Circulating cell-free Epstein-Barr virus DNA levels in patients with EBV-associated lymphoid malignancies.

Epstein-Barr virus (EBV) is a human lymphotrophic herpesvirus implicated in the development of several lymphoid malignancies. Recently, detection of cell-free EBV DNA in sera or plasma from patients with EBV-associated malignancies has been reported. However, most published studies are qualitative in nature, with only a few providing quantitative data. We have described the temporal changes of plasma EBV DNA levels in patients with EBV-associated lymphoid malignancies during therapy using quantitative real-time PCR. A close correlation between plasma EBV DNA levels and therapeutic response was observed. Our aim was to update our results and to assess the role of the plasma EBV DNA levels as a molecular marker for disease monitoring in patients with EBV-associated lymphoid malignancies.

Primary non-Hodgkin's lymphoma of the liver.

Primary non-Hodgkin's lymphoma of the liver is an extremely rare lymphoma subset that often presents with diagnostic difficulties to both clinicians and pathologists. Using MEDLINE search, 90 cases of primary hepatic lymphomas reported in the literature were reviewed. The epidemiology and etiology, clinical presentation, pathologic features, management, and outcome of these patients have been summarized and described. Results of this review show that middle-aged males are most often affected. Abdominal pain or discomfort, weight loss and fever are the most frequent presenting symptoms. Most cases have a solitary or multiple mass lesions in the liver, and are frequently misdiagnosed as having a primary liver tumor or metastatic cancer. Diffuse large cell lymphoma is the most commonly encountered histologic subtype. Surgery, chemotherapy and radiotherapy have been used alone or in combination as treatment but the outcome is generally poor. Although primary hepatic lymphoma is an aggressive disease, it is resectable, and responsive to chemotherapy and radiotherapy. Because of the profound therapeutic implications, it should be considered in the differential diagnosis for patients presenting with mass lesions in the liver or hepatic disease.

A prospective randomized study of Chop versus Chop plus alpha-2B interferon in patients with intermediate and high grade non-Hodgkin's lymphoma: the International Oncology Study Group NHL1 Study .

UNLABELLED: The addition of a brief alpha interferon regimen to each CHOP induction cycle, plus one year of alpha interferon thrice weekly maintenance therapy, has no early effect on response rates or survival in patients with Intermediate or High grade cell NHL. BACKGROUND: The CHOP (Cyclophosphamide, Adriamycin. Vincristine, Prednisone) regimen is the most widely used first-line therapy for patients with Intermediate or High Grade (IG/HG) non-Hodgkin's lymphoma (NHL). Alpha 2b interferon (INF) enhances response rates and improves survival in low-grade NHL. The International Oncology Study Group (IOSG) conducted a prospective randomized study comparing CHOP alone or combined with INF in patients with IG/HG-NHL. The primary study aim was to compare the objective response rates in these patient cohorts. PATIENTS AND METHODS: Patients with a confirmed diagnosis of measurable NHL of International Working Formulation (IWF) groups D to H histology were randomized to receive CHOP alone or CHOP with 5Mu INF s.c. for 5 days on days 22 to 26 of each 28 day cycle with INF 5 million units (Mu) given three times per week subcutaneously for 52 weeks in those patients who responded to CHOP plus INF. RESULTS: The overall response rates were equivalent in both groups: CHOP alone (214 patients) 81% (complete 55%, partial 26%); CHOP plus INF (221 patients) 80% (complete 54%, partial 26%). At 36 months, the actuarial survival rate was equivalent in both groups. CONCLUSIONS: There is no apparent early advantage in terms of response or survival conferred by adding the study INF regimen to CHOP therapy for patients with IG/HG-NHL.

MRI of neck nodes in non-Hodgkin's lymphoma of the head and neck.

