间变性淋巴瘤激酶阴性的间变性大细胞淋巴瘤泛发性皮肤侵犯一例

患者男，37岁，入院前7个月无明显诱因右大腿出现一鹅蛋大小肿物，无明显不适，肿物逐渐增大，右大腿、臀部出现弥漫性、非凹陷性肿胀，入院前2个月全身皮肤出现暗红色丘疹、结节、斑块，部分斑块渐出现大小不一的糜烂、溃疡。实验室检查：白蛋白降低，乳酸脱氢酶显著升高。B超示浅表淋巴结肿大、融合，彩色多普勒示淋巴结内部较丰富的树枝样血流信号。CT显示右大腿及会阴部广泛淋巴结肿大伴软组织水肿，上腹部广泛淋巴结肿大，纵膈内淋巴结肿大。皮损组织病理：真皮全层致密分布单一核细胞，部分有异形性及不典型核分裂；免疫组化：CD3、CD8、CD30（阳性细胞占80%）、CD4、CD45RＯ、粒酶B 阳性，CD56、间变性淋巴瘤激酶（ＡＬＫ）、T细胞胞质内抗原1阴性。淋巴结病理：淋巴结结构完全破坏，肿瘤弥漫成片生长，肿瘤细胞比一般的大细胞淋巴瘤瘤细胞大，胞质丰富，嗜碱性或嗜双色性，细胞核偏位，呈马蹄形、肾形或分叶状，核染色质稀疏，可见单个或多个嗜碱性小核仁；免疫组化：CD2、CD4、CD3、粒酶B、上皮膜抗原（EMA）、Ki-67、CD30阳性，CD8、CD56、T细胞胞质内抗原（TIA）-1、ＡＬＫ均为阴性。诊断：间变性淋巴瘤激酶阴性的原发系统型间变性大细胞淋巴瘤泛发性皮肤侵犯。

Anaplastic lymphoma kinase-negative anaplastic large cell lymphoma with generalized cutaneous involvement:a case report

A rare case of anaplastic lymphoma kinase （ALK）-negative anaplastic large cell lymphoma（ALCL） with generalized cutaneous involvement is reported in a 37-year-old man. Seven months prior to the presentation, he developed a goose egg-sized mass in his right thigh without obvious triggers, which gradually grew and no significant discomfort was felt. Diffuse and nonpitting edema gradually appeared in his right thigh and hip. Two months prior to the presentation, multiple dark red papules, nodules, and plaques emerged over the body surface with erosions and ulcers of varying size arising on some of the plaques. Laboratory examination revealed reduced albumin and significantly elevated lactate dehydrogenase in serum. B-mode sonography showed swelling and mutual fusion of superficial lymph nodes, and color Doppler flow imaging revealed markedly increased branch blood flow signals in lymph nodes. Computed tomography（CT） displayed generalized swelling of lymph nodes associated with soft-tissue edema in the right thigh and perineal region, as well as extensive enlargement of epigastric and mediastinal lymph nodes. Pathological examination of the skin lesion revealed a dense dermal infiltrate with mononuclear cells, some of which presented with cellular atypia and atypical nuclear division. Immunohistochemistry of the skin lesion showed that the mononuclear cells stained positive for CD3, CD8, CD30 （80% positive）, CD4, CD45RO and granzyme B, but negative for CD56, ALK and T cell intracellular antigen-1（TIA-1）. Pathology of lymph nodes indicated that the lymph node structure was completely destroyed with a diffuse growth of tumor cells, which were larger than common large cell lymphoma cells, and contained basophilic or bi-color abundant cytoplasm, deviating, horseshoe-, kidney-shaped, or lobulated cell nuclei, sparse nuclear chromatin and single or multiple small basophilic nucleoli. Angiogenesis, stromal fibrosis and infiltration of varying number of plasma cells and lymphocytes were seen in pathological lymphoid tissue. Immunohistochemistry of lymph nodes showed that the tumor cells stained positive for CD2, CD4, CD3, granzyme B, epithelial membrane antigen （EMA）, Ki-67 and CD30, but negative for CD8, CD56, TIA-1 and ALK. The patient was diagnosed with ALK-negative primary systemic ALCL with extensive cutaneous involvement.