Proliferation Of Small Vessels Research Articles

Adipose-derived mesenchymal stem cells markedly attenuate brain infarct size and improve neurological function in rats

BackgroundThe therapeutic effect of adipose-derived mesenchymal stem cells (ADMSCs) on brain infarction area (BIA) and neurological status in a rat model of acute ischemic stroke (IS) was investigated.MethodsAdult male Sprague-Dawley (SD) rats (n = 30) were divided into IS plus intra-venous 1 mL saline (at 0, 12 and 24 h after IS induction) (control group) and IS plus intra-venous ADMSCs (2.0 × 106) (treated interval as controls) (treatment group) after occlusion of distal left internal carotid artery. The rats were sacrificed and brain tissues were harvested on day 21 after the procedure.ResultsThe results showed that BIA was larger in control group than in treatment group (p < 0.001). The sensorimotor functional test (Corner test) identified a higher frequency of turning movement to left in control group than in treatment group (p < 0.05). mRNA expressions of Bax, caspase 3, interleukin (IL)-18, toll-like receptor-4 and plasminogen activator inhibitor-1 were higher, whereas Bcl-2 and IL-8/Gro were lower in control group than in treatment group (all p < 0.05). Western blot demonstrated a lower CXCR4 and stromal-cell derived factor-1 (SDF-1) in control group than in treatment group (all p < 0.01). Immunohistofluorescent staining showed lower expressions of CXCR4, SDF-1, von Willebran factor and doublecortin, whereas the number of apoptotic nuclei on TUNEL assay was higher in control group than in treatment group (all p < 0.001). Immunohistochemical staining showed that cellular proliferation and number of small vessels were lower but glial fibrillary acid protein was higher in control group than in treatment group (all p < 0.01).ConclusionsADMSC therapy significantly limited BIA and improved sensorimotor dysfunction after acute IS.

Angiomatoid Intradermal Melanocytic Nevus or Chimeric Nevus?: A Potential Diagnostic Pitfall

Angiomatoid Intradermal Melanocytic Nevus or Chimeric Nevus?: A Potential Diagnostic Pitfall

Multinucleated Cells Angiohistiocytoma: A Reactive Lesion?

Multinucleated Cells Angiohistiocytoma: A Reactive Lesion?

Intravascular large B-cell lymphoma originating in the left epididymis

Dear Editor, During a routine physical examination of a 55-year-old man, we found that he had a mass in the head of his left epididymis, which was harder than normal, with no obvious margin. He had no abnormality of other organs, including his skin, and imaging studies did not demonstrate masses or lymphadenopathy. The urologist decided to resect the left testicle along with the epididymis. Preoperative laboratory workups showed a white blood cell count of 3.8×10/L, a red blood cell count of 3.9×10/L, a leukocyte count of 0.9×10/L, serum calcium level of 2.18 mmol/L, and a serum phosphorus level of 0.78 mmol/L; all these values were lower than normal. His prostate-specific antigen level was 8.6 μg/L and his lactate dehydrogenase level had increased to 837 U/L. The patient underwent left orchectomy. Macroscopically, the left testicle appeared healthy and measured 5.5×4.5× 3.0 cm. The cut surface showed that the left epididymis was gray but the left testicle was healthy. Microscopically (Fig. 1), there were dilated capillaries and thin-walled small-vessel proliferation in the epididymis. The lumina of the vessels were filled with large, atypical lymphoid cells, but no tumor cells were apparent in the testicle. Immunohistochemical staining of the tumor cells produced positive findings for leukocyte common antigen, CD20 (Fig. 2), CD45RA, and CD79 and negative findings for CD3, CD43, and CD45RO. Test findings for CD5 and Epstein–Barr virus were negative. Test findings for prostatic acid phosphatase (PAP), a marker of prostatic cancer, were positive; findings for high-molecular-weight cytokeratin and low-molecular-weight cytokeratin were negative. The proliferation rate detected by monoclonal antibody Ki67 was nearly 85%. Therefore, the diagnosis was intravascular large B-cell lymphoma (IVLBL). We believe that the cancer occurred initially in the left epididymis. The patient’s marrow did not reveal large, atypical lymphoid cells. Seven days after surgery, the patient reported having a headache. Magnetic resonance imaging of his brain showed normal findings. However, 15 days later, a second round of imaging showed that the patient had several brain masses. The patient grew progressively weaker, so he was given intravenous nutrition in the hope that he would be able to withstand chemotherapy. Three days later, his condition had deteriorated markedly; 7 days after nutritional support began, he lapsed into a coma and died 3 days later. That is, the patient died without chemotherapy 1 month after surgery. According to the 2001 World Health Organization classification, IVLBL is a rare subtype of extranodal diffuse large B-cell lymphoma (DLBCL) characterized by the presence of lymphoma cells only in the lumina of small vessels, particularly capillaries. This uncommon lymphoma of B-cell lineage was originally described in 1959 by Pfleger and Tappeiner [5]. It occurs in adults, and the central nervous system and skin are the most common sites, although it can occur primarily in almost any organ. Imaging techniques have limited value because the tumor usually is not a visible mass, making the diagnosis of IVLBL difficult. The diagnosis is not even made in some patients until after their death. Clinical symptoms are variable; neurologic symptoms and skin lesions are perhaps the most common. Some patients have presented with a fever of unknown origin, with X. Ma :H. Liu (*) Department of Pathology, Changzheng Hospital, Second Military Medical University, No. 415, Fengyang Road, Shanghai 200003, China e-mail: liuhuimin2001@126.com

