人原发性胃恶性淋巴瘤裸小鼠原位移植模型的建立

目的为探讨胃恶性淋巴瘤的发病机制和治疗方法提供理想的动物模型。方法采用人胃恶性淋巴瘤术中原发灶和肝转移灶新鲜瘤组织植入裸小鼠胃黏膜下层,观察原位移植成瘤率,移植瘤的侵袭和转移率,进行形态学、染色体核型和流式细胞分析。结果13例人胃恶性淋巴瘤标本9例移植成功。依据WHO新分类标准,从中筛选出1株人胃原发性非霍奇金B细胞恶性淋巴瘤裸鼠原位移植肝转移模型HGBL-9903,1株人胃原发性非霍奇金B细胞恶性淋巴瘤裸鼠原位移植模型HGBL-9904和1株人胃原发性霍奇金B细胞恶性淋巴瘤裸鼠原位移植模型HGBL-9902。免疫组织化学示CD19、CD20、CD22、CD45和CD79a均阳性。染色体众数范围75~87条,流式细胞分析示DI值1.23~1.47,均为异倍体。3株模型分别传至83代、87代和89代,共移植裸鼠785只;自第3代起肿瘤的移植生长率和液氮冻存复苏成活率均为100%。HGBL-9903肝转移率为100%,脾转移率为36.7%,淋巴结转移率为57.6%。人胃恶性淋巴瘤在裸鼠胃壁内自主侵袭性生长,侵袭破坏胃壁各层组织结构。发生血液(肝,脾)转移,淋巴转移和腹腔内种植转移。结论HGBL-9904、HGBL-9903和HGBL-9902三株人胃原发性恶性淋巴瘤裸鼠原位移植模型,移植瘤的组织病理学、超微结构、DNA含量测定及染色体核型分析结果与来源人胃恶性淋巴瘤细胞相一致。完整的模拟了人胃恶性淋巴瘤患者的自然临床过程。     

人原发性胃恶性淋巴瘤裸鼠原位移植高转移模型的建立

目的 建立人原发性胃恶性淋巴瘤裸小鼠原位移植高转移模型.方法 采用人原发性胃恶性淋巴瘤术中新鲜瘤组织块植入裸小鼠胃壁黏膜下层,观察原位移植的成瘤率和移植瘤的侵袭、转移,并进行形态学（光镜、电镜、免疫组织化学）、染色体核型和流式细胞分析.结果在裸小鼠体内建成了一株人原发性胃恶性淋巴瘤原位移植高转移模型（HGBL-0305）.移植瘤的组织病理学为原发性胃弥漫性大B细胞淋巴瘤.免疫组织化学显示,CD19、CD20、CD22、CD79α阳性,CD3、CD7阴性.染色体众数范围56～69条;移植瘤细胞DNA指数为1.47±0.12,均为异倍体.目前该瘤株在裸鼠体内生长4年,已经传至45代,共移植裸鼠156只;肿瘤移植生长率和液氮冻存复苏成活率均为100%.人胃恶性淋巴瘤在裸鼠胃内自主侵袭性生长,浸润破坏胃壁各层组织结构.HGBL-0305模型的肝转移率为69.5%,脾转移率为55.6%,淋巴结转移率为45.7%,腹腔种植转移率为30.5%.结论 HGBL-0305模型是成功的人原发性胃恶性淋巴瘤裸鼠原位移植自发性高转移模型,完整地模拟了人原发性胃恶性淋巴瘤患者的自然临床病理过程,为研究原发性胃恶性淋巴瘤发病机制、转移生物学和抗转移治疗提供了理想的动物模型.     

