Giuseppe Ingravallo - Academia.edu (original) (raw)
Papers by Giuseppe Ingravallo
Journal of Clinical Medicine, 2021
Classical Hodgkin’s lymphoma (cHL) is one of the most particular lymphomas for the few tumor cell... more Classical Hodgkin’s lymphoma (cHL) is one of the most particular lymphomas for the few tumor cells surrounded by an inflammatory microenvironment. Reed-Sternberg (RS) and Hodgkin (H) cells reprogram and evade antitumor mechanisms of the normal cells present in the microenvironment. The cells of microenvironment are essential for growth and survival of the RS/H cells and are recruited through the effect of cytokines/chemokines. We summarize recent advances in gene expression profiling (GEP) analysis applied to study microenvironment component in cHL. We also describe the main therapies that target not only the neoplastic cells but also the cellular components of the background.
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Background: Erdheim-Chester disease (ECD), a rare disorder of monocyte/macrophage lineage, has be... more Background: Erdheim-Chester disease (ECD), a rare disorder of monocyte/macrophage lineage, has been related to cerebellar dysfunction. To increase the awareness of this rare, protean disease, an unusual, myasthenia-like onset of ECD is reported.Case presentation: A 42-year-old man presented with a 6-year history of mild evening fatigability in his four limbs followed by motor and cognitive symptoms associated with cerebellar atrophy, dentate nuclei and dentato-thalamic pathway degeneration. Magnetic resonance imaging revealed hyperintense signals in T2 and fluid-attenuated inversion recovery sequences within the pons, cerebellar white matter, dentate nuclei and globi pallidi in the absence of any contrast enhancement. Whole-body bone scintigraphy with 99Technetium - methylene diphosphonate and fluorodeoxyglucose-positron emission tomography both revealed symmetric uptake in the lower extremities a finding suggestive of a diagnosis of ECD. Histological examination revealed diffuse in...
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Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, Jan 27, 2017
Multiple cytokines produced by immune cells induce remodeling and aid in maintaining bone homeost... more Multiple cytokines produced by immune cells induce remodeling and aid in maintaining bone homeostasis through differentiation of bone-forming osteoblasts and bone-resorbing osteoclasts. Here, we investigate bone remodeling controlled by the tumor necrosis factor (TNF) superfamily cytokine LIGHT. LIGHT-deficient mice (Tnfsf14-/- ) exhibit spine deformity and reduced femoral cancellous bone mass associated with an increase in the osteoclast number and a slight decrease of osteoblasts compared with WT mice. The effect of LIGHT in bone cells can be direct or indirect, mediated by both the low expression of the anti-osteoclastogenic osteoprotegerin (OPG) in B and T cells and reduced levels of the pro-osteoblastogenic Wnt10b in CD8+ T cells in Tnfsf14-/- mice. LIGHT stimulation increases OPG levels in B, CD8+ T, and osteoblastic cells, as well as Wnt10b expression in CD8+ T cells. The high bone mass in Light and T- and B-cell-deficient mice (Rag- /Tnfsf14- ) supports the cooperative role ...
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Oncotarget, Jan 30, 2014
LIGHT, a TNF superfamily member, is involved in T-cell homeostasis and erosive bone disease assoc... more LIGHT, a TNF superfamily member, is involved in T-cell homeostasis and erosive bone disease associated with rheumatoid arthritis. Herein, we investigated whether LIGHT has a role in Multiple Myeloma (MM)-bone disease. We found that LIGHT was overproduced by CD14+ monocytes, CD8+ T-cells and neutrophils of peripheral blood and bone marrow (BM) from MM-bone disease patients. We also found that LIGHT induced osteoclastogenesis and inhibited osteoblastogenesis. In cultures from healthy-donors, LIGHT induced osteoclastogenesis in RANKL-dependent and -independent manners. In the presence of a sub-optimal RANKL concentration, LIGHT and RANKL synergically stimulated osteoclast formation, through the phosphorylation of Akt, NFκB and JNK pathways. In cultures of BM samples from patients with bone disease, LIGHT inhibited the formation of CFU-F and CFU-OB as well as the expression of osteoblastic markers including collagen-I, osteocalcin and bone sialoprotein-II. LIGHT indirectly inhibited ost...
