Early transformation from follicular lymphoma to Burkitt lymphoma

We report a rare case of follicular lymphoma which rapidly showed transformation to the Burkitt type of lymphoma after a treatment consisting of chemotherapy and irradiation. A 51-year-old male visited our hospital in August 2000 because of bilateral neck lymphadenopathy. He was diagnosed as having follicular lymphoma (grade 2) (clinical stage IIIA) with complex karyotypic abnormalities involving t(14 ; 18)(q32 ; q21) and CD20 expression. Initially he was followed as an outpatient without chemotherapy. Six months later, he was admitted because of hydronephrosis due to an intrapelvic tumor. He underwent chemotherapy with 4 courses of CHOP regimen following irradiation therapy and a partial response was obtained. Four months after initiation of the treatment, his disease recurred with numb chin syndrome. Bone marrow aspiration revealed bone marrow involvement by lymphoma cells which had a Burkitt-like appearance. A cytogenetic study using bone marrow blood showed complex abnormalities involving t(8 ; 22)(q24 ; q11) in addition to t(14 ; 18). In spite of salvage chemotherapy, the patient died in September 2001.     

Ga-67 citrate accumulation in heart in malignant lymphoma of B-cell type accompanied with repeated ECG abnormalities which were normalized with chemotherapy--report of an autopsy case

A 37y/o male developed mass formation in right tibia in Oct. 1986. He had generalized lymphadenopathy. Diagnosis of malignant lymphoma of B cell type (follicular, large cell type) stage IV B was made because of bone marrow involvement. Surface marker analysis of pathologic cells in the peripheral blood, bone marrow, lymph nodes revealed that they were of B cell type with positive EA gamma rosette formation, positive surface immunoglobulin with IgM-kappa and cytoplasmic immunoglobulin with IgM-kappa and positive responses to monoclonal antibodies of OKIal and B1. He responded partially to VEPAM therapy but in Jan. 1987 he developed Ga accumulation in heart and ECG abnormalities such as depression of ST and inverted T in II, III, AVF, V1-V6 leads. After treatment with VEP, ECG abnormalities disappeared in a month. The same ECG abnormalities recurred once more and disappeared again. Autopsy findings revealed accumulation of lymphoma cells in epicardium and myocardial degeneration in right ventricle. Ga scan appears to be a valuable method for detection of early cardiac involvement by malignant lymphoma.     

De novo CD5-positive diffuse large B-cell lymphoma with leukemic dissemination diagnosed by immunohistochemical examinations of bone marrow clot sections

A 61-year-old male visited his doctor in October 2000 because of a high fever. Laboratory examination revealed leukocytosis with blast-like cells and thrombocytopenia. He was referred and admitted to our hospital in November 2000. Although he had mild splenomegaly, he had no lymphadenopathy on the first admission. The white blood cell count was 10,520/microliter with 45% blast-like cells and the platelet count was 51 x 10(3)/microliters. Bone marrow aspiration revealed 82% blast-like cells, which were positive for CD5, CD10, CD13, CD19, and CD20. Immunohistochemistry of the bone marrow clot sections revealed blast-like cells were positive for CD5, but negative for TdT, CD23 and cyclin D1. We diagnosed the patient as having de novo CD5-positive diffuse large B-cell lymphoma (DLBCL) with leukemic dissemination. He obtained a complete remission after two courses of CHOP therapy. The third chemotherapy was postponed because of strangulation of the intestine. He relapsed and died in spite of the third chemotherapy. CD5-positive DLBCL is one of the established disease entities that requires an appropriate therapy regimen because it is characterized by elderly onset, extranodal involvement, and a poorer prognosis.     

Peripheral blood involvement accompanied with hypercalcemia in the malignant lymphoma of iliac bone

