Extranodal Presentation Research Articles

Frequencies of non-Hodgkin’s lymphoma subtypes in Kuwait: comparisons between different ethnic groups

There is a wide variation in the prevalence of various subtypes of non-Hodgkin's lymphoma worldwide. The aim of this study was to determine the relative frequency of different subtypes of non-Hodgkin's lymphoma in Kuwait based on the Revised European-American Lymphoma (REAL) classification. From 1998 to 2006, 738 subjects were included that were registered with non-Hodgkin's lymphoma in the population-based cancer registry at the Kuwait Cancer Control Center. Expert pathologists reviewed histological slides from all subjects. We performed detailed immunohistochemical studies and classified subjects based on the REAL classification. The prevalence of different types of non-Hodgkin's lymphoma was determined based on age, sex, site of disease, and ethnicity. Ethnicity groups comprised Kuwaiti Arabs, non Kuwaiti Arabs, Asians, and others. The prevalence of B- and T-cell lymphomas was 81.8% and 14.2%, respectively. The most common age group was 41-60 years old. The three most common subtypes in Kuwaiti Arabs were diffuse large B-cell lymphoma (46.5%), follicular lymphoma (15.5%), and mycosis fungoides (9.3%). In non-Kuwaiti Arabs, the most common subtypes were diffuse large B-cell lymphoma (48%), B-cell small lymphocytic lymphoma/chronic lymphocytic leukemia (15.8%), and follicular lymphoma (12.7%). Overall, non-Kuwaiti Arabs exhibited the highest prevalence (59%), and 54% of all cases had extranodal presentation. Compared to the Western world, Kuwait had a lower prevalence of follicular lymphoma, a higher prevalence of diffuse large B-cell lymphoma and extranodal presentation, and a high frequency of mycosis fungoides. Compared to other parts of Asia, Kuwait had a lower frequency of peripheral T-cell lymphomas.

A case of extranodal NK/T-cell lymphoma, nasal type mimicking typical manifestations of adult-onset Still’s disease (AOSD) with hemophagocytic syndrome: diagnostic consideration between malignant lymphoma without lymphadenopathy and AOSD

A 25-year-old Japanese man was suffering from high fever, sore throat, arthralgia, and macular salmon-pink eruption. The superficial lymph node was not palpable, and computed tomographic scans from the neck to pelvis demonstrated hepatosplenomegaly without apparent lymphadenopathy. Therefore, the possibility of malignant lymphoma was considered to be extremely low. Serology for Epstein Barr virus (EBV) and cytomegalovirus showed a postinfectious state, and blood culture was negative. Serum rheumatoid factor and antinuclear antibody were negative. Leukocytopenia (2.4 x 10(3)/mul) was observed, and thus a diagnosis of adult-onset Still's disease (AOSD) with hemophagocytic syndrome (HPS) was made. Fifty-five milligrams of prednisolone daily improved his symptoms and leukocytopenia promptly, but high fever with severe and progressive thrombocytopenia occurred 12 days later. Bone marrow aspiration revealed the presence of lymphoma cells and hemophagocytosis, and the CD45 gating analysis showed expanding population of CD2(+), CD3(-), and CD56(+) cells. Further, mucosal ulceration in the nasal cavity was detected. Therefore, a diagnosis of extranodal natural killer (NK)/T-cell lymphoma, nasal type, concomitant with HPS was made, and treatment with dexamethasone, etoposide, ifosfamide, carboplatin (DeVIC) regimen ameliorated his symptoms and platelet transfusion dependency. Later, a high titer of serum EBV-DNA was detected, which supported the diagnosis. Diagnosing AOSD, extranodal presentation of malignant lymphoma such as extranodal NK/T-cell lymphoma, nasal type, should be carefully considered.

Rare Natural Killer Cell Lymphoma Found During Surveillance Endoscopy

Non-Hodgkin's lymphoma is the sixth leading cause of cancer death in the USA and comprises 2-3% of primary neoplasms. Natural killer (NK)/T cell lymphomas are subtypes of non-Hodgkin's lymphoma and are aggressive neoplastic disorders with frequent extranodal presentations. Clinically, most cases of aggressive NK cell lymphomas present in young males with massive hepatosplenic infiltration. The upper aerodigestive tract is the most common site of presentation. NK/T cell lymphomas are subtypes of non-Hodgkin's lymphoma and are aggressive. Here we describe an unusual case of non-Hodgkin's NK/ T cell lymphoma of colon and stomach found during surveillance upper endoscopy followed by a subsequent colonoscopy.