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Analytical and Quantitative Cytology and Histology the International Academy of Cytology and American Society of Cytology, Aug 1, 2011
To give to the clinician an objective numerical assessment tool to evaluate melanomas so that a d... more To give to the clinician an objective numerical assessment tool to evaluate melanomas so that a diagnosis can be reached with the assistance of computerized procedures. The approach adopted for differential diagnosis of melanomas and nevi considers diverse morphologic characteristics intrinsic to the lesions, that is, shape, size, and symmetry in total independence of pigmentation, and proposes that this information can be evaluated quantitatively and separately by morphometric procedures with statistically valid independent numeric variables that guarantee objectivity and, from a method point of view, consistency. The results show that the differential diagnosis on malignant and benign lesions is made on five variables, which all describe the fine irregularities of the contour and have a high significance in comparing melanomas to nevi. The multivariate discriminant analysis demonstrates the ability of the analytic variables to discriminate 88% of the lesions, rising to 90% if two-dimensional variables are included.
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Analytical and quantitative cytology and histology / the International Academy of Cytology [and] American Society of Cytology, 2011
To give to the clinician an objective numerical assessment tool to evaluate melanomas so that a d... more To give to the clinician an objective numerical assessment tool to evaluate melanomas so that a diagnosis can be reached with the assistance of computerized procedures. The approach adopted for differential diagnosis of melanomas and nevi considers diverse morphologic characteristics intrinsic to the lesions, that is, shape, size, and symmetry in total independence of pigmentation, and proposes that this information can be evaluated quantitatively and separately by morphometric procedures with statistically valid independent numeric variables that guarantee objectivity and, from a method point of view, consistency. The results show that the differential diagnosis on malignant and benign lesions is made on five variables, which all describe the fine irregularities of the contour and have a high significance in comparing melanomas to nevi. The multivariate discriminant analysis demonstrates the ability of the analytic variables to discriminate 88% of the lesions, rising to 90% if two-...
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European Journal of Oncology, Mar 1, 2010
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Radiologia Medica, 2002
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Gastrointestinal endoscopy, 2004
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Virchows Archiv, 2003
... Domenico Piscitelli · Giuseppe Ingravallo · Leonardo Resta · Maria G. Fiore · Eugenio Maioran... more ... Domenico Piscitelli · Giuseppe Ingravallo · Leonardo Resta · Maria G. Fiore · Eugenio Maiorano ... Semin Diagn Pathol 17:170 177 6. Damiani S, Dina R, Eusebi V (1999) Eosinophilic and ... Semin Diagn Pathol 16:117125 7. Gonzalez JE, Caldwell RG, Valaitis J (1991) Calcium ...
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British Journal of Haematology, Jun 1, 1999
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International Journal of Rheumatic Diseases, 2015
Giant cell tumor (GCT) of the synovial membrane, also known as pigmented villonodular synovitis, ... more Giant cell tumor (GCT) of the synovial membrane, also known as pigmented villonodular synovitis, causes a progressive, relapsing and destructive arthropathy affecting one or more synovial joints. Systemic therapy can be combined to intra-articular treatments, including surgical synoviectomy, especially when monoarticular. Despite that, the synovial membrane commonly grows again with clinical relapse. Here, we report three case of patients diagnosed with GCT of the knee who had an early relapse of the disease even after surgical synoviectomy. All of them underwent intra-articular therapy with infliximab and subsequent synoviectomy to eradicate residual tissue. A complete remission of CGT was achieved without relapse occurring during the follow-up. These preliminary data need to be confirmed by further clinical trials; however, intra-articular therapy with infliximab might be deemed a potential option to treat CGT of a single joint.
