Biomedical subjects

M Koono

Publications and source records attributed to M Koono.

At least 55 records · Page 3Linked to original sources

PubMed1999

Solitary fibrous tumor of the spinal nerve rootlet: case report and literature survey.

Solitary fibrous tumor (SFT) is a rare tumor that arises most commonly in the pleura. Recent evidence indicated that it is a tumor that originates from mesenchymal, probably fibroblastic, cells and is not restricted to the pleura. This report presents a case of primary SFT occurring as a dumbbell-shaped tumor of the cervical spine (C4/5) in a 46-year-old Japanese female, probably originating from the spinal rootlet. The tumor was predominantly extradural, loosely attached to the dura mater, with a small intradural extramedullary part attached to the C5 anterior and posterior rootlets. Histologically, the tumor was predominantly composed of a haphazard proliferation of spindle cells separated by abundant collagen. Immunohistochemically, the cells were strongly positive for CD34, bcl-2 and vimentin, but were negative for S-100 protein, neuron specific enolase, cytokeratin and epithelial membrane antigen. The present case and review of the literature strongly suggest that SFT is an entity that should be considered in the differential diagnosis of tumors of the cerebrospinal region.

Antigens, Nuclear↗

PubMed1999

Carcinoembryonic antigen and carbohydrate antigen 19-9-producing adenocarcinoma of the prostate: report of an autopsy case.

Prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) are well known as specific tumor markers of prostate cancer, but carcinoembryonic antigen (CEA)- and carbohydrate antigen 19-9 (CA19-9)-producing adenocarcinoma originating in the prostate is rare. We report here a case of prostatic adenocarcinoma positive for these 4 tumor markers in a 50-year-old man who had initially complained about chest pain due to metastatic bone tumor. In spite of the extensive treatment involving hormone and radiation therapy, the patient died of rapid tumor extension only 4 months after initial diagnosis. Autopsy revealed multiple metastases to the bone, liver, lungs and lymph nodes. Histologically, two types of adenocarcinoma were involved in both primary prostate and metastatic sites: one was a poorly differentiated adenocarcinoma positive for PSA and PAP but not CEA or CA19-9, and the other one was a less differentiated adenocarcinoma partially positive for CEA and CA19-9 but not for PSA or PAP. Based on this case and previous cases by review of the literature, CEA- and CA19-9-producing adenocarcinoma of the prostate was suggested to rapidly progress with multiple metastases and to show poor prognosis with strong resistance to any treatment.

Acid Phosphatase↗

PubMed1999

Distribution of hepatocyte growth factor activator inhibitor type 1 (HAI-1) in human tissues. Cellular surface localization of HAI-1 in simple columnar epithelium and its modulated expression in injured and regenerative tissues.

We used a specific monoclonal antibody to human hepatocyte growth factor activator inhibitor type 1 (HAI-1) in immunohistochemical procedures to determine the distribution and localization of HAI-1 in human tissues. In normal adult tissues, HAI-1 was predominantly expressed in the simple columnar epithelium of the ducts, tubules, and mucosal surface of various organs. In all cases, HAI-1 was localized predominantly on the cellular lateral (or basolateral) surface. By contrast, hepatocytes, acinar cells, endocrine cells, stromal mesenchymal cells, and inflammatory cells were hardly stainable with the antibody, and stratified squamous epithelium showed only faint immunoreactivity on the surface of cells of the basal layer. In the gastrointestinal tract, the surface epithelium was strongly stained. RNA blot analysis confirmed the presence of specific mRNA transcript in the gastrointestinal mucosa, and in situ hybridization revealed that HAI-1 mRNA showed a similar cellular distribution pattern. Although HAI-1 was not expressed in normal hepatocytes, strong immunoreactivity was observed on the epithelium of pseudo-bile ducts and on the surface of scattered hepatocytes in fulminant hepatitis. The enhanced expression was also noted in regenerating tubule epithelial cells of the kidney after infarction. We conclude that HAI-1 is preferentially expressed in the simple columnar epithelium of the mucosal surface and duct, that the predominant localization of HAI-1 is the cell surface, and that the expression of HAI-1 can be modulated by tissue injury and regeneration.

Antibodies, Monoclonal↗

PubMed1999

Cohort migration of carcinoma cells: differentiated colorectal carcinoma cells move as coherent cell clusters or sheets.

