朗格汉斯细胞在神经性皮炎组织中的分布和CD40分子表达

通过分析神经性皮炎组织病理变化、炎性细胞浸润、朗格汉斯细胞(LC)的分布以及CD40分子的表达,探讨这些变化与临床分型及病程的相关性。应用常规病理切片分析以及免疫组化的方法,观察LC和CD40分子在不同病期和炎症浸润程度皮损中的分布和表达情况。结果显示神经性皮炎组织呈现慢性炎症反应,炎症细胞的浸润,LC向真皮迁移以及CD40分子表达增加,这些均与疾病严重程度相关。基此表明LC分布的改变和CD40分子的表达与神经性皮炎免疫病理变化有密切的相关性。     

尖锐湿疣皮损中朗格汉斯细胞的变化

目的了解尖锐湿疣(CA)皮损中朗格汉斯细胞(LC)的变化。方法采用免疫组化法对34例CA皮损进行LC染色,光镜下观察其形态和数量变化,并对其中6例标本行电镜观察。结果与正常皮肤相比,CA皮损表皮内LC分布不规则,少见典型的树突状细胞,细胞突明显减少、缩短或消失,半定量计数显示CA皮损中LC为(13.15±9.42)个,较正常明显降低(P<0.01)。超微结构表明LC中的特征性结构———朗格汉颗粒(LG)不仅数目减少,而且形态也不典型。结论CA皮损中LC形态及数量均发生变化,可能在CA的发病中起着一定作用。     

朗格汉斯细胞组织细胞增生症累及甲状腺、颌下腺、淋巴结多器官1例并文献复习

目的探讨甲状腺、颌下腺及淋巴结多器官累及朗格汉斯细胞组织细胞增生症的临床病理特征。方法应用光镜和免疫组化染色对1例甲状腺、颌下腺及淋巴结多器官累及朗格汉斯细胞组织细胞增生症进行观察。结果朗格汉斯细胞在甲状腺、颌下腺及淋巴窦内呈浸润性生长,肿瘤细胞胞质丰富、淡伊红染,核呈圆形、肾形、分叶状、咖啡豆样细胞构成,可见一些多核瘤巨细胞。病变内可见数量不等的嗜酸粒细胞浸润。免疫组化显示瘤细胞CD1a、S-100和CD68(+)。结论甲状腺、颌下腺及淋巴结多器官累及朗格汉斯细胞组织细胞增生症极为罕见,它的诊断主要依靠病理组织学及免疫组化检查。     

以皮疹为首发症状的儿童朗格汉斯细胞组织细胞增生症19例临床病理分析

目的探讨以皮疹为首发症状就诊的朗格汉斯细胞组织细胞增生症(Langerhans-cell histiocytosis,LCH)的临床病理特点,为其早期准确诊断提供有益的帮助。方法收集天津市儿童医院2012年5月～2017年3月以皮疹为首发症状就诊的19例LCH,所有病例均采用直径4.5 mm的皮钻于病变典型部位行皮肤活检,活检标本行常规HE染色及CD1a、S-100、Langerin、CD68、CD3、CD20、CD117免疫组化染色。结果皮疹大体形态多样,镜下病变大部分位于真皮内(10/19),呈灶状或弥漫分布,8例可见表皮侵犯,1例仅在表皮内形成表皮内疱,疱内可见瘤细胞,真皮内未见瘤细胞。典型的肿瘤细胞大小较一致,细胞界限不清,胞质略呈嗜酸性,核不规则、凹陷,可见核沟(15/19),部分病例肿瘤细胞形态不典型,未见明显核沟。免疫表型:CD1a、Langerin、S-100均阳性(19/19),CD68部分阳性(16/19),病灶中或病灶周围均可见CD3阳性的T淋巴细胞,CD117阴性。结论儿童LCH皮疹形态多样,且常为该疾病的最早期表现,提高对LCH皮疹的认识,及时行皮肤活检及免疫组化染色,对儿童LCH的早期诊断和治疗具有重要意义。     