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Annals of Hematology, 2014
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Leukemia Research, 2014
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Virchows Archiv, 2003
Several histological variants of colorectal carcinoma have been reported, some of them bearing pr... more Several histological variants of colorectal carcinoma have been reported, some of them bearing prognostic significance, others only incidental findings showing unusual morphological features. The current report was aimed to describe the histological, immunohistochemical and ultrastructural features of an oncocytic adenocarcinoma of the rectum occurring in a 66-year-old woman. Histologically, it was a moderately differentiated adenocarcinoma composed by glandular structures lined by eosinophilic cells. The latter showed abundant granular cytoplasm and large nuclei with prominent nucleoli. Several glandular structures contained intraluminal, basophilic and non-birifrangent microcalcifications. The tumour cells displayed consistent anti-mitochondrial antigen, carcinoembryonic antigen, p53, CDX2 and cytokeratin 20 immunoreactivity. Ultrastructurally, more than 80% of the cytoplasmic area was occupied by abnormal mitochondria, while exocrine or endocrine granules were undetectable. The tumour infiltrated the intestinal wall through the subserosal tissue, but lymph node or distant metastases were absent. The patient is disease free 22 months after surgery. Based on the above features, this case could be appropriately named oncocytic adenocarcinoma with intraluminal microcalcifications. Like gastric neoplasms showing similar morphologic features, this tumour might have a better prognosis, and the presence of microcalcifcations could help its proper recognition at a pre-operative stage.
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Neuropathology, 2009
Giant cell angiitis of the CNS is an uncommon form of vasculitis. Neurological manifestations, bo... more Giant cell angiitis of the CNS is an uncommon form of vasculitis. Neurological manifestations, both of the peripheral and CNS, are common. The most frequent manifestations are visual loss and stroke. Hemorrhagic onset is uncommon. Most cases have a fatal outcome and a tissue diagnosis is rarely established in life. We describe an unusual case of giant cell angiitis beginning as a hemorrhagic tumoral-like lesion. The results of the histological and ultrastructural analysis have also been reported. Our case illustrates that giant cell angiitis should be considered as a cause of intracerebral hemorrhage, particularly when associated with a relapsing and remitting disease of the CNS.
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Neuropathology, 2009
Solitary fibrous tumors (SFT) are rare neoplasms of mesenchymal origin involving soft tissues, ma... more Solitary fibrous tumors (SFT) are rare neoplasms of mesenchymal origin involving soft tissues, mainly serosal sites; the spinal cord location is uncommon. We report a case of SFT occurring in the thoracic spinal cord, discussing histological, ultrastructural and molecular aspects. A 75-year-old woman with an MRI suggesting a dorsal intracanalar lesion was admitted to our institution. T5-T7 laminectomies were performed and an intramedullary tumor was discovered. The tumor arose within the spinal cord and was completely removed. Tumor samples were processed for histological, ultrastructural and molecular analysis (comparative genomic hybridization [CGH], methylation status of O6-methylguanine-DNA methyltransferase [MGMT], p16, deleted in colorectal cancer [DCC] and death-associated protein kinase 1 [DAPK1]). The histological examination demonstrated a proliferation of spindle-shaped cells with a collagen-matrix background. Immunohistochemical staining was positive for vimentin and CD34 and negative for S-100 and epithelial membrane antigen. A histological diagnosis of SFT was made. The ultrastructural examination showed undifferentiated cells within a collagenous matrix and sparse extravascular basement membrane. CGH analysis revealed deletion of 9p21 and losses on 2q, 3p, 16q and 19q and gains on 7q; furthermore, no aberrant methylation pattern was found in the promoter region of MGMT, p16, DCC and DAPK1 genes. On the second-year follow-up, the patient was neurologically intact. The occurrence of SFT within the spinal cord parenchyma and its histological characteristics demonstrate that SFTs are not restricted to serosal surfaces. The course of spinal cord SFT is unknown and long-term follow-up is necessary. The histological, ultrastructural and molecular findings are important for the diagnosis and the authors provide a literature review of these aspects.
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Leukemia & Lymphoma, 2014
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Journal of Neurosurgery: Spine, 2008
The ventriculus terminalis (VT) is a small ependyma-lined cavity within the conus medullaris that... more The ventriculus terminalis (VT) is a small ependyma-lined cavity within the conus medullaris that is in direct continuity with the central canal of the anterior portion of the spinal cord. Normally, such a cavity is identifiable only histologically in children and adults and can be visualized using common neuroradiological techniques only after dilation. Currently, the mechanisms of isolated dilation are not documented. The present work describes 2 cases of VT in elderly patients. Data from a histological and ultrastructural study of a case of VT dilation are reported, and the results are compared with those obtained from the VT of 5 fetuses to explain the nosological aspects of nontumoral VT lesions. Our data suggest that the site, age, and histological characteristics of the lesion allow us to define VT dilation as a nosological entity distinct from other cystic dilations of the conus medullaris.
