异位错构瘤性胸腺瘤1例及文献复习

目的探讨异位错构瘤性胸腺瘤(EHT)的临床及病理特征。方法复习1例EHT患者的临床病史、肿瘤组织的病理形态和免疫表型及相关文献。结果患者男性,56岁,以左胸锁关节下方皮下肿块为主要表现。肿瘤包膜完整,切面以灰白色实性为主。镜下表现复杂,以束状及平行排列的梭形细胞为主,混合有上皮成分及成熟的脂肪细胞等。瘤细胞均不具异型性,也缺乏坏死。免疫组化显示梭形细胞CK阳性,灶状细胞MSA阳性,S-100蛋白、desm in、vim entin和CD34均呈阴性。结论EHT有独特的发病部位和形态学表现,对梭形细胞上皮本质的认识是正确诊断的关键。     

Mediastinum thymoma diagnosed by FNA and ThinPrep technique: a case report

Thymoma is a primary tumor of the thymus epithelial cells. It may be asymptomatic or accompanied with atypical clinical symptoms or paraneoplastic syndromes, such as myasthenia gravis. The biological behavior of thymomas is unpredictable. The invasion of the capsule or the adjacent tissues is the major diagnostic criterion for the malignant behavior of these tumors. This is an interesting case of thymoma diagnosed by fine-needle aspiration biopsy (FNA) and ThinPrep technique, in a 54-year-old female patient with a history of gastric adenocarcinoma. Cytology of the mediastinum mass revealed a mixed population of epithelial cells and lymphocytes. The tumor was excised and the histopathological examination supported the cytological diagnosis. Thymomas commonly constitute a problem in differential diagnosis of mediastinum masses. FNA biopsy in correlation with ThinPrep technique and immunocytochemistry may play a significant role in clarifying the nature of these lesions and may contribute to the early management and choice of the optimal therapeutic manipulation.     

Expression of matrix metalloproteinases 2 and 7 in tumor cells correlates with the World Health Organization classification subtype and clinical stage of thymic epithelial tumors

To investigate the roles of matrix metalloproteinases (MMPs) in thymic epithelial tumors, we examined the expression of MMP-2, -7, and -9; membrane-type 1 (MT1)-MMP; and tissue inhibitor of metalloproteinase-2 (TIMP-2) in 57 tumors by immunohistochemistry and in selected 15 cases by in situ hybridization. The tumors consisted of 5 type A, 12 type AB, 11 type B1, 11 type B2, 9 type B3, and 9 type C thymomas according to the World Health Organization histologic classification system and of 22 stage I, 13 stage II, 8 stage III, and 14 stage IV thymomas according to the Masaoka staging system. In the positive cases, MMPs and TIMP-2 were expressed in both tumor cells and stromal cells. The cellular localization of MMPs detected by immunohistochemistry was almost identical with that of the mRNA signals detected by in situ hybridization. MMP-2 and MMP-7 were predominantly expressed in type B3 thymoma and type C thymoma, respectively. Expression of MT1-MMP and TIMP-2 correlated with that of MMP-2, indicating a proteolytic activation of the latter. MMP-9 was prominent in type B2 thymoma. Expression in tumor cells of MMP-2 or MMP-7 was also correlated with clinical stage. The present study suggests that certain MMPs may play an important role in the tumor progression of different subtypes of thymic epithelial tumors and that MMP-2 and MMP-7 may contribute to the tumor aggressiveness and malignant potential.     

指突状细胞在胸腺瘤中的分布

采用Ｓ－１００蛋白免疫组化方法对１８例胸腺瘤指突状细胞（ＩＤＣ）的分布、形态和数量进行观察研究，并与胸腺瘤的组织学类型及临床分期相对照。发现：髓质型胸腺瘤多处于早期临床阶段，ＩＤＣ弥散地分布于瘤组织内，数量较多，形态多样。皮质型胸腺瘤多处于晚期临床阶段，ＩＤＣ多分布于血管周围及实质与间质交界处，数量较少。结果提示，ＩＤＣ的多少与胸腺瘤的组织学类型及预后有一定的关联。     

Onchocerca volvulus-specific antibody and cytokine responses in onchocerciasis patients after 16 years of repeated ivermectin therapy

The recommended control option against onchocerciasis is repeated ivermectin treatment, which will need to be implemented for decades, and it remains unknown how repeated ivermectin therapy might affect immunity against Onchocerca volvulus in the long term. O. volvulus-specific antibody reactivity and cellular cytokine production were investigated in onchocerciasis patients receiving ivermectin (150 microg/kg) annually for 16 years. In treated patients, the T helper type 2 (Th2) cytokine interleukin (IL)-5 and T regulatory IL-10 in response to O. volvulus antigen (OvAg) and bacteria-derived Streptolysin O (SL-O) diminished to levels found in infection-free endemic controls; also, cellular release of Th1-type interferon (IFN)-gamma at 16 years post initial ivermectin treatment (p.i.t.) approached control levels. In ivermectin-treated onchocerciasis patients, IL-5 production in responses to the mitogen phytohaemagglutinin (PHA) decreased, but IL-10 in response PHA increased, and neither attained the cytokine production levels of endemic controls. At 16 years p.i.t., O. volvulus-specific IgG1 and IgG4 subclass reactivity still persisted at higher levels in onchocerciasis patients than in O. volvulus exposed but microfilariae-free endemic controls. In addition, cytokine responses remained depressed in onchocerciasis patients infected concurrently with Mansonella perstans and Necator americanus or Entamoeba histolytica/dispar. Thus, long-term ivermectin therapy of onchocerciasis may not suffice to re-establish fully a balanced Th1 and Th2 immune responsiveness in O. volvulus microfilariae-negative individuals. Such deficient reconstitution of immune competence may be due to an as yet continuing and uncontrolled reinfection with O. volvulus, but parasite co-infections can also bias and may prevent the development of such immunity.     

