Squamous cell carcinoma of the oral cavity and circulating tumour cells

Due to a lack of substantial improvement in the outcome of patients suffering from oral squamous cell carcinoma(OSCC) during the past decades, current staging methods need to be revised. This disease is associated with poor survival rates despite considerable advances in diagnosis and treatment. The early detection of metastases is an important indicator of survival, prognosis and relapse. Therefore, a better understanding of the mechanisms underlying metastasis is crucial. Exploring alternative measures apart from common procedures is needed to identify new prognostic markers. Similar to previous findings predominantly for other solid tumours, recently published studies demonstrate that circulating tumour cells(CTCs) and disseminated tumour cells(DTCs) might serve as prognostic markers and could supplement routine staging in OSCC. Thus, the detection of CTCs/DTCs is a promising tool todetermine the individual need for therapeutic intervention. Encouraging results and new approaches point to the future use of targeted therapies for OSCC, an exceedingly heterogeneous subgroup of head and neck cancer. This review focuses on summarising technologies currently used to detect CTCs/DTCs. The translational relevance for OSCC is highlighted. The inherent challenges in detecting CTCs/DTCs will be emphasised.

Long-term prognostic impact of circulating tumour cells in gastric cancer patients

AIM To analyse the long-term prognostic impact of circulating tumour cells(CTCs) in gastric cancer patients who underwent surgery. METHODS A 7.5-m L peripheral vein blood sample was obtained from each patient with treatment-negative gastric adenocarcinoma before surgery. OBP-401, a telomerasespecific, replication-selective, oncolytic adenoviral agent carrying the green fluorescent protein gene, was used to label CTCs. Correlations between the number of CTCs and clinical end points were evaluated. RESULTS The median follow-up period of the surviving patients with gastric cancer was 60 mo. The CTC number tended to increase concomitantly with disease progression. The overall survival of patients with more than five CTCs in 7.5-m L of peripheral blood was lower than that of patients with five or less CTCs, although the difference was not significant(P = 0.183). A significant difference in relapse-free survival was found between patients with more than five and those with five or less CTCs(P = 0.034).CONCLUSION A lower number of CTCs was correlated with higher relapse-free survival rates in patients. Detection of CTCs using OBP-401 may be useful for predicting prognosis in gastric cancer.

Detection of circulating tumour cells in colorectal cancer:Emerging techniques and clinical implications

Despite several advances in oncological management of colorectal cancer,morbidity and mortality are still high and devastating.The diagnostic evaluation by endoscopy is cumbersome,which is uncomfortable to many.Because of the intra-and inter-tumour heterogeneity and changing tumour dynamics,which is continuous in nature,the diagnostic biopsy and assessment of the pathological sample are difficult and also not adequate.Late manifestation of the disease and delayed diagnosis may lead to relapse or metastases.One of the keys to improving the outcome is early detection of cancer,ease of technology to detect with uniformity,and its therapeutic implications,which are yet to come."Liquid biopsy"is currently the most recent area of interest in oncology,which may provide important tools regarding the characterization of the primary tumour and its metastasis as cancer cells shed into the bloodstream even at the early stages of the disease.By using this approach,clinicians may be able to find out information about the tumour at a given time.Any of the following three types of sampling of biological material can be used in the"liquid biopsy".These are circulating tumour cells(CTCs),circulating tumour DNA,and exosomes.The most commonly studied amongst the three is CTCs.CTCs with their different applications and prognostic value has been found useful in colorectal cancer detection and therapeutics.In this review,we will discuss various markers for CTCs,the core tools/techniques for detection,and also important findings of clinical studies in colorectal cancer and its clinical implications.

Three Dimensional Simulation Method in Early Process of Division and Growth for Tumour Cells

The process of division, growth and death for tumour cell mass in the early is simulated. An integrated GUI is provided for users to set the value of each parameters, which are cell growth rates, cell mass division rates, cell mass death rates, simulate type, maximum running time, polarity and cell colour. It can display the growth process of each cell on result GUI. Also, it can display the values of each parameters for observing and analysing in current life cycle on result GUI, which are cell mass division times, cell mass death rate, cell mass division rate and cell mass growth rate. In the process of simulation, The cell growth rate is described by the approach to combine the exponential model with the linear model. In addition, a linked list data structure to store the tumour cells is used by the cellular automata for a reference to determine the position of each cell. It sets up two linked list to store the cells, one of them save the new small division cells and the other one save the big cell. That can make the painting process of cells on result GUI clearer and more organized. At last, the polarity oftumour growth is described for determining the growth direction of cells.