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Journal of Clinical Medicine, 2021
Classical Hodgkin’s lymphoma (cHL) is one of the most particular lymphomas for the few tumor cell... more Classical Hodgkin’s lymphoma (cHL) is one of the most particular lymphomas for the few tumor cells surrounded by an inflammatory microenvironment. Reed-Sternberg (RS) and Hodgkin (H) cells reprogram and evade antitumor mechanisms of the normal cells present in the microenvironment. The cells of microenvironment are essential for growth and survival of the RS/H cells and are recruited through the effect of cytokines/chemokines. We summarize recent advances in gene expression profiling (GEP) analysis applied to study microenvironment component in cHL. We also describe the main therapies that target not only the neoplastic cells but also the cellular components of the background.
Bookmarks Related papers MentionsView impact
Background: Erdheim-Chester disease (ECD), a rare disorder of monocyte/macrophage lineage, has be... more Background: Erdheim-Chester disease (ECD), a rare disorder of monocyte/macrophage lineage, has been related to cerebellar dysfunction. To increase the awareness of this rare, protean disease, an unusual, myasthenia-like onset of ECD is reported.Case presentation: A 42-year-old man presented with a 6-year history of mild evening fatigability in his four limbs followed by motor and cognitive symptoms associated with cerebellar atrophy, dentate nuclei and dentato-thalamic pathway degeneration. Magnetic resonance imaging revealed hyperintense signals in T2 and fluid-attenuated inversion recovery sequences within the pons, cerebellar white matter, dentate nuclei and globi pallidi in the absence of any contrast enhancement. Whole-body bone scintigraphy with 99Technetium - methylene diphosphonate and fluorodeoxyglucose-positron emission tomography both revealed symmetric uptake in the lower extremities a finding suggestive of a diagnosis of ECD. Histological examination revealed diffuse in...
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Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, Jan 27, 2017
Multiple cytokines produced by immune cells induce remodeling and aid in maintaining bone homeost... more Multiple cytokines produced by immune cells induce remodeling and aid in maintaining bone homeostasis through differentiation of bone-forming osteoblasts and bone-resorbing osteoclasts. Here, we investigate bone remodeling controlled by the tumor necrosis factor (TNF) superfamily cytokine LIGHT. LIGHT-deficient mice (Tnfsf14-/- ) exhibit spine deformity and reduced femoral cancellous bone mass associated with an increase in the osteoclast number and a slight decrease of osteoblasts compared with WT mice. The effect of LIGHT in bone cells can be direct or indirect, mediated by both the low expression of the anti-osteoclastogenic osteoprotegerin (OPG) in B and T cells and reduced levels of the pro-osteoblastogenic Wnt10b in CD8+ T cells in Tnfsf14-/- mice. LIGHT stimulation increases OPG levels in B, CD8+ T, and osteoblastic cells, as well as Wnt10b expression in CD8+ T cells. The high bone mass in Light and T- and B-cell-deficient mice (Rag- /Tnfsf14- ) supports the cooperative role ...
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Oncotarget, Jan 30, 2014
LIGHT, a TNF superfamily member, is involved in T-cell homeostasis and erosive bone disease assoc... more LIGHT, a TNF superfamily member, is involved in T-cell homeostasis and erosive bone disease associated with rheumatoid arthritis. Herein, we investigated whether LIGHT has a role in Multiple Myeloma (MM)-bone disease. We found that LIGHT was overproduced by CD14+ monocytes, CD8+ T-cells and neutrophils of peripheral blood and bone marrow (BM) from MM-bone disease patients. We also found that LIGHT induced osteoclastogenesis and inhibited osteoblastogenesis. In cultures from healthy-donors, LIGHT induced osteoclastogenesis in RANKL-dependent and -independent manners. In the presence of a sub-optimal RANKL concentration, LIGHT and RANKL synergically stimulated osteoclast formation, through the phosphorylation of Akt, NFκB and JNK pathways. In cultures of BM samples from patients with bone disease, LIGHT inhibited the formation of CFU-F and CFU-OB as well as the expression of osteoblastic markers including collagen-I, osteocalcin and bone sialoprotein-II. LIGHT indirectly inhibited ost...