Angiolipoma in head and neck: report of two cases and review of the literature

Angiolipomas are either encapsulated or non-encapsulated fatty tumours. They are distinguished from other lipomas by the excessive degree of vascular proliferation and because they are mixed with mature adipocytes. They commonly occur in the trunk and extremities and are rare in the maxillofacial area. Only 36 cases in the head and neck have been reported in the literature. The authors report the first non-infiltrating intramasseterine angiolipoma, and a case of non-infiltrating angiolipoma of the cheek. These tumours appear as homogenous low-density areas on CT with no contrast enhancement. MRI gives better tumour delineation and clear definition of the location and longitudinal extent of the mass. Histopathology demonstrates mature adipose tissue and the proliferation of numerous small branching blood vessels. Management of angiolipomas requires complete surgical excision.

Commentary: massive osteolysis or Gorham-Stout disease

In this issue of the Journal, three interesting case reports, one in the print version 1 Tong A.C.K. Leung T.M. Cheung P.T. Management of massive osteolysis of the mandible: a case report. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010; 109: 239-242 Google Scholar and two online, 2 Pedroletti F. Rangarajan S. McCain J.P. Velez I. The conservative treatment of a pathologic fracture in a patient with Gorham-Stout disease. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010; 109: e49-e52 Google Scholar , 3 Gondivkar S.M. Gadbail A. Gorham-Stout syndrome—a rare clinical entity and a review of literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010; 109: e41-e48 Google Scholar discuss a rare condition characterized by a massive and progressive loss of bone. Although rare, this disease is recognized by several names, including disappearing bone disease (phantom bone), Gorham syndrome, Gorham-Stout syndrome, Idiopathic massive osteolysis, massive Gorham osteolysis, massive osteolysis, Morbus Gorham-Stout disease, progressive massive osteolysis, vanishing bone disease, and essential osteolysis. This bone resorption abnormality can affect different sites of the skeleton and in some instances the head and neck region, as described in these 3 cases. Gorham-Stout disease (GSD) is characterized by massive bone loss, which can affect different skeletal sites, and excessive intraosseous proliferation of small blood or lymphatic vessels, resulting in resorption and destruction of bone. The case reports and literature review update the reader in the various aspects that involve this rare condition, including the fact that the condition is often diagnosed by exclusion and late.

