Superficial fibromas with CTNNB1 mutation.

Superficial fibromas are a group of mesenchymal spindle cell lesions with pathomorphological heterogeneity and diverse molecular backgrounds. In part, they may be indicators of an underlying syndrome. Among the best-known entities of superficial fibromas is Gardner fibroma, a plaque-like benign tumor, which is associated with APC germline mutations and occurs in patients with familial adenomatosis polyposis (Gardner syndrome). Affected patients also have an increased risk to develop desmoid fibromatosis (DTF), a locally aggressive neoplasm of the deep soft tissue highly prone to local recurrences. Although a minority of DTFs occur in the syndromic context and harbor APC germline mutations, most frequently their underlying molecular aberration is a sporadic mutation in Exon 3 of the CTNNB1 gene. Up to date, a non-syndromic equivalent to Gardner fibroma carrying a CTNNB1 mutation has not been defined. Here, we present two cases of (sub-)cutaneous tumors with a hypocellular and collagen-rich Gardner fibroma-like appearance and pathogenic, somatic CTNNB1 mutations. We aim to differentiate these tumors from other fibromas according to their histological appearance, immunohistochemical staining profile and underlying somatic CTNNB1 mutations. Furthermore, we distinguish them from locally aggressive desmoid fibromatosis regarding their biological behavior, prognosis and indicated therapeutic strategies. Consequently, we call them CTNNB1-mutated superficial fibromas as a sporadic counterpart lesion to syndromic Gardner fibromas.

When molecular outsmarts morphology: Malignant ossifying fibromyxoid tumors masquerading as osteosarcomas, including a novel CREBZF::PHF1 fusion.

We present two cases of malignant ossifying fibromyxoid tumor (OFMT) which eluded diagnosis due to compelling clinicopathologic mimicry, compounded by similarly elusive underlying molecular drivers. The first is of a clavicle mass in a 69 year-old female, which histologically showed an infiltrative nested and trabeculated proliferation of monomorphic cells giving rise to scattered spicules of immature woven bone. Excepting SATB2 positivity, the lesion showed an inconclusive immunoprofile which along with negative PHF1 FISH led to an initial diagnosis of high-grade osteosarcoma. Next generation sequencing (NGS) revealed a particularly rare CREBBP::BCORL1 fusion. The second illustrates the peculiar presentation of a dural-based mass in a 52 year-old female who presented with neurologic dyscrasias. Sections showed a sheeted monotonous proliferation of ovoid to spindle cells, but in contrast to Case #1, the tumor contained an exuberance of reticular osteoid and woven bone deposition mimicking malignant osteogenic differentiation. NGS showed a novel CREBZF::PHF1 fusion. Both tumors recurred locally less than 1 year post-operatively. As such we reiterate that careful morphologic examination is axiomatic to any diagnosis in our discipline, but this paradigm must shift to recognize that molecular diagnostics can provide closure where traditional tools have notable limitations.

What is in a name-Perifollicular fibroma or fibrofolliculoma?

So far, confusion exists regarding the question of whether hereditary perifollicular fibromas and fibrofolliculomas can be distinguished from each other. Here, histopathological arguments are presented to clarify this terminological problem. In 1977, Birt et al. described a large kindred affected with hereditary multiple "fibrofolliculomas," which they thought were "a hitherto unrecognized pilar hamartoma," but they never claimed the fibrofolliculomas were part of a syndrome. A careful microscopic comparison shows, however, that the tumors are clinically and histopathologically identical to perifollicular fibromas, as first described by Burnier and Rejsek in 1925. Their familial occurrence was discovered in 1971 by Civatte and Le Tréguilly. Before 1977, the term "perifollicular fibroma" was used for these skin tumors. By contrast, Hornstein and Knickenberg described in 1975 perifollicular fibromas as a cutaneous marker of a syndrome characterized by a predisposition to colon cancer and pneumothorax. Later, two French groups erroneously proposed the term "Birt-Hogg-Dubé syndrome" to describe the co-occurrence of fibrofolliculomas, trichodiscomas, and acrochordons, which was contrary to what Birt et al. had in mind. Hence, today, we should discriminate between the hereditary nonsyndromic perifollicular fibromas, as documented by Civatte and Le Tréguilly and later by Birt et al., and the syndromic perifollicular fibromas, as delineated by Hornstein and Knickenberg.

Superficial desmoplastic fibroblastoma (collagenous fibroma): Clinicopathologic study of 11 cases.

