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.

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.

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.

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.

Adipocytic tumors in Children: A contemporary review.

Adipocytic neoplasms in the pediatric population demonstrate a different histologic spectrum and frequency than in adults. The vast majority of these tumors are benign, with lipoma being the most common entity. The identification of signature cytogenetic and molecular alterations for certain lesions, such as PLAG1 gene rearrangement in lipoblastoma and FUS-DDIT3 fusion in myxoid liposarcoma, has been helpful in approaching these neoplasms and aiding in confirming the diagnosis. Furthermore, it is important for pathologists to recognize that adipocytic neoplasms may be associated with different syndromes with potential impact in managing such patients. This review provides a summary of the clinical pictures, histologic characteristics, molecular alterations, differential diagnoses, and syndromic associations of the commonly encountered fatty tumors in children.

A contemporary review of myxoid adipocytic tumors.

Myxoid adipocytic tumors encompass a broad heterogeneous group of benign and malignant adipocytic tumors, which are typically myxoid (e.g. myxoid liposarcoma, lipoblastoma and lipoblastoma-like tumor of the vulva) or may occasionally appear predominantly myxoid (e.g. pleomorphic liposarcoma, atypical lipomatous tumor, dedifferentiated liposarcoma, chondroid lipoma, spindle cell/pleomorphic lipoma, atypical spindle cell lipomatous tumor and atypical pleomorphic lipomatous tumor). There have been significant advances in recent years in classification and understanding the pathogenesis of adipocytic tumors, based on the correlation of histologic, immunohistochemical, and cytogenetic/molecular findings. Despite these advances, the morphologic diagnosis and accurate classification of a myxoid adipocytic tumor can be challenging due to major morphologic overlap between myxoid adipocytic and non-adipocytic tumors. This article will provide a review on the currently known morphological, immunohistochemical and molecular features of myxoid adipocytic tumors and their differential diagnosis.

Molecular updates in adipocytic neoplasms✰.

Adipocytic neoplasms include a diversity of both benign tumors (lipomas) and malignancies (liposarcomas), and each tumor type is characterized by its own unique molecular alterations driving tumorigenesis. Work over the past 30 years has established the diagnostic utility of several of these characteristic molecular alterations (e.g. MDM2 amplification in well- and dedifferentiated liposarcoma, FUS/EWSR1-DDIT3 gene fusions in myxoid liposarcoma, RB1 loss in spindle cell/pleomorphic lipoma). More recent studies have focused on additional molecular alterations which may have therapeutic or prognostic impact. This review will summarize several of the important molecular findings in adipocytic tumors that have been described over the past 10 years.

[Tumors with predominantly adipocytic morphology]. / Tumoren mit prädominant adipozytärer Morphologie.

More than 20% of soft-tissue tumors belong to the group of adipocytic neoplasms. Difficulties may occur in the differential diagnosis of lipomas versus atypical lipomatous tumors/well-differentiated liposarcomas, in the distinction of dedifferentiated liposarcomas from other soft-tissue sarcoma entities and in the detailed subtyping of liposarcomas. Especially in biopsies, the correct diagnosis and grading may be hampered due to limited tissue. Because of the ever-increasing molecular-pathological knowledge of soft-tissue tumors and the rising distribution of molecular diagnostic assays in institutes of pathology, differential diagnosis has been facilitated, as more than 90% of adipocytic tumors carry more or less specific genomic alterations. In the following, the most important subtypes of adipocytic tumors are described morphologically and genomically.

Loss of the tumour suppressor gene AIP mediates the browning of human brown fat tumours.

Human brown fat tumours (hibernomas) show concomitant loss of the tumour suppressor genes MEN1 and AIP. We hypothesized that the brown fat phenotype is attributable to these mutations. Accordingly, in this study, we demonstrate that silencing of AIP in human brown preadipocytic and white fat cell lines results in the induction of the brown fat marker UCP1. In human adipocytic tumours, loss of MEN1 was found both in white (one of 51 lipomas) and in brown fat tumours. In contrast, concurrent loss of AIP was always accompanied by a brown fat morphology. We conclude that this white-to-brown phenotype switch in brown fat tumours is mediated by the loss of AIP. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Quantification of fat content in lipid-rich myxoid liposarcomas with MRI: a single-center experience with survival analysis.