Inflammatory Pseudotumor of Splenic Hilar Node Mimicking Gastric Submucosal Tumor

Inflammatory pseudotumor (IPT) is an uncommon clinical condition characterized by proliferation of spindle cells, inflammatory cells, and small vessels. IPT has been reported in various anatomical sites, including the orbit, lung, liver, spleen, and so on. IPT of the lymph node is very rare. We recently experienced a 65-year-old woman diagnosed with IPT of the lymph node in the splenic hilar, or distal supra-pancreatic area, mimicking gastric submucosal tumor. The tumor was removed without event using the laparoscopic method. This lesion in the splenic hilum is extremely rare and has not been cited in the current literature. We describe such a rare case of IPT with a review of the literature.

Animal models of pulmonary arterial hypertension: the hope for etiological discovery and pharmacological cure

At present, six groups of chronic pulmonary hypertension (PH) are described. Among these, group 1 (and 1') comprises a group of diverse diseases termed pulmonary arterial hypertension (PAH) that have several pathophysiological, histological, and prognostic features in common. PAH is a particularly severe and progressive form of PH that frequently leads to right heart failure and premature death. The diagnosis of PAH must include a series of defined clinical parameters, which extend beyond mere elevations in pulmonary arterial pressures and include precapillary PH, pulmonary hypertensive arteriopathy (usually with plexiform lesions), slow clinical onset (months or years), and a chronic time course (years) characterized by progressive deterioration. What appears to distinguish PAH from other forms of PH is the severity of the arteriopathy observed, the defining characteristic of which is "plexogenic arteriopathy." The pathogenesis of this arteriopathy remains unclear despite intense investigation in a variety of animal model systems. The most commonly used animal models ("classic" models) are rodents exposed to either hypoxia or monocrotaline. Newer models, which involve modification of classic approaches, have been developed that exhibit more severe PH and vascular lesions, which include neointimal proliferation and occlusion of small vessels. In addition, genetically manipulated mice have been generated that have provided insight into the role of specific molecules in the pulmonary hypertensive process. Unfortunately, at present, there is no perfect preclinical model that completely recapitulates human PAH. All models, however, have provided and will continue to provide invaluable insight into the numerous pathways that contribute to the development and maintenance of PH. Use of both classic and newly developed animal models will allow continued rigorous testing of new hypotheses regarding pathogenesis and treatment. This review highlights progress that has been made in animal modeling of this important human condition.

Spinal cord biopsy findings of anti‐aquaporin‐4 antibody‐negative recurrent longitudinal myelitis in a patient with sicca symptoms and hepatitis C viral infection

We describe the pathological features of a spinal cord biopsy from a 69-year-old woman with anti-aquaporin-4 antibody-negative recurrent longitudinal myelitis. Spinal cord MRI showed T2 high-intensity lesions with strong gadolinium enhancement, when episodes of sensory-motor impairment were repeated. The radiological abnormality was corrected by corticosteroid administration, but improvement of the symptoms was minimal. Although the patient had sicca symptoms and fulfilled four of the diagnostic criteria for Sjögren syndrome, the diagnosis was excluded, because of infection with hepatitis C virus, an exclusion criterion of Sjögren syndrome. In the spinal cord lesions, necrotic changes affected both myelin and axons. Infiltrating lymphocytes were predominantly T-cells. The proliferation of small vessels with hyalinization and concomitant occlusive change was remarkable. These pathological findings resembled those previously reported in Sjögren syndrome. Ultrastructurally, the endothelial cells of the small vessels showed features of activated cells and contained vesiculo-tubular structures in the cytoplasm, indicating that increased blood-brain barrier (BBB) permeability might contribute to pathogenesis. We speculated that increased BBB permeability and T-cell entry in the spinal parenchyma triggered pathological reactions resulting in necrotic changes in the spinal cord. Obstruction of small vessels might add ischemic damage to the lesions. The clinical course and pathological findings indicated that damage progressed rapidly in the spinal cord and was irreversible. The lesions apparently differed from typical demyelination plaques. Faced with such spinal cord lesions, a preventive therapeutic approach is necessary to avoid attack-associated disability.

