A novel HMGA2::KITLG fusion in a dedifferentiated liposarcoma with amplification of MDM2 and HMGA2.

High-mobility group AT-hook 2 (HMGA2) is rearranged in various types of mesenchymal tumors, particularly lipomas. HMGA2 is also co-amplified with mouse double minute 2 (MDM2) in well-differentiated liposarcoma/dedifferentiated liposarcoma (WDLPS/DDLPS). We report a case of relapsed DDLPS with a novel in-frame fusion between HMGA2 and KITLG, which encodes the ligand for KIT kinase, a critical protein involved in gametogenesis, hematopoiesis, and melanogenesis. The HMGA2 breakpoint is in intron 3, a commonly observed location for HMGA2 rearrangements, while the KITLG breakpoint is in intron 2, leading to a fusion protein that contains almost the entire coding sequence of KITLG. By immunohistochemical staining, tumor cells expressed KIT and showed phosphorylated MAPK, a major KIT downstream target. We suggest an oncogenic mechanism that involves the overexpression of KITLG caused by its rearrangement with HMGA2, leading to the constitutive activation of KIT kinase. While MDM2 amplification was observed in both the primary tumor and the relapsed tumor, the HMGA2::KITLG was only present in the relapsed tumor, indicating the role of HMGA2::KITLG in disease progression.

Atypical Spindle Cell/Pleomorphic Lipomatous Tumor With Sarcomatous Transformation: Clinicopathologic and Molecular Analysis of 4 Cases.

Atypical spindle cell/pleomorphic lipomatous tumor (ASPLT) is a recently described adipocytic tumor predominantly affecting the subcutaneous soft tissues of adults. Previous studies have shown that ASPLT follows a benign clinical course with a 4% to 12% local recurrence rate and no risk of dedifferentiation. Herein, we describe the clinicopathologic and molecular findings of 4 cases of ASPLT showing unequivocal sarcomatous transformation. Three patients were male and one was female, aged 65, 70, 74, and 78 years. Two cases presented as mass-forming lesions, while 1 case was incidentally discovered. The tumors measured 30, 55, 80, and 110 mm and occurred in the chest wall (n = 2) or arm (n = 2); all were subcutaneous. Microscopically, they showed a biphasic appearance comprising a low-grade ASPLT component and a high-grade sarcomatous component. The low-grade components showed features in the spectrum of either atypical pleomorphic lipomatous tumor (n = 2) or atypical spindle cell lipomatous tumor (n = 2). The high-grade components displayed leiomyosarcoma-like (n = 2), pleomorphic liposarcoma-like (n = 1) or undifferentiated sarcoma-like (n = 1) morphology. On immunohistochemistry, tumors were negative for MDM2 and showed loss of RB1 expression. In addition, the leiomyosarcoma-like areas seen in 2 cases were positive for smooth muscle actin and H-caldesmon. Single-nucleotide polymorphism array, performed in 3 cases, showed deletions of TP53, RB1, and flanking genes in both components. In contrast, the sarcomatous components showed more complex genomic profiles with rare segmental gains and recurrent loss of PTEN (n = 3), ATM (n = 2), and CDKN2A/B (n = 2) among other genes. Whole exome sequencing identified a TP53 variant in one case and an ATRX variant in another, each occurring in both tumor components. Limited clinical follow-up showed no recurrence or metastasis after 1 to 13 months (median, 7.5 months) postsurgical excision. Altogether, our data support that ASPLT can rarely develop sarcomatous transformation and offer insights into the molecular mechanisms underlying this event.

CYP1A1 immunohistochemistry is highly specific for angiofibroma of soft tissue among morphological mimics.

