POEMS syndrome: A rare entity

POEMS syndrome is a rare paraneoplastic syndrome due to an underlying plasma cell disorder. The diagnosis of POEMS syndrome can be a challenge. A good history, physical examination, and appropriate testing can aid in establishing its diagnosis. We are presenting the case of a 75-year-old man who was diagnosed with POEMS syndrome.

Clinical Characteristics and Survival Analysis of Patients with Plasma Cell Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical characteristics, therapeutic response and prognosis of patients with plasma cell leukemia (PCL) and improve the understanding of this disease.@*METHODS@#The clinical manifestations, laboratory tests and treatment response of 27 patients with plasma cell leukemia treated in The Second Hospital of Shanxi Medical University from December 2010 to August 2019 were analyzed retrospectively, and their clinical characteristics were summarized. Kaplan-Meier method was used for survival analysis.@*RESULTS@#There were 18 cases of primary plasma cell leukemia (pPCL) and 9 cases of secondary plasma cell leukemia (sPCL). The male to female ratio was 1.7∶1. The median age was 62 years old. The first manifestations were bone pain, fatigue, fever, splenomegaly and bleeding, and a large number of plasma cell infiltration was observed in the morphological examination of peripheral blood and bone marrow cells. 13 cases were detected by immunotyping and all of them expressed CD38/CD138. 8 cases underwent karyotype analysis, and 3 cases were normal, clonal abnormalities occurred in 5 cases. FISH detection was performed in 12 cases, of which 8 cases were abnormal. In 17 cases of bortezomib based chemotherapy, the ovevall response rate was 52.9%, which was higher than that in the non-bortezomib group, but there was no significant difference between the two groups (P =0.242). The overall median survival time of 27 patients was 6.4 months, the median progression-free survival time was 3.5 months, and the median survival time of patients with pPCL and sPCL was 8.2 months and 2.4 months, respectively, the difference between the two groups was statistically significant (P =0.031).@*CONCLUSION@#PCL is highly invasive and has diverse clinical manifestations, and is not sensitive to traditional chemotherapy. The median survival time of patients with pPCL is relatively longer than that of patients with sPCL. The chemotherapy regimen based on bortezomib improves the treatment effectiveness and prolongs the survival time of PCL patients.

Diagnostic and prognostic value of bone marrow plasma cell morphology in patients with plasma cell myeloma / 中华检验医学杂志

Objective:To investigate the value of bone marrow plasma cell morphology in the diagnosis and prognosis of plasma cell myeloma (PCM).Method:Observational study.Collect the bone marrow morphology image reports and corresponding monoclonal protein (M protein) identification results of 1071 patients [629 males and 442 females, Median age 62 (29, 93) years] diagnosed with PCM in the outpatient and inpatient departments of Beijing Chaoyang Hospital affiliated to Capital Medical University from January 1, 2017 to February 28, 2022. Combined with Durie‐Salmon(DS) and International Staging System (ISS) of 427 patients diagnosed with PCM and overall survival time (OS) of 436, summarize the relevant plasma cell morphological characteristics. Statistical methods include chi-square test, Kruskal-Walls test, Spearman correlation analysis and Kaplan-Meier survival analysis.Result:The bone marrow morphology reports showed that the typical morphological features of peripheral blood in 573 patients with PCM included plasma cells (40.84%), immature granulocytes (30.89%), rouleaux formation in erythrocytes (68.94%) and nucleated red blood cells (8.55%). The types of bone marrow plasma cells in 1 071 patients diagnosed with PCM included 372 (34.73%) plasmablasts, 674 (62.93%)immature plasma cells, and 25 (2.34%) mature plasma cells. There is a significant positive correlation between the number of bone marrow plasma cells (proportion of nuclear cells) and the concentration of IgG and IgA type, from M protein identification( r=0.55, r=0.60, P<0.01). The proportions of M protein types in 1 071 patients with PCM from high to low were IgG (45.75%), IgA (23.53%), light chain (19.61%), IgD (4.76%), non-secretory (4.3%), biclonal (1.78%), IgE (0.19%), IgM (0.08%). The typical characteristics of the bone marrow plasma cells in various M protein types included clustered distribution, different cell body sizes, inclusions in the cytoplasm, binuclear, polynuclear, and abnormal nuclear. The proportion of plasmablasts in DSⅢ stage was 44.81% (164/366), higher than 21.57% (11/51) in DSⅡstage, and the difference was statistically significant(χ 2=10.2, P<0.05). There was a significant positive correlation between the number of bone marrow plasma cells and DS and ISS stages( r=0. 0.23, r=0.30, P<0.01). The median OS of the PCM patients in the plasmablasts group was significantly shorter than that in the immature plasma cells group [56.0 (23.0, 101.8) months vs 75.9(31.6, 121.5) months, HR=1.42,95% CI 1.05-1.91, P=0.02]. The median OS of the PCM patients in the group of tumor plasma cells burden≥37.5% was shorter than that of the tumor plasma cells burden<37.5% [75.9 (21.4, 122.6)months vs 81.3 (36.6, 108) months, HR=1.54,95% CI 1.14-2.07, P<0.05]. Conclusion:The morphology and tumor burden of bone marrow plasma cells provide an important basis for the diagnosis of PCM and can be used as a prognostic indicator for patients with PCM.

