Benign clear (sugar) cell tumor of the lung with CD1a expression

Reported herein is a case of benign clear cell tumor of the lung in a 60-year-old man. Chest X-ray and CT examination revealed an abnormal nodule with homogenous density and a clear margin in the lower lobe of the left lung. The resected tumor was 13 mm in size, well-circumscribed and was graysh-white on cut surface. Histological examination showed a diffuse growth pattern of polygonal tumor cells with indented and pleomorphic nuclei, and clear abundant cytoplasm with a distinct cell border surrounded by thin-walled vascular spaces and sinusoid-type vessels. The clear cytoplasm contained numerous glycogen granules as demonstrated by PAS staining. In the present case there was focal immunoreactivity for S-100 protein, HMB-45, neuron-specific enolase, cathepsin B and melan A, which are consistent with reported immunohistochemical staining patterns of benign clear cell tumor. Based on these findings, the tumor was diagnosed as a benign clear cell tumor of the lung. Although most clear cell tumors are considered to belong to the family of neoplasms with perivascular epithelioid cell differentiation (PEComas), histogenesis of benign clear cell tumor of the lung has remained unclear. This first report of CD1a expression in this tumor might provide a new insight into its histogenesis and diagnosis.     

PEComa: what do we know so far?

PEComas (tumours showing perivascular epithelioid cell differentiation) are a family of related mesenchymal neoplasms that include angiomyolipoma, lymphangiomyomatosis, clear cell "sugar" tumour of the lung, and a group of rare, morphologically and immunophenotypically similar lesions arising at a variety of visceral and soft tissue sites. These tumours all share a distinctive cell type, the perivascular epithelioid cell or "PEC' (which has no known normal tissue counterpart). PEComas show a marked female predominance and are composed of nests and sheets of usually epithelioid but occasionally spindled cells with clear to granular eosinophilic cytoplasm and a focal association with blood vessel walls. PEComas appear to arise most commonly at visceral (especially gastrointestinal and uterine), retroperitoneal, and abdominopelvic sites, with a subset occurring in somatic soft tissue and skin. Nearly all PEComas show immunoreactivity for both melanocytic (HMB-45 and/or melan-A) and smooth muscle (actin and/or desmin) markers. A subset of PEComas behave in a malignant fashion. This review examines the members of the PEComa family, with an emphasis on lesions arising outside of the kidney, lung and liver, and discusses preliminary evidence for pathological features that might predict malignant behaviour.     

尖锐湿疣组织CD1a、上皮细胞钙粘素分子及其mRNA的表达和朗格汉斯细胞的电镜观察

目的:研究尖锐湿疣(Condyloma accuminatum,CA)组织中朗格汉斯细胞(Langerhans cell,LC)数目、形态和功能改变及其分子机制.方法:免疫组化SP法和逆转录RT-PCR法分别检测LC表面标记分子CD1a、粘附分子上皮细胞钙粘素(E-cadherin)及其mRNA表达,透射电镜观察LC的超微结构,并以正常包皮组织作为对照.结果:与正常对照组(21.59±10.48)相比,CA组织中CD1a+LC数目(10.66 ±11.71)减少(P＜0.05),胞体缩小,树突减少.CD1a mRNA表达(0.4066±0.2671)低于正常(0.744 4±0.3667)(P＜0.01);CA组织中E-cadherin染色变淡,平均积分值(2.36±1.41)低于正常对照(7.67±1.64)(P＜0.01),E-cadherin mRNA表达(0.173 7±0.108 3)较正常对照(0.378 6±0.146 0)相比显著降低(P＜0.01);CD1a+细胞数目与E-cadherin表达强度之间存在正相关关系(r=0.940 4,P＜0.05)、CD1a mRNA与E-cadherin mRNA的表达呈正相关(r=0.838 1,P＜0.05);CA组织LC胞质内细胞器稀少,Birbeck颗粒少见.结论:CA组织中存在着LC的缺失和抗原提呈功能异常,可能导致HPV持续性感染,LC的减少可能与E-cadherin表达下降导致LC在表皮内难以滞留有关.     

尖锐湿疣表皮CD1a和CD207的表达

目的:了解尖锐湿疣(CA)表皮中CD1a和CD207的表达情况及其意义.方法:采用寡核苷酸芯片对6例CA表皮和6例正常表皮中的CD1a和CD207的mRNA表达进行检测,应用半定量RT-PCR验证CD1a和CD207的mRNA表达,采用Western blot法检测6例CA表皮和6例正常表皮中的CD1a和CD207的蛋白表达.结果:基因芯片检测到CD1a和CD207的mRNA在CA表皮中表达下调,半定量RT-PCR证实CD1a和CD207的mRNA在CA表皮中表达下调,Western blot法检测到CD1a和CD207蛋白在CA表皮中的显著下调表达.结论:CA表皮中CD1a和CD207的表达下调,提示CA表皮中LC可能出现了数目的减少及功能的受损.     

