原发性乳腺非霍奇金淋巴瘤20例临床分析

目的:探讨原发性乳腺非霍奇金淋巴瘤(NHL)的临床特点、诊治及其预后。方法:对20例原发性乳腺非霍奇金淋巴瘤患者的临床资料进行回顾性分析。结果:20例原发性乳腺非霍奇金淋巴瘤患者中,女19例,男1例,中位年龄38岁(25~76岁),其中Ⅰ期9例(45.0%),Ⅱ期7例(35.0%),Ⅲ期3例(15.0%),Ⅳ期1例(5.0%)。1例(5.0%)为未化分型NHL,19例(95.0%)为B细胞性NHL。总的3、5年生存率分别为85.0%、65.0%,Ⅰ期 Ⅱ期3、5年生存率分别为93.75%、81.25%。结论:原发性乳腺非霍奇金淋巴瘤的预后与分期和治疗方式有关,手术 化疗综合治疗可获得较好疗效。     

乳腺恶性淋巴瘤形成及免疫组织化学研究

目的：研究乳腺非霍奇金淋巴瘤（ＮＨＬ）的组织形态特点及免疫表型。方法：对１７例乳腺ＮＨＬ作形态学分析，其中１１例进行了免疫学标记，结果：１３例为原发性，４例为继发性，８例（４７．０６％）见“淋巴上皮病变”，１３例（７６．４７％），见肿瘤浸润脉管，４例（２３．５３％）伴有“淋巴细胞性乳腺病”，３例（１７．６５％）见局部瘤细胞呈靶环样排列，免疫组化示１６例（９４．１２％）为Ｂ细胞ＮＨＬ，其中２例（１２．５０％）ＫＰ１阳性，１例（６．２５％）ＵＣＨＬ－１阳性，结论：（１）大多数乳腺原发性ＮＨＬ为ＭＡＬＴ型淋巴瘤，（２）淋巴细胞性乳腺病可能是一些乳腺ＮＨＬ的前驱病变；（３）少数Ｂ细胞ＮＨＬ能与ＫＰ１或ＵＣＨＬ－１发生交叉反应。     

原发性甲状腺非霍奇金淋巴瘤三例临床病理分析

目的 观察原发性甲状腺非霍奇金淋巴瘤(NHL)的病理学形态特征.方法 通过HE及免疫组织化学染色观察3例原发性甲状腺NHL的病理资料,并复习文献.结果 3例原发性甲状腺NHL中,弥漫性大B细胞淋巴瘤(DLBCL)2例,其中1例为中心母细胞型,1例为免疫母细胞型.另1例为黏膜相关淋巴组织(MALT)淋巴瘤.免疫组织化学结果显示瘤细胞均表达LCA、CD20、CD79a.结论 原发性甲状腺NHL具有多种不同病理形态特征,应与包括淋巴细胞甲状腺炎和未分化癌鉴别等.     

鼻腔鼻窦非霍奇金淋巴瘤免疫表型及其与EB病毒感染的关系

背景与目的:鼻腔鼻窦非霍奇金淋巴瘤(non-Hodgkin's lymphoma,NHL)的患病率和免疫表型组成具有地域性差异.本研究探讨中国广州地区57例鼻腔鼻窦NHL免疫表型及其与EB病毒(Epstein-Barr virus,EBV)感染的关系.方法:收集2000年4月1日至2006年10月31日中山大学肿瘤防治中心病理科57例鼻腔鼻窦NHL标本.免疫组化染色确定免疫表型,EBER原位杂交及PCR检测EBV感染情况.结果:在同期诊断的1 412例NHL中,71例(5.03%)发生于鼻腔鼻窦,其中仅有57例适用于本研究.57例鼻腔鼻窦NHL患者中,男性38例,女性19例,年龄3～75岁,中位年龄50岁;44例(77.19%)为鼻型NK/T细胞淋巴瘤,其中37例(84.09%)为EBV /CD56 NK细胞肿瘤,7例(15.91%)为EBV /CD56-细胞毒性T细胞表型;11例(19.30%)为B细胞淋巴瘤,其中6例为弥漫大B表型,2例为Burkitt(Burkitt样)淋巴瘤(EBV ),1例为髓外浆细胞瘤(EBV ),1例为MALT淋巴瘤(EBV-),1例为小淋巴细胞性淋巴瘤(EBV-);2例(3.51%)为外周T细胞淋巴瘤(EBV-).37例适用DNA检测的病例中,25例(67.57%)感染缺失型LMP1(del-LMP1)EBV株,12例(32.43%)感染野生型LMP1(wt-LMP1)EBV株.结论:鼻腔鼻窦NHL最常见的类型为鼻型NK/T细胞淋巴瘤,可进一步分为EBV /CD56 NK细胞及EBV /CD56-细胞毒性T细胞表型.NK/T细胞淋巴瘤均感染了EBV,EBV株主要为del-LMP1型.     