Solitary Plasmacytoma of Mandible – A Rare Dyscrasia- Case Report and Review of Literature

Introduction: The plasma cell neoplasms may present in soft tissue as extramedullary plasmacytomas, bone as a solitary plas- macytoma of bone, or as part of the multifocal disseminated disease multiple myeloma. Aim of study: The study aims to report solitary plasmacytoma in the gnatic bone oral cavity, which is also mimicking as malig- nant neoplasm of bone, seen in a female patient. Case Report: A 38-year-old female patient reported to the outpatient department of our hospital complaining of pain and swelling over the left lower one-third region of the face for one month CBCT analysis shows a hypodense area involving 35 regions extending towards ascending rami of the mandible. Conclusion: Plasmacytoma, despite being a lesion with slow, asymptomatic growth, can assume large volumes, making proper treatment difficult. When there is no bone involvement and it is diagnosed early, the success of treatment is generally higher. The treatment of choice is radiotherapy, with good results for the remission of the lesion

Leucemia plasmocitária primária: relato de caso e revisão sistemática sobre seus fatores prognósticos / Primary plasma cell leukemia: a case report and systematic review of prognostic factors / Leucemia primaria de células plasmáticas: reporte de caso y revisión sistemática de sus factores pronósticos

A leucemia de células plasmocitárias (LCP) é uma neoplasia hematológica rara, de caráter agressivo, ainda sem consenso quanto ao melhor esquema terapêutico e prognóstico da doença. Alguns estudos a consideram como uma variante do mieloma múltiplo. O objetivo deste estudo foi realizar um relato de caso e desenvolver uma revisão sistemática da literatura sobre os fatores prognósticos relacionados a essa enfermidade. Esta revisão sistemática seguiu o protocolo PRISMA, utilizou o PubMED como base de dados, buscando estudos que avaliassem fatores prognósticos da LCP. Os estudos selecionados foram posteriormente avaliados quanto a sua qualidade pelo protocolo STROBE. A primeira busca identificou 260 artigos. Após aplicado critério de exclusão, dez foram selecionados. Destes, oito avaliaram fatores prognósticos clínicos e laboratoriais; cinco avaliaram, além disso, fatores citogenéticos; e um avaliou apenas a idade como fator prognóstico. A qualidade dos estudos, avaliada pelo protocolo STROBE, apresentou uma classificação média de 79,1%. Nos estudos analisados, idade > 65 ou > 60 anos, performance status ECOG > 2, hipercalcemia, aumento de lactato desidrogenase (LDH), aumento da creatinina, plaquetopenia e hipoalbuminemia foram encontrados como preditores de prognóstico ruim. Foram também demonstradas alterações citogenéticas consideradas de alto risco, como as translocações e deleções de genes. Diversas condições clínicas, laboratoriais e citogenéticas parecem estar associadas ao pior prognóstico na LCP. O conhecimento desses fatores pode interferir na prática clínica. Entretanto, ainda são necessários estudos mais robustos, multicêntricos e com maior número amostral para aprofundar o conhecimento sobre essa patologia.

