[Relationship between Coombs-positive autoimmune hemolytic anemia and development of malignant tumors: a retrospective study].

Autoimmune hemolytic anemia (AIHA) is secondary to underlying diseases, such as autoimmune diseases and lymphoid malignancies. Recently, solid cancers have also been reported to be associated with AIHA, although there is not much information available. In this study, we retrospectively examined the correlation between AIHA and onset of malignancy in 100 patients diagnosed with AIHA based on the broad definition of AIHA at our hospital and cooperating institutions from January 1, 1995 to May 31, 2016. Malignancies were detected in 52 of the 100 patients (hematological malignancies: 39 patients; solid cancers: 22 patients; total malignancies including multiple primary malignancies: 67 patients). Of the 67 patients with malignancies, 28 were diagnosed with malignancies within 6 months of AIHA diagnosis. All patients with cold agglutinin disease (CAD) were associated with malignancies. Compared with warm AIHA, solid cancers were significantly more common among the patients with CAD. These findings emphasize the importance of investigating the malignancies upon diagnosis of AIHA.

WRN protein as a novel erythroblast immunohistochemical marker with applications for the diagnosis of Werner syndrome.

Genetic testing for mutations in the WRN gene is critical for the diagnosis of Werner syndrome (WS); however, these tests cannot be performed in a clinical setting. Nearly all of the WRN mutations result in expression of truncated WRN proteins that are missing the C-terminal nuclear localization signal. We evaluated the use of WRN protein immunohistochemistry for diagnosing WS using paraffin-embedded bone marrow sections. Using a well-defined commercially available polyclonal antibody against the C terminus of WRN, we found that of all the cell types tested, bone marrow erythroid precursors showed the strongest nuclear expression of WRN. Immunohistochemical analysis of bone marrow samples from 120 patients with non-WS hematological disorders (age range, 7 days-90 years) revealed WRN staining of the nuclei of CD71-positive early and late erythroid precursors. Erythroblasts negative for WRN immunostaining were only observed in two patients, both of whom were diagnosed with WS: one with concomitant myelodysplastic syndrome and the other with erythroleukemia with overexpression of TP53. Western blot analysis and immunocytochemistry indicated WRN was localized in the nuclei of the four positive control cell lines from non-WS patients but not in the five cell lines from WS patients, who had three different types of WRN mutations. Thus, immunohistochemical detection of WRN in erythroblasts from bone marrow paraffin sections could be useful in screening of WS cases and worthy of further molecular confirmation.

Monocyte/Macrophage-specific marker CD163+ histiocytic sarcoma: case report with clinical, morphologic, immunohistochemical, and molecular genetic studies.

We report a case of a very rare disorder, histiocytic sarcoma, from a review of our autopsy cases. The neoplastic cells that proliferated in organs throughout the body were large cells containing eosinophilic cytoplasm and pleomorphic nuclei with prominent nucleoli. In the bone marrow, erythrophagocytosis by neoplastic cells was observed. The neoplastic cells were positive not only for lysozymes and CD68 (KP-1, PG-M1, and Ki-M1P) but also for a monocyte/macrophage-specific marker, CD163. In contrast, the results of tests for markers of myeloid cells, lymphoid cells, and epithelial cells were all negative. In a polymerase chain reaction study of paraffin-embedded tissues, analyses for the rearrangement of immunoglobulin heavy chain and T-cell receptor-gamma genes were negative. The current World Health Organization diagnostic criteria for histiocytic sarcoma regard immunohistochemical investigation as crucial. In this regard, the highly specific positivity for CD163 in this patient indicates that immunohistochemical staining of CD163 is very useful for the diagnosis of histiocytic sarcoma.

MLL/AF-1p fusion in therapy-related early pre-B acute lymphoblastic leukemia with t(1;11)(p32;q23) translocation developing in the relapse phase of acute promyelocytic leukemia.

