Persistent Hemarthrosis of the Knee after Arthroscopic Meniscal Repair.

Introduction: In this case report, we report a patient with complicated with persistent hemarthrosis following arthroscopic meniscal repair. Case Presentation. A 41-year-old male patient presented with persistent swelling of the knee 6 months after arthroscopic meniscal repair and partial meniscectomy performed for lateral discoid meniscal tear. The initial surgery was performed at another hospital. Four months after the surgery, swelling of the knee was noted when he resumed running. At his initial visit to our hospital, intra-articular blood accumulation was revealed via joint aspiration. A second arthroscopic examination performed 7 months after the initial procedure showed healing of the meniscal repair site and synovial proliferation. The suture materials identified during the arthroscopy were removed. Histological examination of the resected synovial tissue showed inflammatory cell infiltration and neovascularization. In addition, a multinucleated giant cell was identified in the superficial layer. After the second arthroscopic surgery, the hemarthrosis did not recur, and the patient was able to resume running without symptom one and a half years post-surgery. Conclusion: Bleeding from the proliferated synovia at or near the periphery of the lateral meniscus was thought to be the cause of the hemarthrosis as a rare complication following arthroscopic meniscal repair.

Progressive peripheral CD8+ T lymphocytosis complicated by pure red cell aplasia following immunosuppressive therapy for thymoma-associated myasthenia gravis.

We herein report a unique case of type B2 thymoma-associated myasthenia gravis which was ameliorated by immunosuppressive therapy in combination with chemotherapy. However, the patient subsequently developed pure red cell aplasia and marked lymphocytosis after additional chemotherapy aimed at improvement of thymoma. While a separate immunosuppressive regimen was effective for anemia, lymphocytosis was exacerbated. The biopsied thymoma specimen contained CD4+, CD8+, and CD4+/CD8+ T cells, some of which were CD3-, suggesting immature thymocytes. In contrast, majority of the peripheral lymphocytes were polyclonal CD3+/CD8+/T cell receptor (TCR)αß+ T cells. The CD4/CD8 ratio in the present patient might be affected by immunosuppressive agents, resulting in CD8+ T cell expansion associated with pure red cell aplasia. Although several cases of thymoma accompanied by peripheral T cell lymphocytosis were reported, marked CD8+ T cell proliferation is extremely rare.

Monocyte Chemoattractant Protein-1 (MCP-1) as a Potential Therapeutic Target and a Noninvasive Biomarker of Liver Fibrosis Associated With Transient Myeloproliferative Disorder in Down Syndrome.

Liver fibrosis is one of the common complications of transient myeloproliferative disorder (TMD) in Down syndrome (DS), but the exact molecular pathogenesis is largely unknown. We herein report a neonate of DS with liver fibrosis associated with TMD, in which we performed the serial profibrogenic cytokines analyses. We found the active monocyte chemoattractant protein-1 expression in the affected liver tissue and also found that both serum and urinary monocyte chemoattractant protein-1 concentrations are noninvasive biomarkers of liver fibrosis. We also showed a prospective of the future anticytokine therapy with herbal medicine for the liver fibrosis associated with TMD in DS.

Slow-Growing Mediastinal Grey Zone Lymphoma Originating From a Formerly Resected Multilocular Thymic Cyst.

We report a unique case of mediastinal grey zone lymphoma that was considered to originate from CD20+CD30+ Hodgkin cell-like cells associated with a multilocular thymic cyst that had been completely removed 4 years previously. In the formerly resected thymus, irregular-shaped cysts were observed, and large CD20+CD30+ Hodgkin cell-like cells proliferated in close association with the proliferating thymic epithelial cells. This case suggests the important role of thymic columnar epithelial cells in the proliferation of thymic B cells and the tumorigenesis of mediastinal grey zone lymphoma. Also, it suggests that mediastinal grey zone lymphoma can proliferate slowly in the very early stage.

Severe cytomegalovirus colitis with highly elevated sIL-2R mimicking aggressive transformation of adult T-cell lymphoma.

