Role of epidural fat in the local milieu: what we know and what we don't.

PURPOSE: Traditionally, the epidural fat (EF) is known as a physical buffer for the dural sac against the force and a lubricant facilitating the relative motion of the latter on the osseous spine. Along with the development of the studies on EF, controversies still exist on vital questions, such as the underlying mechanism of the spinal epidural lipomatosis. Meanwhile, the scattered and fragmented researches hinder the global insight into the seemingly dispensable tissue. METHODS: Herein, we reviewed literature on the EF and its derivatives to elucidate the dynamic change and complex function of EF in the local milieu, especially at the pathophysiological conditions. We start with an introduction to EF and the current pathogenic landscape, emphasizing the interlink between the EF and adjacent structures. We generally categorize the major pathological changes of the EF into hypertrophy, atrophy, and inflammation. RESULTS AND CONCLUSIONS: It is acknowledged that not only the EF (or its cellular components) may be influenced by various endogenic/exogenic and focal/systematic stimuli, but the adjacent structures can also in turn be affected by the EF, which may be a hidden pathogenic clue for specific spinal disease. Meanwhile, the unrevealed sections, which are also the directions the future research, are proposed according to the objective result and rational inference. Further effort should be taken to reveal the underlying mechanism and develop novel therapeutic pathways for the relevant diseases.

Stromal transdifferentiation drives lipomatosis and induces extensive vascular remodeling in the aging human lymph node.

Lymph node (LN) lipomatosis is a common but rarely discussed phenomenon associated with aging that involves a gradual exchange of the LN parenchyma into adipose tissue. The mechanisms behind these changes and the effects on the LN are unknown. We show that LN lipomatosis starts in the medullary regions of the human LN and link the initiation of lipomatosis to transdifferentiation of LN fibroblasts into adipocytes. The latter is associated with a downregulation of lymphotoxin beta expression. We also show that isolated medullary and CD34+ fibroblasts, in contrast to the reticular cells of the T-cell zone, display an inherently higher sensitivity for adipogenesis. Progression of lipomatosis leads to a gradual loss of the medullary lymphatic network, but at later stages, collecting-like lymphatic vessels are found inside the adipose tissue. The stromal dysregulation includes a dramatic remodeling and dilation of the high endothelial venules associated with reduced density of naïve T-cells. Abnormal clustering of plasma cells is also observed. Thus, LN lipomatosis causes widespread stromal dysfunction with consequences for the immune contexture of the human LN. Our data warrant an increased awareness of LN lipomatosis as a factor contributing to decreased immune functions in the elderly and in disease. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

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.

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.

Modified Ileal Conduit for Pelvic Lipomatosis: Technique Description and Outcome.

INTRODUCTION: The aim of this study was to present the surgical technique and clinical outcomes of modified ileal conduit for pelvic lipomatosis (PL). METHODS: From 2020 to 2022, we prospectively enrolled 9 patients with PL undergoing modified ileal conduit. The patient characteristics, perioperative variables, and follow-up outcomes as well as the description of surgical technique were reported. RESULTS: All 9 patients successfully completed the operation. Two patients had perioperative complications of Clavien-Dindo grade I. The mean operation time and bleeding volumes were 253 ± 51.4 min and 238.9 ± 196.9 mL, with a mean postoperative follow-up time of 13.0 ± 5.6 months. The postoperative 3-month and 1-year creatinine values were significantly decreased versus the preoperative (p = 0.006 and p = 0.024). The postoperative 3-month and 1-year estimated glomerular filtration rate values were significantly increased compared with those before operation (p = 0.0002 and p = 0.018). The separation value of left renal pelvis collection system after operation was significantly reduced compared with preoperative evaluation (p = 0.023 at 3 months and p = 0.042 at 1 year) and so was the right side (p = 0.019 and p = 0.023). CONCLUSION: Modified ileal conduit is safe and feasible for PL. A large sample cohort with long-term follow-up is needed to evaluate the clinical outcomes of PL.

Next generation sequencing aids diagnosis and management in a case of encephalocraniocutaneous lipomatosis.

