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Dan Jones

Publications and source records attributed to Dan Jones.

At least 73 records · Page 4Linked to original sources
PubMed2002

A stable aberrant immunophenotype characterizes nearly all cases of cutaneous T-cell lymphoma in blood and can be used to monitor response to therapy.

BACKGROUND: Abnormal variations in the expression level of some commonly expressed T-cell antigens are a feature of many T-cell malignancies. METHODS: We sought to assess the frequency of such abnormal antigen expression by flow cytometry in peripheral blood (PB) samples from patients with mycosis fungoides (MF) and Sézary syndrome (SS). We correlated presence of morphologically identifiable tumor cells on PB smear with the frequency of abnormalities in the level of expression of CD3, CD4, CD7, CD8 and CD26. We also examined the degree of stability of these abnormal findings in tumor cells over the course of disease. The flow cytometric findings in 100 PB samples from 44 patients, including 38 who had multiple sequential PB samples (2-8 samples each), were assessed. RESULTS: Abnormalities were seen in the expression level of one or more T-cell markers in 41 cases (93%) including CD3 in 34% of patients, CD4 in 54%, CD26 in 86% and CD 45 in 40% (10 cases tested). In all but 2 cases, the abnormal T-cell immunophenotype remained similar over the course of treatment and correlated with the relative numbers of tumor cells counted on PB smear. CONCLUSIONS: Using a standard T-cell panel, stable phenotypically aberrant T-cell populations representing the tumor are detected in the vast majority of involved PB samples in MF/SS and can be used to monitor response to therapy.

Journal Article↗
PubMed2002

Clonal heterogeneity in mycosis fungoides and its relationship to clinical course.

Mycosis fungoides (MF) is a cutaneous T-cell lymphoma characterized by multifocal disease and protracted clinical course. The few studies that have assessed T-cell receptor (TCR) gene rearrangements (GRs) present at different anatomic sites in MF have generally reported a common clone. We used a previously validated 4-color polymerase chain reaction (PCR) assay to assess the size and V-family usage of TCR-gamma GRs in 102 concurrent and/or sequential morphologically involved biopsy specimens (91 skin and 11 lymph nodes) from 39 MF patients. This assay detected TCR-gamma clonal GRs in 89 samples (87%) from 36 patients (92%). In 24 patients (77%), an identical clonal GR was present in at least 2 skin samples. However, in one third of these patients, additional different clonal GRs were also noted. Four patients (13%) had clonal GRs that were distinct in different skin samples. In 3 patients (10%), no GR was detected in any sample. In a comparison of lymph node and skin samples, 8 patients had the identical clonal GRs at both sites, 2 patients had different clonal GRs, and 1 patient had no GR identified at either site. Independent of clinical stage, patients who had the same GR detected in multiple concurrent biopsy specimens at the time of diagnosis were more likely to have progressive disease than those who had different GRs (P =.04). Four-color TCR-gamma PCR analysis can uncover multiple distinct clonal GRs in different samples consistent with multiclonal or oligoclonal disease in a significant proportion of MF patients. Demonstration of identical clonal GRs in multiple biopsy specimens at the time of diagnosis may provide prognostic information related to disease progression.

Adolescent↗
PubMed2002

CD56(+) TdT(+) blastic natural killer cell tumor of the skin: a primitive systemic malignancy related to myelomonocytic leukemia.

