Adult T-cell leukemia lymphoma with metastatic calcification

A 52-year-old man, who came from Kagoshima prefecture, was hospitalized because of lumbago and lymphadenopathy. On admission, mild anemia and leukocytosis with atypical lymphoid cells were seen in the peripheral blood. Flow cytometry of the abnormal lymphocytes showed that they expressed CD4, and CD25, but not CD8. Anti HTLV I antibody was expressed in the serum. Atypical lymphoid cells had proviral DNA with restriction enzyme EcoRI. Lymphnode biopsy was performed and the specimens of lymphnode showed diffuse infiltration of abnormal lymphocytes. So we diagnosed Adult T-cell leukemia lymphoma. The patient's serum calcium level was increased, so he lost consciousness and became oliguric and developed acute renal failure. Hemodialysis was required to control azotemia. During the time of hemodialysis, cardiac arrest was occurred and he died. Autopsy confirmed the presence of a metastatic calcification in various organs, such as myocardium, alveolar septa of the lungs, and gastric mucosa. A metastatic calcinosis was found in the myocardium, which was thought to be the cause of his heart failure. But at the ATLL cells didn't infiltrate in the myocardium. Calcinosis was a significant complication of neoplastic disease in these patients and contributed to morbidity and mortality.     

Peripheral T-cell lymphoma with a nodular growth pattern

Peripheral T-cell lymphomas (PTCL) with nodular growth patterns are very rare, with only 17 cases reported previously. Here, we report a case of PTCL with a nodular growth pattern. The patient was an 81-year-old Japanese woman who complained of malaise, fever and generalized lymph node swelling. Cervical lymph node biopsy was performed, and histological examination revealed proliferation of medium- to large-sized atypical lymphoid cells with indented to irregular nuclei, distinct nucleoli and clear cytoplasm. The nodular growth pattern of the lymphoma cells was obvious. On immunohistochemistry, the atypical lymphoid cells proved to be of T-helper cell origin (CD2+CD3CD4+CD5+CD7+ CD8-CD10-CD25-CD30-CD57-). Polymerase chain reaction analysis of the T-cell receptor gamma-chain revealed a monoclonal rearrangement band. This unusual growth pattern should be distinguished among PTCL, as such cases could be confused with reactive nodular hyperplasia, nodular lymphoma, mantle cell lymphoma and marginal zone lymphoma with nodular colonization.     

Normal sister chromatid exchange frequencies during growth of a transplantable murine myeloid leukemia

Frequencies of sister chromatid exchange (SCE) were analyzed in normal and coexisting leukemic cells harvested from the bone marrow of mice 10, 15, 18, and 21 days after transplantation of myeloid leukemic cells. These posttransplantation stages correspond to no abnormal physical or clinical symptoms (day 10) through the terminal stage of leukemia (day 21). The data indicate that the SCE frequencies in normal cells of leukemic mice did not differ from those in normal cells of normal mice. Furthermore, the frequencies in the coexisting normal and leukemic cells remained statistically constant throughout the posttransplantation period. It is concluded from this study that spontaneous cellular SCE frequencies may not be altered by the presence or growth of leukemic cells.     

Changing metastatic patterns of a transplantable rat osteosarcoma

Metastatic behavior patterns in 303 untreated Sprague-Dawley rats bearing a transplantable cerium-144-induced osteosarcoma is described. The influence of survival time, sex, age of donor and recipient animals at time of transplantation, on the development of metastasis in lungs, kidneys, lymph nodes and liver was investigated.Nearly all (98·7 per cent) rats bearing osteosarcomas in the knee region developed primary hematogeneous lung metastases and 10·6 per cent of these developed secondary metastasis in the kidneys. A further primary, lymphogenous metastatic spread occurred in 15·5 per cent of the animals. Ninety-two per cent of the rats died because of lung metastases, but animals with long survival times developed significantly more extrapulmonary metastases than animals with a shorter survival time. This is in agreement with the observed change in metastatic patterns in osteosarcoma patients with prolonged survival after adjuvant chemotherapy. Moreover, the age of the donor-tumors and the recipient animals influenced survival time and consequently metastatic patterns. It was therefore possible to keep available several groups of osteosarcoma-bearing animals with different expectations of survival time. The results of transplantation of the same tumor by the intraperitoneal and the intravenous route are also presented.     