Active migration of tumor cells is usually assessed as single cell locomotion in vitro using Boyden chamber-type assays. In vivo, however, carcinoma cells, malignant cells of epithelial origin, frequently invade the surrounding tissue as coherent clusters or nests of cells. We have called this type of movement "cohort migration". In our work, the invasion front of colon carcinomas consisted of compact tumor glands, partially resolved glands or markedly resolved glands with scattered tumor cell clusters or single cells lying ahead. In the former two types, which constituted about a half of all cases, cohort migration seems to be the predominant mechanism, whereas both cohort migration and single cell locomotion may be involved in the last one. In this light, it is very advantageous to investigate the mechanisms involved in the cohort migration. In this review, we present a two-dimensional motility assay as a cohort migration model, in which human colorectal carcinoma cells move outwards from the cell islands mainly as localized coherent sheets of cells when stimulated with 12-O-tetradecanoylphorbol-13-acetate (TPA) or hepatocyte growth factor/scatter factor (HGF/SF). Within the migrating cell sheets, wide intercellular gaps occur at the lower portion of the cells to allow the cells to extend leading lamellae forward while close cell-cell contacts remain at the upper portion of the cells. This localized modulation of cell-cell adhesion at the lower portion of the cells is associated with increased tyrosine phosphorylation of the E-cadherin-catenin complex in TPA-induced cohort migration and with reduced alpha-catenin complexed with E-cadherin in HGF/SF-induced cohort migration. Furthermore, fibronectin deposited by migrating cells is essential for their movement, and on the gelatin-coated substrate even degradation and remodeling of the substrate by matrix metalloproteinases are also needed. Thus, in cohort migration it is likely that cells are released from cell-cell adhesion only at the lower portion of the cells via modulation of E-cadherin-catenin-based mechanism, and this change allows the cells to extend leading lamellae onto the extracellular matrix substrate remodeled by deposition of fibronectin and organized digestion.

Animals↗

PubMed1999

Secretion of protease nexin-II/amyloid beta protein precursor by human colorectal carcinoma cells and its modulation by cytokines/growth factors and proteinase inhibitors.

Trypsin inhibitors secreted by human colorectal adenocarcinoma cell lines were analyzed by reverse zymography. Among eleven cell lines analyzed, the major inhibitor secreted was protease nexin-II (PN-II), a secreted form of amyloid beta protein precursor (APP) containing a Kunitz-type serine proteinase inhibitor domain. Expression of the APP gene was also confirmed in the cell lines and the main APP mRNA species were PN-II types. The APP gene expression was constant during cell growth in vitro. On the other hand, the rate of extracellular PN-II accumulation markedly increased after long-term serum-free maintenance of the confluent culture. The extracellular accumulation of PN-II was also strongly stimulated either by interleukin-1beta (IL-1beta) treatment or to a lesser extent by basic fibroblast growth factor, tumor necrosis factor-alpha, hepatocyte growth factor or epidermal growth factor. Neither serum depletion- nor IL-1beta-induced stimulation of extracellular PN-II accumulation were accompanied by obvious alteration of the levels of APP mRNA and cellular APP holoprotein, suggesting that the enhanced extracellular accumulation of PN-II might result from up-regulation of the secretory pathway of APP. The IL-1beta-induced PN-II secretion was significantly inhibited by relatively high concentrations (50-200 microg/ml) of aprotinin, a serine proteinase inhibitor, in a dose-dependent manner without obvious cell-toxic effects.

Adenocarcinoma↗

PubMed1999

Cholesterol embolism in a patient with inflammatory abdominal aortic aneurysm.

A 66-year-old man whose renal function had progressively deteriorated had an elevated blood pressure and also was found to have an inflammatory abdominal aortic aneurysm (AAA). Blood examination revealed that he had eosinophilia. Livedo reticularis of the toes developed, and a skin biopsy specimen showed embolization of atheromatous plaques in the arterioles of the subcutaneous tissue. Progressive enlargement of inflammatory AAA may have dislodged the atheromatous plaques, resulting in cholesterol embolism.

Aged↗

PubMed1999

Expression of hepatocyte growth factor/scatter factor and its receptor c-Met in brain tumors: evidence for a role in progression of astrocytic tumors (Review).

