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PubMed2000

Frequency of malignant solid tumors in children.

OBJECTIVE: To find out the frequency of malignant solid tumors in children (< 15 years). SETTING: All cases of pediatric malignant solid tumors which were diagnosed in the section of histopathology at the Aga Khan University Hospital, Karachi during the period of two years. METHODS: These tumors were initially evaluated on H&E stained sections and special stains were also performed whenever indicated. The undifferentiated tumors were evaluated immunohistochemically by using a panel of antibodies on sections from routinely processed, formalin fixed, paraffin embedded tissue blocks. RESULTS: Of two hundred and fifty three (253) consecutive cases of paediatric malignant solid tumors, lymphoma (26.1%) was the most common tumor followed by central nervous system tumors (16.6%), osteosarcoma (7.5%), rhabdomyosarcoma (6.7%), neuroblastoma (5.1%), Wilm's tumor (5.1%), Ewing's sarcoma (4.7%), retinoblastoma (4.7%), germ cell tumor (4.4%) and primitive neuroectodermal tumor (4%) in order of frequency. In seven cases (2.8%), the nature of lesion remained undetermined even after immunohistochemical staining. Rest of malignant tumors (12.3%) included the rare entities like synovial sarcoma, nasopharyngeal carcinoma, leiomyosarcoma, malignant schwannoma and thyroid carcinoma, etc. CONCLUSION: Lymphoma was the most frequent Paediatric tumor. The frequency of childhood central nervous system tumors was quite high as compared to the other series from different regions of Pakistan.

Adolescent↗
PubMedDate not supplied

Controversies on the prognostic significance of tumor infiltrating leukocytes in solid human tumors.

We have performed immunophenotypical (IP) analyses of tumor infiltrating leukocytes (TIL) in both childhood brain tumors (medulloblastomas[MEDs]/primitive neuroectodermal tumors [PNETs] and astrocytomas [ASTRs]) and malignant melanomas (both primary and metastatic) employing a well-characterized library of monoclonal antibodies (MoABs) directed against leukocyte differentiation/activation associated antigens. The antigens were detected by an indirect, biotinstreptavidin conjugated alkaline phosphatase (AP) immunocytochemical technique. Our systematic cell-surface antigen expression profile analysis of 76 primary childhood brain tumors (34 MEDs/PNETs and 42 ASTRs) identified CD8+ CTL in 58/76 brain tumors. CD4+, MHC class II restricted helper lymphocytes were present in 65/76 brain tumors and represented 1-10% of the observed cells. Macrophages were present in 74/76 childhood brain tumor cases observed by us. Leukocyte common antigen (LCA) expression was demonstrated in all 76 brain tumors studied. MoAB UJ 308 detected the presence of premyelocytes and mature granulocytes in 60/76 brain tumors. They were localized perivascularly, within the tumor tissue, or close to necrotic regions. Natural killer (NK) cells were not defined in the childhood brain tumors observed in this study. The IP characteristics of the heterogeneous leukocytic infiltrate of 30 primary (PMs) and 10 metastatic melanomas (MMs) was also investigated by us. We established the presence of some type of melanoma infiltrating host's immunological effector cells in all 40 observed melanoma cases. More specifically, we found NK cells, macrophages and granulocytes in 30/30 PMs and 10/10 MMs. These effector cells represented the vast majority (> 80%) of the melanoma infiltrating immunocompetent cells. T lymphocytes were observed in 20/30 PMs and 6/10 MMs, but their numbers represented only between 5% to 10% of the heterogeneous leukocytic infiltrate. B cells were found in 22/30 PMs and 8/10 MMs, their numbers representing less than 5%. Presence of cells of the dendritic reticulum, involved in antigen presentation was not determined in any of the observed PMs and MMs. The notion that infiltration of the neoplastically transformed mass of cells by TIL is always a prognostically positive phenomenon has changed in recent years as research on extracellular matrix remodeling and angiogenesis have identified numerous secreted factors which are common to both neoplastically transformed cells and infiltrating leukocytes.

Brain Neoplasms↗
PubMed1992

Expression of glial fibrillary acidic protein in human medulloblastoma cells treated with recombinant glia maturation factor-beta.

Medulloblastoma, a common pediatric brain tumor, is a primitive neuroectodermal tumor which often displays neuronal and/or glial characteristics. We have investigated the consequences of treating cell lines derived from a human medulloblastoma with glia maturation factor-beta (GMF-beta), a protein found in mammalian brain. GMF-beta promotes growth arrest and morphological alteration of cultured glioma and neuroblastoma cells. The proliferation of medulloblastoma cells was arrested 24-48 hr after exposure to human recombinant GMF-beta. During the same period, treated cells acquired a morphology similar to that of mature astrocytes. By 72 hr, all treated cells bound an antibody against glial fibrillary acidic protein (GFAP), a distinguishing biochemical feature of mature astrocytes. Immunoreactivity was accompanied by de novo expression of GFAP mRNA. Our observations are the first demonstration of the induction of morphological and biochemical characteristics of mature astrocytes in cultured medulloblastoma-derived cells by an exogenous factor.

