细胞淋巴瘤.ppt

NK/T细胞淋巴瘤,包括： 结外NK/T细胞淋巴瘤，鼻型 侵袭性NK细胞白血病 慢性NK细胞淋巴增生性疾病,NK细胞的免疫表型特点,No single marker unequivocally identifies all NK cells,CD2 70-90% s-CD3 0% c-CD3 95% CD4 0% CD5 0% CD7 80-90% CD8 30-40%,CD11b* 80-90% CD16* 80-90% CD56* 95% CD57* 50-60% CD25 95%,* Commonly used NK markers, but expressed in both NK cells and NK-like T cells,Discrepancy of CD3 expression in NK cells,CD3 is a TCR-associated complex Formed by 6 chains: , , 2, 2 NK cells have cytoplasmic or , but cannot assemble intact CD3 complex Conventional CD3 antibody detects chain “cytoplasmic CD3”,Surface CD3 (as detected by Leu4/OKT3) by flow cytometry or on frozen tissue is NEGATIVE,TCR,Leu4, OKT3,结外NK/T细胞淋巴瘤，鼻型,a鼻腔、鼻咽部、鼻窦及腭部最常见，皮肤、软组织、胃肠道和睾丸亦常见。 b鼻腔者表现为鼻塞、鼻衄，粘膜坏死及溃疡。皮肤病变表现为结节并多伴有溃疡。发生在肠道者常发生穿孔。 c肿瘤常有噬血管性，多伴有血管破坏和坏死。 d常坏死明显，活检取材要取及非坏死瘤组织，常需多次取材才能确诊。,大多数病例为EBV（+）、CD56（+）的NK细胞表型，而少数病例具有EBV（+）、CD56（-）的细胞毒性T细胞表型。,Small,Medium-sized,Large,Broad cytologic spectrum,Morphologic features,Surface squamous epithelium can show florid pseudoepitheliomatous hyperplasia Entrapped nasal mucosal glands often show clear cell change Skin: infiltrate often perivascular and periadnexal, but sometimes diffuse dermal; subcutis can be involved Intestine: Ulceration and perforation common,Skin,Intestine,Testis,Muscle,结外NK/T细胞淋巴瘤的免疫表型 CD2 + 表面 CD3 -; 胞浆 CD3 + (polyclonal CD3; PS1) CD56 +, CD57和CD16常- CD4, CD5, CD7, CD8: 常-,CD43, CD45RO: 常+ 细胞毒颗粒 + Ki67 : 高 CD25和 CD30偶尔+ TCR-;,CD3,CD5,CD56,Granzyme B,Extranodal NK/T cell lymphoma: Genotype,TCR genes: germline in most cases studied,EBV Present in clonal episomal form Nasal: 95% positive, irrespective of ethnic origin Extra-nasal: 90% positive in Asians, but lower % in Caucasians,Extranodal NK/T cell lymphoma: Main problems in diagnosis,Biopsies may show extensive coagulative necrosis, rendering it impossible to make a definitive diagnosis. Repeat biopsy is required. Some examples comprise small cells with minimal cytologic atypia: distinction from reactive lymphoid infiltrate very difficult,BEWARE: Mucosal small lymphoid cells often appear slightly larger than small lymphocytes, and can show irregular nuclei,Histologic features favoring a neoplastic process,Abnormal architecture: Dense expansile infiltrate with wide separation and loss of mucosal glands Tissue ulceration and necrosis Evidence of invasion: Angiocentric growth Cytologic atypia: Clear cytoplasm Medium-sized; nuclear irregularities; granular chromatin Readily found mitotic figures in a small cell lesion,Immunohistochemical analysis: First-tier panel,CD20, CD3, CD56, (Ki67),Nodular aggregates of B cells separated by T cells; few CD56+ cells,Reactive lymphoid infiltrate,Dense sheets of B cells,B cell lymphoma,Dense sheets of CD3+ CD56+ cells,NK/T cell lymphoma,Dense sheets of CD3+ CD56- cells,Reactive or CD56- NK/T lymphoma or T cell lymphoma,How to confirm a suspicion of NK/T cell lymphoma?,Immunostain for CD56: large clusters or sheets of positive cells strongly support diagnosis of lymphoma Pitfall: herpes infection In-situ hybridization for EBER: large groups of positive cells support diagnosis of lymphoma Immunostain for Ki67: High