, who had a radical hysterectomy for carcinoma of the uterine cervix 5 years ago, underwent F-18 FDG PET/CT. An expansile bone tumor with high glucose metabolism in the middle turbinate of the left nasal cavity was incidentally demonstrated. A subsequent Tc-99m methylene diphosphonate 3-phase bone scan revealed focal increased uptake of radionuclide in all 3 phases at the corresponding tumor. Histology confirmed a benign osteoblastoma that was composed of proliferating osteoblasts with woven bone spicules and rich vascular stroma. Scintigraphic findings, including F-18 FDG PET/CT and 3-phase bone scan, reflected the pathologic features well.

Cellular Integration and Vascularisation Promoted by a Resorbable, Particulate‐Leached, Cross‐Linked Poly(ε‐caprolactone) Scaffold

Flexible, strong scaffolds were created by crosslinking PCL with 1,6-hexamethylenediisocyanate, using paraffin beads as a porogen. Particulate leaching generated homogeneous scaffolds with interconnected spherical pores of 5-200 µm. Subcutaneous implantation in rats for 3 months resulted in minimal scaffold resorption and a non-inflammatory regenerative host response, with complete infiltration by alternatively-activated CD68(+) macrophages. In addition, scaffolds were populated extensively along microfractures by a stromal matrix, which was highly vascularised and contained a subset of stromal cells that expressed the anti-inflammatory CD163 antigen. Such microfractures may be an important physical feature for directing stromal integration and vascularisation events.

Deep Intrastromal Bevacizumab Injection for Management of Corneal Stromal Vascularization After Deep Anterior Lamellar Keratoplasty, A Novel Technique

To report the effect of intrastromal injection of bevacizumab in an eye with extensive corneal stromal vascularization after deep anterior lamellar keratoplasty. Bevacizumab (2.5 mg/1 mL) was injected into the deep corneal stroma of an eye with severe and extensive stromal vascularization. Corneal vascularization regressed dramatically after deep stromal injection of bevacizumab with no recurrence after 6 months. Visual acuity was improved, and the patient's complaints subsided. Corneal intrastromal injection of bevacizumab can be considered for management of intrastromal vascularization after deep anterior lamellar keratoplasty.

Olfactory Neuroblastoma

Olfactory neuroblastomas (esthesioneuroblastomas, ONB) are rare malignant neoplasms that arise from sensory neuroepithelial (neuroectodermal) olfactory cells found in the superior nasal concha and the cribriform plate of the ethmoid sinus. ONBs comprise approximately 5% of sinonasal tract malignancies, affect both genders equally and primarily involve the middle aged adult group (range 3 – 79 years). The most common presenting symptoms are unilateral nasal obstruction, epistaxis and a fairly slow-growing mass high in the nasal cavity or ethmoid region. Anosmia is also characteristic. A classic, though advanced, radiologic presentation is that of a “dumbbell-shaped” mass on either side of the cribriform plate, with an expansion into the nasal vault and an opposite expansion into the intracranial cavity. 1, 2, 3
 We present here two illustrative cases. The first is a 67 year old male who has had three recurrences of a left nasal mass over a span of 24 years. The initial occurrence was treated with excision and radiotherapy, while subsequent recurrences were treated with excision alone. The material shown herein is from the latest recurrence. All previous slides were not available for review. The second case is a 52 year old male who presented with a 6 month history of a right nasal cavity mass that on initial consult already extended into the maxillary, ethmoid, sphenoid, and bilateral frontal sinuses, penetrated the cribriform sinus, and involved the right frontal lobe of the brain. A craniofacial resection was performed.
 The typical case is best described as a “malignant small round cell tumor” arranged in rounded lobules in a vascularized stroma (Fig. 1). This general architecture is found irrespective of the grade of the tumor. The cells are neuroendocrine in appearance, with uniform, small round nuclei that have “salt-and-pepper” nuclear chromatin (Fig. 2) and scanty cytoplasm. Tumors are graded according to the Hyams’ grading system. Grades 1 – 2 tumors have nil to few mitoses, minimal nuclear pleomorphism, absent necrosis and presence of Homer-Wright pseudorosettes (Fig. 3), while Grades 3 – 4 tumors have brisk mitoses, prominent nuclear pleomorphism, frequent necrosis and predominance of Flexner-Wintersteiner true rosettes (Fig. 4, 5). The first case is an example of a Grade 2 ONB, while the second shows a Grade 4 morphology. Immunohistochemistry typically shows diffuse positivity for the neuroendocrine markers neuron-specific enolase, chromogranin and synaptophysin (Fig. 6), and negative reactions for cytokeratins, desmin and CD99. The latter three stains are significant in that the differential diagnoses include Sinonasal Undifferentiated Carcinomas (SNUC), Rhabdomyosarcomas and Primitive Neuroectodermal Tumors/Ewing Sarcomas (PNET/ES) in which these stains are expected to be positive, respectively.1, 3, 4 Other differential diagnosis include a Non-Hodgkin Lymphoma and a Mucosal Malignant Melanoma for which a Leukocyte Common Antigen (LCA) and melanoma markers (e.g. HMB-45 or Melan-A) may be performed. The two cases were however sufficiently distinct as to rule out these two entities on morphologic grounds.
 Prognosis is stage- (90% 5-year survival rate for early-stage versus 40% for advanced-stage cases), and grade-dependent (80% for low-grade versus 40% for high-grade cases). Recurrence occurs in approximately 30% of cases, usually within two years. The long-term recurrences seen in the first case is compatible with its low-grade morphology. In contrast, the shorter history and high stage (Kadish stage C)4 at presentation of the second case are both compatible with its high-grade morphology. Metastases develop in about 20% of cases and usually involve the lymph nodes, lungs and bone. Complete surgical excision with post-operative radiotherapy is the mainstay of treatment. 1,2
 