小儿原发性胃肠道非霍奇金淋巴瘤5例报告并文献复习

目的:对5例原发性胃肠道非霍奇金淋巴瘤(NHL)引发急腹症的临床资料进行分析,讨论其临床病理特点及手术效果.方法:收集2001年1月-2006年5月我院收治的5例原发性胃肠道非霍奇金淋巴瘤引发急腹症的病例,结合文献对其临床表现、诊断、治疗及预后等进行总结分析.结果:5例均为经病理、免疫组化等检查确诊的胃肠道非霍奇金淋巴瘤,其中肠梗阻2例,肠套叠3例(其中回结型2例,节结型1例);病理免疫类型:5例均为B细胞性非霍奇金氏淋巴瘤.5例均急诊行手术治疗,1例术中死亡,术后辅以联合化疗,方案为COP或CHOP.4例可随访,随访率80%.结论:小儿胃肠道非霍奇金淋巴瘤以B细胞性最多见,本病术前诊断率较低,往往以急腹症就诊.完整手术切除是NHL的治疗     

骨髓细胞学检查对恶性淋巴瘤病理诊断、临床分期及预后价值

[目的]探讨骨髓细胞学检查对恶性淋巴瘤病理诊断和临床分期的价值.[方法]总结回顾101例恶性淋巴瘤患者的骨髓细胞学检查和临床分期结果.[结果]霍奇金淋巴瘤(HL)24例;非霍奇金淋巴瘤(NHL)77例.NHL分型:B细胞型49例,T细胞型26例和NK细胞型2例.恶性淋巴瘤的骨髓侵犯(BMI)32例(31.68%),其中恶性淋巴瘤性白血病(MLL)8例.HL的淋巴细胞削减型和混合细胞型;NHL的小淋巴细胞淋巴瘤,前B淋巴母细胞淋巴瘤和T淋巴母细胞淋巴瘤BMI多见.10例无明显浅表淋巴结肿大的NHL患者经骨髓活检确诊为BMI,分期则由原Ⅱ、Ⅲ期升为Ⅳ期.恶性淋巴瘤发展至MLL的间期＜3.5年,生存期＜28个月,预后不良.[结论]骨髓细胞学检查对恶性淋巴瘤的诊断和临床分期有重要价值,尤其对无淋巴结病理证据的患者可提供诊断依据,伴有BMI患者为临床晚期,可能进展为白血病.     

原发性乳腺淋巴瘤7例临床病理分析

目的：探讨原发性乳腺恶性淋巴瘤的临床病理特征。方法：对我院收治的7例原发性乳腺淋巴瘤作了临床病理形态观察和免疫组织化学分析(S-P法)。结果：7例PBL均为女性，中位年龄45a，全部为非霍奇金淋巴瘤(NHL)，B细胞来源，占同期乳腺恶性肿瘤的0．15％。右乳4例，左乳2例，双侧累及1例。结论：PBL，以NHL占绝大多数，多数为B细胞来源。右乳常比左乳多见。治疗宜选择联合化疗为主加手术、放疗的综合治疗模式。     

原发性乳腺恶性淋巴瘤六例临床分析

目的 分析原发性乳腺恶性淋巴瘤的临床特点,探讨其诊断、分期和治疗方法。方法回顾分析我院自1995～2002年收治的6例原发性乳腺恶性淋巴瘤和1980～2002年国内主要文献报道的279例原发性乳腺恶性淋巴瘤的临床特征、诊断情况和治疗方法,进行对比分析。结果 285例病例均为非霍奇金淋巴瘤(NHL),免疫学检查证实有282例为B细胞源性(98.9％);女性268例,占94.0％;病灶位于右侧163例,占57.2％;Ⅰ期和Ⅱ期的原发性乳腺恶性淋巴瘤占89.8％。经手术、化疗、放疗等综合治疗后,生存期2～206个月,中位生存期最短23个月,最长56个月。结论 原发性乳腺恶性淋巴瘤绝大部分为B细胞源性非霍奇金淋巴瘤(NHL),Ⅰ期、Ⅱ期多见。对于原发性乳腺恶性淋巴瘤,诊断是关键,确诊后经手术、化疗、放疗等综合治疗,可以获得较长的生存期,疗效十分满意。     

