Ultrasound performance in pediatric deep soft-tissue tumor characterization.

This study investigated the performance of ultrasonography in diagnosing deep soft-tissue tumors and tumor-like lesions in children with histological results. Demographic information and ultrasound characteristics of benign and malignant masses were statistically analyzed. Three radiologists (Radiologists 1, 2, and 3) independently reviewed the ultrasonography studies while being blinded to the medical history and other imaging findings. The 82 lesions included in the study were histopathologically classified as malignant (n = 25) or benign (n = 57). No statistically significant differences were observed between the benign and malignant subgroups regarding age (p = 0.059), sex (p = 1.0), disease course (p = 0.812), presence or absence of symptoms (p = 0.534), maximum diameter (p = 0.359), margin (p = 1.0), calcification (p = 0.057), or blood Adler type (p = 0.563). However, statistically significant differences were observed between the benign and malignant subgroups in terms of isolated or Multiple occurrences (p < 0.001), history of malignancy (p < 0.001), shape (p < 0.001), and echogenicity (p < 0.001). Parameters such as tumor shape (p = 0.042, OR = 6.222), single or multiple occurrences (p = 0.008, OR = 17.000), and history of malignancy (p = 0.038, OR = 13.962) were identified as independent predictors of benign and malignant tumors. The diagnostic sensitivities evaluated by the three radiologists were 68.0%, 72.0%, 96.0%, respectively, while the specificities were 77.2%, 82.5%, 77.2%, respectively. Ultrasound demonstrates good performance in the diagnosis of benign deep lesions such as hemangiomas/venous malformation and adipocytic tumors. Multiple irregular morphologies and a history of malignancy were identified as independent risk factors for malignant masses. The experience of radiologists in recognizing specific tumors is important. Careful attention should be paid to masses with ambiguous ultrasound features, as well as small lesions.

Differences in MRI findings of superficial spindle cell lipoma and atypical lipomatous tumor/well-differentiated liposarcoma.

OBJECTIVE: This study aimed to evaluate the efficacy of using MRI findings to differentiate superficial spindle cell lipomas (SCLs) from atypical lipomatous tumor/well-differentiated liposarcomas (ALT/WDLs). METHODS: This study included 12 patients with histopathologically proven superficial SCLs and 11 with ALT/WDLs. MRI findings for both pathologies were retrospectively reviewed and compared between the two pathologies. RESULTS: The neck, upper back, and shoulder regions were more frequent locations of SCLs than of ALT/WDLs (100% vs 55%, p < 0.05), whereas no significant differences were observed in age and sex. The median maximum diameter of the lesion was smaller in SCLs than in ALT/WDLs (44 mm [interquartile range (IQR): 35-63] vs 102 mm [IQR: 86-119], p < 0.05). On T 1 weighted images, non-fatty area was more frequently observed in SCLs than in ALT/WDLs (73% vs 25%, p < 0.05), and the median rate of non-fatty area was larger in SCLs than in ALT/WDLs (7.5% [IQR: 1.0-53] vs 0% [IQR: 0-0.2], p < 0.05). On fat-suppressed T 2 weighted images, a solid hyperintense area was more frequently observed in SCLs than in ALT/WDLs (83% vs 27%, p < 0.05). CONCLUSION: The maximum diameter, non-fatty area on T 1 weighted images, and solid hyperintense area on fat-suppressed T 2 weighted images were useful imaging features for differentiating superficial SCLs from ALT/WDLs. ADVANCES IN KNOWLEDGE: In superficial lipomatous tumors, small tumor size and non-fatty solid area were valuable findings for diagnosing SCLs.

Prediction of lipomatous soft tissue malignancy on MRI: comparison between machine learning applied to radiomics and deep learning.

