Ying Chen ,Jian-Chuan He ,Zhu-Fa Hou＊

1Hospital of Chengdu University of Traditional Chinese Medicine,Chengdu 610075,Sichuan,China.

Myelodysplastic syndrome(MDS)is a malignant clonal disease of human hematopoietic stem cells.In this paper,a case of MDS with fever and rash as the first symptom was reported in our hospital,and the related literature was reviewed and summarized to provide ideas for the diagnosis of MDS.Case summary:The patient,male,62 years old,with systemic rash and fever as the initial symptoms,early multiple bone marrow examination showed no typical abnormalities.With the progress of the disease,bone marrow cytology,flow cytometry,molecular karyotype,chromosomal karyotype,skin biopsy and pathological diagnosis were performed,and the diagnosis was MDS.

Key words:Erythra,Heat,Myelodysplastic Syndromes

Case data

The patient,male,is a 62-year-old Chinese.He was admitted to the Hospital of Chengdu University of Traditional Chinese Medicine on February 11,2019 because of"systemic rash for more than one year and fatigue for one week".One year ago,the patient developed erythema and nodules of the size of Red Coins scattered throughout the body.Some of them disappeared in a ring shape and faded when pressed.No scales,blisters,erosion and exudation were found.The patient had pain in the right finger joint,difficulty in clenching a fist,normal muscle strength and no other muscle and joint pain.No fatigue,alopecia,bleeding,light sensitivity and other discomfort,the local hospital,diagnosed as mycosis fungoides,given acitretin,methylprednisolone and other treatment,the effect is not good.He has visited many municipal hospitals and improved the blood routine,erythrocyte sedimentation rate,CRP,immune indicators and other tests.The skin biopsy pathology considered atypic al lymphoproliferative disease of the skin,peripheral T-cell lymphoma,non-specific type is not excluded,diagnosis considered lymphoproliferative disease,bone marrow puncture examination,bone marrow smear showed no definite abnormality.Bone marrow histopathology:the ratio of hematopoietic tissue to adipose tissue is about 2-3:1;the ratio of granulocyte to red is about 6-8:1,mainly with lobulated nuclear granulocytes(MPO(+)，A few small megakaryocytes and naked megakaryocytes can be seen,and a few lymphocytes and plasma cells are scattered and distributed in small foci.Immunohistochemical staining showed scattered lymphocytes CD20 (+,P),CD3 (+,P),CD56 (-),plasma cell CD38 (+,accounting for about 8% of nuclear cells),κ (+,P),λ(+,P).TCR gene rearrangement showed a low amplification peak,considering the diagnosis of"lymphoproliferative disease",interferon,hormone and other treatments,rash aggravation,poor efficacy.One week ago,the patient felt weak limbs with repeated fever,with a maximum temperature of 40.2℃.Physical examination:facial erythema,desquamation,ecchymosis of both lower limbs,integration into the film,partial ulceration (Figure 1a).The abdomen was scattered with infiltrating erythema and nodules 1～2 cm in diameter (Figure 1b),axillary and inguinal lymph nodes were palpable,and the remaining superficial lymph nodes were not palpable and significantly enlarged.The liver and spleen were not palpable under the hypochondrium,and no redness and swelling were seen in the joints of the whole body.Relevant examinations after admission:blood routine:PLT 36*10^9/L,RBC 1.29*10^12/L,Hb 37g/L.Histopathology of skin lesions (Figure 2a) showed squamous epithelial fibrous tissue hyperplasia with infiltration of numerous atypical cells around small vessels and skin appendages.Bone marrow cytology showed that granulocyte hematopoiesis was vigorous (primordial cells account for 4%),the erythronmegakaryocyte and megakaryocyte hematopoiesis was inhibited with cell morphological changes (erythroid nucleus malformation,H-J corpuscles,megakaryocytes occasionally small megakaryocytes) and monocytes accounted for 8%.Flow cytometry showed an increased proportion of granulocytes (91.7%) with some cells expressing CD56.Immunohistochemical results of bone marrow pathology (Figure 2b and Figure 2c) showed Ki-67 (70%+),MPO (+),CK-P(epithelial+),CD13 (+),CD33 (+),CD68 (+),CD14(+).Molecular karyotype analysis showed that some regions of chromosomes 2,13 and 22 were missing.Bone marrow karyotype analysis suggested that 46,XY,del (13) (q14.13q14.3) [24].Analysis of 24 mitotic phases revealed partial band loss on the long arm of chromosome 13.Monoclonal rearrangements of TCR-related genes were not monitored by TCR gene results.After the diagnosis of MDS,the patient was treated with demethylation therapy (decitabine 10mg d1-d5 5 cycles of chemotherapy).After one cycle of treatment,the rash gradually disappeared.After five cycles,the patient was discharged in September 2019.The outpatient treatment of traditional Chinese medicine so far,there is no rash,no fever,and no abnormality in blood routine reexamination.