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Analytical and Quantitative Cytology and Histology the International Academy of Cytology and American Society of Cytology, Aug 1, 2011
To give to the clinician an objective numerical assessment tool to evaluate melanomas so that a d... more To give to the clinician an objective numerical assessment tool to evaluate melanomas so that a diagnosis can be reached with the assistance of computerized procedures. The approach adopted for differential diagnosis of melanomas and nevi considers diverse morphologic characteristics intrinsic to the lesions, that is, shape, size, and symmetry in total independence of pigmentation, and proposes that this information can be evaluated quantitatively and separately by morphometric procedures with statistically valid independent numeric variables that guarantee objectivity and, from a method point of view, consistency. The results show that the differential diagnosis on malignant and benign lesions is made on five variables, which all describe the fine irregularities of the contour and have a high significance in comparing melanomas to nevi. The multivariate discriminant analysis demonstrates the ability of the analytic variables to discriminate 88% of the lesions, rising to 90% if two-dimensional variables are included.
Bookmarks Related papers MentionsView impact
Analytical and quantitative cytology and histology / the International Academy of Cytology [and] American Society of Cytology, 2011
To give to the clinician an objective numerical assessment tool to evaluate melanomas so that a d... more To give to the clinician an objective numerical assessment tool to evaluate melanomas so that a diagnosis can be reached with the assistance of computerized procedures. The approach adopted for differential diagnosis of melanomas and nevi considers diverse morphologic characteristics intrinsic to the lesions, that is, shape, size, and symmetry in total independence of pigmentation, and proposes that this information can be evaluated quantitatively and separately by morphometric procedures with statistically valid independent numeric variables that guarantee objectivity and, from a method point of view, consistency. The results show that the differential diagnosis on malignant and benign lesions is made on five variables, which all describe the fine irregularities of the contour and have a high significance in comparing melanomas to nevi. The multivariate discriminant analysis demonstrates the ability of the analytic variables to discriminate 88% of the lesions, rising to 90% if two-...
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European Journal of Oncology, Mar 1, 2010
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Radiologia Medica, 2002
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Gastrointestinal endoscopy, 2004
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Virchows Archiv, 2003
... Domenico Piscitelli · Giuseppe Ingravallo · Leonardo Resta · Maria G. Fiore · Eugenio Maioran... more ... Domenico Piscitelli · Giuseppe Ingravallo · Leonardo Resta · Maria G. Fiore · Eugenio Maiorano ... Semin Diagn Pathol 17:170 177 6. Damiani S, Dina R, Eusebi V (1999) Eosinophilic and ... Semin Diagn Pathol 16:117125 7. Gonzalez JE, Caldwell RG, Valaitis J (1991) Calcium ...
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British Journal of Haematology, Jun 1, 1999
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International Journal of Rheumatic Diseases, 2015
Giant cell tumor (GCT) of the synovial membrane, also known as pigmented villonodular synovitis, ... more Giant cell tumor (GCT) of the synovial membrane, also known as pigmented villonodular synovitis, causes a progressive, relapsing and destructive arthropathy affecting one or more synovial joints. Systemic therapy can be combined to intra-articular treatments, including surgical synoviectomy, especially when monoarticular. Despite that, the synovial membrane commonly grows again with clinical relapse. Here, we report three case of patients diagnosed with GCT of the knee who had an early relapse of the disease even after surgical synoviectomy. All of them underwent intra-articular therapy with infliximab and subsequent synoviectomy to eradicate residual tissue. A complete remission of CGT was achieved without relapse occurring during the follow-up. These preliminary data need to be confirmed by further clinical trials; however, intra-articular therapy with infliximab might be deemed a potential option to treat CGT of a single joint.
