Histological And Immunohistochemical Characteristics Of Low-grade Endometrial Stromal Sarcoma With Smooth Muscle Differentiation

OBJECTIVE:Low-grade endometrial stromal sarcoma with smooth muscle differentiation(LGESS-SMD)is a rare mesenchymal tumor of the uterus.It is a challenging work to make diagnosis in daily practice due to its atypical histological features,morphology,and immunohistochemistry,in many respect share the similiarities with low-grade endometrial stromal sarcoma(LGESS)and highly cellular leiomyoma(HCL).With the extensive development of minimally and non-invasive surgeries in gynecology,specimens submitted for examination are often relatively fragmented,and it is difficult to judge the growth pattern of tumors and boundary infiltration,making diagnosis even more difficult.In this study,LGESS-SMD was studied,and LGESS and HCL were used as controls.Through histopathological observation and immunohistochemical studies,the morphological characteristics and immunohistochemical expression patterns were confirmed to find out the best differential diagnosis antibody panel.It provides the basis for the diagnosis and differential diagnosis of low-grade endometrial stromal sarcoma with smooth muscle differentiation.Materials and methods:The experimental subjects were surgical specimens from Peking Union Medical College Hospital.All specimens were fixed in neutral buffered formalin for 8 to 72 hours.The dehydration was performed by an automatic dehydrator and routinely paraffin-embedded to prepare serial slices of 4 u m in thickness for HE staining and immunohistochemical staining.All the sections were double-blind histological evaluated,immunohistochemical observation and scoring confirmed by two pathologists of senior gynecological pathology independantly.Cases with disagreement in diagnoses were determined under a multi-headed microscope.The histological diagnosis was based on the classification criteria of WHO gynecologic tumors in 2014.Histological observations included tumor growth patterns,tumor cell morphology,presence or absence of thick blood vessels in tumors,and the types of vascular structures shown by CD34 immunostaining.Immunohistochemical staining included the muscle-derived markers Desmin,SMA,Caldesmon,and Calponin;the endometrial mesenchymal markers included CD10;additional staining for CD34 was mainly used to display the vascular network structure in the tumor and myometrium.Muscle-derived and endometrial stromal markers were rated as 0 to 3 points in 4 grades based on their staining intensity and percentage of positive cells,respectively.0 is defined as full negative,positive cells 0%;1 is defined as weakly positive,the proportion of positive cells<30%;2 is defined as moderately positive,the proportion of positive cells is greater than or equal to 30%and less than or equal to 50%;3 is defined as strong positive and the proportion of positive cells is greater than 50%.Statistics performed with SPSS19.0 statistical software,count data using non-parametric chi-square test,measurement data using the t test,rank sum test was used when the heterogeneity of variance exist.Results:According to the growth pattern,Study showed in 31 cases of LGESS-SMD,16 cases(51.6%)were diffusely infiltrated,15 cases(48.4%)were focal infiltrative;while in 27 cased of LGESS,19 cases(70.4%)were diffusely infiltrated and 8 cases(29.6%)were focal infiltrating type;All the 27 cases of HCL were nodular growth(100%)type;from the view of tumor cell morphology,LGESS-SMD cells were spindle-shaped with reddish cytoplasm,so the tumor appeared "Pink" color under the microscope;LGESS tumor cells are short fusiform,often with high cellularity,some with myxoid changes;HCL cells are long spindle-shaped,highly cellular;Because of the high cellularity,LGESS and HCL was "Blue" under the microscope.In LGESS-SMD,most of the cases with smooth muscle differentiated cells showed a diffuse distribution in the tumor,but some cases showed nodular,patchy,cord-like distribution.Further observations revealed that thick-wal led blood vessels were seen in 17 cases(54.8%)of LGESS-SMD,while only 3 cases of thick-wal led blood vessels(11.1%)observed in LGESS.There was a significant difference between the two groups(P<0.05).The muscle-derived markers such as SMA.Desmin,and Caldesmon showed significant differences in three tumors(P<0.05).All the three smooth muscle markers in HCL were strongly diffuse positive,and the myogenic expression rate in LGESS-SMD was between that of HCL and LGESS.Calponin was negative in all three tumors.In LGESS-SMD cases,the sensitivity of the three myogenic markers was SMA>Desmin>Caldesmon.CD10 staining indicated that the positive rate of LGESS-SMD was significantly lower than that of LGESS,while all cases of HCL were negative for CD10.CD34 staining shows that the normal uterine smooth muscle vessels are spongy with long fissures,with large vessels in the center and a small number of capillaries around;LGESS is usually a certain number of spiral arteries and a large number of capillary vessels;thick blood vessels and capillaries are present in HCL.CD34 can reveal the relationship between invasive tumors(LGESS and LGESS-SMD)and the uterus intrinsic muscularis.Conclusions:Firstly,combined with the tumor growth pattern and the immunotyping of SMA,Desmin,Caldesmon,CD10 and CD34 antibodies can effectively diagnose and differentially diagnose the LGESS-SMD,LGESS and HCL.Secondly,CD34 staining helps to distinguish whether tumors in the uterine muscularis propria are invasive or nodular.Thirdly,whether there are thick-walled blood vessels in the stroma has a referential value for the identification of LGESS and LGESS-SMD.Last but not the least,when the tumor grows infiltratively,no matter how is the result the CD10 expresses,that we should diagnose as LGESS-SMD only one of the muscle biomarkers is positive,otherwise we could consider it as LGESS.Based on the above results,this paper presents a flowchart for the diagnosis and differential diagnosis of LGESS-SMD,LGESS,and HCL.