OBJECTIVES: Malignancy of lipomatous soft-tissue tumours diagnosis is suspected on magnetic resonance imaging (MRI) and requires a biopsy. The aim of this study is to compare the performances of MRI radiomic machine learning (ML) analysis with deep learning (DL) to predict malignancy in patients with lipomas oratypical lipomatous tumours. METHODS: Cohort include 145 patients affected by lipomatous soft tissue tumours with histology and fat-suppressed gadolinium contrast-enhanced T1-weighted MRI pulse sequence. Images were collected between 2010 and 2019 over 78 centres with non-uniform protocols (three different magnetic field strengths (1.0, 1.5 and 3.0 T) on 16 MR systems commercialised by four vendors (General Electric, Siemens, Philips, Toshiba)). Two approaches have been compared: (i) ML from radiomic features with and without batch correction; and (ii) DL from images. Performances were assessed using 10 cross-validation folds from a test set and next in external validation data. RESULTS: The best DL model was obtained using ResNet50 (resulting into an area under the curve (AUC) of 0.87 ± 0.11 (95% CI 0.65-1). For ML/radiomics, performances reached AUCs equal to 0.83 ± 0.12 (95% CI 0.59-1) and 0.99 ± 0.02 (95% CI 0.95-1) on test cohort using gradient boosting without and with batch effect correction, respectively. On the external cohort, the AUC of the gradient boosting model was equal to 0.80 and for an optimised decision threshold sensitivity and specificity were equal to 100% and 32% respectively. CONCLUSIONS: In this context of limited observations, batch-effect corrected ML/radiomics approaches outperformed DL-based models.

[Lipoblastoma-like tumor of the vulva: A case report and review of the literature]. / Tumor vulvar similar a lipoblastoma: descripción de un nuevo caso y revisión de la literatura.

Lipoblastoma-like tumor of the vulva (LBLTV) was first described as a benign mesenchymal neoplasia; it was not recognized as a separate diagnosis in the 2013 WHO classification of soft-tissue tumors. To date, only 19 cases have been reported. LBLTV differential diagnosis includes other tumors of the vulvoperineal region and tumors with adipocytic differentiation, most of which are benign and thus a misdiagnosis has few clinical consequences. However, LBLTV may also mimic some aggressive lipomatous neoplasms. We describe a case of LBLTV in a 28 year-old woman and review the literature.

MDM2 analysis in the management of benign lipomas versus atypical lipomatous tumors/well-differentiated liposarcomas: A useful prognostication tool?

INTRODUCTION: Well-differentiated liposarcomas (WDLS) are low-grade lipomatous tumors with low malignant potential. Previous review identified controversy on whether upfront wide resection is necessary when they occur on the trunk or the extremities. MDM2 amplification is a genetic mutation typically present in WDLS and absent in benign lipomas (BL). We aimed to study the influence of MDM2 status on the management/recurrences of lipomatous tumors in the trunk or the extremities. METHODS: All patients with lipomatous tumors with MDM2 testing in the Province of Alberta between 2015 and 2020 were identified from the Cancer Cytogenetics Laboratory dataset. High grade sarcomas, retroperitoneal, head/neck, or groin tumors were excluded. Primary outcome measures including MDM2 status, surgical margin, local recurrence, reoperation rate, dedifferentiation, and metastasis were abstracted from chart review. Descriptive statistics were used to analyse treatment patterns and recurrence rates according to MDM2 status. RESULTS: Total of 764 charts were retrieved, and 282 were included for analysis. 33 showed MDM2 amplification (11.7%), and 2 of them had local recurrence (6.1%). Two patients with recurrent tumors underwent limb-salvaging reoperation (6.1%), but no dedifferentiation or metastasis was seen. CONCLUSION: Findings in this study confirmed the benign behaviour of truncal/extremities lipomas with no MDM2 amplification. Given we found a 6.1% recurrence rate in MDM2 amplified tumors, a prolong follow up of this subset of patients is warranted. Overall, regardless of the MDM2 status, we believe an initial marginal excision is a reasonable surgical approach as recurrences are rare, and they can be managed with re-excision when they occur.

What's new in adipocytic neoplasia?