Hepatocyte growth factor (HGF) is a multifunctional cytokine which is believed to have important roles in tissue development and regeneration, and tumor progression. It is indistinguishable from scatter factor (SF), a motility factor. HGF/SF is believed to be a mesenchymal cell-derived cytokine acting for epithelial cells bearing its receptor tyrosine kinase, c-Met. Recently, we found that glioblastoma multiforme (GBM), a highly malignant brain tumor of astrocytic origin, concomitantly express HGF/SF and c-Met. This finding indicates a presence of autocrine loop of HGF/SF signaling pathway in GBM. Moreover, GBM cells also co-express HGF activator, a recently identified serine proteinase having efficient HGF/SF activating activity. The expression of HGF/SF and c-Met was low or hardly detectable in low-grade astrocytoma, and c-Met immunoreactivity was correlated with the histological grade of the tumor suggesting that the creation of HGF/SF autocrine loop occurs along with the progression of astrocytic brain tumors. Experimental evidence indicated that HGF/SF exhibits potent migration/invasion-inducing activity for GBM cells bearing c-Met receptor. It is also a significant angiogenesis factor in GBM, and may serve as a cellular growth factor for certain GBM cells. These lines of evidence suggest that HGF/SF signaling pathway may serve as a promising new target of therapeutic intervention of GBM.

Brain Neoplasms↗

PubMed1999

Roles of intestinal trefoil factor (ITF) in human colorectal cancer: ITF suppresses the growth of colorectal carcinoma cells.

Intestinal trefoil factor (ITF) is a member of trefoil peptide family and is expressed almost exclusively in the goblet cells of small intestine and colon. Its expression is up-regulated by inflammatory and ulcerative conditions in the intestinal mucosa, and ITF has a role to maintain the mucosal integrity and repair the damaged mucosa. On the other hand, human colorectal carcinoma cells also express ITF peptide. In this review, we discussed the current views on the biological functions of ITF in the intestinal mucosa, and its suppressive effect on the growth of colorectal carcinoma cells.

Cell Differentiation↗

PubMed1998

Hepatocyte growth factor/scatter factor induces not only scattering but also cohort migration of human colorectal-adenocarcinoma cells.

We presented earlier a 2-dimensional cell-motility assay using a highly metastatic variant (L-10) of human rectal-adenocarcinoma cell line RCM-1 as a motility model of tumor cells of epithelial origin. In this model, L-10 cells moved as coherent cell sheets when stimulated with 12-O-tetradecanoylphorbol-13-acetate (TPA), and we called this type of movement "cohort migration". Electron- and immunoelectron-microscope study of the migrating cell sheets demonstrated localized release from cell-cell adhesion only at the lower portion of the cells with loss of E-cadherin immunoreactivity, and this change was associated with increased tyrosine phosphorylation of the E-cadherin-catenin complex, including beta-catenin. In the present study, to obtain evidence to support the relevance of our model to carcinoma-cell movement in vivo, we sought a naturally occurring motogenic factor(s) able to induce this cohort migration. Among the factors examined, hepatocyte growth factor/scatter factor (HGF/SF) clearly induced cohort migration of L-10 cells. Additionally, not only L-10 but several other human colorectal-carcinoma cell lines showed this type of migration in response to HGF/SF, while yet others showed scattering-type motility. In this HGF/SF-induced migration, localized release from cell-cell adhesion was induced only at the lower portion of the cells, allowing them to extend leading lamellae, whereas close cell-cell contacts remained at the upper portion of the cells, as seen in TPA-induced cohort migration. Scattering-type cell lines tended to express more c-Met (receptor for HGF/SF) mRNA than the cell lines that showed cohort-type migration. LoVo, one of the scattering-type cell lines, expressed more c-Met protein and less E-cadherin than L-10, which showed cohort-type migration. HGF/SF treatment of LoVo reduced the amount of alpha-catenin complexed with E-cadherin more markedly than in L-10, but in both cell lines this reduction was not accompanied by increased tyrosine phosphorylation of beta-catenin, suggesting the presence of a mechanism other than phosphorylation for release from cell-cell adhesion during cell motility.

Adenocarcinoma↗

PubMed1998

Up-regulation of vascular endothelial growth factor induced by hepatocyte growth factor/scatter factor stimulation in human glioma cells.

