Primary Large Cell Lymphoma Research Articles

Diffuse large B-cell lymphoma (DLBCL): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Diffuse large B-cell lymphoma (DLBCL): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

EComment. Primary cardiac malignancy

An interesting case report is presented by Liu et al [1]. A 41-year old immunocompetent female patient underwent a surgical excision of a primary cardiac B-cell lymphoma (74 mm x 49 mm) from the right atrium. Only 25% of primary cardiac tumours are malignant, and sarcomas represent more than two-thirds of these malignancies. Primary cardiac lymphoma (PCL) is the second most common malignancy affecting the heart. Thus, PCL is a very rare entity and is classified as primary lymphomas inside the heart chamber, primary lymphomas developing in the epicardial space and primary large cell lymphomas involving the pericardium. PCL is defined by the absence of lymphoma outside the pericardium after a complete clinical and radiological examination and by the confinement of the bulk of the tumour to the pericardial sac. Cardiac metastases of extra-cardiac lymphomas are far more common than PCL. This case report has an interesting feature that could be of use to all of us when faced with a symptomatic right a trial tumour in a young patient. Cardiac surgeons should be highly suspicious of primary cardiac malignancy when the signs are suggestive. Right-sided cardiac tumours are usually malignant and appear as infiltrative, bulky and fast- growing masses that develop in an outward fashion. They do not present with congestive heart failure until the later stages of disease progression. The diagnostic algorithm of choice when suspecting a primary cardiac malignancy is to perform after transthoracic echocardiography, cardiac computed tomography and cardiac magnetic resonance imaging [2]. Cardiovascular magnetic resonance can recognize, with high specificity, non-surgical cardiac masses: pseudo-tumours, lipomas, thrombi, and lipomatous hypertrophy. Most other cardiac tumours will necessitate tissue sample diagnosis to help in the establishment of a treatment plan. Should the use of multiple imaging techniques fail to identify the cardiac mass at the outset, a biopsy (percutaneous endomyocardial biopsy or a biopsy by thoracotomy) is best obtained if it can be done safely [3]. This will not only diagnose the tumour but will exclude benign masses and other malignant tumours, such as lymphoma, that are best treated non-surgically. Treatment of PCL is usually bimodal [4] with aggressive systemic chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone) as well as radiation therapy. Conflict of Interest: None declared

Uncertainty and discordance in the staging and prognosis of diffuse large B‐cell lymphoma with isolated bilateral testicular involvement