Plasma Cell Leukemia (PCL) is rare and aggressive hematologic disorder, with no consensus on the best therapeutic scheme or disease prognosis. Some studies consider it to be a variant of multiple myeloma. This research sought to report a PCL case and to present a systematic literature review on its prognostic factor related. Bibliographic search followed the PRISMA protocol, and was conducted on the PubMED database to identify studies on PCL prognostic factors. Of the 260 articles identified, only ten were included after application of exclusion criteria. Of these, eight evaluated clinical and laboratorial prognostic factors; five assessed cytogenetic factors; and only one investigated age as a prognostic factor. Quality of the selected studies was evaluated by STROBE protocol, presenting a median classification of 79.1%. Age >65 or >60 years old, status performance ECOG>2, hypercalcemia, increased DHL, increased creatinine, thrombocytopenia, and hypoalbuminemia were the factors identified as predictors of a bad prognosis. Studies also showed high-risk cytogenetic abnormalities such as genetic translocation and deletions. Many clinical, laboratorial and cytogenetic conditions seem to be related to a worse PCL prognosis. Since knowledge of these factor can interfere in the clinical practice, more robust studies are needed on this pathology.

La leucemia de células plasmáticas (LCP) es una neoplasia hematológica rara, de carácter agresivo, sin consenso sobre el mejor régimen terapéutico y pronóstico de la enfermedad. Algunos estudios la consideran como una variante del mieloma múltiple. El objetivo de este estudio fue realizar un reporte de caso y desarrollar una revisión sistemática de la literatura sobre los factores pronósticos relacionados con esta enfermedad. Esta revisión sistemática siguió el protocolo PRISMA, utilizó PubMED como base de datos para la búsqueda de estudios que evaluaran los factores pronósticos para LCP. Los estudios seleccionados fueron posteriormente evaluados por su calidad mediante el protocolo STROBE. La primera búsqueda identificó 260 artículos. Después de aplicados los criterios de exclusión, se seleccionaron diez. De estos, ocho evaluaron los factores pronósticos clínicos y de laboratorio, cinco evaluaron también los factores citogenéticos y uno evaluó la edad solo como factor pronóstico. La calidad de los estudios, evaluada por el protocolo STROBE, presentó una calificación promedio del 79,1%. En los estudios analizados, la edad > 65 o > 60 años, el estado funcional ECOG > 2, la hipercalcemia, el aumento de lactato deshidrogenasa (LDH), el aumento de creatinina, la trombocitopenia y la hipoalbuminemia fueron los predictores de mal pronóstico. También se demostraron alteraciones citogenéticas que se consideraron de alto riesgo, como translocaciones y deleciones de genes. Varias condiciones clínicas, de laboratorio y citogenéticas parecen estar asociadas con peor pronóstico en LCP. El conocimiento de estos factores puede interferir en la práctica clínica. Sin embargo, aún se necesitan estudios más robustos, multicéntricos y con mayor tamaño muestral para profundizar en el conocimiento sobre esta patología.

Massive splenomegaly as the presenting feature of multiple myeloma in an elderly man

A 70-year-old man presented with generalized weakness, easy fatigability, and early satiety of 2-month duration. On examination, he had severe pallor and massive splenomegaly. Hematological investigations revealed bicytopenia with hypergammaglobulinemia and acute kidney injury. Bone marrow aspiration cytology was suggestive of plasma cell dyscrasia. Monoclonal protein peak (due to heavy chain of IgG type) was found on serum protein electrophoresis, and lambda light chains and IgG heavy chains were elevated on immunofixation. The patient was diagnosed as a case of multiple myeloma and was started on bortezomib杔enalidomide杁examethasone regimen. After 7 months of chemotherapy, his spleen had regressed, and the patient had become asymptomatic. Presentation with massive splenomegaly is usually a feature of Waldenstrom抯 macroglobulinemia. However, rarely multiple myeloma may have extramedullary manifestations such as splenomegaly as the primary presenting feature.

Clinical characteristics of plasma cell leukemia and progress in its diagnosis and treatment / 白血病·淋巴瘤

Plasma cell leukemia (PCL) is a plasma cell proliferative disorder with strong invasiveness, rapid progression and poor prognosis. The incidence of PCL is about (0.04-0.05)/100 000 per year. According to the multiple myeloma (MM) history, PCL can be divided into primary plasma cell leukemia (PPCL) and secondary plasma cell leukemia (SPCL). PPCL accounts for about 60% of PCL, and it is in the stage of leukemia at diagnosis and has no history of MM. SPCL accounts for the remaining 40% of PCL, and mostly shows as the MM end-stage manifestation, but also can be secondary to Waldenstrom macroglobulinemia, B-cell lymphoma, chronic lymphoblastic leukemia, amyloidosis, etc. Patients who progress from MM to SPCL account for 2%-4% of all MM patients. Due to the low incidence and strong clinical heterogeneity of PCL, the evidence-based medicine about PCL is relatively lacking, this article reviews the clinical characteristics of PCL and progress in its diagnosis and treatment.

