Circulating Tumor DNA in Patients with Desmoid Fibromatosis during Active Surveillance.

BACKGROUND: Sporadic desmoid fibromatosis (DF) is a rare locally aggressive tumor characterized by mutation in exon 3 of CTNNB1 (T41A, S45F, and S45P). Standard of care is active surveillance (AS), but 30% require treatment. DF clinical course is unpredictable and identification of prognostic markers is needed to tailor strategy. In this prospective study, we investigated the consistency between mutation detected in tumor biopsies with that detected in plasma by digital droplet PCR (ddPCR) and the association between circulating tumor DNA (ctDNA) abundancy with clinical outcome. PATIENTS AND METHODS: A total of 56 patients and 10 healthy donors were included. CTNNB1 mutation status of DF biopsies was determined by Sanger and in case of WT CTNNB1 with NGS. In matched plasma samples at enrollment and during AS at specific timepoints, we evaluated cfDNA quantity and ctDNA. RESULTS: ctDNA levels were measured in 46 patients with CTNNB1 mutation. Detection rate for T41A, S45F and S45P was 68%, 42% and 100%, respectively. S45P variant has been detected in all patients with S45P mutation. Longitudinal assessment of ctDNA during AS in nine patients (four with regression and five with progression as first event according to RECIST) showed a concordance between the event and ctDNA level change in six out of nine patients tested (4/5 with progression and 2/4 with regression). CONCLUSIONS: Results of ctDNA analysis support its potential clinical implementation as diagnostic tool in specific clinical scenarios where biopsy can be challenging. A prospective clinical trial needs to be performed to evaluate the potential role of ctDNA as predictive biomarker.

Pediatric Fibromatosis Lacks the Internal Tandem Duplication of EGFR Seen in Congenital Mesoblastic Nephroma.

Classical and mixed congenital mesoblastic nephroma (CMN) are characterized by an internal tandem duplication (ITD) of the EGFR gene, in contrast to cellular CMN that usually harbors an ETV6::NTRK3 gene fusion. This same fusion occurs in infantile fibrosarcoma, and this tumor can be considered as the soft tissue equivalent of cellular CMN. A soft tissue equivalent of classic/mixed CMN remains undefined at the genetic level. Since classical CMN resembles fibromatosis of soft tissue histologically, we asked whether fibromatosis in children might show EGFR ITD. ITD was investigated using the polymerase chain reaction and primers for exons 18 and 25 of the EGFR gene. Seven of the eight cases of classical or mixed CMN were positive by this approach, but none of the five cellular CMNs. Of 11 cases of fibromatosis (six plantar, two digital, and three desmoid), none were positive for EGFR ITD. Within the limits of this small study, we conclude that pediatric fibromatosis is likely not characterized by EGFR ITD. There are isolated reports of pediatric soft tissue tumors that harbor EGFR ITD, but these have the appearance of infantile fibrosarcoma or mixed CMN rather than fibromatosis. We did not find any such cases, since all 14 cases of infantile fibrosarcoma in our study had an ETV6::NTRK3 fusion. The soft tissue tumors with EGFR ITD are not a morphologic match for the low-grade histology of classical CMN. Whether they have a similar favorable biology or behave more like fibrosarcoma with an ETV6::NTRK3 fusion or an alternative fusion involving other kinases remains to be determined.

Mesenchymal Tumor Management: Integrating Surgical and Non-Surgical Strategies in Different Clinical Scenarios.

Mesenchymal tumors originate from mesenchymal cells and can be either benign or malignant, such as bone, soft tissue, and visceral sarcomas. Surgery is a cornerstone treatment in the management of mesenchymal tumors, often requiring complex procedures performed in high-volume referral centers. However, the COVID-19 pandemic has highlighted this need for alternative non-surgical approaches due to limited access to surgical resources. This review explores the role of non-surgical treatments in different clinical scenarios: for improving surgical outcomes, as a bridge to surgery, as better alternatives to surgery, and for non-curative treatment when surgery is not feasible. We discuss the effectiveness of active surveillance, cryoablation, high-intensity focused ultrasound, and other ablative techniques in managing these tumors. Additionally, we examine the use of tyrosine kinase inhibitors in gastrointestinal stromal tumors and hypofractionated radiotherapy in soft tissue sarcomas. The Sarculator tool is highlighted for its role in stratifying high-risk sarcoma patients and personalizing treatment plans. While surgery remains the mainstay of treatment, integrating advanced non-surgical strategies can enhance therapeutic possibilities and patient care, especially in specific clinical settings with limitations. A multidisciplinary approach in referral centers is vital to determine the optimal treatment course for each patient.