BACKGROUND: Desmoplastic fibroblastoma (collagenous fibroma) is a rare soft tissue tumor that usually arises in the subcutis or skeletal muscle. Cases superficial to fascia are unusual and can cause diagnostic difficulty. We present 11 cases of superficial desmoplastic fibroblastoma involving a wide anatomic distribution. METHODS: Archives were searched using the term "desmoplastic fibroblastoma" over a 10-year period (2012-2022). Cases superficial to fascia were retrieved, and available clinicopathologic features were recorded. Only cases involving the dermis were included. RESULTS: Eleven cases were identified, all of which were received in consultation. Tumors involved the head and neck (2), lower extremity (2), back (2), foot (1), shoulder (1), axilla (1), hand (1), and breast (1). Each consisted of a hypocellular proliferation of bland stellate to spindled fibroblasts set in a collagenous to focally myxoid stroma. The immunohistochemical stains available for review demonstrated SMA positivity (4/7) and negative immunoreactivity for CD34 (0/6), EMA (0/3), desmin (0/3), and S100 (0/7). CONCLUSIONS: Desmoplastic fibroblastoma may present superficially in the dermis to subcutis, posing a potential source of diagnostic difficulty. Recognition of the characteristic histopathologic features of desmoplastic fibroblastoma with judicial use of immunohistochemical stains should allow for accurate diagnosis.

Elastofibromatous changes in giant cell fibroma and amalgam tattoo: Unusual findings in common oral lesions.

Several cases of elastofibromatous lesion affecting the oral mucosa have been reported. Clinically, these lesions may appear as small exophytic lesions or less often as white lesions. Therefore, fibrous hyperplasia and leukoplakia are not uncommonly considered in clinical differential diagnosis. Microscopically, elastic and fibrous connective tissue deposition is seen. Rarely, elastofibromatous changes can be detected when assessing intraoral lesions, including cysts, salivary gland neoplasms, and epithelial dysplasia. Here we report two oral lesions showing elastofibromatous changes, expanding their clinicopathological spectrum. The first case was a 46-year-old man with a history of asymptomatic nodular lesion on the palate 1 year ago, diagnosed as giant cell fibroma with elastofibromatous changes. The second case was a 79-year-old woman who presented a pigmented and mildly symptomatic lesion on the mandibular alveolar mucosa several months ago, diagnosed as amalgam tattoo associated with elastofibromatous changes.

Giant cell collagenoma in a patient with Cowden syndrome: A rare case report and literature review with a focus on the spectrum of sclerotic fibroma and giant cell collagenoma.

Sclerotic fibroma (SF) is a rare subset of dermal fibromas that occurs sporadically or in association with Cowden syndrome (CS). We report a case of a patient with known CS and a solitary lesion on the scalp. Histologic examination demonstrated a well-circumscribed lesion with sclerotic dermis and a whorled collagen pattern, multinucleated giant cells, and dendritic spindle cells. Nuclear atypia or mitotic figures were not noted. The giant cells were negative for Melan-A, SOX-10, EMA, SOX-10, and factor XIIIa. These findings are consistent with a giant cell collagenoma (GCC). Despite possible overlap with SF, GCC has not been associated with CS. This makes our case unique and suggests that GCC should be included in the spectrum of CS-associated cutaneous lesions. The diagnosis of SF may lead to the identification of previously undiagnosed CS; accordingly, GCC, even when present as a solitary lesion, may indicate the need for further work-up and screening for CS.

Giant cell collagenomas associated with Cowden syndrome: A case report.

Storiform collagenoma, also known as sclerotic fibroma, is a relatively rare benign cutaneous tumor consisting of a proliferation of fibroblasts that shows increased production of type I collagen. It may appear as a solitary, sporadic lesion, or, especially when multiple, associated with Cowden syndrome. Giant cell collagenoma has a histopathologic appearance similar to that of storiform collagenoma with the addition of floret-type giant cells. Herein, we report the finding of multiple giant cell collagenomas arising in an individual with Cowden syndrome. In a review of the published literature, this histopathologic variant appears to be rarely observed in association with Cowden syndrome.

Pediatric Plexiform Fibromyxoma: A Case Report.