Progress of bcl-2 inhibitors in treatment of plasma cell disorders with t(11;14) / 白血病·淋巴瘤

Plasma cell disorders are a group of heterogeneous diseases originating from plasma cells, including multiple myeloma, plasma cell leukemia and light-chain amyloidosis, etc. Monoclonal plasma cells are detected in bone marrow and affected tissues, monoclonal immunoglobulin or components are detected in serum or urine, and some end-organs are injured. Plasma cell disorders accompanied by t(11;14) have unique biological characteristics and unsatisfactory response to proteasome inhibitors. With t(11;14) translocation, the expressions of cyclin D1 and anti-apoptotic protein bcl-2 are relatively high, which lead to the occurrence of plasma cell disorders and have implications for the prognosis of disease. Venetoclax is a bcl-2 inhibitor, and its single agent or combined with other drugs has achieved good efficacy in treatment of plasma cell disorders with t(11;14). This article reviews the progress of bcl-2 inhibitors in treatment of plasma cell disorders.

The role of MYCN and PHOX2B gene combined with plasma cell-free DNA detection in risk stratification and predicting the prognosis of high-risk neuroblastoma / 中华实用儿科临床杂志

Objective:To explore the clinical significance of the MYCN gene, PHOX2B gene and plasma cell-free DNA (cfDNA) in risk stratification and predicting the prognosis of high-risk neuroblastoma (NB). Methods:This was a prospective study involving 94 high-risk NB children admitted to Beijing Children′s Hospital, Capital Medical University from August 2017 to December 2018.Relative levels of MYCN and PHOX2B and cfDNA at diagnosis, and 4 and 6 cycles of chemotherapy were detected, and their differences were compared by the Chi- square test.Kaplan-Meier survival analysis was performed to explore their prognostic potential in high-risk NB. Results:Among the 94 high-risk NB children, 14 cases (14.9%) had MYCN amplification, 76 cases (80.8%) had positive expression of PHOX2B and 56 cases (59.6%) had cfDNA level higher than 100 μg/L.The proportion of high lactate dehydrogenase (LDH, ≥1 500 U/L) level in the MYCN gene amplification group (6/14 cases) was higher than that in the normal group (9/80 cases) ( P=0.009). The proportion of multi-site metastasis (54/76 cases) and high neuron specific enolase (NSE) level (NSE≥370 μg/L, 37/76 cases) in PHOX2B positive group were significantly higher than those in the negative group (5/14 cases, 2/14 cases) ( P=0.015, 0.020). The proportion of high LDH and high NSE in high cfDNA concentration (≥229.6 μg/L)group (13/37 cases, 28/37 cases) were significantly higher than those in low cfDNA concentration group (2/48 cases, 10/48 cases) (all P<0.001). With the decreased tumor burden during the treatment, the copy number of PHOX2B gene and cfDNA level were significantly lower than those at the initial diagnosis [0 (0-719.6) copies vs.1 723.5 (0-186 000.0) copies; 19.0 (1.1-225.5) μg/L vs.200.6 (8.0-5 247.4) μg/L, all P<0.001]. The 2-year event-free survival (EFS) rate of the MYCN gene amplification group was significantly lower than that of the normal group[(33.3±13.1)% vs.(58.5±7.1)%, P=0.020]. The 2-year EFS rate of PHOX2B positive group was significantly lower than that of the negative group[(47.9±7.1)% vs.(79.1±11.1)%, P=0.043]. EFS rate in high cfDNA concentration group was significantly lower than that in cfDNA low concentration group[(38.6±9.8)% vs.( 71.7±8.2)%, P=0.001]. After 6 cycles of chemotherapy, EFS rate in the PHOX2B positive group was significantly lower than that in the negative group [(16.7±14.4)% vs.( 60.6±6.6)%, P=0.014]; which was significantly lower in the Metaiodobenzylguanidine (MIBG) positive group than that of the negative group[(35.2±11.7)% vs.(65.8±7.1)%, P=0.037]. The MYCN gene and cfDNA concentration were not correlated with the prognosis of high-risk NB.Survival analysis of the combination of PHOX2B and MYCN gene ( PHOX2B+ /MIBG + , PHOX2B+ or MIBG + , PHOX2B-/MIBG -) showed a significant difference in the survival among three groups[0 vs.(53.6±1.2)% vs.(65.5±7.4)%, P=0.003]. Conclusions:The MYCN and PHOX2B gene and cfDNA concentration are of significance in risk stratification and predicting the prognosis of high-risk NB.Compared with the MYCN gene and cfDNA concentration, the PHOX2B gene is more suitable for monitoring the curative effect of chemotherapy on high-risk NB.A combined analysis of PHOX2B gene and MIBG before treatment can be more accurate in evaluating the treatment effect and residual lesions.