AIMS: Angiofibroma of soft tissue (AFST) is a benign, morphologically distinctive tumour type that harbours recurrent AHRR::NCOA2 fusions in 60-70% of cases and shows a non-specific immunophenotype, expressing EMA in roughly half of cases. The AHRR::NCOA2 fusion results in increased expression of cytochrome P450 1A1 (CYP1A1); a recent study demonstrated CYP1A1 immunohistochemistry (IHC) to be moderately sensitive and highly specific for AFST. METHODS AND RESULTS: In this study, we sought to validate these findings in a larger independent cohort of 30 AFST, as well as 215 morphological mimics, including 30 solitary fibrous tumours, 29 myxoid liposarcomas, 28 low-to-intermediate grade myxofibrosarcomas (MFS), 20 atypical spindle cell lipomatous tumours (ASCLT), 20 cellular angiofibromas, 10 cases each of spindle cell lipoma, neurofibroma, malignant peripheral nerve sheath tumour, superficial angiomyxoma, cellular myxoma, soft tissue perineurioma and deep fibrous histiocytoma, and nine cases each of low-grade fibromyxoid sarcoma and mammary-type myofibroblastoma. We found CYP1A1 IHC to be 70% sensitive for AFST, with granular cytoplasmic staining in 21 of 30 tumours, and 98% specific, with staining in only five morphological mimics: two deep fibrous histiocytomas, one MFS, one cellular angiofibroma and one ASCLT. CONCLUSIONS: These findings confirm that CYP1A1 is 70% sensitive, consistent with the prevalence of AHRR::NCOA2 fusions that up-regulate this protein, and that it is highly specific among morphological mimics.

Lingual neoplasia in nonhuman primates: Description of five cases and a literature review.

BACKGROUND: Documentation of lingual tumors is scarce in nonhuman primates. METHODS: Through a multi-institutional retrospective study we compile cases of primary and metastatic neoplasia in non-human primates. RESULTS: We describe five cases of lingual neoplasia. Three cases are primary lingual tumors: chondro-osteoblastic lipoma in a howler monkey, squamous cell carcinoma, and fibroma in two baboons. We describe two cases of metastatic lymphoma in the tongue in rhesus macaques. A literature review of published lingual neoplasia in nonhuman primates is included in this manuscript. CONCLUSION: Lingual neoplasia is seldom reported in non-human primates.

A case of Wilson's disease combined with intracranial lipoma and dysplasia of the corpus callosum with review of the literature.

BACKGROUND: Wilson's disease (WD) is an inherited disorder of copper metabolism. Agenesis of the corpus callosum is the complete or partial absence of the major united fiber bundles connecting the cerebral hemispheres. Intracranial lipoma is an adipose tissue tumor resulting from an abnormal embryonic development of the central nervous system. The simultaneous occurrence of these three disorders is rare and has not been reported. This report focuses on the pathogenesis and association between the three disorders and highlights the importance of recognizing and effectively managing their coexistence. CASE PRESENTATION: The purpose of this study was to present a patient with coexisting WD, intracranial lipoma, and corpus callosum dysplasia. We reviewed a female patient hospitalized in 2023 with clinical manifestations of elevated aminotransferases and decreased ceruloplasmin, as well as genetic testing for an initial diagnosis of Wilson's disease. Subsequently, a cranial MRI showed corpus callosum dysplasia with short T1 signal changes in the cerebral falx, leading to a final diagnosis of Wilson's disease combined with intracranial lipoma and corpus callosum dysplasia. The patient's WD is currently stable after treatment with sodium dimercaptosulfonamide (DMPS) and penicillamine, and the patient's abnormal copper metabolism may promote the growth of intracranial lipoma. CONCLUSION: The pathogenesis of WD combined with intracranial lipoma and corpus callosum dysplasia is complex and clinically rare. The growth of intracranial lipomas may be associated with abnormal copper metabolism in WD. Abnormal copper metabolism affects lipid metabolism and triggers inflammatory responses. Therefore, early diagnosis and treatment are beneficial for improvement. Each new case of this rare co-morbidity is important as it allows for a better assessment and understanding of these cases' more characteristic clinical manifestations, which can help estimate the course of the disease and possible therapeutic options.

Targeted therapy in patients with PIK3CA-related overgrowth syndrome.

CLOVES syndrome (congenital lipomatous overgrowth, vascular malformations, epidermal naevi, scoliosis/skeletal and spinal syndrome) is a genetic disorder that results from somatic, mosaic gain-of-function mutations of the PIK3CA gene, and belongs to the spectrum of PIK3CA-related overgrowth syndromes (PROS). This rare condition has no specific treatment and a poor survival rate. Here, we describe a postnatal mouse model of PROS/CLOVES that partially recapitulates the human disease, and demonstrate the efficacy of BYL719, an inhibitor of PIK3CA, in preventing and improving organ dysfunction. On the basis of these results, we used BYL719 to treat nineteen patients with PROS. The drug improved the disease symptoms in all patients. Previously intractable vascular tumours became smaller, congestive heart failure was improved, hemihypertrophy was reduced, and scoliosis was attenuated. The treatment was not associated with any substantial side effects. In conclusion, this study provides the first direct evidence supporting PIK3CA inhibition as a promising therapeutic strategy in patients with PROS.

