| Background and ObjectiveMyeloid sarcoma(MS),also means chloroma,granulocytic sarcoma,extramedullary myeloid tumor.It is a tumor mass consisting of myeloid blasts with or without maturation occurring at an anatomic site other than the bone marrow.It is often concurrent with acute myeloid leukemia(AML).So far,there is no exact data on the incidence of MS in the general population.Foreign clinical studies have reported that the incidence of MS in patients with AML is 2.5%～9.1%.It has also been reported that the ratio can be as high as 40%among children.At present,most of the domestic literature on MS in children is limited to case reports and small retrospective studies.The imaging findings of masses suspected of MS are not diagnosed by biopsy,and chemotherapy is performed directly,so the clinical diagnosis rate of MS is usually low.The World Health Organization(WHO)recognizes a variety of extramedullary manifestations of myeloid neoplasms:Category Ⅰ.MS with AML;Category Ⅱ.Isolated MS(normal peripheral blood smear and bone marrow biopsy,and no history of myeloid tumor);Category Ⅲ.Extramedullary relapse of AML,including recurrence after hematopoietic stem cell transplantation(HSCT);Category Ⅳ.MDS/MPNs blast/conversion phase.In most patients with myeloproliferative diseases,the diagnosis of MS may be relatively simple.However,the diagnosis of isolated MS is difficult.In the 1980s,Meis et al reported in a retrospective study that the misdiagnosis rate of isolated MS was as high as 75%.The misdiagnosis rate in the recent series of reports has dropped to 25%～47%.It is often misdiagnosed as malignant lymphoproliferative disease,local infection,inflammation and so on.It was not corrected until bone puncture biopsy was diagnosed as acute leukemia,and treatment was often delayed.There is no unified standard for the treatment of MS in children.Clinically,it is often treated by systemic chemotherapy,surgical resection,radiotherapy,HSCT and so on.But the prognosis is still very poor.The 5-year OS rate is between 20%and 30%.The data about the prognostic significance of MS is also limited.It is urgent to solve the problems such as whether transplantation can improve the prognosis of MS and explore new treatment methods.At present,most of the domestic literature on MS in children is limited to case reports,and the clinical diagnosis rate is low,the prognosis is poor,and there are still many ambiguities in clinical knowledge of diagnosis,treatment and prognosis.This study analyzed the clinical data of 16 MS patients admitted to the first affiliated Hospital of Zhengzhou University from January 1,2013 to January 1,2021 retrospectively.The involved sites,initial clinical manifestations,imaging features,pathological immunohistochemistry,gene chromosome results,treatment and prognosis were analyzed and summarized in order to improve the ability of Chinese clinicians in early identification,diagnosis and treatment of MS.Methods1.Cases data:This study is a single center retrospective study.16 patients with MS confirmed by biopsy from January 1,2013 to January 1,2021 were studied.The involved sites,initial clinical manifestations,imaging features,pathological immunohistochemistry,gene chromosome results,treatment and prognosis were analyzed and summarized.2.Statistical analysis:SPSS 21.0 software was used for statistical analysis.The quantitative data accord with normal distribution and are expressed by median(numerical range).The number of cases(%)was used for qualitative data.The survival rate was evaluated by Kaplan-Meier method.Log-rank test were used to compare the difference of survival curve between groups.The difference was statistically significant(P=0.05).The drawing was carried out by GraphPad Prism7.00 software.Results1.General clinical data:There were 7 cases of category I,5 cases of category Ⅱand 4 cases of category Ⅲ.There were 8 males and 8 females,with a ratio of 1 to 1.The ratio of male to female in category Ⅰ,Ⅱ and Ⅲ was 2:5,4:1 and 1:1,respectively.The median age of the first onset of the disease was 8.3 years(0.5year～16.0 years).2.The first site of category Ⅰ was the orbit(42.8%).Category Ⅱ and Ⅲ were mostly in the upper and lower jaw(50.0%,33.3%).75%of the patients included orbital mass,upper mandible,nasopharynx,cervical lymph