BACKGROUND: An unusual cutaneous tumor that has blastic morphology and coexpresses CD56 and terminal deoxynucleotidyl transferase (TdT) has been recently recognized and termed blastic natural killer cell lymphoma. METHODS: The authors identified seven cases of such CD56(+)TdT(+) blastic tumors presenting in skin at their institution. The authors correlated clinical course with histomorphology and immunophenotype. RESULTS: All 7 patients (6 men, 1 woman, 52-85 years) presented with rapidly growing, frequently multiple cutaneous nodules. All patients had low level bone marrow involvement at diagnosis and frequently had lymph node involvement. Tumor cells were of intermediate size with irregular nuclear contours, fine chromatin, and indistinct small nucleoli. The expression of TdT varied between 5% and over 90% of the neoplastic cell population. Tumor cells were negative for surface CD3, CD5, and CD20 in all cases, but some patients showed expression of CD2 (three out of five), cytoplasmic CD3 (two out of seven), CD4 (six out of seven), and CD16 (three out of seven). Molecular studies showed absence of T-cell receptor gene rearrangements in all cases. All seven patients had rapid progression of disease, and six patients have died of their disease or complications. Three patients developed progressively increasing numbers of bone marrow blasts that had a myeloid immunophenotype and were negative for TdT and CD56. Two patients met criteria for acute myeloid leukemia at 11 and 22 months after presentation, respectively. CONCLUSIONS: CD56(+) TdT(+) blastic tumor presenting in skin is a systemic malignancy likely of primitive/undifferentiated hematopoietic origin. Patients might subsequently develop tumors of myeloid or myelomonocytic phenotype, indistinguishable from acute myelogenous leukemia.

Aged↗
PubMed2002

European Organization for Research and Treatment of Cancer and Groupe d'Etude des Lymphomes de l'Adulte very favorable and favorable, lymphocyte-predominant Hodgkin disease.

BACKGROUND: Lymphocyte-predominant Hodgkin disease (LPHD) is rare and has a natural history different from that of classic Hodgkin disease. There is little information in the literature regarding the role of chemotherapy in patients with early-stage LPHD. The objective of this study was to examine recurrence free survival (RFS), overall survival (OS), and patterns of first recurrence in patients with LPHD who were treated with radiotherapy alone or with chemotherapy followed by radiotherapy. METHODS: From 1963 to 1996, 48 consecutive patients ages 16-49 years (median, 28 years) with Ann Arbor Stage I (n = 30 patients) or Stage II (n = 18 patients), very favorable (VF; n = 5 patients) or favorable (F; n = 43 patients) LPHD, according to the European Organization for Research and Treatment of Cancer and Groupe d'Etude des Lymphomes de l'Adulte (EORTC-GELA) criteria, received radiotherapy alone (n = 37 patients) or received chemotherapy followed by radiotherapy (n = 11 patients). The percentages of patients with VF disease (11% vs. 9% in the radiotherapy group vs. the chemotherapy plus radiotherapy group, respectively) or F disease (89% vs. 91%, respectively) within the two treatment groups were similar (P = 1.00). A median of three cycles of chemotherapy with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) or with mitoxantrone, vincristine, vinblastine, and prednisone (NOVP) was given initially to six patients and five patients, respectively. A median total radiotherapy dose of 40 grays (Gy) given in daily fractions of 2.0 Gy was delivered to both treatment groups. RESULTS: The median follow-up was 9.3 years, and 98% of patients were observed for > or = 3.0 years. RFS was similar for patients who were treated with radiotherapy alone and patients who were treated with chemotherapy followed by radiotherapy (10-year survival rates: 77% and 68%, respectively; P = 0.89). The OS rate also was similar for the two groups (10-year survival rates: 90% and 100%, respectively; P = 0.43). MOPP or NOVP chemotherapy did not reduce the risk of recurrence outside of the radiotherapy fields. CONCLUSIONS: MOPP or NOVP chemotherapy did not improve RFS or OS significantly in patients with VF or F LPHD, although the statistical power was limited. Ongoing clinical trials will help to clarify the role of a watch-and-wait strategy or systemic therapy, including anthracycline (epirubicin or doxorubicin), bleomycin, and vinblastine-based chemotherapy or antibody-based approaches, in the treatment of these patients.

Adolescent↗
PubMed2002

Clinical and pathological spectrum of CD8-positive cutaneous T-cell lymphomas.

