Malignant T-cell Lymphoma Research Articles

T-cell Malignant Lymphoma With Conjunctival Involvement

Purpose: To report a rare case of T-cell malignant lymphoma involving the conjunctiva. Methods: A 63-year-old woman had rapid onset of bilateral perilimbal congestion and chemosis. Perilimbal thickening with corneal infiltration developed 20 days later. Computed tomography incidentally disclosed a right maxillary sinus mass. Biopsy specimens from the maxillary sinus mass and the left limbus were subjected to histopathologic examination and immunohistochemical study. Results: T-cell malignant lymphoma of diffuse large cell type, stage IV, was diagnosed. The patient was treated with combination chemotherapy plus 13- cis-retinoic acid and remained in remission 1 1 2 years after diagnosis. Conclusion: Conjunctival involvement with T-cell lymphoma may present as episcleritis and chemosis.

Genotype Configuration in a Case of Primary Gastric Lymphoma with T-cell Phenotype

T-cell malignant lymphoma of the gastrointestinal tract is rare. The genotype of gastric T-cell lymphoma remains unclear. The aim of this study was to elucidate the pathogenesis of a case of primary gastric T-cell lymphoma by using cytogenetics and molecular biology. Gastric biopsy specimens and lymphoma cells in the ascites were examined by immunocytology, cytogenetic analysis, and Southern blot analysis. The histological diagnosis of the gastric lymphoma was diffuse large cell type. T-cell markers were positive in immunocytochemistry of the gastric lymphoma cells and in FACS analysis of lymphoma cells in the ascites. All lymphoma cells in the ascites had complex abnormal karyotypes containing t(8;14)(q24;q32). Southern blot analysis revealed rearrangement of the IgH and C-MYC genes of the lymphoma cells in both the stomach and the ascites, but no comigration of the C-MYC with the JH locus could be detected. The TCR-β and -γ genes were in their germ-line configurations. In this patient, although the phenotype was T-cell lymphoma, the karyotype t(8;14)(q24;q32) and genotype had the characteristics of B-cell lymphoma. The unique B-cell genotype configuration and the C-MYC activation suggested that the cellular origin of this rare case of malignant lymphoma with a T-cell phenotype was quite immature lymphocytes.

Suppression of Proliferation and Phosphorylation of Jak3 and STAT5 in Malignant T-cell Lymphoma Cells By Derivatives of Octylamino-Undecyl-Dimethylxanthine

IL-2R signal transduction involves tyrosine phosphorylation of several proteins including Jak3 and STAT5. In the present study we examined the effect of two octylamino-undecyl-dimethylxanthine (OUDMX) derivatives, designated CT2576 and CT5589, on proliferation and protein tyrosine phosphorylation in human malignant T-cell lymphoma lines. These T-cell lines (PB-1, 2A, and 2B), obtained from a progressive T-cell lymphoma involving skin, are IL-2 independent but have constitutively activated IL-2R-associated signal transduction pathway common to IL-2 and several other cytokines: IL-4, IL-7, IL-9, and IL-15. CT2576, characterized previously on the functional level as an inhibitor of IL-2 signaling and, on the biochemical level, as an inhibitor of phosphatidic acid biosynthesis, suppressed completely growth of the malignant T cell lymphoma lines. CT5589 which is a novel analog of the CT2576, displayed a similar, although weaker, effect. Furthermore, both CT compounds inhibited constitutive tyrosine phosphorylation of two proteins: Jak3 and STAT5 which are key downstream elements in the signal transduction pathway activated by IL-2 and the other cytokines. The CT compounds inhibited also Jak3 phosphorylation induced by IL-2 in the IL-2 dependent SZ-4 cells. Inhibition of phosphorylation by CT2576 and CT5589 was only partially selective since phosphorylation of several other proteins was also affected. Phosphorylation of many others was, however, unaffected. These findings demonstrate that the OUDMX derivatives suppress proliferation of malignant T lymphocytes. Furthermore, they suggest that this suppression may be mediated by inhibition of the IL-2R-associated Jak/STAT signaling pathway. A potential role for OUDMX derivatives in therapy of human T-cell lymphoma should be further explored.