We reported a rare case of non-Hodgkin's lymphoma of iliac bone which developed peripheral blood involvement associated with hypercalcemia. 42-year-old man was admitted to Fukui Medical School Hospital because of right iliac bone pain. An X-ray film of the pelvis disclosed the osteolytic change of right iliac bone. A CT scan of the pelvis showed soft tissue density tumors involved bilateral iliac bone. He had no superficial lymphadenopathy or organomegaly. Examination of peripheral blood and bone marrow did not show any abnormalities. Monoclonal immunoglobulin was not detected in serum. Examination of biopsied specimens from iliac bone tumor showed infiltration of round cells. Immunocytochemical analysis showed only MT-1 positive. He was treated with combination chemotherapy of vindesine, cyclophosphamide, prednisolone and pirarubicin followed by radiation therapy. But, there was no significant response. Following radiation therapy, he developed coma. Serum calcium was 9.8 mEq/l. The pathologic immature cells were found in peripheral blood. The bone marrow aspirates showed 63% pathologic cells. These cells expressed CD19, CD20, HLA-DR antigens. He was diagnosed as having leukemic non-Hodgkin's lymphoma, B-cell type, and was treated with combination chemotherapy. But he died of systemic fungal infection.     

Nodal gamma/delta T cell lymphoma in complete remission following allogeneic bone marrow transplantation from an HLA-matched unrelated donor

Gamma/delta T cell lymphoma is very rare, and usually occurs as an extranodal tumor. We describe the case of a 16-year-old Japanese man with an unusual nodal gamma/delta T cell lymphoma with generalized lymphadenopathy and bone marrow involvement. No tumor involvement was observed in the liver, spleen, or nasal cavity. Examination for surface antigens on lymphoma cells revealed a unique phenotype, positive for CD3 and T cell receptor (TCR) gamma/delta, but negative for CD2. Genotypic analysis revealed the tumor to be of monoclonal origin and characterized by TCR gamma-chain gene rearrangement, but there was no rearrangement of the TCR beta-chain gene. Our patient's tumor responded to combination chemotherapy and subsequent allogeneic bone marrow transplantation from an HLA-matched unrelated donor. He has remained well and free of disease for 35 months.     

Follicular lymphoma-related colitis resembling ulcerative colitis

Among the various manifestations of colonic involvement in malignant lymphomas, an ulcerative colitis-like appearance is rare. Herein, we describe a case in which extranodal colonic involvement resembled ulcerative colitis in a patient with advanced follicular lymphoma. A 59-year-old Japanese man with diarrhea and body weight loss was referred to our hospital. Computed tomography (CT) revealed systemic lymphadenopathy, splenomegaly, and thickening of the sigmoid colon and rectum walls. ¹⁸F-fluorodeoxy-glucose positron emission tomography (¹⁸F-FDG-PET/CT) revealed intense tubular ¹⁸F-FDG accumulation extending from the rectum to the colon at the hepatic flexure and much weaker accumulation in the systemic lymph nodes, bone marrow, and spleen. The isotope-enriched areas had an ulcerative colitis-like appearance as shown via colonoscopy. The patient was ultimately diagnosed with follicular lymphoma (stage IV A, grade 1) based on a pathological examination of the neck lymph nodes, iliac bone marrow, and colon. After six courses of chemotherapy (R-CHOP), ¹⁸F-FDG-PET/CT confirmed complete remission of the lymphoma including the colonic lesion. This is presumably the first case of ulcerative-like colitis caused by a follicular lymphoma. As a novel approach, the lymphoma-related colitis was detected by comparing the pathology results and the ¹⁸F-FDG-PET/CT results.     

Histologic transformation of follicular lymphoma after allogeneic bone marrow transplantation

A 38-year-old man with refractory follicular lymphoma underwent allogeneic BMT from an HLA-identical sibling donor. He had generalized lymphadenopathy, hepatosplenomegaly and lymphoma infiltration of the marrow, all of which disappeared within 3 months following transplantation. Six months post-transplant, progressive hepatomegaly developed in the absence of splenomegaly and lymphadenopathy, and he died from hepatic failure. Autopsy disclosed diffuse large B cell lymphoma of the liver, into which the follicular lymphoma had transformed. Future issues to be investigated should include the optimal timing of allogeneic BMT for low-grade lymphomas.     

