滤泡型小裂细胞性淋巴瘤利妥昔单抗治疗后转变为CD20阴性的弥漫大B细胞淋巴瘤临床病理分析并文献复习

目的：探讨B细胞恶性肿瘤美罗华(rituximab)治疗后复发伴CD20抗原表达丢失患者的临床病理学特征、免疫学表型、治疗及预后。方法：回顾性分析1例滤泡型小裂细胞性淋巴瘤患者经美罗华治疗后转变为CD20阴性的弥漫大B细胞淋巴瘤的临床病理资料，并结合相关文献进行复习。结果：患者于1987年以左侧腮腺区淋巴结肿大为首发症状，1988年行左侧腮腺区淋巴结活检诊断为滤泡型小裂细胞性淋巴瘤，先后进行了50个疗程的“COP、OP”方案化疗及短期局部放疗。1998年出现白细胞升高及淋巴细胞百分数升高，骨髓穿刺诊断为慢性淋巴细胞白血病。2012年3月至2014年3月因白细胞急剧增高多次使用“美罗华”治疗，2014年3月患者出现咽喉部不适，行会厌部取检，诊断为右侧舌根部CD20阴性的弥漫大B细胞淋巴瘤，经过3个疗程的“mini-CHOP”治疗及2次“美罗华”治疗后右侧会厌部肿块消失，2015年5月再次出现右侧颈部淋巴结肿大，经活检诊断为CD20阳性的弥漫大B细胞淋巴瘤。结论：美罗华治疗恶性B细胞淋巴瘤后CD20抗原表达丢失在临床中并非罕见，建议临床中对于美罗华治疗复发或不敏感的病例重新取组织活检进行病理诊断、免疫标记，必要时进行分子遗传学检测，以免误诊，并可对复发病因的药物调整起到的积极指导作用。     

原发性甲状腺非霍奇金淋巴瘤12例临床病理分析

目的探讨原发性甲状腺非霍奇金淋巴瘤(primary thyroid non-Hodgkin’s lymphoma,PTNHL)的临床病理特征、诊断及鉴别诊断。方法回顾性分析2010～2018年诊断的12例PTNHL的临床病理特征、免疫表型,并复习相关文献。结果所有病例均经术后病理及免疫组化染色确诊,其中男性3例,女性9例,平均发病年龄56. 7岁; 10例伴淋巴细胞性/桥本甲状腺炎背景; 12例均为B细胞淋巴瘤,8例病理类型为弥漫大B细胞淋巴瘤,4例病理类型为黏膜相关淋巴组织结外边缘区淋巴瘤,其中1例伴大细胞转化; 3例浸润甲状腺周围组织,1例伴颈部淋巴结受侵;免疫表型:瘤细胞均表达CD20和CD79a等B细胞标记,不表达CKpan、TG、EMA等甲状腺滤泡上皮标记。结论 PTNHL临床罕见,好发于老年女性,病理类型均为B细胞来源,多伴淋巴细胞性/桥本甲状腺炎背景,临床表现缺乏特异性,确诊依赖术后病理检查及免疫组化染色结果。     

原发性浆细胞白血病与淋巴瘤伴浆细胞增多的诊断与鉴别诊断

目的探讨原发性浆细胞白血病(primary plasma cell leukemia,PPCL)及淋巴瘤伴浆细胞增多的临床病理特征、诊断及鉴别诊断。方法采用临床资料及细胞形态学、流式细胞术、免疫固定电泳及免疫组化Eli Vision两步法等检测7例PPCL及3例淋巴瘤伴浆细胞增多,并进行分析。结果 7例PPCL及3例淋巴瘤伴浆细胞增多的临床特点均以进行性贫血、血小板减少、发热、肝脾及淋巴结肿大最为常见;外周血细胞形态学分类浆细胞比例均大于20%,且伴形态学异常;外周血流式细胞免疫表型显示7例PPCL均表达CD38及CD138,2例表达CD56,2例表达CD20,轻链(Lamda、Kappa)均呈单克隆限制性表达,符合PPCL诊断;3例淋巴瘤伴浆细胞增多CD19、CD45呈弱阳性,CD38、CD138呈阳性,轻链Ig L未见限制性表达,属于正常浆细胞的免疫表型。3例轻链(Ig)未见限制性表达,经淋巴结切除活检病理学检查确诊血管免疫母细胞性T细胞淋巴瘤2例,CD30阳性窦内大B细胞淋巴瘤1例。结论 PPCL与淋巴瘤伴浆细胞增多有相同的临床表现及相似的细胞形态学特征,PPCL的诊断需结合免疫固定电泳及流式细胞免疫表型;而淋巴瘤伴浆细胞增多还需结合淋巴结组织学检查才能确诊。     