Adipocytic tumours are among the most common mesenchymal neoplasms, and constitute a clinically, biologically and pathologically diverse group. Their wide histological spectrum and frequent morphological overlap have made classification and diagnosis challenging, with accurate classification being critical because of the considerable differences in prognosis and management between morphologically overlapping neoplasms. Ongoing advances in molecular genetics have aided significantly to our understanding of these neoplasms, with continuing evolution in classification. This review summarises the new developments in benign and malignant adipocytic neoplasms, with discussion of new entities and genetic findings, updates on the clinical and morphological spectrum, and the use of diagnostic immunohistochemistry and molecular markers in the differential diagnosis.

Update of pediatric soft tissue tumors with review of conventional MRI appearance-part 1: tumor-like lesions, adipocytic tumors, fibroblastic and myofibroblastic tumors, and perivascular tumors.

There are numerous soft tissue tumors and tumor-like conditions in the pediatric population. Magnetic resonance imaging is the most useful modality for imaging these lesions. Although certain soft tissue lesions exhibit magnetic resonance features characteristic of a specific diagnosis, most lesions are indeterminate, and a biopsy is necessary for diagnosis. We provide a detailed update of soft tissue tumors and tumor-like conditions that occur in the pediatric population, emphasizing each lesion's conventional magnetic resonance imaging appearance, using the recently released 5th edition of the World Health Organization Classification of Soft Tissue and Bone Tumors as a guide. In part one of this review, pediatric tumor-like lesions, adipocytic tumors, fibroblastic and myofibroblastic tumors, and perivascular tumors are discussed. In part two, vascular lesions, fibrohistiocytic tumors, muscle tumors, peripheral nerve sheath tumors, tumors of uncertain differentiation, and undifferentiated small round cell sarcomas are reviewed. Per the convention of the WHO, these lesions involve the connective, subcutaneous, and other non-parenchymatous-organ soft tissues, as well as the peripheral and autonomic nervous system.

Cardiac lipoblastoma of the pulmonary valve: A rare tumor in an unusual location.

BACKGROUD: Lipoblastoma is a rare, benign, fatty tissue tumour tumor that occurs in infancy and early childhood. Intrathoracic and mediastinal involvement of this tumour is rare, and an intracardiac location is even rarer. AIMS: To report the first case of a lipoblastoma in the pulmonary valve. MATERIALS: In this study, we report the case of a 15-month-old girl who presented with a tumour in the pulmonary valve. RESULTS: The tumour was completely resected macroscopically. Histological examination of the lesion confirmed the diagnosis of lipoblastoma. DISCUSSION: Most primary cardiac tumours are benign in the sense they are not invasive. However, benign tumours maintain the potential for serious illness related to significant haemodynamic compromise or life-threatening dysrhythmias. Due to the association of lipoblastoma with other heart malformations, preoperative diagnosis remains challenging. CONCLUSION: Tumours on the heart valve are more likely to cause haemodynamic disturbances. Complete resection yields an excellent prognosis.

Cross-flow microfiltration for isolation, selective capture and release of liposarcoma extracellular vesicles.

We present a resource-efficient approach to fabricate and operate a micro-nanofluidic device that uses cross-flow filtration to isolate and capture liposarcoma derived extracellular vesicles (EVs). The isolated extracellular vesicles were captured using EV-specific protein markers to obtain vesicle enriched media, which was then eluted for further analysis. Therefore, the micro-nanofluidic device integrates the unit operations of size-based separation with CD63 antibody immunoaffinity-based capture of extracellular vesicles in the same device to evaluate EV-cargo content for liposarcoma. The eluted media collected showed ∼76% extracellular vesicle recovery from the liposarcoma cell conditioned media and ∼32% extracellular vesicle recovery from dedifferentiated liposarcoma patient serum when compared against state-of-art extracellular vesicle isolation and subsequent quantification by ultracentrifugation. The results reported here also show a five-fold increase in amount of critical liposarcoma-relevant extracellular vesicle cargo obtained in 30 min presenting a significant advance over existing state-of-art.

Image-Guided Core Needle Biopsy of Adipocytic Tumors: Diagnostic Accuracy and Concordance With Final Surgical Pathology.

