Lymphomas in the immunocompromised patient

Lymphoma is a common opportunistic complication of immunosuppression. Lymphomas in patients with the acquired immunodeficiency syndrome (AIDS) may broadly be divided into four major types: intermediate- or high-grade systemic lymphoma, primary central nervous system (CNS) lymphoma, Hodgkin's disease (HD) and primary effusion lymphoma. Multiple active regimens have been identified for patients with AIDS-related systemic lymphoma. However, despite high initial complete response rates, most studies have reported a median survival of less than 1 year for these patients, with approximately half of the patients dying from lymphoma and half from opportunistic infections or other AIDS-related complications. The standard therapeutic approach for patients with AIDS-related primary CNS lymphoma is radiotherapy, although recent studies using combinations of chemotherapy with radiotherapy may offer an improvement in therapy for this group of patients who have very poor overall prognosis. Lymphoproliferative disease in patients after solid organ or bone marrow transplantation represents with a spectrum of disorders. No standard approach for therapy in this group of patients has been clearly established.     

Primary muscle lymphoma: clinical and imaging findings

PURPOSE: To assess the clinical and imaging findings in primary muscle lymphoma. MATERIALS AND METHODS: Seven patients with biopsy-proved primary muscle lymphoma without evidence of systemic disease underwent imaging with plain radiography or computed tomography (CT) and magnetic resonance (MR) imaging. Four underwent bone scintigraphy, and two underwent gallium scintigraphy and fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) before and after therapy. RESULTS: Plain radiographs at initial examination (n = 5) showed no bone abnormalities. Soft-tissue masses and bone marrow involvement showed isoattenuation at CT (n = 3), but at MR imaging (n = 7), all masses demonstrated increased signal intensity on T2-weighted images that involved multiple muscle compartments and typically spanned a long segment of the extremity. Adjacent bone disease was less extensive than muscle disease, and, in most cases, subcutaneous stranding or extension was observed adjacent to the masses. Good size correlation was observed between findings at MR imaging, gallium scintigraphy, and FDG PET. Two patients developed recurrent multifocal muscle lymphoma several years after initial examination. CONCLUSION: The presence of an extensive soft-tissue mass with infiltration of adjacent subcutaneous fat and minimal or no extension into the bone marrow cavity at MR imaging and normal plain radiographic findings may suggest primary muscle lymphoma.     

Central nervous system involvement of leukemia and systemic lymphoma in children: CT and MR findings

The purpose of this paper is to retrospectively evaluate CT and MR findings of central nervous system (CNS) involvement of leukemia and systemic lymphoma in children. Over a 12-year period, sixty-five patients with leukemia and fifteen patients with systemic lymphoma underwent cerebral CT and/or MR imaging. Nine patients (11.3%) were diagnosed as CNS involvement of leukemia and lymphoma. The diagnostic criteria of CNS involvement were as follows; 1) Histological proof was confirmed by surgery, 2) Tumor cells were found in the cerebrospinal fluid examinations, 3) Increase in size of the lesion during observation without specific treatment, and 4) Response to the treatment for leukemia or lymphoma. All of nine patients fulfilled more than two criteria of 1)-4). The CT and MR abnormalities in these patients were correlated with the findings of histology, cerebrospinal fluid cytology, and/or treatment. The age of the patients ranged from 0 to 15 years old. They consisted of 6 boys and 3 girls. The CT examinations were performed before and after contrast administration. MR examinations were performed on a 1.5-T unit, and T1-weighted, T2-weighted, and proton density-weighted images were obtained using spin-echo or fast spin-echo sequences. Tumor masses were present in seven with leukemia (acute lymphoblastic leukemia 4; acute myeloblastic leukemia 1; acute promyelocytic leukemia 1; acute monocytic leukemia 1), and in two with malignant lymphoma. On the CT scan, tumor masses were hyperdense with contrast enhancement. On the MR images, their signals were variable. In all of nine patients, tumor masses were contiguous with a meningeal surface. Postcontrast T1 weighted images were valuable in demonstrating meningeal infiltration. Tumoral hemorrhage was found in two patients. In a patient with tumor at the superior sagittal sinus, venous infarct was observed. CNS leukemic and lymphomatous masses are almost hyperdense on the CT and they are characteristically contiguous with a meningeal surface. MR imaging was valuable in demonstrating meningeal infiltration. Findings of CT and MR imaging, cerebrospinal fluid examinations, and response to the treatment are useful in the differentiation of CNS involvement of leukemia and lymphoma from other lesions such as infectious diseases and leukoencephalopathy.     

