central nervous system ( cns ) involvement is a rare complication of acute promyelocytic leukemia ( apl ) and is encountered more frequently at the relapse stage than at presentation . the cns is the most commonly affected site of extramedullary relapse in apl [ 1 , 2 ] . the incidence of cns relapse ranges between 0.6% and 2% [ 2 - 4 ] . furthermore , cns involvement at the time of presentation is very rare , and only few cases have been reported in medical literature [ 5 - 9 ] . in this paper , we report 2 cases of apl with cns involvement at the time of disease presentation . a 43-yr - old woman presented with easy bruising for a month and stuporous mentality for several hours in february 2009 . initial laboratory evaluation showed a white blood cell ( wbc ) count of 48.610/l with 87% blasts , a hemoglobin count of 31 prothrombin time ( pt ) and activated partial thromboplastin time ( aptt ) at the time of admission were 14.5 sec ( 59% of normal ) and 28.3 sec , respectively . the findings of other coagulation tests were as follows : fibrinogen level , 1.14 g / l ; fibrin / fibrinogen degradation product level , 546.8 mg / l ; and d - dimer level , 283,600 g / l . numerous hypergranular promyelocytes ( 42% ) and myeloblasts ( 41% ) were visualized on bone marrow ( bm ) examination . immunophenotyping of the bm revealed that leukemic cells were positive for cd13 , cd33 , cd117 , and cd65 and negative for cd34 , cd15 , and cd2 . the chromosomal analysis of bm cells showed the karyotype 46,xx , t(15;17)(q22;q21)/46,xx , der(15)t(15;17)(q22;q21),ider(q10)(15;17 ) in 17 of the 20 metaphase cells . reverse transcriptase pcr ( rt - pcr ) showed a bcr1 isoform of the pml - rar fusion transcript in the bm specimen . for rt - pcr , total rna was extracted from the bm cells using a high pure rna isolation kit ( roche diagnostics , mannheim , germany ) , and reverse transcription was performed using moloney murine leukemia virus transcriptase enzyme ( invitrogen , carlsbad , ca , usa ) and a hexanucleotide mixture ( roche diagnostics ) . nested pcr was performed using geneamp pcr system 9600 ( perkin - elmer , norwalk , ct , usa ) . a lumbar puncture was performed to investigate the cause of her stuporous mentality ; and cerebrospinal fluid ( csf ) analysis revealed a wbc count of 2.210/l , red blood cell ( rbc ) count of 0.1610/l , and leukemic promyelocyte proportion of 97% in the bloody background ( fig . cytospins were prepared from csf cells using a shandon cytospin 3 ( shandon , astmoore , uk ) . the loading volume was 5 drops and centrifugation was performed at 700 rpm for 5 min . induction chemotherapy with all - trans - retinoic acid ( atra ) and idarubicin was initiated and intrathecal methotrexate ( 20 mg ) was administered simultaneously . however , the patient 's mentality and clinical condition worsened progressively and she died due to septic shock by infection and rapid disease progression only 3 days after admission . a 3-yr - old girl presented with easy bruising and epistaxis for several days in august 2007 . her initial laboratory evaluation revealed pancytopenia with a wbc count of 3.810/l and 8% blasts , hemoglobin level of 46 immunophenotyping of bm leukemic cells showed that they were positive for cd13 , cd33 , and cd117 and negative for cd34 , hla - dr , and cd2 . the chromosomal analysis showed the karyotype 46,xx , t(15;17)(q22;q21 ) in 7 of 20 metaphase cells . rt - pcr of the bm specimen showed the bcr3 isoform of the pml - rar fusion transcript and the ratio of pml - rar/abl determined by with quantitative pcr was 0.33 . csf analysis revealed 9.5% leukemic promyelocytes ( 2 of 21 cells ) with a wbc count of 0.00210/l without rbcs . the patient received induction chemotherapy with atra , idarubicin , and cytarabine , and intrathecal cytarabine ( 40 mg ) as per the protocol . a 43-yr - old woman presented with easy bruising for a month and stuporous mentality for several hours in february 2009 . initial laboratory evaluation showed a white blood cell ( wbc ) count of 48.610/l with 87% blasts , a hemoglobin count of 31 prothrombin time ( pt ) and activated partial thromboplastin time ( aptt ) at the time of admission were 14.5 sec ( 59% of normal ) and 28.3 sec , respectively . the findings of other coagulation tests were as follows : fibrinogen level , 1.14 g / l ; fibrin / fibrinogen degradation product level , 546.8 mg / l ; and d - dimer level , 283,600 g / l . numerous hypergranular promyelocytes ( 42% ) and myeloblasts ( 41% ) were visualized on bone marrow ( bm ) examination . immunophenotyping of the bm revealed that leukemic cells were positive for cd13 , cd33 , cd117 , and cd65 and negative for cd34 , cd15 , and cd2 . the chromosomal analysis of bm cells showed the karyotype 46,xx , t(15;17)(q22;q21)/46,xx , der(15)t(15;17)(q22;q21),ider(q10)(15;17 ) in 17 of the 20 metaphase cells . reverse transcriptase pcr ( rt - pcr ) showed a bcr1 isoform of the pml - rar fusion transcript in the bm specimen . for rt - pcr , total rna was