 
 
 Acknowledgements: 
 The author would like to acknowledge Drs. Ramon Antonio B. Lopa and Arsenio Claro A. Cabuncal for the two cases, and Drs. Treah May D. Suacillo and David Brian U. Olveda for the assistance in the pathologic sign-out and preparation of the microscopic images.

Airway branching morphogenesis in three dimensional culture

BackgroundLungs develop from the fetal digestive tract where epithelium invades the vascular rich stroma in a process called branching morphogenesis. In organogenesis, endothelial cells have been shown to be important for morphogenesis and the maintenance of organ structure. The aim of this study was to recapitulate human lung morphogenesis in vitro by establishing a three dimensional (3D) co-culture model where lung epithelial cells were cultured in endothelial-rich stroma.MethodsWe used a human bronchial epithelial cell line (VA10) recently developed in our laboratory. This cell line cell line maintains a predominant basal cell phenotype, expressing p63 and other basal markers such as cytokeratin-5 and -14. Here, we cultured VA10 with human umbilical vein endothelial cells (HUVECs), to mimic the close interaction between these cell types during lung development. Morphogenesis and differentiation was monitored by phase contrast microscopy, immunostainings and confocal imaging.ResultsWe found that in co-culture with endothelial cells, the VA10 cells generated bronchioalveolar like structures, suggesting that lung epithelial branching is facilitated by the presence of endothelial cells. The VA10 derived epithelial structures display various complex patterns of branching and show partial alveolar type-II differentiation with pro-Surfactant-C expression. The epithelial origin of the branching VA10 colonies was confirmed by immunostaining. These bronchioalveolar-like structures were polarized with respect to integrin expression at the cell-matrix interface. The endothelial-induced branching was mediated by soluble factors. Furthermore, fibroblast growth factor receptor-2 (FGFR-2) and sprouty-2 were expressed at the growing tips of the branching structures and the branching was inhibited by the FGFR-small molecule inhibitor SU5402.DiscussionIn this study we show that a human lung epithelial cell line can be induced by endothelial cells to form branching bronchioalveolar-like structures in 3-D culture. This novel model of human airway morphogenesis can be used to study critical events in human lung development and suggests a supportive role for the endothelium in promoting branching of airway epithelium.