霍奇金淋巴瘤侵犯骨髓的形态学及免疫表型分析

目的探讨霍奇金淋巴瘤侵犯骨髓的形态学、免疫表型特征及诊断与鉴别诊断要点。方法通过骨髓活检组织行HE、免疫组化Eli Vision两步法染色及EBER原位杂交,并结合临床资料进行分析。结果 10例经典型霍奇金淋巴瘤均可见由肿瘤性的大细胞(HRS细胞)及背景细胞和造血细胞形成的实体性或肉芽肿样结构;2例结节性淋巴细胞为主型霍奇金淋巴瘤可见由"爆米花"样细胞及背景细胞和造血细胞形成的实体瘤样结构。骨髓增生明显活跃者8例,造血组织三系增生减低者4例。有病态造血变化者8例表现为粒、红、巨三系分化及成熟异常,原始造血细胞增多。PET/CT示4例有骨质破坏,且伴骨髓纤维化及造血组织细胞三系减低的现象。免疫表型:2例结节性淋巴细胞为主霍奇金淋巴瘤CD20、BCL-6、OCT-2、CD45、EMA及BOB-1均阳性,而CD30、CD15均阴性;10例经典型霍奇金淋巴瘤CD30阳性,6例CD15阳性,9例Pax-5弱阳性,3例OCT-2阳性,3例CD20阳性。对8例混合细胞型经典型霍奇金淋巴瘤行EBER原位杂交检测,其中4例阳性。结论霍奇金淋巴瘤侵犯骨髓时,造血组织有病态造血的变化,尤其是粒细胞形态学的变化易与肿瘤性的大细胞混淆,在免疫表型上CD15亦阳性,需借助Pax-5加以鉴别,因为大多数肿瘤细胞Pax-5弱阳性,而粒细胞不表达Pax-5。骨髓活检可确诊霍奇金淋巴瘤骨髓浸润,对于无淋巴结侵犯或取材受限(如原发于呼吸道、纵隔等)的患者,在PET/CT引导下骨髓穿刺活检不仅可对其直接进行病理诊断,还有望提高淋巴瘤侵犯骨髓的检出率。     

血管内淋巴瘤

目的：探讨血管内淋巴瘤的临床病理特征。方法：对1例血管内淋巴瘤进行免疫表型分析及原位杂交检测与EB病毒的关系，并文献复习，结果：女性，48岁，不明原因发热伴体重下降3个月，CT扫描示子宫肿块而行子宫加双侧附件切除，病理学检查发现瘤细胞位于血管内，伴少许管周浸润，瘤细胞免疫表型CD45（LCA）和CD20（L26）呈阳性表达，原位杂交显示E－BERs阴性，患者经CHOP联合化疗后获得完全缓解，结论：血管内淋巴瘤是一种极罕见的B细胞肿瘤，此瘤的诊断只能依赖病理学检查，治疗上应予以积极联合化疗。     

子宫原发性血管内大B细胞淋巴瘤1例并文献复习

目的探讨子宫原发性血管内大B细胞淋巴瘤(primary uterine intravascular large B-cell lymphoma,PU-IVLBCL)的临床病理学特征、治疗及预后。方法收集1例PU-IVLBCL的临床病理资料,观察其形态学及免疫表型特征,并复习相关文献。结果患者女性,80岁,因子宫脱垂2年而行全子宫切除术,病理检查时偶然发现子宫多处小血管内异型淋巴瘤细胞聚集。免疫表型:肿瘤细胞CD45、CD20、CD79a、PAX-5、MUM1、CD5和BCL-2均弥漫阳性,Ki-67增殖指数为80%。结论 IVLBCL是一种罕见的高度侵袭性结外大B细胞淋巴瘤亚型,早期不易被发现。病理检查是确诊的金标准。PU-IVLBCL极其罕见,该肿瘤需与其他类型淋巴瘤、白血病、癌栓、血管源性肿瘤等进行鉴别;其预后差,部分病例于确诊后短期内死亡。     

