Yukinari Sanada

Pneumocystis jiroveci pneumonia detected by FDG-PET

Dear Editor, A 57-year-old woman suffered a relapse of follicular lymphoma and underwent high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (auto-PBSCT). Six months after auto-PBSCT, she developed dyspnea on exertion. Her chest X-ray findings were normal (Fig. 1a). The laboratory data revealed increased serum levels of LDH (723 IU/l) and soluble interleukin-2 receptor (3,945 U/ml). A recurrence of follicular lymphoma was suspected, and a whole-body FDG-PET was performed. FDG-PET images showed patchy increased FDG uptake in both lungs (Fig. 1b). An elevated level of β-D glucan of 2,645 pg/ml and KL-6 of 814 U/ml suggested Pneumocystis jiroveci pneumonia (PCP). Computed tomography (CT) scanning revealed patchy interstitial infiltrates in both lungs (Fig. 1c). Bronchoscopy with transbronchial lung biopsies was performed. Bronchoscopy revealed normal airways, and the biopsies demonstrated nonspecific findings. Microscopy for Pneumocystis was negative but a PCR analysis of bronchoalveolar lavage fluid revealed the P. jiroveci DNA to be positive. She was therefore administered with sulfamethoxazole-trimethoprim (ST) and prednisolone and thereafter the symptoms clinically improved. FDG-PET images after ST treatment of PCP showed complete resolution of the abnormal uptake in both lungs (Fig. 1d). A gallium scan is known to demonstrate changes resulting from Pneumosystis pneumonia even before chest X-ray changes occur [1]. The use of FDG-PET imaging has been documented in human immunodeficiency virus disease [2–4] and in infectious diseases [5]. FDG-PET may therefore also play a role in the early diagnosis of P. jiroveci pneumonia in immunocompromised patients with hematological malignancies.

PET-negative pulmonary intravascular large B cell lymphoma diagnosed by a random transbronchial lung biopsy.

Dear Editor, An 84-year-old male consulted our hospital because of thrombocytopenia (platelets, 9.7×10/μl) and elevated serum lactate dehydrogenase (LDH, 641 IU/l) in October 2009. An infection, collagen disease, or malignant lymphoma was suspected, but microbiological examinations were negative, and the evaluation for autoimmune disease was unremarkable. Bone marrow aspiration and biopsy provided no evidence of a hematological malignancy. Neither a computed tomography scan nor chest Xrays detected any specific findings. The elevation of the soluble interleukin-2 receptor (2,238 U/ml) suggested the possibility of malignant lymphoma, but neither hepatosplenomegaly nor lymphadenopathy was found. Intravascular large B cell lymphoma (IVLBCL) was suspected, but a random skin biopsy showed no specific findings. In December 2009, he was admitted to our hospital because of progressive dyspnea and hypoxemia. His serum LDH was elevated at 1,120 IU/l. Arterial blood gasses revealed hypoxemia (53.3 mmHg) and hypocapnia (34.7 mmHg). The alveolo-arterial difference of oxygen partial pressure was markedly increased (53.1 mmHg). Chest perfusion scintigraphy was performed on suspicion of pulmonary artery thromboembolism, but no perfusion defect was found. A fluorodeoxyglucose positron emission tomography (FDG-PET) scan showed nonspecific findings except for mild FDG uptake (SUV max of 3.0) in the right hilar lymph node, but a fusion CT scan demonstrated no lymph node enlargement adjacent to this uptake (Fig. 1). Although there was no abnormal accumulation of FDG in bilateral lung fields, we strongly suspected pulmonary IVLBCL because of his clinical symptoms and the evidence of hypoxemia. A random transbronchial lung biopsy (TBLB) was performed, and the pathological analysis showed massive proliferation of large tumor cells in the lumina of the small vessels (Fig. 2a). The intravascular tumor cells were positive for CD20 (L26) (Fig. 2b) and CD79a, and they were negative for CD3. Based on these results, pulmonary IVLBCL was diagnosed. Combined chemotherapy consisting of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) was started immediately after the definitive diagnosis of IVLBCL. His clinical symptoms and laboratory findings were dramatically improved. He received a total of eight courses of RCHOP, and complete remission (CR) was achieved. He still remains in CR 15 months after treatment. IVLBCL is a rare lymphoma characterized by the presence of large tumor cells within the blood vessels [1]. It has been considered that IVLBCL is a highly malignant disease with a poor prognosis [2]. The disease T. Nakazato (*) :Y. Sanada :A. Mihara : C. Ito :Y. Aisa Department of Hematology, Yokohama Municipal Citizen’s Hospital, 56 Okazawa-cho, Hodogaya-ku, Yokohama 240-8555, Japan e-mail: n-tomo@eurus.dti.ne.jp