胃孤立性朗格汉斯细胞组织细胞增生症1例

目的探讨胃孤立性朗格汉斯细胞组织细胞增生症(Langerhans cell histiocytosis,LCH)的组织形态和免疫表型及鉴别诊断。方法胃体大弯黏膜隆起性病灶活检组织石蜡包埋HE切片及免疫组化EnV ision两步法染色,进行形态学和免疫表型分析。结果胃体大弯黏膜隆起性病灶,胃壁固有层和黏膜下层可见单一、无特别组织结构的细胞聚集。细胞体积比较大,胞质淡红色;核椭圆形,高倍镜下核呈咖啡豆样,有一条纵向核沟,免疫组化标记CD1a、S-100均阳性;背景炎症反应明显,主要为中性粒细胞、小淋巴细胞、浆细胞及一些嗜伊红细胞。结论 LCH的诊断主要依赖形态学及免疫组化标记,胃孤立性LCH预后显著好于系统性病变。     

温热对HPV感染皮肤LC成熟功能的影响

目的探讨不同局部温热条件对人乳头瘤病毒（HPV）感染皮损朗格汉斯细胞（LCs）CD1a／CD83表达变化的影响,为病毒疣的治疗提供理论依据。方法采用共聚焦显微镜检测正常皮肤组织和尖锐湿疣皮损内LCCD1a／CD83的表达变化;利用37℃,42℃,45℃不同温热条件处理正常皮肤组织和尖锐湿疣皮损,采用流式分析技术检测游走至培养液中CD1a^＋／CD83^＋LC的数量变化。结果正常皮肤组织和尖锐湿疣皮损内只见CD1a^＋LC,无CD83^＋LC;正常皮肤组织和尖锐湿疣组织游走细胞中CD1a^＋／CD83^＋LC的百分比均随局部温度升高而逐渐增多。温热对尖锐湿疣组织游走LC中CD1a CD83表达影响显著高于正常皮肤组织。结论局部温热可能通过促进LC的迁移和成熟,在局部细胞免疫应答中发挥作用。     

正常皮肤中单核巨噬细胞和树枝状细胞的分布规律

目的：观察正常真皮内的单核-巨噬细胞和树枝状细胞的分布、排列规律，探讨单核-巨噬细胞在皮肤免疫防御中的作用。方法：正常皮肤8例，取面部、躯干、四肢近端、四肢远端、手掌和足跖6个部位皮肤，进行纵行与水平切片。CD1a和CD68单克隆抗体染色，观察朗格汉斯细胞（LC）和单核．巨噬细胞的分布形态和密度。结果：真皮浅层CD68阳性细胞呈网状分布，其密度为361-562个／mm^2。真皮内血管周围及附属器周围亦见CD68阳性细胞。真皮深层CD68阳性细胞多为树枝状，散在分布于粗大的胶原纤维之间。不同解剖部位真皮浅层CD68阳性细胞密度分别为：四肢远端562个／mm^2，腹部517个／mm^2，面部509个／mm^2，手掌507个／mm^2，四肢近端472个／mm^2，足跖361个／mm^2。真皮浅层CD68阳性细胞在手掌和足跖部位高于相应部位的表皮内CD1a和CD68细胞。结论：在真皮浅层形成数层单核．巨噬细胞网，此网在接近真表皮交界处较致密。真皮内单核-巨噬细胞的这种分布形式说明这些细胞在真皮内有明确的方向性，其防御的方向是穿透表皮进入真皮的入侵物。     

系统性朗格汉斯细胞组织细胞增生症的临床病理分析

朗格汉斯细胞组织细胞增生症(LCH)是一种朗格汉斯细胞的克隆性、肿瘤性增生性疾病,其肿瘤细胞表达CD1a、Langerin和S-100蛋白,电镜下可见特征性的Birbeck小体.根据病变部位及范围,临床上分为三型:(1)单系统、单病灶(嗜酸性肉芽肿,EG);(2)单系统、多病灶(Hand-Schuller-Christian病);(3)多系统、多病灶(Letterer-Siwe病).     