淋巴结细胞毒性自然杀伤/T细胞淋巴瘤

目的 探讨淋巴结细胞毒性自然杀伤（NK/T）细胞淋巴瘤的临床病理学特征。方法 对5例淋巴结细胞毒性NK/T细胞淋巴瘤作临床病理观察及随访、用ISAB法做免疫表型分析（CD35RO、CD8、CD56、CD30、CD20、TIA-1）及EBER1/2原位杂交检测。结果 淋巴结细胞毒性NK/T细胞淋巴瘤的瘤 理组织学特点为：（1）淋巴结结构明显破坏并被瘤细胞所取代：（2）瘤细胞呈多形性;（3）我数肿瘤细胞表达淋巴细胞分化抗原。5例中CD45RO阳性的有4例,其中3例瘤细胞同时呈CD56阳性;1例为无标记细胞性;所有病例的TIA-1和EBER均为阳性。结论 淋巴结细胞毒性NK/T细胞淋巴瘤有特征性的形态改变和免疫表型。提示肿瘤进展及预后不良。     

多脏器恶性肿瘤术后肝黏膜相关淋巴组织淋巴瘤

目的 探讨肝黏膜相关淋巴组织淋巴瘤的临床病理特征。方法 对1例罕见多脏器恶性肿瘤术后肝黏膜相关淋巴瘤病例结合文献进行临床、病理和免疫组化分析。结果 患者于8年和3年前先后发生胃恶性间质瘤、阴囊阴茎皮肤湿疹样癌，有长期化疗史。肿瘤组织学以单核样B细胞为主，并有淋巴滤泡和淋巴上皮病变形成。免疫表型示瘤细胞CD45、CD79α、CD20阳性，CD5、CD10、ALK、TdT阴性，bcl—2、Ki—67少数肿瘤细胞阳性。结论 肝黏膜相关淋巴瘤可以发生于多脏器恶性肿瘤术后，其发病可能与长期使用免疫抑制剂有关，诊断本病时需与肝继发性淋巴瘤及肝的炎性假瘤鉴别。     

肝脾T细胞淋巴瘤6例临床病理分析

目的 探讨肝脾T细胞淋巴瘤(hepatosplenic T cell lymphoma,HSTCL)的临床病理学特征、免疫表型、诊断及鉴别诊断。方法 收集6例HSTCL的临床病理资料,采用免疫组化EnVision法染色,应用EBER原位杂交法检测EB病毒的感染,并复习相关文献。结果 6例患者均表现为间歇性高热(3周～2个月)、脾肿大、三系下降;均无免疫抑制状态;3例肝肿大伴肝酶增高,4例伴胸腹腔内淋巴结轻度增大,脾脏平均最大径22 cm。镜下均为明显扩张充血的髓窦索,3例散在单个或小簇状分布、略多形性的中～大异型淋巴样细胞,3例为弥漫分布、较一致的中等大小淋巴样细胞,均可见组织细胞吞噬红细胞现象。1例累及脾门淋巴结,肿瘤浸润在淋巴窦内。免疫表型:6例CD3、CD56均阳性,5例CD4/CD8均阴性,3例Granzyme B、TIA-1、Perforin阳性,2例CD30阳性,Ki-67增殖指数为40%～80%。EBER原位杂交检测均阴性(5/5)。4例行骨髓活检,其中3例骨髓累及,2例间质浸润,1例血窦浸润。5例患者术后辅以化疗,4例于术后22天～33个月死亡。结论 HSTCL肿瘤分布于脾脏红髓,表达细胞毒标记和CD56,与EB病毒感染无相关性;诊断需结合临床表现、病理学特征、免疫表型和分子检测综合判断。     