OBJECTIVE: To determine the fat content of myxoid liposarcomas (MLS) on MRI and to identify any association between lipid content and survival. MATERIALS AND METHODS: The fat percentage of MLS diagnosed between January 2006 and December 2016 at a single institution was assessed by two radiologists on preoperative MR images. A Cox proportional hazard model was used to determine any association between tumor fat percentage and survival time. Tumor fat percentage was the single predictor in the model. A significance level of 0.05 was used. The Kaplan-Meier estimator was also used to provide a nonparametric estimate of the survivor function within the entire sample and within two patient subgroups consists of lipid-rich and lipid-poor tumors. Lipid-rich tumors were defined as any tumors showing more than 20% of fat on MRI. A 20% cutoff was determined arbitrarily. RESULTS: Of the 43 cases identified through retrospective review, 8 tumors demonstrated ≥10% fat on MRI, and 4 tumors demonstrated ≥20% fat (highest fat percentage, 38%). There was no significant survival difference between patients with high tumor fat, which was defined as ≥20% fat, compared with those with little to no tumor fat. CONCLUSION: Myxoid liposarcomas may demonstrate a higher fat content on MRI than has previously been reported in the literature. Increased tumor fat percentage in lipid-rich tumors was not found to be associated with increased risk of death. Radiologists must be aware of the existence of MLS lesions with higher fat content.

FXYD5 (dysadherin) may mediate metastatic progression through regulation of the ß-Na+-K+-ATPase subunit in the 4T1 mouse breast cancer model.

FXYD5 is a Na+-K+-ATPase regulator, expressed in a variety of normal epithelia. In parallel, it has been found to be associated with several types of cancer and effect lethal outcome by promoting metastasis. However, the molecular mechanism underlying FXYD5 mediated invasion has not yet been identified. In this study, using in vivo 4T1 murine breast cancer model, we found that FXYD5-specific shRNA significantly inhibited lung cancer metastasis, without having a substantial effect on primary tumor growth. Our study reveals that FXYD5 participates in multiple stages of metastatic development and exhibits more than one mode of E-cadherin regulation. We provide the first evidence that FXYD5-related morphological changes are mediated through its interaction with Na+-K+-ATPase. Experiments in cultured 4T1 cells have indicated that FXYD5 expression may downregulate the ß1 isoform of the pump. This behavior could have implications on both transcellular interactions and intracellular events. Further studies suggest that differential localization of the adaptor protein Annexin A2 in FXYD5-expressing cells may correlate with matrix metalloproteinase 9 secretion and adhesion changes in 4T1 wild-type cells.

A diagnostic approach to popliteal fossa masses.

There is a myriad of potential mass lesions that occur in the popliteal fossa, which present as palpable masses or are found incidentally on imaging. With a thorough knowledge and understanding of the appearances and locations of these different entities, one can narrow the differential diagnoses in the majority of cases. This will eliminate unnecessary additional investigations and enable a more rapid management. We present a review of frequently encountered and less common entities using an anatomical sieve, with the aim of providing a diagnostic approach to popliteal fossa masses.

Intraoperative optical coherence tomography for soft tissue sarcoma differentiation and margin identification.

BACKGROUND AND OBJECTIVE: Sarcomas are rare but highly aggressive tumors, and local recurrence after surgical excision can occur in up to 50% cases. Therefore, there is a strong clinical need for accurate tissue differentiation and margin assessment to reduce incomplete resection and local recurrence. The purpose of this study was to investigate the use of optical coherence tomography (OCT) and a novel image texture-based processing algorithm to differentiate sarcoma from muscle and adipose tissue. STUDY DESIGN AND METHODS: In this study, tumor margin delineation in 19 feline and canine veterinary patients was achieved with intraoperative OCT to help validate tumor resection. While differentiation of lower-scattering adipose tissue from higher-scattering muscle and tumor tissue was relatively straightforward, it was more challenging to distinguish between dense highly scattering muscle and tumor tissue types based on scattering intensity and microstructural features alone. To improve tissue-type differentiation in a more objective and automated manner, three descriptive statistical metrics, namely the coefficient of variation (CV), standard deviation (STD), and Range, were implemented in a custom algorithm applied to the OCT images. RESULTS: Over 22,800 OCT images were collected intraoperatively from over 38 sites on 19 ex vivo tissue specimens removed during sarcoma surgeries. Following the generation of an initial set of OCT images correlated with standard hematoxylin and eosin-stained histopathology, over 760 images were subsequently used for automated analysis. Using texture-based image processing metrics, OCT images of sarcoma, muscle, and adipose tissue were all found to be statistically different from one another (P ≤ 0.001). CONCLUSION: These results demonstrate the potential of using intraoperative OCT, along with an automated tissue differentiation algorithm, as a guidance tool for soft tissue sarcoma margin delineation in the operating room. Lasers Surg. Med. 49:240-248, 2017. © 2017 Wiley Periodicals, Inc.

A case of Trousseau syndrome associated with a mucosa-associated lymphoid tissue lymphoma disseminated to the mesenteric adipose tissue.