The plexiform fibromyxoma is a rare mesenchymal tumor in adults that generally originates in the antrum of stomach, being its occurrence in pediatric patients exceptional. It was classified as a distinct entity by World Health Organization in 2010. No recurrences and metastases have been documented in many of the reported patients to date, being the surgical treatment curative. We report the case of a 3-month-old infant who presented to the emergency department with an episode of intestinal subocclusion requiring an emergent surgery. During the surgical intervention, a mass was identified in the jejunum, causing partial occlusion of its lumen. The surgical pathology report revealed an infiltrative tumor composed of spindle-shaped cells disposed in a stroma with a plexiform pattern alternating myxoid areas. These findings and the immunohistochemical characteristics of the neoplastic cells led to classify the tumor as a plexiform fibromyxoma. A description of the immunophenotype of this tumor is made and differential diagnosis with other gastrointestinal tumors is also discussed.

Sclerosing Dermatofibrosarcoma Protuberans: A Possible Diagnosis When a Small Biopsy Shows Sclerotic Fibroma-Like Features.

ABSTRACT: Dermatofibrosarcoma protuberans (DFSP) is a neoplasm of intermediate malignancy with high local recurrence rates. The sclerosing variant is characterized by the presence of sclerotic areas in more than 50% of tumors and is rarely reported. In this report, we describe a case of sclerosing DFSP with areas histopathologically resembling sclerotic fibroma, where the initial biopsy tissue presented a diagnostic challenge. A 77-year-old man presented with a 2-cm firm, erythematous nodule on the chest. A punch biopsy revealed plywood-like sclerosis and spindle cells with a vaguely storiform pattern. The tumor cells were positive for CD34. Sclerotic fibroma and DFSP were considered differential diagnoses. Subsequent excisional biopsy revealed that the tumor comprised 3 different histopathological areas: classic DFSP, sclerotic fibroma-like, and giant cell fibroblastoma-like. This report highlights the importance of reevaluating the clinical context and excision for further characterization.

Histogenetic insights and genetic landscape of fibromatosis-like undifferentiated gastric carcinoma: a focused study.

BACKGROUND: The aim of this study was to elucidate the histogenesis and genetic underpinnings of fibromatosis-like undifferentiated gastric carcinoma (FLUGC), a rare pathological entity. METHOD: Through a detailed analysis of seven cases, including histopathological evaluation, CTNNB1 gene mutation screening, human epidermal growth factor receptor 2 (HER2) protein level quantification, and HER2 gene amplification assessment to identify the pathological and molecular characteristics of FLUGC. RESULTS: Of the seven patients in this study, five were male and two were female (age: 39-73 years). Four patients presented with lesions in the gastric antrum and three had lesions in the lateral curvature of the stomach. Histopathologically, over 90% of the tumor consisted of aggressive fibromatosis-like tissue, including proliferating spindle fibroblasts and myofibroblasts and varying amounts of collagenous fibrous tissues. Undifferentiated cancer cells, accounting for less than 10%, were dispersed among the aggressive fibromatosis-like tissues. These cells were characterized by their small size and were relatively sparse without glandular ducts or nested mass-like structures. Immunophenotyping results showed positive expression of CKpan, CDX2, villin, and p53 in undifferentiated cancer cells; positive expression of vimentin in aggressive fibromatosis-like tissue; positive cytoplasmic expression of ß-catenin; and focal cytoplasmic positive expression of smooth muscle actin (SMA). Genetic analysis did not reveal any mutations in the CTNNB1 gene test, nor was there amplification in the HER2 gene fluorescence in situ hybridization (FISH) test. Additionally, the Epstein-Barr encoding region (EBER) of in situ hybridization was negative; and the mismatch repair (MMR) protein was positive. Programmed cell death-1 (PD-1) was < 1-5%; programmed cell death ligand 1 (PD-L1): TPS = 1-4%, CPS = 3-8. CONCLUSION: The study highlights the significance of CTNNB1, HER2, EBER, and MMR as pivotal genetic markers in FLUGC, underscoring their relevance for diagnosis and clinical management. The rarity and distinct pathological features of FLUGC emphasize the importance of accurate diagnosis to prevent underdiagnosis or misdiagnosis and to raise awareness within the medical community.

Jaffe-Campanacci syndrome; a case series and review of the literature.