Specific expression of miR-17-5p and miR-127 in testicular and central nervous system diffuse large B-cell lymphoma

Recent studies have shown that certain non-coding short RNAs, called miRNAs, play an important role in diffuse large B-cell lymphomas. Patients with diffuse large B-cell lymphoma have great diversity in both clinical characteristics, site of presentation and outcome. The aim of our study is to validate the differential expression in germinal center and non-germinal center diffuse large B-cell lymphoma,s and to study to the extent to which the primary site of differentiation is associated with the miRNA expression profile. We studied 50 cases of de novo diffuse large B-cell lymphoma for the expression of 15 miRNAs (miR-15a, miR-15b, miR-16, miR-17-3p, miR-17-5p, miR-18a, miR-19a, miR-19b, miR-20a, miR-21, miR-92, miR-127, miR-155, miR-181a and miR-221). Apart from 19 nodal cases without extranodal dissemination (stages I and II), we selected two groups with unambiguous stages I and II extranodal presentation; 9 cases of primary central nervous system, 11 cases of primary testicular and 11 cases of other primary extranodal diffuse large B-cell lymphomas. All cases were analyzed with qRT-PCR. In situ hybridization for the most differentially expressed miRNAs was performed to show miRNA expression in tumor cells, but not in background cells. MiR-21 and miR-19b showed the highest expression levels. No significant differences were seen between germinal center and non-germinal center diffuse large B-cell lymphomas in either the total or the nodal group for any of the 15 miRNAs. Two miRNAs showed significant differences in expression levels for diffuse large B-cell lymphoma subgroups according to the site of presentation. MiR-17-5p showed a significant higher expression level in the central nervous system compared with testicular and nodal diffuse large B-cell lymphomas (P<0.05). MiR-127 levels were significantly higher in testicular than in central nervous system and in nodal diffuse large B-cell lymphomas (P<0.05). We conclude that the location of diffuse large B-cell lymphoma is an important factor in determining the differential expression of miRNAs.

Primary testicular non-Hodgkin lymphoma: A single institution experience from India

Primary testicular non-Hodgkin lymphoma (NHL) is an uncommon extra nodal presentation, constituting 1% of all NHL. Median age at time of presentation is 60 years. Anthracycline based chemotherapies are most frequently used. There is not enough data on use of monoclonal antibody (Rituximab) in testicular NHL. We screened approximately eight hundred and fifty NHL cases registered from January 2002 to May 2008 and found six primary testicular NHL patients. These six cases were analyzed for baseline clinical features, investigations, staging, treatment and outcome variables. Median age was 55 years (range 7-72 years) and median duration of symptoms was 3.5 months (range 1-8 months). All patients had testicular swelling and abdominal lymphadenopathy. Five patients (83%) had stage IV and one had stage IE disease. Majority had diffuse large B-cell histology (83%). All patients were treated with anthracycline based combination chemotherapy and CNS prophylaxis after local therapy except one pediatric patient who did not receive any local therapy. Four patients completed therapy and are on follow up while two patients having extensive disease with poor performance status died of neutropenic sepsis after 1-2 cycles of chemotherapy. The surviving four patients achieved complete remission and are without any recurrence with a median follow up of 26 months (1-78 months). Primary testicular NHL is an uncommon entity and with current combined modality treatment and CNS prophylaxis, the outcome may be as good as nodal NHL.

Marginal Zone Lymphoma: Factors That Affect the Final Outcome, a Study of 275 Patients