Cutaneous Nontuberculous Mycobacterial Infection: A Clinicopathological Study of 7 Cases

Nontuberculous mycobacteria (NTM) are human opportunistic pathogens with an environmental source of infection. The reports of cutaneous NTM infections has increased, and NTM have been regarded as important pathogens in recent years. This study aimed to identify characteristic clinical and histological features of cutaneous NTM infections. We evaluated the medical records and histopathologic slides of 7 cases of NTM infections that were confirmed by polymerase chain reaction between 2003 and 2007. The results showed that cutaneous NTM infections occurred in various aged people independent of their immune states and were associated with fish-related jobs or intramuscular medicinal injection. The main clinical feature was a painful erythematous nodule. Histopathologically, the most common findings were diffuse infiltration of mixed inflammatory cells and small vessel proliferation in the dermis (100%). Epidermal proliferation (71%) and dermal granuloma (71%) were also very common. Suppurative granuloma was found in 43% of the cases, and eosinophil infiltration was uncommon (14%). The lesions disappeared after a mean of 7 months (range, 1.5-12 months) with treatment by oral clarithromycin alone or in combination with other antimycobacterial agents. These clinical and histopathological data should assist clinicians in the diagnosis of NTM.

Cutaneous Reactive Angiomatosis Associated With Chronic Lymphoid Leukemia

Cutaneous reactive angiomatosis is an unusual benign vascular disorder of the skin usually associated to systemic diseases. It is characterized by lobular or diffuse proliferation of small blood vessels with hyperplasia of endothelial cells, pericytes, and sometimes histiocytes. We report a 59-year-old man with asymptomatic erythematous-violaceous patches on back, palms, and elbows for 9 months. Laboratory examination revealed changes consistent with B-chronic lymphocytic leukemia. Cutaneous biopsy showed a predominantly lobular small blood vessel proliferation in dermis with pericytic hyperplasia and mild perivascular lymphoplasmacytic infiltrate. Spontaneous involution of lesions occurred after 6 months. A second biopsy performed at the beginning of clinical involution showed a less prominent vascular component with perivascular giant cells with coexpression of CD68 and CD 31. To our knowledge, this is the first case of cutaneous reactive angiomatosis with documented histopathological findings of clinical involution.

Progressive Gorham Disease of the Forearm

Gorham's-Stout disease is a rare but potentially debilitating disease consisting of massive bone osteolysis and bone resorption associated with vascular proliferation and increased osteoclastic activity. Although it can present in a wide variety of forms, it typically involves bones formed by intramembranous ossification such as the skull, pelvis, and scapula. It can occur spontaneously or after trauma. Most cases are monofocal and resolved spontaneously, although there are reports of multifocal and rapidly progressing disease. It typically presents as disuse muscle atrophy or pathologic fracture during the second through fourth decades of life, yet it has also been reported in childhood and in the elderly. The etiology of Gorham's disease remains to be fully elucidated. Gorham attributed the origin of the disease to uncontrolled proliferation of small vessels eating away bone tissue. Other authors attribute the cause of the disease to increased osteoclastic activity mediated by elevated cytokine levels and increased osteoclastic differentiation. Treatment is not established and focuses at stopping osteoclastic activity and angiogenic proliferation. Radiation therapy, chemotherapy, bone grafting, and antiresorptives medications have all been used with different degrees of success. In an effort to further characterize this elusive disease, we report on an unusual presentation of a patient with Gorham's disease of the radius spreading to the ulna and then the proximal humerus with a 13-year follow-up. To our knowledge this is the first report in the literature of a saltatory type of Gorham's disease spreading from bone to bone across a joint.

Angiolipomas, a rare manifestation of HIV-associated lipodystrophy

Angiolipomas, a rare manifestation of HIV-associated lipodystrophy

Inflammatory pseudotumor of lymph nodes presenting as pyrexia of unknown origin

Inflammatory pseudotumor (IPT) is an uncommon benign disorder characterized by proliferation of spindle cells, inflammatory cells, and small vessels. The IPT of lymph nodes is a rare cause of lymphadenopathy that usually affects one or two nodal groups. We describe a 27-year-old male presenting with generalized lymphadenopathy, hepatosplenomegaly and fever for 1 year. Histologic examination of lymph node revealed few remnant lymphoid aggregates with marked sclerosis and numerous anastomosing blood vessels in lymph node parenchyma. Interspersed in between the fibrotic bands was a polymorphic infiltrate composed of lymphocytes, plasma cells, eosinophils, and immunoblasts. Also, many histiocytes, multinucleated giant cells some being Langhan's type and at places forming ill-defined granulomas were observed. The presence of granulomas and Langhan's type of giant cells can lead to a misdiagnosis of tuberculosis as was also done in the present case. It is thus not only important to be aware of this rare benign pathologic entity while dealing with a case of lymphadenopathy, but also consider it in the differential diagnosis of granulomatous disease.