The aim of this study is to describe the imaging features of neck nodes in non-Hodgkin's lymphoma (NHL). The MR scans of 61 patients undergoing staging of a primary extranodal NHL of the head and neck were reviewed retrospectively. Those MR images with nodal disease were assessed for (a) the pattern of nodal disease, (b) presence of nodal necrosis and (c) presence of extracapsular neoplastic spread (ENS) and nodal matting. The features of the nodal disease were analysed in relationship to the sites of the primary NHL (palatine tonsil (PT) n=23, nasal cavity (NC) n=24, nasopharynx (NP) n=6, other extralymphatic sites (OES) n=8), and histology (natural killer/T-cell (NK/T) n=26, diffuse large cell (DLC) n=24, other subtypes (OS) n=11). Nodal disease was present in 26 patients (43%) and occurred in NHL of the PT n=16 (70%), NP n=3 (50%), NC n=5 (21%) and OES n=2 (25%) and in DLC n=15 (63%), NK/T n=6 (23%) and OS n=5 (45%). Nodal disease was significantly more frequent in DLC than NK/T lymphomas (p=0.0053). Nodal disease spread in a contiguous fashion in 25 (96%) patients with nodes. Necrosis was present in 7 of 26 (27%) being present in DLC of the PT in 5, NK/T of the NP in one and NK/T of the NC in one. ENS and matting were present in 19 (73%) and 13 (50%) patients with nodes, respectively. ENS was found in DLC, NK/T, OS, NC, NP, PT, OES (11, 4, 4,1, 2, 14, 2, respectively) and matting was found in DLC, NK/T, OS, NC, NP, PT, OES (9, 3, 1, 0, 2, 10, 1, respectively). Nodal NHL spreads in a contiguous fashion and is most commonly associated with DLC lymphoma of the NP and PT in Waldeyer's ring. Extracapsular nodal spread is frequent and found in most histological subtypes especially those arising from Waldeyer's ring. Necrosis is more common than previously believed.

MRI of primary non-Hodgkin's lymphoma of the palatine tonsil.

Non-Hodgkin's lymphoma (NHL) arising primarily in the palatine tonsil is uncommon. The aims of the study were to describe the appearances on MRI and to identify the features that help to distinguish NHL from other tonsillar tumours. The clinical records and MR images of eight patients with primary NHL of the palatine tonsil were reviewed. Patients had a short duration of symptoms (mean 1 month). Systemic symptoms (fever, weight loss or night sweats) occurred in two patients. Tumours were round or lobulated and ranged in size from 30 mm to 70 mm. The signal intensity on T2 weighted, T1 weighted and T1 weighted contrast enhanced images was homogeneous and similar to that of normal tonsil in six patients. Two large tumours were mildly heterogeneous and one of these showed small foci of necrosis. NHL of the tonsil displaced rather than invaded local structures in seven patients and locally invaded the soft palate in only one patient. Lymphadenopathy was present in five patients and the nodes were of similar signal intensity to the primary tumour. There was involvement of the ipsilateral upper internal jugular chain in all cases of lymphadenopathy. The posterior triangle was involved in two patients, the periparotid node in one patient and the retro-oropharyngeal region in one patient. The presence of a large tumour without deep invasion together with homogeneous non-necrotic nodes suggests the diagnosis of NHL. As NHL frequently has similar signal intensity to normal tonsil, MRI may not be able to detect lymphomatous involvement in the non-enlarged tonsil.

Aggressive primary natural killer cell lymphoma of the caecum: a case report and literature review.

An unusual case of aggressive Stage IIE(B) primary natural killer cell lymphoma of the caecum is described in a 16-year old Chinese girl. The immunophenotype of the tumour cells was CD2+, CD3-, CD4-, CD5-, CD7+, CD8-, CD45RO+, CD45RA-, CD56+, CD57-. Southern blot analysis showed a normal germline arrangements of the T-cell antigen receptor and immuno-globulin heavy chain genes. This lymphoma pursued a highly aggressive clinical course, with the rapid development of an extensive local recurrence after an apparently complete resection and combination cytotoxic therapy. The patient died 7 months after diagnosis, despite receiving salvage treatment. Given the aggressiveness and poor prognosis in this biologically distinct primary gastrointestinal lymphoma, a more vigorous systemic therapy should be considered in addition to surgery.

Acute monoblastic leukaemia with conjunctival tumours.

