NK细胞淋巴瘤讲义

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 cellsand NK-like T cells,Discrepancy of CD3 expressionin NK cells,CD3 is a TCR-associated complexFormed by 6 chains: , , 2, 2NK cells have cytoplasmic or , but cannot assemble intact CD3 complexConventional 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 hyperplasiaEntrapped nasal mucosal glands often show clear cell changeSkin: infiltrate often perivascular and periadnexal, but sometimes diffuse dermal; subcutis can be involvedIntestine: 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,EBVPresent in clonal episomal formNasal: 95% positive, irrespective ofethnic originExtra-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 lymphoidcells often appear slightlylarger 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 glandsTissue ulceration and necrosisEvidence of invasion:Angiocentric growthCytologic atypia:Clear cytoplasmMedium-sized; nuclear irregularities; granular chromatinReadily 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 lymphoidinfiltrate,Dense sheets of B cells,B celllymphoma,Dense sheets of CD3+ CD56+ cells,NK/T celllymphoma,Dense sheets of CD3+ CD56- cells,Reactive orCD56- NK/Tlymphoma orT cell lymphoma,How to confirm a suspicion ofNK/T cell lymphoma?,Immunostain for CD56: large clusters or sheets of positive cells strongly support diagnosis of lymphoma Pitfall: herpes infectionIn-situ hybridization for EBER: large groups of positive cells support diagnosis of lymphomaImmunostain for Ki67: High in