人原发性结肠恶性淋巴瘤裸小鼠原位移植肝转移模型的建立

目的 为探讨结肠恶性淋巴瘤的发病机制和实验治疗提供理想的动物模型。方法将结肠恶性淋巴瘤术中原发灶和肝转移灶新鲜瘤组织块植入裸小鼠结肠黏膜层内，观察原位移植的成瘤率，移植瘤的侵袭和转移率。进行形态学（光镜、电镜、免疫组织化学）、染色体核型和流式细胞分析。结果人结肠淋巴瘤原发灶和肝转移灶新鲜瘤组织均获得移植成功。依据WHO新的分类标准，建成1株人结肠原发性（原发灶）非霍奇金B细胞性恶性淋巴瘤裸鼠原位移植高转移模型（HCBL-0303）和1株人结肠原发性（肝转移灶）非霍奇金B细胞性恶性淋巴瘤裸鼠原位移植肝转移模型（HCBL-0304）。移植瘤组织病理学为（非霍奇金B细胞性）高度恶性淋巴瘤；免疫组化显示CDl9、CD20、CD22阳性，CD3、CD7阴性。染色体数目55—59条；流式细胞DI值1．59—1．71，均为异倍体。HCBL-0303肝转移率为63．7％，淋巴结转移率为56．4％；HCBL-0304肝转移率和淋巴结转移率为100％。移植瘤在裸鼠结肠内自主侵袭性生长，发生血液转移、淋巴转移和腹腔内种植性转移。结论HCBL-0303和HCBL-0304是首次成功建立的人结肠恶性淋巴瘤裸鼠原位移植自发性肝转移模型，可用于结肠恶性淋巴瘤的发病机制、侵袭、转移及实验治疗的研究。     

人原发性直肠恶性淋巴瘤裸小鼠原位移植模型的建立及其生物学特性

目的 建立人原发性直肠恶性淋巴瘤裸小鼠原位移植模型，探讨其生物学特性。方法 采用人直肠原发性恶性淋巴瘤切除术中的新鲜瘤组织块植入裸鼠的直肠黏膜层内，观察原位移植的成瘤率、移植瘤的侵袭和转移率。进行形态学（光镜、电镜）、免疫组织化学、染色体核型、流式细胞分析。结果 依据WHO新的分类标准，建成1株人直肠原发性（非霍奇金B细胞性）恶性淋巴瘤裸鼠原位移植模型HRBL-0305。移植瘤组织病理学为（非霍奇金B细胞性）高度恶性淋巴瘤，免疫组织化学示CD19、CD20、CD22、CD45阳性，CD3、CD7阴性，染色体56～69条，流式细胞DI值为1．57～1．61，均为异倍体。HRBL-0305已传至31代，共移植裸鼠187只。其肿瘤移植生长率和液氮冻存复苏成活率均为100％。肝转移率为45．4％，淋巴结和腹腔种植转移率均为38．0％，移植瘤在裸鼠的直肠内自主侵袭性生长，发生血液转移、淋巴转移和腹腔内种植性转移。移植瘤组织病理学、超微结构的观察、流式细胞DNA含量测定及染色体核型的分析，表明与人源直肠恶性淋巴瘤细胞相一致。结论 HRBL-0305是首次建立成功的人直肠原发性恶性淋巴瘤裸鼠原位移植模型。该模型完整地重现了人直肠原发性恶性淋巴瘤的自然临床病理过程，且转移模式与临床患者相似。为研究直肠恶性淋巴瘤的生物学特性和实验治疗提供了理想动物模型平台。     

人原发性直肠恶性淋巴瘤裸小鼠原位移植模型的建立及其生物学特性

目的建立人原发性直肠恶性淋巴瘤裸小鼠原位移植模型,探讨其生物学特性。方法采用人直肠原发性恶性淋巴瘤切除术中的新鲜瘤组织块植入裸鼠的直肠黏膜层内,观察原位移植的成瘤率、移植瘤的侵袭和转移率。进行形态学(光镜、电镜)、免疫组织化学、染色体核型、流式细胞分析。结果依据WHO新的分类标准,建成1株人直肠原发性(非霍奇金B细胞性)恶性淋巴瘤裸鼠原位移植模型HRBL-0305。移植瘤组织病理学为(非霍奇金B细胞性)高度恶性淋巴瘤,免疫组织化学示CD19、CD20、CD22、CD45阳性,CD3、CD7阴性,染色体56~69条,流式细胞DI值为1.57~1.61,均为异倍体。HRBL-0305已传至31代,共移植裸鼠187只。其肿瘤移植生长率和液氮冻存复苏成活率均为100%。肝转移率为45.4%,淋巴结和腹腔种植转移率均为38.0%,移植瘤在裸鼠的直肠内自主侵袭性生长,发生血液转移、淋巴转移和腹腔内种植性转移。移植瘤组织病理学、超微结构的观察、流式细胞DNA含量测定及染色体核型的分析,表明与人源直肠恶性淋巴瘤细胞相一致。结论HRBL-0305是首次建立成功的人直肠原发性恶性淋巴瘤裸鼠原位移植模型。该模型完整地重现了人直肠原发性恶性淋巴瘤的自然临床病理过程,且转移模式与临床患者相似。为研究直肠恶性淋巴瘤的生物学特性和实验治疗提供了理想动物模型平台。     