Hemodynamic Shear Stress Regulates the Survival of Circulating Tumour Cells Through Piezo1-Actomyosin-Mediated YAP/TAZ Nuclear Translocation

It is critical to combat tumor metastasis by eradicating disseminated tumor cells in any step during the metastasis process.After entering the blood circulation system,tumor cells are in suspension and experience considerable levels of fluid shear stress.However,the influence of hemodynamic shear stress on the survival of CTCs and the underlying mechanotransduction mechanisms remain unclear.This study shows that fluid shear stress can eliminate the majority of CTCs and the viability of suspended tumor cells depends on the stress magnitude,indicating that tumor cells can sense and respond to fluid shear stress.Mechanistically,the expression of Piezo1 but not Piezo2 is greatly upregulated in suspended tumor cells after shear stress treatment.Inhibiting/activating Piezo1 increases/decreases the viability of suspended tumor cells in shear flow,which depends on Piezo1-mediated calcium entry.These findings suggest that Piezo1 may be the major mechanosensor by which suspended tumor cells sense fluid shear stress.As the downstream effector of Piezo1,actomyosin in tumor cells is significantly activated under increasing shear stress.Its activity influences the survival of CTCs in shear flow and rescues the effects of Piezo1 on tumor cell survival,suggesting that hemodynamic shear stress regulates the survival of CTCs through Piezo1 mediated actomyosin activity.Importantly,fluid shear stress considerably up-regulates YAP/TAZ activity of suspended tumor cells and promotes their nuclear translocation in a magnitude-dependent manner.Inhibiting YAP/TAZ enhances the viability of suspended tumor cells in shear stress,while activating their activity decreases tumor cell survival,suggesting that YAP/TAZ activation promotes the apoptosis of suspended tumor cells,which is different from the findings that YAP/TAZ facilitates the survival of adherent cells to shear flow.Further,blocking the nuclear import of YAP/TAZ inactivates the sensation of suspended tumor cells to fluid shear flow and attenuates the dependence of tumor cell survival on different magnitudes of hemodynamic shear stress.The influence of Piezo1-actomyosin pathway on suspended tumor cells can be rescued by YAP/TAZ activity,suggesting that Piezo1-mediated signaling induces tumor cell apoptosis via nuclear translocation of YAP/TAZ.In addition,fluid shear stress can also activate the expressions of LATS1/2 and MST1/2 in Hippo pathway through Piezo1,which is known to inhibit YAP/TAZ activity.Silencing/activating LATS1/2 or MST1/2 inhibits/enhances the viability of CTCs under shear stress,the effects of which can be further rescued by YAP/TAZ.These findings suggest that the responses of suspended tumor cells to hemodynamic shear stress are partially mediated by Hippo signaling.After nuclear translocation,YAP/TAZ directly bind p73/PUMA,which further promotes the transcription of pro-apoptotic genes and induces the apoptosis of suspended tumor cells.In summary,these findings show that hemodynamic shear stress considerably influences the survival of CTCs in blood circulation.We have identified the calcium channel Piezo1 as a novel mechanosensor for the response of CTCs to fluid shear stress.Hemodynamic shear stress induces the apoptosis of suspended tumor cells through Piezo1-actomyosin-YAP/TAZ-p73/PUMA signaling,which is different from the mechanotranduction mechanisms for tumor cells in adherent.Therefore,this study has unveiled the novel mechanosensor of suspended CTCs in response to fluid shear stress and the subsequent mechanisms and identified Piezo1 and YAP/TAZ as the potential therapeutic targets,through which CTCs may be effectively eradicated in the vasculature to prohibit tumor metastasis.