Figure 1 a Both lower limbs petechiae,LOs synthesis of films,some broken here;Figure 1b Abdominal in diameter 1-2cm infiltrating erythema,nodules

Figure 2 a Histopathology of skin lesions（HE×200）;Figure 2b Positive of myeloperoxidase（MPO×400）;Figure 2c Positive of Ki-67（Ki67×400）

Discuss

Myelodysplasticsyndromes(MDS)area heterogeneous group of myeloid clonal diseases originatingfromhematopoieticstemcells,characterized by abnormal myeloid cell development,manifested by ineffective hematopoiesis,refractory cytopenia,and high risk of transformation to acute myeloid leukemia [1].The symptoms and signs of MDS patients are mainly the response of various types of cytopenia.The early patients usually have the related manifestations of intractable anemia [2],and the patients with systemic rash and fever as the first symptoms are rare.The patient had previously considered the diagnosis of "cutaneous atypical lymphoproliferative disease",and after relevant treatment,the symptom relief was not obvious.Because of the patient's morbid hematopoiesis,the bone marrow image suggested MPO (+),considering the possibility of myeloid tumors.Relevant examinations were completed after this admission.Histopathology of the lesion showed proliferation of squamous epithelial fibrous tissue,and infiltration of numerous atypical cells around small vessels and skin appendages.Thehistopathologicaland immunohistochemical results of the lesions were comprehensively analyzed.The heterotypic cells expressed CD33,CD43,CD4 and partially expressed CD56 and MPO.The lesions were considered to be caused by skin infiltration of myeloid tumors.The diagnosis of myelodysplastic syndrome was established by combining the results of hematopenia,morbid hematopoiesis,cytogenetic abnormalities,pathological changes,and in vitro hematopoietic progenitor cell colony culture.

MDS cases with rash symptoms are rare and the rate of misdiagnosis is high.This patient presents with erythema and nodules,which need to be differentiated from the following diseases:①Mycosis fungoides is the most common type of cutaneous T lymphoma,which can manifest as patchy skin lesions in the early stage,as flat atrophic patches with scales covering a single or multiple orange to dark red surfaces[3].TCR gene rearrangement and immunohistochemical molecular pathology can be used for differential diagnosis.②Sweet syndrome,also known as acute febrile neutrophilic dermatosis,is characterized by red patches or nodules with pain or tenderness,occasional blisters,pustules,or bullae,but its histopathology is characterized by neutrophil infiltration in the dermis,whereas the patient's biopsy pathology is atypical cell infiltration.③Lymphoid dysplasia refers to the presence of lymphoid tissue hyperplasia that is different from typical reactive hyperplasia in histology and cytology,suspected but not definitely lymphoma,is a morphological change between typical hyperplasia and lymphoma,or is not completely hyperplasia and not entirely lymphoma,and its diagnosis adopts exclusion method [4].The patient was misdiagnosed because he had some clues that could easily lead to confusion:①Rash and fever are the first symptoms of the disease and persist throughout the disease.②No obvious abnormalities were found in the early multiple bone marrow examinations of the patients,and typical bone marrow images were only seen with the progression of the disease.③The preconceived thinking was limited and the possibility of myeloid neoplasms was not further considered.

In conclusion,MDS with fever and rash as the first symptoms is relatively rare and difficult to diagnose.The establishment and exclusion of other diseases are mainly based on skin pathology,peripheral blood analysis,bone marrow puncture and other related examinations.The natural course and prognosis of MDS patients vary greatly,and the treatment goals are to improve hematopoiesis,improve quality of life,delay disease progression,prolong survival and cure.This patient was initially treated with interferon,and the rash was aggravated,which belonged to misdiagnosis and mistreatment.After the diagnosis of MDS,the symptoms slowed down after 1 cycle of demethylation treatment,and after 5 cycles of treatment,the patient improved and discharged from the hospital.Since the outpatient follow-up treatment,there are no fever,fatigue,rash and other conditions.No abnormalities were found in the blood routine reexamination,and the treatment effect proved that the diagnosis was correct.The misdiagnosis process of this patient requires us to reflect and summarize our experience.When a certain diagnosis can not explain all clinical symptoms,we should expand our thinking,think from multiple angles,and further examine to avoid misdiagnosis and delay in treatment.