T淋巴母细胞性淋巴瘤/髓系肉瘤合并朗格汉斯细胞组织细胞增生症的临床病理分析

目的探讨T淋巴母细胞性淋巴瘤(T-LBL)/髓系肉瘤(MS)合并朗格汉斯细胞组织细胞增生症(LCH)的临床病理学特征、免疫表型及预后。方法收集中山大学附属佛山医院和首都医科大学北京友谊医院2013年12月至2019年4月间6例T-LBL/MS合并LCH患者临床及病理资料,采用HE染色、免疫组织化学EnVision法、原位杂交法进行染色分析,检索文献并复习。结果6例患者中,男性2例,女性4例。4例为T-LBL合并LCH,1例为T-LBL/MS合并LCH,1例为MS合并LCH。患者年龄5~77岁,中位年龄59岁。3例为多发淋巴结内病变,另3例为多发淋巴结及皮肤/肝脾病变。5例显示淋巴结结构破坏,3例可见数个残留萎缩的滤泡。瘤细胞有2种形态,一种为体积中等大小的淋巴样细胞,呈片巢状分布。核圆形、卵圆形,这类细胞主要分布于残留的滤泡旁和副皮质区。另一种为组织细胞样细胞,体积大,胞质丰富淡染或嗜双色性。核卵圆形、不规则形,呈折叠状,主要分布于淋巴结边缘窦、髓窦和滤泡间区。所有病例的背景嗜酸性粒细胞浸润不明显。中等大小淋巴样细胞表现为末端脱氧核苷酸转移酶(TdT)、CD99、CD7阳性,不同程度表达CD34、髓过氧化物酶(MPO)、CD2、CD3,Ki-67阳性指数多在30%~50%之间。而组织细胞样细胞表现为CD1a阳性、S-100蛋白阳性、Langerin表达不一,不同程度表达CD163/CD68,不表达T和B细胞标志物,Ki-67阳性指数多在10%~20%之间。所有病例均无EB病毒感染。随访4例(随访时间6~63个月,中位时间18.5个月),其中1例死亡,3例带病生存。结论T-LBL/MS合并LCH是一种少见的混合型幼稚淋巴造血系统疾病,多发生于皮肤、淋巴结,临床进展凶猛,预后差,故充分认识同一组织内两种病变成分有助于精准诊断与治疗。     

组织工程皮肤细胞对朗格汉斯细胞表型的影响

目的:研究异体组织工程皮肤种子细胞(角质形成细胞、成纤维细胞)对朗格汉斯细胞的表型影响.方法:外周血单个核细胞在粒细胞巨噬细胞集落刺激因子(GM-CSF)、白介素4(IL-4)和转化生长因子β1(TGF-β1)的诱导下培养出朗格汉斯细胞.培养的朗格汉斯细胞与异体组织工程皮肤种子细胞共同培养后,检测其表型变化情况.随后将朗格汉斯细胞与淋巴细胞共培养后检测淋巴细胞的增殖程度.结果:诱导培养的朗格汉斯细胞低表达HLA-DR、CD80和CD86,不表达CD83.与异体组织工程皮肤种子细胞共培养后朗格汉斯细胞表型无明显变化,共培养后的朗格汉斯细胞无法刺激自体淋巴细胞增殖.结论:与异体组织工程皮肤种子细胞共培养后,朗格汉斯细胞仍保持不成熟的状态,这提示组织工程皮肤种子细胞免疫原性较低,移植后不易引起宿主的免疫排斥反应.     

Immunohistochemical detection of granulocyte/macrophage colony-stimulating factor in Langerhans' cell histiocytosis

Granulocyte/macrophage-colony stimulating factor (GM-CSF) induces in vitro activation of Langerhans' cells. The association of GM-CSF and tumour necrosis factor α (TNFα) induces the differentiation of Langerhans' cells from CD34 positive haematopoietic progenitors. Intradermal administration of recombinant GM-CSF is associated with local accumulation of Langerhans' cells. We investigated the presence of GM-CSF in tissue samples of 10 patients with Langerhans' cell histiocytosis. Four patients had skin involvement, three had bone and three had diffuse disease. Eight normal skin samples were analysed as controls. Immunohistochemistry was performed on frozen tissue samples with two specific monoclonal antibodies directed against two different epitopes of GM-CSF. We detected GM-CSF in all the histiocytosis tissue samples. The GM-CSF was detected within the cytoplasm of all the tumoral Langerhans' cells. We did not find GM-CSF in any other cell type. These results suggest that GM-CSF may be implicated in the pathogenesis of Langerhans' cell histiocytosis.     