乳腺原发性淋巴瘤的临床病理及预后

目的 对乳腺原发性淋巴瘤的临床病理诊断、免疫表型进行分析.方法 对1998年1月至2007年5月诊治的乳腺原发性淋巴瘤8例,回顾性分析其临床表现、病理特征及免疫组织化学标记分型.结果 8例乳腺原发性淋巴瘤中,弥漫性大B细胞淋巴瘤5例,黏膜相关淋巴组织淋巴瘤2例,淋巴浆细胞性淋巴瘤1例.免疫组织化学标记,LCA、CD20、CD79a肿瘤细胞膜阳性;CD45RO、CD3、CD23、CD10、CD5肿瘤细胞阴性.临床分期,5例为ⅠE期,3例为ⅡE期.采用CHOP方案化疗,随访2～110个月,其中1例随访108个月后,另一侧乳腺肿瘤复发.结论乳腺原发性淋巴瘤主要为B细胞淋巴瘤,以弥漫性大B细胞淋巴瘤和黏膜相关淋巴组织淋巴瘤较多见,而淋巴浆细胞性淋巴瘤少见.对于临床ⅠE期和ⅡE期的早期患者,采用CHOP方案化疗有较好的治疗效果.     

5例乳腺原发性恶性淋巴瘤临床病理学观察

目的:观察乳腺原发性恶性淋巴瘤(PBL)的临床病理特点.方法:采用HE和免疫组化技术对5例PBL进行病理组织学观察.结果:5例PBL临床都被误诊为乳腺癌,术后随访4年,其中1例于术后1年死亡,余4例存活.PBL的病理组织学特征为边界清楚的肿块,HE切片显微镜观察见淋巴瘤细胞灶性浸润导管/小叶上皮,免疫组化染色瘤细胞LCA、CD20阳性.结论:淋巴瘤细胞灶性浸润导管/小叶上皮是PBL的重要特征,应与乳腺典型髓样癌、乳腺假淋巴瘤鉴别.     

Prostacyclin and thromboxane in breast cancer: relationship between steroid receptor status and medroxyprogesterone acetate

To study the production and significance of prostacyclin (PGI2) and thromboxane A2 (TxA2) in breast cancer, tissue fragments of breast cancer (n=23) and mastopathy (n=10) were superfused in vitro and the release of 6-keto-PGF1 alpha (a metabolite of PG12) and TxB2 (a metabolite of TxA2) measured by radioimmunoassay. Breast cancer formed more 6-keto-PGF1 alpha (4.5 +/- 0.9 ng min-1 g-1 of tissue dry weight, mean +/- s.e.) and TxB2 (2.5 +/- 0.6 ng min-1 g-1) (P less than 0.01) than did mastopathic breast (1.4 +/- 0.5 and 0.4 +/- 0.1 ng min-1 g-1, respectively). These productions were similar in steroid receptor positive and negative tumours. Breast cancer metastasized in 15 patients during the follow-up time of 3.7 +/- 0.7 years, but the initial prostanoid productions in these patients were not different from those in nonmetastatic patients. Two patients died from metastases, but their initial mammary production of prostanoids was not profoundly different from those in the survivors. In 8 patients (4 with steroid receptor positive and 4 with negative tumour), the cancer tissue was superfused in the presence or absence of medroxyprogesterone acetate (100-5000 ng ml-1), which is commonly used for treatment of breast cancer. This hormone had no effect on mammary PGI2 and TxA2 production. We thus conclude that the PGI2 and TxA2 productions are increased in mammary cancer but that this may not be of primary significance for metastastic spread.     