A smouldering adult T-cell leukaemia/lymphoma (ATLL) patient was admitted because of multiple erosions in the colon, which were infiltrated by a mixed population of lymphocytes. PET/CT demonstrated diffuse 18F-Fluorodeoxyglucose accumulation in the whole colon accompanied by multiple lymph node swelling. Histological examinations of lymph node suggested aggressive transformation to lymphoma type of ATLL. However, the general condition worsened with extremely elevated LDH, cytomegalovirus pp65 and sIL-2R after the administration of prednisolone. By contrast, subsequent administration of ganciclovir with tapered prednisolone ameliorated the laboratory findings. Differential diagnosis for aggressive ATLL and serious cytomegalovirus infection is needed.

CD27-positive hairy cell leukemia-Japanese variant.

We report a very rare case of a 45-year-old Japanese male patient with hairy cell leukemia-Japanese variant (HCL-JV) expressing CD27. The patient showed a high number of abnormal peripheral lymphocytes, thrombocytopenia, and severe splenomegaly but no lymphadenopathy. Histology of the resected spleen showed small-sized lymphoma cells diffusely infiltrating the red pulp without follicle formation. By immunohistochemistry, lymphoma cells were negative for CD3, CD5, CD8, CD10, CD34, cyclin-D1, and annexin A1 but positive for CD20 and BCL2. BRAF V600E mutation was not observed. Bone marrow aspirate showed preserved normal hematopoietic cells with invasion of lymphoma cells in an interstitial pattern without obvious nodules. The cells had abundant pale cytoplasm and round nuclei with inconspicuous nucleoli. After natural drying, the cells had unevenly distributed microvilli. Flow cytometric analysis demonstrated positivity for CD11a, CD11c, CD19, CD20, CD22, CD27, surface IgG, and λ but not for CD2, CD3, CD4, CD5, CD7, CD8, CD10, CD21, CD23, CD25, CD30, CD34, CD38, CD43, CD56, CD57, CD103, IgD, IgM, and κ. Monoclonal expansion of B cells was confirmed by an immunoglobulin heavy chain (IgH) rearrangement band as demonstrated by Southern blot hybridization. The lymphoma cells had unevenly distributed long, large, and broad-based microvilli, which resembled splenic diffuse red pulp small B cell lymphoma (SDRPL) cells. CD27 expression is extremely rare in HCL-JV, but the young age of the patient and high peripheral WBC counts were similar to HCL-JV, which suggests, in this case, an intermediate disease between SDRPL and HCL-JV.

Bone marrow macrophages in Waldenström's macroglobulinemia: a report of four cases.

It is well known that some B-cell lymphomas are accompanied by a prominent epithelioid cell response, caused by activated macrophages, such as marginal zone B-cell lymphoma of a mucosa-associated lymphoid tissue. We investigated six bone marrow samples from four cases of Waldenström's macroglobulinemia and report a unique observation that large conjugates of tumor cells around a macrophage were prominent in all cases, particularly in one case, the bone marrow of which contained increased CD163-positive macrophages. Mast cells were increased in all the samples, some of which seemed to be in close contact with tumor cells. We consider that the conjugates represented close interactions of tumor cells, macrophages, and mast cells by cell-to-cell contact. Three of the present cases showed a favorable course. On the other hand, one case suffered from severe anemia and thrombocytopenia due to hemophagocytic syndrome at the second admission and showed a severe clinical course. Clinicians should be aware of the risk of lymphoma-associated hemophagocytic syndrome in this low-grade lymphoma, although many of the patients with hemophagocytic syndrome in Japan have aggressive lymphomas such as diffuse large B-cell lymphoma.

CD5- and CD23-positive splenic diffuse large B-cell lymphoma with very low CD20 expression.

We report a rare primary splenic diffuse large B-cell lymphoma demonstrating CD5(+) and CD23(+) with very low CD20 expression. The only lesion was detected in the spleen, which was extremely enlarged with multiple large white-colored nodules. The lesion was characterized by a diffuse growth pattern of medium- to large-sized lymphoma cells with abundant cytoplasm. Immunohistochemical and flow cytometric study demonstrated that the lymphoma cells were negative for CD2, CD3, CD4, CD8, CD10, CD56, CD138, ALK-1, λ-light chain, and cyclin-D1, and positive for CD5, CD19, CD23, CD25, CD38, CD43, CD79a, IgM, IgD, κ-light chain, BCL2, BCL6, BOB. 1, Oct-2, Pax5, and MUM-1. CD20 was very weakly positive immunohistochemically, and negative by flow cytometric analysis. These findings resembled Richter syndrome, although chronic lymphocytic leukemia was not preexisting. Extremely poor outcome might be supposed because the effect of rituximab might be quite limited since CD20 was very weakly positive, in addition to an inferior prognosis of both CD20(-) and CD5(+) diffuse large B-cell lymphoma. Careful management is thus necessary.