Encephalocraniocutaneous lipomatosis (ECCL) is a rare neurocutaneous disorder caused by somatic FGFR1 and KRAS variants. It shares significant phenotypic overlap with several closely related disorders caused by mutations in the RAS-MAPK pathway (mosaic RASopathies). We report a diagnostically challenging case of ECCL in which next-generation sequencing of affected tissue identified a pathologic FGFR1 p.K656E variant, thereby establishing a molecular diagnosis. Patients with FGFR1-associated ECCL carry a risk of developing malignant brain tumors; thus, genetic testing of patients with suspected ECCL has important management implications.

Management of Pediatric Patient with Multiple Cranial, Intracranial, and Spinal Manifestations of Penttinen Syndrome: A Case Report.

INTRODUCTION: Penttinen premature aging syndrome is caused by mutations in the PDGFRB gene. We describe the case of a 10-year-old girl with a de novo c.1994T>C variant in PDGFRB who developed multiple cranial, intracranial, and spinal manifestations, including macrocephaly, enlarged convexity subarachnoid spaces crossed by numerous vascularized arachnoid trabecule, hydrocephalus, spinal epidural lipomatosis, a low conus medullaris, calvarial thinning with large anterior fontanelle, and a skull fracture with bilateral epidural hematomas. Vascularized arachnoid granulations, spinal epidural lipomatosis, and low conus medullaris have not been previously described in Penttinen syndrome. CASE PRESENTATION: A female with Penttinen syndrome diagnosed at 9 years of age initially presented as an infant with cutaneous hemangiomas and macrocephaly; imaging showed enlarged convexity subarachnoid spaces. Her convexity subarachnoid spaces continued to expand, leading to subdural shunt placement. At surgery, her enlarged subarachnoid spaces were found to contain numerous abnormally thick, vascularized arachnoid trabecule. Eventually, her subdural shunt failed and her ventricles enlarged, leading to ventricular shunt placement. A large, sunken anterior fontanelle which did not diminish in size led to cranioplasty with a custom implant. She later developed chronic back pain and imaging revealed spinal epidural lipomatosis, a low conus medullaris, and mild scoliosis. At 10 years of age, a fall from a chair resulted in a depressed skull fracture and bilateral parietal epidural hematomas. Emergency left parietal craniotomy was performed for evacuation of the left hematoma, and the patient recovered without complications. Intraoperatively, it was noted that her skull was extremely thin. CONCLUSION: This case report highlights the clinical presentation and multifaceted neurosurgical management of a patient with Penttinen syndrome. The patient exhibited characteristic features including hypertrophic skin lesions, macrocephaly, and skeletal abnormalities. Our patient's vascularized arachnoid trabecule, spinal epidural lipomatosis, and low conus medullaris have not previously been reported in Penttinen syndrome. Her thin skull potentially contributed to the extent of her depressed skull fracture after her backwards fall and predisposed her toward developing epidural hematomas. Patients with Penttinen syndrome can have multiple cranial, intracranial, and spinal manifestations which may need the attention of a neurosurgeon.

A new comprehensive MRI classification and grading system for lumbosacral central and lateral stenosis: clinical application and comparison with previous systems.