American Journal of HematologyVolume 84, Issue 11 p. 762-763 LetterFree Access Uncertainty and discordance in the staging and prognosis of diffuse large B-cell lymphoma with isolated bilateral testicular involvement† Ronald S. Go, Corresponding Author Ronald S. Go [email protected] Center for Cancer and Blood Disorders, Gundersen Lutheran Health System, La Crosse, WisconsinCenter for Cancer and Blood Disorders, Gundersen Lutheran Health System, Mail Stop: EB2-001, 1900 South Avenue, La Crosse 54601, WI 54601Search for more papers by this authorJacob D. Gundrum, Jacob D. Gundrum Department of Medical Research, Gundersen Lutheran Medical Foundation, La Crosse, WisconsinSearch for more papers by this author Ronald S. Go, Corresponding Author Ronald S. Go [email protected] Center for Cancer and Blood Disorders, Gundersen Lutheran Health System, La Crosse, WisconsinCenter for Cancer and Blood Disorders, Gundersen Lutheran Health System, Mail Stop: EB2-001, 1900 South Avenue, La Crosse 54601, WI 54601Search for more papers by this authorJacob D. Gundrum, Jacob D. Gundrum Department of Medical Research, Gundersen Lutheran Medical Foundation, La Crosse, WisconsinSearch for more papers by this author First published: 10 August 2009 https://doi.org/10.1002/ajh.21522Citations: 4 † Conflict of interest: Nothing to report. AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL References 1 Carbone PP,Kaplan HS,Musshoff K, et al. Report of the committee on Hodgkin's disease staging classification. Cancer Res 1971; 31: 1860– 1861. 2 Gospodarowicz M. Individuality versus conformity. Is perfection necessary in staging and prognostic classifications of specific primary extranodal lymphomas? Ann Oncol 1999; 10: 1405– 1407. 3 Armitage JO. Staging non-Hodgkin lymphoma. CA Cancer J Clin 2005; 55: 368– 376. 4 Zucca E,Conconi A,Mughal TI, et al. Patterns of outcome and prognostic factors in primary large-cell lymphoma of the testis in a survey by the international extranodal lymphoma study group. J Clin Oncol 2003; 21: 20– 27. 5 Bentley RC,Devlin B,Kaufman RE, et al. Genotypic divergence precedes clinical dissemination in a case of synchronous bilateral B-cell malignant lymphoma of the testes. Hum Pathol 1993; 24: 675– 678. 6 Salvatore JR,Ross RS. Primary bilateral adrenal lymphoma. Leuk Lymphoma 1999; 34: 111– 117. 7 Ryan G,Martinelli G,Kuper-Hommel M, et al. Primary diffuse large B-cell lymphoma of the breast: Prognostic factors and outcomes of a study by the international extranodal lymphoma study group. Ann Oncol 2008; 19: 233– 241. 8 Hoffman PM,McKelvie P,Hall AJ, et al. Intraocular lymphoma: A series of 14 patients with clinicopathological features and treatment outcomes. Eye 2003; 17: 513– 521. 9 Kojima M,Shimizu K,Nishikawa M, et al. Primary salivary gland lymphoma among Japanese: A clinicopathological study of 30 cases. Leuk Lymphoma 2007; 48: 1793– 1798. 10 Decaudin D,de Cremoux P,Vincent-Salomon A, et al. Ocular adnexal lymphoma: A review of clinicopathologic features and treatment options. Blood 2006; 108: 1451– 1460. 11 Cordier JF,Chailleux E,Lauque D, et al. Primary pulmonary lymphomas. A clinical study of 70 cases in nonimmunocompromised patients. Chest 1993; 103: 201– 208. 12 Cortelazzo S,Mian M,Rossi A, et al. Primary extranodal diffuse large B-cell lymphomas (DLBCL) arising in distinct sites of head and neck have different clinical characteristics and outcome. Haematologica 2007; 92 (s1). Abstract 0863. 13 Rohatiner A,d'Amore F,Coiffier B, et al. Report on a workshop convened to discuss the pathological and staging classifications of gastrointestinal tract lymphoma. Ann Oncol 1994; 5: 397– 400. 14Surveillance, Epidemiology, and End Results. Available at: http://seer.cancer.gov/Accessed on July 2, 2009. Citing Literature Volume84, Issue11November 2009Pages 762-763 ReferencesRelatedInformation

Examination of the proliferative activity of tumor cells in human lymphoid neoplasms using a morphometric approach.

The genesis of lymphoid neoplasia is accompanied by alterations in cell proliferation control mechanisms. Thus, proliferative indices (PIs) provide valuable prognostic information in this setting. Nonetheless, one shortcoming of PI measurements is that they depend not only on the proliferative activity of the neoplastic cells in a given lesion, but also on the activity of any admixed reactive cells. The current report describes an approach to identifying neoplastic and reactive subpopulations in cytologic preparations and to comparatively characterizing the morphologic features of neoplastic cells and assessing their proliferative activity. Reactive and malignant lymph node samples were obtained from 37 patients during surgical biopsy. Giemsa stained touch imprints were used for morphometric and high-resolution videomicroscopic analyses. Immunofluorescence-based detection of pKi-67-positive cells was used in conjunction with morphometric analysis to assess the proliferative activity of tumor cells. Morphometric analysis allowed the selective identification of neoplastic cells in large cell lymphomas (LCLs). The morphologic characteristics of neoplastic cells in primary and secondary LCLs were found to be similar. The PI was highly dependent on the proportion of tumor cells present in the tissue sample analyzed, and in some samples with large proportions of reactive cells, the overall percentage of pKi-67-positive cells was low, but the majority of neoplastic cells nonetheless were positive for pKi-67. Most primary LCLs had very high tumor cell PIs (80-100%), whereas all secondary LCLs had moderate tumor cell PIs. Neoplastic cell subpopulations in LCLs can be identified on morphometric analysis, which can be performed using touch imprints; this technique allows evaluation of the proliferative activity of tumor cells. The authors propose that the use of tumor cell PIs rather than PIs for overall cell populations will result in more accurate assessment of disease prognosis.