OBJECTIVE. Diagnostic accuracy of core needle biopsy (CNB) for adipocytic tumors can be low because of sampling error from these often large, heterogeneous lesions. The purpose of this study was to evaluate the diagnostic accuracy of image-guided CNB for various adipocytic tumors in comparison with excisional pathology. MATERIALS AND METHODS. Adipocytic tumors (n = 77) of all adult patients undergoing image-guided CNB and subsequent surgical excision of an adipocytic tumor at a tertiary referral center between 2005 and 2019 were studied. To determine concordance, we compared pathologic diagnoses based on CNB to the reference standard of pathologic diagnoses after surgical excision. Tumors were divided into three categories (benign lipomatous tumors [lipoma, lipoma variants, hibernomas], atypical lipomatous tumors [ALTs] or well-differentiated liposarcomas [WDLs], and higher grade liposarcomas [myxoid, dedifferentiated, pleomorphic]), and diagnostic accuracy was calculated for each category. RESULTS. In 73 of 77 adipocytic tumors (95%), diagnosis at CNB and diagnosis after excision were concordant. Accuracy of diagnosis was poorer for ALTs and WDLs than for the other two categories, and the difference was statistically significant (p < .002). For the 29 benign lipomatous tumors and the 27 higher-grade liposarcomas, diagnoses at CNB and after excision were concordant in all cases (100%). Seventeen of the 21 tumors (81%) diagnosed as ALTs or WDLs at CNB had a concordant diagnosis after excision; four of the 21 were upgraded (dedifferentiated liposarcoma, n = 3; myxoid liposarcoma, n = 1). CONCLUSION. CNB provides high diagnostic accuracy for adipocytic tumors, particularly for benign lipomatous tumors and higher grade liposarcomas. However, though still high at 81%, diagnostic accuracy of CNB is not as high for tumors diagnosed as ALTs or WDLs. Awareness of this limitation is important when determining management, particularly of cases of ALT or WDL for which surgery is not planned.

Multiexponential T2 relaxometry of benign and malignant adipocytic tumours.

BACKGROUND: We investigated a recently proposed multiexponential (Mexp) fitting method applied to T2 relaxometry magnetic resonance imaging (MRI) data of benign and malignant adipocytic tumours and healthy subcutaneous fat. We studied the T2 distributions of the different tissue types and calculated statistical metrics to differentiate benign and malignant tumours. METHODS: Twenty-four patients with primary benign and malignant adipocytic tumours prospectively underwent 1.5-T MRI with a single-slice T2 relaxometry (Carr-Purcell-Meiboom-Gill sequence, 25 echoes) prior to surgical excision and histopathological assessment. The proposed method adaptively chooses a monoexponential or biexponential model on a voxel basis based on the adjusted R2 goodness of fit criterion. Linear regression was applied on the statistical metrics derived from the T2 distributions for the classification. RESULTS: Healthy subcutaneous fat and benign lipoma were better described by biexponential fitting with a monoexponential and biexponential prevalence of 0.0/100% and 0.2/99.8% respectively. Well-differentiated liposarcomas exhibit 17.6% monoexponential and 82.4% biexponential behaviour, while more aggressive liposarcomas show larger degree of monoexponential behaviour. The monoexponential/biexponential prevalence was 47.6/52.4% for myxoid tumours, 52.8/47.2% for poorly differentiated parts of dedifferentiated liposarcomas, and 24.9/75.1% pleomorphic liposarcomas. The percentage monoexponential or biexponential model prevalence per patient was the best classifier distinguishing between malignant and benign adipocytic tumours with a 0.81 sensitivity and a 1.00 specificity. CONCLUSIONS: Healthy adipose tissue and benign lipomas showed a pure biexponential behaviour with similar T2 distributions, while decreased adipocytic cell differentiation characterising aggressive neoplasms was associated with an increased rate of monoexponential decay curves, opening a perspective adipocytic tumour classification.