It is time to beelieve the CD1a hype!

Conventional T cells have historically been linked to exacerbating allergy. By efficiently generating primarily T_H2 cells, allergens skew the immune response to produce IL‐4, IL‐13, and IgE. Previously, CD1a‐responsive T cells were shown to functionally respond to bee and wasp venom allergens. In this issue of the European Journal of Immunology, Subramaniam et al. [Eur. J. Immunol. 2016. 46 : 242–252] show that more functionally active CD1a‐restricted cells are present in bee venom‐allergic patients than in healthy patients. Additionally, the authors show that these cells are not as frequently found in individuals receiving venom immunotherapy. Consequently, this study implicates CD1a‐reactive cells as the primary responders to venom allergy, which considerably regulate the downstream immune response.     

CD151 expression can predict cancer progression in clear cell renal cell carcinoma

Yoo S H, Lee K, Chae J Y & Moon K C
(2011) Histopathology  58 , 191–197
CD151 expression can predict cancer progression in clear cell renal cell carcinoma Aims: CD151 is known to be implicated in cancer progression and metastasis. The aim was to evaluate the expression of CD151 in clear cell renal cell carcinoma (CCRCC) and to assess its prognostic significance. Methods and results: The expression of CD151 was evaluated in 489 cases of CCRCC by immunohistochemistry. Immunoreactivity was classified into four categories (minimal, 0–10% positive cells; focal, 10–50% positive cells; diffuse moderate, >50% positive cells with moderate staining intensity; diffuse strong, >50% positive cells with strong staining). To determine the statistical significance of CD151 expression in CCRCC, all cases were divided into two groups based on their CD151 expression level: a CD151‐low group (n = 257; minimal and focal) and a CD151‐high group (n = 232; diffuse). Expression of CD151 was correlated positively with pT, pN, pM categories, pathological tumour–node–metastasis (pTNM) stage, nuclear grade, tumour size and patient’s age. The CD151‐high group had significantly shorter cancer‐specific survival (P < 0.001) and progression‐free survival (P < 0.001) times. Furthermore, multivariate analysis showed that CD151 expression was an independent predictor for tumour progression in patients with CCRCC (P = 0.040). Conclusions: High CD151 expression is associated with advanced stage and high nuclear grade in CCRCC. CD151 is a prognostic marker for tumour progression in CCRCC patients.     

The expression of the B-cell marker mb-1 (CD79a) in Hodgkin's disease

Recent evidence indicates that membrane-bound immunoglobulin on B lymphocytes is associated with a molecule which comprises the products of the mb-1 and B29 genes. This molecule is a highly specific marker for B-cells, presumably because of its central functional role in antigen triggering, and has recently been clustered as CD79a at the 5th Leucocyte Workshop. Recently there has been controversy surrounding reports of B-cell antigen expression by Reed–Sternberg and related cells, and we have therefore studied 108 cases of Hodgkin's disease immunohistochemically using a novel antibody which detects mb-1 protein in paraffin sections. The results were compared with those achieved using antibody L26 to detect CD20. The mb-1 protein was present in the neoplastic cells in all 14 cases of lymphocyte predominance Hodgkin's disease studied, and CD20 immunoreactivity was also found in seven of the eight cases of this subtype studied. Of the non-lymphocyte predominance cases, 20% (19/94) expressed mb-1 and 30% (20/67) CD20 in the Reed–Sternberg cells, but the cells positive for either of these two markers usually constituted only a very small proportion of the neoplastic population. However, in occasional cases (one of 94 for mb-1 and five of 67 for CD20), more than 50% of the neoplastic cells expressed one or both B-cell antigens. These results confirm the B-cell origin of the neoplastic cells in lymphocyte predominance Hodgkin's disease, but they also indicate that, contrary to our previous study, mb-1 expression may occasionally be found in what appears, on histological grounds, to be other types of Hodgkin's disease.     

CD1a and CD1b surface expression is independent from de novo synthesized glycosphingolipids

CD1 molecules resemble classical MHC molecules in structure, bind self and bacterial glycolipids and present them to T cells. Whether the CD1 antigen-binding groove becomes filled during maturation and traffic to the cell surface is an important and still unsolved biological question. As most cell types synthesize complex glycosphingolipids (GSL), which also stimulate CD1-restricted T cells, it could be possible that these ligands associate with nascent CD1 molecules. Here, we show that treatment of cells with drugs blocking at different levels the de novo and salvage pathways of GSL synthesis does not prevent surface expression of CD1a and CD1b. Furthermore, transfection of CD1A and CD1B genes in a mutant cell line unable to synthesize glucosylceramides and galactosylceramides showed normal surface expression of both CD1 molecules. Lack of GSL did not induce intracellular CD1 accumulation as indicated by confocal microscopy. The same results were obtained by transfecting the Lec series of mutants, which are deficient in sugar addition to glycolipids and glycoproteins. These findings demonstrate that endogenous de novo synthesized GSL are not mandatory for CD1a and CD1b negotiating surface expression.     