Epstein–Barr virus-related reactive lymphoproliferative disorders in middle-aged or elderly patients presenting with atypical features. A clinicopathological study of six cases

We report six cases of Epstein–Barr virus (EBV)-associated lymphoproliferative disorders (LPDs) in middle-aged and elderly patients exhibiting atypical clinical findings. The patients, two males and four females, ranged in age from 52 to 74 years, with a median age of 64 years. Clinically, they were characterized by tonsillar tumor, cervical lymphadenopathy, and absence of atypical lymphocytosis of the peripheral blood. “B”symptoms were recorded in only two cases. Pancytopenia was recorded in one case during the disease course. The clinical course was self-limited. Histologically, all lesions were characterized by effacement of the follicles and expansion of the interfollicular area with proliferation of small vessels, indicating atypical lymphoid proliferation. In the interfollicular area, there was a mixed infiltrate, including small-to-medium-sized lymphocytes, plasma cells, and T-and B-immunoblasts. Immunoblasts resembling Reed–Sternberg cells were observed in four lesions. Three lesions contained numerous mature plasma cells, plasmacytoid cells, and immature plasma cells in some areas. In situ hybridization demonstrated a varying number of EBV-infected lymphocytes in the interfollicular area. The overall histomorphologic findings of the present six cases were similar to those of infectious mononucleosis (IM) in younger patients. However, the clinical findings were quite different from those of IM in the younger age population. To avoid overdiagnosis and overtreatment, we emphasize the need to be aware of the atypical clinical presentation of EBV-related LPDs in middle-aged or elderly patients, and to turn careful attention to these clinical and laboratory findings as well as to the morphologic features.

Cortical fibrosis and blood-vessels damage in human ovaries exposed to chemotherapy. Potential mechanisms of ovarian injury

Chemotherapy destroys primordial follicles and can lead to ovarian atrophy. Although reports indicate that apoptosis is the mechanism responsible for follicle loss, additional pathways can be involved. This study investigates the damage in human ovaries after administration of non-sterilizing doses of chemotherapy. In a blind study, pathological changes in ovarian tissue harvested for cryopreservation were evaluated. The study group comprised young non-sterile cancer patients, previously exposed to chemotherapy who were (mean +/- SD), when compared with non-exposed patients. Thirty-five cancer patients aged 28.7 +/- 6.74; 17 were previously exposed to non-sterilizing chemotherapy and 18 were not. In all samples, primordial follicles were present. In previously exposed patients, damage to cortical blood vessel and proliferation of small vessels was observed. The cortex showed focal areas of fibrosis with disappearance of follicles (sensitivity 76%, positive predictive value 75% for <37 years old patients). Older patients, not exposed to chemotherapy (5/7) showed similar pathological changes. Injury to blood vessels and focal ovarian cortical fibrosis are aspects of ovarian damage caused by chemotherapy. These findings indicate a potential additional mechanism of damage to the direct apoptotic effect of chemotherapy on follicles. The possibility that these changes are involved in ageing ovaries should be further investigated.