Recent findings suggest that hepatocyte growth factor/scatter factor (HGF/SF) contributes to the malignant progression of human gliomas. We investigated the effect of HGF/SF on vascular endothelial growth factor (VEGF) expression of c-Met/HGF receptor-positive human glioma cell lines. Treatment of the glioma cells with various concentrations of HGF/SF resulted in an enhanced secretion of VEGF proteins accompanying increased transcription of VEGF mRNA in a dose-dependent fashion. Since malignant gliomas frequently co-express HGF/SF and its receptor, these results suggest that HGF/SF could act as an indirect angiogenic factor through autocrine induction of VEGF expression and secretion in malignant gliomas.

Endothelial Growth Factors↗

PubMed1998

Cell density-dependent regulation of fibronectin splicing at the EDA region in fibroblasts: cell density also modulates the responses of fibroblasts to TGF-beta and cancer cell-conditioned medium.

Recently we reported that cancer cell-fibroblast interactions can modulate the expression of fibronectin (FN) isoforms in vitro, i.e. conditioned medium of human rectal adenocarcinoma cell line RCM-1 (RCM-1 CM) stimulated the expression of EDA-containing FN (EDA(+)FN) mRNA by fibroblasts and this stimulation was partly mediated by transforming growth factor-beta (TGF-beta) included in RCM-1 CM. In the present study, cell density was shown to regulate FN splicing at the EDA region in fibroblasts. Fibroblasts plated at a low cell density expressed a significantly higher percentage of EDA(+)FN mRNA than those plated at a high cell density. Moreover, fibroblast cell density modulated the effects of TGF-beta and RCM-1 CM on FN splicing at the EDA region differently. The time courses of their effects were similar to each other at a high cell density. At a low cell density, however, they were different. TGF-beta showed a relatively short-lived stimulation of EDA(+)FN mRNA, with the peak response 24 h after treatment, followed by a decline to the base line by 72 h. On the other hand, RCM-1 CM caused a prolonged stimulation, maintaining almost the maximum responses from 24 to 72 h. Thus, these results at a low cell density indicated the presence of a factor(s) other than TGF-beta in RCM-1 CM that stimulates the expression of EDA(+)FN mRNA directly or modulates the effect of TGF-beta. The use of several different cell densities might help in the search for new factors affecting FN splicing.

Adenocarcinoma↗

PubMed1998

Evaluation of hepatocyte growth factor activator inhibitor expression in normal and malignant colonic mucosa.

Gene expression of hepatocyte growth factor activator inhibitor (HAI), a recently identified Kunitz-type serine proteinase inhibitor, was analyzed in a series of human colorectal carcinoma cell lines and in human colorectal tissues. All of the 14 cell lines derived from adenocarcinoma of the colorectum expressed HAI in vitro, whereas a colon carcinoma cell line of neuroendocrine origin did not. In vivo, HAI was consistently expressed in the normal colorectal mucosa. Although the expression of HAI mRNA was conserved in adenocarcinoma tissues of the colorectum, the levels of expression were decreased in the adenocarcinoma tissues compared to the normal counterparts. There was a tendency towards an inverse correlation, albeit not well defined, between the amounts of HAI mRNA and the tumor progression. Immunohistochemical study indicated that HAI protein is present predominantly on the surface of epithelial cells of the colon and the immunoreactivity was decreased in the adenocarcinoma cells.

Adult↗

PubMed1998

Comparative analysis of expression of hepatocyte growth factor and its receptor, c-met, in gliomas, meningiomas and schwannomas in humans.

Expression of hepatocyte growth factor (HGF) and c-met, a proto-oncogene that encodes a receptor for HGF, was examined in 45 cases of human primary intracranial tumors by means of RT-PCR. In gliomas, HGF and c-met mRNAs were preferentially expressed in high-grade tumors. Co-expression of both genes was observed in glioblastomas (6/15) and in one anaplastic astrocytoma (1/5) but not in low-grade astrocytomas (0/3). By contrast, the c-met gene was consistently expressed in meningiomas (12/14) and schwannomas (8/8). The presence of c-Met protein was confirmed in the tumor cells of glioblastoma, meningioma and schwannoma by immunohistochemical staining. Moreover, all of the schwannoma cases co-expressed the HGF gene. These observations suggest that HGF/c-met expression is somehow related to the disease progression in gliomas, whereas c-Met protein might have an important fundamental biological role in meningioma and schwannoma. Moreover, since all of the schwannoma cases concomitantly expressed the ligand (HGF) and the receptor (c-met) genes, HGF may act in an autocrine fashion in schwannoma.