Expression of adhesion molecules in Langerhans' cell histiocytosis

Expression of adhesion molecules was investigated in six biopsy specimens of Langerhans' cell histiocytosis using immunocytochemistry. Cells with Langerhans' cell histiocytosis morphology were stained for ICAM-1, for the beta-1 integrins alpha-4 (VLA-4) and alpha-5 (VLA-5), and for the beta-2 integrins LFA-1, MAC-1 and p150,95. This pattern of reactivity was different from that of epidermal Langerhans' cells of the normal skin which were not immunostained. A variable number of CD68+ multinucleated giant cells was present in five biopsies. They were less reactive than the cells of Langerhans' cell histiocytosis for alpha-4 (VLA-4) and LFA-1, were positive for MAC-1 and p150,95 and were characterized by prominent expression of the beta-1 integrins alpha-2 (VLA-2), alpha-3 (VLA-3) and of VnR (alpha-v/ beta-3). The repertoire of adhesion molecules expressed by giant cells is indicative of profound cell-matrix interactions, whereas that of Langerhans' histiocytosis cells suggests particularly active cell–cell interactions. Blood vessels of the lesions were stained for beta-1 integrins, for vitronectin receptor and for molecules involved in adhesion and trans-endothelial migration of circulating leukocytes, such as ICAM-1, VCAM-1 and E-selectin. Additional findings were the observation of CD1a+ multinucleated giant cells in a single case, suggesting a possible lineage relationship with the histiocytosis cells, and the demonstration of some Ki-67+ Langerhans' cell histiocytosis cells and CD1a+ mitotic figures in four of six cases, indicating local proliferation of Langerhans' histiocytosis cells.     

肺郎格汉斯细胞组织细胞增生症的病理诊断及鉴别诊断

目的 探讨肺郎格汉斯(Langerhans)细胞组织细胞增生症诊断和鉴别诊断。方法 常规HE染色及免疫组织化学链霉素抗生物素蛋白-过氧化物酶(SP)法染色观察7例肺郎格汉斯细胞组织细胞增生症的形态学及S-100、CD68、CD1a免疫组织化学表达特点并分析其临床资料。结果 7例均可见明确郎格汉斯细胞性肉芽肿改变,并可见中等量炎细胞浸润、局灶间质纤维化及灶性坏死。免疫组织化学阳性检出情况分别为S-100 7／7、CD68 3／7、CD1a 5／5。结论 临床及影像学检查(X线及CT)怀疑郎格汉斯细胞组织细胞增生症患者应尽早行开胸或胸腔镜肺活组织检查,病理学确诊对肺郎格汉斯细胞组织细胞增生症的治疗和控制其发展有很重要作用,免疫组织化学S-100及CD1a染色对鉴别诊断有意义。     

A rare case of coexistence of pulmonary adenocarcinoma with Langerhans’ cell histiocytosis

We report a rare case of coexisting pulmonary adenocarcinoma and Langerhans' cell histiocytosis (LCH) in a 78-year-old woman who did not smoke. During follow-up of diabetes mellitus, she had complained of chest pain and was found to have a nodular lesion in S9 of the left lower lobe, which was resected surgically. No abnormal laboratory findings were obtained. Before surgical resection, needle biopsy specimens confirmed the existence of adenocarcinoma. The resected tumor in the left lower lobe was 3.0 x 1.8 x 3.0 cm, and histologically both acinar and bronchioloalveolar cell subtypes of adenocarcinoma were found in cancer foci. In addition to pulmonary adenocarcinoma, Langerhans' cell proliferation associated with marked eosinophil infiltration was incidentally found in a small nodule, approximately 3 x 2 mm in size in the subpleural region. The Langerhans' cells contained interdigitated nuclei, exhibiting rather clear nucleoplasm and cytoplasm; they were positive for S-100 protein, CD1a, and also CD4. Massive eosinophil infiltration was found around the focus of Langerhans' cell proliferation. This nodule appeared to be LCH. The adenocarcinoma and LCH were adjacent, and cancer cells were infiltrated only in the peripheral parts of LCH. The coexistence of adenocarcinoma and LCH appeared to be incidental. The association of adenocarcinoma and LCH is rare, and only several reports of it can be found in the English literature.     

Diffuse large B-cell lymphoma initially manifesting in bone marrow. A case report

We presented the case of diffuse large B-cell lymphoma initially manifesting in bone marrow without lymph nodes' swelling and other extranodal lesion. A 68-year-old woman was suffering from general fatigue and fever. Because atypical cells were identified in the peripheral blood, a bone marrow puncture and random skin biopsy were performed. In myelogram, it was suspicious for myelodysplastic disease because lymphoma cells resembled other atypical hematopoietic cell. In biopsy specimen of bone marrow, atypical cells diffusely infiltrated, which could be called "paced bone marrow". On the other hand no atypical cell identified in the vessels of dermis and subcutaneous tissue by random skin biopsy. Immunohistochemically, atypical cells in bone marrow were diffusely positive for B-cell marker (CD20). These results lead this case to be diagnosed as diffuse large B-cell lymphoma initially manifesting in the bone marrow. In this case, it was very useful that bone marrow biopsy and myelogram were evaluated simultaneously. Quick and accurate diagnosis is possible by combining immunohistochemical analysis using both myelogram and biopsy specimen.     

