Mantle cell lymphoma associated with hyper-IgE syndrome

A 69-year-old woman was admitted with generalized lymph node swelling and huge splenomegaly. CD5(+), Sm-IgM (+) and SmIgD (+) lymphocytes were increased in lymph nodes, spleen and bone marrow, and she was diagnosed as having mantle cell lymphoma. A diagnosis of hyper-IgE syndrome was also made, because IgE was markedly increased (174,780 u/ml) and chronic dermatitis, which was often complicated with infection, occurred repeatedly on her extremities. In this case, interleukin-4 was considered to be one of the factors involved in the hyper-IgE syndrome, because increased IgG1 and reduced IgG2 were observed. Immunological abnormality associated with the hyper-IgE syndrome seemed to contribute to the development malignant lymphoma in this case.     

Mantle cell lymphoma: a clinicopathologic study of 80 cases

Mantle cell lymphoma (MCL) is a relatively uncommon yet distinct type of malignant lymphoma whose clinical and pathological characterization has been limited by the small numbers of cases published to date. We studied 80 cases of MCL seen at a single institution over 7 years to determine both clinical and pathological prognostic factors. The patients in this study were predominantly male (70%) and older (mean age, 63 years) and presented with advanced-stage disease (88%). Extranodal involvement was common. Median overall survival (OS) was 43 months. Except for performance status, prognosis was not significantly influenced by clinical prognostic factors. Histologically, MCL architecture was classified as diffuse (78%), nodular (16%), or mantle zone (6%); the OS among these groups was identical. Increased mitotic activity (>20 mitotic figures per 10 high power fields), blastic transformation, and peripheral blood involvement at diagnosis also predicted for a worse outcome, but bone marrow involvement did not. The presence or absence of a translocation t(11; 14) by cytogenetic analysis or a bcl-1 rearrangement by Southern analysis did not significantly predict outcome. In summary, this study of 80 cases of MCL highlights its distinctive clinicopathologic features and shows that increased mitotic activity, blastic morphology, and peripheral blood involvement at diagnosis are prognostically important factors.     

Mantle cell lymphoma: correlation of clinical outcome and biologic features with three histologic variants

PURPOSE: Clinical data and histologic material were retrospectively analyzed in 46 cases of previously untreated mantle cell lymphoma (MCL) to more fully characterize the clinical response pattern of these lymphomas and to determine whether growth pattern significantly affected clinical outcome. MATERIALS AND METHODS: The histologic pattern was classified as diffuse (61%), nodular (13%), and mantle zone (26%) in accordance with stated criteria. RESULTS: Bone marrow infiltration was detected in 69% of cases; the frequency of involvement correlated with histologic pattern, being most common in diffuse variants and least common in mantle zone variants. Other sites of extranodal involvement were observed in 50% of cases. Cyclin-D1 staining revealed nuclear positivity in 23 of 25 patients (92%) and no difference was observed between the various histologic patterns. Rearrangement at the bcl-1 major translocation cluster (MTC) was detected in seven of 21 cases, without regard for histologic pattern. Complete response rates to doxorubicin-based regimens showed a striking correlation with histologic pattern. Seventy-three percent of patients with a mantle zone pattern attained a complete response compared with only 25% of patients with a nodular pattern and 19% with a diffuse pattern. Three-year survival rates were 100%, 50%, and 55% for patients with mantle zone, nodular, and diffuse histologic patterns, respectively. CONCLUSION: We conclude that (1) diffuse and nodular MCL are associated with a poor treatment response and a poor overall survival rate; (2) the mantle zone variant exhibits the clinical attributes of a low-grade lymphoma; and (3) the poor survival rates of patients with nodular and diffuse MCL suggest that these variants be classified as intermediate-grade lymphomas. However, the trend of the time to treatment failure curve does not indicate that current regimens can cure MCL.     

Primary non-Hodgkin's lymphoma of the liver

Primary non-Hodgkin's lymphoma of the liver is an extremely rare lymphoma subset that often presents with diagnostic difficulties to both clinicians and pathologists. Using MEDLINE search, 90 cases of primary hepatic lymphomas reported in the literature were reviewed. The epidemiology and etiology, clinical presentation, pathologic features, management, and outcome of these patients have been summarized and described. Results of this review show that middle-aged males are most often affected. Abdominal pain or discomfort, weight loss and fever are the most frequent presenting symptoms. Most cases have a solitary or multiple mass lesions in the liver, and are frequently misdiagnosed as having a primary liver tumor or metastatic cancer. Diffuse large cell lymphoma is the most commonly encountered histologic subtype. Surgery, chemotherapy and radiotherapy have been used alone or in combination as treatment but the outcome is generally poor. Although primary hepatic lymphoma is an aggressive disease, it is resectable, and responsive to chemotherapy and radiotherapy. Because of the profound therapeutic implications, it should be considered in the differential diagnosis for patients presenting with mass lesions in the liver or hepatic disease.     