NSE-positive lymphoblastic lymphoma in a boy with cutaneous involvement, giant splenomegaly, and hyper-gamma globulinemia

We report a 6-year-old boy who was diagnosed as having neuron-specific enolase (NSE)-positive pro-T cell type lymphoblastic lymphoma preceded with a variety of symptoms such as skin rash, giant splenomegaly, and hyper-gamma globulinemia. He first showed cervical lymphadenopathy in June 1999, followed by a fever of unknown origin with atypical erythema, hepatosplenomegaly, and a few lymphoblastoid cells present in the bone marrow in September. However, no specific treatments were started at this point because a cervical lymph node biopsy failed to show malignancy and the patient's signs and symptoms resolved spontaneously. Two months later, oral prednisolone therapy was started due to recurrence of the fever and erythema, but resulted in exacerbation of the skin lesions and generalized lymphadenopathy. A biopsy of the right inguinal lymph node performed in January 2000 revealed proliferation of lymphoblastic cells positive for CD3, CD5 and NSE with a rearrangement of T cell receptor gene Jdelta, leading to the diagnosis of lymphoblastic lymphoma. After intensified chemotherapy, he received an autologous peripheral blood stem cell transplantation and has been in complete remission for 4 years.     

Mantle cell lymphoma mimicking chronic lymphocytic leukemia

A 62-year-old male was admitted to our hospital complaining of dyspnea in March, 2002. He had remarkable bone marrow invasion with a significant number of leukemic cells, anemia and thrombocytopenia. In addition he had generalized lymphadenopathy including a bulky mass in the left cervix. Surface marker analysis of abnormal cells showed CD 5+, 10-, 19+, 20+, 23+, and kappa+, and immunohistochemistry revealed cyclin D1-positive cells. Chromosome analysis showed del(11q). The patient was diagnosed as having mantle cell lymphoma, stage IVB, and received combination chemotherapy. He could not obtain complete remission and died after 29 months. We found it very difficult in this case to make a differential diagnosis between mantle cell lymphoma and chronic lymphocytic leukemia. We report on this case and summarize the problem of the differential diagnosis.     

CD30-negative diffuse large B-cell lymphoma expressing ALK

A 33-years-old man was diagnosed as having undifferentiated carcinoma presenting with right neck lymphadenopathy in December 2000. He obtained complete remission (CR) following chemotherapy, radiation and lymphadenectomy on the right neck. He had multiple para-aorta lymphadenopathy and splenomegaly in December 2001. An open-abdominal lymph node biopsy was performed from which a diagnosis of anaplastic large cell lymphoma was made. CR was achieved with biweekly CHOP, however, the patient suffered from a relapse twice. He underwent allogeneic peripheral blood stem cell transplantation (PBSCT) from his HLA-matched sister while in non-CR in November 2002. Engraftment was achieved on day 14, and at the same time, complete chimerism was confirmed. Acute grade III graft-versus-host disease (GVHD) developed and was controlled with cyclosporine A and prednisolone. Extensive chronic GVHD was subsequently observed and required systemic immunosuppression. His condition returned to CR after the PBSCT and he sustained complete chimerism. He suddenly died of fulminant thrombotic microangiopathy seven months after the PBSCT. The tumor cells were ALK-positive, CD30-negative and JH rearrangement was detected, and were therefore classified as diffuse large B-cell lymphoma with expression of ALK according to the WHO classification, though they differed from this subtype in some points. Although this case was refractory for chemotherapy with a complex karyotype, the graft-versus-lymphoma effect might have contributed to the sustained CR following the PBSCT.     

Central nervous system involvement in diffuse large B‐cell lymphoma

Background: Malignant lymphoma with central nervous system (CNS) involvement has an extremely poor prognosis. We retrospectively studied the risk factors for CNS involvement in patients with diffuse large B‐cell lymphoma (DLBCL) treated by cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or rituximab (R) ‐CHOP chemotherapy. Patients and methods: We studied 375 consecutive patients who were newly diagnosed with DLBCL between 1996 and 2006. Patients with primary CNS involvement and patients who received CNS prophylaxis were excluded. All the patients received CHOP (n = 172) or R‐CHOP (n = 203) chemotherapy. The following variables were assessed for their potential to predict CNS involvement: gender, age, serum lactate dehydrogenase (LDH) level, performance status, clinical stage, number of extranodal involvements, International Prognostic Index (IPI), bone marrow involvement, presence of a bulky mass, presence of B symptom, and treatment. Results: CNS involvement was observed in 13 cases (3.5%). In univariate analysis, LDH more than normal range, LDH more than twice as normal range, high IPI, bone marrow involvement, and systemic relapse were the predictors for CNS involvement. In multivariate analysis, no risk factors were detected for CNS involvement. The use of rituximab did not have an impact on CNS involvement. Conclusions: The incidence of CNS involvement dose not decrease in rituximab‐era.     