February 2002: 29-year-old woman with a skull mass for 2 months

A 29-year-old woman had a 2-month history of an enlarging lesion over her left frontal bone following minor trauma. CT scan showed an osteolytic lesion with an overlying soft tissue mass, thought to be an unhealed skull fracture with pseudomeningocele. Left frontal craniotomy revealed a soft tissue mass, which was resected. Histologic examination revealed multinucleated giant cells mixed with Langerhan's cells that showed the characteristic "coffee bean nuclei." Eosinophils were scant. Immunostaining for CD1a and S100 revealed strong positive staining primarily in the Langerhans' cells while giant cells and inflammatory cells were negative. Immunostaining for CD68, in contrast, stained the osteoclast-like giant cells and macrophages. Electron microscopy confirmed the presence Birbeck granules. The final diagnosis was Langerhans' cell histiocytosis (histiocytosis X) of the skull.     

Langerhans-Zell-Histiozytose der Leber

We report on the difficult differential diagnosis of liver involvement in disseminated Langerhans' cell histiocytosis (LCH). Three years after treatment of LCH involving the skull and pelvic bones, an 18-year-old girl presented with abdominal pain and cholestatic liver disease. At this time, liver biopsy showed portal infiltrates which were diagnosed as chronic non-suppurative destructive cholangitis. Two years later, she was icteric under progredient hepatic failure. A second liver biopsy revealed biliary fibrosis and granulomatous inflammation with destruction of the portal bile ducts. The morphological changes in both liver biopsies could be identified as LCH by immunohistochemical detection of CD1a and S-100-positive Langerhans' cells. Morphological changes and clinical findings in LCH of the liver may resemble primary sclerosing cholangitis or chronic non-suppurative destructive cholangitis. Therefore, LCH is an important differential diagnosis of chronic destructive cholangitis with cholestatic liver disease, especially in children and young adults. The diagnosis can be verified by S-100 and CD1a immunohistochemistry.     

Liver involvement in Langerhans' cell histiocytosis: a study of nine cases.

Nine cases of Langerhans' cell histiocytosis (LCH) of the liver are presented. Five of the patients had liver involvement only. Other organ systems, notably the lymph nodes and skin, were involved in the other four patients. Four of the patients had sclerosing biliary disease with infiltration of the bile ducts by Langerhans' cells, whereas in two other patients, the biliary sclerosis was not associated with direct hepatic involvement by Langerhans' cells. Histologically, the lesions were composed of focal aggregates of Langerhans' cells in a polymorphous background of mature eosinophils, lymphocytes, neutrophils, and plasma cells. LCH encompasses a syndrome that has a broad range of clinical presentations and that might involve the liver solely as tumor-like lesions or cystic lesions, or as part of systemic disease. Even when Langerhans' cells are not demonstrable, sclerosing cholangitis can be seen in LCH.     

Histiocytic lesions and proliferations in the lung

Pulmonary lesions encountered by the pathologist in which histiocytes are the dominant finding histologically are reviewed. Lesions discussed include neoplasms of histiocytes and nonneoplastic processes. The nonneoplastic processes are divided into those that present as nodular histiocytic proliferations in the lung, those that present as diffuse proliferations of histiocytes in the lung, and those with a mixed pattern. Entities discussed include pulmonary Langerhans' cell histiocytosis, pneumonoconioses, infections, diffuse panbronchiolitis, crystal storing histiocytosis, respiratory bronchiolitis, alveolar hemorrhage, eosinophilic pneumonia, obstructive pneumonia, exogenous lipoid pneumonia, some drug reactions, and some metabolic/storage diseases. Entities of uncertain histogenesis, including Rosai-Dorfman disease and Erdheim-Chester disease, are also discussed. Qualitative features of the histiocytes are addressed, including the presence of foreign dust, hemosiderin, foamy change, and histiocytes showing features of Langerhans' cells.