Patterns of outcome and prognostic factors in primary large-cell lymphoma of the testis in a survey by the International Extranodal Lymphoma Study Group.

To determine clinical features and patterns of outcome of primary testicular diffuse large B-cell lymphomas (DLCL). A retrospective international survey of 373 patients with primary testicular DLCL. Most patients presented with localized disease (stage I to II), and the median age at diagnosis was 66 years (range, 19 to 91 years). Anthracycline-based chemotherapy was administered to 255 patients (68%), and prophylactic intrathecal chemotherapy was given to 68 patients (18%); 133 patients (36%) received prophylactic scrotal radiotherapy. Median overall survival was 4.8 years, and median progression-free survival was 4 years. The survival curves showed no clear evidence of a substantial proportion of cured patients. A favorable international prognostic index score (IPI), no B-symptoms, the use of anthracyclines, and prophylactic scrotal radiotherapy were significantly associated with longer survival at multivariate analysis. However, even for patients with stage I disease and good-risk IPI, the outcome seems worse than what was reported for DLCL at other sites. At a median follow-up of 7.6 years, 195 patients (52%) had relapsed. Extranodal recurrence was reported in 140 cases. Relapses in CNS were detected in 56 patients (15%) up to 10 years after presentation. A continuous risk of recurrence in the contralateral testis was seen in patients not receiving scrotal radiotherapy. Testicular DLCL is characterized by a particularly high risk of extranodal relapse even in cases with localized disease at diagnosis. Anthracycline-based chemotherapy, CNS prophylaxis, and contralateral testicular irradiation seem to improve the outcome. Their efficacy is under evaluation in a prospective clinical trial.

Initial chemotherapy for primary resectable large-cell lymphoma of the stomach

We aimed to evaluate the safety and effectiveness of a conservative approach with short-term chemotherapy with or without consolidation radiotherapy in primary resectable large-cell gastric lymphoma in patients not requiring emergency surgery at presentation. Seventeen consecutive patients presenting with resectable primary large-cell lymphoma of the stomach not requiring immediate surgery were initially treated with chemotherapy with or without consolidation radiotherapy. Subtotal or total resection of the stomach was planned only as salvage treatment for those patients who failed locally, or as emergency surgery in instances of acute iatrogenic complications of treatment. Chemotherapy included four to six cycles of an anthracycline-containing regimen, and consolidation radiotherapy was planned on the entire stomach and surrounding lymph node areas for complete responders readily capable of compliance with a daily treatment schedule at our Institution. None of the patients in the present series experienced acute iatrogenic morbidity or mortality from local complications. After a median follow-up of almost six years, two patients failing first-line chemotherapy have died of progressive lymphoma, while 15 patients are well and currently disease-free. Up-front chemotherapy as initial treatment for primary gastric large-cell lymphoma appears to be a safe and effective treatment by which most patients can probably be spared surgical gastrectomy. Consolidation radiation therapy on the stomach can probably improve on the effectiveness of chemotherapy alone. More experience is needed to elucidate the prognostic factors, treatment-related long-term toxic effects and the feasibility of such a treatment administered outside of highly specialized institutions.