GLUT-1 staining of squamous cell carcinomas of the uterine cervix identifies a novel element of invasion

Perturbation of the normal tissue architecture in solid malignant tumors is perceived to be the consequence of actively migrating cancer cells which invade the adjacent normal host tissue. The opposite, invasion of cancer cell clusters by a vascularized stroma, has not been considered. The latter process should, however, be expected to occur since the hypoxic cores of tumor cell aggregates, under the control of HIF-1, are known to secrete cytokines (e.g., bFGF, VEGF) which attract fibroblasts and induce blood vessel formation. In this study, the expression of glucose transporter (GLUT)-1, a major HIF-1 target gene, was examined in 51 squamous cell carcinomas of the uterine cervix by immunohistochemistry to identify the localization of hypoxic tumor cell areas. The relationship of the expression pattern of GLUT-1 with the localization and morphology of the tumor stroma was analyzed. We identified three recurrent histological signs which represent strong evidence in favor of an invasion of solid tumor masses by actively migrating stromal cells. According to our findings, the histological structure of squamous cell carcinomas of the uterine cervix may in part result from the interplay between the inherent tendency of neoplastic epithelial cells to expand in the form of coherent aggregates and the fragmentation of these aggregates by invading, finger- or wedge-like stromal protrusions which carry new blood vessels, driven by gradients of hypoxia-induced pro-angiogenic, pro-migratory and growth-promoting molecules emanating from the hypoxic core.

Comparative evaluation in the use of topical corticosteroid in the management of corneal alkali burn ulcers in rabbits

This study was performed to evaluate the addition of steroidal or non-steroidal, anti-inflammatory agents or topical medroxyprogesterone acetate to tetracycline and vitamin C in the management of ocular alkali burns. Alkali wounds were created on the central corneas of rabbits by applying a round filter paper, 12 mm in diameter, soaked in 1 M NaOH for 30 s. Only one eye in each rabbit was treated. A total of 25 rabbits were divided into five groups with five animals each. Five rabbits without treatment after the alkali burn were designated as the control group. In the remaining four groups, topical tetracycline and systemic vitamin C treatment were included. In group A, 1% topical medroxyprogesterone acetate, in group B, 1% topical prednisolone acetate and in group C, topical diclofenac were used. In group D, corneal ulcers were treated with only tetracycline and vitamin C. Clinical outcome was monitored daily by corneal opacity, duration of blepharospasm, corneal vascularization, and duration of ocular discharge. After 3 weeks, corneas were excised for histopathological analysis. Samples were monitored by evaluating corneal thickness (μm), numbers of epithelial rows, keratocyte density, stromal vascularization, stromal inflammation, and stromal collagen arrangement. Comparison between groups showed that groups A, B, and C had significantly lower discharge days, and groups B and C had significantly shorter duration of blepharospasm than the control group. In the microscopic evaluation of the corneas, groups B and C had a significantly lower degree of corneal vascularization, and group B had significantly lower degree of corneal inflammation than the control group. In conclusion, the topical application of 1% prednisolone combined with vitamin C and tetracycline may be therapeutically valuable in the early treatment (first 3 weeks) of corneal alkali burns.

Simple two-layer reflectance model for biological tissue applications: lower absorbing layer

A simple two-layer tissue reflectance model is described. This work is a continuation of our investigations on modeling reflectance from two-layered tissues that we recently initiated. In the present article, we describe a variation of a two-layer model that assumes a lower absorbing and scattering layer and an upper scattering-only layer. This two-layer configuration is a realistic model for biological tissues in the visible and near-IR spectral ranges, where the upper layer may be an epithelial layer and the lower layer is a vascularized stroma layer. Application of the model yields estimates for tissue parameters, such as the thickness of the upper layer or the absorption properties of the lower layer. These parameters are of great interest for the noninvasive study of a wide range of epithelial biological tissues. The validity range and accuracy of the model are tested on tissue phantoms in both the forward and inverse modes of application.

Radiologic-Pathologic Correlation of Ductal Carcinoma in Situ

Ductal carcinoma in situ (DCIS) accounts for 20%-25% of breast cancers detected at screening mammography. The lesions are diverse and commonly are classified on the basis of their mammographic features and histologic characteristics such as nuclear grade and presence or absence of necrosis. The most common mammographic finding in DCIS is microcalcifications, but a low-grade lesion without necrosis is less likely to manifest with calcifications than either an intermediate- or a high-grade lesion. Other mammographic findings might include a mass or architectural distortion. Magnetic resonance (MR) imaging has higher sensitivity than mammography for the detection of DCIS and greater accuracy for depicting the extent of disease. The MR imaging appearance of DCIS depends primarily on the presence and extent of abnormal periductal or stromal vascularity. Nonmasslike enhancement, the most common MR imaging finding, is often seen in association with clumped internal enhancement. The enhancement kinetics in dynamic MR studies vary, and no kinetic pattern is pathognomonic of a particular nuclear grade of DCIS. However, the kinetic pattern at delayed imaging does appear to be correlated with the mammographic findings: Mass lesions show strong washout; fine pleomorphic, fine linear, and fine linear-branching calcifications demonstrate a plateau enhancement pattern; and amorphous calcifications exhibit persistent enhancement. Multidetector computed tomography might be a useful adjunct to MR imaging for preoperative mapping.