Micronuclei-associated MYC amplification in the form of double minute chromosomes in acute myeloid leukemia

A 41-year-old male was admitted to our hospital due to fever and purpura. Peripheral blood values were hemoglobin 89 g/L, platelets 16 3 10/L, and white blood cells 3.4 3 10/L with 46% myeloblasts. Bone marrow examination showed hypercellular marrow with 71.0% myeloblasts and 23.0% other myeloid cells. Some of myeloblasts in the peripheral blood and bone marrow had one or two micronuclei (Image 1A, B). Furthermore, many large granules, suggestive of pseudo-Chediak–Higashi granules, were found in the cytoplasm of bone marrow myeloblasts (Image 1C). Dysplastic changes including degranulation and abnormal lobulation were observed in differentiated myeloid cells. Myeloblasts stained positive for myeloperoxidase and chloroacetate esterase. These cells were also positive for CD13, CD33, and HLA-DR, but negative for CD34. G-banding analysis of the bone marrow cells showed 43,X,-Y,-5,add(7)(q22),-20,1 40dmin[20] (Image 2A, B). Fluorescence in situ hybridization (FISH) with IGH/MYC/ CEP 8 probe on metaphase spreads revealed multiple MYC signals on the double minute chromosomes, indicating marked amplification of the MYC gene (Image 2C). In addition, FISH on interphase nuclei confirmed that micronuclei were heavily labeled with the MYC probe in 2 of 100 cells (Image 2D). Taking these hematological and cytogenetic findings into consideration, we made a diagnosis of acute myeloid leukemia (AML) with myelodysplasia-related changes according to the World Health Organization classification, or AML M2 by the French–American–British classification. The patient received two courses of standard induction therapy, but did not achieve complete remission. He underwent allogeneic stem cell transplantation because of worst prognosis cytogenetics including monosomal karyotype [1]. Micronuclei are defined as small nucleus-like structures that can be expelled from the nucleus. They usually contain amplified oncogenes, acentric chromosomal fragments, or whole damaged chromosomes [2]. Double minute chromosomes (dmin) are small chromatin bodies that lack centromeres and frequently mediate oncogene amplification in human tumors, although they are rarely found in AML. These chromosomes are commonly correlated with amplification of MYC at 8q24 or less commonly MLL at 11q23 [3–5]. The presence of dmin as part of complex karyotypes in AML appears to bring about chemotherapy resistance and rapid progression of the disease. To our knowledge, the association between micronuclei in myeloblasts and dmin with MYC amplification has previously been demonstrated in only one study [2]. In the present case, it is confirmed that dmin on metaphase cells and micronuclei on interphase cells also contained markedly amplified MYC. Image 1. Peripheral blood (A) and bone marrow (B) smears showing myeloblasts with micronuclei. Black arrows indicate micronuclei (May-Gr€ unwald–Giemsa staining, 31000)

Extramedullary T-lymphoid blast crisis of an ETV6/ABL1-positive myeloproliferative neoplasm with t(9;12)(q34;p13) and t(7;14)(p13;q11.2)