extracted from the bm cells using a high pure rna isolation kit ( roche diagnostics , mannheim , germany ) , and reverse transcription was performed using moloney murine leukemia virus transcriptase enzyme ( invitrogen , carlsbad , ca , usa ) and a hexanucleotide mixture ( roche diagnostics ) . nested pcr was performed using geneamp pcr system 9600 ( perkin - elmer , norwalk , ct , usa ) . a lumbar puncture was performed to investigate the cause of her stuporous mentality ; and cerebrospinal fluid ( csf ) analysis revealed a wbc count of 2.210/l , red blood cell ( rbc ) count of 0.1610/l , and leukemic promyelocyte proportion of 97% in the bloody background ( fig . cytospins were prepared from csf cells using a shandon cytospin 3 ( shandon , astmoore , uk ) . the loading volume was 5 drops and centrifugation was performed at 700 rpm for 5 min . induction chemotherapy with all - trans - retinoic acid ( atra ) and idarubicin was initiated and intrathecal methotrexate ( 20 mg ) was administered simultaneously . however , the patient 's mentality and clinical condition worsened progressively and she died due to septic shock by infection and rapid disease progression only 3 days after admission . a 3-yr - old girl presented with easy bruising and epistaxis for several days in august 2007 . her initial laboratory evaluation revealed pancytopenia with a wbc count of 3.810/l and 8% blasts , hemoglobin level of 46 immunophenotyping of bm leukemic cells showed that they were positive for cd13 , cd33 , and cd117 and negative for cd34 , hla - dr , and cd2 . the chromosomal analysis showed the karyotype 46,xx , t(15;17)(q22;q21 ) in 7 of 20 metaphase cells . rt - pcr of the bm specimen showed the bcr3 isoform of the pml - rar fusion transcript and the ratio of pml - rar/abl determined by with quantitative pcr was 0.33 . csf analysis revealed 9.5% leukemic promyelocytes ( 2 of 21 cells ) with a wbc count of 0.00210/l without rbcs . the patient received induction chemotherapy with atra , idarubicin , and cytarabine , and intrathecal cytarabine ( 40 mg ) as per the protocol . apl is a unique disease entity associated with distinctive morphology and chromosomal abnormality , and it is often accompanied by severe coagulopathy . in these cases , performing a lumbar puncture at disease presentation or induction therapy is extremely hazardous because of frequently encountered bleeding diathesis and therefore , not recommended in patients with newly diagnosed apl in general . however , the presence of neurological symptoms such as headache , vertigo , nausea , vomiting , visual disturbance , seizure , and altered mental state [ 13 , 14 ] , necessitate a lumbar puncture both for diagnostic and therapeutic purposes [ 9 , 12 ] . in our cases , the first patient presented with altered mentality , and the second patient had no neurological symptoms . however , in the hematology and oncology division of the pediatric department in our institution , all apl patients undergo prophylactic lumbar punctures irrespective of their age or presence of neurological symptoms . recommended lumbar puncture at the time of apl diagnosis , immediately after the resolution of coagulopathy in order to diagnose cns involvement . in case 2 , the 3-yr - old girl was unable to express the disease - related symptoms accurately . in addition , csf analysis , showed a smaller number of leukemic cells ( 2 of 21 cells , wbc count , 0.00210/l ) than that in case 1 ( leukemic promyelocytes , 97% ; wbc 2.210/l ) . there have been several reports of patients with apl presenting with cns involvement in apl at the time of initial diagnosis ( table 1 ) . two cases of apl with cns involvement have been reported in korea [ 13 , 15 ] , and in both of these cases , cns was affected during relapse : one showed cns involvement with molecular relapse in the bm , and the second showed cns involvement with hematologic remission in the bm . to our knowledge , our report is the first to present cases of cns involvement at the time of diagnosis of apl in korea . treatment of cns involvement in apl can be diverse and can also be case - specific . cns therapy comprises of intrathecal chemotherapy , for example , cytarabine , methotrexate and hydrocortisone , and cns irradiation , while systemic therapy involves the administration of atra in addition to chemotherapy [ 3 , 14 ] . no molecular studies were performed with the csf specimen in either of the patients , because cytological examination of csf was considered sufficient to diagnose cns involvement . however , this limited the comparison of our cases with a recently reported case , because we did not have data on the pml - rar fusion transcript in the csf leukemic cells . in summary , we describe 2 cases of apl with cns involvement at the time of presentation . although cns involvement is a very rare event in apl at the time of initial diagnosis , we believe that apl patients with neurological symptoms must be evaluated for cns involvement by performing a lumbar puncture .