PURPOSE: The purpose of our study was to provide a novel schematized and comprehensive classification of causes and severity grading system for lumbosacral stenosis. MATERIALS AND METHODS: The MRI system proposed consisted of a severity grading scale for central and lateral (recess and foramen) stenosis, together with a schematized indication of the main causes of the disease (disc, arthritis, epidural lipomatosis, and their combinations). The system was applied to a cohort of patients from a single Institution in the last 2-years. Two radiologists evaluated all the MRIs to determine intra- and inter-observer reliability according to Cohen Kappa (Kc, for non-ordered categorical variables) and weighted Kappa (Kw, for ordered variables). Two orthopaedic surgeons clinically evaluated all patients and provided a schematic grading system with a central and lateral stenosis clinical score (CS-CS and LS-CS). Associations between ordinals were tested with chi-square test and measured with the Goodman and Kruskal's gamma index (Gi, with 95% confidence interval [95% CI]). Lastly, the most used previous MRI systems were applied, and their performances were compared to the new system proposed. RESULTS: One hundred and twelve patients were included (55 females-mean age 63.3 ± 10.7 years). An almost perfect intra-observer agreement for the assessment of central stenosis, foramen stenosis, and lateral recess stenosis was found (Kw = 0.929, 0.928, and 0.924, respectively). The inter-observer agreement was almost perfect for central stenosis and foramen stenosis and substantial for lateral recess stenosis (Kw = 0.863, 0.834, and 0.633, respectively). Whatever the aetiologies involved in central and lateral stenosis, the intra-observer agreement was perfect (all Kc = 1), whereas the inter-observer agreements were almost perfect for arthritis (Kc = 0.838) and lipomatosis (Kc = 0.955) and substantial for disc (Kc = 0.691) regarding central stenosis. The inter-observer agreement for the causes of lateral stenosis was lower and variable, ranging from perfect (lipomatosis) to fair (disc, Kc = 0.224). The grading system revealed a strong association with CS-CS for both readers, with GI = 0.671 (95% CI 0.535-0.807) and 0.603 (95% CI = 0.457-0.749), respectively. The association with MRI grading and LS-CS was moderate for foraminal stenosis and for the concomitant presence of foraminal and lateral recess stenosis, with Gi = 0.337 (95% CI 0.121-0.554) and Gi = 0.299 (95% CI 0.098-0.500), respectively. A weak association was found between lateral recess grading alone and LS-CS with Gi = 0.102 (95% CI 0.193-0.397). The new grading systems showed higher Gi for associations with clinical symptoms, compared with previous ones, both for CS-CS and LS-CS. CONCLUSIONS: A standardized visual grading system for lumbar spinal stenosis that takes into account all of the major contributing factors-including disc, arthritis, and lipomatosis, for the central canal, lateral recess, and neural foramina could be a useful and practical tool for defining the stenosis, lowering inter-observer variability, and directing the various treatment options.

Vascular Anomalies and Congenital Infiltrating Lipomatosis May Affect Dental Maturation and Development - a Case Control Study.

OBJECTIVE: Vascular anomalies are often associated with hypertrophy and asymmetry of soft tissues and bony structures. The aim of this retrospective cross-sectional radiographic study was to evaluate dental maturation and development in patients with facial vascular anomalies and congenital infiltrating lipomatosis. DESIGN: A sample of 342 patients with different vascular anomalies or congenital infiltrating lipomatosis involving the head and neck area was narrowed down to 31 patients with dental panoramic radiographs taken in the mixed dentition. A control group of 172 age-matched healthy subjects was used. Individual permanent teeth were given a maturation score from 1 to 12 and alveolar eruption stage according to Haavikko et al. 1970. The laterality of the anomaly was noted if applicable. Differences in dental development between affected and unaffected sides were recorded. RESULTS: The study data included both syndromic and non-syndromic vascular anomalies as well as congenital infiltrating lipomatosis and segmental odontomaxillary dysplasia. Teeth on the side of the anomaly were more developed and the eruption of teeth was accelerated with canines, premolars and second molars being most affected. Interestingly all the patients with Sturge-Weber syndrome (n = 4) and infiltrating lipomatosis (n = 2) showed accelerated dental maturation of multiple permanent teeth on the side of the anomaly. Hypodontia, dental root resorption and macrodontia were also found. CONCLUSIONS: Accelerated development and eruption of permanent teeth unilaterally in patients with vascular anomalies and congenital infiltrating lipomatosis may have a significant impact on the developing occlusion and should be thus followed by an orthodontist.

Recurrent PIK3CA H1047R-Mutated Congenital Infiltrative Facial Lipomatosis: A Case Report and Review of Literature.

Congenital infiltrating lipomatosis of the face (CILF) is a rare, congenital, nonhereditary facial overgrowth due to post-zygomatic activating mutations in PIK3CA gene. It is unilateral and involves hypertrophy of both the soft and hard tissue structures on the affected side of the face. This commonly results in early eruption of the teeth, hypertrophy of the facial bones, macroglossia, and proliferation of the parotid gland. Less than 80 cases of CILF have been reported in the literature so far. Treatment modalities include liposuction and surgical excision. However, since the hallmark of CILF is mutation in the PIK3CA gene, PI3K inhibitors may play a therapeutic role in CILF. We report a case of an 8-year-old boy with recurrent CILF of the scalp and nose, with PIK3CA H1047R mutation. We discuss the differential diagnoses, clinical outcomes, and management of this rare entity.