Radiologic-histopathologic correlation of fatty island sign with fat necrosis in atypical lipomatous tumor and lipoma.

AIM: This study aimed to assess the imaging features of atypical lipomatous tumors (ALTs) and lipoma with fat necrosis. METHODS: This study included patients with histopathologically proven fat necrosis within adipocytic tumors who underwent preoperative imaging. Magnetic resonance imaging (MRI) and/or computer tomography (CT) findings of fat necrosis associated with lipomatous tumors were retrospectively reviewed, emphasizing the "fatty island sign (FIS)." FISs were defined as well-demarcated, focal fat-containing areas surrounded by more thickened septa compared with other intratumoral septa. Imaging findings of FIS were compared between ALT and lipoma. RESULTS: Fat necrosis was histopathologically confirmed in 17 patients (6 ALTs and 11 lipomas). Among them, 18 FISs were observed in 10 lesions (59%). Multiple FISs within a lesion were observed in 4 (40%) patients. The median maximum diameter of the FISs was 37 mm. Hypointense areas within FISs relative to the subcutaneous fat on T1- and T2-weighted images were observed in 8 (80%) and 9 (90%), respectively, whereas hyperintense areas within FISs on fat-suppressed T2-weighted images were observed in 2 (20%). Nonfatty solid components within FISs were observed in 2 (20%). On CT, increased fat attenuation and pure fat attenuation within FISs were observed in 6 (86%) and 1 (14%), respectively. The imaging findings of FIS were not significantly different between ALT and lipoma. CONCLUSION: FISs were observed in 59% of the histologically proven ALT and lipoma patients with fat necrosis. The hypointense areas relative to the subcutaneous fat on T1- and T2-weighted images and increased fat attenuation on CT were usually observed within FISs.

Practical surgical technique using the SMISS approach for lip reduction in involuted lip infantile hemangiomas.

BACKGROUND: Lip infantile hemangiomas tend to show less volumetric regression and are more susceptible to visible sequelae in the involuted stage. Some of them still require surgical management after propranolol therapy. This study aimed to evaluate the efficacy and safety of the Stepwise, Multi-Incisional, and Single-Stage (SMISS) approach applied to lip reduction for those with involuted lip hemangiomas. METHODS: A retrospective review was performed to evaluate patients with lip hemangioma who received previous propranolol treatment and underwent the aforementioned procedure. Demographic characteristics, lesion morphology, and medical history were reviewed. The Visual Analog Scale was applied to assess the postoperative appearance. Complications within 12 months postoperatively were recorded. RESULTS: A total of 18 patients with lip hemangioma were eligible. All patients received oral propranolol therapy before surgery, with treatment duration ranging from 6.0 to 23.0 months. Their age at surgery ranged from 2.5 to 9.0 years. The median Visual Analog Scale scores were 8.0, ranging from 4.0 to 10.0. No severe complications were reported. CONCLUSIONS: This modified technique based on the SMISS approach has proven reliable and effective in improving the aesthetic outcome for involuted lip infantile hemangiomas. Practical surgical techniques still play an important part in the propranolol era.

Melanocytic Nevus With Spindle Cell Lipomatous Metaplasia.

ABSTRACT: Melanocytic nevi can show a great number of morphological, cytoarchitectural, and stromal variations. Some of these histopathological patterns, infrequent or unusual, can occasionally produce diagnostic doubts or problems. A 22-year-old female patient presented a poorly pigmented cutaneous polypoid lesion of the scalp. Histopathological examination showed an intradermal melanocytic nevus composed of aggregates, nests, and cords of benign melanocytes, with collagenous stroma and large lipomatous areas. In the lipidized portion of the lesion, nevus cells, arranged in clusters, nests, and cords, were intimately associated with mature-appearing adipocytes, CD34-positive spindle cells, Alcian Blue-positive fibromyxoid stroma, and eosinophilic collagen bundles, findings resembling those typically seen in spindle cell lipoma. Spindle cell lipomatous metaplasia, rarely observed in some benign nonmelanocytic skin lesions, can be considered an additional unusual, not previously described, stromal variation occurring in melanocytic nevi.

Superficial Atypical Lipomatous Tumor With Pleomorphic Features: Case Report and Discussion of the Literature.