Prognostic factors for wellbeing in patients with hyaline fibromatosis syndrome.

BACKGROUND: Hyaline fibromatosis syndrome (HFS) is a congenital disorder characterized by subcutaneous skin nodules, congenital multiple arthrogryposis, gingival hyperplasia, and chronic pain. The intellectual ability of patients with HFS is generally normal. This syndrome arises from variants of ANTXR2. Thus far, about 100 cases have been reported but few of these were reported from Japan. METHODS: This study reports five additional Japanese patients with genetically confirmed HFS, from unrelatd families, and discusses the clinical course and quality of life of these patients. RESULTS: At our last visit the ages of the patients were 3-19 years (the median age was 5 years). All the patients had arthrogryposis, skin nodules, and gingival hyperplasia, and four patients had chronic pain, all of which are distinctive, clinical characteristics of HFS. Four of the patients (80%) had pruritic skin nodules, and three experienced sleep disruptions due to pruritis. The visceral complications are an index of HFS severity. One patient in the present cohort had a mucosal abnormality without any gastrointestinal symptoms. CONCLUSION: Preventive and routine management of pruritis caused by skin nodules should be shared with the patient's family. Even asymptomatic patients might have endoscopic finding, which would be a soft marker that could predict the development of protein losing enteropathy.

Ledderhose's Disease.

Ledderhose disease, also known as plantar fibromatosis, is a rare fibroproliferative disorder characterized by the development of fibrous nodules within the plantar fascia of the foot. These nodules cause discomfort, pain, and impaired mobility, particularly during activities like walking, and are often associated with other fibromatoses, such as Dupuytren's disease. In this case, a 60-year-old woman presented with significant plantar pain exacerbated by walking, along with swelling in the arch of her foot. The diagnosis involved a clinical examination that revealed nodules and tenderness in the plantar fascia, and ultrasound imaging confirmed the presence of fibrotic tissue. Due to the patient's preference for non-surgical management, a conservative approach was adopted. This included the use of medications, orthotic devices, and physical therapy. This case underscores the effectiveness of non-surgical interventions in managing Ledderhose disease, highlighting the importance of personalized treatment plans tailored to patient preferences.

Radial Nerve Palsy Caused by Desmoid-Type Fibromatosis: A Case Report and Review of the Literature.

Radial nerve palsy (RNP) is classified as traumatic, non-traumatic, or iatrogenic. The most frequent etiologic agent is the fracture of the humerus of the shaftand distal. We experienced a case of RNP caused by desmoid-type fibromatosis around the radial nerve. The RNP caused by desmoid-type fibromatosis has not been reported in the literature. We present this case here with a review of the RNP literature. The patient is a 16-year-old female, right-hand dominant, who became aware of the difficulty in extending her right little finger without any triggers five months ago. She was also aware of the difficulty in extending the ring finger, and her symptoms gradually worsened. She was referred to our hospital after consulting a home doctor. MRI of the elbow showed a high-intensity occupying lesion on T2-weighted images (T2WI) slightly proximal to the elbow joint. Ultrasonography (US) showed a partial nerve constriction and radial nerve enlargement on the distal side of the constriction. The approach was made from the posterior lateral side of the distal upper arm, and the radial nerve was exposed. There was a 1 cm white tissue strongly adherent on the radial nerve, which was compressing the radial nerve, and it was resected piece by piece. After the resection, the radial nerve was indented. The pathological diagnosis of the resected tissue was fibromatosis. Gradually, she was able to extend her fingers after the surgery and recovered completely in six months.

Initial treatment for surgery-naïve desmoid tumors by high intensity focused ultrasound.

