Richter’s syndrome (RS) of the central nervous system (CNS) is known to have an extremely poor prognosis. Ibrutinib has been reported to have some activity in patients with RS, despite its poor prognosis. Although ibrutinib crosses the blood-brain barrier, its efficacy in RS patients with CNS involvement remains unknown. Here, we report a case of RS isolated in the CNS that was confirmed to be clonally related to chronic lymphocytic leukemia (CLL) by immunoglobulin heavy chain gene analysis. Although the median survival of patients with RS clonally related to CLL was significantly shorter than that of patients with RS clonally unrelated to CLL, the patient received ibrutinib monotherapy without experiencing any significant adverse events, and the disease remained stable with ibrutinib until 6 weeks later. Following whole-brain radiation therapy (40 Gy in 20 fractions) with dexamethasone, the patient has survived for five months after diagnosis. Thus, ibrutinib may be a safe and effective therapeutic option for patients with RS and CNS involvement.
We describe two patients with primary diffuse large B-cell lymphoma of the central nervous system (PCNS-DLBCL). The first patient (case 1) was a woman in her late 70s who presented with a tumor in the left frontal lobe, whereas the second patient (case 2) was a man in his early 70s who presented with a left frontal lobe tumor associated with intratumoral hemorrhage. The histopathology of the tumor specimen disclosed the proliferation of large cells with centroblastic (case 1) or immunoblastic/plasmablastic (case 2) cytomorphology and an accumulation of the tumor cells within the perivascular space. The cells in both cases were positive for CD20, CD79a, BCL6, IRF4/MUM1, MYC, and BCL2 and negative for CD5 and CD10. G-banding revealed t(8;14)(q24;q32) in case 1, and the tetraploid-range karyotype including two or three copies of der(3)t(3;14)(q27;q32) and der(14)t(3;14)(q27;q32) in case 2. Fluorescence in situ hybridization applied to metaphase spreads confirmed colocalization of MYC and IGH (case 1) and BCL6 and IGH (case 2) hybridization signals on the relevant derivative chromosomes. Case 1 carried the MYD88L265P mutation. This case report provides clear evidence for the occurrence of t(8;14)(q24;q32) and t(3;14)(q27;q32) in PCNS-DLBCL using metaphase-based cytogenetic analysis.
It is difficult to histologically differentiate extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) from chronic gastritis (CG)/ reactive lymphoid hyperplasia (RLH). To determine whether immunohistochemistry for IRTA1 and MNDA can differentiate gastric MALT lymphoma from CG/RLH, we investigated 81 stomach biopsy specimens [Wotherspoon grade (WG) 1, 11 cases; WG 2, 9 cases; WG 3, 20 cases; WG 4, 31 cases; and WG 5, 10 cases]. According to a previously reported algorithm involving PCR for immunoglobulin heavy (IgH) chain locus rearrangement, all 81 cases were divided into three groups: CG/RLH (55 cases), MALT lymphoma (19 cases) groups, and IgH undetectable group (7 cases). We analyzed the CG/RLH and MALT lymphoma groups. The median percentage of IRTA1-positive cells was 0% (range 0%–90.6%) in the CG/RLH group and 43.5% (range 0%–97.6%) in the MALT lymphoma group (p < 0.0001). The median percentage of MNDA-positive cells was 32.4% (range 0%–97.6%) in the CG/RLH group and 55.1% (range 0%–97.6%) in the MALT lymphoma group (p = 0.0044). These results indicate that immunohistochemistry for IRTA1 and MNDA can help differentiate gastric MALT lymphoma from CG/RLH.
Cholesterol uptake via LDL receptor (LDLR) is increased in some malignant tumors, and incorporated LDL contribute to lipid droplet formation. Burkitt’s lymphoma is known to have a large number of vacuoles in the cytoplasm, however, intracellular vacuoles are also seen in high-grade lymphomas such as adult T-cell leukemia/lymphoma, diffuse large B-cell lymphoma and primary central nervous system lymphoma. Recent studies have shown that esterified cholesterol is the main component of these vacuoles and the expression of cholesterol metabolism-related molecules such as LDLR, acetyl-CoA acetyltransferase 1 (ACAT1) which esterifies free cholesterol, and scavenger receptor class B type I (SR-BI) which effluxes free cholesterol, was significantly upregulated in lymphoma cells. Moreover, negative feedback of LDLR was not regulated even under cholesterol-rich conditions in lymphoma cells. We found that cytoplasmic free cholesterol was increased by ACAT and SR-BI inhibitors (CI-976 and BLT-1, respectively), and the accumulation of free cholesterol induced lymphoma cell apoptosis. In addition, overexpression of lipid droplet surface proteins has been correlated with poor prognosis in several malignant tumor such as ovarian cancer and clear cell renal cell carcinoma, and it is important to evaluate lipid droplet formation in malignant tumors including lymphomas.