Purpose: Retrospective review and analysis of 275 patients with marginal zone lymphoma (MZL) to determine the prognostic factors that affect outcome in an effort to find a specific prognostic score.Materials and Methods: Two hundred and seventy five patients with pathologically confirmed MZL were studied. Their median age was 60 years (range 18–89). Male sex was found in 123 patients (45%). Ann Arbor stage I was present in 104 patients (38%), stage II in 27 (10%), stage III in 16 (6%), stage IV in 124 (45%), and unknown in 4 (1%). Most patients were asymptomatic at presentation (90%), with 96% presenting with Zubrod score of 0 or 1. Patients were divided into three groups according to sites of involvement: extranodal (211), nodal (27), and splenic (37). Treatment strategy consisted of: observation in 75 (27%), chemotherapy in 103 (37%), combined chemotherapy and radiation in 24 (9%), and definitive radiation in 71 (26%).Results: Both univariate and multivariate analysis showed that splenic presentation had a better outcome with a hazard ratio (HR) of 0.14 and p value=0.006, while extranodal presentation with bone marrow involvement had an inferior outcome with HR of 2.27 and p value =0.045. Two factors were found to be associated with decreased overall survival (OS) in the multivariate analysis: Older age (p=0.007) and beta 2 microglobulin >1.8 mg/L (p <0.0001). On the other hand splenic presentation and being asymptomatic at presentation were associated with an improved OS with a p value of 0.002 and 0.017, respectively. Stage at presentation had no impact on the overall survival or disease free survival, and although all patients with splenic MZL were stage IV, these patients had the best outcome. Nodal presentation had a similar survival to extranodal presentation.Conclusion: Splenic presentation even at advanced stage is associated with a better outcome. Bone marrow involvement in patients with extranodal presentation had a lower OS. Older age, high beta 2 microglobulin, and symptoms at presentation adversely affected the overall survival of patients with MZL.

Diffuse Large Cell Lymphoma Transformed from Rosai-Dorfman Disease

INTRODUCTION: Rosai-Dorfman disease, also known as Sinus Histiocytosis with Massive Lymphadenopathy, is an almost rare benign entity which mimics non-Hodgkin's lymphoma, and is characterized by enlargement of lymph nodes. Knowing the difference between these two diseases is critical for the adequate therapeutic approach. The most common presentation of the disease is within the cervical basin, and most of the times, lymph node dissection and removal of their chains is enough for cure.PATIENT AND METHODS: We describe a 23-yo white woman with past history of persistent cervical lymphadenopathy, who underwent 4 surgical procedures to remove left cervical nodes, diagnosed as Rosai-Dorfman disease within the last 3 years. When relapse after the 4th surgery happened, the patient came to our Service and sought for a 2nd opinion consultation.RESULTS: Pathology reviews were done on the previously collected material, corroborating Rosai-Dorfman disease, except for the review of the slides of the last material, which showed inconclusiveness. Histopathology and immunohistochemistry were then repeated for the last surgical specimens at 2 different Pathology labs, and both confirmed diffuse large cell lymphoma. Patient started on chemo with CHOP 6×, and showed a partial response up to the 3rd cycle, when the tumor started progressing during the 4th cycle. Chemo was then changed to ESHAP, which was well-tolerated and promoted CR after 6 cycles. The patient is currently in CR and asymptomatic.CONCLUSION: Rosai-Dorfman disease is a proliferative reaction to an unknown, unidentified pathogen or specific cause, which leads to lymph node enlargement and extra nodal involvement in 25% of the cases. Some studies have attempted to correlate the presence of klebsiella as a proliferative stimulus present in this disease, but there is not enough evidence to confirm this hypothesis. Interestingly, it may seem that Rosai-Dorfman is a middle step between a truly benign process and malignancy itself because, not only other cases of lymphoma transformed after Rosai-Dorfman's disease have been reported, but also extra nodal cancer following extra nodal presentation of the disease. Although many clues point to its involvement in the process of carcinogenesis, more clinical and molecular evidence are necessary to tie the link between Rosai-Dorfman disease and cancer.