Mutational Analysis of OCT4+ and OCT4− Circulating Tumour Cells by Single Cell Whole Exome Sequencing in Stage I Non-Small Cell Lung Cancer Patients

Circulating tumour cells(CTCs)were enriched in the peripheral blood of four patients with Stage I non-small cell lung cancer(NSCLC).Octamer-binding transcription factor-4 positive(OCT4+)and negative(OCT4−)CTCs were identified and captured by interphase fluorescence in situ hybridisation(iFISH).Single cell whole exome sequencing(WES)was performed and the corresponding bioinformatics data were analysed.OCT4+cells were successfully detected in peripheral blood collected from all four Stage I lung cancer patients.Moreover,the tumour mutational burden(TMB)values observed for OCT4+samples from the same patients were slightly smaller than those of the OCT4−samples;the difference was not statistically significant(P>0.05).Thirteen and six characteristic mutations were found in negative samples and positive samples,respectively.The findings indicate that this methodology provides a potential diagnostic index for the early detection of NSCLC.

A Preliminary Study of Killing Effect of Ultrasound Irritated HpD on S180 Tumour Cells

Hematoporphyrin derivative （HpD） is a photosensitive agent with the characteristic of prior gathering to cancer tissue and producing O? of cellulotoxicity after radiation; therefore, the laser photo dynamic method has been used widely at home and abroad. However, it is quite limited for deep part cancer treatment.

Interaction between the Wilms tumour factor-1 element in the promoter of Amh and a downstream enhancer is required for a strong expression of the gene in pre-pubertal sertoli cells

Amh (anti-Müllerian hormone) is a single copy gene which is expressed strongly in Sertoli cells in the foetal testis and participates in the onset of sexual differentiation. Its promoter driving the expression of a reporter gene (d2EGFP) has been used to analyse the role of certain defined putative elements and a downstream enhancer element in gene expression. These experiments were carried out in vitro using a line of pre-pubertal mouse Sertoli cells, transienly transfected with circular DNA constructs with variously mutated promoter elements. A downstream enhancer element, situated immediately 3’ of the polyadenylation (PA) signal for Amh, has been inserted in an equivalent position in the d2EGFP construct. When the Amh promoter is unmodified, the downstream enhancer (DE) is positively associated with a large increase in EGFP expression. This is at least partly the consequence of an increased rate of expression by individual cells. Experiments using variously truncated Amh promoters indicate that an upstream region (-214 to -336) may play a minor role in facilitating enhancement. However mutation of the Wilms tumour factor-1 element, situated between the tata box and the start of translation, results in an almost complete suppression of enhancement.

Oncologic Trogocytosis Protects Tumour Stromal Cells from γδ Cell Cytotoxicity

Tumours progressively develop chemoresistance and immunoescape abilities thanks to support from their stromal microenvironment. In ovarian carcinomas, for instance, tumour-associated mesenchymal stem cells （TAMC） can transfer multi-drug-resistant proteins to develop metastases. However, since the microenvironment of such carcinomas is frequently infiltrated by both TAMC and γδ T lymphocytes, the consequences of interactions between these cell types were unclear. Here, we report that whilst γδ T lymphocytes were not activated when co-incubated in vitro with TAMC, their cell membranes were trogocytosed by the TAMC. Since TAMC constitutively express a low level of HLA class I, which is increased by trogocytosis of γδ cell-derived HLA class I, the interaction increased the expression of HLA class-I molecules on TAMC. In addition, γδ T lymphocytes are HLA-unrestricted cytolytic cells and their activity is regulated by inhibitory receptors （KIR） for self-HLA class I. Hence, although the lytic activity of γδ T lymphocytes for unrelated target cells was unaffected by trogocytosis, it spared the TAMC. Therefore, interactions between TAMC and cytolytic γδ T cells avoided the killing of these stromal cells due to an active transfer of their protective HLA class-I molecules. These results suggest that trogocytosis contributes to the maintenance of cancer-associated stromal cells.

Histidine decarboxylase and urinary methylimidazoleacetic acid in gastric neuroendocrine cells and tumours