BACKGROUND: Jaffe-Campanacci syndrome is a rare syndrome, characterized by multiple non-ossifying fibromas (NOF) and cafe-au-lait patches. The name was coined in 1982 by Mirra after Jaffe who first described the case in 1958. Although it's suggested there is a relation with Neurofibromatosis type 1, there is still no consensus on whether Jaffe-Campanacci syndrome is a subtype or variant of neurofibromatosis-1(NF-1). CASE PRESENTATION: In this article, we present a case series of 2 patients. The first case is a 13-year-old male with Jaffe-Campanacci syndrome who presented with a distal femur fracture. His father had positive features of both Jaffe-Campanacci syndrome and NF-1, while his sister only had features of NF-1, so we presented both. CONCLUSION: Jaffe-Campanacci has a clear relationship with type 1 neurofibromatosis, which still has to be genetically established. Due to the presence of several large non-ossifying fibromas of the long bones, it is linked to a significant risk of pathological fractures. We concur with previous authors, that an osseous screening program should be performed for all patients with newly diagnosed type 1 neurofibromatosis, to identify non-ossifying fibromas and assess the potential for pathological fracture. Moreover, siblings of patients with NF-1 should be screened for multiple NOFs that may carry a high risk of pathological fractures.

Ovarian fibromatosis associated with large pedunculated fibroma in a 30-year-old woman: A rare coincidence or variant?

A 30-year-old nulligravida was referred under suspicion of large subserosal myoma. T2-weighted magnetic resonance imaging revealed multilobulated solid mass in the left lower abdomen measuring 16 cm in longitudinal diameter. The ovarian surface was covered with a marked T2-hypointense thick rim called "black garland sign," forming multiple nodular masses ranging from 1 to 5 cm in diameter in some portions of the bilateral ovaries. By laparoscopic-assisted minilaparotomy, the stalk of pedunculated mass originating from the left ovarian hilum was excised, followed by carrying out of the body after in-bag morcellation using a surgical scalpel. Right ovarian exophytic nodular masses larger than 1 cm were excised using monopolar electrode needle. Pathological examination of excised right and left masses showed fibroblast-like spindle cell proliferation with collagenous stroma; however, differences between right and left masses cannot be distinguished on a histological level. Postoperative diagnosis was ovarian fibromatosis coexisting with large pedunculated fibroma.

The Role of Surveillance in Predicting Fracture in Pediatric Patients With Incidentally Discovered Nonossifying Fibromas and Fibrous Cortical Defects: Is It Worth It?

BACKGROUND: Nonossifying fibroma (NOF) and fibrous cortical defect (FCDs), the most common benign pediatric bone lesions, are usually incidental x-ray findings. Surveillance of characteristic lesions has been recommended to monitor for enlargement and assess fracture risk. However, no accepted fracture risk prediction guidelines exist, so indications for prophylactic surgery are unclear. The study's purposes were to (1) characterize the timing of NOF/FCD-associated fractures, (2) quantify the resources devoted to surveillance, and (3) evaluate the potential for surveillance to prevent pathologic fracture. METHODS: A single institution retrospective review was conducted to identify pediatric patients (below 18 y old) with clinical-radiographic documentation of an NOF or FCD diagnosis from 2012 to 2020. Patients who presented with fracture were tallied but excluded from the surveillance analysis. Patients without at least one follow-up visit were also excluded. Lesional radiographic features were characterized on initial imaging. The number of visits and imaging studies devoted to surveillance were tabulated. The number of fractures and prophylactic surgeries were recorded to quantify the potential of surveillance to prevent pathologic fractures. RESULTS: The study population presenting without fracture consisted of 301 patients with 364 lesions with a mean follow-up of 20 months. By contrast, over the same period, 38 patients presented with NOF/FCD associated pathologic fractures. Surveillance included 1037 additional imaging tests over 1311 follow-up visits, or on average, 3.4 imaging studies and 4.4 visits per patient. During surveillance, only 2 (0.55%) lesions fractured. Another 10/364 (2.8%) patients underwent curettage and grafting, suggesting that-at best-the potential for preventing pathologic fracture by surveillance, assuming all 10 patients who underwent surgery would have subsequently fractured along with the 2 documented fractures, is 3.3% of lesions (12/364). CONCLUSIONS: The small number of fractures and surgeries during the follow-up period probably does not justify additional resources for surveillance beyond the initial visit, except in symptomatic patients with large lesions. However, subsequent visits may play a role in educating patients and their families regarding the natural history of these lesions. LEVEL OF EVIDENCE: Prognostic Level II-retrospective study.

Plexiform Fibromyxoma in the Stomach: Immunohistochemical Profile and Comprehensive Genetic Characterization.

Plexiform fibromyxoma (PF), also referred to as plexiform angiomyxoid myofibroblast tumor, is an exceedingly rare mesenchymal neoplasm primarily affecting the stomach. Herein, we present a case of PF diagnosed in a 71-year-old male with a history of lung cancer, initially suspected to have a gastrointestinal stromal tumor (GIST) of the stomach, who subsequently underwent subtotal gastrectomy. The histopathological and molecular features of the tumor, including mutations in ABL1, CCND1, CSF1R, FGFR4, KDR, and MALAT1-GLI1 fusion, are elucidated and discussed in the context of diagnostic, prognostic, and therapeutic considerations.