Difference in the distribution of tumor-infiltrating CD8+ T cells and FOXP3+ T cells between micronodular thymoma with lymphoid stroma and micronodular thymic carcinoma with lymphoid stroma

Micronodular thymoma with lymphoid stroma (MNT) is a rare thymic epithelial neoplasm subtype characterized by a micronodular tumor cell growth pattern and abundant lymphoid stroma. Micronodular thymic carcinoma with lymphoid stroma (MNCA) is considered as a malignant counterpart of MNT and exhibits a growth pattern similar to that of MNT but has histologic features reminiscent of thymic squamous cell carcinoma, such as cytologic atypia and CD5 and CD117 immunoexpression. Although both MNT and MNCA are characterized by abundant lymphoid stroma, it remains unknown whether there are differences in infiltrating lymphocytes between MNT and MNCA. We analyzed the immune microenvironment profile in eight MNT and three MNCA cases. The cell density of CD8-positive T cells was significantly higher in MNT than in MNCA, whereas that of FOXP3-positive T cells was significantly higher in MNCA than in MNT. There was no significant difference in the cell density of programmed death protein 1-positive T cells and programmed death ligand 1 expression between the MNT and MNCA cases. Our findings indicated that the immune microenvironment of MNCA differed from that of MNT and, compared with the T-cell profile of MNT, that of MNCA was more suppressive to patients′ antitumor immune response.     

Paraneoplastic myasthenia gravis: immunological and clinical aspects

Paraneoplastic myasthenia gravis (MG) is accompanied by a neoplasm, usually thymoma. In patients with thymoma and a specific genetic make‐up, the paraneoplastic immune response develops further in thymic remnant or peripheral lymphatic tissue. Paraneoplastic MG and late‐onset MG (age ≥ 50 years) share a similar immunological profile with high titin and ryanodine receptor (RyR) antibody prevalence. This profile is the most important predictor of clinical outcome in paraneoplastic MG. The presence of a thymoma per se does not cause more severe MG. MG severity is linked to the patient’s immunological profile. Paraneoplastic MG causes a distinctive non‐limb symptom profile at MG onset, characterized by bulbar, ocular, neck, and respiratory symptoms. When the diagnosis of paraneoplastic MG is established, the neoplasm should be removed surgically. Pre‐thymectomy plasmapheresis or iv‐IgG should be considered in these patients to minimize post‐thymectomy MG exacerbation risk. Paraneoplastic MG usually continues after thymectomy. The pharmacological treatment of paraneoplastic MG does not differ from non‐paraneoplastic MG, except for tacrolimus that should be considered in difficult cases. Tacrolimus is an immunosuppressant acting specifically in RyR antibody positive patients through enhancing RyR‐related sarcoplasmic calcium release that in theory might be blocked by RyR antibodies, causing symptomatic relief in paraneoplastic MG.     

Ruptured Pseudo-aneurysm of the Popliteal Artery after Percutaneous Transluminal Angioplasty

An 88-year-old female presented with gangrene of two toes of the left foot. Angiography revealed a calcified occlusion of the left popliteal artery, 8 cm in length. Recanalisation was performed and the occlusion was successfully dilated. On day 13 after the procedure, the patient experienced acute pain in the left popliteal fossa. Ultrasound revealed a large pseudo-aneurysm of the popliteal artery. Angiography not only confirmed this finding but showed rupture of this pseudo-aneurysm. An above-knee amputation was performed.

Pseudo-aneurysm formation at the site of previous PTA is considered as a rare complication and has not been reported in the literature. The incidence of pseudo-aneurysm formation at a PTA site is unknown because it is not routinely detected. Predisposing general and local factors are discussed. The present case illustrates that pseudo-aneurysms can cause other major complications with disastrous consequences for the patient.

Pseudo-aneurysms after previous PTA should be treated by conventional bypass surgery or by endovascular means. Further studies should be undertaken to evaluate the risk of pseudo-aneurysm formation after previous PTA and to define which patients should be monitored closely.     

恶性胸腺瘤侵犯大血管的手术治疗及术后生存调查

目的分析恶性胸腺瘤患者的手术方式及其预后,以期寻找到侵犯大血管的恶性胸腺瘤的最佳治疗方案。方法回顾性总结2003年1月至2008年12月期间有明确肿瘤侵犯大血管的患者19例,其中行Y型血管置换术2例,行双根人工血管置换6例,行单根上腔静脉和(/或)其属支置换术6例,行上腔静脉和(/或)其属支成形术5例。5例患者行主动脉和(/或)其属支外膜剥离。13例患者同时切除受侵犯肺组织,行解剖学肺段切除2例,行肺叶切除11例。12例患者因肿块完全侵犯膈神经,行单侧膈神经切除11例,行双侧膈神经切除1例。结果 19例患者平均生存期44.1(3～114)个月。1年生存率88.2%(15/17),3年生存率64.7%(11/17),5年生存率50%(4/8)(截至2012年10月)。结论恶性胸腺瘤侵犯上腔静脉和无名静脉并致梗阻不应成为纵隔肿瘤局部根治性切除的禁忌。掌握手术指征和禁忌,争取根治性切除是提高生存率的关键。术后的后续治疗,尤其是放疗,也是延长患者生存时间的因素之一。