白藜芦醇提高CD34+CD38-KG1a白血病细胞对人外周血单个核细胞的杀伤敏感性

目的:研究白藜芦醇(Resveratrol)作用前后CD34+CD38-KG1a白血病细胞对IL-15介导的人外周血单个核细胞(PBMC)杀伤敏感性的变化及机制的初步探讨.方法:应用CCK-8法检测白藜芦醇对白血病细胞的IC50值,以此量的白藜芦醇作用于白血病细胞.,并用LDH释放法检测白藜芦醇作用前后,效靶比分别为5∶1、10∶1、20∶1的IL-15介导的PBMC对CD34+CD38-KG1a细胞杀伤能力.流式细胞仪(FACS)检测IL-15介导前后PBMC表面NKG2D的表达.流式细胞仪(FACS)检测作用前后CD34+CD38-KG1a细胞表面NKG2D配体(MICA、MICB、ULBP1、ULBP2、ULBP3)表达.结果:白藜芦醇作用前后在不同效靶比时对IL-15介导的PBMC杀伤敏感性差异有统计学意义(P＜0.05).IL-15介导PBMC前后表面NKG2D的表达有显著变化,差异有统计学意义.白藜芦醇作用前后CD34+CD38-KG1a细胞表面NKG2D各配体中MICA、MICB无显著变化(P＞0.05),ULBP1、ULBP2、ULBP3有显著变化,差异有统计学意义(P＜0.05).结论:白藜芦醇可以提高CD34+CD38-KG1a细胞对IL-15介导PBMC的杀伤敏感性,其机制可能与白藜芦醇提高CD34+CD38-KG1a细胞表面NKG2D配体的表达有关.     

Evidence for cell surface association of CD2 and LFA-1 (CD11a/CD18) on T lymphocytes

Previous studies have reported an association of the cell surface adhesion molecule CD2 with the T cell receptor and with CD45 on mouse and human T lymphocytes. In this study the association of CD2 with cell surface molecules was investigated using cell surface biotinylation of T lymphocytes, coupled with immunoprecipitation using two CD2-specific monoclonal antibodies (mAb) (RM2–5 and 12–15) and analysis by SDS-PAGE. Although both CD2 mAb immunoprecipitated CD2 from lysates of murine lymphocytes, it was found that mAb 12–15, but not RM2–5, co-precipitated two other molecules of 95 and 180 kDa. Subsequent studies revealed that the 95- and 180-kDa molecules were associated with a subspecies of CD2 (? 5%) on thymocytes, the antigen-specific T cell line D10, and splenic T cells but not B cells. Two lines of evidence were obtained consistent with the 95- and 180-kDa molecules being the β and α chains of LFA-1. Firstly, an analysis of 12–15 mAb immunoprecipitates on 4–12% gels under reducing and nonreducing conditions shows that the 95- and 180-kDa molecules have a molecular weight and migration pattern identical to LFA-1. Secondly, depletion of LFA-1 from lysates with LFA-1 mAb abolished the ability of CD2 mAb 12–15 to co-precipitate the 95- and 180-kDa molecules, thereby identifying these as the β and α chains of mouse LFA-1, respectively. These results provide evidence for the first time for an association of LFA-1 and CD2 on mouse T lymphocytes, and suggest that the association occurs with an immunologically distinct subspecies of CD2 molecules.     

Age-related accumulation of LFA-1high cells in a CD8+CD45RAhigh T cell population

