A revised concept of anaplastic large cell lymphoma (ALCL) on both historical and practical grounds is presented. The main histological findings are illustrated with special reference to the cytological spectrum that is characteristic of the tumor. The phenotype is described in detail. The expression of the ALK protein as well as the chromosomal abnormalities that sustain it, are discussed along with potential pathogenetic implications. The clinical features of ALCL are presented by underlying the dramatic difference in terms of response to therapy and survival between ALK-positive and ALK-negative forms. The possibility of limiting the term ALCL to systemic ALK+ anaplastic tumors with T/null phenotype is considered.
The distinction of de novo diffuse large B-cell lymphomas (DLBCL) from transformed MALT lymphomas is difficult in the absence of MALT-component. This study aims to study the phenotypic expression profiles of extranodal lymphomas, focusing on the characteristics of high-grade tumors. We categorized 52 extranodal B-cell lymphomas into Grade 1 (low-grade MALT lymphoma), Grade 2 (DLBCL with MALT component), and Grade 3 (DLBCL without MALT component) tumors based on histomorphology. There were 26 (50%) Grade 1, 9 (17%) Grade 2, 15 (29%) Grade 3 tumors. We could not assess the grade of two tumors (4%) due to limiting tumor tissues. The expression of CD10, Bcl-2, Bcl-6, and p53 was also investigated by immunohistochemistry. CD10 expression was present in one Grade 1 and six Grade 3 tumors. Bcl-6 expression was more common in high-grade tumors (p=0.001), while Bcl-2 expression was associated with lower-grade tumors (p=0.001). CD10 expression was more useful as a marker in distinguishing Grade 2 from Grade 3 tumors than Bcl-6 expression. p53 was more frequently expressed in high-grade tumors; the higher frequency of p53 expression in Grade 2 tumors may suggest a potential role in the transformation of Grade 1 to Grade 2 tumors.
Fluid retention of more than 2kg, with no sign of pitting edema, was observed in 5 of 15 patients with refractory multiple myelomas treated by thalidomide. Cardiac function in all except one patient, who developed overt heart failure, were controlled well by diuretics. Median time from starting thalidomide to developing fluid retention was ten days (range 6 to 41 d). The fluid retention was transient in most patients, allowing thalidomide therapy to continue. However, when fluid retention could not be controlled by diuretics, thalidomide had to be discontinued. It is important that fluid retention is a significant adverse reaction to thalidomide therapy and that even overt heart failure can be obvious.
The neoplastic cells of adult T-cell leukemia/lymphoma (ATLL) invade various body organs, typically the lymph nodes (LN) and skin. The present study was designed to clarify the mechanism of invasion, by using a DNA array that allowed comparison of gene expression among ATLL cells in different sites, namely peripheral blood (PB), LN, and skin. The expression of matrix metalloproteinase 2 (MMP-2) mRNA was significantly up-regulated in skin relative to PB. Immunohistochemistry showed higher MMP-2 expression in ATLL cells found in the skin than in LN. Expression of membrane-type1-MMP (MT1-MMP), an activator of pro-MMP-2, was detected in fibroblasts present in the skin stroma. The proportion of MMP-2-positive cells in PB was not different between patients with or without skin invasion. Our results indicate that MMP-2 does not account for migration of ATLL cells to the skin, but once these cells reach the skin, this molecule seems to play an important role in proliferation of ATLL cells and/or their invasion of skin tissue.
Lymphangiomatosis is a rare disorder believed to result from a developmental malformation of the lymphatic system. Lymphangiomatosis involves bone, soft tissues, and viscera in a diffuse fashion. We describe an unusual case of splenic lymphangiomatosis that was accompanied by remarkable inflammatory signs. A 38-year-old Japanese woman was admitted to our hospital because of gross splenomegaly. She presented with fatigue, anemia, elevated serum C-reactive protein and polyclonal hypergammaglobulinemia. Her serum concentration of interleukin-6 (IL-6) was also elevated. She was born with lymphangiomatosis in the right leg, which was partially resected during infancy. Because of the risk of traumatic rupture, a total splenectomy was performed two weeks after admission. During postoperative follow-up examinations the patient's inflammatory signs and her serum IL-6 level returned quickly to normal. This could have been caused by a large release of IL-6 from the spleen. We confirmed by immunohistochemistry that IL-6 was produced within the spleen. Our findings indicate a strong association between splenic lymphangiomatosis and IL-6 production.