Extranodal lymphoma: a reappraisal

Approximately one-third of non-Hodgkin lymphomas (NHLs) arise primarily from sites other than lymph nodes, spleen or the bone marrow and even from sites which normally contain no native lymphoid tissue [1, 2]. Indeed, extranodal lymphomas can arise in almost every organ [1, 2]. However most of the presentations appears to be clustered in a few sites: skin, stomach, brain, small intestine and—when included in the reports—the Waldeyer’s ring [3, 4]. The extranodal lymphomas represent a challenge in routine lymphoma diagnosis, due to the variety of histological types, molecular abnormalities and clinical pictures that can be present. Correct diagnosis and appropriate treatment of extranodal lymphoma are also complicated by the relative rarity of many of these tumours. Moreover, in comparison with nodal presentation, Band T-cell lymphomas diagnosed at extranodal sites may have quite different outcomes and may frequently require different therapeutic approaches due to specific organ-related problems. The definition of primary extranodal lymphoma is controversial, particularly in the presence of both nodal and extranodal disease. Strict criteria were first proposed in 1961 by Dawson, who defined primary gastric lymphoma as presentation with main disease manifestation in stomach, with or without involvement of regional lymph nodes. Later these criteria were extended to allow for contiguous involvement of other organs (e.g. liver, spleen) and for distant nodal disease providing that the extranodal lesion was the presenting site and, after routine staging procedures, constituted the predominant disease bulk, to which primary treatment must be directed [3]. The inclusion among primary extranodal lymphomas of cases presenting with stage III and IV is also questionable and several authors consider only stage I and II presentation as primary extranodal disease. Since many extranodal lymphomas have the potential to disseminate, this approach may, however, lead to an imperfect representation. On the other hand, extranodal involvement in a disseminated disease may represent a secondary spread. Any chosen definition inevitably introduces a selection bias; in a recent Dutch study the frequency of extranodal NHL fluctuated from 20% to 34% depending on the definition criteria adopted [5]. The incidence of extranodal NHL in Western countries has increased substantially in the last 40 years [4, 6]. This may in part be due to improved diagnostic procedures (particularly in brain and gastrointestinal lymphomas) and changes in classification systems, but much of the change is real and the AIDS epidemic in the 1980s does not completely explain this rise [4]. The aetiology of extranodal lymphomas appears to be multifactorial and includes immune suppression, infections, both viral and bacterial, and exposure to pesticides and other environmental agents. Nevertheless, despite the considerable progress made in the understanding of MALT lymphoma and its relationship to bacterial infections [7], the precise cause of most lymphoid neoplasms remains unknown [1–3]. The proportion of NHL presenting at extranodal sites comprises 25–50% of new lymphoma cases with important geographic variations that may be explained by the variability of the reporting criteria (variable definitions of primary extranodal disease) as well as by different types of data source (referral cancer centres versus tumour registry). True geographic differences are, however, present, for example, the incidence of Epstein–Barr virus and human T-cell lymphotropic virus 1-associated T-cell lymphomas is higher in Asia than in Europe and North America. The histological spectrum of extranodal lymphomas somehow differs from that of nodal lymphomas. Nearly half of the extranodal cases are of diffuse large cell histology. Aggressive subtypes, mainly diffuse large B-cell lymphomas (DLBCLs) are predominant in NHL of central nervous system (CNS), testis, bone and liver while in the gastrointestinal tract a large spectrum of histological disease entities can be seen, comprising DLBCL, MALT lymphoma (including the immunoproliferative small intestinal disease), Burkitt’s lymphoma, enteropathy-associated T-cell lymphoma, mantle cell lymphoma and follicular lymphoma. Although extranodal lymphomas are not rare, the frequency of involvement of any particular site is not high enough for a single institution to answer the major question about their natural history and proper therapy. Attempting to overcome these difficulties, in the late 1990s, the International Extranodal Lymphoma Study Group (IELSG) was created to provide an adequate network to study the extranodal lymphomas. This international collaboration has originated a number of retrospective and prospective trials aimed to clarify the management issues distinct to extranodal presentations (http://www.ielsg.org). Whether or not extranodal lymphomas as a whole have a worse overall survival in comparison with that of nodal cases The author reports no relationships with companies whose products or services are mentioned in this manuscript.

Sudden Extramedullary T-Lymphoblastic Blast Crisis in Chronic Myelogenous Leukemia

Imatinib has dramatically altered the natural history of chronic myelogenous leukemia (CML), with the majority of patients now experiencing long-term remission and improved survival. However, in addition to the well-described phenomenon of resistance to imatinib, typically due to point mutations, uncommon consequences (eg, the development of Philadelphia chromosome-negative clones) may infrequently occur. We report 2 cases of sudden BCR/ABL1+ blast crisis in patients with CML who had achieved complete hematologic remission with imatinib therapy but were obligated to discontinue therapy owing to pancytopenia. These sudden blast crises were unusual at 3 levels: first, they were of precursor T lymphoblastic lineage; second, they had a primary extranodal presentation without overt bone marrow involvement; and third, they developed after recent cessation of imatinib. These observations suggest that the occurrence of 2 such rare cases in a single institution within a 1-year time frame may reflect another unusual consequence of imatinib therapy.

Distribution and Pathology Characteristics of Non Hodgkin Lymphoma in Peru: A Study of 1014 Cases Using WHO Classification of Lymphoid Neoplasm.

