Multiple and recurrent inflammatory fibroid polyps in three generations of a Devon family: a new syndrome.

Abstract

SUMMARY The recurrence of multiple inflammatory fibroid polyps is reported in three generations of a Devon family. Only one female in each has been affected in a direct line of descent. The grandmother has had nine polyps resected over 11 years, the mother seven over 18 years, and the daughter six over six years. None of the patients or their relatives are known to have any allergies, dietary fads, or gastrointestinal infections. Chromosome studies have been normal in two patients. No cancer risk has been identified. Conventional histology, electron microscopy, and immunohistology suggest that the lesion is a self-limiting proliferation of histiocytes; the initiating event or stimulus remains unknown. A genetic factor is likely to operate in this unique family which is probably polygenic and multifactorial in nature.

PDGFRA-mutant syndrome

“…Interestingly, three families displaying multiple inflammatory fibroid polyps have been described without mutational data, [11][12][13][14] and 'neurofibromata' or even neurofibromatosis had previously been pathologically diagnosed in gastrointestinal tumors from patients later recognized as members of kindreds with familial multiple inflammatory fibroid polyps 11 or found to bear a germline PDGFRA mutation. 9 These events support the overlap between these conditions and the disease formerly called INF/NF3b.…”

“…1-3 Possible differences in phenotype probably depend on the specific PDGFRA mutation involved. Hereditary inflammatory fibroid polyp syndromes [11][12][13][14] and cases featuring both gastric GISTs and gastrointestinal lipomas 39,40 also possibly belong to this group; an assessment of their PDGFRA status could be confirmatory. The unprecedented awareness that inflammatory fibroid polyp, a relatively frequent lesion among gastrointestinal mesenchymal tumors, 41 and gastrointestinal lipomas are part of the spectrum of 'INF/NF3b', at least the former often accounting for the majority of tumors found in affected individuals, could increase the detection rate of 'INF/NF3b', possibly ultimately showing that this syndrome is not as rare as was formerly believed.…”

“…The former usually consist of bowel obstruction/ intussusception. 2,3,9,[11][12][13][14][15] Oncologic risk appears to be mainly restricted to gastric tumors, as the stomach proved to be selective for PDGFRA mutations to progress to GIST, and GIST appears to be the only tumor potentially malignant in PDGFRA-mutant syndrome. This indicates that although histological assessment of tumors (i.e., using endoscopic ultrasound-fine-needle tissue acquisition 25 ) is always recommended, it is particularly warranted in gastric tumors.…”

“…[5][6][7][8] More recently, CD34 + fibrous tumors of uncertain classification (henceforth simply referred to as 'fibrous tumors') have been reported in a germline PDGFRA-mutated context, constituting another possible PDGFRAmutant tumor. 9 Although GISTs and inflammatory fibroid polyps can sometimes be multiple and/or syndromic, [9][10][11][12][13][14] germline PDGFRA mutations have rarely been described, with only two familial examples. 3,9,10,15 We had the opportunity of studying a kindred presenting heterogeneous gastrointestinal mesenchymal tumors bearing an unreported inherited PDGFRA mutation.…”

Gastrointestinal tract spindle cell lesions—just like real estate, it's all about location

“…Inflammatory fibroid polyps have been reported in a family in which three generations of women have had these 'Devon polyposis' lesions. 41,42 These polyps were believed to be reactive in the past, but they are now known to have mutations in the platelet-derived growth factor receptor alpha (PDGFRA) gene, 43 a feature that they share with a subset of GISTs. However, in constrast to GISTs, inflammatory fibroid polyps are always benign.…”