ABSTRACT: Among liposarcomas, well-differentiated liposarcoma and dedifferentiated liposarcoma are the most common. The majority of these tumors are found in deep retroperitoneum or extremities. When found outside the retroperitoneum, these adipose-derived tumors are known as atypical lipomatous tumors (ALT). Superficial ALT are particularly rare; thus, little is known about their clinical presentation, genomic status, and management. Here, we present the case of a 54-year-old man with an intermittently bothersome, slowly growing mass on his left upper back for over 2 years, which was incidentally diagnosed as ALT. This patient's ALT, however, showed a profound degree of pleomorphism with MDM2 and control centromere 12 (CEP12) coamplification and negative CD34 and S100 and RB1 expression, unlike most other ALT described in the literature. This case report details the diagnostic workup and histopathological findings for adipose tumors and summarizes the different subtypes, including atypical spindle cell/pleomorphic lipomatous tumor, pleomorphic liposarcoma, and spindle cell/pleomorphic lipoma, with brief discussion on management.

Preoperative interactive virtual simulation applying three-dimensional multifusion images using a haptic device for lumbosacral lipoma.

PURPOSE: Untethering surgery for lumbosacral lipoma is a preventive procedure, and avoidance of complications and good long-term outcomes are required. We introduced presurgical interactive virtual simulation (IVS) applying three-dimensional multifusion images using a haptic device aimed at improving operative outcomes. METHODS: Fourteen patients with newly diagnosed lumbosacral lipoma were recruited and underwent preoperative IVS. The median age at surgery was 8 months. A three-dimensional image analysis system was used to extract and fuse structures necessary for surgery, such as the lipoma, spinal cord and skin, from CT and MRI, and create three-dimensional multifusion images. The created images were individually converted to standard triangulated language format and loaded onto a workstation (Geomagic freeform™) that could be freely transformed, and the laminectomy range and lipoma extraction procedure were examined. Presurgical IVS was performed, and the actual surgery was performed. RESULTS: The disease types were dorsal, caudal, lipomyelomeningocele, transitional, and filum in 5, 5, 2, 1, and 1 patients, respectively. The surgical procedure and extent of the laminectomy were as planned for all patients. Resection of the lipomas tended to be less than expected preoperatively because of positive reactions on intraoperative monitoring. No postoperative complications were observed. The median postoperative follow-up period was 29 months, and there were no reoperations during the observation period. CONCLUSIONS: Although there are various types of lumbosacral lipoma, surgery can be safely performed by performing presurgical IVS. The short-term course is good; however, long-term follow-up is necessary for the appearance of neurological symptoms associated with growth and re-tethering.

Lumbosacral lipoma in childhood, how strong is the evidence base? A systematic review.

OBJECTIVE: Conus region lumbosacral lipomas (LSLs) are highly heterogeneous in their morphology, clinical presentation, and outcome, with an incompletely understood natural history and often treacherous surgical anatomy. This systematic review aims to critically evaluate and assess the strength of the current LSL evidence base to guide management strategies. METHODS: According to a systematic review following PRISMA guidelines, a search was conducted using the key term "lumbosacral lipoma" across MEDLINE (OVID), Embase, Cochrane Library, and PubMed databases from January 1951 to April 2021. All studies containing ten or more paediatric conus lipomas were included. Data heterogeneity and bias were assessed. RESULTS: A total of 13 studies were included, containing 913 LSLs (predominantly transitional type-58.5%). Two-thirds (67.5%) of all patients (treated and non-treated) remained clinically stable and 17.6% deteriorated. Neuropathic bladder was present in 8.6% at final follow-up. Of patients managed surgically, near-total resection vs. subtotal resection deterioration-free survival rates were 77.2-98.4% and 10-67% respectively. 4.5% (0.0-27.3%) required re-do untethering surgery. Outcomes varied according to lipoma type. Most publications contained heterogeneous populations and used variable terminology. There was a lack of consistency in reported outcomes. CONCLUSION: Amongst published series, there is wide variability in patient factors such as lipoma type, patient age, and methods of (particularly urological) assessment. Currently, there is insufficient evidence base upon which to make clear recommendations for the management of children with LSL. There is an imperative for neurosurgeons, neuroradiologists, and urologists to collaborate to better standardise the terminology, assessment tools, and surgical interventions for this challenging group of conditions.

Spinal cord lipomas: lessons learned in the era of total resection.