Astrocytoma↗

PubMed1998

TPA-induced cohort migration of well-differentiated human rectal adenocarcinoma cells: cells move in a RGD-dependent manner on fibronectin produced by cells, and phosphorylation of E-cadherin/catenin complex is induced independently of cell-extracellular matrix interactions.

We have already presented a two-dimensional cell motility assay using a highly metastatic variant (L-10) of human rectal adenocarcinoma cell line RCM-1 as a motility model of tumour cells of epithelial origin. In this model, L-10 cells showed locomotion as a coherent sheet when stimulated with 12-O-tetradecanoylphorbol-13-acetate (TPA), and we called this type of movement "cohort migration". Electron and immunoelectron microscopic study of the migrating cell sheets demonstrated localized release from cell-cell adhesion only at the lower portion of the cells with loss of E-cadherin immunoreactivity, and this change was associated with increased tyrosine phosphorylation of the E-cadherin-catenin complex, including beta-catenin. Cell-extracellular matrix (ECM) interactions involved in this TPA-induced cohort migration and their effect on tyrosine phosphorylation of the E-cadherin-catenin complex have now been investigated. L-10 cell cohort migration was almost completely inhibited by addition of Arg-Gly-Asp (RGD) peptide into the medium, and thus RGD dependent. Cohort migration was stimulated on type I and IV collagens, fibronectin (FN)- and laminin-coated substratum, but was inhibited by RGD only on FN-coated surface. By using immunofluorescent techniques, FN was demonstrated preferentially around migrating cells, and a protein synthesis inhibitor, cycloheximide, inhibited the migration by about 75%. FN produced by L-10 cells were found to be mostly EDA+ FN when analysed by RT-PCR. Moreover, anti-FN antibody, but not anti-vitronectin antibody, inhibited the TPA-induced cohort migration almost completely. Thus, it was likely that L-10 cells produced FN themselves and moved on the FN substrate in an RGD-dependent manner. However, stimulation of migration by type I collagen coating and inhibition by RGD treatment did not affect the tyrosine phosphorylation of the E-cadherin-catenin complex induced by TPA, indicating that cell-cell interactions were adjusted to suit cell migration, irrespective of the condition of cell-ECM adhesion, during TPA-induced cohort migration.

Adenocarcinoma↗

PubMed1997

Analysis of tissue factor and tissue factor pathway inhibitor expression in human colorectal carcinoma cell lines and metastatic sublines to the liver.

To investigate the expression of tissue factor (TF) and tissue factor pathway inhibitor (TFPI) in human colorectal carcinomas, Northern blot analysis was performed in a series of human colorectal carcinoma cell lines and in normal or tumoral colorectal tissues. Of 16 human colorectal carcinoma cell lines examined, most expressed TF mRNA, though the levels of expression varied significantly. Considerably higher expression was observed in the cell line CaR-1, while lines established from metastatic lesions tended to express abundant TF mRNA. By contrast, TFPI mRNA levels were low in these high TF-expressing cell lines. TFPI was expressed abundantly in WiDr and in a few other cell lines which expressed a very low level of TF mRNA. Immunocytochemically, both proteins were stained predominantly on the cell surface; however, diffuse cytoplasmic staining for TF also was observed in CaR-1 cells. In addition, the cell surface TF activity was significantly higher in CaR-1 cells than in WiDr cells, confirming the results of mRNA analysis. The level of TF mRNA in colorectal carcinoma tissue in vivo and its ratio to the normal counterpart also varied significantly among the cases. To search for a possible role of TF/TFPI in metastasis of colorectal carcinoma cells, the expression of these genes was compared between a rectal adenocarcinoma cell line, RCM-1, and its highly metastatic subline, RCM-1 L-10. Compared with the parent line, RCM-1 L-10 expressed 7.5-fold higher levels of TF mRNA, whereas TFPI expression was not altered significantly or even decreased slightly. The higher cellular TF activity was confirmed in the metastatic subline in comparison with the parent line.

Adenocarcinoma↗

PubMed1997

Hepatocellular carcinoma with sarcomatous change arising in primary biliary cirrhosis.