脑脊液流式细胞术在诊断非霍奇金淋巴瘤累及软脑/脊膜中的应用

目的 探讨脑脊液流式细胞术(CSF-FCM)在诊断非霍奇金淋巴瘤(NHL)脑脊膜转移(LM)中的价值.方法 回顾性分析3例影像学检查及脑脊液(CSF)病理检查均不典型的继发中枢神经系统淋巴瘤(SCNSL)的临床资料并复习相关文献.结果 病例1诊断为睾丸弥漫大B细胞淋巴瘤,查体无神经系统症状,CSF细胞学检查阴性,但CSF-FCM检到少量单克隆B淋巴细胞(CD19+B细胞10个,表达kappa,不表达lambda),予R-CHOP-HD-MTX化疗及腰穿鞘内注射治疗,患者停化疗7月复发,脑组织活检证实中枢复发.病例2诊断为小B细胞淋巴瘤(脾边缘区淋巴瘤可能性大),查体有神经系统症状,CSF细胞学检查阴性,CSF-FCM检测到单克隆B细胞占CSF有核细胞65.8％,表达CD19 kappa,不表达lambda,确诊NHL脑脊膜累及.病例3确诊小B细胞淋巴瘤(淋巴浆细胞淋巴瘤可能),停化疗8月后出现神经系统症状,骨髓检查﹑CSF细胞学检查及脑活检均未明确诊断,CSF-FCM提示脑脊液单克隆B细胞增多,表达CD45dim+CD19+CD20dim+CD5-CD10-CD22dim+CD2部分+FMC7部分+KAPPA-LAMBDA+CD200+CD79b+CD25+CD103-CD11C-CD38部分+,确诊NHL的脑脊膜受累.结论 所有存在CNS受累风险的淋巴瘤患者均应接受腰椎穿刺(LP)检查,CSF的流式细胞术分析有助于隐匿性脑脊膜受累的诊断.CSF样本的全面评估还包括二代测序基因检测、免疫球蛋白重链(IgH)或T细胞受体基因重排检测及细胞因子检测.     

Intravascular lymphomatosis

Intravascular lymphomatosis (IVL) is a rare angiotrophic large cell lymphoma producing vascular occlusion of arterioles, capillaries, and venules. Antigenic phenotyping shows that these lymphomas are mostly of B cell type, and less commonly T cell or Ki-1 lymphomas. The central nervous system and skin are the two most commonly affected organs; patients usually present with progressive encephalopathy with mental status changes and focal neurological deficits and skin petechia, purpura, plaques, and discolouration. Other involved organs include adrenal glands, lungs, heart, spleen, liver, pancreas, genital tract, and kidneys. Bone marrow, blood, cerebrospinal fluid, and lymph nodes are typically spared. Fever of unknown origin is another common presentation. Only one case of IVL presenting with disseminated intravascular coagulation and anasarca (generalised oedema) has been reported in the literature. This report describes a postmortem case of a patient with IVL who initially presented with disseminated intravascular coagulation complicated by intracerebral haemorrhage.     

The phenotype of mantle zone lymphoma studied by monoclonal antibodies

The clinical, pathological and immunological features of a case of mantle zone lymphoma are described. The patient presented at the age of 16 with a history of painless enlargement of the inguinal lymph nodes, biopsy of which revealed a nodular small cell lymphoma. During the course of 11 yr he was treated with total nodal irradiation, splenectomy and combination chemotherapy at different times. A recent lymph node biopsy reviewed along with the previous node biopsies was diagnosed as mantle zone lymphoma. At this stage, the immunological studies showed that the neoplastic lymphoid cells had characteristic markers of mantle zone lymphocytes. He is asymptomatic with mild generalized lymphadenopathy 11 yr after the initial diagnosis. This case illustrates the diagnostic and therapeutic problems which may be encountered. Detailed immunological marker studies with an extended panel of monoclonal antibodies are described.     

