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Dermatofibrosarcoma protuberans with a novel COL6A3-PDGFD fusion gene and apparent predilection for breast.

ABSTRACT: Dermatofibrosarcoma protuberans is a locally aggressive superficial mesenchymal neoplasm. It typically occurs in adulthood, and has been reported to have a slight male predilection. Tumors have a characteristic histopathologic appearance, including: storiform architecture, infiltrative "honeycomb" growth within subcutaneous adipose tissue, and immunoreactivity for CD34. Virtually all molecularly characterized cases to date have been found to harbor a COL1A1-PDGFB fusion product. Following identification of an index patient with a novel COL6A3-PDGFD fusion gene, we undertook a molecular investigation, using a combination of RNA sequencing and fluorescence in situ hybridization (FISH), to assess the prevalence of PDGFD rearrangement in dermatofibrosarcoma protuberans (N?=?63). Three additional patients were found to have balanced PDGFD rearrangements. Interestingly, all 4 tumors arose on the breast of females. As a result, we subsequently examined 16 additional cases of primary breast dermatofibrosarcoma protuberans, identifying 2 additional tumors with PDGFD rearrangement. The morphology and immunophenotype of all 6 cases was analogous to those with the canonical COL1A1-PDGFB fusion; none of the cases showed fibrosarcomatous transformation. This study illustrates that the COL6A3-PDGFD fusion product is rare in dermatofibrosarcoma protuberans, and associated with an apparent predilection for breast. An awareness of this variant is important for pathologists, as it will not be detected using conventional reverse transcription polymerase chain reaction or FISH-based diagnostic assays for dermatofibrosarcoma protuberans.

SUBMITTER: Dickson BC

PROVIDER: S-EPMC6762016 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Dermatofibrosarcoma protuberans with a novel COL6A3-PDGFD fusion gene and apparent predilection for breast.

Dickson Brendan C BC Hornick Jason L JL Fletcher Christopher D M CDM Demicco Elizabeth G EG Howarth David J DJ Swanson David D Zhang Lei L Sung Yun-Shao YS Antonescu Cristina R CR

Genes, chromosomes & cancer 20180814 9

Dermatofibrosarcoma protuberans is a locally aggressive superficial mesenchymal neoplasm. It typically occurs in adulthood, and has been reported to have a slight male predilection. Tumors have a characteristic histopathologic appearance, including: storiform architecture, infiltrative "honeycomb" growth within subcutaneous adipose tissue, and immunoreactivity for CD34. Virtually all molecularly characterized cases to date have been found to harbor a COL1A1-PDGFB fusion product. Following identi ...[more]