We describe an unusual occurrence of bilateral conjunctival tumours in a 25-year-old woman. This was the first sign of relapse of acute monoblastic leukaemia. There was also both marrow relapse and subsequent skin infiltration. No central nervous system involvement was detected. The tumours appeared as pink raised lesions in the upper conjunctivae of both eyes. They were not associated with pain or visual impairment. Conjunctival tumour biopsy revealed a dense mononuclear cell infiltration. Complete remission (conjunctival tumours, skin infiltration and bone marrow) was attained following systemic chemotherapy in combination with intrathecal chemotherapy.

Primary nasal and nasopharyngeal lymphomas: a comparative study of clinical presentation and treatment outcome.

Primary nasal lymphoma (NSL) and nasopharyngeal lymphoma (NPL) are uncommon extranodal lymphomas that have often been grouped together in studies published in the literature. It is unclear whether or not NSL and NPL are biologically different entities. We reviewed the records of 25 NSL and 19 NPL patients who were managed between 1985 and 1995, to evaluate and compare their clinical characteristics and treatment outcome. Clinical variables, including age, sex, stage, tumour bulk and treatment modality, were assessed for their prognostic influence on survival. Nasal obstruction (80%), nasal discharge (64%) and epistaxis (60%) were the predominant symptoms in NSL patients; neck swelling/mass (42%), nasal obstruction (37%) and hearing impairment (32%) were common findings in NPL patients. Limited stage disease (I/II) was present in all NSL and in 80% of the NPL patients. Thirty-six per cent of the NSL and 32% of the NPL patients had bulky disease. The majority of the immunophenotyped NSLs were of T-cell lineage (75%, 12/16) and most immunophenotyped NPLs were of B-cell lineage (69%, 11/16). The patients were treated with radiotherapy alone (14%), chemotherapy alone (23%) or chemotherapy plus radiotherapy (64%). NSL patients showed a lower complete remission rate and higher relapse rate than NPL patients, although the difference did not reach statistical significance. Both the 5-year disease-free survival (36% versus 76%; P = 0.007) and overall survival (33% versus 82%; P = 0.003) were significantly worse in NSL compared with NPL patients. Advanced age (>60 years; P = 0.03) and bulky disease (P = 0.04) were also associated with inferior survival times. The analysis of sex, stage and type of therapy showed no evidence of significant impact on the survival. Despite the close anatomical relationship in origin, NSL and NPL were noted to behave as biologically distinct entities, in which the NSLs demonstrated a higher frequency of T-cell tumours and a much worse prognosis than NPL. In addition to the primary site, advanced age and bulky disease were also associated with reduced survival.

The prognostic significance of serum levels of soluble intercellular adhesion molecules-1 in patients with primary extranodal non-Hodgkin lymphomas.

BACKGROUND: Elevated levels of soluble intercellular adhesion molecules (sICAM)-1 in serum have been shown to be associated with poor prognosis in Hodgkin disease and non-Hodgkin lymphomas. However, little is known about the significance of serum sICAM-1 levels in extranodal lymphomas. The objective of this study was to examine the sICAM-1 levels in patients with extranodal lymphomas and the correlation with clinical features and outcome. METHODS: The serum levels of sICAM-1 were measured in stored serum samples of 88 patients with primary extranodal lymphomas at presentation using enzyme-linked immunoassay. The correlation between serum sICAM-1 levels and clinical characteristics, pathologic features, and disease outcome were retrospectively analyzed. RESULTS: Serum sICAM-1 levels in patients with extranodal lymphomas (mean, 372 +/- 198.8 ng/mL; interquartile range, 252-466 ng/mL) were significantly higher than that of healthy control subjects (mean, 214 +/- 78.5 ng/mL; interquartile range, 160-241 ng/mL; P < 0.0001). High serum sICAM-1 levels (>/= 371 ng/mL) were significantly associated with B-symptoms, elevated lactate dehydrogenase level, advanced stage (III/IV; Ann Arbor Staging System), and poor response to therapy. Univariate analysis demonstrated a significantly poorer 5-year disease free (41% vs. 64%; P = 0.01) and overall (44% vs. 73%; P = 0. 003) survival in patients with high serum sICAM-1 as compared with those with normal sICAM-1. In multivariate analysis, both disease free (P = 0.0085) and overall (P = 0.0003) survival were independently associated with high serum sICAM-1 levels. CONCLUSIONS: Serum sICAM-1 levels are elevated in patients with extranodal lymphomas. In these individuals, high serum sICAM-1 levels are associated with adverse disease features and poor outcome.

