The present study investigated histological subtypes of lymphoma in patients newly diagnosed with malignant lymphoma in the human T-cell leukemia virus type 1 (HTLV-1) endemic area of Japan, and further analyzed the clinicopathological features and clinical outcomes of patients with primary sinonasal lymphoma. We retrospectively examined 151 patients aged 18-90 years in Fukuoka, Japan. Subtypes of lymphoma were determined according to the WHO classification. Among the 151 patients, 104 were diagnosed with malignant lymphoma, including 96 at the time of initial diagnosis. Ninety-two of the 96 lymphomas (96%) were non-Hodgkin lymphoma. Mature B-cell neoplasms comprised 78% (n = 75). Primary lymphoma of the sinonasal cavity was found in six patients (6%). The histological subtype of sinonasal lymphoma was diffuse large B-cell lymphoma (DLBCL) in all six tumors. Furthermore, overall survival was significantly different among three distinct DLBCL patient groups, including primary sinonasal lymphoma patients (p = 0.0016; 3-year overall survival: sinonasal DLBCL group, 53%; DLBCL of the CNS group, 0%; other DLBCL group, 83%). Our study suggests that primary DLBCL of the sinonasal tract is a distinct disease entity of DLBCL.
We examined 13 patients with adult T-cell leukemia-lymphoma (ATL) diagnosed between 2007 and 2018 at a single center in a metropolitan area non-endemic for human T-cell leukemia virus type I (HTLV-1). The median age of the patients (eight male, five female) was 65 years (range, 48-83). The time from onset of symptoms to referral to our center was relatively short (median, 2 months; range, 1-9 months). Upon referral, all patients were suspected to have lymphoma, five were examined for soluble IL-2 receptor and two were examined for anti-HTLV-1 antibody. In ten of the 13 (77%), the patient themselves or their relatives were born in Kyushu. The birth places of the remaining three patients were unknown. Three patients (23%) had family histories of lymphoma. They all exhibited aggressive ATL (five acute, eight lymphoma type); however, the disease status was generally stable, with relatively stable performance status and low scores for prognostic indices. After combination chemotherapy, eight (62%) achieved remission. However, long-term remission was achieved in only one patient with localized lymphoma-type ATL and one young patient after allogeneic hematopoietic stem cell transplantation. In conclusion, at a center in a metropolitan and HTLV-1 non-endemic area in Japan, patients with ATL were relatively young and mainly presented with aggressive subtypes. At initial referral to our center, all 13 patients were suspected of having lymphoma but only two of having ATL. For centers in similar areas of Japan, prompt diagnosis and appropriate treatment of ATL patients will become increasingly necessary following the recent migration of HTLV-1 carriers to non-endemic areas.
The large Maf transcription factors are expressed in immune cells including macrophages and lymphocytes. To investigate the distribution of Maf expression in human organs, immunostaining for Maf was performed using sections of several human organs. High Maf expression was seen in the nucleus of macrophages in the gastrointestinal tract and lymph node sinus macrophages (LySMs). Then, we assessed whether Maf expression in LySMs was correlated with CD169 expression and the clinical prognosis in patients with esophageal cancer. Maf expression was associated with CD169 expression, but Maf expression in LySMs was not associated with the clinical course in patients with esophageal cancer. We determined which cytokines stimulate Maf expression using cultured macrophages. Immunocytochemistry showed that Maf expression was significantly elevated by interferon-γ. These results are the first report of Maf expression in human samples. Maf expression may be a marker for the macrophage population in humans.
Gamma-heavy chain disease (γ-HCD) is a rare B-cell tumor producing truncated IgG lacking the light chain. The clinical features of γ-HCD are heterogeneous, similar to lymphoplasmacytic lymphoma, and most patients have generalized and progressive disease. In some γ-HCD patients, autoimmune diseases are associated. Thus, γ-HCD as a restricted or indolent disease is exceptional. A 66-year-old male was referred to our hospital because of subungual hemorrhage at the bilateral halluces. Physical and laboratory examination results were nonspecific, and the hemorrhage was revealed to be traumatic. However, serum electrophoresis demonstrated a small M-peak, which was monoclonal IgG-Fc without the corresponding light chain on immunofixation and immunoelectrophoresis. Bone marrow aspirate demonstrated a small number of lymphoplasmacytic cells that were positive for CD19, CD38, CD138, and cyIgG, but negative for cyκ- and -λ light chains on flow cytometry. A diagnosis of γ-HCD was made. Chest and abdominal CT demonstrated neither hepatosplenomegaly, lymphadenopathy, nor bone lytic lesions. The serum concentrations of IgG and M-peak configuration have remained relatively unchanged for nearly 3 years. Therefore, this γ-HCD may correspond to a rare form of monoclonal gammopathy with undetermined significance.