人小肠原发性恶性淋巴瘤裸小鼠原位和皮下移植高转移模型的建立

目的为探讨小肠恶性淋巴瘤的发病机制和实验治疗提供理想的动物模型。方法将人小肠恶性淋巴瘤术中原发灶新鲜组织块和肝转移灶瘤组织分别移植于裸小鼠的小肠黏膜层内和肩胛间皮下,观察原位移植和皮下移植的成瘤率、移植瘤的侵袭和转移率;进行形态学、染色体核型和流式细胞分析。结果5例人小肠恶性淋巴瘤标本3例移植成功。从中筛选出1株同一人体瘤源人小肠原发性(非霍奇金B细胞性)恶性淋巴瘤裸鼠原位移植高转移模型(HSIL-0101)和皮下移植高转移模型(HSIL-0102)。移植瘤病理组织学为非霍奇金(大B细胞性)高度恶性淋巴瘤;免疫组织化学示CD19、CD20、CD22、CD45阳性,CD3、CD7阴性。染色体众数范围55～59条;流式细胞分析示DI值1.47～1.61,均为异倍体。HSIL-0101和HSIL-0102分别传至32和38代;共移植裸鼠357只;肿瘤的移植生长率和液氮冻存复苏成活率均为100%。HSIL-0101肝和淋巴结转移率为100%;HSIL-0102肝转移率为63.5%,淋巴结转移率为62.7%。移植瘤在裸鼠的小肠内和皮下侵袭性生长,发生血液(肝、脾)转移、淋巴转移和腹腔内种植性转移。结论HSIL-0101和HSIL-0102是首次建立成功的人小肠恶性淋巴瘤裸鼠原位移植和皮下移植均出现自发性高转移模型,可用于小肠恶性淋巴瘤的发病机制、侵袭和转移及实验治疗的研究。     

人脾原发性恶性淋巴瘤裸小鼠皮下及原位移植模型的建立

目的 建立人脾原发性恶性淋巴瘤裸小鼠皮下和原位移植模型,为探讨其发病机制和实验治疗提供工具。方法 将人脾原发性恶性淋巴瘤新鲜组织块分别种植于裸鼠肩胛间皮下和脾实质内,观察皮下和原位移植的成瘤率、移植瘤的侵袭和转移及其形态学特征（光镜、电镜、免疫组织化学）。结果11例人脾原发性恶性淋巴瘤标本7例移植成功,从中筛选出一株同一人体瘤源人脾原发性（非霍奇金B细胞性裂核细胞型）恶性淋巴瘤裸鼠皮下移植模型BFNHL-HMN-1和原位移植模型BFNHL-HMN-2,瘤株生长稳定,已分别传至50代和51代。共移植裸鼠308只,其肿瘤移植生长率和液氮冻存复苏成活率均达到100％。BFNHL-HMN-1移植瘤呈结节状生长,均可向周围组织侵润,BHNHL-HMN-2移植瘤在脾内自主呈结节状生长,伴有脾门淋巴结累及和肝转移。移植瘤病理学、超微结构观察、流式细胞仪DNA含量测定及染色体核型的分析,表明与人脾原发性恶性淋巴瘤细胞相似。结论 经我们检索BFNHL-HMN-1和BFNHL-HMN-2是首次建立成功的人脾原发性恶性淋巴瘤裸鼠皮下和原位移植模型。为研究人脾原发性淋巴瘤的生物学和实验治疗提供了理想的动物模型。     