CD3−CD56+ Non-Hodgkin's Lymphomas With an Aggressive Behavior Related to Multidrug Resistance

AbstractCD56 expression has been reported previously in some non-Hodgkin's lymphoma (NHL) characterization. They principally involve the nasopharynx, are related to Epstein-Barr virus (EBV), and may be classified as either T- or non–T-natural killer (NK) cells according to CD3/T-cell receptor (TCR) status at the genomic or protein level. The present study reports three cases of non-nasal NK-NHL with the following characteristics: an agressive clinical behavior, heterogenous morphological data evoking pleomorphic T-cell malignant lymphoma, a non–T-NK phenotype using flow cytometry, and immunochemistry. The three cases were CD56+ without membrane expression of specific T markers (CD3, CD5, and TCR). Heterogenous results were observed concerning different antigens: CD2, CD4, CD8, CD16, CD94, CD122, TiA1, perforin, and granzyme B. There was no evidence of detectable clonal TCR gene rearrangement with polymerase chain reaction. No NK activity was detected in the two tested cases, and no relation was found with EBV. Multidrug resistance investigations suggest that agressive clinical findings could be related to MDR1 gene expression as confirmed by MDR1 mRNA detection, MDR1 gene product (Pgp) expression, and a functional multidrug resistance study using rhodamine efflux by flow-cytometry.

405 Malignant skin diseases: Malignant melanoma and cutaneous T-cell lymphoma

7: The incidence of MM has one of the fastest growth rates In the world. By the year 2000, one of every 90 Americans will develop MM. Wide local excision is the treatment of choice for stage I-II cutaneous MM. Five-year survival rates depend on (a> sex: female-63%, male-40%: (b> tumor thickness: t c 0.75mm 90%. t> 4mm-25%; (c) location: extremitydO%, trunk-41%; and cd> regional lymph node status: negative-77%. positive-31%. Despite adequate surgery, 45%&I% of MM patients will develop metastatic disease.

Primary malignant T-cell lymphoma of large intestine

Primary malignant T-cell lymphoma of large intestine

Cystic degeneration of mesenteric lymph nodes in enteropathy associated T-cell lymphoma

Mycosis fungoides (MF) is a malignant T-cell lymphoma which arises in skin and may subsequently involve lymph nodes and viscera as part of the natural

406 Malignant skin diseases: Malignant melanoma and cutaneous T-cell lymphoma

406 Malignant skin diseases: Malignant melanoma and cutaneous T-cell lymphoma

Multinodular keratoacanthoma and T cell lymphoma

This is a report of a case of multinodular keratoacanthoma (MNKA), a rare variety of solitary keratoacanthoma (KA) characterized by a collection of multiple KA nodules on the margins of a necrotic ulcerative lesion spreading centrifugally for 3 weeks in a patient with malignant non-Hodgkin's T-cell lymphoma. The very infiltrative nature of the main lesion made differential diagnosis difficult in the presence of extremely differentiated squamous cell carcinoma (SCC). Later, a KA lesion was to appear opposite a cutaneous lymphoma. The authors discuss the close links between the MNKA and the KA lesions and the immunosuppressed state of the patient.

A case of primary gastric T-cell malignant lymphoma

A case of primary gastric T-cell malignant lymphoma

Mycosis fungoides with central nervous system involvement—a case report: T-cell lymphoma of the brain

Mycosis fungoides is a rare malignant T-cell lymphoma, involving mainly the skin. It can, in 50%–75% of cases, involve visceral organs and, in 11%–14% of cases, metastasize to the central nervous system. The prognosis is poor. A case with cerebral involvement is presented and the relevant literature reviewed.

Hepatosinusoidal leukaemia/lymphoma consisting of Epstein-Barr virus-containing natural killer cell leukaemia/lymphoma and T-cell lymphoma; mimicking malignant histiocytosis.