Dear Editor, Chromosomal translocations involving ETV6 at 12p13 and ABL1 at 9q34 are very rare, but are very rare but recurrent aberrations in hematological malignancies including BCR / ABL1-negative chronic myeloid leukemia (CML), myeloproliferative neoplasm (MPN), and acute leukemia [1, 2]. The resultant ETV6/ABL1 fusion protein is thought to play a crucial role in leukemic transformation by the constitutive activation of tyrosine kinase [1]. Similar to BCR /ABL1-positive CML, it has been reported that several cases of ETV6 /ABL1 -positive CML/MPN presented with blast crisis (BC) in lymph nodes as well as bone marrow [3–7]. Here, we describe the first case of extramedullary T-lymphoid BC of ETV6 /ABL1 -positive MPN. A 31-year-old man was admitted because of generalized lymphadenopathy and leukocytosis. Peripheral blood values were hemoglobin 113 g/L, platelets 438×10/L, and leukocytes 50.7×10/L with 20 % myelocytes, 17 % metamyelocytes, 10 % band forms, 32 % segmented neutrophils, and 11 % eosinophils. Bone marrow was hypercellular with myeloid hyperplasia and prominent eosinophilia, and compatible with MPN (Fig. 1a–c). Pathological examination of inguinal lymph nodes was consistent with T-lymphoblastic lymphoma (T-LBL) (Fig. 1d). Immunohistochemistry showed that lymphoma cells were positive for CD3, CD1a, and TdT (Fig. 1e). The patient was treated by dasatinib with hyper-CVAD protocol followed by myeloablative allogeneic stem cell transplantation (SCT). However, he died of idiopathic pneumonia syndrome, 11 months after initial diagnosis. G banding and spectral karyotyping of bone marrow cells on admission showed 46,XY,der(9)t(9;12)(q34;p13), del(12)(p13)[1]/46,sl,t(7;14)(p13;q11.2)[18]/47,sdl1,+19[1] (Fig. 2a). The karyotype of lymph node cells was similar as fol lows: 46,XY,t (7 ;14)(p13;q11.2) ,der(9) t (9 ;12) (q34;p13),del(12)(p13)[4]. Fluorescence in situ hybridization (FISH) on metaphase spreads of bone marrow cells detected the ETV6 /ABL1 fusion signal on the der(9)t(9;12)(q34;p13) (Fig. 2b). FISH on interphase nuclei of lymph node cells also confirmed the ETV6 /ABL1 fusion signals (Fig. 2c). Reverse transcription-polymerase chain reaction (RTPCR) demonstrated two types of ETV6 /ABL1 fusion transcripts (types B and A) only in bone marrow cells of the patient (Fig. 2d) [2]. Southern blot analyses of lymph node cells showed rearrangement of TRD@ Jδ1, but germline configuration of IGH@ JH, TRB@ Cβ1, and TRG@ Jγ (data not shown). We have detected a rare translocation der(9)t(9;12) (q34;p13) resulting in an ETV6 /ABL1 fusion gene. We confirmed an expression of the fusion transcripts in K. Yamamoto (*) :K. Yakushijin :Y. Miyata :Y. Sanada : A. Okamura :H. Matsuoka :H. Minami Division of Medical Oncology/Hematology, Department of Medicine, Graduate School of Medicine, Kobe University, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan e-mail: kyamamo@med.kobe-u.ac.jp

