Massive bone marrow infiltration of neuroendocrine carcinoma mimicking aggressive hematological malignancy
Massive bone marrow infiltration of neuroendocrine carcinoma mimicking aggressive hematological malignancy
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神经内分泌癌的大量骨髓浸润模仿侵袭性血液恶性肿瘤
DOI：
10.1007/s12308-021-00475-3
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发表时间：
2021
影响因子：
0.6
通讯作者：
Harigae Hideo
中科院分区：
文献类型：
--
作者：
Ichikawa Satoshi;Inokura Kyoko;Kawamura Yoshifumi;Fukuhara Noriko;Yokoyama Hisayuki;Ouchi Kota;Fujishima Fumiyoshi;Harigae Hideo
一名42岁的男子，一般状况不佳，腰痛加剧，入院时，在他的计算机断层扫描（CT）上检测到肱骨和股骨骨髓中的高密度区域，提示血液恶性肿瘤。他以前很健康，没有患过恶性疾病。全血细胞计数显示白色细胞计数增加（12，100/μL，正常范围3300-8600），伴成白细胞增多症（中性粒细胞60%，嗜酸性粒细胞1%，单核细胞6%，淋巴细胞22%，髓细胞4%，晚幼粒细胞6%，原始细胞1%，每100个白色血细胞6个有核红细胞），轻度贫血（血红蛋白12.5 g/dL，正常范围13.7-16.8）和血小板减少症（60，000/μL，正常范围158，000 - 348，000）。凝血试验显示纤维蛋白原水平（698 mg/dL，正常范围200-400）和纤维蛋白变性产物（16.7 μg/mL，正常范围0-5.0）升高。凝血酶原时间和活化部分凝血活酶时间在正常范围内。血清生化分析显示乳酸脱氢酶水平显著升高（5351 U/L，正常范围124-222）。正电子发射断层扫描（PET）结合CT显示，全身骨髓和肝脏中存在强烈的氟脱氧葡萄糖蓄积（图1a）。骨髓穿刺显示大的异常细胞大量浸润，具有高核质比、精细染色质结构和少量苍白细胞质（图1b），这些细胞部分聚集，占骨髓中所有有核细胞的90%。未观察到其他异常结果，如发育异常变化或原始细胞增加。流式细胞术（FCM）显示CD 56强阳性，但CD 45（图1c）、CD 3和CD 20（分析抗原CD 2、CD 3、CD 4、CD 5、CD 7、CD 8、CD 10、CD 11b、CD 13、CD 14、CD 19、CD 20、CD 33、CD 34、CD 35、CD 38、CD 45、CD 56、HLA-DR、IGκ和IGλ）为阴性。骨髓活检也显示大的异常细胞大量浸润（图1d）。在免疫组织化学中，它们对CD 45、CD 3、CD 20、嗜铬粒蛋白A和细胞角蛋白呈阴性，对CD 56和突触素呈阳性（图1 e-g）。Ki-67标记指数> 90%。患者被诊断为非血液恶性肿瘤伴来源不明的大量骨髓转移，血清神经元特异性烯醇化酶显著升高（9920 ng/mL）支持这一诊断。他开始接受紧急化疗，包括依托泊苷和顺铂，导致临床症状和实验室数据迅速改善。基于恶性CD 56 +/突触素+细胞聚集伴未确定的原发性病变，给出的病理诊断为神经内分泌癌。神经内分泌癌有时缺乏细胞角蛋白的表达，就像在这种情况下，特别是在转移性环境中[1]。
A 42-year-old man, who was in poor general condition with exacerbating lumbago, was admitted to the hospital as high-density areas in the bone marrow of the humerus and femur were detected on his computed tomography (CT), suggestive of a hematological malignancy. He was previously healthy and had not experienced malignant diseases. Complete blood count showed increase in white blood cell count (12,100/μL, normal range 3300–8600), with leukoerythroblastosis (neutrophils 60%, eosinophils 1%, monocytes 6%, lymphocytes 22%, myelocytes 4%, metamyelocytes 6%, blasts 1%, and 6 nucleated red blood cells per 100 white blood cells), mild anemia (hemoglobin 12.5 g/dL, normal range 13.7–16.8), and thrombocytopenia (60,000/μL, normal range 158,000–348,000). Coagulation tests revealed increases in fibrinogen level (698 mg/dL, normal range 200–400) and fibrin degenerative product (16.7 μg/mL, normal range 0–5.0). Prothrombin time and activated partial thromboplastin time were within normal ranges. Biochemical analysis of serum showed a markedly elevated lactic dehydrogenase level (5351 U/L, normal range 124–222). Positron emission tomography (PET) combined with CT showed intense fluorodeoxyglucose accumulation in the systemic bone marrow and liver (Fig. 1a). Bone marrow aspiration revealed massive infiltration of large abnormal cells with a high nucleocytoplasmic ratio, fine chromatin structure, and scant pale cytoplasm (Fig. 1b), which aggregated partially and occupied 90% of all nucleated cells in the bone marrow. No other abnormal findings, such as dysplastic changes or increase of in blast cells, were observed. Flow cytometry (FCM) revealed strong positivity for CD56 but negativity for CD45 (Fig. 1c), CD3, and CD20 (analyzed antigens CD2, CD3, CD4, CD5, CD7, CD8, CD10, CD11b, CD13, CD14, CD19, CD20, CD33, CD34, CD35, CD38, CD45, CD56, HLA-DR, Igκ, and Igλ). Bone marrow biopsy also showed massive infiltration of large abnormal cells (Fig. 1d). On immunohistochemistry, they were negative for CD45, CD3, CD20, chromogranin A, and cytokeratins, and positive for CD56 and synaptophysin (Fig. 1e–g). The Ki-67 labeling index was> 90%. The patient was diagnosed with nonhematological malignancy with massive bone marrow metastases of undetermined origin, which was supported by marked elevation of serum neuron-specific enolase (9920 ng/mL). He was started on emergent chemotherapy, including etoposide and cisplatin, which resulted in rapid improvement of clinical symptoms and laboratory data. The pathological diagnosis given was neuroendocrine carcinoma, based on the aggregation of malignant CD56+/synaptophysin+ cells with undetermined primary lesions. Neuroendocrine carcinomas sometimes lack the expression of cytokeratins, like in this case, especially in the metastatic setting [1].
常规免疫表型分析中非造血肿瘤的流式细胞术鉴定
影响因子：
3
作者：
A. Stacchini;S. Aliberti;A. Demurtas;F. Maletta;L. Molinaro;L. Godio;M. Papotti
通讯作者：
M. Papotti
影响因子：
1.2
作者：
Kawashima, Ichiro;Fukasawa, Hiroko;Kirito, Keita
通讯作者：
Kirito, Keita