Bilateral non-Hodgkin''s lymphoma of the breast mimicking mastitis

We recently encountered a case of recurrent non-Hodgkin's lymphoma manifested after a long period of quiescence as bilateral involvement of the breasts. This 37-year-old woman had stage IVA nodular poorly differentiated lymphocytic lymphoma diagnosed 9 years previously and was followed up without treatment. She was lost to follow-up after 4 years but had been in good health until seen with malaise and fever and pain, swelling, and erythema involving both breasts. Biopsies of lymph node and bone marrow showed a high-grade non-Hodgkin's lymphoma (lymphoblastic lymphoma) of B cell origin with central nervous system involvement. Combination chemotherapy produced a dramatic remission, but the patient died of Pseudomonas septicemia.     

Identity in molecular structure between "differentiation enhancing factor" of murine erythroleukemia cells and the 30 kD heparin-binding protein of developing rat brain

Bone marrow involvement by anaplastic large cell anaplastic large cell (ALC) lymphoma can be difficult to detect on routine morphologic examination alone. In a series of 42 patients with ALC lymphoma, the authors analyzed: (1) the usefulness of a limited panel of monoclonal antibodies directed against CD30 (Ber-H2, HRS4) and epithelial marrow involvement on routinely processed biopsy specimens; and (2) the prognostic significance of bone marrow involvement as detected on both morphologic and immunohistochemical grounds. On conventional examination, 17% of the patients were found to have bone marrow involvement at diagnosis. However, after immunohistochemical analysis, occult malignant cells were detected in 23% of the patients with negative bone marrow biopsy on routine histology. The low percentage of positive cases on routine morphologic examination compared to immunohistochemical examination was related to: (1) the scarcity of neoplastic cells which were scattered among hematopoietic cells; (2) the difficulty of distinguishing malignant cells from immature hematopoietic elements; and (3) the absence of alteration of the reticulin network. The authors observed a significant association between marrow infiltration and the presence of hematologic abnormalities (mostly anemia or cytopenias) at diagnosis, both in children and adult patients. More importantly, a significant lower survival was seen in patients with bone marrow involvement compared to those without bone marrow involvement. Immunohistochemistry with anti-CD30 and anti-EMA antibodies should be performed systematically in bone marrow biopsies from patients with ALC lymphoma to reliably identify the presence of bone marrow involvement that appears to carry a poor prognosis.     

An aggressive case of Burkitt's lymphoma with t(8;14) and c-myc rearrangement transformed from CD5+ B-cell lymphoma

We experienced a case of Burkitt's lymphoma showing an unusual surface phenotype, CD5 expression, at an early stage of the disease. Initially, this patient showed massive abdominal para-aortic lymph node swelling which rapidly developed into leukemic change. Based on the clinical course and cytogenetic features of lymphoblasts in the bone marrow, which showed t(8;14) and c-myc gene rearrangement, the patient was diagnosed with Burkitt's lymphoma. Combination chemotherapy induced short-term remission, but central nervous system (CNS) involvement developed, followed by a regrowth of lymphoma cells in the bone marrow. The bone marrow at the end stage showed monotonous expansion of large cells with conspicuous vacuolation in the basophilic cytoplasm. The initial lymphoma cells showed pan-B markers and were CD5 positive but weakly CD10 positive; however, the lymphoma cells obtained from the bone marrow at the terminal stage did not express CD5. The chromosomal t(8;14) was seen, and identical rearrangement of immunoglobulin heavy chain joining gene and c-myc gene were detected by Southern blot analysis in the bone marrow lymphoblasts throughout the clinical course. This case is evidence that remarkable transformation of CD5-positive lymphoblasts to CD5-negative lymphoblasts occurred in an identical clone of Burkitt's lymphoma.     

Exploratory laparotomy and splenectomy in the diagnosis of Hodgkin''s disease in children

Thirty-three children with histologically proved Hodgkin's disease underwent exploratory laparotomy with splenectomy and biopsy of lumbar lymph nodes, liver, and bone marrow. In 13 patients (39%) the lesion of spleen and/or splenic hilar lymph nodes was diagnosed. The involvement of spleen was mostly found in patients with mixed cellularity type, in the presence of systemic symptoms ("B"), and in the biological stage "b." Involvement of the liver was found in 1 patient, of the hepatic hilar lymph nodes in 3 patients, and of the bone marrow in 4 patients. The lymphographic and histologic data as regards lumbar lymph nodes coincided in 65% of cases. After operation the stage of the disease was changed in 48% patients. The early and late complications were not numerous.     