Primary malignant lymphoma of the breast: clinicopathological study of nine cases

Primary lymphoma of the breast is rare, accounting for 1.7-2.2% of extranodal lymphomas and 0.38-0.7% of non-Hodgkin's lymphomas (NHL). The aim of this study was to evaluate the clinicopathological features and treatment outcomes of patients with primary breast lymphomas (PBL). We conducted a retrospective review of the NHL cases diagnosed at Korea Cancer Center Hospital between 1989 and 2002. Nine (0.9%) of the 1,050 cases fulfilled the criteria for PBL. All patients were women (median age, 45 years) and usually presented with breast masses that had recently become enlarged. Six cases involved the breast alone (stage IE), whereas 3 cases also involved the ipsilateral axillary lymph nodes (stage IIE). Histopathologic studies revealed a diffuse large B cell lymphoma in 7 cases, marginal zone B cell lymphoma in 1 case, and small lymphocytic lymphoma in 1 case. Immunohistochemical analysis revealed a B-cell phenotype in all cases. There was no uniform approach to the treatment of PBL. Modified radical mastectomy and chemotherapy was performed in 4 cases, modified radical mastectomy and chemoradiotherapy was performed in 1 case, chemoradiotherapy alone, modified radical mastectomy alone, chemotherapy alone, and radiotherapy alone were performed in 1 case each. All cases achieved complete remission, but median overall survival was 12 months, showing very poor prognosis irrespective of the type of treatment modality.     

Primary cultures of human benign mastopathies and mammary carcinomas; growth factor requirements

Primary cultures of non malignant human breast tissues, benign mastopathies and breast carcinoma were performed in defined culture conditions. Epithelial cells from these primary cultures were characterized for mammary epithelial cell specific markers, for in vitro cell proliferation, for steroid receptors and hormone sensitivity (estradiol, progesterone and prolactin) and for EGF sensitivity. We show that although some mastopathies have estradiol and progesterone receptors, they did not respond to hormone treatment. Human prolactin had no effect on the proliferation of one mastopathy but stimulates the cell growth of another fibrocystic mastopathy. EGF was capable of stimulating the three types of primary cultures. As regards growth characteristics, steroid hormone receptors and prolactin sensitivity, phenotypes of mastopathy cells differ from each other; some are similar to non malignant cells, whereas others are comparable to tumor cells.     

非霍奇金淋巴瘤侵犯骨髓的病理形态及免疫表型特点分析

目的:探讨非霍奇金淋巴瘤(NHL)侵犯骨髓的病理形态、免疫表型特点.方法:对骨髓活检标本,石蜡包埋切片,HE染色,光镜观察形态免疫组化进行表型分析.结果:65例中,B细胞淋巴瘤39例,T细胞淋巴瘤26例.形态学上,B细胞淋巴瘤多以混合型、弥漫型侵犯为主,外周T细胞淋巴瘤(PTCL)以间质型、混合型侵犯多见,伴有浆细胞、嗜酸细胞等反应性成分.毛细胞白血病(HCL)呈蜂窝样外观,具有诊断特异性.26例有髓外原发淋巴瘤者,瘤细胞形态与相应骨髓活检形态一致.免疫组化可对大部分淋巴瘤分型.6例小B细胞淋巴瘤不能分型的,2例结合脾脏病理特点确诊,4例仅有骨髓活检标本的,有待进一步检查确定.结论:多数NHL骨髓侵犯具有明确的形态学及免疫表型特点,可以诊断并分型.少数需结合原发部位及其它检查确诊.     

Evaluation of KISS1 Receptor Gene Expression in Egyptian Female Patients with Breast Cancer