The differential expression of CD45 isoforms has been suggested as a marker for stages of post-thymic T cell development, that is, CD45RA+CD45R0^? T cells and CD45RA^?CD45R0⁺ T cells are supposed to be virgin and memory cells respectively. Recently, several adhesion molecules have been shown to be up-regulated on the cell surface of memory T cells, and have been suggested to serve as a memory marker. In this study, we investigated the levels of LFA-1 expression on T cells in various subpopulations defined by CD45 isoform expression in donors of various ages. In CD4⁺ T cells, the proportion of LFA-1^high cells among CD45RA^highCD45R0-T cells remained low in all age groups and did not show significant accumulation with age. CD4⁺CD45RA^?CD45R0^highTcells expressed LFA-1 at a higher level than CD4⁺CD45RA^highCD45R0^? T cells. Thus, the currently prevailing view that CD45RA and CD45R0 can be markers for virgin and primed cells was consistent with LFA-1 expression in CD4⁺ T cell population. In CD8⁺ T cells, however, CD45RA^highCD45R0^? T cells consisted of two distinct subpopulations, LFA-1^low and LFA-1^high cells, whereas CD45RA^?CD45R0^high T cells were almost exclusively LFA-1^high When CD29 expression was examined in place of LFA-1 expression, similar results were obtained; CD45RA^high CD45R0^? T cells consisted of two distinct subpopulations, CD29-^{to low} and CD^29high cells, while CD45RA-CD45R0^high T cells were mostly CD29^high. The proportion of LFA-1^high cells in the CD8+CD45RA^high T cell subpopulation increased significantly as a function of age (r = 0.9, p < 0.001). It ranged from 8% in a 14-year-old donor to 94% in a 79-year-old donor. Furthermore, the proportion of CD8⁺CD45RA^highLFA-1^high cells in the CD8⁺ T cell population increased significantly as a function of age (r = 0.85, p < 0.001). On the other hand, the proportion of LEA-1^high cells in CD8⁺CD45RA^? T cell subpopulation exceeded 90% in most donors irrespective of age. These results indicate that the CD8⁺CD45RA^highCD45R0^? T cell subpopulation contains a considerable number of LFA-1^high cells and CD29^high cells, phenotypically similar to previously activated cells. Thus, in terms of LFA-1 and CD29 expressions, the simple scheme that CD45RA is a marker of virgin cells is not applicable to the CD8⁺ T cell population.     

Immunohistochemical application of an antibody specific for human CD1a to the diagnosis of canine mast cell tumour

Canine mast cell tumours (MCTs) may be graded microscopically for prognostic purposes. Grade I (well-differentiated) and grade II (intermediate differentiation) tumours have an abundance of metachromatic granules within the cytoplasm; however, grade III (poorly differentiated) MCTs may be difficult to diagnose as they frequently have fewer discernable granules. Herein we report that a cross-reactive anti-human CD1a monoclonal antibody (clone O10) may be used in immunohistochemistry to identify canine MCTs of all grades. The antibody was applied to tissue sections from 48 canine MCTs of different histological grades. Serial sections from each tumour were stained with toluidine blue and safranin O to compare diagnostic sensitivity. All MCTs were labelled positively by the CD1a antibody, but histochemical staining was often equivocal and identification of mast cells was extremely difficult in some cases. This antibody did not label neoplastic cells in cases of canine histiocytoma, plasmacytoma or amelanotic melanoma; therefore, the reagent may be a valuable marker for the diagnosis of canine MCTs, especially those tumours of histological grade III.     

Aberrant expression of CD7, CD56, and CD79a antigens in acute myeloid leukemias

The prognostic significance of selected markers of leukemic cells is well known. CD7 and CD56 expression at diagnosis has been associated with low remission rates and biological aggressiveness in a significant proportion of acute leukemias. Among 46 patients with acute myeloid leukemia, we found CD7 expression in 15 cases (32.6%) and CD56 positivity in 10 patients (21.7%). Six of these myeloid leukemia cases (13%) showed expression of both CD7 and CD56. Four of 46 (8.7%) patients expressed CD79a. Among the 10 that were acute myeloblastic leukemia, 8 expressed CD7, 4 expressed CD56, and 4 were positive for CD79a. Thus, these markers were expressed early in hemopoietic ontogeny in the lesser-differentiated acute myeloid leukemia subtypes, including FAB M0, M1, and M2. Whereas CD7 and CD56 were each positive in 4 cases of acute myelomonocytic leukemia (FAB M4 subtype), there was no CD79a expression in the M4 cases. CD7 is expressed by mature T cells, NK cells, and an immature myeloid cell subset. NK cells and a T cell subset express CD56. By contrast, CD79a is a B cell marker that is assigned a high score of 2.0 in the differentiation of acute leukemias of ambiguous lineage in the WHO classification. The aberrant expression of CD7, CD56, and CD79a, representing the capacity of these leukemias for trilineal expression of leukocyte differentiation antigens, portends a poor prognosis.     

儿童急性白血病骨髓活检组织中bcl-2、CD20、CD79a的表达及临床意义

目的 探讨儿童急性白血病骨髓活检组织中bcl-2、CD20、CD79a的表达与发病和预后的关系.方法 对31例儿童急性白血病及10例对照组病例骨髓活检组织进行bcl-2、CD20、CD79a免疫组化检测.结果 bcl-2、CD20、CD79在初发白血病骨髓活检组织中的表达均增高,与对照组差异存在统计学意义(P＜0.05).缓解组骨髓活检组织6例bcl-2阳性表达中2例临床复发(33.3%),4例临床缓解(66.7%),13例bcl-2阴性表达临床均CR(P＜0.05).CD20、CD79a阳性表达与临床复发/CR差异无显著性意义(P＞0.05).结论 儿童急性白血病骨髓活检组织中bcl-2的检测可作为协助临床疗效判断、指导治疗的参考依据.