Cutaneous intravascular natural killer/T cell lymphoma with peculiar immunophenotype

Intravascular lymphoma (IVL) is a rare entity. Most cases are a variant of extranodal diffuse large B cell lymphoma, and fewer than 10% of the published cases are of T cell origin. Only intravascular B cell lymphoma is recognized as a distinct entity in the most recent World Health Organization (WHO) classification of lymphoproliferative disorders. We describe a case of cutaneous natural killer (NK)/T IVL, with a cytotoxic immunophenotype and Epstein–Barr virus (EBV) positivity. However, our case was immunohistochemically negative not only for T cell receptor (TCR)‐βF1 and TCR‐γ (TCR‐silent), but also for CD56, making it the first triple‐negative NK/T IVL case to be described. We urge recognition of this NK/T cell lineage intravascular lymphoma due to its particular immunophenotypical profile and its unvarying relationship with EBV. Its occurrence should not be considered a coincidence, but rather a key aspect of the pathogenic background of this haematological neoplasm.     

Morphologie neurologischer Komplikationen bei der intravaskulären Lymphomatose

Intravascular lymphomatosis (IVL) is a rare lymphoproliferative disease characterized by intravascular growth of lymphoma cells in small vessels. Most frequently, its first manifestations occur in the central nervous system or skin. Based on autoptical findings in a 68-year-old-man with IVL, the pathological morphology in the central nervous system is compared to the course of neurological symptoms. The disease could not be diagnosed during his lifetime. The spectrum of neurological deficits can be explained histopathologically by occlusive intravascular aggregations of lymphomatous cells in small vessels of the spinal leptomeninges and nerve roots causing perfusion deficits and areas of ischemic necrosis of up to 4 mm in diameter in the medulla. Aggregations of lymphoma cells in the vessels of other organs are also found, but did not result in clinical symptoms. In reference to the present case, a survey of other literature reports on IVL with neurological and psychiatric manifestations is given. In patients with this condition, even an invasive biopsy has to be considered in order to make the correct diagnosis at an early clinical stage.     

Hodgkin's lymphoma associated with plasma cell neoplasia: cytological features and review of the literature

Hodgkin's lymphoma (HL) associated with plasma cell neoplasia is extremely rare. Here, we report one case diagnosed by fine-needle aspiration biopsy (FNAB) and review the clinical features of 15 previously reported cases. Our specimen was obtained by FNAB of an enlarged right inguinal lymph node. Air-dried Diff-Quik (DQ)-stained slides and alcohol-fixed slides stained with hematoxylin-eosin (H&E) and Papanicolaou stains were reviewed. The specimen was cellular, consisting of lymphocytes and plasma cells. Flow cytometric analysis revealed a monoclonal (M) plasma-cell population. Admixed large atypical mono- and binucleated cells immunoreactive for CD30 were noted also. A diagnosis of plasma-cell neoplasm associated with classic HL was confirmed histologically after surgical removal of the lymph node. The diagnosis of both HL and plasma-cell neoplasia in the same patient is exceedingly rare. Adding another case to the 15 previously reported cases was unique because our case was diagnosed through FNAB.     

Transformation of hairy cell leukemia to high-grade lymphoma: a case report and review of the literature

The coexistence of hairy cell leukemia (HCL) and non-Hodgkin's lymphoma is extremely rare. In the few reports demonstrating such coexistence, the relationship between the 2 entities was mostly inconclusive. We report a case of HCL that transformed to large cell lymphoma. This case has been followed for more than 4 years with immunohistochemical, flow cytometric, and molecular genetic studies on multiple bone marrow biopsy specimens, a splenectomy specimen, and a lymph node biopsy. In our case, the immunophenotype and tartrate-resistant acid phosphatase stain confirmed that the large cell lymphoma was of HCL origin. The markedly increased Ki-67 staining (proliferation fraction) in the lymph node biopsy specimen compared to the earlier splenectomy specimen indicated the transformation of a low-grade leukemia to a high-grade lymphoma. The overexpression of p53 in the lymph node implies that p53 mutation was probably involved in the pathogenesis of HCL transformation.     