PMID: 30014607

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Project description:Importance:Dermatofibrosarcoma protuberans (DFSP) may have a deceptively benign clinical appearance, including a nonprotuberant presentation. Patients with DFSP often perceive misdiagnoses and delays in receiving a diagnosis. Use of existing, patient-designed Facebook patient support groups (FBSGs) to recruit large numbers of patients with rare diseases may be an effective novel research method. Objectives:To collaborate with patients with rare disease through social media and answer questions important to both patients and the medical field, including sources of diagnostic delay, risk of recurrence, and flat presentation of DFSP. Design, Setting, and Participants:A multiple-choice survey created by a team of medical practitioners and patients with DFSP was administered to 214 patients with DFSP or family members from international DFSP FBSGs and a nonprofit foundation patient database via Lime Survey from October 30 to November 20, 2015. The survey asked questions designed to determine risk of recurrence and metastasis, surgical outcomes, sources of diagnostic delay, symptoms of recurrence, number of recurrences, scar size, and number of clinicians seen before biopsy. Statistical analysis was performed from January 1, 2016, to April 1, 2019. Main Outcomes and Measures:The study goal was to collect at least 200 survey responses. Results:Of 214 survey respondents (169 females and 45 males; mean [SD] age, 40.7 [12.1] years; range, <1 to 72 years), 199 were patients with DFSP and 15 were family members. Delays occurred between the patient noticing the DFSP lesion and receiving a diagnosis of DFSP (median, 4 years; range, <1 to 42 years). Most patients (112 [52.3%]) believed that they received a misdiagnosis at some point: by dermatologists (35 of 107 [32.7%]), primary care clinicians (80 of 107 [74.8%]), or another type of physician (27 of 107 [25.2%]). The most frequent prebiopsy clinical suspicion included cyst (101 [47.2%]), lipoma (30 [14.0%]), and scar (17 [7.9%]). Many patients first noticed their DFSP as a flat plaque (87 of 194 [44.8%]). Of these lesions, 73.6% (64 of 87) became protuberant eventually. Surgical treatments included Mohs micrographic surgery (56 of 194 [28.9%]), wide local excision (122 of 194 [62.9%]), and conservative excision (16 of 194 [8.2%]). The reported rate of recurrence was 5.4% (3 of 56) for Mohs micrographic surgery, 7.4% (9 of 122) for wide local excision, and 37.5% (6 of 16) for conservative excision. The higher rate of recurrence for conservative excision was significant (P?=?.001); there was no significant difference in the rate of recurrence between Mohs micrographic surgery and wide local excision (P?=?.76). Conclusions and Relevance:This study reports what appears to be disease-relevant statistics from the largest survey of patients with DFSP to date. Because of the dissonance between the name of the neoplasm and its clinical presentation, the alternative term dermatofibrosarcoma, often protuberant is proposed. This study suggests that FBSGs are useful tools in medical research, providing rapid access to large numbers of patients with rare diseases and enabling synergistic collaborations between patients and medical researchers.

Project description:BackgroundDermatofibrosarcoma protuberans (DFSP) is a rare malignant skin tumor associated with a characteristic chromosomal translocation (t[17;22][q22;q13]) resulting in the COL1A1-platelet-derived growth factor β(PDGFB) fusion gene. This malignancy is rarely diagnosed in childhood.ObjectiveWe observed an unexpected high incidence of this DFSP in children affected with adenosine deaminase-deficient severe combined immunodeficiency (ADA-SCID) and set out to evaluate the association of these 2 clinical entities.MethodsTwelve patients with ADA-SCID were evaluated with a complete dermatologic examination and skin biopsy when indicated. Conventional cytogenetic and molecular analyses (fluorescence in situ hybridization, RT-PCR, or both) were performed when possible.ResultsEight patients were found to have DFSP. Six patients had multicentric involvement (4-15 lesions), primarily of the trunk and extremities. Most lesions presented as 2- to 15-mm, round atrophic plaques. Nodular lesions were present in 3 patients. In all cases CD34 expression was diffusely positive, and diagnosis was confirmed either by means of cytogenetic analysis, molecular testing, or both. The characteristic DFSP-associated translocation, t(17;22)(q22;q13), was identified in 6 patients; results of fluorescence in situ hybridization were positive for fusion of the COL1A1 and PDGFB loci in 7 patients; and RT-PCR showed the COL1A1-PDGFB fusion transcript in 6 patients.ConclusionsWe describe a previously unrecognized association between ADA-SCID and DFSP with unique features, such as multicentricity and occurrence in early age. We hypothesize that the t(17;22)(q22;q13) translocation that results in dermal overexpression of PDGFB and favors the development of fibrotic tumors might arise because of the known DNA repair defect in patients with ADA-SCID. Although the natural course of DFSP in the setting of ADA-SCID is unknown, this observation should prompt regular screening for DFSP in patients with ADA-SCID.

Dataset Information

Dermatofibrosarcoma protuberans with a novel COL6A3-PDGFD fusion gene and apparent predilection for breast.

Publications

Dermatofibrosarcoma protuberans with a novel COL6A3-PDGFD fusion gene and apparent predilection for breast.

Similar Datasets

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