Rakheja Dinesh, Cunningham Jacqulin C, Mitui Midori, Patel Ashish S, Tomlinson Gail E, Weinberg Arthur G
Department of Pathology, Children's Medical Center, UT Southwestern Medical Center, Dallas, TX 75390-9073, USA.
Mod Pathol. 2008 Nov;21(11):1330-6. doi: 10.1038/modpathol.2008.112. Epub 2008 Jun 27.
Cranial fasciitis, an unusual fibroproliferative lesion that occurs in the scalp of infants, is considered a posttraumatic reactive process similar to nodular fasciitis. Its pathobiology has not been investigated. Over the last 15 years, we diagnosed cranial fasciitis in six children; in one case, the lesion recurred after 4 years. This lesion and two others showed aberrant, diffuse nuclear reactivity for beta-catenin. One of the lesions with aberrant nuclear beta-catenin occurred in a child with a history of familial adenomatous polyposis (FAP) and a germline frameshift adenomatous polyposis coli (APC) mutation, c.878delG. The other APC allele in this tumor showed an acquired nonsense mutation, c.4132C --> T. Both these mutations lead to translation of a truncated APC protein. The other two cases of cranial fasciitis with aberrant nuclear beta-catenin occurred sporadically. One of these showed a point mutation, c.122C --> T, in exon 3 of CTNNB1. This mutation causes replacement of threonine with isoleucine at codon 41, leading to loss of a phosphorylation site in the beta-catenin protein. The third case with nuclear beta-catenin staining was the single one that showed recurrence. This tumor did not show mutations in exon 3 of CTNNB1 or in exons 8/9/16 of APC. The results of this small study indicate a dysregulation of the Wnt/beta-catenin pathway in a subset of cranial fasciitis, suggesting that this subset is pathobiologically related to desmoid fibromatoses rather than to nodular fasciitis. Occasional cases of cranial fasciitis may be associated with FAP and serve as an early indicator of this disease, information that would be important in the early diagnosis of FAP in patients without a family history of polyposis.
颅骨筋膜炎是一种发生于婴儿头皮的罕见纤维增生性病变，被认为是一种类似于结节性筋膜炎的创伤后反应性过程。其病理生物学尚未得到研究。在过去15年中，我们诊断出6例儿童颅骨筋膜炎；其中1例病变在4年后复发。该病变及另外两例病变显示β-连环蛋白有异常的弥漫性核反应。其中1例有异常核β-连环蛋白的病变发生在一名有家族性腺瘤性息肉病（FAP）病史且种系移码腺瘤性息肉病（APC）基因发生c.878delG突变的儿童身上。该肿瘤中的另一个APC等位基因显示出一个获得性无义突变，即c.4132C→T。这两个突变均导致截短的APC蛋白的翻译。另外两例有异常核β-连环蛋白的颅骨筋膜炎病例为散发性。其中1例在CTNNB1基因第3外显子中显示一个点突变，即c.122C→T。该突变导致第41密码子处的苏氨酸被异亮氨酸取代，致使β-连环蛋白蛋白中一个磷酸化位点缺失。第三例有核β-连环蛋白染色的病例是唯一显示复发的病例。该肿瘤在CTNNB1基因第3外显子或APC基因第8/9/16外显子中未显示突变。这项小型研究的结果表明，在一部分颅骨筋膜炎中Wnt/β-连环蛋白信号通路失调，提示这部分颅骨筋膜炎在病理生物学上与硬纤维瘤病相关，而非与结节性筋膜炎相关。偶尔的颅骨筋膜炎病例可能与FAP相关，并可作为该病的早期指标，这一信息对于无息肉病家族史患者的FAP早期诊断很重要。