Phenotypic Diversity in Chondromyxoid Fibroma Reveals Differentiation Pattern of Tumor Mimicking Fetal Cartilage Canals Development: An Immunohistochemical Study

Chondromyxoid fibroma represents a rare benign cartilaginous tumor of young patients occurring in a subcortical metaphyseal location. The histogenesis of chondromyxoid fibroma has not yet been postulated, even though the conventional histology and recent immunohistochemical studies on phenotype of the mesenchymal cells and extracellular matrix components suggested its origin in immature cartilage. Therefore, we wished to compare the morphological pattern of immature cartilage tissue with chondromyxoid fibroma to investigate a possible developmental counterpart of chondromyxoid fibroma. Archival paraffin-embedded tissues from 4 fetal femora and 10 cases of chondromyxoid fibroma were analyzed simultaneously using histochemistry (safranin O) and established immunohistochemical antibodies (CD34, CD163, and smooth muscle actin). Vascularized cartilage canals growing into the fetal cartilage from the perichondrium displayed characteristic glomeruloid structures with central arterioles within the immature mesenchymal stroma and numerous superficial sinusoidal blood vessels accompanied by macrophage infiltration. Similarly, each case of chondromyxoid fibroma demonstrated admixture of two characteristic components: immature fibrous tissue of vascularized stroma with accumulation of macrophages in areas of superficial sinusoidal proliferation, and variable amounts of lobulated chondroid tissue. Based on the observed substantial morphological similarity between the cartilage canals and chondromyxoid fibroma, we suggest that the chondromyxoid fibroma represents a neoplasm originating from or mimicking the fetal cartilage canals within the immature cartilage.

Stromal elements and engraftment (ENG) in autologous hematopoietic progenitor cell transplant (autoHCT) for myeloma.

8149 Background: ENG after autoHCT involves stromal elements of the stem cell niche. We present a retrospective analysis of marrow biopsies (BM) from patients with myeloma prior to autoHCT and correlate stromal variables with ENG. Methods: BM done just prior to autoHCT from 26 patients (pts) with good engraftment and those from 12 pts with delayed engraftment, were compared. Hematoxylin/eosin stained sections were examined for: stromal components (fat, regenerating adipocytes, fat necrosis, stromal edema, granular degeneration, vascular sinusoids and hemorrhage); bone remodeling (osteoblasts vs osteoclasts); hematopoeisis (endosteal vs peri-sinusoidal hematopoesis); cellularity; and reticulin fibrosis. Reticulin fibrosis was graded using Gomori's silver and Trichrome stains. Duration of disease before autoHCT; total viable CD34 stem cells infused; time to WBC ENG (ANC>500) and platelet ENG (20,000/mm3 and 50,000/mm3) were determined. Univariate and multivariate regression were applied to determine, the correlation of significant stromal parameters with ENG between groups and for the two groups combined Results: Median time to WBC ENG among good and poor engrafters was 12 and 14.5 days respectively. Median time to platelet count of 20,000/cmm and 50,000/cmm for good engrafters was 12.5 and 16 days respectively and for poor engrafters it was 45.5 and 57 days respectively. Endosteal hematopoesis was significantly correlated with WBC and platelet ENG (p < 0.01 and Hazards ratio of > 2.7). Stromal vascularity was significantly associated with platelet ENG but not WBC ENG (p < 0.05 and p > 0.1 respectively). Osteoblastic activity showed significant correlation with WBC ENG (p = 0.003) and platelet ENG to 20,000 (p = 0.016). In univariate analysis between the groups, osteoblastic activity had marginal significance in good engrafters (OR 8.3 with p = 0.05) as did stromal vascularity (OR 8.1 and p = 0.06). No other variables were statistically significant. Conclusions: Pretransplant BM evaluation for stromal elements such as endosteal hematopoesis, stromal vascularity and osteoblastic activity may be useful to predict good WBC and platelet ENG. No significant financial relationships to disclose.