Richter syndrome with follicular colonization of chronic lymphocytic leukemia/small lymphocytic lymphoma cells mimicking follicular lymphoma.

Follicular colonization is occasionally observed in marginal zone lymphoma. In rare cases, it has also been associated with mantle cell lymphoma. Chronic lymphocytic leukemia typically involves nodal or extranodal tissues as diffuse proliferation by complete effacement of the normal architecture. The involvement of chronic lymphocytic leukemia may be less frequently limited to the interfollicular areas. Here, we report a case of Richter syndrome of the small intestine that was initially diagnosed as follicular lymphoma of the gastrointestinal tract because of a partial follicular growth pattern in addition to a mainly diffuse proliferation pattern. The follicular pattern mimicking follicular lymphoma was shown to be composed of reactive follicles with follicular colonization of the original chronic lymphocytic leukemia cells. As the prognoses of Richter syndrome and follicular lymphoma of gastrointestinal tract are quite different, clinicians must carefully diagnose these conditions to avoid a misdiagnosis.

Double-hit lymphoma demonstrating t(6;14;18)(p25;q32;q21), suggesting two independent dual-hit translocations, MYC/BCL-2 and IRF4/BCL-2.

Here, we report a rare case of double-hit lymphoma, demonstrating t(6;14;18)(p25;q32;q21), suggesting two independent dual-translocations, c-MYC/BCL-2 and IRF4/BCL-2. The present case had a rare abnormal chromosome, t(6;14;18)(p25;q32;q21), independently, in addition to known dual-hit chromosomal abnormalities, t(14;18)(q32;q21) and t(8;22)(q24;q11.2). Lymph node was characterized by a follicular and diffuse growth pattern with variously sized neoplastic follicles. The intrafollicular area was composed of centrocytes with a few centroblasts and the interfollicular area was occupied by uniformly spread medium- to large-sized lymphocytes. CD23 immunostaining demonstrated a disrupted follicular dendritic cell meshwork. The intrafollicular tumor cells had a germinal center phenotype with the expression of surface IgM, CD10, Bcl-2, Bcl-6, and MUM1/IRF4. However, the interfollicular larger cells showed plasmacytic differentiation with diminished CD20, Bcl-2, Bcl-6, and positive intracytoplasmic IgM, and co-expression of MUM1/IRF4 and CD138 with increased Ki-67-positive cells (> 90%). MUM1/IRF4 has been found to induce c-MYC expression, and in turn, MYC transactivates MUM1/IRF4, creating a positive autoregulatory feedback loop. On the other hand, MUM1/IRF4 functions as a tumor suppressor in c-MYC-induced B-cell leukemia. The present rare case arouses interest in view of the possible "dual" activation of both c-MYC and MUM1/IRF4 through two independent dual-translocations, c-MYC/BCL-2 and IRF4/BCL-2.

Effect of cyclosporine on lymphocytic variant hypereosinophilic syndrome.

Lymphocytic variant hypereosinophilic syndromes (L-HES) is thought to be caused by the over-production of interleukin (IL)-5 by type 2 helper cells, which leads to reactive eosinophil expansion and activation. Here we demonstrate the effect of cyclosporine in a patient with L-HES. In the present case, the surface markers of cells from resected lymph nodes or peripheral blood were analyzed by flow cytometry. Serum concentrations of IL-4, IL-5, and IL-8 were measured using an enzyme-linked immunosorbent assay. Methyl-prednisolone pulse therapy followed by the administration of 150 mg/day of cyclosporine combined with 15 mg/day of prednisolone ameliorated eosinophilia. However, abnormal CD3-CD4+ T cell clones remained even when the eosinophil count recovered to normal levels. An elevated IL-8 level was observed only when eosinophils increased. On the other hand, serum IL-4 and IL-5 levels were under detectable limits during the course. Cyclosporine was effective in decreasing the eosinophil count without the elimination of abnormal T cell clones in the present case. Cytotoxic agents may be necessary to cure this serious disease. Moreover, target therapy for IL-8 may be a new strategy for L-HES with high IL-8 and low IL-5 concentrations.