Aggressive primary hepatic lymphoma in Chinese patients. Presentation, pathologic features, and outcome.

BACKGROUND: Primary non-Hodgkin's lymphoma of the liver is rare. In this study, the presentation, pathologic features, and outcome of seven Chinese patients with primary hepatic lymphoma are described. METHODS: From 1984 to 1994, the clinical records of 14 Chinese patients with non-Hodgkin's lymphoma and histologically proven liver involvement were reviewed. Seven (four males, three females; median age, 54 years) were considered to have primary hepatic lymphoma. Histologic and immunohistochemical studies were performed on paraffin embedded liver tissue. RESULTS: "B" symptoms including fever (86%) and weight loss (57%) were the most striking presenting features. Hepatomegaly was present in all patients, splenomegaly in three (43%), and thrombocytopenia in six (86%). Only one patient was hepatitis B surface antigen-seropositive. None had preexisting liver disease. Histologic subtypes, though heterogeneous, were mostly unfavorable and consisted of diffuse large cell lymphoma (two patients), small lymphocytic lymphoma (one patient), lymphoblastic lymphoma (one case), mantle cell lymphoma (one patient), anaplastic large cell Ki-1 lymphoma (one patient), and hepatosplenic T-cell lymphoma (one patient). Three patients expressed B-cell and 2 expressed T-cell phenotypes. Six patients received cytotoxic chemotherapy. One had resection and one had splenectomy, but none achieved complete remission, and only one remained alive as of this writing. The median survival was 3.7 months (range, 8 days to 47.7 months). CONCLUSION: Chinese patients with primary non-Hodgkin's lymphoma of the liver have prominent "B" symptoms, disease with a highly aggressive course, a poor response to local and systemic treatment, and short survival. Hepatitis B virus infection is not a major etiologic factor for these patients.

Serious pulmonary complications in patients receiving recombinant granulocyte colony-stimulating factor during BACOP chemotherapy for aggressive non-Hodgkin's lymphoma.

Four of 12 Chinese patients receiving BACOP, in combination with recombinant human granulocyte colony-stimulating factor, for aggressive non-Hodgkin's lymphoma developed a rapidly progressive pneumonic illness characterised by diffuse pulmonary infiltrates and hypoxaemia. The condition proved fatal in three, and in none could an infective cause be identified. A retrospective analysis revealed only one episode of pneumonia in the previous 24 patients in whom the same BACOP regimen was administered without granulocyte colony-stimulating factor support. Granulocyte colony-stimulating factor, by augmenting white cell production, pulmonary sequestration and margination and production of toxic oxygen species, may exacerbate underlying subclinical bleomycin pulmonary toxicity. Caution should be exercised before using granulocyte-stimulating factors in bleomycin-containing regimens.

Plain radiography and computed tomography of invasive thymomas: clinico-radiologic-pathologic correlation.

Fifteen computed tomography (CT) scans in nine patients with invasive thymoma are presented. The CT findings were an anterior mediastinal mass (89%), pleural deposits (78%), local infiltration of the mediastinum (100]), invasion of the cardiovascular structures (22%), lung invasion (11%) and diaphragmatic or subdiaphragmatic deposits (33%). Radiologic-pathologic correlation available in six patients showed a sensitivity of 89.5%, specificity of 87.5% and accuracy of 88.6% for CT. We conclude that CT is superior to plain radiography in the diagnosis of invasive thymoma. It provides an accurate pre-operative assessment by better demonstration of the full extent of abnormalities, and is useful in surgical planning, monitoring of therapeutic response and detecting recurrence.

'Spontaneous' regression of advanced leiomyosarcoma of the urinary bladder.