HPV related p16INK4A and HSV in benign and potentially malignant oral mucosa pathologies.

BACKGROUND: The association of Human Papilloma Virus (HPV) and Human Syncytial Virus (HSV) infection with inflammatory and potentially malignant disorders of the oral cavity (OPMD) is unknown. The aim of this cross-sectional study was to stablish the expression of the p16INK4A and HSV proteins, to test potential correlation between those parameters in biopsies from clinically diagnosed oral lesions. METHODS: Immunochemical analysis of 211 formalin-fixed, paraffin-embedded (FFPE) blocks from 211 individuals was provided. The clinical diagnosis included in the research were Oral lichen planus (N = 30), Oral Leukoplakia (N = 13) Mucocele (N = 25), Erosion/ulceration/ inflammation of mucosa (N = 8), Overgrowth of mucosa (N = 135). RESULTS: Two hundred eleven analyzed FFPE samples resulted with the median age of 58.5 years (the average age 54.0 years and SD ± 17 years). The female/male ratio was 2.3 (69.7% vs 30.3% respectively). All the samples positive for HSV also expressed p16INK4A (p = 0.000), that's showed various levels of association with the diverse clinical diagnosis reaching the higher level in OM 49.1% (29 positive samples) and OLP 30.5% (18). p16INK4A was associated with OLP at 30.5% (18), and fibroma 30.5%. HSV expression was mostly present in fibroma at 47.6% (10 positive samples). CONCLUSION: HSV and p16INK4A positivity in relation to diagnosis of the biopsies showed statistically most often p16INK4A in OLP and fibroma. The results of co-expression of p16INK4A and HSV in mucocele and fibroma in oral mucosa suggest a cooperation between the molecular alterations induced by these two viruses. Squamous papilloma samples positive for p16INK4A were also positive for HSV, suggesting that the putative pro-oncogenic action of HSV could be an early event.

Expanding the molecular signatures of malignant ossifying fibromyxoid tumours with two novel gene fusions: PHF1::FOXR1 and PHF1::FOXR2.

AIMS: Ossifying fibromyxoid tumor (OFMT) is a rare enigmatic tumor of uncertain differentiation that can be classified as typical, atypical, and malignant subtypes based on cellularity, nuclear grade, and mitotic activity. The majority of OFMTs, regardless of the risk of malignancy, harbor genetic translocations. We report two malignant OFMTs, including one with evidence of dedifferentiation, with novel genefusions. METHODS AND RESULTS: Case 1 was a 63-year-old male with a dedifferentiated OFMT arising in the right wrist, while case 2 was a 41-year-old male with a malignant OFMT presenting as a posterior mediastinal mass. Case 2 showed multifocal expression with EMA and synaptophysin, while desmin and S100 were absent in both tumors. NGS sequencing studies detected PHF1::FOXR1 and PHF1::FOXR2 gene fusions in cases 1 and 2, respectively. Despite aggressive regimens, both progressed with wide spread metastases resulting in death within six years of diagnosis. CONCLUSIONS: We expand the genetic spectrum of OFMTs with two novel gene fusions, PHF1::FOXR1 and PHF1::FOXR2. These cases confirm the previously reported tendencies for OFMTs with rare variant fusions to demonstrate malignant behavior, unusual morphology, and non-specific immunophenotype.

Onychomatricoma: a clinicopathological, immunohistochemical, and molecular study of 10 cases highlighting recurrent RB1 deletion and the potential diagnostic value of LEF-1.