IgA-producing lymphoplasmacytic lymphoma (LPL) is rare and IgH/c-myc translocation is rare in LPL. This is the first report of a case of IgA-producing LPL carrying t(8;14). An 86-year-old woman presented inguinal and intra-abdominal lymph node swelling, and lytic bone lesions in the lumbar vertebrae. A diagnosis of IgA-producing LPL was immunohistochemically made by inguinal lymph node biopsy. The serum IgA level was 1,180 mg/dL, which was revealed to be composed of IgA-λ monoclonal protein. Bone marrow chromosomal analysis demonstrated a complex abnormal karyotype, including t(8;14)(q24;q32), which was confirmed by FISH analysis. Abnormal lymphocytes positive for CD19, CD20, cyIgA, and cyλ were detected on flow cytometry analysis of marrow cells. Best supportive care was selected because of dementia and refractory urinary tract infection. Circulating lymphoplasmacytic cells with the same phenotype and karyotype were observed, and increased in number. The aggressive clinical course, including lytic bone lesions, may have been due to IgH/c-myc translocation or the nature of IgA-producing LPL.
Hodgkin-like adult T-cell leukemia/lymphoma (ATLL) is a rare variant of ATLL, which represents the early neoplastic phase of ATLL that follows an indolent clinical course compared with typical ATLL. Human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a neurological disorder characterized by the paralysis of lower limbs and urinary disturbance. Although these diseases are caused by HTLV-1 infection, there are no reports describing the coexistence of Hodgkin-like ATLL and HAM/TSP. Here, we report the first case of Hodgkin-like ATLL complicated by HAM/TSP. The patient was a 56-year-old man with right inguinal lymphadenopathy who had been using the neurology outpatient service for 13 years after being diagnosed with HAM/TSP. He was unable to receive intensive chemotherapy or allogeneic stem cell transplantation due to a poor performance status, but his condition was stable for approximately two years.
t(14;20)(q32;q11)/IGH-MAFB is a rare chromosomal abnormality in plasma cell myeloma (PCM), accounting for 1-2% of PCM cases. Patients with this translocation may have a poor prognosis. However, the clinicopathological features and response to novel agents have not been well clarified. We present a 63-year-old Japanese female with PCM positive for t(14;20). The tumor responded well to a proteasome inhibitor, bortezomib, and the patient achieved complete remission. Six months after remission, tumor relapse was noted in the left cerebellum and the right frontal lobe of the cerebrum. After whole brain radiation therapy, the tumor masses decreased in size. The patient was followed up with best-care support, but died of the disease 29 months after the initial PCM diagnosis. t(14;20)-positive PCM responded well to bortezomib at the time of the initial treatment. The CNS tumor involvement, which is rare in PCM, may be associated with the clinical aggressiveness of the t(14;20)-positive form of this myeloma.
Intravascular large B-cell lymphoma (IVLBCL) is a rare type of extranodal large B-cell lymphoma, and initial or predominant presentation in the lungs is uncommon. The synchronous occurrence of IVLBCL and malignant tumors is less frequent, and no such reports have described pulmonary presentations. We report a rare case of pulmonary IVLBCL accompanying lung cancer and interstitial lesions. A 73-year-old man with a history of pneumonia underwent a follow-up examination. Computed tomography revealed diffuse, bilateral ground-glass opacities (GGO) with a partial solid mass. Histologically, the mass consisted of adenocarcinoma. However, two other types of interstitial lesions were scattered throughout the resected lung: 1) peribronchovascular thickening with the aggregation of macrophages and anthracosis, and 2) alveolar septal thickening in the centrilobular area with atypical CD20-positive large cells in the capillaries. These two types of lesions were not mixed. Computed tomography and positron emission tomography demonstrated no other organ involvement. The patient was considered to have the synchronous occurrence of pulmonary IVLBCL and lung cancer (adenocarcinoma). After R-CHOP therapy, GGO on CT disappeared. Lung cancer often accompanies benign background lesions, and the combination of these lesions with lung cancer may make it difficult to detect the presence of pulmonary IVLBCL. However, the histological distribution pattern of IVLBCL may be a clue to the correct diagnosis.