Lenalidomide is active for extramedullary disease in refractory multiple myeloma

Dear Editor, An 87-year-old male was diagnosed with multiple myeloma (IgG lambda, Durie and Salmon stage 3A, ISS stage 2) in January 2007. He received eight courses of chemotherapy with melphalan and prednisolone (MP) and thus maintained a partial remission. Because he became refractory to MP, he was then treated with 15 courses of high-dose dexamethasone from December 2007 to September 2010 and had another partial remission. However, he showed a progressive rise in IgG with a drop in hemoglobin. A laboratory evaluation revealed a serum IgG level of 5,364 mg/dl and hemoglobin of 7.6 g/dl, while the IgA and IgM levels were low. He was treated with one course of vincristine/ cyclophosphamide/doxorubicin/prednisolone, but there was no response. A CT scan revealed extramedullary plasmacytomas in the right chest wall and paravertebral space (Fig. 1). These abnormalities were not seen on CT scans performed 2 months before that presentation. Combination treatment with lenalidomide (10 mg orally, everyday continuously) and dexamethasone (20 mg/day, 4 days) was started. However, after 10 days, it was necessary to discontinue lenalidomide treatment because of febrile neutropenia and bacterial pneumonia. Despite the short duration of the administration of lenalidomide, a dramatic clinical improvement was achieved within 2 weeks. There was a significant reduction in the size of the palpable chest wall plasmacytoma, and his serum IgG level also decreased from 5,364 to 2,455 mg/dl. Repeat CT scans showed a marked reduction in the size of the extramedullary plasmacytomas in the right chest wall and paravertebral space (Fig. 2). Unfortunately, it was not possible to restart lenalidomide treatment because of his advanced age and poor performance status. Although he has not received any further treatment for his myeloma, the patient was still alive without any evidence of disease progression at the 6-month follow-up examination. Extramedullary (EM) disease of multiple myeloma may be present either at diagnosis or may occur during the course of the disease. Few studies have so far systematically evaluated the incidence of EM disease in patients with multiple myeloma. A longitudinal study of EM disease in 1,003 consecutive myeloma patients showed a rising incidence of EM in the last few decades from 4% in the period from 1971 to 1993 to 12% between 2000 and 2007 [1]. This trend has been attributed to more sensitive imaging techniques and prolonged patient survival. The presence of EM disease at any time during the course of the disease was associated with a significantly shorter overall

Sustained complete remission in an elderly patient with a blastic plasmacytoid dendritic cell neoplasm following autologous peripheral blood stem cell transplantation

Dear Editor, A 67-year-old male presented with a solitary 3-cm skin lesion on his left shoulder. The lesion comprised dark-red maculopapules without itching and pain (Fig. 1a). The patient was in a good general condition with no weight loss or systemic disorders. A skin biopsy showed diffuse dermal infiltrates composed of monomorphic medium-sized blasts with irregular nuclei and finely dispersed chromatin. The flow cytometric analysis showed that the tumor cells were positive for CD4 and CD56, and negative for CD19, CD20, CD34, CD117, cCD3, NKp46, and myeloperoxidase (MPO). Immunohistological staining showed that the tumor cells were positive for CD4 and CD56 and were also positive for CD123 (Fig. 1b). Based on these results, a diagnosis of blastic plasmacytoid dendritic cell neoplasm (BPDCN) was made. The skin lesions increased in size and then subsequently spread over the whole body. A complete blood count showed a white blood cell count of 10,800/μl with 28 % blastoid cells. The patient’s serum lactate dehydrogenase level was significantly elevated at 4930 IU/L. A bone marrow smear showed 87.5 % similar medium-sized blastoid cells (Fig. 1c). The cytochemical stainings showed that these blastoid cells were negative for MPO and for both specific and nonspecific esterases. A flow cytometric analysis of the bone marrow blastoid cells showed that they were identical to those of the skin, thus suggesting a similar clonal origin. The patient was treated with three cycles of CHOP. The skin lesions resolved, and the peripheral blasts disappeared promptly. As reported previously in BPDCN patients, while the response to initial chemotherapy usually results in CR, relapses occur rapidly. For this reason, we subsequently performed peripheral blood stem cell collection after one course of ESHAP therapy. He then received high-dose chemotherapy (MCE regimen; CY 60 mg/kg on days 7 and 6, VP16 500 mg/m on days 6 to 4, and MCNU 250 mg/m on days 3 and 2) and auto-PBSCT during the first remission. The patient has sustained a CR for 40 months after auto-PBSCT without any complications, and his general condition is good. BPDCN is a rare aggressive neoplasm that has been recognized as an independent entity in the WHO 2008 classification [1]. BPDCN is highly refractory to conventional chemotherapy, and it has a dismal overall prognosis. Although many of the patients initially respond to chemotherapy, most relapse within a year [2]. The median overall survival is only 13 months, and the Y. Sanada : T. Nakazato (*) :A. Mihara :C. Ito :Y. Aisa Department of Hematology, Yokohama Municipal Citizen’s Hospital, 56 Okazawacho, Hodogaya-ku, Yokohama 240-8555, Japan e-mail: n-tomo@eurus.dti.ne.jp