A case of spinal epidural lipomatosis presenting as a stroke mimic.

Here we present the case of a patient with right upper extremity and right lower extremity weakness of a three-day duration, which triggered a stroke evaluation. Ultimately, the diagnosis of spinal epidural lipomatosis (SEL) was made. Non-stroke diagnoses that present with stroke-like symptoms are referred to in the medical literature as stroke mimics. Such cases present with neurological deficits that imitate acute ischemic stroke. The frequency of such presentations occurs in up to 30% of initially suspected stroke. This case illustrates that SEL can present as a stroke mimic. To our knowledge, this is the first description of a presentation in the medical literature of SEL as a stroke mimic.

Facial infiltrating lipomatosis with hemimegalencephaly and lymphatic malformations caused by nonhotspot phosphatidylinositol 3-kinase catalytic subunit alpha mutation.

We report an unusual case of facial infiltrating lipomatosis with hemimegalencephaly and lymphatic malformations. In addition to the clinical data and imaging findings, detection of a heterozygous PIK3CA nonhotspot known pathogenic variant C420R in a facial epidermal nevus provided novel insight into the pathogenic effect of somatic PIK3CA mutations.

Outcome of posterior decompression for spinal epidural lipomatosis.

BACKGROUND: In contrast to osteoligamentous lumbar stenosis (LSS), outcome of surgical treatment for spinal epidural lipomatosis (SEL) is still not well defined. We present risk factors for SEL and clinical long-term outcome data after surgical treatment for patients with pure SEL and a mixed-type pathology with combined SEL and LSS (SEL+LSS) compared to patients with pure LSS. METHODS: From our prospective institutional database, we identified all consecutive patients who were surgically treated for newly diagnosed SEL (n = 31) and SEL+LSS (n = 26) between 2018 and 2022. In addition, a matched control group of patients with pure LSS (n = 30) was compared. Microsurgical treatment aimed for posterior decompression of the spinal canal. Study endpoints were outcome data including clinical symptoms at presentation, MR-morphological analysis, evaluation of pain-free walking distance, pain perception by VAS-N/-R scales, and patient's satisfaction by determination of the Odom score. RESULTS: Patients with osteoligamentous SEL were significantly more likely to suffer from obesity (body mass index (BMI) of 30.2 ± 5.5 kg/m2, p = 0.03), lumbar pain (p = 0.006), and to have received long-term steroid therapy (p = 0.01) compared to patients with SEL+LSS and LSS. In all three groups, posterior decompression of the spinal canal resulted in significant improvement of these symptoms. Patients with SEL had a significant increase in pain-free walking distance during the postoperative course, at discharge, and last follow-up (FU) (p < 0.0001), similar to patients with SEL+LSS and pure LSS. In addition, patients with pure SEL and SEL+LSS had a significant reduction in pain perception, represented by smaller values of VAS-N and -R postoperatively and at FU, similar to patients with pure LSS. In uni- and multivariate analysis, domination of lumbar pain and steroid long-term therapy were significant characteristic risk factors for SEL. CONCLUSIONS: Surgical treatment of pure SEL and SEL+LSS allows significant improvement in pain-free walking distance and pain perception immediately postoperatively and in long-term FU, similar to patients with pure LSS.

Cervical syringomyelia with caudal thoracic epidural lipomatosis: case report and literature review.

Syringomyelia associated with epidural lipomatosis is a rare finding. Only three published cases of epidural lipomatosis associated with syringomyelia exist in the literature.We report the case of a 46-year-old woman who presented with progressive myelopathy over an 18-month period. Imaging revealed significant thoracic spinal cord compression secondary to epidural lipomatosis from T3 to T8 with cephalad cervical syringomyelia extending from C7 to T1. Imaging was unremarkable for Chiari malformation or a craniospinal space-occupying lesion. A T2 to T8 laminoplasty was performed, removing excessive epidural adipose tissue to decompress the thoracic spinal cord. Postoperatively, the patient reported symptom improvement with complete symptom resolution at 3 months. Follow-up imaging at 3-months demonstrated thoracic spinal cord decompression with mild syrinx reduction. At two-year follow-up the patient remained asymptomatic with unchanged imaging.Syringomyelia in the setting epidural lipomatosis is a rare finding.