AIM: To study histidine decarboxylase(HDC) expression in normal and neoplastic gastric neuroendocrine cells in relationship to the main histamine metabolite. METHODS: Control tissues from fundus(n = 3) and corpus(n = 3) mucosa of six patients undergoing operations for gastric adenocarcinoma, biopsy and/or gastric surgical specimens from 64 patients with primary gastric neuroendocrine tumours(GNETs), as well as metastases from 22 of these patients, were investigated using conventional immunohistochemistry and double immunofluorescence with commercial antibodies vs vesicular monoamine transporter 2(VMAT-2), HDC and ghrelin. The urinary excretion of the main histamine metabolite methylimidazoleacetic acid(U-Me Im AA) was determined using highperformance liquid chromatography in 27 of the 64 patients.RESULTS: In the gastric mucosa of the control tissues, co-localization studies identified neuroendocrine cells that showed immunoreactivity only to VMAT-2 and others with reactivity only to HDC. A third cellpopulation co-expressed both antigens. There was no co-expression of HDC and ghrelin. Similar results were obtained in the foci of neuroendocrine cell hyperplasia associated with chronic atrophic gastritis type A and also in the tumours. The relative incidence of the three aforementioned markers varied in the tumours that were examined using conventional immunohistochemistry. All of these GNETs revealed both VMAT-2 and HDC immunoreactivity, and their metastases showed an immunohistochemical pattern and frequency similar to that of their primary tumours. In four patients, increased U-Me Im AA excretion was detected, but only two of the patients exhibited related endocrine symptoms. CONCLUSION: Human enterochromaffin-like cells appear to partially co-express VMAT-2 and HDC. Coexpression of VMAT-2 and HDC might be required for increased histamine production in patients with GNETs.

DNA damage in exfoliated buccal cells and antioxidant status of saliva in brain tumour patients

The present investigation was carried out in exfoliated buccal cells and saliva collected from pre-operative brain tumour patients. The DNA damage in these cells was assessed by alkaline comet assay and micronucleus (MN) assay. Salivary flow rate, pH, osmolality, total antioxidant activity (AOA) and vitamin C levels were also assessed in unstimulated whole saliva of these patients. In the comet assay a significant increase in the tail length (P<0.02) was observed when control and malignant groups were compared. A significant (P<0.02) difference in tail length was also noted between benign and malignant groups. Non significant results were found when control and benign groups were compared. Further, a marked increase in % MN (P<0.002) was observed when control and benign groups were compared. A significant increase in % MN (P<0.029) was also observed in benign cases when compared to malignant tumours. No significance was obtained when % MN in control and malignant cases was compared. Moreover, salivary flow rate and pH was significantly decreased and osmolality was markedly increased in brain tumour patients. The AOA levels in saliva were markedly decreased in brain tumours and vitamin C levels exhibited no change when compared to controls. Thus, as noted above susceptibility to free radical induced DNA damage also exists in the exfoliated buccal cells conducive to the lowered salivary antioxidant status of brain tumour patients.

Radiofrequency ablation for renal tumours: A retrospective study from a tertiary centre

Objective:This study aimed to evaluate the safety and efficacy outcomes of percutaneous radiofrequency ablation(RFA)for localised renal cell carcinoma(RCC)in a tertiary hospital patient who remained unfit for surgical intervention.Methods:We retrospectively analysed survival outcomes for patients with biopsy proven RCC treated by RFA at Royal Perth Hospital between September 2009 and May 2018.Complication data were gathered for all patients that underwent renal RFA along with 2-and 5-year recurrence-free survival(RFS)rate and compared the outcomes with data from previous studies.Results:A total of 69 patients(73 procedures)were eligible for the study,and those patients had biopsy-proven RCC with a minimum of 2-year follow-up.The complication rate was 8.2%(6/73)and local recurrence rate 9.6%(7/73).Two-year RFS is 95.7% and 5-year RFS is 78.8% on a median 3.82-year follow-up(interquartile range 1.90-5.75 years).Conclusion:RFA performed at our centre was found to be safe and effective with low complication rates and durable RFS in line with expectations from existing research.Our study demonstrated that RFA is an alternative modality of treatment for small renal tumours in patients unfit for surgical approach.