BACKGROUND: The frequency of various subtypes of non-Hodgkin's lymphoma (NHL) differs in various regions worldwide.OBJECTIVE: To investigate the clinical and pathological features of non-Hodgkin's lymphoma (NHL) and to evaluate the applicability of the new WHO classification of lymphoid neoplasms.METHODS: According to the new WHO classification, a total of 1014 cases of non-Hodgkin's lymphoma diagnosed during the period 2002–2006 were reviewed and reappraised with their morphological, immunological and clinical characteristics in one general hospital from Lima, Peru. All cases corresponded >18 years old.RESULTS: There were 535 males and 479 females, mean age was 62.1 years (range 18 – 97 years) and the median was 64 years. B-cell neoplasms accounted for 763 cases (75.2%) and T/NK-cell neoplasms for 189 (18.6%). Sixty two cases (6.1%) were not classified. It was seen compared to that in the other Asian countries. Indolent lymphomas accounted for 17%, and aggressive ones for 83%. Among indolent lymphomas follicular grade I and II were the most common subset while MALT was second with low frequency. Among the aggressive lymphomas diffuse large cell lymphoma (DLCL) was the most common subtype, and accounted for 58.8% of all B cell lymphomas. Mantle and Burkitt lymphoma were very low incidence. Among the T cell lymphomas, peripheral T cell lymphomas, mycosis fungoides, Adult T Lymphoma/Leukemia (ATLL), T/NK nasal type Lymphoma were the most common subtypes. Nodal NHL occurred in 52% and extranodal in 48% of the cases. The more common extranodal presentation was stomach (14.1%), skin (8.1%), small intestine (2.9%) and nose (2.3%)CONCLUSIONS: The high incidence of T cell lymphomas, extranodal presentation and reduced frequency of indolent lymphoma in the current study is comparable to that reported from Asian countries.

A Comparative Study of Diffuse Large B-Cell Lymphoma (DLBCL) between African Americans and Caucasians: Single-Center Experience at the University of Alabama at Birmingham (UAB).

Background: SEER data indicate that African Americans (AA) have a lower incidence of DLBCL but a higher mortality rate than Caucasians (C). To investigate this, we conducted a single-center analysis of AA and C patients with DLBCL at UAB. UAB is a primary care facility and the main tertiary referral center in Alabama. It is located in Jefferson County where the average African American population of 39% is nearly triple the national average.Methods: After IRB approval, patients diagnosed with DLBCL from 1995 to 2007 were identified from pathology, referral, and UAB tumor registry databases. Baseline demographic data including race, age at diagnosis, stage, treatment administered, response to treatment, and survival were extracted. Serum LDH levels and performance status were not consistently available in medical records and therefore not included in the final analysis. Patients with monomorphic post-transplant lymphoproliferative disease and primary CNS lymphoma were excluded. Associations between race and stage, treatment (first-line rituximab, anthracycline, or combination therapy), response, and outcome were analyzed using Chi-squared or Cochran Mantel-Haenszel statistical analysis.Results: A total of n=309 (n=32 AA and n=277 C) patients were identified. AA patients were diagnosed at a significantly younger age than C patients [median age 49 (range: 22–90) vs. 61 (range: 16–91), respectively; p=0.0131]. AA patients also presented with advanced stage disease (Ann Arbor stage III–IV) more frequently (69% vs. 52%, p=0.046). No difference in extranodal disease presentation or in complete response rate to first-line therapy was noted. As expected, those with early stage disease, age <60, and those given first-line rituximab +/− anthracycline therapy had superior survival regardless of race. No difference in overall survival was seen between AA and C patients (p=0.1306). However, AA patients had an inferior survival to C patients when the analysis was restricted to patients who received either first-line treatment with rituximab (p=0.0658), anthracycline (p=0.0188), or combination (p=0.0196). [Display omitted] Conclusions: Compared to C patients, AA patients were diagnosed with DLBCL at a significantly younger age, more advanced stage, and had worse survival despite first-line rituximab +/− anthracycline therapy. This single-center experience confirms SEER data and suggests a possible difference in tumor biology or treatment effect, although potential socioeconomic factors can not be excluded.