Intravascular large B-cell lymphoma presenting with mass lesions in the central nervous system: a report of five cases

We have encountered five cases of intravascular large B-cell lymphoma (IVL) presenting with central nervous system (CNS) mass lesions during their clinical course. The age of the patients ranged from 50 to 74 years and three patients were male. All of these cases histopathologically showed typical intravascular localization of the neoplastic cells in the initial biopsy specimens obtained from sites other than the CNS. Despite multiagent chemotherapy, patients suffered from single or multiple CNS mass lesions 5-44 months after the initial diagnosis of IVL, except for one case in which IVL and the CNS mass lesion were diagnosed at the same time. The subsequent biopsy and autopsy specimens obtained from the CNS mass lesions revealed diffuse infiltration of the tumor cells with perivascular spreading, but minimal or no intravascular components. Immunohistochemical analysis of intravascular tumor cells and CNS mass lesions revealed expression of CD20, CD79a, bcl-2 and negative for CD3e and Epstein-Barr virus encoded RNA. The overall features of the CNS mass lesions were very similar to or indistinguishable from those of the primary CNS lymphomas. This implies that CNS mass lesions in the IVL cases can be correctly diagnosed only by careful attention to clinical and pathological findings. Moreover, there is the possibility that some cases previously diagnosed as primary CNS lymphomas may have include IVL cases. Further investigation is needed to explore this unusual phenomenon.     

Fine-needle aspiration cytology of metastatic squamous-cell carcinoma arising in a pilonidal sinus, with literature review.

Fewer than 50 cases of carcinoma arising in a pilonidal sinus have been reported, with only 5 patients having documented inguinal lymph node metastases. This is the first report of the fine-needle aspiration (FNA) diagnosis of this uncommon clinical situation of squamous-cell carcinoma arising in a pilonidal sinus, metastatic to an inguinal lymph node. We report on a 59-yr-old male with squamous-cell carcinoma arising in a pilonidal sinus who presented with inguinal adenopathy. FNA biopsy of a lymph node was performed, resulting in a diagnosis of metastatic squamous-cell carcinoma. FNA biopsy is useful in the evaluation of patients with inguinal adenopathy and a history of malignancy arising in a pilonidal sinus. The possibility of this rare complication should also be considered when metastatic squamous-cell carcinoma to an inguinal lymph node is diagnosed by FNA cytology in patients having an unknown primary except for a change in a long-standing pilonidal cyst.     

Intravascular lymphomatosis of the lung and liver following eyelid lymphoma in a Chinese man and review of primary pulmonary intravascular lymphomatosis

Intravascular lymphomatosis (IVL) is characterised by an almost exclusive intravascular proliferation of malignant lymphoid cells, with the diagnosis often made only when the illness is in its terminal phase or at autopsy. We detail a case of IVL affecting the lung and liver of a 49-year-old Chinese man presenting primarily with lung symptoms and incidental findings of abnormal serum transaminase levels, the ante-mortem diagnosis being established on transbronchial lung biopsy and percutaneous liver biopsy specimens, respectively. Histology disclosed CD20 + CD5 - CD10 [corrected] - malignant large mononuclear B cells within the lumina of the blood vessels of the affected organs as well as sinusoids of the liver. Significantly, the patient had a history of large B cell lymphoma affecting the eyelid 18 months prior to the angiotropic disease, suggesting a possible link between the more common types of non-Hodgkin's lymphoma and IVL. A brief review of all cases of primary pulmonary intravascular lymphomatosis is also presented.     

Angiotropic lymphoma: report of a case with histiocytic features.

Angiotropic lymphoma, also known as intravascular lymphomatosis, is characterised by widespread intravascular proliferation of malignant lymphoid cells, usually without evidence of focal disease. A case of a 52 year old man referred for investigation of a two year history of pyrexia of unknown origin, skin rash and multiple organ failure is described. Angiotropic lymphoma was seen in gastric, colonic and skin biopsy specimens, and review of an earlier skin biopsy specimen showed similar morphological features. In contrast to previous cases which showed B or T cell differentiation, immunohistochemical examination was positive for histiocyte markers. Molecular studies showed no evidence of immunoglobulin heavy chain gene or T cell receptor gene rearrangement. The patient responded to combination chemotherapy, comprising cyclophosphamide, doxorubicin, etoposide, and prednisolone. This case highlights the fact that advanced lymphoma may be present without evidence of focal disease and that the diagnosis may be missed easily both clinically and histologically.