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.

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.

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 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.

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.

[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.

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.

[Adipocytic tumors]. / Tumeurs adipeuses.

Adipocytic tumors are the most common mesenchymal neoplasms, liposarcoma accounting for approximately 20% of soft tissue sarcomas. The differential diagnosis between benign and malignant tumors is often problematic and represents a significant proportion of consultation cases. The goal of this article is to review liposarcoma subtypes, the main benign adipocytic neoplasms: lipoblastoma, hibernoma, spindle/pleomorphic cell lipoma, chondroid lipoma, as well as non adipocytic neoplasms with a lipomatous component such as lipomatous solitary fibrous tumor, emphasizing on practical differential diagnosis issues, and immunohistochemical and molecular tools allowing their resolution.

Absence of chromosomal abnormalities in herniated orbital fat.

AIMS: Lipomatous tumours of the orbit are rare, and can sometimes be difficult to characterize. Herniated orbital fat is thought to be a reactive process, but its presentation can mimic a lipomatous tumour such as an atypical lipomatous tumour or spindle cell/pleomorphic lipoma. Genetic studies to determine if it is indeed a reactive process rather than an adipocytic neoplasm have not been performed. METHODS AND RESULTS: Four samples of herniated orbital fat were reviewed clinically, histopathologically and immunohistochemically. Array comparative genomic hybridization (aCGH) was used to search for genome-wide copy number alterations within the tumours. Histological evaluation revealed that all four tumours contained collections of adipocytes surrounded by fibrous septae. Lochkern cells and floret-like multinucleated giant cells were present, consistent with herniated orbital fat. CD34 was positive in all tumours. Staining for MDM2 and CDK4 was negative. ACGH analysis demonstrated no copy number alterations. CONCLUSIONS: Herniated orbital fat may share some histopathological features with lipoma and atypical lipomatous tumour, but the absence of copy number gains or losses is consistent with the impression that herniated orbital fat is a reactive process. Genetic analysis may be another method to help differentiate herniated orbital fat from a lipomatous orbital tumour when the diagnosis is in question.

Real-time polymerase chain reaction analysis of MDM2 and CDK4 expression using total RNA from core-needle biopsies is useful for diagnosing adipocytic tumors.

BACKGROUND: Diagnosing adipocytic tumors can be challenging because it is often difficult to morphologically distinguish between benign, intermediate and malignant adipocytic tumors, and other sarcomas that are histologically similar. Recently, a number of tumor-specific chromosome translocations and associated fusion genes have been identified in adipocytic tumors and atypical lipomatous tumors/well-differentiated liposarcomas (ALT/WDL), which have a supernumerary ring and/or giant chromosome marker with amplified sequences of the MDM2 and CDK4 genes. The purpose of this study was to investigate whether quantitative real-time polymerase chain reaction (PCR) could be used to amplify MDM2 and CDK4 from total RNA samples obtained from core-needle biopsy sections for the diagnosis of ALT/WDL. METHODS: A series of lipoma (n = 124) and ALT/WDL (n = 44) cases were analyzed for cytogenetic analysis and lipoma fusion genes, as well as for MDM2 and CDK4 expression by real-time PCR. Moreover, the expression of MDM2 and CDK4 in whole tissue sections was compared with that in core-needle biopsy sections of the same tumor in order to determine whether real-time PCR could be used to distinguish ALT/WDL from lipoma at the preoperative stage. RESULTS: In whole tissue sections, the medians for MDM2 and CDK4 expression in ALT/WDL were higher than those in the lipomas (P < 0.05). Moreover, karyotype subdivisions with rings and/or giant chromosomes had higher MDM2 and CDK4 expression levels compared to karyotypes with 12q13-15 rearrangements, other abnormal karyotypes, and normal karyotypes (P < 0.05). On the other hand, MDM2 and CDK4 expression levels in core-needle biopsy sections were similar to those in whole-tissue sections (MDM2: P = 0.6, CDK4: P = 0.8, Wilcoxon signed-rank test). CONCLUSION: Quantitative real-time PCR of total RNA can be used to evaluate the MDM2 and CDK4 expression levels in core-needle biopsies and may be useful for distinguishing ALT/WDL from adipocytic tumors. Thus, total RNA from core-needle biopsy sections may have potential as a routine diagnostic tool for other tumors where gene overexpression is a feature of the tumor.

[Most musculoskeletal soft tissue tumors are benign]. / Fetthaltiga mjukdelstumörer i rörelseapparaten ofta godartade.

Most musculoskeletal soft tissue tumors are benign, lipoma being the most common. Malignant soft tissue tumors may be difficult to clinically distinguish from benign. Scandinavian recommendations are that all lesions suspicious for sarcoma be referred to a sarcoma center. This has led to improved tumor control and less post-operative functional deficits. Magnetic resonance imaging (MRI) can reliably diagnose lipomas, and further work-up is not necessary. Lipomas can be treated at the local hospital. All deep seated musculoskeletal tumors (under the muscle fascia) not unequivocally lipomas should be referred to a sarcoma center. All superficial (subcutaneous) musculoskeletal tumors larger than 5 cm and not unequivocally lipomas should be referred to a sarcoma center.

Imaging of fat-containing lesions of the breast: a pictorial essay.