We report the development of therapy-related early pre-B acute lymphoblastic leukemia in a patient administered a topoisomerase II inhibitor, etoposide, a consolidation therapy agent for acute promyelocytic leukemia. Our case is of interest because of simultaneous relapse of the original leukemia and onset of therapy-related leukemia and relatively rare t(1;11)(p32;q23) translocation with confirmed MLL/AF-1p fusion. This case suggests that careful monitoring for MLL gene rearrangements is necessary after administration of topoisomerase II inhibitors.

Multiple myeloma complicated by autoimmune hemolytic anemia.

A 57-year-old man was admitted with severe anemia and hypergamma globulinemia. After a diagnosis of multiple myeloma and autoimmune hemolytic anemia was made, chemotherapy rapidly decreased the M-protein level and improved his anemia with normalization of the direct Coombs test. The immunoglobulin binding to the patient's red cells was immunoglobulin G kappa chain like the myeloma M-protein. However, monoclonal immunoglobulin G derived from short-term culture of the patient's bone marrow mononuclear cells did not bind to a panel of red cells. Therefore, the relationship between the M protein produced by his myeloma cells and hemolysis remained unclear.

[Acute myelogenous leukemia associated with severe esophageal stricture after chemotherapy].

A 41-year-old woman with relapsed acute myelogenous leukemia was treated twice with idarubicin hydrochloride and cytarabine. She developed a 6-cm-long stricture in the lower esophagus 12 days after re-induction therapy. Although she had preceding candida infection, it is suspected that her stricture was caused by mucosal damage due to chemotherapeutic agents. This case suggests that the possibility of esophageal stricture should be considered in patients with swallowing disturbance after intensive chemotherapy.

[Seven patients with stage I and II primary testicular lymphoma].

Seven patients with stage I and II primary testicular lymphoma (PTL) have been treated since 1990 to the present at Kawasaki Medical School. All patients, whose median age was 56 yrs, had initially complained of swelling of the scrotal contents. The lesions were on the right in two patients, on the left in five, and no patient had bilateral lesions. The histological diagnosis was diffuse large B-cell type in all patients. Five patients were classified as Ann Arbor stage I, and two at stage II. After high-orchiectomy for resection of tumor, two patients received chemotherapy alone, with a combination of chemotherapy and irradiation of the contralateral testis in the remaining five. Complete remission was achieved in all seven patients, but relapse occurred later in one. As it is recognized that, even in localized stage or low risk group PTL patients, the relapse rate in the central nervous system (CNS) and contralateral testis is quite high, chemotherapy, prophylactic CNS treatment and radiation of the contralateral testis after tumor resection should be included in the management of PTL.

Detection of bone marrow and extramedullary involvement in patients with non-Hodgkin's lymphoma by whole-body MRI: comparison with bone and 67Ga scintigraphies.

The aim of this study was to evaluate the diagnostic potential of whole-body MRI (WB-MRI) for the detection of bone marrow and extramedullary involvement in patients with non-Hodgkin's lymphoma. WB-MRI, which was performed on 34 patients, consisted of the recording of T1-weighted spin-echo images and a fast STIR sequence covering the entire skeleton. The WB-MRI findings for bone marrow and extramedullary involvement were compared with those from (67)Ga and bone scintigraphies and bone marrow biopsy results. Two MRI specialists reviewed the WB-MRI results and two expert radiologists in the field of nuclear medicine reviewed the bone and (67)Ga scintigraphy findings. Bone marrow and extramedullary involvement of non-Hodgkin's lymphoma were confirmed by follow-up radiographs and CT and/or a histological biopsy. The detection rate of WB-MRI was high. More bone marrow involvement was detected by biopsy, and more lesions were detected by scintigraphies. In total, 89 lesions were detected by WB-MRI, whereas 15 were found by biopsy, 5 by (67)Ga scintigraphy, and 14 by bone scintigraphy. WB-MRI could also detect more extramedullary lesions than (67)Ga scintigraphy; i.e., 72 lesions were detected by WB-MRI, whereas 54 were discovered by (67)Ga scintigraphy. WB-MRI is useful for evaluating the involvement of bone marrow and extramedullary lesions throughout the skeleton in patients with non-Hodgkin's lymphoma.