Intracranial Inflammatory Myofibroblastic Tumor: A Review of 49 cases

Inflammatory Myofibroblastic Tumor (IMT) is a rare pathologic entity that was first described in 1973. This lesion is most commonly found in the lungs, but other organs' involvement has also been reported. Intracranial location of Inflammatory Myofibroblastic Tumor is rare, and the first case was reported in 1980. An intriguing fact about the intracranial IMT is its resemblance with meningioma on clinical presentation and neuroimaging. We came across a case of intracranial Inflammatory Myofibroblastic Tumor (IIMT) in a 27-year-old male who presented with recurrent episodes of seizures and was diagnosed as meningioma on neuroimaging. The lesion did not subside with medical management and kept on progressing in size. The patient had to undergo surgery, and diagnosis of Inflammatory Myofibroblastic Tumor was ascertained on histopathology. This 'surprise' diagnosis prompted us to review the literature on all cases of IIMTs reported to date to better understand the entity and its implications. In this review article, we present our observations regarding various studied parameters, including patient profile, clinical presentation, site of involvement, focality of the lesion, special associations, and lines of management of the 49 published cases of IIMTs.

Lung adenocarcinoma misdiagnosed as IgG4-related lung disease:A case report and literature review / 中南大学学报(医学版)

IgG4-related disease (IgG4-RD) is a recently recognized disorder characterized by elevated serum IgG4 levels and infiltration of IgG4 positive blood cells in the affected organs. However, other conditions like malignancy as well as connective tissue diseases, may show similar findings. A 56-year-old male patient visited Second Xiangya Hospital, Central South University for recurrent fever and chest pain for more than 1 month. Preliminary tests diagnosed as IgG4-related lung disease (IgG4-RLD). However, the improvement of symptoms was absent after the treatment with methylprednisolone. The patient underwent the second biopsy and the result eventually demonstrated lung adenocarcinoma. The role of IgG4 in the pathogenesis or prognosis for lung adenocarcinoma remains unclear. Therefore, a thorough evaluation of symptoms, test of specific serum markers and eventually pathological confirmation are required to avoid misdiagnosis.

Sarcoidose como diagnóstico diferencial de mieloma múltiplo / Sarcoidosis as a differential diagnosis of multiple myeloma

A sarcoidose caracteriza-se como doença granulomatosa que acomete diferentes órgãos humanos, especialmente os pulmões, sendo sua patogênese pouco conhecida. No caso em questão, a paciente iniciou com sintomas inespecíficos, como fraqueza, perda ponderal e tosse seca esporádica, sendo internada para extensão da propedêutica. Sugeriu-se como hipótese diagnóstica inicial possível quadro de mieloma múltiplo, tendo em vista a anemia, a disfunção renal, a hipercalcemia e, sobretudo, as lesões osteolíticas apresentadas pela paciente. Todavia, o diagnóstico de sarcoidose foi selado a partir das biópsias de medula óssea e de linfonodo inguinal, que evidenciaram mielite e linfadenite granulomatosas, respectivamente. A terapêutica instituída baseou-se na administração de corticosteroides e em medidas de redução da calcemia. A paciente recebeu alta, com melhora do quadro clínico, para acompanhamento ambulatorial da doença. Conclui-se que a sarcoidose não possui tratamento curativo, mas a terapêutica imunossupressora é eficaz no controle da progressão da enfermidade, fazendo com que o paciente tenha um prognóstico favorável.

Sarcoidosis is characterized as a granulomatous disease that affects different human organs, especially the lungs, and its pathogenesis is little known. In this case, the patient started with nonspecific symptoms, such as weakness, weight loss, and sporadic dry cough, being hospitalized for extension of the propaedeutics. The initial diagnostic hypothesis suggested was a possible case of multiple myeloma, based on the anemia, renal dysfunction, hypercalcemia and, above all, the osteolytic lesions presented by the patient. However, the diagnosis of sarcoidosis was made after bone marrow and inguinal lymph node biopsies that showed granulomatous myelitis and lymphadenitis, respectively. The therapy instituted was based on the administration of corticosteroids and on measures to reduce the level of calcium. The patient was discharged, with clinical improvement, for outpatient follow-up of the disease. It is concluded that sarcoidosis has no curative treatment, but immunosuppressive therapy is effective in controlling the progression of the disease, giving the patient a favorable prognosis.