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Annals of Hematology, 2014
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Leukemia Research, 2014
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Virchows Archiv, 2003
Several histological variants of colorectal carcinoma have been reported, some of them bearing pr... more Several histological variants of colorectal carcinoma have been reported, some of them bearing prognostic significance, others only incidental findings showing unusual morphological features. The current report was aimed to describe the histological, immunohistochemical and ultrastructural features of an oncocytic adenocarcinoma of the rectum occurring in a 66-year-old woman. Histologically, it was a moderately differentiated adenocarcinoma composed by glandular structures lined by eosinophilic cells. The latter showed abundant granular cytoplasm and large nuclei with prominent nucleoli. Several glandular structures contained intraluminal, basophilic and non-birifrangent microcalcifications. The tumour cells displayed consistent anti-mitochondrial antigen, carcinoembryonic antigen, p53, CDX2 and cytokeratin 20 immunoreactivity. Ultrastructurally, more than 80% of the cytoplasmic area was occupied by abnormal mitochondria, while exocrine or endocrine granules were undetectable. The tumour infiltrated the intestinal wall through the subserosal tissue, but lymph node or distant metastases were absent. The patient is disease free 22 months after surgery. Based on the above features, this case could be appropriately named oncocytic adenocarcinoma with intraluminal microcalcifications. Like gastric neoplasms showing similar morphologic features, this tumour might have a better prognosis, and the presence of microcalcifcations could help its proper recognition at a pre-operative stage.
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Neuropathology, 2009
Giant cell angiitis of the CNS is an uncommon form of vasculitis. Neurological manifestations, bo... more Giant cell angiitis of the CNS is an uncommon form of vasculitis. Neurological manifestations, both of the peripheral and CNS, are common. The most frequent manifestations are visual loss and stroke. Hemorrhagic onset is uncommon. Most cases have a fatal outcome and a tissue diagnosis is rarely established in life. We describe an unusual case of giant cell angiitis beginning as a hemorrhagic tumoral-like lesion. The results of the histological and ultrastructural analysis have also been reported. Our case illustrates that giant cell angiitis should be considered as a cause of intracerebral hemorrhage, particularly when associated with a relapsing and remitting disease of the CNS.
Bookmarks Related papers MentionsView impact
Neuropathology, 2009
Solitary fibrous tumors (SFT) are rare neoplasms of mesenchymal origin involving soft tissues, ma... more Solitary fibrous tumors (SFT) are rare neoplasms of mesenchymal origin involving soft tissues, mainly serosal sites; the spinal cord location is uncommon. We report a case of SFT occurring in the thoracic spinal cord, discussing histological, ultrastructural and molecular aspects. A 75-year-old woman with an MRI suggesting a dorsal intracanalar lesion was admitted to our institution. T5-T7 laminectomies were performed and an intramedullary tumor was discovered. The tumor arose within the spinal cord and was completely removed. Tumor samples were processed for histological, ultrastructural and molecular analysis (comparative genomic hybridization [CGH], methylation status of O6-methylguanine-DNA methyltransferase [MGMT], p16, deleted in colorectal cancer [DCC] and death-associated protein kinase 1 [DAPK1]). The histological examination demonstrated a proliferation of spindle-shaped cells with a collagen-matrix background. Immunohistochemical staining was positive for vimentin and CD34 and negative for S-100 and epithelial membrane antigen. A histological diagnosis of SFT was made. The ultrastructural examination showed undifferentiated cells within a collagenous matrix and sparse extravascular basement membrane. CGH analysis revealed deletion of 9p21 and losses on 2q, 3p, 16q and 19q and gains on 7q; furthermore, no aberrant methylation pattern was found in the promoter region of MGMT, p16, DCC and DAPK1 genes. On the second-year follow-up, the patient was neurologically intact. The occurrence of SFT within the spinal cord parenchyma and its histological characteristics demonstrate that SFTs are not restricted to serosal surfaces. The course of spinal cord SFT is unknown and long-term follow-up is necessary. The histological, ultrastructural and molecular findings are important for the diagnosis and the authors provide a literature review of these aspects.
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Leukemia & Lymphoma, 2014
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Journal of Neurosurgery: Spine, 2008
The ventriculus terminalis (VT) is a small ependyma-lined cavity within the conus medullaris that... more The ventriculus terminalis (VT) is a small ependyma-lined cavity within the conus medullaris that is in direct continuity with the central canal of the anterior portion of the spinal cord. Normally, such a cavity is identifiable only histologically in children and adults and can be visualized using common neuroradiological techniques only after dilation. Currently, the mechanisms of isolated dilation are not documented. The present work describes 2 cases of VT in elderly patients. Data from a histological and ultrastructural study of a case of VT dilation are reported, and the results are compared with those obtained from the VT of 5 fetuses to explain the nosological aspects of nontumoral VT lesions. Our data suggest that the site, age, and histological characteristics of the lesion allow us to define VT dilation as a nosological entity distinct from other cystic dilations of the conus medullaris.
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