AIMS: Onychomatricoma (OM), an uncommon benign fibroepithelial neoplasm of the nail unit, is sometimes diagnostically challenging for clinicians and pathologists. OM consistently expresses CD34, but no specific immunohistohemical markers or recurrent genetic alterations have been identified to date. Recent studies have suggested that Wnt signalling is a key molecular characteristic of OM. METHODS AND RESULTS: Ten cases were analysed: four classical OM including two with pleomorphic cells; two superficial acral fibromyxoma-like variants of OM; three micropapilliferum variants of OM including one with pleomorphic cells; and one proliferating variant of OM. Immunohistochemically, the spindle cells were positive with CD34 (n = 10) and CD99 (n = 1), with focal reactivity for CD10 (n = 5). The epithelial component of the tumours expressed immunopositivity for LEF-1. Using array comparative genomic hybridization (aCGH), we demonstrated that all OM, including its variants that were tested (n = 8), harboured a few copy number alterations with losses of whole or part of chromosome 13 including the RB1 gene (n = 8) and chromosome 16 (n = 6). CONCLUSION: We report a recurrent loss of RB1 (13q) as a possible driver molecular event in OM indicating a relationship between OM and other lesions of the spectrum of the so-called '13q/RB1' family of tumours. We did not identify a role for the Wnt/beta-catenin signalling pathway, as has been proposed in a recent study. LEF-1 could be a potential sensitive and specific marker of OM and should be used in the differential diagnosis between OM, superficial acral fibromyxoma, and the CD34-positive fibrosing family of tumours.

Fibroblastic and Myofibroblastic Soft-Tissue Tumors: Imaging Spectrum and Radiologic-Pathologic Correlation.

Fibroblastic and myofibroblastic tumors are a variable group of neoplasms ranging from benign to malignant. These lesions may affect patients of any age group but are more frequently encountered in the pediatric population. Patient clinical presentation depends on the location, growth pattern, adjacent soft-tissue involvement, and pathologic behavior of these neoplasms. In the 2020 update to the World Health Organization (WHO) classification system, these tumors are classified on the basis of their distinct biologic behavior, histomorphologic characteristics, and molecular profiles into four tumor categories: (a) benign (eg, fibrous hamartoma of infancy, nodular fasciitis, proliferative fasciitis, fibroma of the tendon sheath, calcifying aponeurotic fibroma); (b) intermediate, locally aggressive (eg, desmoid fibromatosis); (c) intermediate, rarely metastasizing (eg, dermatofibrosarcoma protuberans, myxoinflammatory fibroblastic sarcoma, low-grade myofibroblastic sarcoma, infantile fibrosarcoma); and (d) malignant (eg, sclerosing epithelioid fibrosarcomas; low-grade fibromyxoid sarcoma; myxofibrosarcoma; fibrosarcoma, not otherwise specified). Detection of various components of solid tumors at imaging can help in prediction of the presence of corresponding histopathologic variations, thus influencing diagnosis, prognosis, and treatment planning. For example, lesions with a greater myxoid matrix or necrotic components tend to show higher signal intensity on T2-weighted MR images, whereas lesions with hypercellularity and dense internal collagen content display low signal intensity. In addition, understanding the radiologic-pathologic correlation of soft-tissue tumors can help to increase the accuracy of percutaneous biopsy and allow unnecessary interventions to be avoided. ©RSNA, 2023 Quiz questions for this article are available in the supplemental material.

Pleomorphic acquired digital fibrokeratoma: A novel clinicopathologic entity.

A 26-year-old male presented with a 2-year history of a hyperkeratotic growth from the left index finger. Histopathology was consistent with an acquired digital fibrokeratoma with changes of a pleomorphic fibroma. Lesional cells were negative for CD34, Rb, and p53, and were positive for FXIIIa. We introduce the pleomorphic acquired digital fibrokeratoma as a novel clinicopathologic entity.

Oral Focal Mucinosis of the Tongue: A Rare Localization for a Rare Entity.

ABSTRACT: Oral focal mucinosis (OFM) is a rare connective tissue disorder that is characterized by the excessive production of hyaluronic acid due to myxoid degeneration of submucosal connective tissue. The disorder typically presents as an asymptomatic nodule or mass in the gingiva or hard palate, and OFM of the tongue is even more unusual. In this report, we present a case of OFM on the tongue in a 72-year-old female patient who presented with a symptomatic lump that had been growing for 6 months on the dorsum of her tongue. The patient reported discomfort and pain while speaking and swallowing, and the lump was visually apparent on examination. OFM is a benign condition that does not have any specific clinical or radiographical features that distinguish it from other more common oral lesions, such as lipoma or fibroma. Therefore, histopathological examination is essential for a definitive diagnosis. The management of OFM typically involves surgical excision of the lesion. In this case, complete surgical removal of the lesion under general anesthesia was performed, and the patient was followed up for 10 months postoperatively. During the follow-up period, there was no evidence of recurrence, and the patient reported significant improvement in her symptoms. In conclusion, OFM is a rare connective tissue disorder that can occur in the oral cavity. Although OFM of the tongue is even rarer, it should be considered in the differential diagnosis of oral lesions. Histopathological examination is essential for definitive diagnosis, and surgical excision is typically the preferred treatment modality.