Fat-containing breast lesions constitute a heterogeneous group of predominantly benign tumors and non-neoplastic conditions. The role of imaging is to distinguish leave-me-alone lesions from rarely occurring malignant fat-containing tumors that require histologic analysis. Correlating mammographic findings with appearance at ultrasonography often helps in identifying lesions that do not require further work-up. MRI can be valuable to confirm the presence of fat and characterize lesions indeterminate on conventional imaging. The purpose of this multimodality imaging review is to exemplify the radiologic appearances of common and uncommon fat-containing breast lesions to facilitate accurate diagnosis, avoid unnecessary interventions, and ensure appropriate management.

[Morgagni hernia mimicking intrathoracic lipomatous tumor]. / Hérnia de Morgagni mimetizando lipoma intratorácico.

Morgagni hernia is the rarest type of diaphragmatic hernia, accounting for 2% of all cases. It consists in the thoracic protrusion of fat and/or abdominal viscera through a congenital defect in a retro or parasternal position. The clinical importance of this pathological entity is associated with the fact that it can be asymptomatic, mimicking other diseases, such as a large intrathoracic lipoma, as it happened in the case presented here. Incorrect diagnosis can cause catastrophic complications during surgery.

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.

Giant abdomino-pelvic adipose tumors of childhood.

Adipose tumors are rare in pediatric age and are commonly represented by benign forms: lipoma and lipoblastoma/lipoblastomatosis. Generally localized in subcutaneous tissue of the trunk and extremities, they can exceptionally occur as giant intra-peritoneal or pelvic masses. These tumors could reach considerable size prior to diagnosis since they are asymptomatic. The authors report a case series of three giant abdomino-pelvic adipose tumors.

Contributions of cytogenetics and molecular cytogenetics to the diagnosis of adipocytic tumors.

Over the last 20 years, a number of tumor-specific chromosomal translocations and associated fusion genes have been identified for mesenchymal neoplasms including adipocytic tumors. The addition of molecular cytogenetic techniques, especially fluorescence in situ hybridization (FISH), has further enhanced the sensitivity and accuracy of detecting nonrandom chromosomal translocations and/or other rearrangements in adipocytic tumors. Indeed, most resent molecular cytogenetic analysis has demonstrated a translocation t(11;16)(q13;p13) that produces a C11orf95-MKL2 fusion gene in chondroid lipoma. Additionally, it is well recognized that supernumerary ring and/or giant rod chromosomes are characteristic for atypical lipomatous tumor/well-differentiated liposarcoma and dedifferentiated liposarcoma, and amplification of 12q13-15 involving the MDM2, CDK4, and CPM genes is shown by FISH in these tumors. Moreover, myxoid/round cell liposarcoma is characterized by a translocation t(12;16)(q13;p11) that fuses the DDIT3 and FUS genes. This paper provides an overview of the role of conventional cytogenetics and molecular cytogenetics in the diagnosis of adipocytic tumors.

Surgical technique of the transoral approach to remove a lipoma of the buccal fat pad.

BACKGROUND: In 1727, Heister (Compendium anatomicum. Altdorf, Guill, Koleshii: editio tertia 1727: 134, table VIII and figs. 36-37) described the buccal fat pad (BFP) as an independent anatomic structure of the face; in 1801, Bichat (Anatomie generale appliquee a la physiologie et a la medecine. Paris, France: Brosson, Gabon et Cie Libraires, 1801:60) reported his fatty histologic finding. According to the literature, several pathologic tumorous conditions can arise from BFP, such as lipoma, lipoblastomatosis, liposarcoma, hemangioma, arteriovenous malformation, and nodular fasciitis; all of which are rare. After a revision of the English literature performed through PubMed between 1948 and 2008, we found 10 cases of lipomas arising from the BFP (7 cases are simple subtype, 2 are spindle cell lipoma, and 1 is fibrolipoma). The aims of this study were to introduce our clinical report of this rare pathologic entity, describe the surgical technique of the transoral approach, and discuss the potential pitfalls regarding the preoperative diagnosis and the close interrelation among the BFP, the facial buccal branches (FBBs), and the parotid duct (PD). CLINICAL REPORT: A 43-year-old man was referred to the Maxillofacial Unit of the Novara Major Hospital with a 6-month history of a painless swelling in the right cheek. Clinical examination revealed a clearly visible, tender, slightly fluctuant mass, situated anterior to the masseter muscle and extended to the submandibular region. The patient underwent an ultrasound, a computed tomography, and a magnetic resonance imaging. Under general anesthesia with nasotracheal intubation, the patient underwent intraoral resection of BFP lipoma. DISCUSSION: The 2 major areas of discussion are the potential pitfall regarding the preoperative diagnosis and the close anatomic interrelation among the BFP, the FBB, and the PD. First, the spindle cell lipoma, one of the most common BFP lipoma variant, can be histologically and clinically similar to a well-differentiated liposarcoma, which can be recurrent and metastatic. This issue warrants that a careful workup of the tumorous mass of the buccal space and a BFP origin must be considered in every situation. Finally, according to the recent literature, the anatomic variations of the interrelation between the FBB and the BFP are classified into 2 groups: (1) FBB passing lateral to the BFP and (2) branches crossing inside the BFP. The anatomic variations of the interrelation between the PD and the BFP are classified into 3 groups: (1) PD passing lateral to the BFP, (2) PD crossing deep to the BFP, and (3) PD running along the superior border of the BFP.