人脾原发性恶性淋巴瘤裸小鼠皮下及原位移植模型的建立

目的 建立人脾原发性恶性淋巴瘤裸小鼠皮下和原位移植模型，为探讨其发病机制和实验治疗提供工具。方法 将人脾原发性恶性淋巴瘤新鲜组织块分别种植于裸鼠肩胛间皮下和脾实质内，观察皮下和原位移植的成瘤率，移植瘤的侵袭和转移及其形态学特征（光镜，电镜，免疫组织化学）。结果 11例人脾原发性恶性淋巴瘤标本7例移植成功，从中筛选出一株同一人体瘤源人脾原发性（非霍奇金B细胞性裂核细胞型）恶性淋巴瘤裸鼠皮下移植模型BFNHL－HMN－1和原位移植模型BFNHL－LMN－2，瘤株生长稳定，已分别传至50代和51代。共移植鼠308只，其肿瘤移植生长率和液氮冻存复苏成活率均达到100％。BFNHL－LMN－1移植瘤呈瘤呈结节状生长，均可向周围组织侵润，BFNHL－LMN－2移植瘤在脾内自主呈结节状生长，伴有脾门淋巴结累及和肝转移。移植瘤病理学，超微结构观察，流式细胞仪DNA含量测定及染色体核型的分析，表明与人脾原发性恶性淋巴瘤细胞相似。结论 经我们检索BFNHL－LMN－1和BFNHL－LMN－2是首次建立成功的人脾原发性恶性淋巴瘤裸鼠皮下和原位移植模型。为研究人脾原发性淋巴瘤的生物学和实验治疗提供了理想的动物模型。     

人原发性小肠恶性黑色素瘤裸小鼠原位移植肝转移模型的建立

目的为探讨小肠恶性黑色素瘤的发病机制和实验治疗提供理想的动物模型。方法将原发性小肠恶性黑色素瘤患者术中原发灶和肝转移灶新鲜瘤组织块分别植入裸小鼠的小肠黏膜层，观察原位移植成瘤率，移植瘤的侵袭和肝转移率。进行形态学[光镜、电镜和免疫组织化学（免疫组化）]染色体核型和流式细胞分析。结果人小肠恶性黑色素瘤原发灶和肝转移灶新鲜瘤组织均获移植成功。建成一株人原发性小肠（原发灶）恶性黑色素瘤裸鼠原位移植模型（HSIM-0501）和一株人原发性小肠（肝转移灶）恶性黑色素瘤裸鼠原位移植肝转移模型（HSIM-0502）。移植瘤组织病理学为高度恶性黑色素瘤；免疫组化显示S-100蛋白；黑色素瘤单克隆抗体45阳性；电镜下瘤细胞质内可见大量黑色素颗粒及黑色素复合体。染色体众数55～59条；流式细胞DNA指数值1．49-1．61；均为异倍体。HSIM-0501和HSIM-0502分别传至25代和27代；共移植裸鼠317只；肿瘤移植成瘤率和液氮冻存复苏成活率均为100％。HSIM-0501肝转移率为46．2％，淋巴结转移率为36．7％；HSIM-0502肝转移率和淋巴结转移率均为100％。移植瘤在裸鼠小肠内自主侵袭生长，发生血液转移、淋巴结转移和腹腔内种植性转移。结论HSIM-0501和HSIM-0502是首次成功建立的人原发性小肠恶性黑色素裸鼠原位移植肝转移模型，可用于小肠恶性黑色素瘤的发病机制、侵袭和转移及抗转移实验治疗的研究。     

人胃癌裸鼠原位移植高转移模型的建立

目的 为探讨胃恶性淋巴瘤的发病机制和实验治疗提供理想的动物模型。方法 采用显微外科原位移植技术，将人胃癌新鲜组织移植裸鼠胃（黏膜层）壁内，观察原位移植成瘤率，侵袭和转移，及形态学特征（光镜，免疫组化电镜）。结果 从47例胃癌标本中筛选出一株人胃腺癌。裸鼠原位移植高转移模型已传至27代，一株人胃鳞腺癌裸鼠原位移植转移模型，已传至25代和一株人胃鳞癌裸鼠原位移植模型，已传至21代。共移植裸鼠426只。肿瘤的移植生长率为96．5％。自发转移率和液氮冻存复苏成活率均为100％。人胃癌在裸鼠胃壁内自主侵袭性生长，侵袭破坏胃壁各层组织结构，并直接侵袭到邻器官和组织。经血行转移到肝、肺、脾、肾等。淋巴道转移到胃的黏膜和黏膜下淋巴丛。局部及远处淋巴结。多伴发幽门梗阻癌性腹水，卵巢和腹腔内广泛种植转移。具有分泌癌胚抗原CEA的功能。移植瘤对p53、C－erbB-2、rasp21癌基因呈阳性表达，并与肿瘤的生长方式侵袭的深度和淋巴结转移有关。移植瘤细胞病理学，超微结构观察，流式细胞仪DNA含量测定，染色体核型分析，结果表明与人胃癌细胞相似。结论 三株人胃癌裸鼠原位移植高转移模型，完整的模拟了人胃癌患的临床过程，且转移模式与临床患相似。为研究人胃癌转移机制及实验治疗提供了理想的动物模型。     