Tumor miofibroblástico inflamatorio de vías biliares en un paciente pediátrico / Inflammatory miofibroblastic tumor of the biliary tract in a pediatric patient

RESUMEN El tumor miofibroblástico inflamatorio es una neoplasia mesenquimal infrecuente, realizar el diagnóstico clínico así como el patológico por biopsias es un desafío. Presentamos un caso de un paciente pediátrico con tumor miofibroblástico inflamatorio localizado a nivel de las vías biliares. Se realizaron estudios de laboratorio así como imagenológicos en los cuales se planteó un diagnóstico inexacto, del mismo modo cuando se envió la muestra de la lesión para el análisis intraoperatorio a través de técnicas de congelación, el reporte microscópico también fue incorrecto. Sin embargo cuando se realizó la revisión de las láminas tras la inclusión de la lesión y complementando con estudios de inmunohistoquimica, se concluyó que la lesión correspondió a un tumor miofibroblástico inflamatorio.

ABSTRACT The inflammatory myofibroblastic tumor is an infrequent mesenchymal neoplasm, making the clinical as well as the pathological diagnosis by biopsies is a challenge. We present a case of a pediatric patient with an inflammatory myofibroblastic tumor located at the level of the bile ducts. We sent the lesion sample for intraoperative analysis through freezing techniques, the microscopic report was also incorrect. However, when the plates were reviewed after the inclusion of the lesion and supplemented by immunohistochemical studies, it was concluded that the lesion corresponded to an inflammatory myofibroblastic tumor.

Early relapse after complete remission of primary plasma cell leukaemia manifesting clonal evolution: A case report

@#Introduction: Plasma cell leukaemia (PCL) is a rare variant of multiple myeloma. We report a case of PCL to demonstrate the clonal evolution, resulting in disease relapse after achieving complete remission, and its aggressive nature of the disease, leading to poor clinical outcome. Case Report: A 69-year-old man presented with a three-day-history of worsening generalized body weakness, poor oral intake, nausea, significant loss of weight and lower back pain. He was diagnosed as primary PCL, based on hypercalcaemia, renal insufficiency, anaemia, thrombocytopenia, lytic bone lesions, 24% abnormal plasma cells in peripheral blood, immunophenotype of clonal plasma cells which were positive for CD38, CD138 and CD56 markers with kappa light chain restriction, 49% abnormal plasma cells in bone marrow, monoclonal paraprotein (IgG kappa) in serum and urine, and positive IGH rearrangement (Fluorescence in-situ hybridisation, FISH). He achieved complete remission after four cycles of Bortezomib-based therapy. There was a plan for high-dose therapy plus autologous haematopoietic cell transplantation. A month later, the disease relapsed, as evidenced by 94% abnormal plasma cells in his bone marrow aspirate, complex karyotype and abnormal FISH results. He passed away a few days later, from severe septicaemia. Time-to-progression of disease was 1 month and overall survival was 5 months. Discussion: This case report illustrates the clonal evolution and aggressive nature of primary PCL with older age at presentation, leading to a shorter duration of remission and overall survival.

Plasma cell cheilitis: the diagnosis of a disorder mimicking lip cancer

Plasma cell cheilitis (PCC) is an inflammatory disorder of unknown etiology that affects the lip. It is characterized histologically by a dense infiltrate of plasma cells with a variety of clinical features. The response to different therapeutic modalities is controversial, especially regarding the effectiveness of corticosteroids. We present a case of a 56-year-old Caucasian man with a painful ulcerated and crusted area in the lower lip, resembling a squamous cell carcinoma or actinic cheilitis. Topical corticosteroid was used for one week, which resulted in partial regression and motivated a biopsy. The histological examination provided the diagnosis of PCC. The patient has been disease-free for six months. We also provide a discussion on the criteria of differential diagnosis and management of this rare condition.