Introduction: Desmoid tumor (DT) is a rare proliferative disease occurring in connective tissues, characterized by high infiltration and recurrence rates. While surgery remains the primary treatment, its recurrence risk is high, and some extra-abdominal desmoid tumors are inoperable due to their locations. Despite attempts with radiotherapy and systemic therapy, the efficacy remains limited. Methods: We used low-power cumulative high-intensity focused ultrasound (HIFU) therapy as an initial treatment for desmoid tumor patients either ineligible or unwilling for surgery. Low-power cumulative HIFU employs slower heat accumulation and diffusion, minimizing damage to surrounding tissues while enhancing efficacy. Results: Fifty-seven non-FAP desmoid tumor patients, previously untreated surgically, underwent low-power cumulative HIFU therapy. Among them, 35 had abdominal wall DT, 20 had extra-abdominal DT, and 2 had intra- abdominal DT, with an 85% median ablation ratio. Abdominal wall DT patients showed significantly better response rates (91.4% vs. 86%) and disease control rates (100% vs. 32%) than that of non-abdominal wall DT patients. Median event- free survival time was not reached after a median follow-up duration of 34 months. Discussion: With its high response rate, durable efficacy, and mild adverse effects, our findings suggest that low-power cumulative HIFU presents a promising novel treatment for desmoid tumors, particularly abdominal wall DT patients.

Palmar Fibromatosis, Updated Review With Relationship to the A1 Pulley, Trigger Finger, and Presence of the Sonographic Comb Sign.

OBJECTIVES: Updated retrospective review of the sonographic appearance of palmar fibromatosis (PF) with evaluation of the utility of the Comb Sign previously described in plantar fibromas. Additional evaluation was conducted on the location relative to the flexor tendon, anatomic proximity of palmar fibromas to the A1 pulley and evaluate any potential association with trigger finger. METHODS: Medical record and imaging review was performed from 2017 to 2023, for patients with a new onset ultrasound or clinical diagnosis of PF. Clinical associations and imaging morphology were reviewed including presence of the Comb Sign, fibroma association with the A1 pulley, and fibroma association with trigger finger. RESULTS: Exactly 87 total fibromas in 53 patients were evaluated. The Comb Sign was present in 39% of fibromas, usually seen in transverse plane, more prevalent in multifocal disease and larger fibromas. Most (72%) palmar fibromas were within 1 cm of, contacted, or covered the A1 pulley (P < .001). Lateral extension beyond the flexor tendon axis can be seen (44%). Trigger finger and tenosynovitis were rare. However, volume and SI dimension of fibromas were associated with tenosynovitis (P < .0001) and all nine patients with concomitant trigger finger had fibromas within 1 cm from the A1 pulley. CONCLUSIONS: The Comb Sign can aid in sonographic diagnosis of PF. Lateral extension of fibromas can occur. Most palmar fibromas have a significant intimate association with the A1 pulley, and presence of trigger finger with adjacent palmar fibroma can exist and is important for hand surgeons to know preoperatively.

Giant Submucosal Fibromatosis of the Base of Tongue Presenting as Paediatric Obstuctive Sleep Apnoea: A Rare Case Report.

A nodular lesion of the tongue encompasses a range of conditions, from reactive to malignant. It can be challenging to diagnose when a solitary and firm submucosal mass appears in the oral cavity. Following an essential investigation protocol is necessary for reaching a definitive diagnosis. Leiomyomas are benign tumors that infrequently occur in the oral cavity and typically affect individuals between their forties and fifties. This case report presents a rare and unique case of a giant submucosal fibromatosis located at the base of the tongue in a 3-year-old child presenting with features of pediatric OSA. Immunohistochemical analysis revealed the positivity of tumor cells for beta-catenin and CD 34 aberrant expression, though SMA and STAT 6 were negative. The lesion was removed submucosally in toto and post-surgery the patient showed no symptoms and had no evidence of tumors during the one-year follow-up visit.

The variable histogenesis and biology of selected bland fibroblastic lesions of the breast - pitfalls in the differential diagnostics and optimal therapeutic approach (three case reports).