Congruent uptake in bone and gallium scans in primary large-cell lymphoma of bone

A 24-YEAR-OLD woman was admitted with a 3-year history of pain in her left knee that gradually worsened. Recently, the knee also became swollen and indurated. No other clinical findings were noted. A plain radiograph taken 2 years before her presentation was reported at that time as normal, but was now, retrospectively, interpreted as abnormal with slight and nonspecific periosteal reaction in the distal femur. Six months before admission the patient underwent distal femur bone biopsy which yielded fibrosis and chronic inflammation consequently treated with antibiotics with the diagnosis of chronic osteomyelitis. However, with the worsening of clinical features despite treatment, the patient was reevaluated. Plain radiograph performed at this point showed slight periosteal thickening (Fig 1). Magnetic resonance imaging revealed not only periosteal thickening but also abnormal bone marrow signal in the distal femur. The patient was referred to the Department of Nuclear Medicine for a bone scan and a gallium study, with the clinical suspicion of chronic osteomyelitis. A three-phase bone scan was obtained by intravenous administration of 740 MBq (20 mCi) of technetium 99m-MDP that showed increased perfusion to the distal left femur, including the condylar regions (Fig 2A) as well as increased soft tissue blood pool and bone uptake in the same regions. Both early and the delayed scans (Fig. 2B) also demonstrated diffuse nonhomogeneous uptake in the distal two thirds of the femur, as well as a photopenic region in the mid-shaft of the femur. While not excluding sequestrum as a possible explanation, the findings were also suggestive of neoplastic changes with the possibility of skip type lesions. The remaining whole body survey was normal. The gallium scan performed 48 hours after administering 148 MBq (4 mCi) similarly yielded diffuse nonhomogeneous uptake in the femur with a mid-shaft photopenia congruent with results of the delayed bone scan images (Fig 3). The findings on the bone scan in conjunction with the gallium scan could be consistent with chronic osteomyelitis, as well as neoplasm. A repeat biopsy yielded histological findings consistent with primary large-cell lymphoma of bone. This is a rare tumor, accounting for only 5% of all primary bon e malignancies.l These tumors constitute a morphologically heterogeneous group of neoplasms, mostly classified as either diffuse mixed-cell, or diffuse large-cell lymphoma. Lymphoma is considered to be primary in bone when it arises in the medullary cavity, and without concurrent regional lymph node or visceral involvement. It is a rare subtype of extra nodal lymphoid malignancies accounting for approximately 1% of all non-Hodgkins lymphomas.I While a permeative destructive lesion is considered typical, the plain film may be normal. 2 MRI features include linear cortical foci that correlate with histologically shown cutting zones. They are considered to be the tumor tunnels via which the lymphoma may exit the intrameduUary space, and may subsequently form local soft tissue masses without concomitant cortical bone destruction. 2 These minute cortical changes are responsible for the pitfalls in the interpretation of plain radiographs. After diagnosis, both chemotherapy and radiotherapy were administered, Regress!on of scintigraphic findings was consequently noted. Possible

Pleomorphic Large Cell Lymphomas of the Mediastinum

Nine cases of primary non-lymphoblastic, non-Hodgkin's large cell lymphomas of the mediastinum characterized by a highly pleomorphic histologic appearance are described. The patients, four women and five men, were aged 30 to 65 years. All patients presented with symptoms referable to their tumors, including cough, chest pain, dyspnea, pleural effusion, and superior vena cava syndrome. Clinical and pathologic staging in all patients showed that the bulk of the tumor was confined to the chest cavity at the time of initial diagnosis, with local infiltration into the neck, lung hilum, and surrounding mediastinal structures. Three different histological growth patterns were observed: one composed of a diffuse proliferation of pleomorphic, highly atypical cells with bizarre nuclear features that closely resembled a high grade sarcoma; another one composed of sheets of large, epithelial-appearing atypical cells suggestive of anaplastic carcinoma; and another pattern characterized by a pleomorphic proliferation of large lymphoid cells admixed with numerous scattered Reed-Sternberg-like cells reminiscent of the lymphocyte-depleted variant of Hodgkin's disease. Immunohistochemical studies on paraffin-embedded tissue sections in all cases showed positive staining of the tumor cells with CD20 and CD45 antibodies and negative staining with a large panel of markers, including broad-spectrum keratin, CAM 5.2, carcinoembryonic antigen, epithelial membrane antigen, vimentin, actin, desmin, HMB 45, S-100 protein, CD3, CD15, CD30, and CD45RO. Because of their location restricted to the anterior mediastinum, frequent lack of recognizable lymph node architecture, and bizarre cytologic features, the present group of lesions posed difficulties for diagnosis, their correct identification was achieved through the application of a panel of immunohistochemical markers. An awareness of these unusual histologic appearances of primary large cell lymphoma in the mediastinum and inclusion of a broad panel of lymphoid markers are therefore recommended for the evaluation of pleomorphic, undifferentiated malignant neoplasms of this anatomic region.