Characterization of adipocyte differentiation from human mesenchymal stem cells in bone marrow

BackgroundAdipocyte hyperplasia is associated with obesity and arises due to adipogenic differentiation of resident multipotent stem cells in the vascular stroma of adipose tissue and remote stem cells of other organs. The mechanistic characterization of adipocyte differentiation has been researched in murine pre-adipocyte models (i.e. 3T3-L1 and 3T3-F442A), revealing that growth-arrest pre-adipocytes undergo mitotic clonal expansion and that regulation of the differentiation process relies on the sequential expression of three key transcription factors (C/EBPβ, C/EBPα and PPARγ). However, the mechanisms underlying adipocyte differentiation from multipotent stem cells, particularly human mesenchymal stem cells (hBMSCs), remain poorly understood. This study investigated cell cycle regulation and the roles of C/EBPβ, C/EBPα and PPARγ during adipocyte differentiation from hBMSCs.ResultsUtilising a BrdU incorporation assay and manual cell counting it was demonstrated that induction of adipocyte differentiation in culture resulted in 3T3-L1 pre-adipocytes but not hBMSCs undergoing mitotic clonal expansion. Knock-down and over-expression assays revealed that C/EBPβ, C/EBPα and PPARγ were required for adipocyte differentiation from hBMSCs. C/EBPβ and C/EBPα individually induced adipocyte differentiation in the presence of inducers; PPARγ alone initiated adipocyte differentiation but the cells failed to differentiate fully. Therefore, the roles of these transcription factors during human adipocyte differentiation are different from their respective roles in mouse.ConclusionsThe characteristics of hBMSCs during adipogenic differentiation are different from those of murine cells. These findings could be important in elucidating the mechanisms underlying human obesity further.

Aggressive osteoblastoma of the sphenoid bone

For osteoblastoma, with its predilection for the spinal column and appendicular skeleton, the skull is an unusual site, and paranasal sinus involvement is very rare. Herein, we report on a case in which the disease was located within the sphenoid bone. To the best of our knowledge, this is the 4th reported case of osteoblastoma with a sphenoid origin (1). We report an osteoblastoma of the sphenoid sinus in a 12-year-old girl who presented with exophthalmos. Computed tomography (CT) demonstrated an expansile lesion of the sphenoid which caused the orbital contents to be compressed and deviated to the right. In the magnetic resonance imaging scan, the lesion was found to invade the cranial base in the frontal and temporal region, approximating to the cavernous sinus and internal carotid artery on the right. Bilateral fronto-orbital craniotomy was performed. Histologically, the lesion was composed of proliferating osteoblasts along with vascular stroma. The tumor was described as an aggressive osteoblastoma. In the follow-up CT four months later, a pathological mass was observed in the area of the nasal septum, and a signal void was present on all sequences in the densely sclerotic areas. A second resection was performed. The patient has been disease-free for 61 months. Herein, we present the diagnosis and management of this unusual lesion. The histopathology and the imaging characteristics are shown.

Clinical and histopathologic review on 28 cases of nodular fasciitis

Background: Nodular fasciitis presents as a solitary, slightly painful, rapidly growing nodule. It is associated with a reactive, proliferative process of unknown cellular origin and can be misdiagnosed as a sarcoma. Objective: Our study was designed to investigate the process and cellular origin of the disease. Methods: The clinical and histopathologic findings from 28 cases of nodular fasciitis were reviewed. Additional histochemical and immunohistochemical staining was done. Results: The mean age of onset was 29.8 years. A majority of patients with nodular fasciitis had a duration of symptoms of less than 6 months. The upper extremity and face were most frequently involved. Most of the lesions had diameters less than 2 cm. Total excisions were performed in 23 lesions; 3 lesions recurred thereafter. Histopathologically, a subcutaneous plane was most frequently involved. The nodule consisted of numerous large, pleomorphic fibroblasts growing haphazardly in a vascular stroma containing varying amounts of mucoid ground substance, which was confirmed by histochemical stains. In the immunohistochemical stain, most lesions had positive findings for smooth muscle actin (SMA), vimentin and negative findings for CD34 except in a few cases. The stains for desmin and S-100 were negative in all cases. Conclusion: It is suggested that nodular fasciitis is associated with a reactive proliferation of myofibroblasts rather than with a sarcomatous process. (Korean J Dermatol 2009;47(6):649∼657)