[Lipid cell variant urothelial carcinoma of the renal pelvis. A case report and literature review]. / Carcinoma urotelial lipoideo de pelvis renal. Aportación de un nuevo caso y revisión de la literatura de esta variante de carcinoma urotelial.

There are many variants of urothelial carcinoma. One of the most infrequent is formed by cells with a lipid content and an adipose tissue appearance. Only 43 cases have been reported in the bladder, 2 in the renal pelvis and 1 case in the ureter. We present a third case in the renal pelvis; the patient is alive and free of disease 103 months post diagnosis.

Lipomatous hypertrophy of the interventricular septum.

BACKGROUND AND AIMS: Lipomatous hypertrophy of the interatrial septum is an uncommon type of cardiac adipose tumor. It is extremely rare for these lesions to be located in the interventricular septum. METHODS: We report this case of incidentally diagnosed lipomatous hypertrophy of the interventricular septum with right ventricular outflow obstruction which caused minimal symptoms and Wolff-Parkinson-White pattern on EKG. CONCLUSION: We also discuss the diagnosis and management of this condition.

A Diagnostic Dilemma of a Subcutaneous Hibernoma: Case Report.

BACKGROUND Subcutaneous lipomatous lesions are commonly encountered in clinical practice. Hibernoma is a rare subtype of the benign lipomatous tumor, representing 1% of all types. It poses a challenge due to the difficulty of differentiating it from atypical lipomatous lesions and liposarcomas, which may lead to possible inappropriate diagnosis and management. CASE REPORT We report a case of a 33-year-old male who presented with a right upper thigh swelling noticed some time prior to presentation that had started increasing in size prior to his presentation. The magnetic resonance imaging (MRI) was unable to rule out atypical lipomatous tumor and liposarcoma. An ultrasound-guided biopsy gave a diagnosis of hibernoma. The patient underwent a wide local excision, which confirmed the diagnosis of hibernoma. At the 3-year follow-up, there was no evidence of local recurrence. CONCLUSIONS Hibernoma has been reported in the literature to be discovered incidentally by radiological imaging done for other causes. However, hibernomas raise a diagnostic challenge because in most imaging modalities they are indistinguishable from other malignant tumors. A wide local excision with negative margins is key to resolving the diagnostic dilemma that a hibernoma presents, as it will provide a definitive diagnosis differentiating it from other lipomatous lesions and prevent any future recurrence. Caution is advised when dealing with lipomatous lesions, as they often overlap with malignancy. Furthermore, an MRI should be done for any subcutaneous lesion that is larger than 5 cm or shows recent growth. A biopsy can resolve the diagnostic dilemma with caution to the hypervascularity of such tumors.

Surgical management of truncal and extremities atypical lipomatous tumors/well-differentiated liposarcoma: A systematic review of the literature.

INTRODUCTION: Atypical lipomatous tumors or well-differentiated liposarcomas (ALT/WDLS) are low-grade soft tissue tumors that are commonly located on the trunk and extremities. There is no consensus on the best surgical approach for ALT/WDLS. METHODS: A systematic literature review of PubMed, Medline, Embase, Scopus, and google scholar was performed. All published studies on trunk or extremities ALT/WDLS with reported outcome data were considered and independently screened for inclusion by at least two of the authors. RESULTS: A total of eighteen studies comprising 793 patients with ALT/WDLS were included. 580 patients underwent marginal excision, with local recurrence observed in 69 (11.9%). 213 patients underwent wide excision with local recurrence in 7(3.3%). Recurrent tumors were successfully re-resected with marginal or wide excision. Dedifferentiation was confirmed in 9 patients (1.1%), and a distant pulmonary metastasis in 1 patient (0.1%). DISCUSSION: Marginal excision of truncal or extremities ALT/WDLS results in a slightly higher local recurrence rate. However, recurrences are almost always amenable to re-resection. The findings support the use of marginal excision for truncal or extremities ALT/WDLS.

Compression-induced dedifferentiation of adipocytes promotes tumor progression.