Presented are three casuistics of seemingly identical breast lesions which even by adopting advanced laboratory techniques may represent diagnostic challenge. Microscopic features of some bland spindle cell lesions of different histogenesis (epithelial or mesenchymal) are misleading and a potential source of unaware errors, which might affect optimal therapeutic strategy. In the setting of three diverse entities (low-grade spindle cell metaplastic carcinoma, desmoid fibromatosis and phyllodes tumor) is documented both demanding diagnostic algorithm and revealing molecular landscape on one side as well as evolving predictive/prognostic parameters on the other one. Close interdisciplinary cooperation is inevitable for accurate interpretation/understanding of revealed diagnostic facts which is required for adjustment of competent rational and individualized therapy.

A rare non-malignant cauliflower vulvar mass in a post-menopausal woman: Case report and insight into vulval fibromatosis.

INTRODUCTION AND IMPORTANCE: Vulvar fibromas are benign tumours that primarily occur in women of reproductive age but very rarely among postmenopausal women. Evidence of its occurrence in Sub-Saharan Africa is scant, with hardly any data among postmenopausal women. CASE PRESENTATION: A 54-year-old multiparous (para 4) Ghanaian female presented at the Gynaecology Outpatient Department of Korle Bu Teaching Hospital, with a three-year history of a painless vulval mass. Her general condition was satisfactory. Vulvar examination revealed a prominent, 20 cm × 15 cm cauliflower-like mass originating from the right labium majus, attached by a 5 cm long and 1 cm thick stalk. There was no inguinal lymphadenopathy. Mass was excised under regional anesthesia and histology confirmed benign vulva fibromatosis. The patient made a satisfactory post-operative recovery. CLINICAL DISCUSSION: This case was managed successfully surgically, and histology confirmed a benign tumour. These benign vulval tumours typically occur in younger premenopausal women, but very rarely after menopause as was in the case of our patient who was 7 years postmenopausal. This further emphasizes the exceptional nature of this pathology. CONCLUSION: Our report adds valuable insight to the limited literature on vulvar fibromatosis, particularly in postmenopausal patients, emphasizing the need for careful diagnostic and management strategies for best patient outcomes.

Transarterial doxorubicin-eluting beads embolization for the treatment of desmoid fibromatosis in the pubic region.

Desmoid fibromatosis (DFs) is rare, low-grade neoplasm. Although it poses no risk of metastasis, DFs exhibits a range of clinical manifestations characterized by local infiltrative growth tendencies and a propensity for recurrence. Despite its nonmalignant nature, DFs can be highly debilitating and occasionally life-threatening, causing severe pain and functional limitations. Traditionally, surgery served as the conventional primary treatment approach; nevertheless, a recent shift in paradigm towards a more conservative management has emerged, accompanied by efforts to standardize the strategy among clinicians. Systemic doxorubicin has been demonstrated to be effective in treating DFs; however, it carries potential risks of adverse effects on the cardiovascular, digestive, and hematologic systems. The novel intravascular intervention employing drug-eluting beads loaded with doxorubicin represents an effective treatment for DFs, optimizing drug delivery to the target lesion and reducing systemic toxicity. In this article, we present a rare case of DFs in the right pubic region treated with transarterial doxorubicin-eluting beads embolization.

Aggressive fibromatosis of the sigmoid colon: A case report.

BACKGROUND: Aggressive fibromatosis (AF), also known as desmoid tumor or desmoid-type fibromatosis, is a rare soft tissue neoplasm that can occur in almost any part of the body. Although it is a benign disease, AF is aggressive and infiltrative and has a high recurrence rate after surgery. Common sites for intra-abdominal AF are the small bowel mesentery, retroperitoneum, and pelvis. AF in the colon is extremely rare. CASE SUMMARY: Here, we report the first case of sigmoid colon AF, which was accidentally discovered in a 27-year-old woman during laparoscopic myomectomy. Computed tomography confirmed a slightly enhanced mass in the sigmoid colon. Subsequent colonoscopy did not reveal a mass in the colonic lumen, but a suspected external compress was found in the sigmoid colon. Surgical disease involving a gastrointestinal stromal tumor was suspected. The patient underwent laparoscopic exploration, and sigmoidectomy with a negative margin was performed to excise the mass. Postoperative immunohistochemistry revealed that the mass was an AF. The patient recovered well and was recurrence-free at the 30-month follow-up without adjuvant therapy. CONCLUSION: AF should be considered in the differential diagnosis of subepithelial colon masses. Radical resection alone can achieve good outcomes.