CD8+ T-cell lymphomas presenting in the skin are rare. We describe the clinical and histological features of 18 patients with CD8+ cutaneous T-cell tumors, which have been divided into four groups. Seven patients had precedent long histories of rashes, which progressively spread in a presentation similar to that of CD4+ mycosis fungoides (MF). Three patients had long-standing localized plaques consistent with a pagetoid reticulosis (PR) pattern. Two patients presented with erythroderma and had peripheral blood involvement consistent with a Sezary syndrome (SS) pattern and had rapidly progressive clinical courses. Six patients presented with cutaneous nodules of varying sizes and had variable outcomes, with two having rapidly progressive disease, two with indolent recurrences and a further two with complete responses to treatment. Histologically, 12 of the 18 cases showed an epidermotropic tumor infiltrate that was most marked in the three PR cases. Prominent periadnexal infiltration was seen in 11 cases. Similar to CD4+ MF, the skin-homing antigen, (cutaneous lymphocyte antigen: CLA), was strongly expressed in 13 of 16 tested cases. Expression of the cytotoxic granule protein granzyme B was noted in a majority of tumor cells in only three of 16 tested cases. We conclude that approximately half of CD8+ cutaneous T-cell lymphomas clinically and histologically resemble CD4+ MF/SS, whereas presentation as discrete nodular lesions are more common in CD8+ tumors as compared to those that express CD4.

Adult↗
PubMed2002

Apoptosis and proliferation in subcutaneous panniculitis-like T-cell lymphoma.

Subcutaneous panniculitis-like T cell lymphoma (SPTCL), designated recently as a distinct clinicopathologic entity in the World Health Organization Classification, is a neoplasm composed of cytotoxic T-cells that preferentially involves subcutaneous adipose tissue. Histologically, SPTCL is characterized by extensive karyorrhectic debris and tumor necrosis suggesting that apoptotic mechanisms are involved in its pathogenesis. We assessed the apoptotic index (AI) and proliferation rate (PR) of 13 cases of SPTCL by TUNEL test and Ki-67 immunostaining, respectively. We also immunohistochemically assessed for expression of BCL-2 (anti-apoptosis), BAX (pro-apoptosis), and P53 and correlated the results with apoptosis and proliferation. We detected a high AI (median 8.1%) in 11 cases of SPTCL, and 12 cases had low BCL-2 and high BAX expression. BCL-2 expression inversely correlated with AI (P <.001) and BAX (P <.001). We found a low PR (cutoff > or = 25%) in eight (61%) cases. There was an inverse correlation between AI and PR (r = -.58, P =.04). Ten cases were assessed for P53; immunostaining results were heterogeneous but P53 expression correlated with large cell cytologic features. Our findings demonstrate that SPTCLs have a high AI that may be explained by differential expression of BCL-2 and BAX in the neoplastic cells.

Adult↗
PubMed2002

The stromal composition of malignant lymphoid aggregates in bone marrow: variations in architecture and phenotype in different B-cell tumours.

We present evidence that different B-cell tumours, in bone marrow, have different relationships to stroma. Marrow core biopsies from 46 patients with B-cell tumours were immunostained with antibodies for distinct stromal cells. Cases included follicular lymphoma (FL), chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL), mantle cell lymphoma (MCL), lymphoplasmacytic lymphoma (LPL), and nodal, extranodal and splenic marginal zone lymphoma (NMZL, MALT, SMZL). In normal marrow, low-affinity nerve growth factor receptor (LNGFR) highlighted a fine network of adventitial reticular cells (ARC). The nodular aggregates of CLL/SLL, NMZL, MALT and SMZL were characterized by distortion of the ARC network and downregulation of LNGFR. In contrast, the aggregates of FL, LPL and MCL were composed of linear arrays of ARC in tight association with individual tumour cells. LNFGR+ was upregulated in ARC associated with the aggregates in FL, LPL and focally in MCL. Upregulation of CD35, vascular cell adhesion molecule (VCAM-1) and CD40 on ARC was noted exclusively in FL. Marrow lymphoid aggregates in CLL/SLL, NMZL, MALT and SMZL probably grow by displacing the pre-existing marrow stroma, while FL and LPL maintain a close association with the ARC network. In FL, expression of follicular dendritic cell-associated markers is modulated in pre-existing marrow stromal cells.

Bone Marrow↗
PubMed2002

CCR6 is a functional chemokine receptor that serves to identify select B-cell non-Hodgkin's lymphomas.