Primary large cell lymphoma of the rectum

Primary large cell lymphoma of the rectum

Primary large cell lymphoma of the splenic sinuses: A variant of angiotropic B-cell lymphoma (neoplastic angioendotheliomatosis)?

A case of large cell lymphoma of B-cell lineage originating in the splenic sinuses is described. In addition to widening the spectrum of primary malignant lymphomas of the spleen, this case raises the possibility that variants of angiotropic large cell lymphomas may exist that do not involve blood vessels but do involve the spleen and lymph node sinuses.

Primary large-cell lymphoma of the thymus: A diffuse B-cell neoplasm presenting as primary mediastinal lymphoma

Primary mediastinal nonlymphoblastic non-Hodgkin's lymphoma (NLNHL) has distinct clinical, histologic (diffuse large-cell morphology, often with sclerosis and clear cytoplasm), and immunohistochemical features (predominantly B-cell lineage, usually immunoglobulin-negative), which suggest origin from a unique B-cell population. The thymus has a resident population of B cells with a unique immunophenotype, and can be involved by primary mediastinal NLNHL, in some cases selectively. Fifteen cases of NLNHL involving the thymus were studied by paraffin-section immunohistochemistry using antibodies to formalin-resistant epitopes of B cells (4KB5 [CD45RA] and L26 [CD20]) and T cells (L60 [CD43] and UCHL1 [CD45RO]). All were diffuse large-cell or immunoblastic lymphomas with sclerosis, and were also similar to primary mediastinal NLNHL in clinical features. Neoplastic cells stained with L26 in all but one case, which stained with 4KB5 and an antibody to a leukocyte-common antigen (PD7/26 [CD45RB]), and were uniformly nonreactive with L60 (with one exception) and UCHL1. Intermingled small lymphocytes were uniformly L26-negative and positive for T-cell markers, even in one case with atypia suggesting a lymphoma of mixed morphology. These findings demonstrate that primary thymic and primary mediastinal NLNHL are similar B-lineage neoplasms, and support previous suggestions that both may originate in thymic B cells.

Primary large cell lymphoma of the mediastinum. A histologic and immunophenotypic study of 29 cases.

We studied the morphologic and immunologic features of 29 cases of primary nonlymphoblastic non-Hodgkin's lymphoma of the mediastinum. The patients ranged in age from 15 to 73 years, with a median of 32 years. The mean age for the 11 men (50 years) was significantly higher than that for the 18 women (32 years) (p less than 0.05). All had diffuse large cell lymphomas (six immunoblastic, 14 large cell not otherwise specified, six large cell noncleaved, one large cell cleaved, and two not subclassifiable). Sclerosis was prominent in 11 cases, none of them immunoblastic, and did not correlate with superior vena cava syndrome. The mean age (54 years) of patients with immunoblastic lymphomas was higher than that for patients with other subtypes (35 years) (p less than 0.02). Frozen-section immunoperoxidase staining disclosed monotypic immunoglobulin in 13 cases, with a high frequency of heavy-chain class switching (seven IgG, two IgA, four IgM). Sixteen cases were immunoglobulin negative; 14 of 15 cases expressed B-lineage antigens, and none expressed T-lineage antigens. Three of four cases showed immunoglobulin heavy- or light-chain gene rearrangement by the Southern blot technique. None showed rearrangement of the T-cell receptor beta-chain-gene constant region. There was no correlation between immunophenotype and morphologic subtype. The immunoglobulin-negative group was predominantly female (13 of 16 cases; p less than 0.02), and younger (mean age, 34 years versus 44 years; p = NS) than the immunoglobulin-positive group; however, the difference in age was not statistically significant. The actuarial 5-year survival was 57%, and there was no correlation between survival and either histologic subtype or immunophenotype. Mediastinal large cell lymphoma is a B-cell tumor, which frequently lacks immunoglobulin, may be primary in the thymus, has a predilection for young women, and can be cured with aggressive therapy.