PURPOSE: Recent years have seen a paradigm shift towards total/near-total resection in spinal cord lipoma surgery. As this procedure is technically challenging, surgical candidates need to be selected appropriately through accurate image assessment and classification. The purpose of this paper is to describe a surgical series of paediatric spinal cord lipomas, their diagnosis, results and complications. METHODS: We undertook a retrospective review of paediatric patients with spinal cord lipomas who underwent surgery between 2008 and 2022. The variables studied were age, gender, preoperative symptoms according to the Necker Functional Score (NFS), type of lipoma according to Morota's classification, functional and radiological surgical outcomes using the cord-sac ratio (CSR), need for re-operation, complications and follow-up. RESULTS: A total of 25 patients (average age 36 months) underwent surgery. According to Morota's classification, MRI showed 13 type 1 lipomas, two type 2, two type 3 and eight type 4. The preoperative NFS was 16.06, with urological abnormalities being the most frequent manifestation. Total/near-total resection was attempted since 2015. Five patients with type 1 lipoma required re-operation due to clinical deterioration with suspected retethering, all of them with a CSR > 0.3. The series average CSR was 0.417. CONCLUSIONS: This paper highlights the importance of proper classification for a correct surgical approach to obtain favourable results and minimise possible complications. Based on our experience, given our results regarding the percentage of fistulae and retethering rates, we limited radical resection to symptomatic type 1 lipomas. Our future aim is to obtain better CSR rates and to decrease the retethering percentage.

Navigating the complexities of encephalocraniocutaneous lipomatosis: a case series and review.

INTRODUCTION: Encephalocraniocutaneous lipomatosis (ECCL) is a rare congenital syndrome with complex skin, eye, and central nervous system (CNS) symptoms. Diagnosis and treatment are challenging due to its rarity and diverse manifestations. It often involves issues like porencephalic cysts, cortical atrophy, and low-grade gliomas in the CNS, resulting in developmental delays. The spinal cord is frequently affected, leading to problems like medullary compression and radiculopathy, causing back pain and sensory/motor deficits. Surgical interventions are reserved for symptomatic cases to address hydrocephalus or alleviate spinal lipomas. This article reviews a case series to assess surgical risks and neurological outcomes. CASE SERIES: We present a case series ECCL, focusing on the diffuse lipomatosis of the spinal cord and the intricate surgical procedures involved. A multi-stage surgical approach was adopted, with continuous neuromonitoring employed to safeguard motor pathways. We discuss clinical characteristics, imaging studies, and indications for neurosurgical interventions. DISCUSSION: ECCL is a complex syndrome. Diagnosis is challenging and includes clinical evaluation, neuroimaging, and genetic testing. Treatment targets specific symptoms, often requiring surgery for issues like lipomas or cerebral cysts. Surgery involves laminectomies, spinal fusion, and motor pathway monitoring. Thorough follow-up is crucial due to potential CNS complications like low-grade gliomas. Hydrocephalus occurs in some cases, with endoscopic third ventriculostomy (ETV) preferred over ventriculoperitoneal shunt placement. CONCLUSION: Neurosurgery for ECCL is for symptomatic cases. ETV is preferred for hydrocephalus, while the treatment for lipoma is based on the presence of symptoms; the follow-up should assess growth and prevent deformities.

Intramedullary spinal capillary hemangioma with secondary neurulation defect in children.

Intramedullary spinal capillary hemangioma is a rare occurrence in pediatric patients, and only limited cases have been reported. This study presents the first two cases of spinal capillary hemangioma co-present with retained medullary cord and one case of spinal capillary hemangioma with lumbosacral lipomatous malformation. Previous literature on ten patients with this pathology was reviewed. We speculated pathogenesis, imaging features, and histopathologic findings of the disease.

Association of spinal cord abnormalities with vertebral anomalies: an embryological perspective.

PURPOSE: To analyze the relationship between spinal cord and vertebral abnormalities from the point of view of embryology. METHODS: We analyzed the clinical and radiological data of 260 children with different types of spinal cord malformations in combination with vertebral abnormalities. RESULTS: Among 260 individuals, approximately 109 presented with open neural tube defects (ONTDs), 83 with split cord malformations (SCMs), and 83 with different types of spinal lipomas. Pathological spina bifida emerged as the most frequent vertebral anomaly, affecting 232 patients, with a higher prevalence in ONTD. Vertebral segmentation disorders, including unsegmented bars, butterfly vertebrae, and hemivertebrae, were present in 124 cases, with a higher prevalence in SCM. The third most common spinal anomaly group consisted of various forms of sacral agenesis (58 cases), notably associated with blunt conus medullaris, spinal lipomas, and sacral myelomeningocele. Segmental aplasia of the spinal cord had a typical association with segmental spinal absence (N = 17). CONCLUSION: The association between SCM and neuroenteric cyst/canal and vertebral segmentation disorders is strong. High ONTDs often coincide with pathological spina bifida posterior. Type 1 spinal lipomas and focal spinal nondisjunction also correlate with pathologic spina bifida. Segmental spinal absence or dysgenesis involves localized spinal and spinal cord aplasia, sometimes with secondary filar lipoma.