MRI gadolinium enhancement of bone marrow: age-related changes in normals and in diffuse neoplastic infiltration

OBJECTIVE: To quantify gadolinium-related enhancement in the bone marrow of the spine in normals and in patients with homogeneous diffuse malignant bone marrow infiltration. DESIGN AND PATIENTS: The patients consisted of two groups: group 1 comprised 94 healthy adults (18-86 years) without bone marrow disease and group 2 comprised 30 patients with homogeneous diffuse malignant bone marrow infiltration due to myeloma (n = 20) or breast carcinoma (n = 10). All patients received intravenous gadopentetate dimeglumine (Gd-DTPA), 0.1 mmol/kg body weight. Pre- and postcontrast signal intensity (SI) on T1-weighted spin-echo (SE) images (TR/TE: 572 ms/15 ms) was measured over a region of interest (ROI) and the percentage SI increase was calculated. The results were confirmed by bone marrow biopsy (n = 20) and clinical parameters (n = 10). Dynamic contrast-enhanced studies using a spoiled gradient-recalled-echo (GRE) sequence (TR/TE/alpha: 68 ms/6 ms 75 degrees) were performed in 10 controls with normal bone marrow. RESULTS AND CONCLUSION: Contrast material enhancement in healthy persons can vary greatly (range 3-59%, mean 21%, SD 11%). With increasing age there is a significant decrease in contrast enhancement (Pearson's correlation, P < 0.01). The percentage SI increase in patients with intermediate-grade (biopsy 20-50 vol%) and high-grade (biopsy > 50 vol%) diffuse malignant bone marrow infiltration was significantly higher than in normals (mean 67%, SD 34%, P < 0.001). Low-grade (biopsy < 20 vol%) diffuse malignant bone marrow infiltration can not be assessed by non-enhanced T1-weighted SE images or Gd-DTPA application. In conclusion, contrast material enhancement in healthy persons can vary greatly and is dependent on age, while intermediate-grade and high-grade diffuse malignant bone marrow infiltration can be objectively assessed with SI measurements.     

Frequency and significance of anemia in non-Hodgkin's lymphoma patients

OBJECTIVES: Retrospective evaluation of anemia frequency and its prognostic value in patients with different subtypes of non-Hodgkin's lymphoma and comparison with other clinical characteristics. PATIENTS AND METHODS: Anemia was defined as a hemoglobin value less than or equal to 12 g/dl for all men and women over 50 years of age, and less than or equal to 11 g/dl for women under 50 years of age. The study included 1077 adult lymphoma patients treated between 1980 and 1995 with the following histologic subtypes: 127 patients with small lymphocytic or lymphoplasmacytoid, 62 with marginal zone, 50 with mantle-cell, 208 with follicular, 104 with T-cell lymphoma, 426 with diffuse large-cell and, finally, 73 patients with other high-grade lymphomas. RESULTS: Anemia was present in 341 patients (32%). It was an adverse prognostic factor (P < 0.0001) for overall survival (OS) and progression-free survival (PFS) but not for relapse-free survival (RFS). When patients with and those without bone marrow involvement were considered separately, anemia remained an adverse factor. Anemia was significantly associated with shorter PFS in small lymphocytic or lymphoplasmacytoid, mantle cell, diffuse large cell and high-grade lymphomas and with shorter OS in all histologic subgroups except marginal zone lymphoma. In multivariate analysis, anemia was a significant prognostic factor for OS and PFS for the population as a whole (P = 0.0001 and P = 0.0048, respectively) and in patients with bone marrow involvement (P = 0.007 and P = 0.005, respectively) but not in patients without bone marrow involvement. Finally, the addition of anemia to the International Prognostic Index led to an improvement for OS (P = 0.0004) and PFS (P = 0.0004). CONCLUSIONS: Anemia is an important adverse prognostic factor for the outcome of lymphoma patients, particularly in some histologic subgroups and in patients with bone marrow involvement.     

