Kaplan F S, Tabas J A, Gannon F H, Finkel G, Hahn G V, Zasloff M A
Department of Orthopaedic Surgery, University of Pennsylvania School of Medicine, Philadelphia.
J Bone Joint Surg Am. 1993 Feb;75(2):220-30. doi: 10.2106/00004623-199302000-00009.
In order to better characterize the biological features of fibrodysplasia ossificans progressiva, we reviewed the histopathological specimens from eleven patients (twelve biopsies) who had a confirmed diagnosis of the disease. All of the biopsies had been performed in children, to exclude the diagnosis of a malignant lesion. In no instance was the diagnosis of fibrodysplasia ossificans progressiva considered before the biopsy. The results of a lesional biopsy in all eleven patients revealed normal endochondral osteogenesis at heterotopic sites. The results of biopsy of an early lesion in six children were misinterpreted as revealing a diagnosis of fibromatosis or sarcoma before the roentgenographic appearance of ossification. Immunohistochemical studies of sections of the earliest lesion demonstrated S-100 antigen positivity before the histological appearance of differentiated osteochondral tissue. The presence of congenital malformation of the great toes and of postnatal heterotopic endochondral osteogenesis strongly suggests that fibrodysplasia ossificans progressiva is a disorder of defective induction of endochondral osteogenesis. This study established the predominant histopathological findings associated with fibrodysplasia ossificans progressiva and can serve as a basis for postulation of a candidate gene in the pathogenesis of the disorder. A lesional biopsy is not needed to make the diagnosis; biopsy uniformly exacerbates the condition and should be avoided.
为了更好地描述进行性骨化性纤维发育不良的生物学特征，我们回顾了11例确诊为该病患者（12次活检）的组织病理学标本。所有活检均在儿童期进行，以排除恶性病变的诊断。在活检前均未考虑进行性骨化性纤维发育不良的诊断。11例患者的病变活检结果显示异位部位软骨内成骨正常。6例儿童早期病变的活检结果在X线出现骨化之前被误诊为纤维瘤病或肉瘤。最早病变切片的免疫组织化学研究显示，在分化的骨软骨组织出现组织学表现之前，S-100抗原呈阳性。大脚趾先天性畸形和出生后异位软骨内成骨的存在强烈提示，进行性骨化性纤维发育不良是一种软骨内成骨诱导缺陷的疾病。本研究确立了与进行性骨化性纤维发育不良相关的主要组织病理学发现，并可为该疾病发病机制中候选基因的推测提供依据。诊断不需要进行病变活检；活检会使病情普遍加重，应避免进行。