Clinical and genetic evaluations of Zimmermann-Laband syndrome with gingival fibromatosis: a rare case report.

Zimmermann-Laband Syndrome (ZLS; MIM 135500) is a rare genetic disorder with the main clinical manifestations of gingival fibromatosis and finger/toe nail hypoplasia. KCNH1 (potassium channel, voltage-gated, subfamily H, member-1), KCNN3 (potassium channel, voltage-gated, subfamily H, member-3) and ATP6V1B2 (ATPase H+ transporting V1 subunit B2) genes are considered causative genes for ZLS. However, there are limited reports about the diverse clinical presentation and genetic heterogeneity. Reporting more information on phenotype-genotype correlation and the treatment of ZLS is necessary. This case reported a 2-year-old patient with gingival enlargement that failure of eruption of the deciduous teeth and severe hypoplasia of nails. Based on a systemic examination and a review of the relevant literature, we made an initial clinical diagnosis of ZLS. A novel pathogenic variant in the KCNH1 gene was identified using whole-exome sequencing to substantiate our preliminary diagnosis. The histopathological results were consistent with gingival fibromatosis. Gingivectomy and gingivoplasty were performed under general anesthesia. After surgery, the gingival appearance improved significantly, and the masticatory function of the teeth was restored. After 2-year follow-up, the gingival showed slightly hyperplasia. Systemic examination and gene sequencing firstly contribute to provide information for an early diagnosis for ZLS, then timely removal of the hyperplastic gingival facilitates the establishment of a normal occlusal relationship and improves oral aesthetics.

Idiopathic Gingival Enlargement: A Case Report.

Gingival enlargement (GE) is an increase in the size of the gingiva. It may be due to inflammation caused by extensive plaque accumulation, intake of drugs, systemic conditions like pregnancy and puberty, systemic diseases such as leukemia or Wegener's granulomatosis, hereditary gingival fibromatosis, and neoplastic or false enlargement. Idiopathic GE is the massive increase in the size of the gingiva with an unknown etiology. It may have a hereditary basis, be linked to physical impairment, or begin with eruption of primary or permanent dentition. It is also referred as gingivomatosis, hereditary gingival fibromatosis, elephantiasis gingivae, gigantism of the gingiva, or congenital macrogingivae. The enlarged gingiva compromises oral hygiene maintenance, which secondarily adds to the inflammatory component of enlargement. Altogether, this exaggerates the existing condition. This type of extensively disfigured gingiva affects speech, mastication, and esthetics, causes halitosis, and disturbs the overall well-being of the individual. Surgical removal of the enlarged gingiva along with meticulous non-surgical means of plaque control is expected to provide a satisfactory functional and esthetic outcome. This case report presents a rare case of long-standing massive grade III GE extending up to the occlusal level in a 17-year-old systemically healthy, non-syndromic young female involving both arches, thereby posing a diagnostic dilemma. It was treated by gingivectomy using a conventional technique to facilitate precise incision, lower cost, and faster re-epithelialization. This was followed by gingivoplasty using electrocautery. The postoperative results of three months were satisfactory in terms of function and esthetics with uneventful healing. Further follow-up is ongoing for the same.

Genetic Variants in the TBC1D2B Gene Are Associated with Ramon Syndrome and Hereditary Gingival Fibromatosis.