AIDS-related lymphoid neoplasia. The Memorial Hospital experience.

The clinical features and laboratory results of 63 patients with or at risk for AIDS with lymphoid neoplasias seen from November 1980 through November 1986 are reviewed. Forty-three had systemic non-Hodgkin's lymphoma (NHL), nine had primary large cell lymphomas of the brain, 11 had Hodgkin's disease (HD), and one had plasmacytoma evolving to myeloma. Those with systemic NHL included 40 (93%) with intermediate or high-grade histologies, 35 (81%) with advanced stage (III, IV), and 28 (65%) with extranodal disease at presentation (predominantly marrow and meninges). Overall survival was short (median, 10.5 months from diagnosis) with the majority of deaths attributable to AIDS-related opportunistic infections (OI). However, 17 patients with diffuse NHL achieved a complete clinical remission, and nine now have been disease-free for more than 1 year (median follow-up, 28 months; range, 12 to 73 months). Early stage and lack of systemic symptoms were features associated with prolonged disease-free survival. Primary brain NHL was a uniformly lethal manifestation of AIDS, being diagnosed at postmortem in seven of nine severely immunosuppressed homosexual men. As with NHL, a propensity towards advanced disease and extranodal involvement was also observed in HD, suggesting that the atypical clinical behavior of HD may be an additional epiphenomenon of AIDS. This experience tends to argue for the use of intensive therapy in at least some patients with AIDS-related systemic NHL since it has resulted in a proportion of long-term disease-free survivors.

Primary large-cell lymphoma of the central nervous system.

Primary non-Hodgkin's lymphoma of the central nervous system (CNS) is a rare disease. Seven patients were seen and treated at the University of Michigan Medical Center between January 1969 and December 1983. All patients had histologically proven diagnoses of large cell lymphoma with clinical and radiologic evidence of involvement limited to the CNS. Five of seven patients received postoperative radiation therapy, two of whom have had apparent local control at 1- and 2-year follow-up. The two patients without postoperative radiation died of local recurrence 2 and 3 months following subtotal resection. These poor results suggest that adjuvant therapy may be required for improved control of this type of extranodal lymphoma.

Primary large cell lymphomas of the mediastinum: an analysis of 20 cases.

Malignant lymphomas originating primarily in the mediastinum consist predominantly of Hodgkin's disease of the nodular sclerosis type, lymphoblastic lymphomas, and large cell non-Hodgkin's lymphomas of diffuse growth pattern (DHL). This analysis of 20 cases of primary mediastinal DHL presents the clinical and pathologic findings in nine patients with T-immunoblastic sarcoma (T-IBS), six with sclerosing variants of follicular center cell lymphoma (FCCL), and five with B-immunoblastic sarcoma (B-IBS). T-IBS patients were predominantly young adult women (mean age 31 years) presenting with relatively well confined mediastinal tumors; four of nine manifested the SVC syndrome. The immunomorphologic findings in T-IBS were similar to those of node-based peripheral T-cell lymphomas. Patients with FCCL and B-IBS were predominantly men, exhibited a broad age range, and presented with larger tumors with a high incidence of contiguous involvement of intrathoracic structures (83% in FCCL, 60% in B-IBS). Chemotherapeutic intervention attained CR in 19 of 20 patients, with 14 of 20 remaining alive in relapse-free CR a median of 26 months after completion of therapy. Durable CR was attained in eight of nine T-IBS patients, in four of six patients with FCCL, and in three of five patients with B-IBS. The morphologic features of these lymphoma subtypes are presented in detail and discussed in relation to the complex differential diagnosis of mediastinal neoplasms.