Small integral membrane protein 10 like 1 downregulation enhances differentiation of adipose progenitor cells.

Small integral membrane protein 10 like 1 (SMIM10L1) was identified by RNA sequencing as the most significantly downregulated gene in Phosphatase and Tensin Homologue (PTEN) knockdown adipose progenitor cells (APCs). PTEN is a tumor suppressor that antagonizes the growth promoting Phosphoinositide 3-kinase (PI3K)/AKT/mechanistic Target of Rapamycin (mTOR) cascade. Diseases caused by germline pathogenic variants in PTEN are summarized as PTEN Hamartoma Tumor Syndrome (PHTS). This overgrowth syndrome is associated with lipoma formation, especially in pediatric patients. The mechanisms underlying this adipose tissue dysfunction remain elusive. We observed that SMIM10L1 downregulation in APCs led to an enhanced adipocyte differentiation in two- and three-dimensional cell culture and increased expression of adipogenesis markers. Furthermore, SMIM10L1 knockdown cells showed a decreased expression of PTEN, pointing to a mutual crosstalk between PTEN and SMIM10L1. In line with these observations, SMIM10L1 knockdown cells showed increased activation of PI3K/AKT/mTOR signaling and concomitantly increased expression of the adipogenic transcription factor SREBP1. We computationally predicted an α-helical structure and membrane association of SMIM10L1. These results support a specific role for SMIM10L1 in regulating adipogenesis, potentially by increasing PI3K/AKT/mTOR signaling, which might be conducive to lipoma formation in pediatric patients with PHTS.

Alpelisib for the treatment of PIK3CA-related head and neck lymphatic malformations and overgrowth.

PURPOSE: PIK3CA-related overgrowth spectrum (PROS) conditions of the head and neck are treatment challenges. Traditionally, these conditions require multiple invasive interventions, with incomplete malformation removal, disfigurement, and possible dysfunction. Use of the PI3K inhibitor alpelisib, previously shown to be effective in PROS, has not been reported in PIK3CA-associated head and neck lymphatic malformations (HNLMs) or facial infiltrating lipomatosis (FIL). We describe prospective treatment of 5 children with PIK3CA-associated HNLMs or head and neck FIL with alpelisib monotherapy. METHODS: A total of 5 children with PIK3CA-associated HNLMs (n = 4) or FIL (n = 1) received alpelisib monotherapy (aged 2-12 years). Treatment response was determined by parental report, clinical evaluation, diary/questionnaire, and standardized clinical photography, measuring facial volume through 3-dimensional photos and magnetic resonance imaging. RESULTS: All participants had reduction in the size of lesion, and all had improvement or resolution of malformation inflammation/pain/bleeding. Common invasive therapy was avoided (ie, tracheotomy). After 6 or more months of alpelisib therapy, facial volume was reduced (range 1%-20%) and magnetic resonance imaging anomaly volume (range 0%-23%) were reduced, and there was improvement in swallowing, upper airway patency, and speech clarity. CONCLUSION: Individuals with head and neck PROS treated with alpelisib had decreased malformation size and locoregional overgrowth, improved function and symptoms, and fewer invasive procedures.

Expending the Phenotypic Spectrum of Encephalocraniocutaneous Lipomatosis: About a Prenatal Case With Complete Autopsy.

Encephalocraniocutaneous lipomatosis (ECCL) or Haberland syndrome (MIM #613001) is a rare congenital neurocutaneous disorder. It is characterized by unilateral ocular, cutaneous and central nervous system anomalies. Key clinical features include hairless fatty tissue nevus of the scalp, choristoma of the eye and intraspinal and intracerebral lipomas. We report one of the first cases diagnosed after termination of pregnancy at 35 WG, including antenatal and post-mortem imaging, complete autopsy and genetic analysis. Prenatal ultrasound and MRI of the third trimester showed multifocal spinal lesions and left lateral cerebral ventriculomegaly with cerebral atrophy. Diagnosis of ECCL was suggested at complete autopsy which revealed nevus psiloliparus of the scalp, facial hamartomas and intracranial and spinal lipomas. In addition, our case also exhibited a cardiac rhabdomyoma and a multicystic dysplastic kidney, both never reported to date in this syndrome. ECCL was confirmed by the identification of a postzygotic FGFR1 mutation. We reviewed the literature and discuss the pathogenesis of this syndrome.