Multifocal, Extranodal Sinus Histiocytosis With Massive Lymphadenopathy: An Overview

This article provides an overview of the major pathologic manifestations of sinus histiocytosis with massive lymphadenopathy, including patient characteristics and current knowledge about its pathogenesis, with an emphasis on multifocal and extranodal presentation. Sinus histiocytosis with massive lymphadenopathy is a rare, nonneoplastic, idiopathic, proliferative histiocytic disorder; recognition of this disorder is important to avoid misinterpretation and subsequent unnecessary treatment. This is especially true for primary extranodal manifestation of this rare disorder. Although accurate diagnosis of this entity requires a correlation of clinical, radiologic, laboratory, and pathologic studies in most cases, it remains a disorder primarily defined by its histopathologic features and pathologic manifestations, which are key to the diagnosis. To summarize the scientific literature, provide a concise review, and emphasize the diagnostic histopathologic features of extranodal sinus histiocytosis with massive lymphadenopathy. A comprehensive literature review was undertaken to summarize the clinical and pathologic features of this disorder. Sinus histiocytosis with massive lymphadenopathy is characterized by a rare, acquired, nonmalignant proliferation of distinctive histiocytes that present with lymphadenopathy or extranodal disease, primarily in children and young adults. It exhibits a broad range of clinical presentations, thus eliciting a wide differential diagnosis. The diverse clinical manifestations and frequent association with subtle or severe immunologic abnormalities suggest an immune-mediated cause. Additional studies are needed to characterize the interplay between death receptors and cytotoxic mediators and to further elucidate the loss of immune hemostasis that may underlie idiopathic histiocytic proliferations such as this.

Diffuse large B‐cell lymphoma in the young in Japan: A study by the Osaka Lymphoma Study Group

Clinicopathological and immunophenotypical characteristics in 24 patients with diffuse large B-cell lymphoma (DLBCL) under 30 years of age in Osaka, Japan were examined, and the results compared to those of DLBCL patients aged over 40 years in Osaka and of young DLBCL patients in Western countries. The level of LDH and IPI score at initial diagnosis were significantly lower in young than older patients. The sex ratio (M:F) and age range (median) in the young and older groups were 1.18 and 11-30 (24.8) years and 1.59 and 42-87 (62.4) years, respectively. Extranodal presentation was higher in the young group (83.3% versus 60.0%, P < 0.05). Based on immunophenotyping with anti-CD10, bcl-6, and MUM1 antibodies, the cases were categorized as germinal center B-cell (GCB) (CD10+ or CD10-, bcl-6+, MUM1+) or non-GCB phenotype. The frequency of GCB type was significantly lower in the young group than older group (25% vs. 54%, P < 0.05), and much lower than that reported for young patients in Western countries. In situ hybridization revealed one of the young patients to be positive for Epstein-Barr virus (EBV). In the older group, none of 31 cases showed EBV positivity. Three year event-free and overall survival rates of young patients were better than those of the older patients, although not significantly different. DLBCL in the young in Japan is characterized by a much lower frequency of the GCB phenotype compared to that in Western countries.

CMED in the treatment of nasal natural killer cell lymphoma with distant metastases

Introduction: Nasal natural killer (NK) cell lymphoma that showed distant metastases generally showed an poor prognosis. We described a group of patients with these atypical presentation and that were treated with an intensive, short chemotherapy/radiotherapy regimen.Methods: Sixty-one patients fulfilled the criteria for NK cell lymphoma with distant metastases and all have very poor prognostic factors: high clinical risk, multiple extranodal presentation and bulky disease (tumor mass >10 cm). They were treated with CMED (cyclophosphamide 2000 mg/m2, iv, day 1, methotrexate 400 mg/m2, iv, day 1(with leucovorin rescue), etoposide 400 mg/m2 twice and dexametasone 40 mg daily for 4 days). If complete response (CR) was observed, they were received adjuvant radiotherapy (50 Gy) to nasal region. Patients with failure were treated with different salvage treatments.Results: Forty nine patients achieved CR and 12 were considered failure, all patients that were failure and nine that relapse die secondary to tumor progression. Median follow-up were 46 months (range 34-68 months). Median has not been observed in relapse-free survival (RFS) and overall survival (OS). Actuarial curves at 5 years showed that RFS was 81% and OS was 65%. Treatment was well tolerated.Conclusions: Nasal NK cell lymphoma with distant metastases is considered an rare clinical entity, probably is under diagnosis because it has been included as stage III and IV in previous reports, that showed an very poor RFS and OS. The treatment herein report could achieve good response and outcome, but it is evident that more specific and aggressive therapy is necessary in these setting of patients.