Upper Aero-Digestive Tract Lymphomas Presenting as Polypoidal/Pedunculated Lesions: Case Report and Review of Literature

Aim

To describe a case of diffuse large B cell lymphoma (DLBCL) presenting as a pedunculated/polypoidal mass in upper aero-digestive tract and to review pertinent literature.

Methods

Using Pubmed advanced search, case reports and literature were reviewed for this condition.

Results

A 16 year old female presented with history of shortness of breath when lying down, voice change, progressing odynophagia and feeling of throat lump. Direct visualization showed flower like pedunculated mass, attached to the left lateral oropharyngeal wall. Excision of this mass showed DLBCL and no disease anywhere. She received four cycles of Rituximab + CHOP and is disease-free for 4 years. Only 21 cases of pedunculated upper aero-digestive tract lymphomas have been reported in literature. Median age 53 years (16–90 years), males 80 %, females 20 %, localized disease (65 %). Common sites were endobronchial polypoid lesion (7 cases), nasal polyps (7), nasopharyngeal polyps (2), nose and paranasal sinus (1), laryngeal polyp (2) and one each as gum, esophagus and oropharyngeal (current case) polyp. Pathology showed aggressive lymphoma in 94 %.

Conclusion

DLBCL as an extranodal pedunculated lesion in the oropharynx is very rare. Careful pathological evaluation is essential for these lesions for proper diagnosis.     

Primary Lymphoma of the Liver: Report of a Case

(Received for publication on Sept. 11, 1998; accepted on Nov. 11, 1999)     

The Expanding Spectrum of Follicular Lymphoma

Follicular lymphoma is a far more heterogeneous entity than originally appreciated. Clinical and biological variants are increasingly more granularly defined, expanding the spectrum of disease. Some variants associate with age, whereas others with anatomic site. Identification of these biologically distinct diseases has real prognostic and predictive value for patients today and likely will be more relevant in the future. Understanding of follicular lymphoma precursors has also made their identification both scientifically and clinically relevant. This review summarizes the features and understanding of follicular lymphoma, variants, and precursor lesions.     

Primary cutaneous B-cell lymphoma: Role of surgery

PURPOSE:

To evaluate the role of surgery in patients diagnosed with primary cutaneous B-cell lymphoma (PCBCL) – a rare disease entity. The authors offer a rationale for the use of primary surgical excision in the treatment of isolated cutaneous lymphomas.

METHODS:

A literature review examining the use of primary surgical excision in the treatment of PCBCL was conducted. The lymphoma database at the Juravinski Cancer Centre (Hamilton, Ontario) was searched from January 1995 to July 2008, generating a list of 4924 patients. A simulated computer program was subsequently designed to search for all possible PCBCLs. A retrospective chart review was then conducted on the new list of 1325 patients, identifying 25 patients diagnosed with PCBCL.

RESULTS:

The mean age of the 25 patients with PCBCL was 59.9 years; nine (36%) were treated with surgery, and sixteen (64%) with radiation. The average follow-up period for patients was 3.6 years. Twenty-four of the 25 patients were completely cured, with only one patient recurring in the radiation subgroup. There were no complications in the surgery subgroup. There were two local complications in the radiation subgroup consisting of chronic ulcerations.

CONCLUSIONS:

Primary surgical excision is an effective management option in the treatment of PCBCL, particularly the marginal zone and follicle centre subtypes.     