A 66-year-old man with recurrent stroke within a short period of time was referred to our department from the neurology department to rule out any malignancy. An endoscopic examination revealed a white depressed lesion in the body of the stomach, and computed tomography revealed a high-density area in the mesentery around the stomach. A mucosa-associated lymphoid tissue (MALT) lymphoma was detected from both the stomach biopsy and resected mesenteric specimen. Systemic chemotherapy was administered for the MALT lymphoma (Lugano classification stage IV). Cerebral infarction did not occur after the treatment. We concluded that Trousseau syndrome associated with the MALT lymphoma disseminated to the mesenteric adipose tissue. A MALT lymphoma has a small probability of occurring in Trousseau syndrome.

Fat-containing soft-tissue masses in children.

The diagnosis of soft-tissue masses in children can be difficult because of the frequently nonspecific clinical and imaging characteristics of these lesions. However key findings on imaging can aid in diagnosis. The identification of macroscopic fat within a soft-tissue mass narrows the differential diagnosis considerably and suggests a high likelihood of a benign etiology in children. Fat can be difficult to detect with sonography because of the variable appearance of fat using this modality. Fat is easier to recognize using MRI, particularly with the aid of fat-suppression techniques. Although a large portion of fat-containing masses in children are adipocytic tumors, a variety of other tumors and mass-like conditions that contain fat should be considered by the radiologist confronted with a fat-containing mass in a child. In this article we review the sonographic and MRI findings in the most relevant fat-containing soft-tissue masses in the pediatric age group, including adipocytic tumors (lipoma, angiolipoma, lipomatosis, lipoblastoma, lipomatosis of nerve, and liposarcoma); fibroblastic/myofibroblastic tumors (fibrous hamartoma of infancy and lipofibromatosis); vascular anomalies (involuting hemangioma, intramuscular capillary hemangioma, phosphate and tensin homologue (PTEN) hamartoma of soft tissue, fibro-adipose vascular anomaly), and other miscellaneous entities, such as fat necrosis and epigastric hernia.

Subcutaneous panniculitis-like T-cell lymphoma: Pediatric case series demonstrating heterogeneous presentation and option for watchful waiting.

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) and primary cutaneous gamma delta T-cell lymphoma (PCGD-TCL) were initially both classified as subcutaneous panniculitis-like T-cell lymphoma. In 2008, SPTCL with alpha-beta T-cell receptor subtype was separated from primary cutaneous gamma delta T-cell lymphomas (PCGD-TCL). We report four pediatric cases that demonstrate the heterogeneity of each disease and show that PCGD-TCL in children can have an indolent course, whereas SPTCL can behave aggressively. Three patients had spontaneous, durable remissions without treatment, whereas the one patient with disease progression was treated successfully. Watchful waiting may thus be appropriate for initial management of children.

Lipomatous variant of angiomyofibroblastoma involving the vulva: report of 3 cases of an extremely rare neoplasm with discussion of the differential diagnosis.

We report 3 cases of the extremely rare lipomatous variant of angiomyofibroblastoma (AMF) involving the vulva of women aged 35, 45, and 47. The lesions ranged in size from 2.5 to 12 cm in maximum dimension and the largest had a gross "fatty" appearance. The percentage of adipose tissue was approximately 50% in 1 case and over 90% in the other 2. In all the cases, there was a background of typical AMF with bland spindled and epithelioid cells arranged around blood vessels, although in the cases with >90% adipose tissue, this was subtle and diffusely interspersed with the adipose tissue. In all the cases, the spindled and epithelioid cells were positive with estrogen receptor. Given the morphologic features, misdiagnosis as a lipomatous neoplasm is likely, especially in cases with a minor component of typical AMF. We review the literature on lipomatous AMF and discuss the differential diagnosis.

Subconjunctival Herniated Orbital Fat Mimicking Adipocytic Neoplasm.

PURPOSE: To describe and discuss rare and benign conditions of subconjunctival orbital fat herniation that may mimic adipocytic neoplasm. METHODS: Sixteen eyes of 13 patients with subconjunctival orbital fat herniation were included. They all underwent transconjunctival excision owing to cosmesis, discomfort, or suspicion of malignancy. Histopathologic examination, postoperative complications, and recurrent conditions were analyzed. RESULTS: Eleven male and two female patients were included. The lesion was unilateral in 10 and bilateral in 3 cases. Excision was performed via conjunctival wound and removing the prolapsed orbital fat. The conjunctiva was then closed with two to three interrupted sutures. All the histopathologic specimens revealed Lochkern cells, floret cells, and mature adipocytes separated by fibrovascular septae without hyperchromatic cells, consistent with subconjunctival herniated orbital fat. All the patients were treated successfully with transconjunctival excision without recurrence at an average follow-up of 10.6 months (range, 6 to 16 months). CONCLUSIONS: Prolapse of subconjunctival orbital fat is an uncommon entity of intraorbital masses and may mimic adipocytic neoplasm. It is usually associated with a dehiscence in the Tenon capsule. Surgical excision is indicated and pathologic evaluation is necessary if any malignancy is suspected.