CD52 expression in non-mycotic T- and NK/T-cell lymphomas

CD52 antigen (Campath-1) is expressed in high density by lymphocytes and monocytes. Campath-1H or alemtuzumab, a human anti-CD52, has been shown to be effective in T-cell malignancies; however, there is very limited information on CD52 expression in T-cell lymphoma (TCL). This study retrospectively investigated 97 TCL cases by immunohistochemistry using paraffin sections to elucidate the CD52 expression rates in various TCL sub-types. Fourteen cases of angioimmunoblastic T-cell lymphoma (AITL) were excluded as there were no reliable criteria to differentiate whether the CD52-positive cells were neoplastic T-cells, which are usually small-sized, or the usually abundant, small-to-large residual/reactive B-cells in this lymphoma sub-type. In the remaining 83 tumors, CD52 was expressed in 29 (35%) tumors including 8/17 (47%) NK/T-cell lymphomas, 14/35 (40%) unspecified peripheral TCLs and 4/18 (22%) anaplastic large cell lymphomas. There was no statistical significance in CD52 expression in terms of patient age, gender, nodal vs extra-nodal presentation or tumor sub-types. The authors recommend performing CD52 immunostaining for future clinical trials of alemtuzumab on TCL patients and to correlate the staining results with treatment outcome.

Unusual Presentation of Large B Cell Lymphoma- Bone and Stomach- Treated with Autologous Transplantation

Extranodal presentation of diffuse large B cell lymphoma (DLBL) is frequently observed in the gastrointestinal tract, CNS, bone, testes and liver. However, the simultaneous detection of multiple extranodal involvement at presentation is quite an uncommon occurrence. In this study, we report on a patient with an uncommon presentation of DLBL, and he had symptoms of left knee joint pain and hematemesis, characterized by bone and stomach involvement. Computed tomography and fluorodeoxyglucose-positron emission tomography (FDG-PET) scanning revealed a rapid, extensive spread to the bones and soft tissues. Subsequent histopathological examination verified the bony and gastric CD20-positive DLBL localization. We diagnosed this case as DLBL of stage IV with an international prognostic index of 3, and classified him into the high intermediate risk group. This patient was treated via chemotherapy with an R-CHOP regimen. After achieving a partial response, the patient received autologous peripheral blood stem cell transplantation. The patient attained partial remission, as shown on the FDG-PET scan, and he displayed improvement of his left femur pain.

Aggressive Natural Killer Cell Leukemia: Report of a Chinese Series and Review of the Literature

Aggressive natural killer cell leukemia (ANKL) is a rare Epstein-Barr virus (EBV)-associated fulminating disease that is widely disseminated at diagnosis. Because of its typically extranodal presentation, differing degrees of NK cell involvement, and varying bone marrow pathology, ANKL can be confused with a reactive process. These features, coupled with a rapidly fatal course, have hampered systematic study of the pathogenesis of ANKL. Nine cases of ANKL were diagnosed and characterized by a single laboratory over a 2-year period. Constant features at presentation included disseminated disease, high fever, bone marrow involvement, and a high lactate dehydrogenase index. All cases were positive for EBV early region protein and negative for latent membrane protein 1, and all had a germline T-cell receptor gene configuration. Peripheral blood counts were variable, with severe thrombocytopenia being the most frequently encountered abnormality (7 of 9 cases). Hematophagocytosis, dyserythropoiesis, and stromal degeneration were the most frequent findings in the bone marrow. Neoplastic cells in the bone marrow were consistently CD2+, CD56+, CD45+, CD34-, CD117-, CD4-, and surface CD3-. Most cases were HLA-DR+ (8/9) and CD8- (8/9). Complex clonal cytogenetic abnormalities were found in 8 of 9 cases. Because of its aggressive course, rapid and accurate diagnosis of ANKL is essential for a better understanding of the etiology, pathogenesis, and treatment of the disease.

CD56-Positive Large B-cell Lymphoma

CD56 (NCAM), a neural adhesion molecule, is normally expressed on natural killer cells and subsets of T cells and is commonly seen on hematolymphoid neoplasms such as plasma cell myeloma and acute myelogenous leukemia. It is uncommon in B-cell lymphoma. From 2001 to 2003 a cohort of 20 cases of CD56 B-cell lymphomas was identified by flow cytometry (<0.5% of all B-cell lymphomas studied) during a 2-year period. Most (90%) expressed CD10 and 5/5 tested cases were BCL6, suggesting a follicular origin. An extranodal disease presentation was seen in 45% and may be related to CD56 expression. These CD56 B-cell lymphomas may represent a new subset of large B-cell lymphoma. The relationship of cells with this antigenic profile to normal B-cell differentiation is explored.