Adoptive transfer of murine host protection to salmonellosis with T-cell growth factor-dependent, Salmonella-specific T-cell lines.

A spent medium antigen was prepared from the avirulent RIA strain of Salmonella typhimurium. Lymph node cells isolated from female BALB/c mice injected subcutaneously with the spent medium antigen exhibited antigen-specific proliferation. By using these cells and T-cell growth factor, continuous spent medium antigen-specific, Thy 1.2-sensitive lines were generated. These cells exhibited antigen-specific proliferation in vitro and were effective in inducing significant (P less than 0.01) host protection when adoptively transferred to naive syngeneic mice.     

Distinguishing angioimmunoblastic T-cell lymphoma from peripheral T-cell lymphoma, unspecified, using morphology, immunophenotype and molecular genetics

AIMS: To identify distinguishing histological, immunophenotypic and molecular genetic features between angioimmunoblastic T-cell lymphoma (AITL) and peripheral T-cell lymphoma (PTL). METHODS: Nodal T-cell lymphomas examined (n =137), included AITL (n = 89), PTL (n = 22), anaplastic large cell lymphoma (n = 16) and 'AITL/PTL indeterminate' (n = 10) with overlapping features between AITL and PTL, showing morphology typical of AITL but lacking follicular dendritic cell expansion. Immunohistochemistry for CD3, CD20, CD21 and CD10, in situ hybridization for Epstein-Barr virus encoded RNA (EBER) and polymerase chain reaction for T-cell and B-cell clonality analysis were performed. RESULTS: Of the AITLs, 74/89 showed typical morphology, whereas 15/89 showed hyperplastic follicles. AITL and 'AITL/PTL indeterminate' showed a polymorphous infiltrate and prominent vascularity in all cases. In both groups, CD10 was present in the majority and clear cells and EBER positivity were specific (but not universal) features lacking in PTL. Detection of T-cell clonality was significantly higher in AITL (90%) compared with PTLu (59%). CONCLUSION: Clear cells and EBV infection (when present) are useful distinguishing features and CD10 a sensitive and specific marker of AITL. Hyperplastic follicles are present in a significant minority of AITL. AITL/PTL indeterminate probably falls within the spectrum of AITL rather than PTL.     

Organ-specific growth of a murine lymphoma of spontaneous origin in nude mice

The MOC-25 tumour arose spontaneously in a female nude mouse and was established as a continuous line intraperitoneally in nude mice, where it reproduces the topological features of its origin, growing preferentially in the uterus, ovaries and liver. Karyotype analysis showed that MOC-25 cells are hyperdiploid. Tumorigenicity and malignant behaviour were studied by transplanting tumour cells into different sites in nude mice. The comparison of tumour take after i.p. and s.c. injections of scaled concentrations of MOC-25 cell suspension showed preferential growth in the peritoneum. Regardless of the route of implantation (s.c., i.v., i.p.), this tumour rapidly and preferentially disseminated to the liver, uterus, ovaries, spleen and bone marrow. No significant differences in tumour growth and metastatic behaviour were observed when MOC-25 was injected in ovariectomized nude mice or in male nude mice. Morphology studies using light and electron microscopy, immunophenotyping and molecular analysis indicated a B-lymphoid origin of the MOC-25 tumour.     

Epstein-Barr virus-associated B-cell lymphoproliferative disorders in angloimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma, unspecified

Various patterns of Epstein-Barr virus (EBV)-associated B-cell lymphoproliferation occur in patients with immunodeficiency. We studied 17 cases of T-cell lymphoma displaying extensive EBV-driven B-cell lymphoproliferation or simultaneous/subsequent EBV-associated B-cell lymphoma. In 10 cases of angioimmunoblastic T-cell lymphoma, an uncommonly prominent population of EBV+ atypical, activated, focally confluent large transformed B cells was found in the background of T-cell lymphoma. In 4 cases, an EBV-associated B-cell neoplasm (3 diffuse large B-cell lymphomas, 1 plasmacytoma) occurred in patients with T-cell lymphoma. Three cases were composite lymphomas of a peripheral T-cell lymphoma, unspecified, combined with EBV-associated diffuse large B-cell lymphoma. The transformed B-cell population displayed EBV latency types 2 and 3. Monoclonal and oligoclonal B-cell populations were detected in 5 and 6 cases, respectively. Similar to other states of immunodeficiency, disease-related and therapy-induced immunosuppression in T-cell lymphoma may lead to a prominent EBV-associated B-cell lymphoproliferation and to EBV+ B-cell neoplasms.     

