Desmoid Tumors

BackgroundAggressive fibromatosis (AF) is a locally infiltrating soft-tissue tumor. In a population-based study in the Netherlands, we evaluated time trends for the incidence and treatment of AF.MethodsIn PALGA: Dutch Pathology Registry, all patients diagnosed between 1993 and 2013 as having extra-abdominal or abdominal wall aggressive fibromatosis were identified and available pathology data of the patients were evaluated. Epidemiological and treatment-related factors were analyzed with χ (2)and regression analysis.ResultsDuring the study period, 1134 patients were identified. The incidence increased from 2.10 to 5.36 per million people per year. Median age at the time of diagnosis increased annually by B 0.285 (P = 0.001). Female gender prevailed and increased over time [annual odds ratio (OR) 1.022; P = 0.058]. All anatomic localizations, but in particular truncal tumors, became more frequent. During the study period diagnostic histological biopsies were performed more often (annual OR 1.096; P ConclusionsIn this population-based study, an increasing incidence of extra-abdominal and abdominal-wall aggressive fibromatosis was observed. The workup of patients improved and a trend towards a nonsurgical treatment policy was observed.

BackgroundNeoplasia can be driven by mutations resulting in dysregulation of transcription. In the mesenchymal neoplasm, aggressive fibromatosis, subtractive hybridization identified sterile alpha motif domain 9 (SAMD9) as a substantially down regulated gene in neoplasia. SAMD9 was recently found to be mutated in normophosphatemic familial tumoral calcinosis. In this study, we studied the gene structure and function of SAMD9, and its paralogous gene, SAMD9L, and examined these in a variety of species.ResultsSAMD9 is located on human chromosome 7q21.2 with a paralogous gene sterile alpha motif domain 9 like (SAMD9L) in the head-to-tail orientation. Although both genes are present in a variety of species, the orthologue for SAMD9 is lost in the mouse lineage due to a unique genomic rearrangement. Both SAMD9 and SAMD9L are ubiquitously expressed in human tissues. SAMD9 is expressed at a lower level in a variety of neoplasms associated with beta-catenin stabilization, such as aggressive fibromatosis, breast, and colon cancers. SAMD9 and SAMD9L contain an amino-terminal SAM domain, but the remainder of the predicted protein structure does not exhibit substantial homology to other known protein motifs. The putative protein product of SAMD9 localizes to the cytoplasm. In vitro data shows that SAMD9 negatively regulates cell proliferation. Over expression of SAMD9 in the colon cancer cell line, SW480, reduces the volume of tumors formed when transplanted into immune-deficient mice.ConclusionSAMD9 and SAMD9L are a novel family of genes, which play a role regulating cell proliferation and suppressing the neoplastic phenotype. This is the first report as far as we know about a human gene that exists in rat, but is lost in mouse, due to a mouse specific rearrangement, resulting in the loss of the SAMD9 gene.

Desmoids are poorly-understood, locally aggressive, non-metastasizing fibromatoses that occur with disproportionate frequency in patients with familial adenomatous polyposis (FAP). Their nature is controversial with arguments for and against a neoplastic origin. Neoplastic proliferations are by definition monoclonal, whereas reactive processes originate from a polyclonal background. We examined clonality of 25 samples of desmoid tissue from 11 female FAP patients by assessing patterns of X-chromosome inactivation to calculate a clonality ratio. Polymerase chain reaction (PCR) amplification of a polymorphic CAG short tandem repeat (STR) sequence adjacent to a methylation-sensitive restriction enzyme site within the human androgen receptor (HUMARA) gene using fluorescent-labelled primers enabled analysis of PCR products by Applied Biosystems Genescan II software. Twenty-one samples from nine patients were informative for the assay. Samples from all informative cases comprised a median of 66% (range 0-75%) clonal cells but from the six patients with a clonality ratio < or =0.5 comprised a median of 71% (65-75%) clonal cells. FAP-associated desmoid tumours are true neoplasms. This may have implications in the development of improved treatment protocols for patients with these aggressive tumours.

ObjectivePercutaneous cryoablation (PC) has been incorporated among first-line treatment options for desmoid-type fibromatosis (DF). Loco-regional therapies, including PC, induce tissue changes that may precede measurable tumor shrinkage, thereby limiting the reliability of purely dimensional response criteria. To address this limitation, we compared response evaluation criteria in solid tumors (RECIST) 1.1 and magnetic resonance imaging (MRI)-adapted (M-)RECIST in patients with DF treated with PC.Materials and methodsWe retrospectively identified all consecutive patients with progressing extra-abdominal DF treated with PC. Responses were assessed with RECIST 1.1 and M-RECIST, the latter relying on T2- and diffusion-weighted imaging, as well as unenhanced and contrast-enhanced T1-weighted imaging, to define residual viable tumor. Non-progression (NPR) and overall response rates (ORR) were defined as the percentage of patients without radiological progression and partial/complete responses, respectively.ResultsThirty-four patients (females/males, 26/8) and 37 procedures were identified. RECIST 1.1 and M-RECIST were applicable in 35 and 34 procedures, respectively. At a median follow-up of 15.7 months (interquartile range [IQR] 19.5), RECIST 1.1. Responses were: 10/35 (28.6%) partial response (PR), 22/35 (62.9%) stable disease (SD), and 3/35 (8.6%) progressive disease (PD), with ORR 28.6% and NPR 91.4%. At a median follow-up of 16.0 months (IQR 20.5), M-RECIST responses were: 15/34 (44.1%) complete response (CR), 12/34 (35.3%) PR, 4/34 (11.8%) SD, and 3/34 (8.8%) PD, with ORR 79.4% and NPR 91.2%. Overall concordance was negligible.ConclusionM-RECIST yielded higher NPR/ORR than RECIST 1.1. These findings pave the way for studies addressing whether this shift in response categorization associates with improved outcomes prediction.Relevance statementThis work provides supporting evidence for the implementation of residual viable disease assessment in evaluating DF responses to PC.Key pointsIn patients with DF, responses to cryoablation can be characterized using purely dimensional and viability-based criteria. RECIST 1.1 and M-RECIST yielded complete agreement for PD. M-RECIST may refine response categorization below the progression threshold.