A 5-year-old black child presented with a 2-week history of swollen legs, abdominal pain, fever, fatigue, and blisters on her feet and toes. Her spleen was palpable, and she had an elevated white blood count and a low platelet count.

This case of leukemia cutis due to aggressive natural killer cell leukemia is uncommon, and perhaps even unique, according to Dr. Harper N. Price of New York University.

Leukemia cutis seldom occurs in children, and is seen in only 6%-9% of children with leukemia. There have been only a few reports of aggressive natural killer (NK) cell leukemia presenting in childhood. This may be the first case of bullous leukemia cutis and aggressive NK cell leukemia in a child, Dr. Price said.

The girl also tested negative for Epstein-Barr virus (EBV), which commonly is present in aggressive NK cell leukemia. She appears to be the first child to be reported with EBV-negative aggressive NK cell leukemia.

Her white blood count was elevated and her platelet count was low at presentation, and she was admitted to the hospital where she was assessed by hematologic and dermatologic consultants. They found dusky purple plaques on her feet and hemorrhagic bullae on her toes bilaterally. On her legs, pitting edema was noted, said Dr. Price.

Low-power histologic evaluation of punch biopsies showed a dense, small blue-cell infiltrate that was superficial and deep. Higher power revealed secondary ischemic epidermal necrosis and dermal hemorrhage. Small lymphocytes around adnexal and vascular structures extended deeply to the reticular dermal/subcutaneous interface. Even higher power showed angiocentric infiltrate of small banal nonblastic and occasionally plasmacytoid lymphocytes.

The dense perivascular and interstitial infiltrate of relatively small, monomorphic mononuclear cells had somewhat irregular nuclei with a slightly immature chromatin pattern. A battery of stains found that the cells were positive for CD56, CD16, CD8, and cytoplasmic CD3. Stains for CD7 were weakly positive, and were negative for CD4, and myeloperoxidase. There was no evidence of infectious organisms, including EBV. Tissue culture also was negative.

Flow cytometry performed on peripheral blood and bone marrow showed a predominant NK cell proliferation. Like the skin, the peripheral blood and bone marrow cells expressed CD16 and lacked surface CD3 and CD34, among other similarities.

The clinical findings plus the lab results were consistent with an aggressive NK cell neoplasm with a cutaneous presentation, said Dr. Price.

Among the three types of NK cell neoplasms in the World Health Organization classification, aggressive NK leukemia tends to present in young or middle-aged Asian adults and is strongly associated with EBV infection. Patients typically present with fever, hepatosplenomegaly, lymphadenopathy, and other constitutional symptoms, but seldom with skin manifestations of the disease.

Dr. Price found only 12 cases in the medical literature of aggressive NK cell leukemia in children and adolescents, all of them with EBV infection. She also found two reports of EBV-negative aggressive NK leukemia, both in Japanese boys, but neither had skin symptoms.

There is no standard chemotherapy regimen for treating aggressive NK cell leukemia. The prognosis is poor, with survival averaging 1-3 months, she said. Patients who are EBV negative may have a better chance for less aggressive disease and longer survival, based on limited data in adults.

Leukemia cutis in children is seen more with acute myeloid leukemia than with acute lymphocytic leukemia, she added. It usually looks like leukemia cutis in adults – with papules, nodules, and indurated or urticarial plaques – but there have been reports describing presentations resembling seborrheic dermatitis, chilblain, or Darier’s sign, Dr. Price said. There have been no cases reported of hemorrhagic bullae from leukemia cutis, as in this patient.

Chemotherapy rapidly improved the girl’s skin lesions, but the disease in her bone marrow has necessitated multiple chemotherapy regimens. She is a candidate for bone marrow transplant, if a matching donor can be found.

Copyright (c) 2009 Elsevier Global Medical News. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.

5岁黑种人女童，腿部肿胀2周；腹痛、发热、疲劳，足部及脚趾有大水疱；脾脏可扪及，白细胞计数升高，血小板计数降低。

 

美国纽约大学Harper N. Price博士指出，由侵袭性自然杀伤细胞(NK细胞)白血病引起皮肤白血病的病例十分罕见，甚至可能没有先例。

 

皮肤白血病极少发生于儿童，仅占儿童白血病的6%~9%。目前，关于儿童侵袭性NK细胞白血病仅有为数不多的报道。该病例可能是首例儿童大疱性皮肤白血病合并侵袭性NK细胞白血病，Price博士说。

 

侵袭性NK细胞白血病患者的Epstein-Barr病毒(EB病毒)检测结果通常呈阴性，该女童同样如此。她可能是EB病毒阴性侵袭性NK细胞白血病在儿童的首例报道。

 

患儿的白细胞计数明显升高，且血小板计数降低，血液科和皮肤科医生在她入院后检查发现，患儿双脚出现暗紫色斑块，脚趾有出血性水泡。Price博士称她的双腿出现凹陷性水肿。

 

钻取活检的皮肤组织在低倍镜下显示小蓝细胞在皮肤浅表及深部呈密集浸润。高倍镜下显示有继发缺血性表皮坏死以及真皮出血。皮肤附件周围分布有小淋巴细胞，血管样结构延展深达网状真皮与皮下组织交界处。更高倍数的显微镜显示寻常的小个非母细胞性淋巴细胞以血管为中心浸润，偶尔有类浆细胞样淋巴细胞。

 

体积较小且形态单一的单核细胞在血管周围和血管间隙呈密集浸润，其细胞核轮廓稍不规则，染色质分布呈略未成熟型。染色发现胞膜CD56、CD16、CD8及胞浆CD3呈阳性，CD7呈弱阳性，而CD4和髓过氧化物酶呈阴性。未发现传染性生物包括EB病毒的证据。组织培养亦为阴性。

 

外周血和骨髓细胞的流式检测示NK细胞增殖显著。除其他相似点之外，外周血和骨髓细胞同皮肤一样，细胞表面表达CD16，而CD3、CD34表达缺如。

 

临床发现加上检验结果均符合侵袭性NK细胞白血病的皮肤表现，Price博士说。

 

世界卫生组织(WHO)将NK细胞淋巴瘤分为3类，其中侵袭性NK细胞白血病多发生于亚洲中青年人，与EB病毒感染显著相关。患者通常会出现发热、肝脾和淋巴结肿大以及其他全身症状，但很少有皮肤表现。

 

Price博士发现，文献仅报道过12例儿童和青少年侵袭性NK细胞白血病，他们均有EB病毒感染。她还发现了2例EB病毒阴性的侵袭性NK细胞白血病，均为日本男孩，但都没有皮肤症状。

 

侵袭性NK细胞白血病尚无标准化疗方案，预后差，平均生存期为1~3个月，她说。根据有限的成年人数据，EB病毒阴性患者的疾病侵袭性较弱，生存时间较长。

 

“儿童皮肤白血病合并急性髓细胞性白血病较合并急性淋巴细胞白血病多见，” Price博士补充说，“儿童皮肤白血病通常与成人皮肤白血病类似，出现丘疹、结节、硬结斑块或荨麻疹斑块的皮肤表现，但也有报告出现类似于脂溢性皮炎、冻疮或Darier征的皮肤表现。”尚无像该病例一样缘于皮肤白血病的出血性水泡的报告。

 

该女童的皮肤损伤在化疗后迅速好转，但治疗骨髓病变则需采用多种化疗方案。如果能找到配型相符的供体，她可选择进行骨髓移植。

 

 

 

高倍镜下示血管周围和血管内有寻常的非母细胞性淋巴细胞浸润(照片蒙Henry Votava博士惠允使用)。

 

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