Immunotherapy in Hodgkin and non-Hodgkin lymphoma: Innate,adaptive and targeted immunological strategies

Since the clinical introduction of anti-CD20 monoclonal antibodies into lymphoma treatment, immunologic approaches in lymphoma have made substantial progress. Advances in our understanding of tumor immunology have led to the development of strategies to overcome immunologic barriers responsible for an ineffective immune response. Specifically, therapeutic agents have been developed and tested against molecules that are responsible for T-cell exhaustion. The use of monoclonal antibodies against immune checkpoints in the adaptive immune system, such as programmed cell death-1 and cytotoxic T-lymphocyte-associated protein 4, has changed the landscape of cancer therapy including the treatment of lymphoma. This achievement has recently been accompanied by the development of novel immune checkpoint inhibitors targeting the innate immune system, including the CD47-SIRPα signaling pathway, and this approach has yielded promising results. To overcome impaired antigen presentation, antibody-based cytotoxic strategies, namely antibody-drug conjugates (polatuzumab vedotin and brentuximab vedotin) and bispecific T-cell or NK-cell engagers (blinatumomab, REGN1979, RG6206, and AFM13), have rapidly evolved with promising clinical activity. As additional tools become available for lymphoma treatment, formulation of safe, rational combination strategies to combine them with standard therapy will be of paramount importance. A successful approach to the treatment of lymphoma may require both an optimized anti-tumor immune response as well as effective depletion of malignant lymphoid cells.     

Granulomatous slack skin T-cell lymphoma: an important differential diagnosis with giant cell tumor of soft tissue

Granulomatous slack skin is an indolent T-cell lymphoma, considered to be a variant of mycosis fungoides. Clinically it is characterized by areas of redundant skin, wrinkled, inelastic, with variable erythema and infiltration besides a poikilodermic surface. A differential diagnosis unknown to most dermatologists is the giant cell tumor of soft tissue, which is an extremely rare low-grade sarcoma. The authors report a patient who had undergone extensive surgery because of a primary diagnosis of giant cell tumor of soft tissue, but which proved to be granulomatous slack skin after a second interventional procedure with confirmatory histopathology.     

Infectious meningitis with atypical cerebrospinal fluid cells

Cytologic evaluation of the CSF is often difficult when trying to distinguish between truly neoplastic and reactive cells. Several non-neoplastic conditions may be associated with atypical cells in the CSF, a fact the clinician has to consider to avoid inadequate aggressive theraphies. We report here three patients with infectious meningitis (due to Herpes zoster virus in two, and neuroborreliosis in one) and cytologically atypical cerebrospinal fluid lymphocytes. Further characterization showed that the pleocyrosis in these patients was of reactive origin. Cytomorphology is frequently insufficient and histochemical, immuncytochemical and cellular genome analysis techniques may help differentiate atypical reactive cells from neoplastic cells.     

非鼻咽部T细胞淋巴瘤与EB病毒的相关性

目的：探讨EB病毒（EBV）感染与非鼻咽部T细胞淋巴瘤的关系。方法：用单克隆抗体UCHL-1、L26及EB病毒编码的潜在膜蛋白-1（LMP-1），免疫组化染色确定肿瘤的免疫表型及EB病毒转化蛋白的表达。采用原位杂交方法检测EBV编码的EBERs。结果：21例非鼻咽部T细胞淋巴瘤EBERs5例阳性的（23．8％），其中给内淋巴瘤3例，肺和胃肠淋巴瘤各1例。阳性细胞约占肿瘤细胞的10％～70％。5例EBERs阳性病例中仅1例表达LMP-1，为结内淋巴瘤。结论：非鼻咽部T细胞淋巴瘤可能与EBV的感染有关，LMP-1的阳性率较EBERs低。     

Chronic lymphocytic leukaemia and lymphoma in an Iranian fat-tailed sheep: a case report

A 5-year-old Iranian fat-tailed sheep was referred to the Veterinary Clinic of Shiraz University in September 2003 with a history of emaciation, fever, decreased appetite, lethargy and cough. Small cutaneous and subcutaneous nodules were palpable, especially under the ribs on both sides of the thorax. Discrete cutaneous plaques and large scabby lesions were also observed. Very large mammary gland lymph nodes were noticed on palpation. Haematological and serum biochemical values were estimated through standard haematological and biochemical techniques. In this case a normocytic–normochromic anaemia, leukocytosis and lymphocytosis were found. The concentrations of blood urea nitrogen (BUN), creatinine, cholesterol and the activities of aspartate aminotransferase (AST) and gamma-glutamyl transferase (GGT) were higher than the values reported for sheep. Necropsy findings revealed that the lymph nodes were affected in most organs. Malignant lymphoma in the kidney, heart, spleen, mammary glands, liver and bone marrow was observed. The histopathological appearance of the affected tissues varied considerably, depending upon the degree of tumour infiltration. According to the history, clinical signs, laboratory findings, necropsy findings and histopathological examination the case was diagnosed as chronic lymphocytic leukaemia and lymphoma.     