A case of advanced leiomyosarcoma of the urinary bladder is reported in a 25-year old man who, in a short time, experienced a complete 'spontaneous' regression of his fatal illness. He first presented with severe haemoperitoneum resulting from an unresectable bleeding tumour of the urinary bladder. Debulking surgery was performed, followed by salvage chemotherapy. Histological and ultrastructural examinations of the tumour confirmed a poorly differentiated leiomyosarcoma. The residual disease failed to respond to salvage chemotherapy, but regressed 'spontaneously' 5 months after cessation of therapy. The patient is alive without evidence of disease 51 months after the diagnosis. This remarkable phenomenon and relatively long survival in a poor-risk leiomyosarcoma of the urinary bladder has never been reported previously.

MR imaging of nasal T-cell/natural killer cell lymphoma.

OBJECTIVE: Nasal T-cell/natural killer cell lymphoma is a distinct clinicopathologic entity derived from natural killer cells. The purpose of the study was to describe the MR features of this rare nasal cavity tumor and correlate MR findings with stage of disease. CONCLUSION: Nasal T-cell/natural killer cell lymphoma frequently exhibits diffuse invasion of the nasal cavity with necrosis, midline destruction, and extension into the nasopharynx. These features may be seen in both early- and late-stage disease.

Non-Hodgkin's lymphoma of the nasopharynx: CT and MR imaging.

OBJECTIVE: Nasopharyngeal (NP) non-Hodgkin's lymphoma (NHL) is an uncommon tumour. The aim of the study was to describe the appearances on CT and MR imaging, and identify the features which help to distinguish NPNHL from other NP tumours. MATERIALS AND METHODS: The CT (n=8) and MR (n=10) images of 14 patients with NPNHL were reviewed retrospectively. Patients with NPNHL were divided into primary NPNHL, where the primary tumour was in the NP (n=7) and secondary NPNHL where the primary tumour was at another extranodal site in the head and neck (n=7). All NPNHL were assessed for tumour size and distribution, appearance and local tumour invasion, in addition lymphadenopathy was assessed in primary NPNHL. RESULTS: The NPNHL ranged in size from 20-75 mm (mean of 55 mm for primary and 30 mm for secondary NHL) and were homogeneous on CT in eight (100%) and MR in seven (70%) and mildly heterogeneous on MR in three (30%) patients. NPNHL involved all walls of the NP in 10 (71%) (n=1). Primary NPNHL extended superficially in five (71%) to involve the nasal cavity (n=3) and oropharynx (n=2) and lymphadenopathy was present in five (71%) being bilateral and involving multiple nodal sites (n=4) with necrosis (n=2) and matting (n=3). CONCLUSION: NPNHL is a homogeneous tumour that tends to diffusely involve all walls of the nasopharynx and spread in an exophytic fashion to fill the airway, rather than infiltrating into the deep tissues. Deep tumour infiltration, when it occurs, is found in those patients with primary NHL and is usually limited in extent and of small volume. and extended in an exophytic fashion to fill the NP cavity in six (43%). Deep tumour invasion was present in two (14%) both patients with primary NHL, the extent and volume of this tumour invasion was small and involved the prevertebral muscles (n=2), parapharyngeal fat space (n=1) and skull base Primary NHL more commonly spreads superficially to involve the nasal cavity or oropharynx, lymphadenopathy is frequent and extensive. A large tumour that fills the nasopharynx, with no or minimal invasion into deep structures, and a propensity to extend down into the tonsil, rather than up into the skull base, may suggest the diagnosis of NHL over nasopharyngeal carcinoma.

Quantitative analysis of circulating cell-free Epstein-Barr virus (EBV) DNA levels in patients with EBV-associated lymphoid malignancies.