L-Asparaginase-induced fulminating liver dysfunction

A 40-year-old woman with no past medical history was diagnosed with B lymphoblastic leukemia (ALL), and received induction chemotherapy with L-asparaginase (Lasp), cyclophosphamide, doxorubicin, vincristine, and prednisolone. On day 20 of treatment, 2 days after the fifth administration of L-asp at a dose of 3000 KU/m/day, laboratory tests showed deranged liver function with elevated total bilirubin (2.2 mg/dL, normal 0.3–1.0), AST (70 U/L, normal 8–34), and ALT (43 U/L, normal 13–31). A computed tomography (CT) scan on day 26 revealed severely diffuse low-density of the liver (Fig. 1b), which was not observed at the onset of ALL (Fig. 1a). Furthermore, total bilirubin, AST, and ALT increased to 4.1 mg/ dL, 640 U/L, and 693 U/L, respectively. Because L-asp was suspected to have induced the fulminating liver dysfunction, the next dose of L-asp was discontinued, and ursodeoxycholic acid was administered for liver protection. While CT on day 40 showed similar results (Fig. 1c), on day 100 liver density had nearly recovered to its pre-chemotherapy state, followed by normalization of laboratory findings (Fig. 1d). Thereafter, she achieved and maintained a complete remission after the post-remission therapy, which included allogeneic hematopoietic stem cell transplantation. Although liver injury due to L-asp seems to be a wellknown adverse effect, impressive CT images such as in this case, possibly due to severe fatty liver, have rarely been reported. The mechanism of liver steatosis remains to be elucidated, but asparaginase may cause abnormalities in lipid metabolism by inhibiting protein synthesis. Such liver dysfunction may occasionally develop into fatal liver failure. This case suggests the importance of evaluating periodic CT scans for liver dysfunction after treatment with L-asp. CT images may be useful not only for early

Coexistent t(8;21)(q22;q22) Translocation and 5q Deletion in Acute Myeloid Leukemia.

The t(8;21)(q22;q22) translocation is specifically observed in acute myeloid leukemia (AML) M2 subtype, whereas del(5q) is one of the most common cytogenetic aberrations in myelodysplastic syndromes (MDS). Thus, t(8;21)(q22;q22) and del(5q) appear to be mutually exclusive, and the association between them has not been characterized yet. Here, we report an 81-year-old woman with coexistent t(8;21)(q22;q22) and del(5q) at initial diagnosis. The bone marrow was infiltrated with 18.4% myeloblasts, and showed marked myeloid and erythroid dysplasia. Myeloblasts were positive for CD19 and CD56 as well as CD13, CD33, CD34 and HLA-DR. G-banding and spectral karyotyping showed 46,XX,del(5)(q?),t(8;21)(q22;q22)[18]/46,XX[2]. Both del(5)(q?) and t(8;21)(q22;q22) were present in a single clone. Fluorescence in situ hybridization (FISH) on metaphase spreads detected a RUNX1/RUNX1T1 fusion signal on the der(8)t(8;21)(q22;q22), and confirmed deletion of CSF1R signaling at 5q33-q34 on the del(5)(q?). Furthermore, FISH on interphase nuclei revealed that the RUNX1/RUNX1T1 fusion signal and deletion of CSF1R signaling were found in 66.0% and 58.0% of interphase cells, respectively, suggesting that del(5)(q?) occurred in cells with RUNX1/RUNX1T1. These results indicated a diagnosis of AML with t(8;21)(q22;q22)/RUNX1/RUNX1T1 rather than MDS, even though the percentage of bone marrow myeloblasts was less than 20%. Based on these findings, together with those of other reported cases, del(5q) seems to be an extremely rare but recurrent secondary aberration in AML with t(8;21)(q22;q22).