CD20-negative low-grade B cell lymphoma showing immunophenotypic and genotypic features resembling plasma cell myeloma.

Here we demonstrate a unique case of CD20-negative low-grade B cell lymphoma showing immunophenotypic and genotypic features resembling multiple myeloma. The female patient had no abnormal masses, splenomegaly, swelled lymph nodes, or bone lesions. Although serum levels of IgG, IgA, and IgM were decreased without M protein, κ-type Bence-Jones protein was observed. In bone marrow, monotonous proliferation of small to medium-sized lymphoid cells was observed without classical myeloma cells, the same histological findings as lymphoplasmacytic lymphoma. The cells were CD38+, CD138+, CD43+, CD44+, CD3-, CD4-, CD5-, CD7-, CD8-, CD10-, CD11b-, CD19-, CD20-, CD21-, CD23-, CD24-, CD25-, CD27-, CD40-, CD45-, and CD56-. Surface or cytoplasmic IgM, κ, or λ were all negative. Chromosomal analysis demonstrated t(11;14)(q13;q32). The present case may belong to a new entity of low-grade B cell lymphoma with the same histological findings as lymphoplasmacytic lymphoma, mainly proliferated in bone marrow whose immunophenotype and genotype are similar to plasma cell myeloma.

Snail expression is associated with a poor prognosis in malignant pleural mesotheliomas.

BACKGROUND: Malignant pleural mesotheliomas (MPMs) are aggressive tumors with a poor prognosis. We aimed to clarify the mechanisms of epithelial-to-mesenchymal transition (EMT) in MPMs by analyzing the expressions of EMT-associated transcription factors and E-cadherin in relation to tumor proliferation rates and patient survival. METHODS: One hundred nine patients with MPMs were investigated. Among these patients, there were 61 epithelioid tumors, 21 sarcomatoid tumors, 20 biphasic tumors, and 7 desmoplastic tumors. Immunohistochemical analyses were performed to evaluate the expressions of Snail, ZEB1, Twist, E-cadherin, and the Ki-67 proliferation index. RESULTS: The expressions of Snail and ZEB1 were significantly higher in the nonepithelioid tumors than in the epithelioid tumors (p<0.0001 and p=0.0051, respectively). Furthermore, the E-cadherin expression was significantly lower in the Snail-high tumors than in the Snail-low tumors (p=0.0423). The E-cadherin expression was significantly lower in the nonepithelioid tumors than in the epithelioid tumors (p=0.0126). The Ki-67 proliferation index was significantly higher in the nonepithelioid tumors than in the epithelioid tumors (p=0.025). Patient survival was significantly lower in patients with Snail-high MPMs than in those with Snail-low MPMs (p=0.0016), especially in patients with nonepithelioid tumors (p=0.0089). The multivariate analysis also demonstrated that nuclear Snail expression was a significant predictor of poor prognosis in patients with MPMs (p=0.0142). CONCLUSIONS: The Snail expression is associated with EMT and a poor prognosis in MPMs. Snail could be a potential molecular target for the treatment of patients with MPMs.

Nodal marginal zone B cell lymphoma with prominent follicular colonization with deletion of chromosome 13.

Nodal marginal zone B cell lymphoma is a rare type of malignant lymphoma and appears to be heterogeneous. Here we report a 60-year-old woman with stage I splenic type of nodal marginal zone B cell lymphoma with prominent follicular colonization. She was treated only by radiation therapy, and remained free of disease on examination for 4 years. The lymph node cells showed an abnormal chromosome of deletion 13, although neither bone marrow cells nor peripheral blood cells demonstrated the same abnormal chromosome. This type of chromosomal abnormality has not been previously reported and may be related to good prognosis in the present case.