乳腺弥漫大B细胞淋巴瘤临床特征及预后分析

目的:探讨乳腺弥漫大B细胞淋巴瘤(DLBCL)患者的临床特征及预后。方法:回顾性分析2013年1月至2023年1月山西省肿瘤医院收治的28例乳腺DLBCL患者的临床资料,其中原发性乳腺DLBCL(PB-DLBCL)13例、继发性乳腺DLBCL(SB-DLBCL)15例对其临床表现、实验室检查、病理学检查、治疗方案和随访资料进行统计学分析。结果:PB-DLBCL患者与SB-DLBCL患者在IPI评分、LDH、β_(2)-微球蛋白方面比较,差异有统计学意义(P<0.05)。接受规律治疗的23例乳腺DLBCL患者中,13例初始治疗达到完全缓解(PB-DLBCL 9例,SB-DLBCL 4例),至随访截止日期,11例患者复发或进展(PB-DLBCL 5例,SB-DLBCL 6例),9例患者死亡(PB-DLBCL 3例SBDLBCL 6例)。PB-DLBCL组、SB-DLBCL组患者5年OS率分别为(75.0±15.3)%和(32.3±17.1)%,PFS率分别为(59.1±19.8)%和0,PB-DLBCL患者5年OS率及PFS率均高于SB-DLBCL患者(P<0.05);联合中枢预防治疗组5年OS率高于单纯化疗组(P<0.05)。结论:乳腺DLBCL分为PB-DLBCL和SB-DLBCL两大类,PB-DLBCL与SB-DLBCL相比,具有IPI评分、LDH水平、β_(2)-微球蛋白较低等特点,且PB-DLBCL患者生存期更长。此外,接受中枢预防治疗患者的预后更为乐观。

结直肠癌组织联合单细胞转录组测序筛选结直肠癌特异性细胞通讯

目的结直肠癌组织联合单细胞转录组测序筛选特异性细胞通讯。方法首先从GEO数据库下载结直肠癌组织测序数据(GSE110225、GSE87211)和单细胞测序数据(GSE132465);接着利用R语言limma包对组织测序数据进行差异分析,并对差异基因进行功能富集分析,STRING数据库和Cytoscape软件筛选核心基因;最后TSNE降维法对单细胞测序数据进行细胞注释,R语言CellChat包做结直肠癌细胞通讯分析,确定核心基因中参与的核心细胞通讯,并加以分析。结果获得结直肠癌差异基因303个,功能富集在趋化因子介导的信号通路、细胞对趋化因子的反应等方面;信号通路主要富集在细胞因子和受体的相互作用、趋化因子信号通路等方面;筛选后获得15个核心基因,主要参与趋化因子(Chemokine C-X-C motif ligand,CXCL)细胞通讯,巨噬细胞、单核细胞和成纤维细胞是信号发出者,内皮细胞是媒介,T细胞、B细胞和组织干细胞是影响者。结论CXCL信号通路在结直肠癌的发生发展中起着重要的细胞通讯作用。

MND1的生物学功能及在肿瘤发生发展中作用的研究进展

细胞周期进程失控是肿瘤异常增殖的一个显著标志。细胞周期相关基因变化可引起细胞周期失调,从而导致细胞分裂不受控制,是促进肿瘤细胞生长的重要原因。若打破肿瘤细胞周期相关因子内源性动态平衡,可能会导致细胞发生异常增殖而形成肿瘤。减数分裂因子可能是肿瘤治疗和生物监测的重要靶点。目前对于减数分裂核分裂蛋白1同系物(meiotic nuclear divisions 1,MND1)的研究较少,但关于MND1在肿瘤发展中的重要作用的报道日益增多,MND1在多种肿瘤中的异常表达与肿瘤的发生发展密切相关。该文从MND1在肿瘤中的生物学功能、MND1与肿瘤发生发展之间的关系等方面的研究进展进行综述,有助于更加深入地分析该基因在肿瘤中的作用机制。

序贯放化疗与同步放化疗对不可手术切除非小细胞肺癌患者的疗效及毒性反应对比

目的对不可手术切除非小细胞肺癌患者分别实施序贯放化疗与同步放化疗,比较2种治疗方案的临床效果。方法此次研究的观察对象为80例不可手术切除非小细胞肺癌患者,入院就诊时间均为2020年1月至2022年8月,按随机数字表法将80例患者分为对照组(40例)、观察组(40例),前者的治疗方案是序贯放化疗,后者的治疗方案是同步放化疗,比较2组的治疗前、治疗后的血清肿瘤标志物水平,并通过病灶大小对2组患者的近期疗效进行评估,同时记录在治疗过程中两组的毒性反应发生情况。结果放化疗后,观察组的血清肿瘤标志物[糖类抗原125(CA125):(38.9±3.4)U/ml与(42.1±6.7)U/ml,t=2.982,P=0.004;鳞状上皮细胞癌抗原(SCC-Ag):(0.31±0.081)ng/ml与(0.38±0.12)ng/ml,t=2.914,P=0.005;细胞角质蛋白19片段抗原21-1(CYFRA21-1)(20.2±3.2)ng/ml与(17.0±1.6)ng/ml,t=2.430,P=0.017]水平均低于对照组;观察组的疾病缓解率、控制率分别为75.0%(30/40)、95.0%(38/40),对照组分别为50.0%(20/40)、77.5%(31/40),2组相比差异有统计学意义(χ^(2)=4.381,P=0.036;χ^(2)=5.165,P=0.023);观察组的毒性反应略高于对照组,但2组的放射性食管炎、胃肠道反应、放射性肺炎、骨髓抑制的发生情况均差异无统计学意义(P>0.05)。结论同步放化疗对不可手术切除非小细胞肺癌患者血清肿瘤标志物水平的控制效果优于序贯放化疗,且同步放化疗能提升患者的近期疗效,不会增加毒性反应。