Effects of size and growth time of a murine sarcoma on its metastatic spread

The effects of the size of an implanted tumor and of its time of growth on metastasis were examined in the same tumor grown under two different conditions. Tumors were implanted either in the untreated legs of mice or in legs that had been irradiated one day earlier. The radiation slowed the growth of tumors. When the tumors grew to predetermined diameters, the legs were excised and 20 days later the mice were examined for the presence of lung metastases. Equal changes in the time to excision of the tumors grown under the two conditions led to nearly equal changes in the proportions of animals with metastases. Tumor volume effects were not apparent in this consideration of changes in metastasis rates with time. This work reanalyses the data of that study using the variability in growth rates within a tumor growth condition to investigate the effect of tumor size on metastatic intensity. This intensity increased at least linearly with tumor volume for both irradiated and control animals. The finding of equal effect at equal growth times of the implanted tumors under the two growth conditions was confirmed but is due to: (1) metastatic intensity changing five times as rapidly with tumor size in the irradiated group as compared to the control group and (2) non-exponential retarded growth of the tumors in the control treatment group.     

Hodgkin's disease, lymphomatoid papulosis, and cutaneous T-cell lymphoma derived from a common T-cell clone.

BACKGROUND. Lymphomatoid papulosis is a benign cutaneous eruption that in 10 to 20 percent of patients is associated with the development of lymphoma. The atypical cells of lymphomatoid papulosis histologically resemble the malignant cells of cutaneous T-cell lymphoma or the Reed-Sternberg cells of Hodgkin's disease. We studied a patient in whom lymphomatoid papulosis developed in 1971, Hodgkin's disease in 1975, and cutaneous T-cell lymphoma in 1985, to determine whether these diseases are clonally related. METHODS. The T-cell-receptor alpha-chain gene was cloned and sequenced from a cell line derived from the advanced-stage cutaneous T-cell lymphoma, and the polymerase chain reaction was used to search for this rearrangement of the alpha-chain gene in tissues obtained earlier that were affected by Hodgkin's disease or lymphomatoid papulosis. RESULTS. The tumor-specific rearrangement of the alpha-chain gene was detected in the patient's earlier tissues affected by lymphomatoid papulosis and Hodgkin's disease, but not in control tissue, including uninvolved tissues from the staging laparotomy for Hodgkin's disease. Cytogenetic studies revealed a translocation, t(8;9)(p22;p24), in cutaneous T-cell lymphoma lines and in a dermatopathic lymph node removed two years before the clinical onset of the cutaneous T-cell lymphoma. Immunohistochemical findings were consistent with an activated T-cell phenotype for the atypical cells of lymphomatoid papulosis, the Reed-Sternberg cells of Hodgkin's disease, and the malignant cells of the T-cell lymphoma. CONCLUSIONS. Lymphomatoid papulosis, Hodgkin's disease, and cutaneous T-cell lymphoma can be derived from a single T-cell clone. A t(8;9) genetic translocation may be involved in the pathogenesis of lymphomatoid papulosis or its progression to malignant disease.     

Genomic profiling of peripheral T-cell lymphoma, unspecified, and anaplastic large T-cell lymphoma delineates novel recurrent chromosomal alterations