Several recent studies have revealed important contributions of chemokines and their receptors to the development and progression of both hematopoietic and nonhematopoietic neoplasms. The chemokine receptor CCR6 is unusual in that it mediates leukocyte chemotaxis in response to a single chemokine, CCL20 (macrophage inhibitory factor-3alpha), as well as in response to a family of antimicrobial peptides termed "beta-defensins." CCR6 is critical for mucosal immunity, and expression of the receptor is tightly regulated on hematopoietic cells. Here we characterize the expression of CCR6 on B cells and B-cell non-Hodgkin's lymphomas. We demonstrate that CCR6 expression is limited to cells comprising the mantle and marginal zones of the secondary lymphoid tissues and serves to identify the majority of mantle cell, marginal zone, and mucosa-associated lymphoid tissue lymphomas. Furthermore, we show that CCR6 serves as a functional chemokine receptor when expressed by neoplastic cells. Finally, we establish that the cognate ligand for CCR6 is present on mucosal epithelium infiltrated by neoplastic cells in select extranodal lymphomas. Thus, CCR6 is a useful new marker identifying a subset of B-cell non-Hodgkin's lymphomas and likely contributes to the localization of select extranodal lymphomas at mucosal sites.

Antibodies, Monoclonal↗
PubMed2002

Cold urticaria in a patient with mycosis fungoides.

We report what we believe to be the first documentation of a patient with both cold urticaria and mycosis fungoides. The patient described a marked worsening of his long-standing lesions of mycosis fungoides at the same time as the onset of cold sensitivity. We believe this suggests a possible association between these 2 rare diseases.

Adult↗
PubMed2002

Outcomes using doxorubicin-based chemotherapy with or without radiotherapy for early-stage peripheral T-cell lymphomas.

There is little information in the literature on outcomes using doxorubicin-based chemotherapy with or without radiotherapy for early-stage peripheral T-cell lymphomas. The purpose of this study was to analyze The University of Texas M.D. Anderson Cancer Center results in such patients. From 1985 to 1998, 39 patients with Stage I or II World Health Organization classification anaplastic large cell lymphoma (ALCL; n = 20), peripheral T-cell lymphoma, unspecified (PTCLu; n = 11), or nasal-type NK/T-cell lymphoma (NKTCL; n = 8) were treated using doxorubicin-based chemotherapy (median, 6 cycles) with (n = 24) or without (n = 15) radiotherapy (median dose, 40 Gy). Median age was 41 years. Median follow-up of surviving patients was 85 months. Even though patients who presented with bulky disease or who achieved less than a complete response to chemotherapy were the ones typically treated with combined modality therapy rather than chemotherapy alone, there was no significant difference in local control (5-year rates: 60 vs. 70%, p = 0.49), progression-free survival (5-year rates: 65 vs. 60%, p = 0.62), or overall survival (5-year rates: 74 vs. 67%, p = 0.47) between the groups treated with combined modality therapy and chemotherapy alone. Fifteen (38%) patients relapsed. Twelve relapses were limited to the initial site of disease; two involved the initial site and new sites, and one involved only new sites. Based on the significant risk of relapse at the initial site of disease, different approaches, including chemotherapy with concomitant radiotherapy to doses > or = 45 Gy, warrant investigation.

Adult↗
PubMed2002

Cutaneous and systemic plasmacytosis in a patient of Asian descent living in the United States.

Cutaneous and systemic plasmacytosis is a rare disorder characterized by widely disseminated macular skin eruptions composed of polyclonal lymphoplasmacytic infiltrates associated with variable extracutaneous involvement. Previous reports have been largely restricted to the Japanese literature. We present the first documented case of cutaneous and systemic plasmacytosis in a patient residing in the United States. This 49-year-old man, who had immigrated from Korea 19 years earlier, developed innumerable persistent pink-to-brown macular lesions over his trunk and face. Initial and repeat skin biopsy specimens revealed dense perivascular and periadnexal infiltrates of mature plasma cells, and polyclonal plasmacytosis noted on two different biopsy specimens of mildly enlarged lymph nodes. Multiple tiny pulmonary nodules were found to be of the same histologic appearance. No evidence of clonal immunoglobulin gene rearrangements or human herpesvirus type 8 infection was noted in these biopsy specimens. Treatment with antibiotics, systemic chemotherapy, and anti-CD20 antibody therapy failed to eradicate these lesions, which have persisted for 6 years. This case demonstrates that cutaneous and systemic plasmacytosis can arise in a patient of Asian ancestry, even many years after emigration to the United States.