Objective: Breast cancer is the second most common cancer in the world. Many metastasis suppressor genes were identified, including the KISS1 gene which encodes for a 145 amino acid protein (kisspeptin-145), which undergoes proteolytic cleavage resulting in kisspeptin-14, -13 and -10. All of these proteins can activate KISS1 receptor (KISS1R). The role of KP/KISS1R signaling in breast cancer remains controversial. The present study aimed to measure mRNA gene expression of KISS1 receptor in healthy and cancerous breast tissue and to evaluate the association of its level with the available molecular subtypes and the traditional clinico-pathological variables. Methods: The study was done on 41 operable primary breast cancer patients. Biopsies from both tumor tissue and surrounding healthy mammary tissue were taken from all patients. KISS1R mRNA expression level was measured using a quantitative real time PCR.   Results: KISS1R mRNA expression was significantly higher in stage III patients compared to stage II patients. At a cut-off value for KISS1R mRNA expression of 1.75, stage II was discriminated from stage III. A significant positive correlation was found between KISS1R mRNA expression and tumor size as well as lymph nodes metastasis. KISS1R mRNA was highly expressed in ER negative cases compared to ER positive ones, and in PR negative cases compared to PR positive ones. There was a statistically significant difference in KISS1R mRNA expression levels and different molecular subtypes being over-expressed in HER2 and triple negative cancer cases. Conclusion: This study supports other studies suggesting that KISS1/KISS1R may not be acting as a metastasis suppressor in breast cancer. KISS1R mRNA is over expressed in advanced stages of breast cancer and hence it can be used as a prognostic marker for aggressiveness of breast cancer. Also being over expressed in triple negative patients, KISS1R could represent a promising therapeutic target in triple negative cases.     

Immunocytochemical analysis of breast cells obtained by ductal lavage

BACKGROUND: Intraductal breast fluids containing exfoliated mammary epithelial cells can be harvested from the breast by ductal lavage to screen for disease-associated cytologic abnormalities. In addition to epithelial cells, breast fluids contain large numbers of mammary foam cells, and the tissue of origin of these foam cells has been the subject of controversy for many years. Immunocytochemical, morphologic, and molecular studies variously have supported a mammary epithelial origin versus a histiocytic origin for this cell type. In the current study, the authors performed immunocytochemical analysis with epithelial specific and macrophage specific antibodies to characterize and quantify breast cells obtained by ductal lavage. METHODS: Breast fluids were harvested from 19 individual breast ducts in 15 female patients by ductal lavage. Cells from each specimen were processed for immunocytochemical staining using the AE1/AE3 multicytokeratin and CD68 (clone KP1) monoclonal antibodies. Cells were classified as mammary epithelial cells or mammary foam cells on the basis of morphologic criteria, and the cells were counted and evaluated for immunoreactivity with epithelial specific and macrophage specific antibodies. RESULTS: The CD68 macrophage specific antibody stained all ductal lavage cells that exhibited foam cell morphology. The AE1/AE3 multicytokeratin antibody demonstrated strong, positive staining of cells that exhibited epithelial morphology but failed to demonstrate significant staining of mammary foam cells. The lavage specimens contained a range of 3040-278,850 epithelial cells and 2230-90,480 foam cells. The median numbers of epithelial cells and foam cells per lavage sample were 15,680 and 29,200, respectively. The ratio of epithelial cells to foam cells varied among specimens ranging from 3.4 to 0.09 (median, 0.8). Seven of 19 lavage specimens contained more epithelial cells than foam cells, whereas 12 samples contained a greater proportion of foam cells. CONCLUSIONS: Immunocytochemical analysis using the AE1/AE3 multicytokeratin and CD68 antibodies supports a histiocytic origin for the majority of mammary foam cells harvested from the ductal system of the human breast by ductal lavage. Although mammary foam cells constitute a significant proportion of the cellular population obtained by ductal lavage, thousands of epithelial cells also are harvested.     

Immunohistochemical expression of blood group substances and related carbohydrate antigens in breast carcinoma

In forty-one carcinomas and sixteen benign lesions (fibroadenoma and mastopathy) of the human breast, immunohistochemical expression of sialylated and non-sialylated forms of both Lea and Lex, and the A, B, and H type 2 blood group substances were studied by using an indirect immunoperoxidase staining. In normal ductal epithelium and benign lesion of breast, Lewis-related antigens were mostly expressed. Breast carcinomas showed these antigens with the following frequencies: Lea, 31.7% (13/41); sialyl Lea, 56.1% (23/41); Lex, 46.3% (19/41); sialyl Lex, 68.3% (28/41); A/B/H type 2, 38.1% (16/41). Sialylated forms of Lea and Lex were observed more frequently than their respective non-sialylated forms in breast carcinomas. In both one normal epithelium and four carcinomas of breast with Le(a-b-) phenotype, the expressions of type 2 antigens were observed, while type 1 antigens were not consistently expressed. Although compatible expression was observed in all specimens of both normal epithelium and benign lesion of breast, twenty-four cases with the deletion of A and/or B antigens, six cases with H type 2 accumulation and one case with incompatible expression were demonstrated in breast carcinoma. Thirty-one breast carcinomas which showed the deletion of A/B/H type 2 expressed the Lewis-related antigens more frequently than nine cases which showed compatible expression. These results suggested that the activation of terminal fucosyltransferase and sialyltransferase as well as inactivation of some glycosyltransferases had occurred in cancer cell membrane, and sialyl Lex, defined by a new monoclonal antibody CSLEX1, may be useful as a tumor-associated antigen independent of Lewis blood group type in breast cancer.     