To characterize genetic alterations in peripheral T-cell lymphoma, not otherwise specified (PTCL NOS), and anaplastic large T-cell lymphoma (ALCL), 42 PTCL NOS and 37 ALCL [17 anaplastic large cell kinase (ALK)-negative ALCL, 9 ALK-positive ALCL, 11 cutaneous ALCL] were analyzed by comparative genomic hybridization. Among 36 de novo PTCL NOS, recurrent chromosomal losses were found on chromosomes 13q (minimally overlapping region 13q21, 36% of cases), 6q and 9p (6q21 and 9p21-pter, in 31% of cases each), 10q and 12q (10q23-24 and 12q21-q22, in 28% of cases each), and 5q (5q21, 25% of cases). Recurrent gains were found on chromosome 7q22-qter (31% of cases). In 11 PTCL NOS, high-level amplifications were observed, among them 3 cases with amplification of 12p13 that was restricted to cytotoxic PTCL NOS. Whereas cutaneous ALCL and ALK-positive ALCL showed few recurrent chromosomal imbalances, ALK-negative ALCL displayed recurrent chromosomal gains of 1q (1q41-qter, 46%), and losses of 6q (6q21, 31%) and 13q (13q21-q22, 23%). Losses of chromosomes 5q, 10q, and 12q characterized a group of noncytotoxic nodal CD5+ peripheral T-cell lymphomas. The genetics of PTCL NOS and ALK-negative ALCL differ from other T-NHLs characterized genetically so far, among them enteropathy-type T-cell lymphoma, T-cell prolymphocytic leukemia, and adult T-cell lymphoma/leukemia.     

Cutaneous T-cell lymphoma, multilobated type

Three cases of a new type of lymphoma of the skin are described. Clinical manifestations were the development of papules, nodules and tumours which slowly progressed in size and extent in one region of the skin of elderly men. Dissemination to a regional lymph node occurred in only one. Histopathologically the lesions demonstrated a variably perivascular or diffuse dermal infiltrate often with a nodular configuration and sparing the epidermis and a clear subepidermal zone. The infiltrates were dominated by abnormal lymphoid cells with irregular nuclei and blast cells exhibiting a characteristic combination of multilobated nuclei with marginal nucleoli. By immunological and enzyme cytochemical methods the cells were identified as T lymphocytes. It is suggested that the cases described represent different parts of a spectrum running from lymphocytoma cutis-like conditions to disseminated malignant lymphoma.     

Loss of glucocorticoid receptors in B16BL6 murine melanoma associated with serial transplantation,metastatic selection and altered growth properties

Glucocorticoid cytosolic receptors (GR) have been studied in both a primary and in a lung selected (metastatic) series of a B16BL6 routine melanoma. In the primary series tumour there was an initial increase in GR content from 40 to 95·6 fM mg^–1 protein. GR levels then fell over the next 11 transplant generations to 10 fm mg^–1 protein. In the metastatic series, in the course of six transplant generations, GR content of 73 fm mg^–1 protein fell to below detectable levels, i.e. < 5 fm mg^–1 protein. Both the metastatic and primary series tumours showed a significant decrease in doubling times with increasing transplant generation. We therefore suggest that in the primary series tumours, after an initial phase of adaptation from tissue culture to in vivo conditions, the increased growth of the tumours is independent of the loss of hormonal control caused by a reduction in the glucocorticoid receptor content associated with serial transplantation. In the metastatically selected series of tumours, there appears to be a selective growth pressure brought about by the cyclic transplantation procedure which was also accompanied by an increase in metastatic ability.     

Surface immunoglobulin of a mouse T-cell lymphoma

A surface immunoglobulin (Ig) has been extracted from E14, a tissue culture established mouse T-cell lymphoma. The purified protein can be separated into heavy and light chains by reduction with 2-mercaptoethanol. The intact Ig has a molecular weight of 170,000 and the heavy chain has a molecular weight of 64,000.     

