Departments of Pathology.
Sorbonne Université.
Am J Surg Pathol. 2020 Oct;44(10):1389-1397. doi: 10.1097/PAS.0000000000001528.
Hirschsprung disease (HD) is a congenital disorder of the enteric nervous system that occurs in ∼1 in 5000 live births. It is characterized by the absence of ganglionic cells (GCs) in the distal intestine. The diagnosis relies on the thorough analysis of a rectal suction biopsy (RSB), which must show a complete absence of GCs after careful examination of at least 100 serial sections. Such a negative characteristic explains the difficulty of this diagnosis. Moreover, GCs may be immature in very young or preterm born children, making them hard to recognize. Therefore, ancillary techniques have been developed as diagnostic help, such as acetylcholinesterase histochemistry and calretinin immunostaining. These techniques reveal only indirect clues, focusing mainly on the changes in nerve fibers, but not on GCs themselves. As PHOX2B has been shown to be a very specific transcription factor in GCs and in progenitor enteric nerve cells, we have assessed (i) PHOX2B immunostaining in immature enteric ganglia and (ii) the use of PHOX2B immunostaining for the recognition of GCs on RSBs for suspicion of HD. We have observed PHOX2B expression in all GCs, both mature and immature, and its complete absence in Hirschsprung cases. We suggest that the use of PHOX2B immunostaining is of great help (i) in the recognition of GCs on RSBs regardless of their differentiation and therefore (ii) in the diagnosis of HD.
先天性巨结肠（HD）是一种发生在大约每 5000 例活产儿中的肠神经系统先天性疾病。其特征是远端肠段缺乏神经节细胞（GCs）。该疾病的诊断依赖于直肠抽吸活检（RSB）的全面分析，必须在至少 100 个连续切片仔细检查后显示完全缺乏 GCs。这种阴性特征解释了该诊断的难度。此外，GCs 在非常年幼或早产的儿童中可能不成熟，难以识别。因此，已经开发了辅助技术作为诊断帮助，例如乙酰胆碱酯酶组织化学和钙视网膜蛋白免疫染色。这些技术仅揭示了间接线索，主要集中在神经纤维的变化上，而不是 GC 本身。由于 PHOX2B 已被证明是 GCs 和祖肠神经细胞中非常特异性的转录因子，我们评估了 (i) 在不成熟肠神经节中的 PHOX2B 免疫染色，以及 (ii) 在怀疑患有 HD 的 RSB 上使用 PHOX2B 免疫染色识别 GCs。我们观察到 PHOX2B 在所有成熟和不成熟的 GCs 中均有表达，而在 Hirschsprung 病例中则完全缺失。我们建议 PHOX2B 免疫染色的使用非常有帮助：(i) 无论其分化如何，均可在 RSB 上识别 GCs，因此 (ii) 可用于诊断 HD。