Dysregulated physical stresses are generated during tumorigenesis that affect the surrounding compliant tissues including adipocytes. However, the effect of physical stressors on the behavior of adipocytes and their cross-talk with tumor cells remain elusive. Here, we demonstrate that compression of cells, resulting from various types of physical stresses, can induce dedifferentiation of adipocytes via mechanically activating Wnt/ß-catenin signaling. The compression-induced dedifferentiated adipocytes (CiDAs) have a distinct transcriptome profile, long-term self-renewal, and serial clonogenicity, but do not form teratomas. We then show that CiDAs notably enhance human mammary adenocarcinoma proliferation both in vitro and in a xenograft model, owing to myofibrogenesis of CiDAs in the tumor-conditioned environment. Collectively, our results highlight unique physical interplay in the tumor ecosystem; tumor-induced physical stresses stimulate de novo generation of CiDAs, which feedback to tumor growth.

From head and neck lipoma to liposarcoma: a wide spectrum of differential diagnoses and their therapeutic implications.

PURPOSE OF REVIEW: To overview the array of differential diagnoses among lipomatous tumours of the head and neck with special focus on their evaluation, three-dimensional assessment, and their available treatments. RECENT FINDINGS: The head and neck is an infrequent localization for lipomatous tumours, even though they represent the most common mesenchymal lesions. Lipoma, spindle cell/pleomorphic lipoma (SC/PL), atypical lipomatous tumour/well differentiated liposarcoma (ALT/WDLPS), de-differentiated liposarcoma (DDLPS), myxoid liposarcoma (MLPS), and pleomorphic liposarcoma (PLPS) are the most distinctive histotypes. Lipoma and SC/PL present alterations of chromosomes 12 and 13, ALT/WDLPS and DDLPS both show the Mouse Double Minute 2 amplification, whereas MLPS presents a CHOP gene fusion. Diagnosis of PLPS is purely morphological as there is no pathognomonic genetic alteration identified to date. Radiological assessment can be challenging for the presence of nonadipose components within the lesion. Surgery is the mainstay of treatment, even though achieving true radicality in terms of a large cuff of healthy tissue surrounding the tumour is not always realistic in the head and neck. Adjuvant radiation, eventually in combination with systemic chemotherapy, has been shown to improve overall survival in patients with positive margins, high-grade, deep, and more than 5 cm lesions. Further studies should be aimed at the evaluation of the role of hadron therapy, as well as targeted drugs against overexpressed proteins. SUMMARY: Adequate differential diagnosis of the histotypes collected under the umbrella term of head and neck lipomatous tumours plays a fundamental role in treatment and follow-up of these lesions and requires specific expertise with referral to high-volume centres.

Genome sequencing analysis of a family with a child displaying severe abdominal distention and recurrent hypoglycemia.

BACKGROUND: Germline mutations in PTEN are associated with the PTEN hamartoma tumor syndrome (PHTS), an umbrella term used to describe a spectrum of autosomal-dominant disorders characterized by variable phenotypic manifestations associated with cell or tissue overgrowth. We report a boy who developed severe progressive abdominal distention due to a dramatic adipose mass from the age of 7 months and developed recurrent hypoinsulinemic hypoglycemia that led to seizures at the age of 4 years. METHODS: Trio-based whole-genome sequencing was performed by using blood DNA from the child and his parents. The possible pathogenic variants were verified by Sanger sequencing. Functional characterization of the identified variant was completed by western blot. RESULTS: The child inherited a single-nucleotide deletion NM_000314.6:c.849delA (p.Glu284Argfs) in the tumor suppressor gene PTEN from his father. The paternal family members have a history of cancer. It is conceivable that PTEN loss-of-function induced the adipose tumor growth and hypoglycemia, although the proband did not meet the usual diagnosis criteria of Cowden syndrome or Bannayan-Riley-Ruvalcaba syndrome that are characterized by germline mutations of PTEN. CONCLUSION: This case underlines the variability of phenotypes associated with PTEN germline mutations and provides useful information for diagnosis and genetic counseling of PTEN-related diseases for pediatric patients.