Histopathological study of congenital aortic valve malformations in 32 children

The histopathological characteristics of congenital aortic valve malformations in children were investigated. All the native surgically excised aortic valves from 32 pediatric patients suffering from symptomatic aortic valve dysfunction due to congenital aortic valve malformations between January 2003 and December 2005 were studied macroscopically and microscopically. The patients' medical records were reviewed and the clinical information was extracted. The diagnosis was made by the clinical presentation, preoperative echocardiography, intraoperative examination, and postoperative histopathological study, excluding rheumatic or degenerative aortic valve diseases, infective endocarditis and primary connective tissue disorders, e.g. Marfan syndrome. Among 32 children with congenital aortic valve malformations, the age was ranged from six to 18 years, with a mean of 14.9 years, and there were 27 boys and five girls (male: female = 5.4:1). There were five cases of aortic stenosis (AS, 15.62%), 25 cases of aortic insufficiency (AI, 78.13%) and two cases of AS-AI (6.25%), without other valve diseases. Twenty cases still had other congenital heart diseases: ventricular septal defect (19 cases), patent ductus arteriosus (two cases), double-chambered right ventricle (one case), aneurysm of the right anterior aortic sinus of valsalva (three cases). Histopathological examination indicated that the cusps became thickening with unequal size, irregular shape (coiling and prolapse edge), enhanced hardness, and partly calcification. Microscopic investigation revealed the unsharp structure of valve tissue, fibrosis, myxomatous, reduced collagen fiber, rupture of elastic fibers, different degrees of infiltration of inflammatory cells, secondary calcareous and lipid deposit, and secondary fibrosis. Congenital aortic valve malformations in children involve males more than females, mostly associated with other congenital heart diseases. Aortic insufficiency is more common in children with congenital aortic valve malformations. Histopathologically, the leaflets of aortic valve are mainly myxomatous, thickening with unequal size, irregular shape (coiling and prolapse edge), reduced collagen fiber, rupture of elastic fibers, without small vessel proliferation and inflammatory cell infiltration, fibrosis and calcification rarely seen.

Eccrine Angiomatous Harmartoma in an Infant

Eccrine angiomatous hamartoma is a nevoid proliferation of eccrine glands and small vessels. It usually presents as a solitary, slow growing nodule, manifesting at birth or in childhood, which can be accompanied by hyperhidrosis and pain on palpation. We report an occurrence in an otherwise healthy 3-month-old girl who had multiple, asymptomatic, nodular lesions with a linear arrangement localized to the inguinal fold. We also review the literature on adnexal hamartomas of infancy.

Diffuse Dermal Angiomatosis of the Breast

Diffuse dermal angiomatosis is rare and usually considered a variant of reactive angioendotheliomatosis. It generally involves the extremities of patients with severe vascular disease and other comorbidities. Two patients with breast involvement have been described; however, neither had a relevant medical history or a vaso-occlusive disorder, but both had large pendulous breasts, and 1 was positive for IgM anticardiolipin and antinuclear antibodies. A 53-year-old woman had a reticulated, erythematous plaque with superficial ulceration and underlying tender nodules on her left breast. She had a history of cardiovascular disease and was a heavy smoker. Biopsy of the lesion showed diffuse proliferation of additional endothelial cells and small bland vessels within the papillary and upper reticular dermis. Angiography showed almost complete occlusion of the subclavian artery proximally. Diffuse dermal angiomatosis was diagnosed. With isotretinoin therapy, the lesions improved. One month later, after percutaneous subclavian arterial revascularization, the lesion resolved completely. A literature review suggested that a history of heavy smoking, in addition to a history of vascular disease, may be important in the pathogenesis of diffuse dermal angiomatosis. Clinical acumen is crucial to diagnose diffuse angiomatosis of the breast. Appropriate treatment to alleviate hypoxia may improve the patient's condition.

Intussusception due to inflammatory fibroid polyps of the ileum: a report of 12 cases from Africa.

Eleven cases of inflammatory fibroid polyp of the ileum from Malawi and 1 from Sierra Leone are described. All 12 patients presented with acute intestinal obstruction as a result of an intussusception caused by the polyp. The lesions are characterized by a variable proliferation of fibroblasts and small vessels which may involve the whole thickness of the bowel wall. Tissue mast cells and eosinophils were noted in the polyps. The aetiology of these lesions remains obscure but they appear to be reactive rather than neoplastic. The condition appears to occur more commonly in Malawi than in the United Kingdom or North America and is an important cause of small bowel obstruction in that part of Africa.