Humans↗
PubMed2002

CD4-CD8-"Double-negative" cutaneous T-cell lymphomas share common histologic features and an aggressive clinical course.

We report 15 patients with CD4-CD8-"double-negative" T-cell lymphoma arising in skin. There were seven women and eight men with a mean age at diagnosis of 53 years (range 19-77 years). All but two patients presented with solitary or multiple cutaneous nodule(s). Initial and recurrent biopsy specimens showed a dense infiltrate centered in the mid-dermis (extending into subcutis when sampled) of small to intermediate-sized lymphocytes with indistinct nucleoli and frequently irregular nuclear contours. Periadnexal infiltration and epidermal ulceration were present in five cases with the intraepidermal cells being primarily reactive CD4+ T cells. All cases were negative for CD30 and terminal deoxynucleotidyltransferase; one showed expression of CD56, and six of eight tested cases were positive for T-cell receptor-delta expression. Despite systemic chemotherapy, all 12 patients with clinical follow-up showed recurrent or progressive disease with widespread cutaneous dissemination in 10 of 12. Eventual dissemination to lymph nodes or bone marrow occurred in two patients each, with at least nine patients dead of disease or treatment complications. Only two patients achieved lasting clinical remission (with 2'-deoxycoformycin/pentostatin and nelarabine, respectively). CD4-CD8-"double-negative" CTCL has distinctive histologic features and cytomorphology with a marked propensity for rapid multifocal cutaneous dissemination.

Adult↗
PubMed2002

Epstein-Barr virus-positive B-cell lymphoproliferative disorders arising in immunodeficient patients previously treated with fludarabine for low-grade B-cell neoplasms.

We describe five patients with treated low-grade B-cell neoplasms who subsequently developed Epstein-Barr virus (EBV)-positive B-cell lymphoproliferative disorders (BLPDs). The low-grade B-cell neoplasms were B-cell chronic lymphocytic leukemia in four patients and splenic marginal zone lymphoma in one patient. All patients had received treatment with fludarabine for the low-grade B-cell neoplasm, and three had also received Campath-1H. The EBV-BLPDs arose 2-12 months after completion of fludarabine therapy and morphologically resembled the EBV-BLPDs that occur in the setting of iatrogenic immunodeficiency. Molecular genetic studies showed that these lesions were clonally distinct from the low-grade B-cell neoplasm in three of four cases assessed. Two patients did not receive therapy for the EBV-BLPD. The lesions regressed spontaneously in both patients but recurred in one. One patient underwent surgical excision and remains without evidence of the EBV-BLPD. One patient received aggressive multiagent chemotherapy with a complete response initially, but the EBV-BLPD recurred after 12 months. One patient received antiviral therapy and responded completely but died 2 months later of an opportunistic infection. We conclude that patients with low-grade B-cell neoplasms treated with fludarabine, possibly in combination with other immune suppressive agents, may subsequently develop EBV-BLPDs that morphologically resemble other iatrogenic immunodeficiency-associated BLPDs. Most are clonally distinct from the underlying low-grade B-cell neoplasm. A subset of these lesions may regress without systemic therapy.

Antineoplastic Agents↗
PubMed2002

Mantle cell lymphoma involving skin: cutaneous lesions may be the first manifestation of disease and tumors often have blastoid cytologic features.

We describe five cases of mantle cell lymphoma involving skin. Three patients initially presented with skin lesions but had evidence of widespread disease at time of diagnosis or with relatively short follow-up. One patient was known to have disseminated disease before he developed skin lesions. One patient presented with a solitary skin nodule on the thigh and has developed multiple smaller nodules on the same leg, but no other sites of disease over 30 months of clinical follow-up. This case fulfills the criteria for primary cutaneous lymphoma as proposed by the European Organization for Research and Treatment of Cancer. Biopsy of the skin lesions in all cases showed predominantly dermal and focally subcutaneous lymphoid infiltrates, preferentially perivascular and periadnexal in four cases, and nodular in one case. The tumors were composed of small- to medium-sized lymphocytes with irregular nuclear contours. Four cases had blastoid and one case had typical cytologic features. Immunophenotypic studies showed that all cases were positive for CD20 and cyclin D1, and four of five were positive for CD5. Four cases, including the CD5-negative case, had evidence of the t(11;14) shown by either fluorescence in situ hybridization methods performed on skin tumors or conventional cytogenetic analysis performed on involved bone marrow. We conclude that mantle cell lymphoma can involve skin, usually as a manifestation of disseminated disease, and is often associated with blastoid cytologic features. Rare cases of mantle cell lymphoma may arise in skin.