Usefulness of FDG-PET in diagnosing primary lymphoma of the liver

This case report shows for the first time the usefulness of positron emission tomography (PET) with 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) in the diagnosis of primary non Hodgkin's lymphoma of the liver. Results of FDG-PET, which in contrast to other imaging techniques offers the advantage of screening the whole body, demonstrated a high glycolytic activity of a solitary mass in the liver with central necrosis (loss of glycolytic activity), but no spread of lymphoma to the body. These results were confirmed by ultrasound, computed tomography, magnetic resonance imaging and were biopsy proven. From our findings we conclude that in patients with liver masses with high uptake of FDG, lack of liver dysfunction and absence of signs indicating other malignancies, a primary lymphoma of the liver should be considered as a possible diagnosis.     

Large cell lymphoma complicating persistent polyclonal B cell lymphocytosis

Persistent polyclonal B cell lymphocytosis (PPBL) is a rare lymphoproliferative disorder of unclear natural history and its potential for B cell malignancy remains unknown. We describe the case of a 39-year-old female who presented with stage IV-B large cell lymphoma 19 years after an initial diagnosis of PPBL; her disease was rapidly fatal despite intensive chemotherapy and blood stem cell transplantation. Because we had recently identified multiple bcl-2/Ig gene rearrangements in blood mononuclear cells of patients with PPBL, we sought evidence of this oncogene in this particular patient: bcl-2/Ig gene rearrangements were found in blood mononuclear cells but not in lymphoma cells. Owing to the possible role of Epstein-Barr virus (EBV) in the pathogenesis of PPBL, we also hypothesized our patient might have an EBV-related lymphoproliferative disorder. Despite serologies consistent with past exposure to this virus, it was not found in lymphoma cells using a sensitive polymerase chain reaction technique. We conclude that non-Hodgkin's lymphoma may occur during the course of PPBL. However, longer follow-up in more patients will be needed in order to better clarity the risk of hematologic malignancy in patients with PPBL.     

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.     

硼替佐米治疗套细胞淋巴瘤的分子学机制

套细胞淋巴瘤(MCL)是生存期最短的非霍奇金淋巴瘤(NHL),目前尚不能根治.硼替佐米是第一个用于治疗血液系统恶性肿瘤的蛋白酶体抑制剂,主要用于多发性骨髓瘤(MM)及复发难治性MCL的治疗.探讨硼替佐米治疗MCL的相关机制,其中包括调节细胞周期、影响细胞凋亡、干扰MCL的微环境以及与其他抗肿瘤药物的协同作用等,有助于未来合理应用硼替佐米治疗MCL.     

Microsatellite instability in follicle centre cell lymphoma

Fluorescent polymerase chain reaction (PCR) was used to assay 12 microsatellite markers (APC x 2, DCC, P53 x 2, RB1, NM23, WT1, D6S260, D6S262, D6S281 and TNFa) to look for evidence of microsatellite instability in 40 cases of follicle centre cell lymphoma (FCC). Evidence of novel alleles seen in the tumour tissue but not the normal uninvolved tissue was seen in seven cases (17%). In only two of these cases (5%) was more than one locus involved but in these cases multiple affected loci were seen (4/12 and 7/12 respectively). The detection of microsatellite instability indicates a DNA repair defect such as that which would be predicted to occur in cells with mutated mismatch repair genes, a novel finding in FCC lymphoma.     

Mantle cell lymphomas lack expression of p27Kip1, a cyclin-dependent kinase inhibitor

The TCRs expressed on T lymphocytes recognize foreign peptides bound to MHC molecules. This reactivity is the basis of specific immune response to the foreign Ag. How such specificities are generated in the thymus is still being debated. Signals generated through TCR upon interaction with self MHC-peptide complexes are critical for maturation of the CD4+ helper and CD8+ cytotoxic subsets. We have observed maturation of CD4+ but not CD8+ T cells in Ly-6A.2 transgenic MHC null mice. Since there can be no interactions with MHC molecules in these mice, these CD4+ cells must express the T cell repertoire that exists before positive and negative selection. Interestingly, despite an absence of selection by MHC molecules, the CD4+ cells that mature recognize MHC molecules at a frequency as high as in CD4+ cells in normal mice. These results demonstrate that: 1) the germline sequences encoding TCRs are biased toward reactivity to MHC molecules; and 2) CD4+ cells as opposed to CD8+ cells have distinct lineage commitment signals. These results also suggest that signals originating from Ly-6 can promote or substitute for signals generated from TCR that are required for positive selection. Moreover, this animal model offers a system to study T cell development in the thymus that can provide insights into mechanisms of lineage commitment in developing T cells.     