We report an autopsy case of hepatocellular carcinoma (HCC) with sarcomatous change arising in the context of primary biliary cirrhosis (PBC) in a 79-year-old man. Primary biliary cirrhosis was diagnosed (stage I according to Scheuer's classification) by findings on blood biochemical analysis, laparoscopy, and liver biopsy at age 69 years. Five years later, (at age 74 years), a mass lesion was detected in the S6 region of the liver by abdominal ultrasonography, and target biopsy revealed well differentiated HCC. Blood biochemistry, ultrasonography, and computed tomography findings showed that the PBC had progressed to stage IV (cirrhotic stage). Percutaneous ethanol injection therapy (PEIT) was administered to the HCC several times over a 5-year period; however, the patient died of liver failure in February, 1994 (at age 79 years). Viral markers for hepatitis B and C were negative during the course, and hepatitis C virus RNA was not detected by polymerase chain reaction. Autopsy findings showed liver cirrhosis and diffuse involvement of spindle-shaped sarcomatoid cells in the liver, particularly in the S6 region, associated with several nodules of trabecular HCC cells. A zone of transition between the sarcomatoid cells and the trabecular hepatocellular carcinoma cells was observed. The sarcomatoid cells were diffusely disseminated in the peritoneal cavity and had metastasized to multiple organs. Immunohistochemically, the cells were positive for fibrinogen, as were the coexisting trabecular hepatocellular carcinoma cells. The HCC had been treated several times with PEIT. Of interest, PEIT may be an important factor in this type of tumor progression.

Aged↗

PubMed1997

Expression of c-Met correlates with grade of malignancy in human astrocytic tumours: an immunohistochemical study.

AIMS: Recent studies suggest the involvement of hepatocyte growth factor/scatter factor (HGF/SF) in glioma cell invasion and tumour progression. We investigated the distribution and rate of tumour cells that express c-Met protein, which is the cell-surface receptor for HGF/SF, in astrocytic tumours. The type of cells that express c-Met in tumour tissues was also identified. METHODS AND RESULTS: c-Met expression was screened immunohistochemically in a total of 43 astrocytic tumours, including 14 low-grade astrocytomas (A), 13 anaplastic astrocytomas (AA) and 16 glioblastoma multiforme (GBM), c-Met reactivity was demonstrated predominantly in the cytoplasm of tumour cells. Bizarre large tumour cells tended to stain intensely. Higher c-Met expression levels (> or = 2+, more than 25% cells were positive) were noted in 21.4% of (A) vs. 53.8% in (AA) and 87.5% in (GBM) (P < 0.001), indicating a clear relationship between c-Met protein staining and higher grade astrocytic tumours. Moreover, c-Met immunoreactivity was also shown in tumour microvasculature, reactive astrocytes, and neurones in the cortex infiltrated by glioma cells. In 85.7% of cases containing infiltrated cortex, neurones were positive vs. no neurones in non-neoplastic regions (P < 0.002). CONCLUSIONS: This evidence suggests that c-Met expression in the brain could be associated with astrocytoma progression and also reactive process. Immunohistochemical determination of c-Met-expressing cell types helps to understand possible roles of c-Met in tumour tissues.

Adolescent↗

PubMed1997

Lymphoblastic lymphoma expressing natural killer cell phenotype with involvement of the mediastinum and nasal cavity.

Most CD56+ lymphomas display polymorphic and angiocentric/angiodestructive histologic features and are closely related to Epstein-Barr virus (EBV) infection. We report a 47-year-old Japanese man with CD56+ lymphoma that showed histologic features of lymphoblastic lymphoma with mediastinal and nasal involvement and an aggressive course. A sample specimen showed the histology of lymphoblastic lymphoma with a positive reaction for terminal deoxynucleotidyl transferase (TdT) but no angiocentric/angiodestructive features. Transmission electron microscopy revealed a few membrane-bound electron-dense granules in their cytoplasm. Immunohistochemically, lymphoma cells exhibited CD56+ cytoplasmic CD3 (cCD3)+ TdT+. A Southern blot analysis showed no integration of EBV and human T-lymphotrophic virus 1 (HTLV-1) and no rearrangement of the T-cell receptors or immunoglobulin heavy chain genes. This unusual lymphoblastic lymphoma exhibiting cCD3 + CD56 + TdT + TCR- is assumed as an immature or progenitor natural killer cell lineage.

Anatomy, Cross-Sectional↗