Hata Jessica L, Correa Hernan, Krishnan Chandra, Esbenshade Adam J, Black Jennifer O, Chung Dai H, Mobley Bret C
From the Departments of Pathology, Microbiology and Immunology (Drs Hata, Correa, Black, and Mobley), Pediatrics (Dr Esbenshade), and Pediatric Surgery (Dr Chung), Vanderbilt University Medical Center, Nashville, Tennessee; and the Department of Pathology, Dell Children's Medical Center, Austin, Texas (Dr Krishnan).
Arch Pathol Lab Med. 2015 Apr;139(4):543-6. doi: 10.5858/arpa.2014-0255-OA.
Neuroblastoma (NB) is the most common extracranial tumor of childhood. Although most cases have a distinctive histology, a subset of primitive cases require immunohistochemical studies to distinguish them from other small round blue cell tumors of childhood. Immunohistochemistry is also used to detect small amounts of tumor metastatic to the bone marrow and in posttreatment samples with obscuring fibrosis, calcification, or inflammation. The transcription factor PHOX2B is essential for the differentiation and survival of sympathetic neurons and chromaffin cells, and therefore is highly specific for the peripheral autonomic nervous system.
To determine the diagnostic utility of PHOX2B immunohistochemistry as a marker of primary, treated, and metastatic NB.
Neuroblastoma tissue microarrays were stained with PHOX2B, CD57, and synaptophysin. Arrays containing rhabdomyosarcoma, Ewing sarcoma, and Wilms tumor were stained with PHOX2B, and negative bone marrow samples were stained with PHOX2B and CD57.
PHOX2B and CD57 were similar to synaptophysin in their ability to detect NB. PHOX2B and CD57 similarly showed robust staining in posttreatment NB and NB metastatic to the bone marrow. In contrast to the cytoplasmic staining pattern seen with synaptophysin and CD57, clear and strong nuclear PHOX2B permitted identification of individual tumor cells. PHOX2B staining was absent in all cases of rhabdomyosarcoma, Ewing sarcoma, and Wilms tumor, and in the negative bone marrow.
PHOX2B and CD57 are useful markers of NB. PHOX2B is specific for NB in its differential diagnosis with other small round cell tumors, and its nuclear staining may be helpful for accurate bone marrow tumor quantification.
神经母细胞瘤（NB）是儿童最常见的颅外肿瘤。尽管大多数病例具有独特的组织学特征，但一部分原始病例需要进行免疫组织化学研究，以将其与儿童期其他小圆形蓝细胞肿瘤区分开来。免疫组织化学还用于检测少量转移至骨髓的肿瘤以及治疗后样本中存在的纤维化、钙化或炎症导致结构模糊的肿瘤。转录因子PHOX2B对交感神经元和嗜铬细胞的分化及存活至关重要，因此对周围自主神经系统具有高度特异性。
确定PHOX2B免疫组织化学作为原发性、治疗后及转移性NB标志物的诊断效用。
用PHOX2B、CD57和突触素对神经母细胞瘤组织微阵列进行染色。用PHOX2B对包含横纹肌肉瘤、尤因肉瘤和肾母细胞瘤的阵列进行染色，并对阴性骨髓样本用PHOX2B和CD57进行染色。
PHOX2B和CD57在检测NB方面的能力与突触素相似。PHOX2B和CD57在治疗后的NB及转移至骨髓的NB中同样显示出强烈染色。与突触素和CD57的细胞质染色模式不同，清晰且强烈的核PHOX2B染色有助于识别单个肿瘤细胞。横纹肌肉瘤、尤因肉瘤和肾母细胞瘤的所有病例以及阴性骨髓样本中均未出现PHOX2B染色。
PHOX2B和CD57是NB的有用标志物。PHOX2B在与其他小圆形细胞肿瘤的鉴别诊断中对NB具有特异性，其核染色可能有助于准确量化骨髓肿瘤。