Disappearance of double minute chromosomes with MYC amplification in relapsed acute myeloid leukemia after stem cell transplantation.

chromosomes, and revised the karyotype as follows (Fig. 2ab): 44,XY,-2,inv(3)(p25q21),der(5)del(5)(p?) del(5)(q?),der(7)(11?::7p13→7q22::7?::1?),add(9) (p13),-11,der(17)t(2;17)(q11.2;p11.2),der(20)t(2;20) (? ;q11 .2 ) ,2dmin[2] /42 , s l ,de l (1 ) (q? ) , r (6 ) ,de r (7 ) (7? : :p13→qter ) , -12 , -16 , -der (17) t (2 ;17) ,der (17) (2?::?::2?::17p11.2→17q23::12?),-2dmin[1]. Furthermore, dmin were shown to be derived from chromosomes 8. We next performed fluorescence in situ hybridization (FISH) with a probe for MYC located at 8q24 (Vysis LSI IGH/ MYC/CEP 8 Tri-Color Dual Fusion Probes), and detected multiple MYC signals on dmin (Fig. 1c). The patient underwent non-myeloablative cord blood transplantation (CBT) after conditioning with total body irradiation (TBI), fludarabine, and melphalan. However, the disease relapsed due to graft failure. G-banding at relapse after CBT showed 41~42,XY,2,inv(3)(p25q21),-4,der(5)del(5)(p?)del(5)(q?),der(7) (11?::7p13→7q22::7?::1?),add(9)(p13),-11,-12,-16,der(17) (2?::?::2?::17p11.2→17q23::12?),der(20)t(2;20)(?;q11.2) [cp5]/46,XY[15]. Thus, dmin disappeared, although other structural abnormalities remained. The patient next received an unrelated bone marrow transplant (u-BMT) after conditioning with TBI, fludarabine, and busulfan, but the disease progressed again. Unexpectedly, some of the myeloblasts had micronuclei (Fig. 1d). The similar karyotype did not include dmin (Fig. 1e): 40~43,XY,2,inv(3)(p25q21),-4,der(5)del(5)(p?)del(5)(q?),der(7) (11?::7p13→7q22::7?::1?),add(9)(p13),-11,-12,-16,der(17) (2?::?::2?::17p11.2→17q23::12?),der(20)t(2;20)(?;q11.2) [cp14]/41,sl,add(2)(q11.2),add(8)(q24),-add(9),+add(9) (p13)[5]/46,XY[1]. FISH also showed only three or four MYC signals (Fig. 1f). The patient succumbed to pneumonia 19 months after initial diagnosis. Double minute chromosomes (dmin) are small, acentric, extrachromosomal fragments that frequently mediate oncogene amplification and reflect rapid disease progression in human tumors. It has been shown that elimination of dmin can be induced by treating cancer cells with low concentrations of hydroxyurea or gemcitabine in vitro, resulting in reduced tumorigenicity and reversion of phenotype [1, 2]. Morphologically, the loss of dmin is facilitated by incorporation of dmin into micronuclei. However, this phenomenon has been reported only infrequently in primary tumor cells from patients [3]. A 58-year-old man was initially diagnosed with myelodysplastic syndrome, refractory cytopenia with multilineage dysplasia (MDS-RCMD). G-banding showed 44~45,XY,der(2;17)(q10;q10),inv(3)(p25q21),-5,-7,add(9) (p13),-11,-20,+mar1,+mar2,+mar3[cp8]/45,sl,+8[3]/46 ,XY[9]. After 11 months, the disease progressed to acute myeloid leukemia (AML). Peripheral blood values were as follows: hemoglobin 105 g/L, platelets 80 × 10/L and leukocytes 3.9 × 10/L with 22 % myeloblasts. Bone marrow was hypercellular with 46.6 % myeloblasts, which had many granules with vacuoles but no micronuclei (Fig. 1a). G-banding revealed the appearance of dmin (Fig. 1b): 42~45,XY,der(2;17)(q10;q10),inv(3)(p25q21),-5,-7,add(9) (p13),-11,-20,+mar1,+mar2,+mar3,0~85dmin[cp13]/42,sl ,add(1)(q21),add(1)(q32),+der(2)add(2)(p21)add(2)(q21),der(2;17),-inv(3),add(7)(p22),-12,-16,+mar4[2]/46,XY[5]. Spectral karyotyping (SKY) clarified the origin of marker