Tissue Microarray (TMA) Study in DLBC Lymphomas (DLBCL): Could the Extranodal Origin Affect the Prognostic Impact of the Analysis?.

DLBCL can be divided into two prognostically different subgroups, germinal center B-cell-like (GCB) and activated B-cell-like (ABC), according to twodifferent gene patterns identified with cDNA microarray technology. Though valuable, this technology is expensive and not generally available. However, the identification of individual antigens related to different stages of B-cell differentiation using immunohistochemistry, can be used to assess the two profiles yielding comparable results with respect to cDNA microarray technique. We have retrospectively investigated 105 patients (pts) diagnosed with de novo DLBCL and treated at our centre between November 2001 and June 2004; the only inclusion criteria was the availability of a tissue biopsy at diagnosis. Median age was 62 (19–85); stage at diagnosis was I–II in 49 pts (47%), III in 14 pts (13%) and IV in 42 pts (40%); according to IPI, 74 (70%) pts were defined as low (0–2) and 31 (30%) as high risk (3–5). Interestingly, the majority (53%) of our pts, had a primary extranodal lymphoma at diagnosis. TMA analysis was performed with antibodies to CD10, bcl-6 and MUM1 allowing the following classification: 50 pts (48%) were considered having CGB lymphoma and 55 pts (52%) having ABC disease. According to IPI risk score, 38 pts with CGB and 36 with ABC lymphoma were at low risk (0–2) whereas 10 with CGB and 16 with ABC lymphoma were at high risk (3–5). All pts received a median of 6 cycles of a CHOP-like, antracycline-based polychemotherapy. Observed ORR was 89% (94/105); 62 (59%) pts achieved a CR, 32 (30.5%) a PR while 11 (10.5%) failed to respond to treatment. Median follow-up of the surviving pts was 45 months ( 5–110). The 3-year OS for the entire group was 71% and the 3-year EFS was 54%. In terms of CR, PD and resistance to therapy, no difference was observed between the two TMA types of DLBCL. Pts obtaining a CR after 1st line treatment were equally distributed in both groups (28.6% in CGB vs 30.5% in ABC) as were those not responding to therapy (3.8% in CGB versus 6.7% in ABC). A separate analysis in pts with stage IV disease at diagnosis was also performed and showed similar results (40.5% of CR, 23.8% of NR; no difference was observed between the two TMA defined subgroups). Pts who experienced a PD at any time, were equally distributed between the 2 subgroups, either if they relapsed after first line therapy (6 pts in CGB group , 10 in the ABC one) or after any other subsequent treatment (12 in the CGB group, 18 in the ABC one). Furthermore, 39 of 56 (69%) patients with extranodal presentation at diagnosis showed a CR independently of their subgroup distribution (37.5% in the CGL group vs 32.1% in the ABC one), and pts experiencing a PR were equally distributed between the two groups. Our data do not support the use of TMA to predict outcome in DLBCL. However, previously published data supporting the prognostic impact of TMA, have not enrolled pts with lymphomas of primary extranodal origin which, instead, were the majority in our study. Indeed, the study by Colomo et al, which enrolled 39% of pts affected by extranodal lymphomas, also failed to demonstrate a role of TMA in predicting outcome in DLBCL pts. Furthermore, the use of a limited number of antigens to define different subtypes of DLBCL may not be sufficient to identify the same patterns as defined by cDNA microarray technology.

Unusual presentation of large B cell lymphoma: a case report and review of literature

Diffuse large B cell lymphoma (DLBCL) is the largest subtype of non-Hodgkin's lymphomas (NHLs) and is characterized by relatively frequent extranodal presentation. In these cases, the most common extranodal localizations are stomach, CNS, bone, testis and liver. Simultaneous detection of multiple extranodal involvement at presentation is quite uncommon, with the majority of these cases characterized by gastric or intestinal disease localization. Retrospective analysis concerning multifocal extranodal NHLs never pointed out disease features such as those described here. We report a patient with an unusual presentation of DLBCL, characterized by adrenal and renal involvement, associated with symptoms and signs of the cold agglutinin disease and a hypercoagulable state. Subsequently, computed tomography (CT) and fluorodeoxyglucose-positron emission tomography (FDG-PET) scanning disclosed a rapidly extensive spread to nodes and bones. Cytofluorimetric analysis of a renal specimen showed medium-to-large lympho-monocytoid elements positive for CD20 with monoclonal expression of immunoglobulin kappa light chain. Histopathological examination confirmed a renal CD20 positive DLBCL localization.