CXCL13、CD10和bcl-6在血管免疫母细胞性T细胞淋巴瘤的诊断及鉴别诊断中的作用

目的 探讨CXCL13、CD10、bcl-6等标志物在血管免疫母细胞性T细胞淋巴瘤(AITL)的诊断和鉴别诊断中的作用.方法 对四川大学华西医院病理科1990年1月至2008年1月诊断的115例AITL、30例非特指外周T细胞淋巴瘤(PTCL,NOS)和30例以副皮质区增生为主的反应性增生(RH)进行回顾性分析.按2008版WHO关于淋巴造血组织肿瘤分类进行组织学分型,采用9种抗原标志物的免疫组织化学(SP法)染色及TCR-γ基因重排检测.结果 (1)7.8%(9/115)的AITL、6.7%(2/30)的PTCL,NOS和83.3%(25/30)的RH病例观察到生发中心;98.3%(113/115)的AITL、63.3%(19/30)的FTCL,NOS和76.7%(23/30)的RH病例观察到显著血管增生.(2)CXCL13、CD10、bcl-6在RH病例的表达局限在生发中心,在AITL的表达率分别为96.5%(111/115)、50.4%(58/115)和78.3%(90/115),在PTCL,NOS的表达率分别为26.7%(8/30)、3.3%(1/30)和3.3%(1/30),以上三个标记在两种淋巴瘤的表达率差异均具有统计学意义.115例AITL病例均见到滤泡外不规则分布的CD21阳性的滤泡树突状细胞网(FDC).TCR-γ基因克隆性重排在AITL中检出率为83%(83/100).结论 AITL是一种来源于生发中心辅助性T细胞(TFH)的高度侵袭性肿瘤,CXCL13、CD10、bcl-6是AITL诊断和鉴别诊断有用标志物.     

LL2 cell line derived from transplantable murine Lewis lung carcinoma--maintenance in vitro and growth characteristics

LL2 is a new in vitro cell line derived from Lewis lung carcinoma passaged routinely in C57BL mice. It has been in continuous culture for more than 1 year and has survived 72 subcultivations. The cells grow in semi-suspension culture being loosely connected with a culture vessel's surface. The cell line is hypotetraploid, with modal chromosome number 72. Tumorigenicity and metastasibility of the cells are retained but lowered as compared with original in vivo tumor line. The LL2 cell line is being used in studies on phenotypic characteristics (markers) related to its pattern of growth.     

Changes in the tumorigenic and metastatic properties of murine melanoma cells treated with a triazene derivative

Treatment of B16/BL6 murine melanoma cellsin vitro with the xenogenizing agent potassiump-(3-methyl-1-triazeno)benzoate (MM-COOK) had a profound impact on the tumorigenic and metastatic properties of the tumor, an effect that was only detectable in immunologically intact hosts. The treated tumor cells gave rise to a considerably smaller number of experimental and spontaneous pulmonary metastases and displayed an impaired growth ratein vivo, but were highly tumorigenic and metastatic in irradiated recipients. Moreover, the drug-treated cells retained thein vitro growth pattern and plating efficiency of the parent line, and were able actively to immunize intact hosts. Studies aimed at clarifying the mechanisms responsible for the decreased metastatic potential of the cells treated with MM-COOK indicated the involvement of host immune responses largely mediated by cells in the T-dependent compartment with no major contribution of natural immunity effector mechanisms.     

Primary bony peripheral T-cell lymphoma mimicking nasal type NK/T-cell lymphoma: a case report

Primary bony lymphomas are rare, and nearly all are high-grade B-cell lymphomas. Natural killer (NK)/T-cell lymphomas are highly aggressive lymphomas of NK- or T-cell lineage with predominant extranodal presentation and are divided into nasal and nasal-type (extra-nasal). We report a primary bony peripheral T-cell lymphoma mimicking NK/T-cell lymphoma, nasal type. A 22-year-old Taiwanese male presented with a frontal skull bone mass noted for 3 weeks, and received craniectomy with tumor removal. His tumor showed extensive coagulative necrosis with angioinvasion by large lymphoma cells expressing CD2, CD8, CD16, CD43, CD45, CD45RO, CD56, T-cell intracellular antigen-1, and granzyme B, but not CD3, CD4, CD20, CD57, CD68, and betaF1. In situ hybridization for Epstein-Barr virus-encoded mRNA was negative. Polymerase chain reaction study of formalin-fixed tissue showed clonal rearrangement of the T-cell receptor-gamma chain gene. The diagnosis was peripheral T-cell lymphoma, unspecified subtype. The initial stage was I(EA). His lymphoma was refractory to chemotherapy, and bony metastases developed in the right iliac bone 2 months later. He died of disease after 6 months without autopsy. We emphasize the importance of detailed immunohistochemical and gene rearrangement studies for the classification of malignant lymphomas via a very rare primary bony lymphoma of peripheral T-cell subtype.