Ramon syndrome (MIM 266270) is an extremely rare genetic syndrome, characterized by gingival fibromatosis, cherubism-like lesions, epilepsy, intellectual disability, hypertrichosis, short stature, juvenile rheumatoid arthritis, and ocular abnormalities. Hereditary or non-syndromic gingival fibromatosis (HGF) is also rare and considered to represent a heterogeneous group of disorders characterized by benign, slowly progressive, non-inflammatory gingival overgrowth. To date, two genes, ELMO2 and TBC1D2B, have been linked to Ramon syndrome. The objective of this study was to further investigate the genetic variants associated with Ramon syndrome as well as HGF. Clinical, radiographic, histological, and immunohistochemical examinations were performed on affected individuals. Exome sequencing identified rare variants in TBC1D2B in both conditions: a novel homozygous variant (c.1879_1880del, p.Glu627LysfsTer61) in a Thai patient with Ramon syndrome and a rare heterozygous variant (c.2471A>G, p.Tyr824Cys) in a Cambodian family with HGF. A novel variant (c.892C>T, p.Arg298Cys) in KREMEN2 was also identified in the individuals with HGF. With support from mutant protein modeling, our data suggest that TBC1D2B variants contribute to both Ramon syndrome and HGF, although variants in additional genes might also contribute to the pathogenesis of HGF.

Setting the international research agenda for sarcomas with patients and carers: results of phase II of the Sarcoma Patient Advocacy Global Network (SPAGN) priority setting partnership.

BACKGROUND: Typically, researchers and clinicians determine the agenda in sarcoma research. However, patient involvement can have a meaningful impact on research. Therefore, the Patient-Powered Research Network (PPRN) of the Sarcoma Patient Advocacy Global Network (SPAGN) set up a Priority Setting Partnership (PSP). The primary objective of this partnership is to identify priorities for research and patient advocacy topics. METHODS: In the first phase of this PSP, including 264 sarcoma patients and carers from all over the world, 23 research topics regarding sarcomas and 15 patient advocacy topics were identified using an online survey. In the second phase, participants were asked to fill in a top five and a top three of research and patient advocacy topics, respectively. Additionally, sociodemographic characteristics and sarcoma characteristics were collected. Social media channels, local national patient advocacy groups and the SPAGN website were used to distribute the survey. RESULTS: In total, 671 patients (75%) and carers (25%) participated in this survey. The five highest ranked research topics were related to causes of sarcoma (43%), prognosis and risk of recurrence (40%), specific subtypes of sarcoma (33%), the role of immunotherapy, targeted therapy and combined therapy (30%), and hereditary aspects (30%). The three highest ranked patient advocacy topics were improving the diagnostic process of sarcoma (39%), access to tumor DNA analysis (37%) and establishing an international sarcoma registry (37%). CONCLUSIONS: This sarcoma PSP has identified priorities for research and patient advocacy, offering guidance for researchers, assisting funding agencies with assessing project relevance and empowering patient advocates to represent the needs of patients and carers.

Anti-proliferative impact of resveratrol on gingival fibroblasts from juvenile hyaline fibromatosis.

AIM: Resveratrol is a natural polyphenolic compound with biological activities such as anti-inflammation and antioxidation. Its anti-fibrotic effect has been experimentally demonstrated in the pancreas and liver. This study aims to determine the anti-proliferative effect of resveratrol on fibroblasts obtained from hyperplastic gingival tissues from a patient diagnosed with Juvenile Hyaline Fibromatosis (JHF). MATERIALS AND METHODS: Primary gingival fibroblast cell lines were obtained from gingival growth tissues by the gingivectomy of a patient with JHF. Gingival fibroblasts were treated with or without 3 different doses of resveratrol (50, 100, 200 µM). Cytotoxicity and cell proliferation were evaluated after 24, 48, and 72 h. Collagen, TGF, and CTGF were analyzed by ELISA in the 48-hour supernatants. RESULTS: All three doses of resveratrol suppressed the proliferation of JHF gingival fibroblasts at 24 and 48 h without showing any cytotoxic effect compared to the control group (p < 0.0001). At 72 h, 100 and 200 µM resveratrol showed significantly less proliferation (p < 0.0001), less collagen, CTGF, and TGF- ß (p < 0.001) than the control group. CONCLUSION: Resveratrol had a profound anti-proliferative effect on gingival fibroblasts obtained from gingival enlargements with JHF, suggesting that it can be used as a therapeutic to prevent excessive cell growth by suppressing collagen, CTGF, and TGF- ß synthesis in the pathogenesis of hyperplasia.