Previously diagnosed cases of hepatosinusoidal T-cell lymphoma and malignant histiocytosis (MH) may include lymphoid neoplasms of natural killer (NK) cell lineage associated with Epstein-Barr virus (EBV). Such hepatosinusoidal neoplasms were found to demonstrate hepatomegaly but not lymphadenopathy, and all were diagnosed by a liver biopsy. Sixteen adult patients diagnosed with hepatosinusoidal leukaemia/lymphoma (six NK-cell leukaemia/lymphomas [NKLLs], five instances of MH, three T-cell malignant lymphomas [T-MLs], and two adult T-cell leukaemia/lymphomas [ATLLs] were examined for EBV by in situ hybridization, then were studied immunohistochemically and subjected to a DNA analysis. Among our five patients with MH, neoplastic cells showed T-cells, but no histiocytic markers, and they were considered to have either a T-cell or NK-cell lineage. All NKLLs, MHs and T-MLs, except for ATLLs accompanied by reactive hemophagocytic histiocytes, varied in number in each case. In situ hybridization revealed the presence of EBV in the nuclei of atypical cells in all of the six lymphoid neoplasms of NK-cell lineage. Each case of MH and each T-ML which represented EBV demonstrated no definite T-cell or histiocytic markers. Patients with ATLL did not reveal EBV. In all patients with hemophagocytosis, EBV was present in the nuclei of the neoplastic lymphocytes, but not in the hemophagocytic cells. Finally, the 16 cases were reclassified into eight cases with EBV-containing NKLLs, six T-MLs, and two ATLLs. In addition, no true histiocytic neoplasms were observed. The mechanism of hemophagocytosis may be therefore the production of lymphokines (macrophage-activating factors) by neoplastic lymphocytes. EBV-associated hepatosinusoidal leukaemia/lymphoma may thus contain a lymphoid neoplasm of NK-cell lineage, which made it difficult to be distinguished from the previously designated malignant histiocytosis.

A case of digestive fract T-cell malignant lymphoma with clinical course of twenty years.

A case of digestive fract T-cell malignant lymphoma with clinical course of twenty years.

Fatal Course of Malignant Non-Hodgkin's Lymphoma of T-Cell Type During Pregnancy with Metastasis to the Fetus

A 38-year-old Asian female with disseminated malignant T-cell lymphoma presented at 27 weeks estimated gestational age with possible pneumonia and preterm labor unresponsive to betamimetic tocolytic therapy. Her postpartum course was complicated by multisystem organ failure and maternal death. Autopsy demonstrated malignant T-cell lymphoma involving the liver, spleen, lung, and uterus. At 2 months of age the infant developed respiratory failure. Open lung biopsy revealed malignant T-cell lymphoma of identical phenotype. Following multiagent chemotherapy the infant entered remission and has remained in remission for the past 3 years.

Detection of clonal T cell population in peripheral blood of patients with cutaneous malignant T-cell lymphoma

Detection of clonal T cell population in peripheral blood of patients with cutaneous malignant T-cell lymphoma

The BCMA gene, preferentially expressed during B lymphoid maturation, is bidirectionally transcribed.

In a previous study of a t(4;16)(q26;p13) translocation, found in a human malignant T-cell lymphoma the BCMA gene, located on chromosome band 16p13.1, has been characterized. In this study we show that the BCMA gene is organized into three exons and its major initiation transcription site is located 69 nucleotides downstream of a TATA box. RNase protection assays demonstrated that the BCMA gene is preferentially expressed in mature B cells, suggesting a role for this gene in the B-cell developmental process. A cDNA complementary to the BCMA cDNA was cloned and sequenced and its presence was assessed by RNase protection assay and anchor-PCR amplification. This antisense-BCMA RNA is transcribed from the same locus as BCMA, and exhibits mRNA characteristic features, e.g. polyadenylation and splicing. It also contains an ORF encoding a putative 115 aa polypeptide, presenting no homology with already known sequences. RNase protection assays demonstrated the simultaneous expression of natural sense and antisense-BCMA transcripts in the majority of human B-cell lines tested.

T-cell malignant lymphoma with a complex unbalanced translocation (8;11;14)

We report a complex unbalanced translocation (8;11;14) in a female patient with T-cell lymphoma characterized by an aggressive clinical course and a poor response to therapy.