Leucemia de células plasmáticas primaria: experiencia en un hospital público chileno / Primary plasma cell leukemia: report of five cases

Background: Primary plasma cell leukemia (pPCL) is uncommon, aggressive and has a different biology than multiple myeloma (MM). Aim: To report the features of patients with pPCL. Material and Methods: Review of databases of the Hematology Department and the Hematology laboratory. Results: Of 178 patients with monoclonal gammopathies, five (2.8%) patients aged 33 to 64 years (three females) had a pPCL. The mean hemoglobin was 7.3 g/dL, the mean white blood cell count was 52,500/mm3, with 58% plasma cells, and the mean platelet count was 83,600/mm3. The mean bone marrow infiltration was 89%, LDH was 2,003 IU/L, serum calcium was 13 mg/dL, and creatinine 1.5 mg/dL. Two patients had bone lesions. Three were IgG, one IgA lambda and one lambda light chain. CD20 was positive in one, CD56 was negative in all and CD117 was negative in 3 cases. By conventional cytogenetic analysis, two had a complex karyotype. By Fluorescence in situ Hybridization, one was positive for TP53 and another for t (11; 14). One patient did not receive any treatment, three patients received VTD PACE and one CTD. None underwent transplant. Three patients are alive. The mean survival was 14 months. Conclusions: These patients with pPCL were younger and had a more aggressive clinical outcome than in multiple myeloma.

Screening and predication on tumor neoantigen for primary plasma cell leukemia / 中国肿瘤生物治疗杂志

@#Objective:To investigate the tumor-specific neoantigen for primary plasma cell leukemia (PCL) using gene sequencing technology combined with bioinformatic analysis. Methods: Peripheral blood samples of one patient with primary PCL during relapse and remission periods were collected. HLA molecular typing was performed using polymerase chain reaction with sequencing-based typing; whole-exome and transcriptome were sequenced by next-generation sequencing method; and bioinformatics software NetMHCpan was used to predict neoantigens. Results: Six tumor-specific missense mutations were found in the patient's peripheral blood during relapse period, located in genes FRG1, MLL3, SVIL, MYOM1, ZDHHC11 and RFPL4A.Considering patient's HLA sub-types, 43 neoantigens were predicted via bioinformatics. Considering that FRG1 and MLL3 had relatively high gene expression levels, 20 neoantigens derived from mutations of the two genes were preferentially selected, among which four neoantigens had high affinity with the patient's HLA molecules and thus had potential clinical application value. Conclusion: The study has completed a tumor neoantigen screen and prediction for primary PCL. This practice demonstrates that predicting neoantigen based on tumor-specific somatic mutation is feasible for primary PCL.

Mechanisms of triiodothyronine on maturation and differentiation of B cells / 医学研究生学报

Objective Higher expression of B-cell activating factor (BAFF) in patients with Graves' disease can activate B cells and increase proportion of plasma cells. However, the mechanism is still unclear. This study aims to investigate the effects of T3 on the BAFF level and plasma cell ratio in bone marrow, spleen and peripheral blood of mice, and to explore the mechanism of T3 in affecting the mature and differentiation of B cells. Methods 80 C57BL/6J mice were randomly divided into control group and T3 group, and were given isotonic saline or T3 5/10μg once a day for 6 weeks, respectively. The levels of T3 in peripheral blood of each group were measured with ELISA. Flow cytometry was used to detect the proportion of B220+CD138+ plasma cells and IgM, IgG and IgD expression of B cells in the spleen, bone marrow and peripheral blood. Immunohistochemistry, Western blot and PCR were performed to determine the expression of BAFF in spleen and thyroid. ELISA was used to determine the expression of BAFF in peripheral blood. Results Compared with control group, the levels of T3 in peripheral blood, diet and drinking water in the T3 group were significantly increased after 6 weeks T3 intervention. The mRNA and protein expression of BAFF in spleen mononuclear cells of T3 group (2.03±0.52, 0.50±0.03) were higher than those in control group (1.06±0.19, 0.05±0.01) (P<0.01). HE staining showed that the white medulla in the spleen of the T3 group increased and merged. Flow cytometry indicated that the proportion of spleen plasma cells and antibody expression of B cells in T3 group [(3.92±1.55)%, (75.76±8.88)%] increased compared with control group [(2.43±1.18)%, (65.26±8.38)%] (P<0.05); Proportion of bone marrow plasma cells [(8.48±3.62)%] and antibody expression [(40.63±18.96)%] in T3 group were significantly increased compared with control group [(4.96±3.11)%, (22.89±7.32)%](P<0.05); Peripheral plasma cell ratio [(8.56±4.27)%] and antibody expression [(76.15±9.44)%] were lower than those in control group [(14.70±4.76)%, (84.20±3.98)%](P<0.05); Compared with control group [(5.98±0.78) pg/mL], the BAFF level in peripheral blood increased [(7.61±1.72) pg/mL] (P<0.01). Immunohistochemistry showed that the expression of BAFF increased in mononuclear cells of thyroid of the T3 group. Conclusion T3 could activate BAFF expression in bone marrow, spleen, peripheral blood and thyroid mononuclear cells, and induce differentiation of bone marrow and spleen B cells, thus causing pathological changes in thyroid tissue. Such mechanisms might play an important role in the pathogenesis of thyroid autoimmune diseases.