Mechanism of action of a new component of the Ca(2+)-dependent proteolytic system in rat brain: the calpain activator

OBJECTIVE: Using single photon emission computed tomography (SPECT) we evaluated the presence and evolution of changes in brain perfusion in juvenile systemic lupus erythematosus (JSLE). METHODS: SPECT was performed in 14 patients with active JSLE divided in 2 groups: the first included 7 patients without central nervous system (CNS) involvement and the second 7 patients with minor neuropsychiatric symptoms (headache, reactive depression, cognitive impairment, mood swing). SPECT findings were compared to seroimmunological and magnetic resonance imaging (MRI) data. After 6 month followup, a second SPECT scan was performed in 12 of 14 patients. RESULTS: At baseline, SPECT showed perfusion defects in 2 patients without neuropsychiatric symptoms and in 5 patients with CNS involvement. In one of the 7 patients with altered SPECT, MRI showed focal hyperintensities. MRI alterations were observed in another patient who had a normal SPECT scan. Cortical atrophy was present in 5 of 14 patients. Correlation between neuropsychiatric manifestations and SPECT findings was not clearly evident because the major part of JSLE patients with CNS involvement and with SPECT alterations had multiple symptoms, but showed focal hypoperfusion on SPECT imaging. No significant association was found between seroimmunological data and SPECT findings. At followup, improvement of perfusion alterations was observed in 6 of 7 patients with altered SPECT and, in 3 of them, findings might be attributed to changes in steroid treatment. CONCLUSION: Perfusion abnormalities in SLE may represent reversible lesions or subclinical CNS involvement. Moreover, SPECT imaging appears to be useful in detecting and monitoring CNS involvement in SLE.     

Sequence analysis of DNA randomly amplified from the Saccharomyces cerevisiae genome

OBJECTIVES: To report the features of malignancies responsible for a chest wall mass and involving the sternum, the sternocostal and/or sternoclavicular joints, the chondrocostal junction and/or the adjacent soft tissues. METHODS: The medical records of patients with a chest wall mass due to malignant disease were reviewed retrospectively. The following data were abstracted from each record: characteristics of the pain and mass, constitutional symptoms, physical findings, laboratory test results, findings from imaging studies (plain radiographs, computed tomography and magnetic resonance imaging of the chest, radionuclide bone scan), histologic features of the biopsy specimen from the chest wall mass and origin of the mass. RESULTS: Seven men and three women with a mean age of 53.1 years were included in the study. A single patient had a history of malignant disease (lymphoma); in the remaining nine patients the chest wall mass was the first manifestation of the malignancy. All ten patients had pain with a mixed time pattern. The mass was located on the sternum in half the patients and in a parasternal location in the other half. Erythrocyte sedimentation rate elevation was found in seven patients, an increased serum level of lactate dehydrogenase in one and a monoclonal immunoglobulin in three. Sternal lesions were visible on plain radiographs in four patients. Computed tomography of the chest consistently disclosed sternal or sternocostal lytic lesions with spread to the adjacent soft tissues; in five cases, enlarged lymph nodes were visible in the anterior part of the mediastinum. Magnetic resonance imaging of the chest did not add to the information provided by computed tomography. Radionuclide uptake on the bone scan was increased, decreased, or normal at the site of the lesion. The cause was Hodgkin's disease in two cases, non-Hodgkin's lymphoma in three, metastatic bone disease in two (from an adenocarcinoma of the lung and a hepatocarcinoma, respectively), multiple myeloma in one, and solitary plasmacytoma in two. CONCLUSION: A chest wall mass can be caused by a known or as yet undiagnosed malignancy. Chest wall involvement due to malignant disease in rare, however. The specific features of sternal metastases, lymphomas involving the sternum, and sternal plasmacytomas are discussed. Nonmalignant chest wall lesions that can manifest as a bulging or swelling of the chest wall are reviewed.     

Neuropathologic findings and neurologic symptoms in twenty-three children with hemophagocytic lymphohistiocytosis

BACKGROUND: Primary hemophagocytic lymphohistiocytosis (HLH) is an autosomal recessive disorder with very high mortality rates, mainly affecting infants and young children, which is characterized by fever, hepatosplenomegaly, and cytopenias. Of great clinical importance are the neurologic symptoms, which are common and may even dominate the clinical picture and precede the systemic presentation. These symptoms are extremely variable, ranging from irritability, bulging fontanelle, and neck stiffness, to convulsions, cranial nerve palsies, ataxia, hemiplegia/tetraplegia, and unconsciousness. METHODS: To elucidate this neurologic involvement further, we reviewed the neuropathologic postmortem findings from 23 children and their neurologic symptoms. RESULTS: Macroscopically, edema was present in many cases, and in some with advanced disease, softening and destruction of the tissue were conspicuous. The microscopic picture was exceedingly variable, ranging from almost normal to very advanced changes. In the mildest form of HLH, only the meninges were involved with infiltration of lymphocytes and macrophages (stage I), whereas more advanced cases in addition also showed perivascular infiltrates (stage II). In even more advanced disease there was also a diffuse infiltration in the tissue (stage III), as well as a multifocal necrosis. A prominent astrogliosis was present in such cases. Hemophagocytosis was seen in most patients, most commonly in the leptomeninges. CONCLUSIONS: HLH affecting the central nervous system imitates several neurologic disorders and may be misdiagnosed. A staging system for the neuropathologic findings is presented. In children with obscure central nervous systems symptoms and a progressive encephalopathy, the diagnosis of HLH may be considered, in particular because treatments are available.     