Aged↗
PubMed2002

Dismantling the germinal center: comparing the processes of transformation, regression, and fragmentation of the lymphoid follicle.

The pathologic and immunologic features of the formation of the germinal center have been extensively studied. The process of dissolution of the germinal center is not as well understood. Different patterns of germinal-center breakdown are commonly encountered in diagnostic lymph node biopsy specimens and frequently present difficulties in diagnosis. The current immunologic understanding of germinal-center dynamics is reviewed and correlated with the histologic and immunophenotypic features of three broad classes of germinal center dissolution, namely progressive transformation, regression, and follicle fragmentation. The author suggests that these different patterns represent alternate responses to antigenic stimulation. The relationships of progressive transformation to Hodgkin's disease and of follicular regression to Castleman's disease are discussed.

B-Lymphocytes↗
PubMed2002

Peripheral T-cell lymphoma arising in the liver.

We report 3 cases of primary hepatic peripheral T-cell lymphoma (PTCL). All patients were men, 50 to 57 years of age, who sought care because of systemic symptoms including fever, fatigue, and weight loss. Physical examination revealed hepatomegaly in 2 patients, associated with jaundice in 1. Two patients had abnormal serum liver enzyme levels and coagulation profiles. Imaging studies demonstrated marked hepatomegaly without focal lesions in 1 patient and multiple discrete tumor masses in 2 patients. Tumor infiltrates in biopsy specimens were heterogeneous with a large cell component in 2 cases. An inflammatory background was present in all cases, complicating the histologic recognition of PTCL Immunohistochemical studies showed that all tumors were of T-cell lineage, and 2 cases had monoclonal T-cell receptor gamma chain gene rearrangements. One patient died of disease shortly after diagnosis, and 2 patients treated with multiagent chemotherapy are in clinical remission with 12 and 84 months of clinicalfollow-up, respectively. PTCL may rarely arise in the liver. These neoplasms respond to chemotherapy, suggesting that this disease is curable if diagnosed at an early stage.

Cell Lineage↗
PubMed2002

Apoptotic rate in peripheral T-cell lymphomas. A study using a tissue microarray with validation on full tissue sections.

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of non-Hodgkin lymphomas with a wide spectrum of clinicopathologic features, and apoptosis mechanisms may have a role in lymphomagenesis. We assessed apoptotic rate (AR) in 112 PTCLs using a tissue microarray developed in our laboratory and a modified terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay. The mean AR was 1.47% +/- 1.38% for the entire group of PTCLs (range, 0.06%-5.15%), and AR varied significantly among different tumor types. In mycosis fungoides, the mean AR was 0.74%; angioimmunoblastic T-cell lymphoma, 1.02%; PTCL, not otherwise specified, 1.38%; cutaneous anaplastic large cell lymphoma (ALCL), 1.41%; anaplastic lymphoma kinase protein (ALK)-negative ALCL, 1.43%; extranodal natural killer/T-cell lymphoma of nasal type, 2.04%; ALK-positive ALCL, 2.95%; and enteropathy-type T-cell lymphoma, 3.06%. Mean AR was higher in PTCL with large cell vs small/medium cell morphologic features (1.66% +/- 1.1% vs 0.99% +/- 1.0%). In a subset of 33 PTCLs, the tissue microarray results comparedfavorably with those obtained in full tissue sections. We conclude that the highest ARs in PTCLs are found in enteropathy-type T-cell lymphoma and ALK-positive ALCL, and that AR can be assessed reliably by using a tissue microarray.

Anaplastic Lymphoma Kinase↗