Epstein-Barr Virus-Related Oral T-Cell Lymphoma Associated With Human Immunodeficiency Virus Immunosuppression

AbstractEpstein-Barr virus (EBV) is generally held to infect B cells and epithelial cells, although there are now reports of EBV infection in normal T cells and neoplastic T-cell diseases. In patients with human immunodeficiency virus (HIV) infection, EBV is associated with the benign epithelial lesion, hairy leukoplakia, and has been reported in up to 80% of acquired immunodeficiency syndrome (AIDS)-related B-cell lymphoma. This study shows the presence of EBV in malignant oral T-cell lymphoma in three AIDS patients, two of whom had concurrent manifestation of hairy leukoplakia. The T-cell lineage of the tumor cells was determined by positive immunophenotyping for T-cell markers and lack of B-cell or nonhematopoietic (cytokeratin) determinants. All tumors contained monoclonal T-cell populations shown by polymerase chain reaction, which showed amplification of T-cell receptor γ chain DNA without evidence of lg heavy chain gene rearrangement. Furthermore, these lesions showed the presence of EBV DNA and expression of EBV latent gene products in the tumor cells. EBV involvement in AIDS-related T-cell lymphoma has not been widely reported and may represent a further manifestation of opportunistic EBV infection arising in the HIV-immunocompromised host.

Epstein-Barr virus-related oral T-cell lymphoma associated with human immunodeficiency virus immunosuppression

Epstein-Barr virus (EBV) is generally held to infect B cells and epithelial cells, although there are now reports of EBV infection in normal T cells and neoplastic T-cell diseases. In patients with human immunodeficiency virus (HIV) infection, EBV is associated with the benign epithelial lesion, hairy leukoplakia, and has been reported in up to 80% of acquired immunodeficiency syndrome (AIDS)-related B-cell lymphoma. This study shows the presence of EBV in malignant oral T-cell lymphoma in three AIDS patients, two of whom had concurrent manifestation of hairy leukoplakia. The T-cell lineage of the tumor cells was determined by positive immunophenotyping for T-cell markers and lack of B-cell or nonhematopoietic (cytokeratin) determinants. All tumors contained monoclonal T-cell populations shown by polymerase chain reaction, which showed amplification of T-cell receptor gamma chain DNA without evidence of Ig heavy chain gene rearrangement. Furthermore, these lesions showed the presence of EBV DNA and expression of EBV latent gene products in the tumor cells. EBV involvement in AIDS-related T-cell lymphoma has not been widely reported and may represent a further manifestation of opportunistic EBV infection arising in the HIV-immunocompromised host.

The relationship of Epstein-Barr virus to infection-related (sporadic) and familial hemophagocytic syndrome and secondary (lymphoma-related) hemophagocytosis: An in situ hybridization study

Many cases of hemophagocytic syndrome have been associated with viral infections, particularly Epstein-Barr virus (EBV), but the pathogenesis of the syndrome remains unclear. We have examined lymph node, spleen, liver, and bone marrow sections from 12 cases, including four cases of proven or probable infection-related hemophagocytic syndrome (IHPS), three cases of familial hemophagocytic syndrome (FHPS), and five cases of secondary hemophagocytosis associated with T-cell malignant lymphoma (SHPC), for EBV RNA using a sensitive and specific in situ hybridization technique. Epstein-Barr virus RNA was detected in seven of 12 cases (58%), including three cases of IHPS, one case of FHPS, and three cases of SHPC. Numerous EBV-positive cells were detected in two cases of IHPS (in multiple anatomic sites) and in one case of FHPS (in the spleen). Diffuse EBV positivity also was noted within the neoplastic cells of one case of SHPC. Rare to occasional EBV-positive cells were found in multiple sites in another case of IHPS and within admixed, reactive lymphoid cells in two cases of SHPC. The results indicate that numerous EBV-positive cells can be identified in some cases of IHPS, FHPS, and SHPC, suggesting a pathogenetic role for the virus. However, the absence of EBV from a proportion of cases of IHPS and FHPS in this study suggests that other infectious agents also play a role in the pathogenesis of this syndrome.