Comparison of reticuloendothelial scans with bone scans in malignant disease

Thirty patients with histologically proven malignant disease were selected for reticuloendothelial scans and bone scans because of suspected bone or bone marrow involvement. Reticuloendothelial scans were abnormal in 83% of the patients and bone scans were abnormal in 47%. Focal defects on the reticuloendothelial marrow scan correlated better with tumor infiltration of the marrow than did diffusely abnormal scans. Focal defects were found in nine patients (30% of total), four of whom had negative or equivocal bone scans. In multiple myeloma, reticuloendothelial marrow scans were more sensitive than bone scans, but were not clearly better than bone scans in patients with solid tumors. In the interpretation of reticuloendothelial scans, consideration must be given to the effects of radiation, chemotherapy, and uremia, all of which may cause decreased reticuloendothelial uptake and falsely positive reticuloendothelial scans. Reticuloendothelial scans seem most useful for hematologic malignancies that have not been previously treated. The advantages and disadvantages of reticuloendothelial scans are discussed.     

Paratesticular rhabdomyosarcoma in adult patients: 16-year experience at Institut Gustave-Roussy

BACKGROUND: Children with paratesticular rhabdomyosarcoma (RMS) have both a good prognosis and a high survival rate. The clinical behaviour and outcome of the disease in adults is not well described. PATIENTS AND METHODS: We reviewed retrospectively our experience with paratesticular RMS in patients older than 16 years during a 16-year period (1975-1991). RESULTS: Thirteen adult patients with paratesticular RMS are reported. Median age was 21 years (range 16 to 31). Presentation characteristics were scrotal mass in 11 cases, lumbar pain and weight loss in 5 cases, hypercalcemia in 3 cases and thrombocytopenia in 3 cases. There were 5 patients with stage IV, 2 with stage IIB and 6 with stage IA (IRS classification). The 5 stage IV patients are reported in detail, with initial bone marrow infiltration encountered in 4 of them. Objective response to chemotherapy was achieved in all 6 patients with measurable disease (2 CR + 4 PR). Two of 7 patients who received adjuvant chemotherapy relapsed at 7 and 11 months. After a median follow-up of 90 months, 8 patients (5 stage IV, 3 stage IA) died from disease progression. CONCLUSION: Metastatic disease with bone marrow involvement at presentation and aggressive behaviour seem to be more relevant in adult paratesticular RMS patients compared with children.     

Single lung transplantation in patients with systemic disease

OBJECTIVE: To report functional results and survival in patients undergoing single lung transplantation (SLT) for pulmonary involvement associated with systemic disease or prior malignancy, criteria traditionally considered contraindications to SLT. DESIGN: Case series. SETTING: The University of Texas Health Science Center at San Antonio. PATIENTS: Nine patients who have undergone SLT for end-stage lung disease: four patients with sarcoidosis; two patients with limited scleroderma; and three patients with prior malignancies (two with prior lymphoma and bleomycin-induced pulmonary fibrosis and one who received two bone marrow transplants for acute lymphocytic leukemia and subsequently developed chemotherapy-induced pulmonary fibrosis). MEASUREMENTS: Pulmonary function testing, exercise oximetry, quantitative ventilation-perfusion lung scanning. Actuarial survival. RESULTS: All patients had marked improvement in pulmonary function, exercise oximetry, and quantitative ventilation perfusion to the SLT. One patient with scleroderma died 90 days postoperatively from Pseudomonas pneumonia with a sepsis syndrome. One patient with sarcoidosis died 150 days postoperatively from disseminated aspergillosis. At autopsy, there was no evidence of recurrent fibrosis or sarcoidosis in the transplanted lungs in either of these two patients. The seven surviving patients have returned to work or school and are conducting all activities of daily living without pulmonary disability. The 1- and 2-year actuarial survival rates in these nine patients is 68.6 percent as compared with the 1- and 2-year actuarial survival rates of 66.3 percent and 55.8 percent in the remainder of our SLT group as a whole (n = 49). Despite pharmacologic immunosuppression, there is no evidence of recurrent malignancy in the 3 patients with prior malignancies. CONCLUSIONS: We conclude that carefully selected patients with end-stage lung involvement related to systemic disease or chemotherapy-induced fibrosis may benefit from SLT.     