Primary CD30-positive anaplastic large cell lymphoma of the lip

In this paper we report a case of 76-year-old white male patient with skin necrosis induced by subcutaneous prophylactic administration of low-molecular-weight heparin (LMWH). Skin necrosis occurred distant from heparin injection sites and without concomitant thrombocytopenia. This is the first reported case presenting these clinical findings.     

Genetic heterogeneity of AIDS-related small non-cleaved cell lymphoma

AIDS-related small noncleaved cell lymphoma (AIDS-SNCCL) includes Burkitt's lymphoma (BL) and high-grade B-cell Burkitt-like lymphoma (BLL). Due to the marked polymorphism of AIDS-related non-Hodgkin's lymphomas (AIDS-NHL), the morphologic distinction between these two types of lymphomas is frequently controversial, although it may bear clinical relevance. Although the molecular features of AIDS-BL have been clarified to a certain extent, the genetic peculiarities of AIDS-BLL have not been investigated in detail. In this study we have compared morphologic and genetic features of AIDS-BL and AIDS-BLL in a blind coded fashion. Molecular studies were focused on the genetic lesions known to be implicated in AIDS-NHL, including alterations of c-MYC, BCL-6, p53, deletions of 6q, as well as infection by EBV and HHV-8. Alterations of c-MYC occurred in 10/10 AIDS-BL, whereas they were restricted to 2/10 AIDS-BLL (P < 0.01). Mutations of p53 were present in 5/10 AIDS-BL, whereas they were consistently absent among AIDS-BLL (n = 10; P < 0.05). Infection by EBV occurred in 30% of both AIDS-BL and AIDS-BLL. Rearrangements of BCL-6, deletions of 6q and infection by HHV-8 scored consistently negative in both AIDS-BL and AIDS-BLL. Based on the genetic lesions tested, the molecular profile of AIDS-BLL appears to be closer to that of AIDS-related diffuse large cell lymphoma (AIDS-DLCL) than to that of AIDS-BL. In contrast to AIDS-BLL however, AIDS-DLCL carried rearrangements of BCL-6 in a fraction of cases (2/9). This study, the largest of its kind reported so far, suggests that AIDS-BL and AIDS-BLL have a different molecular pathogenesis and that characterization of genetic lesions may help to distinguish between these two lymphomas.     

Calcitriol mediated hypercalcaemia in a T cell rich B cell lymphoma

We report a "walking" catheter resulted in failed epidural anesthesia. An 85-year-old woman was scheduled for insertion of a nail in the left humerus. At 10 a.m. on the day of surgery, a Tuohy needle was inserted into the epidural space between the C6 and C7 vertebrae, and then we inserted an epidural catheter for 5 cm. Epidurography revealed that the catheter was inserted between C5 and C6, and the tip of the catheter was positioned windingly at C4. The contrast medium was found spread bilaterally from the C2 level to the Th2 level. The patient entered the operating room at 3 p.m. We infused 10 milliliters of 1% mepivacaine through the epidural catheter. Hypesthesia was obtained on the right side of her neck, from the C2 to the C5 level, after 10 minutes. Epidurography after surgery showed that the coiled catheter was placed straight into the right side of the epidural space; contrast medium infused through the catheter was found spread only to the right side from the C2 to the C4 level.     

Imaging of follicular dendritic cell tumours of the liver

Follicular dendritic cell tumour of the liver is a recently recognized entity. To date, only two cases have been described, both in the pathology literature. Histologically, it resembles an inflammatory pseudotumour and immunohistochemical and ultrastructural studies are required for its diagnosis. The ultrasound, computed tomography and angiographic features of two cases of follicular dendritic cell tumour of the liver are described in detail. One of the patients had multiple recurrences of this tumour. The imaging features are very similar to those of hepatocellular carcinoma. As follicular dendritic cell tumour is considered to be of low-grade malignant potential, in contrast to the dismal prognosis for hepatocellular carcinoma, it is important to be able to accurately distinguish between the two types of tumour prior to initiating definitive therapy.