透明细胞乳头状肾细胞肿瘤的临床病理特征:附4例报告

目的探讨透明细胞乳头状肾细胞肿瘤(CCPRCT)的临床、病理特征,诊断及鉴别诊断以提高对该肿瘤的认识。方法对4例CCPRCT患者的临床资料、组织病理形态、免疫组织化学及分子检测结果进行回顾性分析,随访并复习文献。结果4例患者男2例、女2例,年龄39~73岁,其中1例有终末期肾病史。肿块最大径1~3.5 cm,界清,呈实性或囊实性,色泽灰白、灰黄、灰红相间。光镜下肿瘤细胞排列成管状、乳头状、腺泡状或囊状等,比例不等,肿瘤细胞体积较小,呈立方形,具有透明的胞质,WHO/国际泌尿病理学会(ISUP)核分级1~2级,可见特征性的胞核远离基底膜整齐地排列于腔缘的现象,均未出现肾窦侵犯、脉管侵犯、凝固性坏死等侵袭性肿瘤的特征。免疫表型:肿瘤细胞阳性表达细胞角蛋白(CK)7、碳酸酐酶(CA)Ⅸ、广谱细胞角蛋白(pCK)AE1/AE3、波形蛋白,部分表达CD10,均不表达P504S、CD117、TFE3。荧光原位杂交未检测到3p缺失。3例获得随访,时间8~78个月,均无肿瘤复发转移。结论CCPRCT是一种少见的肾肿瘤,具有较好的临床预后,需与常见的低级别透明细胞性肾细胞癌和乳头状肾细胞癌鉴别,准确诊断可提高患者的生存质量。

Research Progress of Breast Cancer Stem Cell Stemness and Breast Cancer Recurrence

Currently, breast cancer is the most common malignant tumour in Chinese women with a high incidence rate, and recurrence and metastasis are the main reasons affecting survival. Breast Cancer Stem Cells (BCSCs) are stem cells capable of continuous regeneration in vivo with strong self-renewal ability and multidirectional differentiation potential, which are highly tumourigenic and insensitive to radiotherapy and chemotherapy, and are highly susceptible to breast cancer recurrence. Therefore, exploring the stemness of BCSCs and their mechanism associated with recurrence is important for developing new therapeutic strategies, improving therapeutic efficacy, and improving patient prognosis.

子宫颈储备细胞及相关疾病研究进展

子宫颈鳞柱交界处由不同分化程度的鳞状上皮和储备细胞共同组成。宫颈储备细胞可能来源于Müllerian管或泌尿生殖窦,具有分化成腺上皮和化生成鳞状上皮细胞的潜能。人乳头瘤病毒(human papilloma virus,HPV)感染该区域的幼稚细胞可诱发宫颈上皮内病变乃至癌变。综述了子宫颈储备细胞来源、演变及可能导致的相关病变。

朗格汉斯细胞肉瘤

报告1例朗格汉斯细胞肉瘤。患者男,76岁。全身多发斑丘疹40 d。皮肤科检查:口腔黏膜及牙龈多发结节,头、面、四肢及胸背部多发斑丘疹。皮损组织病理:肿瘤细胞主要位于真皮层,并侵及表皮形成溃疡;细胞大小较为一致,弥漫分布,异形性明显,核分裂像易见。免疫组化:肿瘤细胞S-100蛋白、CD1a蛋白、朗格汉斯细胞特异蛋白(Langerin)均弥漫阳性。诊断:朗格汉斯细胞肉瘤。治疗:CHOP方案化疗后出现骨髓抑制,4个月后去世。