A Case of Primary Pulmonary Diffuse Large B-Cell Lymphoma Diagnosed by Transbronchial Biopsy

A 76-year-old man took a chest X-ray for his medical checkup and an abnormal shadow was detected in the right lower lung field. For more detailed examination, he was referred to our hospital. Chest computed tomography showed a 20-mm nodule with relatively regular margins in the right lower lobe. A compact proliferation of circular to polygonal cells with a high nucleus-cytoplasm ratio was evident in a transbronchial lung biopsy. Based on pathological findings, a mature large B-cell lymphoma was diagnosed. Thoracoscopic right lower lobectomy and mediastinal lymphadenectomy were performed. The post-surgical pathological examination showed that the tumor consisted of diffuse to compact proliferation of medium to large atypical lymphocyte-like cells. Immunohistochemical staining yielded positive results for B-cell lineage markers. Five months after surgical resection, neither local recurrence nor accumulation in remote organs was observed on gallium scintigraphy. The diagnosis of primary pulmonary diffuse large B-cell lymphoma was established.     

T-cell malignant lymphoma of the ileum causing ileac fistulas: report of a case

We herein present a rare case of three fistulas caused by a recurrence of T-cell lymphoma of the ileum. A 67-year-old man presented at a local hospital with left lower abdominal pain in May 1997. Upper and lower gastrointestinal examinations did not reveal any abnormal findings, but an abdominal aortic aneurysm was diagnosed by computed tomography, and thus was determined to be the source of the pain. The patient was referred to our hospital to undergo a grafting operation; however, a laparotomy performed in July 1997 revealed an unexpected small intestinal tumor, and therefore a partial ileectomy between 15 and 70 cm in an oral direction from the terminal ileum was carried out instead. Histopathological and genetic examinations demonstrated diffuse small malignant lymphocytic T-cell lymphomas of the ileum invading all layers. Metastasis of the facial skin and local recurrence were recognized 5 months later, and chemotherapy with THP-COP and ESHAP only resulted in progressive disease. An ileac fistula was found to have formed between the intestine and abdominal wall in March 1998, and the patient died in May 1998. An autopsy revealed three fistulas caused by metastatic tumors, one of which communicated with the duodenum from the ileum, one with the skin from the ileum, and one to the transverse colon from the ileum. Received: February 16, 2001 / Accepted: July 17, 2001     

Successful surgical resection and reconstruction for a huge primary cardiac lymphoma filling the right heart

Primary cardiac lymphoma (PCL) is rare, with a frequency of 1.0%–1.6% among cardiac malignant tumors. Chemotherapy is often selected as a first‐line treatment for PCL. However, when the tumor causes heart failure or life‐threatening hemodynamic collapse, antecedent urgent surgery is required. We herein report a successful case of complete tumor resection and reconstruction of the right atrium and right ventricle using a bovine pericardial patch combined with tricuspid valve replacement in a patient with a huge PCL filling the right heart that manifested as tricuspid valve stenosis and subsequent heart failure.     

T-cell Lymphomas: Updates in Biology and Diagnosis

Nodal-based peripheral T-cell lymphomas are heterogeneous malignancies with overlapping morphology and clinical features. However, the current World Health Organization classification scheme separates these tumors into prognostically relevant categories. Since its publication, efforts to uncover the gene expression profiles and molecular alterations have subdivided these categories further, and distinct subgroups are emerging with specific profiles that reflect the cell of origin for these tumors and their microenvironment. Identification of the perturbed biologic pathways may prove useful in selecting patients for specific therapies and associating biomarkers with survival and relapse.     

EBV Positive Primary Cutaneous CD30+ Large T-Cell Lymphoma in a Heart Transplanted Patient: Case Report

Most post-transplant lymphoproliferative disorders (PTLDs) are of B-cell origin, whereas T-cell lymphomas rarely occur. We detail the clinicopathological features of the first case of Epstein-Barr virus (EBV)-associated primary cutaneous CD30+ anaplastic large cell lymphoma (ALCL) in the setting of heart transplant. A 71-year-old patient, 111 months after transplant, presented with multiple cutaneous lesions on the left thigh; histological and immunohistochemical examinations led to diagnosis of T-cell CD30+ ALCL. In situ hybridization demonstrated the presence of EBV-positive tumour cells. The patient received radiotherapy, but he relapsed at the same cutaneous site with loco-regional nodal spread. Chemotherapy was administered resulting in complete remission; four years later the patient is alive and well. Our findings indicate that primary cutaneous EBV+ CD30+ ALCLs should be included within the T-cell PTLDs spectrum; further studies are required to confirm whether they may be also considered, in transplantation settings, a distinct lymphoma subset with relatively favourable outcome.