SOLAMEN syndrome with cardiovascular damage.

SOLAMEN syndrome is a rare, recently recognized congenital syndrome that is characterized by progressive and hypertrophic diseases involving multiple systems, including segmental overgrowth, lipomatosis, arteriovenous malformation (AVM) and epidermal nevus. According to literatures, SOLAMEN syndrome is caused by heterozygous PTEN mutation. Phenotypic overlap complicates the clinical identification of diseases associated with PTEN heterozygous mutations, making the diagnosis of SOLAMEN more challenging. In addition, SOLAMEN often presents with segmental tissue overgrowth and vascular malformations, increasing the possibility of misdiagnosis as klipple-trenaunay syndrome or Parks-Weber syndrome. Here, we present a case of a child presenting with macrocephaly, patchy lymphatic malformation on the right chest, marked subcutaneous varicosities and capillaries involving the whole body, overgrowth of the left lower limb, a liner epidermal nevus on the middle of the right lower limb, and a large AVM on the right cranial thoracic entrance. Based on the typical phenotypes, the child was diagnosed as SOLAMEN syndrome. detailed clinical, imaging and genetic diagnoses of SOLAMEN syndrome was rendered. Next-generation sequencing (NGS) data revealed that except for a germline PTEN mutation, a PDGFRB variant was also identified. A subsequent echocardiographic examination detected potential cardiac defects. We suggested that given the progressive nature of AVM and the potential severity of cardiac damage, regular echocardiographic evaluation, imaging follow-up and appropriate interventional therapy for AVM are recommended.

All groin swellings are not lipoma.

An interesting case of an abdominal wall swelling near an old operative scar showing epithelial and stromal cells. In this present paper, fine needle aspiration cytology of an inguinal swelling is discussed which may often create diagnostic confusion.

Four-month-old with severe PIK3CA-related overgrowth spectrum disorder successfully treated with alpelisb.

PIK3CA-related overgrowth spectrum (PROS) encompasses different clinical entities caused by somatic activating mutations in PIK3CA. Among PROS, CLOVES syndrome represents a severe phenotype with poor survival rate. We present the case of a 4-month-old girl with CLOVES syndrome successfully treated with alpelisib, a PIKC3A inhibitor.

Nodular cystic fat necrosis: a distinctive rare soft-tissue mass.

We report the case of a 34-year-old female who was evaluated for a right lower extremity soft-tissue mass, found to be a large cystic lesion bound by fibrous tissue containing innumerable, freely mobile nodules of fat. Her presentation suggested the diagnosis of nodular cystic fat necrosis (NCFN), a rare entity that likely represents a morphological subset of fat necrosis potentially caused by vascular insufficiency secondary to local trauma. Her lesion was best visualized using MRI, which revealed characteristic imaging features of NCFN including nodular lipid-signal foci that suppress on fat-saturated sequences, intralesional fluid with high signal intensity on T2-weighted imaging, and a contrast-enhancing outer capsule with low signal intensity on T1-weighted imaging. Ultrasound imaging offered the advantage of showing mobile hyperechogenic foci within the anechoic cystic structure, and the lesion was otherwise visualized on radiography as a nonspecific soft-tissue radiopacity. She was managed with complete surgical excision with pathologic evaluation demonstrating, similar to the radiologic features, innumerable free-floating, 1-5 mm, smooth, nearly uniform spherical nodules of mature fat with widespread necrosis contained within a thick fibrous pseudocapsule. Follow-up imaging revealed no evidence of remaining or recurrent disease on postoperative follow-up MRI. The differential diagnosis includes lipoma with fat necrosis, lipoma variant, atypical lipomatous tumor, and a Morel-Lavallée lesion. There is overlap in the imaging features between fat necrosis and both benign and malignant adipocytic tumors, occasionally making this distinction based solely on imaging findings challenging. To our knowledge, this is the largest example of NCFN ever reported.