nodes,fibula,intramuscular and skin with local tissue painless swelling and mass as the first symptoms.The median length and diameter of the lesion was 4.0cm(1～11.0cm).The median size of category Ⅰ,Ⅱ and Ⅲ was 5.0 cm,3.0 cm,3.0 cm,respectively.There was no significant difference among the three groups(F=0.93,P=0.415).Among them,3 cases were multiple nodules and the rest were solitary nodules.The first visits of 13 cases were in non-hematological departments.No hepatomegaly was found in 16 cases.Only 1 case had splenomegaly.The superficial lymph nodes were enlarged in 4 cases.3.Laboratory results:The first visit to the three lines of blood routine(white blood cell count,hemoglobin content,platelet count)indicated that the two lines decreased in 3 cases(18.7%).The number of primary series decreased in 4 cases(25.0%).All the three systems were normal in 9 cases(56.3%),in which category Ⅰ,Ⅱand Ⅲ accounted for 42.9%,60.0%and 75%,respectively.No immature cells were found in 9 cases,accounting for 14.3%,100%and 75%in category Ⅰ,Ⅱ and Ⅲ,respectively.9 cases of bone marrow cytology showed that the immature cells did not meet the diagnostic criteria of AML,and all of them belonged to category Ⅱ and Ⅲ.4.Imaging features:Most of the lesions showed inhomogeneous enhancement on CT.On T1 of MRI,most of the lesions were isointense or hypointense,and T2 were mostly slight hypointense or hyperintense.Uniform and obvious enhancement can be seen after injection of contrast agent.5.Immunohistochemistry:There was at least one positive antigen reflecting myeloid differentiation(MPO,CD117,CD13,CD33)or mononuclear differentiation(CD68 and CD163,CD14,CD11c)in all cases.The positive rate of MPO was about 66.7%.6.Gene and chromosome results:Chromosome examination was performed in 9 cases.4 cases were normal,and 5 cases were abnormal,of which 1 case was 47,XY,inv(6)(p21p23),+8[7]/46,XY[13],4 cases were 46,XX,t(8;21)(q22;q22),which forming fusion gene of AML1-ETO.FLT3-ITD mutation was detected in 2 cases.KIT mutation was detected in 2 cases.TP53 mutation was detected in 1case.TET2 mutation was detected in 1 case.CEBPA mutation was detected in 1 case.7.Treatment and prognosis:2 cases were only supported by symptomatic treatment after confirmed by biopsy.The remaining 12 cases were treated by operation and/or chemotherapy with AML regimen.HSCT was performed in 3 cases.Among them,2 cases were successful and 1 case failed.2 cases were positive for FLT3-ITD and added sorafenib orally.The total follow-up period was from 0.9 month to 54.7 months.The median survival time was 20.8 months.The 1-year,3-year and 54.7-month overall survival(OS)rates were 64.2%,36.7%and 36.7%,respectively.By pairwise comparison of the survival curves of the three groups,it was found that the OS rate of category Ⅰ was higher than that of category Ⅲ(Log-rank test:χ2=5.277,P=0.022<0.05,).The median survival time of male and female groups were 6.0 months and 20.9 months respectively,and that there was no difference in survival curve between the two groups(Log-rank test:χ2=1.183,P=0.277>0.05).The median survival time of transplantation group and non-transplantation group were 20.9 months and 20.8 months respectively and there was no difference in survival curve between the two groups(Log-rank:χ2=0.113,P=0.737>0.05).The median survival time of multiple nodule group and single nodule group was 3.8 months and 20.9 months,respectively.The survival rate of multiple nodule group was lower than that of single nodule group(Log-rank检验:χ2=9.811,P=0.002).Conclusions1.For suspected category I MS patients with no obvious abnormality in the three lines of blood routine,early morphological analysis of peripheral blood cells or bone marrow cytology examination is helpful for differential diagnosis.2.For AML patients with positive AML1-ETO fusion gene,it is recommended that imaging examination and early screening of MS should be performed as soon as possible.3.For painless masses in children,especially in the orbit and maxilla,it is recommended to make a definite diagnosis by pathological biopsy.4.The prognosis of patients with category Ⅲ and multiple nodular infiltration at the first involved site is very poor,and clinical treatment should be strengthened. |
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