Effects of storage time of bone marrow specimens on the detection results of plasma cells immunophenotyping by flow cytometry / 白血病·淋巴瘤

Objective To explore the effects of different storage time of bone marrow specimens on the expressions of different antigens in normal plasma cells (nPC) and clone plasma cells (cPC) by flow cytometry. Methods The bone marrow samples of 12 patients with multiple myeloma (MM) who were treated in Beijing Chaoyang Hospital from September 2017 to January 2018 were selected as MM group. The minimum residual disease (MRD) level in MM group was 10-3-10-2. The bone marrow samples of 12 patients without plasma cell diseases were used as control group. Bone marrow samples were anticoagulated with ethylenediaminetetraacetic acid dipotassium (EDTA-K2) and stored at 2-8 °C. The fluorescent antibodies CD56, CD138, CD45, CD38, CD117, CD81 and cκ, cλ, CD45, CD38, CD19, CD27 were labeled at 0, 24, 48 and 72 h, respectively. The average fluorescence intensity (MFI) of the above 10 antigens expressed in nPC and cPC was analyzed by Diva software. The proportion and absolute count of nPC in control group and cPC in MM group were analyzed. Results In control group, when stored for 24 h, compared with 0 h, the difference of MFI of antigens in nPC was not statistically significant (P ＞ 0.05). When stored for 48 h, compared with 0 h, the MFI of CD38, CD138, CD27, cκ and cλ in nPC decreased, and the differences were statistically significant (28 943±6 591 vs. 23 569±7 587, P＝ 0.018; 1 412±399 vs. 817±223, P＝ 0.014;12 855±3 734 vs. 9 210±3 660, P＝ 0.005; 26 712±9 025 vs. 17 247±5 078, P＝ 0.026; 17 707±8 633 vs. 8 307±3 158, P ＝ 0.049); the MFI of CD45 increased, and the difference was statistically significant (7 694± 2 525 vs. 9 184±1 332, P ＝ 0.037). When stored for 72 h, compared with 0 h, the MFI of cκ and cλ increased, but the differences were not statistically significant (both P ＞ 0.05). In MM group, when stored for 24 h, compared with 0 h, the difference in MFI of antigens in cPC was not statistically significant (P＞ 0.05). When stored for 48 h, compared with 0 h, the MFI of CD38, CD138, CD81, cκ and cλ decreased, and the differences were statistically significant (16 664±11 744 vs. 10 130±10 026, P＝ 0.003; 2 041±1 145 vs. 1 371±696, P＝ 0.047; 2 679±784 vs. 1 524±1 153, P＝ 0.025; 29 102±18 138 vs. 18 372±10 327, P＝0.038; 16 314±12 728 vs. 9 752±6 271, P＝0.034). When stored for 72 h, compared with 0 h, the MFI of cκ and cλ increased, but the differences were not statistically significant (both P＞ 0.05). The absolute count of nPC and cPC gradually decreased with the prolongation of the storage time, and the difference was statistically significant (both P<0.05) when stored for 0 h and 24 h. There was no significant difference in the percentage of nPC and cPC among different storage time (all P ＞ 0.05). Conclusion Different storage time of bone marrow samples has effects on the MFI of antigens and absolute count of nPC and cPC, and the detection should be completed within 48 h.

Practical stability of whole-genome bisulfite sequencing using plasma cell-free DNA / 生物工程学报

With the development of liquid biopsy technology, plasma cell-free DNA (cfDNA) becomes one of the research hotspots. Whole-genome bisulfite sequencing of plasma cell-free DNA has shown great potential medical applications such as cancer detection. However, the practical stability evaluation is still lacking. In this study, plasma cell-free DNA samples from two volunteers at different time were collected and prepared for sequencing in multiple laboratories. The library preparation strategies include pre-bisulfite, post-bisulfite and regular whole-genome sequencing. We established a set of quality control references for plasma cell-free DNA sequencing data and evaluated practical stability of blood collection, DNA extraction, and library preparation and sequencing depth. This work provided a technical practice guide for the application of plasma cfDNA methylation sequencing for clinical applications.