弥漫性大B细胞淋巴瘤的病理、免疫组化特征及IgH基因重排的检测

目的 探讨弥漫性大B细胞淋巴瘤(DLBCL)临床和病理组织学特征以及免疫组化特异性抗体及IgH基因重排检测在其诊断和鉴别诊断中的价值。方法 收集30例弥漫性大B细胞淋巴瘤及其临床资料，用免疫组化孓P法标记LCA，CD20，CD79a，CD30及bcl-2抗体和用PCR方法检测15例IgH基因重排。结果 70％(21／30)弥漫性大B细胞淋巴瘤发病年龄在40～70岁，淋巴结内外都可累及。组织病理学：中心母细胞淋巴瘤占83．3％(25／30)，免疫母细胞淋巴瘤占3．3％(1／30)，间变性大细胞淋巴瘤占6．7％(2／30)，及富于T细胞B细胞淋巴瘤占6．7％(2／30)。免疫标记LCA均表现阳性，CD20、CD79a、CD30、bcl-2表达率分别为86．7％(26／30)，93．3％(28／30)，6．7％(2／30)，20％(6／30)。15例DLBCL中IgH基因重排阳性为66．7％(10／15)。结论 弥漫性大B细胞淋巴瘤是一组异质性肿瘤，必须结合其组织病理学形态和特异抗体的免疫组化检测，对一些疑难病例需做IgH基因重排检测以进行诊断和鉴别诊断。     

非霍奇金淋巴瘤85例临床及预后分析

目的：分析多种因素对非霍奇金淋巴瘤(NHL)预后的影响。方法：通过SABC法进行免疫分型，采用Kaplan—Meier法分析患者治疗后的生存期，采用Cox比例风险模型分析影响预后的因素。结果：B细胞来源-NHL(B-NHL)发病率为63．3％。T细胞来源-NHL(T—NHL)为36．7％；低度恶性占17．6％，中、高度恶性占74．1％。1、2、3、5年生存率：低度恶性患者为92．1％、84．5％、65．1％、45．1％；中、高度恶性患者为84．9％、67．5％、47．6％、28．4％。I、Ⅱ期患者为98．8％、91.5％、87．5％、70．3％；Ⅲ期、Ⅳ期患者为62．1％、55．5％、40．1％、23．8％。T—NHL为70．8％、53．5％、47．7％、30．2％；B-NHL为82．1％、70．5％、61．1％、50．1％。结论：年龄、乳酸脱氢酶水平、恶性程度、临床分期、免疫分型、身体状况评分(PS)是影响NHL预后的重要因素。     

18F-FDG PET显像在发热待查患者中筛查淋巴瘤的价值

目的　探讨18F 脱氧葡萄糖 (FDG)PET显像在长期发热患者中筛查淋巴瘤的价值。方法　对 5 9例长期发热患者 (发热持续时间至少 3周 ,测 3次体温超过 38 3℃ )的18F FDGPET显像资料进行回顾性分析 ,将18F FDGPET显像诊断结果与病理检查及随访结果进行比较。结果　 5 9例长期发热患者中有 8例PET显像示恶性淋巴瘤可能 ,最后均经病理检查确诊为淋巴瘤 ,其中 2例为霍奇金淋巴瘤 ,6例为非霍奇金淋巴瘤。结论　PET显像示长期发热的淋巴瘤患者其病变淋巴结可在正常范围内 (<1 0cm或在体内较深部位 )。对长期发热患者 ,18F FDGPET显像可初步筛查淋巴瘤及排除其他肿瘤 ,可为穿刺活组织检查提供定位信息。     

Laparoscopically assisted gastric surgery using Dexterity Pneumo Sleeve

Background: Laparoscopic surgery has been successfully applied to several gastrointestinal procedures. Although the totally laparoscopic gastrectomy is feasible, tactile sensation and manipulation of the organ as well as the lesion are decreased when compared to open surgery. The Dexterity Pneumo Sleeve is a new device which allows the surgeon to insert a hand into the abdominal cavity while preserving the pneumoperitoneum. This device was used for patients who underwent laparoscopic gastric surgery. Methods: The first patient presented with a non-Hodgkin's lymphoma of the stomach. A laparoscopically assisted distal gastrectomy was performed with Roux-en-Y reconstruction. The second patient had a 5-cm leiomyoma involving the greater curve of the stomach, and this device was used for manipulation of the tumor. The last patient suffered from morbid obesity with its associated medical complications and a ventral hernia. The Sleeve was applied at the hernia site and a laparoscopically assisted gastric bypass was performed. Results: The Pneumo Sleeve was useful in these cases for tactile localization of the tumor and for retraction and manipulation of the stomach and surrounding upper abdominal organs. Conclusions: The utilization of this device resulted in a more easily performed dissection, resection, and anastomosis and was felt to decrease operation time. Received: 18 September 1996/Accepted: 26 December 1996