Conversion from nuclear bilobation to indentation in BCR/ABL1-positive acute myeloid leukemia lacking CD34 and HLA-DR expression

Dear Editor, Prominent nuclear indentations or invaginations of blasts are also called “cuplike” nuclei. Acute myeloid leukemia with cuplike nuclei (AML-CN) has distinct clinicopathologic and molecular features including lack of CD34 and HLA-DR expression, normal karyotype, NPM1 mutations, and FLT3internal tandem duplication (ITD) and often looks like acute promyelocytic leukemia (APL), microgranular variant [1–3]. Here, we present an interesting nuclear morphology of blasts, that is, nuclear bilobation at diagnosis and nuclear indentation at relapse, in BCR/ABL1-positive, CD34and HLA-DRnegative AML. A 67-year-old man was admitted to hospital because of marked leukocytosis. He had been diagnosed with pharyngeal squamous cell carcinoma 5 years earlier and had received concurrent radiotherapy and chemotherapy with cisplatin. He had no hepatosplenomegaly or lymphadenopathy on admission. Peripheral blood values were hemoglobin 92 g/L, platelets 32×10/L, and leukocytes 282.8×10/L with 84 % blasts. More than half of the blasts had bilobed nuclei with fine chromatin, agranular basophilic cytoplasm, and no Auer rods (Fig. 1a). Bone marrow was hypercellular with 70.0 % blasts stained positive for myeloperoxidase. Immunophenotyping determined that they were also positive for CD13 and CD33, but negative for CD34 and HLA-DR (Fig. 1b). Chromosome analysis of bone marrow cells showed 46,XY,t(1;9;22)(q32;q34;q11.2)[20]. Fluorescence in situ hybridization (FISH) revealed the BCR/ABL1 fusion signal on der(22)t(9;22)(q34;q11.2) (Fig. 1c). Reverse-transcription polymerase chain reaction confirmed the p210-type BCR/ABL1 fusion transcript, whereas PML/RARA fusion and FLT3-ITD were negative. Considering the normal peripheral blood count 12 months before admission and no hepatosplenomegaly, we made a diagnosis of BCR/ABL1-positive AML rather than chronic myeloid leukemia in blast crisis. According to the World Health Organization classification, a diagnosis of therapy-related myeloid neoplasms was also made. The patient received standard induction therapy followed by treatment with dasatinib and achieved complete remission. However, after 3 months, bone marrow examination revealed 23.4 % blasts. The karyotype was 46,XY, t ( 1 ; 9 ; 2 2 ) ( q 3 2 ; q 3 4 ; q 1 1 . 2 ) [ 1 ] / 4 6 , s l , a d d ( 1 ) (q32),add(18)(q21)[15]/46,XY[4]. Spectral karyotyping (SKY) confirmed the complex translocation (Fig. 1d). The leukocyte count increased to 70.8×10/L with 93 % blasts. Unexpectedly, approximately 30 % of the blasts showed nuclear indentation (Fig. 1e), while nuclear bilobation was rare. Because of the appearance of cuplike nuclei, we examined NPM1 mutations and detected the type A mutation in the bone marrow cells at diagnosis and at relapse, although NPM1 mutations are observed at low frequency in therapy-related myeloid neoplasms [4, 5]. FLT3-ITD was also negative at relapse. The patient died of progressive disease 11 months after the initial diagnosis. K. Yamamoto (*) :K. Yakushijin :Y. Sanada : S. Kawamoto : H. Matsuoka :H. Minami Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan e-mail: kyamamo@med.kobe-u.ac.jp