Cell-free Epstein-Barr virus (EBV) DNA has recently been detected in the plasma and serum of patients with Hodgkin's disease, post-transplant lymphoproliferative disease (PTLD) and acquired immunodeficiency syndrome-related lymphoma. However, no data are available on the temporal variation of plasma/serum EBV DNA levels in patients with EBV-associated lymphoid malignancies during the course of therapy. Using a real-time quantitative polymerase chain reaction assay, we studied the plasma EBV DNA levels in 13 patients with EBV-associated lymphoid malignancies (six patients with Hodgkin's disease, four with nasal natural killer/T-cell lymphoma, two cases of PTLD and one patient with Burkitt's lymphoma) at presentation and during therapy. Plasma EBV DNA was detected in 12 of the 13 patients (median 2,266 copies/ml; interquartile range 181-8,379 copies/ml), but not in any of 35 healthy control subjects (P < 0.0001). The EBV status in tumour cells was also examined in 12 of these patients using in situ hybridization for EBV-encoded small RNAs (EBERs). EBER positivity was observed in 11 patients, all of whom had EBV DNA detectable in plasma. The one patient who had no detectable plasma EBV DNA was also negative for EBERs in tumour tissue. Serial measurements of plasma EBV DNA levels were performed in nine of the patients during the course of therapy. All patients who responded to therapy demonstrated a significant reduction of plasma EBV DNA to low or undetectable levels, whereas in two patients with ineffective therapy, disease progression was associated with a rapid increase in plasma EBV DNA levels. We concluded that plasma EBV DNA is detectable in a wide range of EBV-associated lymphoid malignancies. As plasma EBV DNA levels correlate well with the therapeutic response, such analysis may be a valuable tool for monitoring clinical progress.

Combined morphological and interphase fluorescence in situ hybridization study in multiple myeloma of Chinese patients.

To gain insight into the real incidence of the numeric chromosomal aberrations and the cell lineage involvement of the neoplastic process in multiple myeloma (MM), we examined 18 Chinese MM patients by May-Grunwald-Giemsa (MGG) staining and fluorescence in situ hybridization using three DNA centromeric probes specific for chromosomes 3, 7, and 9. In this investigation, cytogenetic abnormalities were detected in plasma cells (PCs), myeloid cells (MCs), and lymphoid cells (LCs) in all of the MM patients studied. This is the first demonstration of the cytogenetic aberration involved in the myeloid series. Furthermore, the MCs and PCs of 16 MM patients had the same aneuploidies in one or more of the chromosomes analyzed. These data suggest that the neoplastic transformation of MM may occur early in the hematopoietic development. Chromosomal aberrations involving mainly subclones and considerable cellular heterogeneity with gain of a variety of copy numbers of the same chromosome were demonstrated within PCs, which may possibly be the result of an underlying defect of PCs in the control of their number of chromosomes. Whereas PCs showed evidence suggestive of increased polyploidization, MCs and LCs, which exhibited similar chromosomal patterns as the former, rarely did. Thus, the clonal evolution from LC to PC, if that happens in MM, is characterized by chromosomal instability favoring growth of tumor cells with polysomies and polyploidies.

Hairy cell leukemia in Hong Kong Chinese: a 12-year retrospective survey.

BACKGROUND: Hairy cell leukemia (HCL) is a unique chronic B cell lymphoproliferative disease (B-LPD), with distinct clinical and pathological features, and excellent treatment response to 2-chlorodeoxyadenosine (2-CDA) and pentostatin. There have been few reports of HCL from oriental countries. PATIENTS AND METHODS: A retrospective survey of HCL in six major hematology units in Hong Kong over a 12-year period. RESULTS: There were 18 cases of HCL identified. Most patients presented with fever, splenomegaly and monocytopenia. Lymphadenopathy was present in three patients, and open biopsy revealed tuberculosis infection in two cases. Seven cases received interferon and 12 cases received 2-CDA. Four patients died from bronchogenic carcinoma, cerebral vascular accident, fulminant hepatitis B virus reactivation and malignant melanoma. The remaining 14 patients are in clinical remission at a median of 6 years' follow-up; two are also surviving from second malignancies (thyroid papillary carcinoma and renal cell carcinoma). CONCLUSIONS: Parallel to the low incidence of B-LPD in Chinese, the incidence of HCL (0.035/100000 population per year) is much lower than in Western series. Other clinical features such as male dominance, clinical presentation, response to 2-CDA treatment, and association with second malignancy are similar to Western reports. However, two common complications in the Chinese population are the fulminant reactivation of hepatitis B infection and disseminated tuberculosis infection.