Bone marrow involvement in lymphoblastic lymphoma and small non-cleaved cell lymphoma: the role of trephine biopsy

Trephine biopsy (TB) combined with bone marrow aspiration (BMA) is the most common method for evaluating bone marrow (BM) involvement in non-Hodgkin's lymphomas. Nevertheless, the role of TB in high-grade lymphomas remains controversial. We reviewed the results of 42 consecutive BMAs and TBs performed simultaneously in 29 patients with lymphoblastic lymphoma (LL) and small, non-cleaved cell lymphoma (SNCL). In LL, 8M involvement was documented in 35.4% of the cases by BMA and 22.5% of the cases by TB. In SNCL it was documented in 45.4% of the cases by BMA and 36.3% by TB. There were no statistically significant differences (p > 0.05) in the rates of BM involvement found by TB or BMA in the two types of lymphoma, although BMA appeared to be more sensitive than TB. These observations suggest that routine TB may not be necessary in assessing BM involvement in patients with LL and SNCL.     

Indications and relative indications for stem cell transplantation in non-Hodgkin's lymphoma

High dose chemotherapy with or without total body irradiation and autologous stem cell rescue has proven to be effective treatment to cure patients with relapsed intermediate grade and high grade non-Hodgkin's lymphoma. Important factors for selection of candidates most likely to do well with these approaches include patients whose disease is responsive to conventional therapy and those who have minimal disease volume at the time of transplant. The treatment-related mortality of autologous stem cell transplantation has diminished from 20% to less than 5% with improved supportive care and selection of patients with less advanced disease. Although the treatment-related mortality of allogeneic stem cell transplantation may be as high as 20-40%, a graft versus lymphoma effect may decrease relapse with the result that overall survival is not substantially different between autologous and allogeneic transplantation. The definitive indications for stem cell transplantation include patients who have relapsed with intermediate or high grade NHL. Relative indications include intermediate/high grade non-Hodgkin's lymphoma patients, "high risk" first complete remission (CR), resistant relapse; low grade non-Hodgkin's lymphoma in sensitive or resistant relapse, advanced disease (sensitive or resistant relapse, transformation), first CR (younger patients). Relative contraindications include specific patient profiles such as bulky high grade lymphoma which progresses on appropriate conventional therapy, poor performance status, active serious infection, serious cardiac, renal, pulmonary or liver dysfunction, active, central nervous system (CNS) disease unresponsive to cranial irradiation/intrathecal therapy. For patients with previous marrow involvement or active marrow involvement at the time of harvest or transplant, "purged" autografts, peripheral blood stem cell transplantation and allografts have been used successfully.     

Bulky centroblastic non-Hodgkin's lymphoma of the cranium vault mimicking brain involvement managed with chemotherapy: a case report

BACKGROUND: Patients with central nervous system (CNS) involvement by high grade non-Hodgkin's lymphoma (NHL) have a poor prognosis. The roles of computed tomography, radiotherapy, and intrathecal and systemic chemotherapy still need to be defined. METHODS: A patient with bulky cranial lymphoma mimicking brain involvement is reported. A 62-year-old man was admitted with a huge scalp lump, headache, fatigue, and focal and generalized neurologic symptoms. Computed tomography showed an abnormal mass in the frontoparietal region involving the subcutaneous scalp, osteolytic destruction of the cranial vault, and a bulky mass that was interpreted to be intracranial. A systemic survey also revealed bulky retroperitoneal involvement and focal involvement of the spleen. Biopsy revealed a B-cell NHL of centroblastic type according to the Kiel classification. RESULTS: The patient was treated with a modified combination of cyclophosphamide plus mitoxantrone plus vincristine plus prednisone (CNOP) and intrathecal methotrexate. The patient responded with complete remission, including partial bone restoration of the cranium. At the time of this writing, his relapse free survival lasted 5 years. CONCLUSIONS: The initial interpretation of this case indicated that systemic chemotherapy with modified CNOP plus intrathecal methotrexate would be useful in the management of NHL with CNS involvement. The clinical outcome with rapid neurologic repair and also bone restoration of the cranial vault within 5 years suggests that the lymphoma probably never penetrated the dura and a successful treatment was achieved with combination chemotherapy only.