PIK3CA Mutational Analysis in Patients With Macrodactyly.

BACKGROUND: Somatic mosaicism for PIK3CA mutations causes various types of growth disorders, which have been summarized under the term PROS (PIK3CA related overgrowth spectrum). Targeted therapy with PI3K inhibitors seems to be a promising alternative for severe PROS cases. Therefore, PIK3CA testing may become more relevant in the future. METHODS: We report on 14 PROS patients, who had surgery for macrodactyly in the majority of cases. Clinical data were retrieved from the patient's records. Macroscopic and microscopic findings were retrospectively reviewed. Mutational analysis was performed on formalin-fixed paraffin-embedded (FFPE) material. RESULTS: Patient age ranged from 7 months to 35 years. Five patients showed additional anomalies. One patient had CLOVES syndrome. The majority of the specimens were ray resections characterized by hypertrophic fat tissue. Overall, microscopy was subtle. The abnormal adipose tissue showed lobules exhibiting at least focally fibrous septa. In each case, we could detect a PIK3CA mutation. CONCLUSION: Histology of affected fat tissue in PROS patients is overall nonspecific. Therefore, mutational analysis represents the key to the diagnosis, especially in unclear clinical cases. We demonstrated that FFPE material is suitable for PIK3CA testing, which can be considered as basis for targeted therapy with PI3K inhibitors.

Bilateral symmetric lipomatosis of the orbit in Madelung's disease.

Madelung's disease is a rare benign systemic lipomatosis, which often presents in the head, neck and upper trunk regions. The appearance of symmetrical, excessive adipose tissue in the subcutaneous layer is its clinical characteristic. Orbital involvement is unusual with only a few cases reported previously. In this study, we describe the clinical and radiological features of Madelung's disease in the orbits. A 42-year-old man with alcohol addiction presented with chronic bilateral masses of the lower eyelids and proptosis. Computed tomography (CT) scan showed excessive symmetrical non-encapsulated fat deposition in the orbital fat, lower eyelids, salivary glands, subcutaneous tissue along the neck and under the sternocleidomastoid muscles and supraclavicular areas bilaterally. Histopathological study of the orbital masses revealed mature adipose tissue interspersed with thin fibrous septae. He developed recurrent lipomatosis 1 year after surgical excision.

Insights on Lipomatosis after Platinum-Based Chemotherapy Use in Pediatric Oncology: A Case Report.

Agents of platinum-based chemotherapy, such as cisplatin or carboplatin, are used in the treatment of a wide range of malignancies that affect children, such as brain tumors, osteosarcoma, neuroblastoma, hepatoblastoma, and germ cell tumors (GCTs). The Cyclophosphamide Equivalent Dose (CED) calculator for reproductive risk does not take platinum-based chemotherapy into account, despite the fact that it accounts for the majority of chemotherapy medications that are typically administered for pediatric GCTs. As a result, exposure to platinum-based drugs throughout infancy can have predictable long-term effects such as infertility, as well as other rare encounters such as lipoma formation and lipomatosis. Lipomas are the most prevalent benign soft tissue tumor subtype. They may be either solitary entities or engaged in multiple lipomatosis, which may have a familial origin or be an acquired disorder. Chemotherapy is a possible cause of lipomatosis. Chemotherapy based on cisplatin has been linked to a variety of long-term consequences, including kidney damage, neurotoxicity, and pulmonary toxicity, and may even create secondary cancers. However, lipoma development is known to occur in fewer than 1 in 100 individuals, and only a few examples of multiple cutaneous lipomatosis triggered by this therapy have been documented. Here we present a very rare case of lipomatosis in a pediatric patient with GCT under cisplatin therapy, which might be the third report of this kind affecting children.