Primary follicular lymphoma arising in the ampulla of Vater

Primary gastrointestinal lymphomas constitute more than one-third of all extranodal lymphomas, but among them follicular lymphomas (FL) are infrequent, accounting for only 1-4%. We report the case of a 55-year-old man diagnosed with a FL of the ampulla of Vater. He complained of dyspepsia. An upper gastroendoscopic study 1 year before showed a slight enlargement of the papilla with the biopsy initially interpreted as atypical follicular hyperplasia. The study performed because of persistence of the symptoms again showed an enlarged papilla, and the histological examination was diagnostic of FL (CD10+, bcl-2+). The full staging study did not show other FL involvement. The patient was treated with six courses of cyclophosphamide, hydroxydaunomycin, vincristine, and prednisone (CHOP), and the endoscopy as well as the biopsies revealed no abnormalities since the third course of chemotherapy. After 2 years of follow-up he remains asymptomatic and the gastroendoscopic study is normal.     

Primary cutaneous diffuse large B cell lymphoma: a clinically aggressive case

An 80-year-old woman was diagnosed with primary cutaneous B cell lymphoma. She had multifocal cutaneous tumors, but no nodal lymphadenopathy or bone marrow involvement. Histopathological examination of a biopsy specimen showed diffuse large B cell lymphoma without a bcl-2 expression. Complete resolution of hypercalcemia and disappearance of tumors were achieved with CHOP therapy, but a rapidly progressive skin lesion was observed soon after the completion of the therapy. The clinical manifestation of primary cutaneous diffuse large B cell lymphoma is diverse and the treatment strategy is not entirely clarified. This case represents another example of this rare lymphoma.     

Acute leukemia in two brothers

A 42-year-old man was diagnosed as having refractory anemia in May, 2001. He developed overt leukemia and received allogeneic bone marrow transplantation (BMT). His younger brother, a 40-year-old man, was diagnosed as having acute leukemia with trilineage myelodysplasia in November, 2001. Although he was treated with conventional chemotherapy, he failed to achieve complete remission. He also received allogeneic BMT. We suggest that environmental factors in addition to a genetic defect in the pluripotent hematopoietic stem cells may be associated with the occurrence of this familial leukemia.     

Non-Hodgkin's lymphoma localized at the right ocular medial rectal muscle

This paper reports a rare case of extranodal non-Hodgkin's lymphoma localized at the ocular muscle, which achieved a long-term remission by combination chemotherapy and irradiation. A 41-year-old man visited the ophthalmology department of Toho University Hospital in December, 1982 because of right conjunctival injection and right exophthalmos which were first manifested in June. The patient was diagnosed as having non-Hodgkin's lymphoma (diffuse medium-sized cell type) by biopsy of the right medial rectal muscle, and was referred to our department on January 17, 1983. A series of examinations revealed that the disease had no invasion into any lymph nodes and other organs. After treatment with two courses of C-MOPP regimen and two courses of ACOP regimen, the patient achieved complete remission and was discharged on July 30. Subsequently he completed two courses of CHOP regimen followed by irradiation (46 Gy). Seven years and three months after the initiation of chemotherapy, the patient has been in a complete remission, requiring no treatment.     

Bell's palsy as an early manifestation of acute lymphoblastic leukemia

A 20-year-old man with the complaints of malaise, fever, and tooth gum bleeding presented at a hospital. He was found to have generalized lymphadenopathy, thrombocytopenia, and leukocytosis. Ensuing bone marrow biopsy led to a diagnosis of acute lymphoblastic leukemia (ALL). He also had a sense of "facial stretching" and difficulty during eating. After clinical examination, he was diagnosed with right-sided peripheral type facial nerve paralysis (Bell's palsy). The magnetic resonance imaging studies demonstrated bilateral facial nerve involvement, predominantly on the right side. The patient received steroid treatment and local facial radiotherapy for Bell's palsy. A concurrent facial exercise program was ordered. Seemingly a less significant diagnosis in a leukemia patient, we considered our case notable since an ALL patient presenting with Bell's palsy, especially at the very beginning of the disease, is not that common. The cases of relapsing ALL reported in the literature initially presenting with the same scenario further strengthen the significance.     