Bone marrow necrosis (BMN) occurs most frequently in hematological malignancies and sometimes in non-hematological disorders. Lymphoid diseases causing necrosis are regarded as high-grade disease. B-lymphoblastic leukemia/lymphoma is the most common malignant cause of BMN. Here, we present two patients with follicular lymphoma (FL) and MYC gene abnormalities who developed BMN. In one case of BMN, the necrosis disappeared in response to chemotherapy, and the patient survived with complete remission. In the other case, BMN remained even after chemotherapy, and effective chemotherapy could not be administered due to suppressed hematopoiesis, which led to the lymphoma worsening and the patient’s death. Indolent lymphomas, such as FL, as in these cases, have the potential to develop BMN. It is important to detect the development of BMN and administer chemotherapy early to improve patient prognosis, since severe BMN prevents patients from receiving effective treatment.
Autoimmune pancytopenia is rarely seen with Hodgkin lymphoma, and only one pediatric case of pancytopenia after autologous hematopoietic stem cell transplantation (HSCT) has been reported. We herein report a case of autoimmune pancytopenia that developed after autologous HSCT for nodular lymphocyte predominant Hodgkin lymphoma (NLPHL). A 56-year-old Japanese woman underwent autologous HSCT for NLPHL. She developed autoimmune pancytopenia seven months after autologous HSCT. In this case, PSL was effective, and the blood cell counts normalized completely. However, the patient suffered from a fatal infection, probably because of immunosuppression caused by prolonged administration of PSL, as well as a history of several chemotherapies and autologous HSCT. To our knowledge, this is the first adult case of autoimmune pancytopenia after autologous HSCT for Hodgkin lymphoma. To further validate the optimal treatment strategy for autoimmune cytopenia after autologous HSCT, more cases are necessary.
In the 2016 update of the World Health Organization (WHO) classification of myeloid neoplasms, acute undifferentiated leukemia (AUL) was defined by a lack of lineage-specific markers. AUL has very poor prognosis and no established therapies due to its rarity. We report a case of a 31-year-old man with AUL who showed complete molecular response to an acute lymphoblastic leukemia (ALL)-based regimen and received allogeneic hematopoietic stem cell transplantation. The patient’s blast cells were CD7-positive and localized to lymph nodes in the neck and to a large mediastinal mass; there was also rearrangement of the T-cell receptor delta locus. Although the tumor showed characteristics of T-cell lymphoblastic lymphoma, it was categorized as AUL based on WHO classification. This case suggests that a high-intensity conditioning regimen could be effective for rare cases of AUL that present only in the extramedullary mass, and chemotherapy for AUL should be selected based on the characteristics of the blasts.
We report a patient with sarcoidosis who developed diffuse large B-cell lymphoma. A 71-year-old woman with persistent cough was diagnosed pathologically with sarcoidosis by resection of the right upper lung lobe with a nodule after an unsuccessful attempt of transbronchial needle aspiration for mediastinal lymphadenopathy. She was referred for an eye examination and found to have spotty retinal degeneration on the lower fundi of both eyes, together with residual macular edema and vitreous opacity in the left eye. At 76 years, she underwent cataract surgery and vitrectomy to gain a visual acuity of 0.6 in the left eye. At 77 years, she developed a cough and fever, and showed leukopenia and thrombocytopenia. Computed tomography showed multiple small nodular lesions in both lungs, and bilateral hilar, mediastinal, and hepatic lymphadenopathy. Fluorodeoxyglucose positron emission tomography demonstrated high uptake in the liver, spleen, pancreatic head, and lymph nodes. Bone marrow biopsy was intact, but liver biopsy revealed anomalous large lymphoid cells in the sinusoids which were positive for CD20 and showed a high Ki-67 index, leading to the diagnosis of diffuse large B-cell lymphoma. Chemotherapy with 8 courses of THP-COP (cyclophosphamide, pirarubicin, vincristine, and prednisolone) with rituximab, followed by intrathecal injection of methotrexate, cytarabine, and dexamethasone, resulted in complete remission. She maintained complete remission for 10 years until 88 years old at present. The literature review found 30 patients, including this case, who developed lymphoma in the course of sarcoidosis. A novel pathological diagnosis is required in the setting of acute symptomatic changes and novel lesions on imaging in patients with sarcoidosis.