Cell Division↗
PubMed1991

Intracranial tumor in infants: characteristics, management, and outcome of a contemporary series.

Since 1980, 22 patients less than 2 years of age have been treated for intracranial tumors at our institution. The most common presentation was elevated intracranial pressure associated with ventriculomegaly (73%). The diagnosis was made by computed tomography or magnetic resonance imaging and confirmed surgically in every case. In 68% of cases, the tumor involved midline structures in the central nervous system. Tumors were infratentorial in 29% of patients less than 1 year of age and in 60% of those more than 1 year of age. Most tumors were either primitive neuroectodermal tumors (41%, 7 of 9 located in midline posterior fossa structures) or astrocytomas (27%, 5 of 6 located in the hypothalamus, chiasm, or optic nerve). Twenty patients had gross or subtotal tumor resection. Surgical mortality and neurological morbidity were 10% and 5%, respectively. Of 5 patients who underwent a second operation for tumor recurrence, 3 demonstrated a change in the pathological features of the tumor from those of the original diagnosis. Of 10 surgical survivors with malignant tumors, 8 received chemotherapy and 5 radiation therapy. Radiation was not administered before 1 year of age. The overall 1-year survival was 70%, and 2-year survival was 58%. Two-year survival for benign and malignant tumors was not significantly different. We think that the interdisciplinary efforts directed toward the treatment of these tumors has improved survival and that all children should be offered entry to a research protocol and aggressive treatment.

Brain Neoplasms↗
PubMed1985

Pathology of midline brain tumors. Immunocytochemical tumor markers and classificatory aspects.

Our understanding of the pathology of human brain tumors has considerably increased in recent years thanks to investigation of nervous tissue markers which can be demonstrated by immunocytochemical techniques in sections of neurosurgical tissue specimens. This development is presented here in a review of the most important entities among midline brain tumors. Detection of neural differentiation markers such as glial fibrillary acidic protein (GFAP), S 100 protein (S 100 p), neurofibrillary proteins and neuron-specific enolase (NSE) greatly contributed to clarifying the histogenesis and differentiation potential of undifferentiated small-cell tumors grouped as primitive neuroectodermal tumors (PNETs) which include cerebellar medulloblastomas and pinealoblastomas as well as neuroblastomas and ependymoblastomas. Among medulloblastomas, the desmoplastic variety (formerly called by some "arachnoidal sarcoma of the cerebellum") shows frequent glioneuronal differentiation. Monoclonal antibodies recognizing antigenic determinants specific for tumor types and grades of malignancy/differentiation will gain significance in brain tumor diagnosis, as demonstrated in some examples. Despite the development of more objective ("scientific") criteria for typing human brain tumors, the "art" of classical histopathologic evaluation is not replaced but supplemented by the wealth of data supplied by such modern accomplishments.

Astrocytoma↗
PubMed1986

Primary pigmented nodular adrenocortical disease: diagnosis and management.

A rare cause of Cushing's syndrome appearing to originate in the adrenal glands is primary pigmented nodular adrenocortical disease (PPNAD). It may be variably associated with a complex of other pathologic characteristics that include cardiac myxomas, cutaneous myxomas, and lentigines, mammary myxoid lesions, testicular tumors, pituitary adenomas, and neuroectodermal tumors. We have reviewed the clinical, biochemical, radiographic, operative, and pathologic details of seven patients with PPNAD who have been evaluated at Mayo Clinic. Biochemical testing supported autonomous adrenal hyperfunction. This was based on the failure of cortisol suppression by high-dose dexamethasone, failure of pituitary stimulation by metyrapone administration, either normal or suppressed basal adrenocorticotropic hormone (ACTH) levels, normal radiographic studies of the sella turcica, and normal abdominal and thoracic computerized tomography in search of an ectopic ACTH-producing tumor. Six patients underwent bilateral total adrenalectomy without postoperative complications. Nelson's syndrome has not occurred, but acute adrenocortical insufficiency may have contributed to the death of one patient. To recognize the possible diagnosis of PPNAD preoperatively is important to proceed directly with adrenalectomy, avoiding unnecessary pituitary surgery. Moreover, if PPNAD is part of the broader pathologic complex, the possible presence of cardiac myxomas that may be multiple, recurrent, in atypical locations, and familial must be borne in mind.

Adolescent↗