Elderly non-Hodgkin's lymphoma presenting with pulmonary squamous cell carcinoma as a complication of chemotherapy for malignant lymphoma]

The authors report a case of pulmonary squamous cell carcinoma which occurred after chemotherapy of non-Hodgkin's lymphoma (NHL). A 76-year-old man, who was admitted to our department because of swelling of cervical lymph nodes, was diagnosed as having NHL (follicular mixed cell lymphoma). He was treated with 11 courses of CHOP therapy. Thereafter, chemotherapy including ifosfamide was carried out for approximately three years. In June, 1991, he was readmitted to our department because of swelling and pain in his left thigh and an abnormal shadow on chest X-ray. Chest CT demonstrated a cavitated shadow (about 5 cm in diameter) with an irregular margin in right S1, which was suggested to be lung cancer or pulmonary infiltration of malignant lymphoma. Bronchoscopy, which was carried out on July 12, showed bloody sputa from the right B1 ramus and markedly reddened mucosa at the orifice of the right upper bronchus. Sputum cytology revealed no malignancy. ACVP-16 chemotherapy including ara-C, CBDCA and VP-16 was initiated on July 14 because of enlarged superficial lymph nodes. On July 18, he fell out of bed and fractured his left femur. He also suffered from respiratory failure. He died of pulmonary haemorrhage on July 26. Autopsy revealed pulmonary squamous cell carcinoma. The occurrence of pulmonary squamous cell carcinoma is rare after the chemotherapy of malignant lymphoma.     

Testicular plasmacytoma with bone dissemination without medullary plasmacytosis

A 34-year-old man was diagnosed as having solitary testicular plasmacytoma. He had received palliative radiotherapy, several combined chemotherapies including CHOP chemotherapy (vincristine, cyclophosphamide, Adriamycin, and prednisone), MP (melphalan and prednisone) and M-2 protocol (melphalan, prednisone, vincristine, carmustine, and cyclophosphamide), and interferon therapy as 3 million units subcutaneous injection three times a week for 1 year. Extensive bone plasmacytoma developed 7 years later without bone marrow involvement. We suggest that early use of combined chemoradiotherapy and high-dose chemotherapy with autologous stem cell support should be investigated in patients with testicular plasmacytoma with dissemination.     

Angio-immunoblastic lymphadenopathy with fibrosis of bone marrow, lymph node, liver and spleen, and proliferation of epithelioid cells in lymph nodes

We report a 47-year-old man diagnosed as angio-immunoblastic lymphadenopathy with dysproteinemia (AILD) with fibrosis of the bone marrow, lymph node, liver and spleen, and proliferation of epithelioid cells in lymph node. He was admitted to a hospital in May, 1980 because of general fatigue, cough, fever and systemic lymphadenopathy. The diagnosis of AILD was based on a biopsy of right cervical lymph node. His symptoms were improved but recurred with the addition of icterus and progressive pancytopenia with decrement of prednisolone. He was referred to our hospital in July, 1980 and his physical examination revealed generalized lymphadenopathy, icterus and hepatosplenomegaly. Hemogram showed pancytopenia, and needle biopsy of the bone marrow disclosed fibrosis. Sections from the lymph node showed AILD with proliferation of epithelioid cells. Administration of 60 mg/day of prednisolone improved the fever, lymphadenopathy and hepatosplenomegaly. However he died suddenly of acute respiratory failure on July 30. Autopsy showed fibrosis of bone marrow, lymph node, liver and spleen with infiltration of abnormal lymphocytes, and pulmonary aspergillosis.     

Primary and isolated adult T-cell leukemia/lymphoma of the bone marrow

The distribution of adult T-cell leukemia/lymphoma (ATLL) is typically systemic. In addition to peripheral blood (PB) and lymph nodes, extranodal sites such as the skin, lung, liver, gastrointestinal tract, and central nervous system are frequently involved. We report a unique case of ATLL in which the patient presented with prolonged fever. A 65-year-old man had high-grade fever lasting for 2 weeks. He showed no lymphadenopathy, hepatosplenomegaly, skin lesions, or PB involvement. Bone marrow examination showed widespread infiltration of ATLL cells. (18)F-fluorodeoxy glucose positron emission tomography (FDG-PET) revealed that the disease was confined to the bone marrow.