Production and characterization of monoclonal antibodies showing a different spectrum of reactivity to human breast tissue

We have generated three hybridoma-producing monoclonal antibodies (MAs) that show a different spectrum of reactivity to human mammary tissues. Two of these antibodies, 1F10B4 and 1F10G2, recognize a cytoplasmic determinant highly expressed in most of the primary and metastatic breast carcinomas studied, and weakly (or not at all) in normal breast and nonbreast tissues. 3C6F9 detected a surface determinant common to both normal and neoplastic mammary epithelium. Five hundred hybridomas were obtained from the fusion of NS-1 myeloma cells with spleen cells of mice hyperimmunized with the well-characterized human breast carcinoma cell line BT-20. After the initial screenings and clonings, three monoclonal antibodies (1F10B4, 1F10G2, and 3C6F9) showing a restricted range of reactivity were selected for further investigation. These three antibodies recognized a panel of neoplastic mammary cell lines; however, the degree of reactivity could not be correlated to any of the various characteristics of these epithelial cell lines. Moreover, immunofluorescence analysis of acetone-fixed cryostat section showed that 1F10B4 and 1F10G2 recognize the vast majority of the 37 primary and metastatic breast cancers tested, binding strongly to 47% and 67% of them respectively. Only one of the primary carcinomas was not recognized by 1F10B4. On the other hand, these two MAs reacted weakly or not at all with normal breast and nonbreast tissues showing only few focal reactivities with the luminal pole of some ducts of the breast; very weak staining in renal tubular epithelial cells, in few keratinocytes and epithelial cells lining some sebaceous glands in the skin; and a moderate staining in biliary ducts of the liver. All mesenchymal structures including smooth and striated muscle tissues, lymph nodes, and connective tissue were negative. On the other hand, 3C6F9 recognized a more limited number of human mammary tumors and reacted with normal ductal epithelium in the breast and with nonbreast tissues. Because of their wide spectrum of reactivity with breast cancer cells and restricted recognition of normal mammary tissues, their cytoplasmic localization, and their heterogeneous distribution within a single neoplasm, 1F10B4 and 1F10G2 are now being used to characterize antigenic phenotypes of tumor-associated antigens in retrospective studies performed on conventional formalin-fixed, paraffin-embedded human mammary carcinomas.     

乳腺癌前哨淋巴结显像的临床价值

目的:探讨乳腺癌前哨淋巴结(SLN)显像的临床价值。方法:91例T1-2N0期乳腺肿瘤术前或局部手术后在患者瘤体上方的皮下注射了99mTc-人血清白蛋白(55.5 MBq/0.5ml)或在瘤周乳腺组织注射99mTc-硫胶体(92.5 MBq,/4ml),其中63例进行了乳腺淋巴显像,70例于注射后2-16小时、在腋淋巴清扫术前进行了术中γ探头引导下的乳腺SLN活检。结果:两种示踪剂均能快速显示淋巴结,以0.5h显像结果为准,SLN显像成功率为81％(51/63),13.7％(7/51)的SLN放射性强度低于第二个淋巴结,其中证实85.7％(6/7)存在转移。乳腺内、外侧部肿瘤的内乳SLN出现率为38.5％(5/13)、26.3％(10/38)。SLN活检成功率为95.7％(67/70),SLN数量1.6±1.1只(1-5只)。SLN预测腋窝淋巴结转移的灵敏度、特异性、准确性、PPV和NPV分别为82.75％(24/29)、100％(38/38)、92.53％(62/67)、100％(24/24)和88.37％(38/43)。结论:乳腺前哨淋巴结显像可以了解所显淋巴结的质与量以帮助活检者正确定位SLN,观察乳腺癌淋巴引流个体变异以引导活检部位和制定辅助治疗方案。