Diagnosis Of Dedifferentiated Liposarcoma Research Articles

Diagnosing liposarcoma on (peri)-renal mass biopsy: A clinicopathological study of 30 cases.

Classification of renal neoplasms on small tissue biopsies is in increasing demand, and maintaining broad differential diagnostic considerations in this setting is necessary. When evaluating a renal or perirenal tumour biopsy with sarcomatoid morphology, together with sarcomatoid renal cell carcinoma and sarcomatoid urothelial carcinoma as top diagnostic considerations, it is vital to additionally consider the possibility of well-differentiated and de-differentiated liposarcoma. This study reports a series of 30 biopsy samples from sites in or around the kidney collected from four institutions in which the correct diagnosis was either well-differentiated or de-differentiated liposarcoma. The majority (26 of 30, 87%) of lesions were accurately diagnosed on biopsy sampling, all of which incorporated testing for MDM2 by immunohistochemistry (IHC), fluorescence in-situ hybridisation (FISH) or a combination of the two as part of the diagnostic work-up. Tumour expression of MDM2 by IHC without confirmatory FISH analysis was sometimes (30%) sufficient to reach a diagnosis, but demonstration of MDM2 amplification by FISH was ascertained in the majority (57%) of biopsy samples. A diagnosis of de-differentiated liposarcoma was not definitively established until resection in four (13%) patients, as no MDM2 testing was performed on the corresponding pre-operative biopsies. When a retroperitoneal tumour is not clinically suspected, histological consideration of a liposarcoma diagnosis may be overlooked. Implementation of ancillary immunohistochemical and cytogenetic testing can ultimately lead to a definitive diagnosis in this potentially misleading anatomical location.

The Characteristics of magnetic resonance imaging and immunohistochemical findings in de-differentiated liposarcoma.

Radiological imaging in Dedifferentiated liposarcoma (DDLPS) often shows the coexistence of fatty and non-fatty solid components; however, it has been shown that when fatty components were not identified on magnetic resonance imaging (MRI), the diagnosis of DDLPS would not have been diagnosed if immunohistochemical (IHC) staining had not been performed. The aim of this study was to investigate the pattern of MRI and relationship between MRI and IHC findings in DDLPS. We retrospectively reviewed the cases of 25 patients with DDLPS. To identify the MRI spectrum of DDLPS, tumors were classified into the following four categories based on MRI findings: I = a well-defined fatty mass and juxtaposed well-defined non-fatty mass, II = a non-fatty component within a predominantly fatty mass, III = a focal fatty component within a large non-fatty mass, and IV = a non-fatty mass with atypical MRI findings. IHC staining for CDK4, MDM2, and p16 were evaluated. Category IV tumor was the most common tumor in this population. Of the 22 patients who underwent IHC staining, MDM2, CDK4, and p16 were positive in 21, 20, and 19 patients, respectively. MDM2 was positive in all 11 patients with category IV tumors; CDK4 and p 16 were positive in 10 and eight patients, respectively. There was no difference of survival between the patients with category I, II and III and category IV. DDLPS without fatty components on MRI scans was mostly found. We recommend IHC staining to screen for DDLPS even if the tumors in STS cases have a non-fatty component.

S2073 Dedifferentiated Liposarcoma Presenting as Dysphagia and Weight Loss: Common Symptoms of an Uncommon Diagnosis

Introduction: Liposarcoma is a malignant soft-tissue tumor that frequently occurs in extremities and retroperitoneum but rarely affects the GI tract. We report a case of dedifferentiated liposarcoma manifesting as dysphagia and early satiety. Case Description/Methods: A 76 year old woman was referred for progressively worsening dysphagia for solids and liquids, early satiety and unintentional weight loss. She denied acid reflux symptoms, regurgitation, odynophagia or chest pain. She never smoked cigarettes nor consumed alcohol. Physical examination did not show cervical, supraclavicular or axillary lymphadenopathy. Esophagogastroduodenoscopy (EGD) showed an area of moderate to severe extrinsic compression in the lower esophagus from 31 cm to 38 cm from the incisors (Figure 1A). Contrast enhanced computed tomography (CT) scan of the chest revealed a 6 × 7 cm solid homogeneous mass in the lower middle/posterior mediastinum, laterally displacing the esophagus and the descending thoracic aorta, with anterior displacement of the heart (Figure 1B). No pathological lymphadenopathy was seen. Endoscopic ultrasound (EUS) showed a hypoechoic and homogenous mass with smooth borders. Fine needle aspiration (FNA) was performed (Figure 1C) for pathological diagnosis. Histopathology of the mass demonstrated a hypocellular infiltrate of pleomorphic cells in a loose collagenous matrix. There was no overt evidence of lipogenic differentiation, and mitotic activity was inconspicuous (Figure 1D). By immunohistochemistry, neoplastic cells were negative for epithelial, vascular, neural, and melanocytic markers. Fluorescent in-situ hybridization (FISH) detected MDM2 amplification in the formalin-fixed, paraffin-embedded tumor sample (Figure E), compatible with a diagnosis of dedifferentiated liposarcoma (DDL). Metastatic lesions were subsequently identified (AJCC stage IV). Discussion: Dedifferentiated liposarcoma (DDL) is one of the four major subtypes of liposarcomas. DDL typically has the appearance of undifferentiated pleomorphic or spindle cell sarcoma, and is associated with more aggressive clinical behavior and with a greater propensity for local recurrence and metastasis. The lack of specific symptoms can lead to delay in diagnosis. Systemic therapy with doxorubicin or other anthracyclines remains the treatment mainstay. The patient is currently receiving doxorubicin-based systemic therapy and under close clinical surveillance. This case highlights potential rare presentations of liposarcomas affecting the GI tract.Figure 1.: CT scan chest showing soft tissue mass in the anterior mediastinum.

Primary dedifferentiated Liposarcoma of vagina: a first case report

BackgroundDedifferentiated liposarcoma, one of the most deadly types of soft tissue sarcoma, is an aggressive and high-grade form of liposarcoma. Liposarcoma occurs most commonly in the retroperitoneum, extremities and trunk, but less frequently in the female genital tract. The vagina is a very rare site of origin. Herein we report the first case of dedifferentiated Liposarcoma deriving from vagina and discuss its clinical course.Case presentationA 38-year-old female patient presented to our institution with a painless vaginal mass. Abdominal computed tomography showed a 17.6 cm× 10.4 cm solid mass originating from the right lateral wall of her vagina. Then she underwent complete surgical resection of the tumor mass, and postoperative pathological result confirmed the diagnosis of dedifferentiated liposarcoma deriving from vagina. Six courses of combination chemotherapy with pirarubicin plus ifosfamide were performed after surgery. The patient remains with no evidence of disease recurrence with 13 months of follow-up.ConclusionsLiposarcoma is very rare in female genital tract, and more rare for dedifferentiated liposarcoma in gynecologic field. Little is known about the clinical characteristics, pathological diagnosis, prognosis and optimal management strategy of vaginal dedifferentiated liposarcoma. Complete surgical resection followed by systemic chemotherapy is suggested to be standard treatment for dedifferentiated liposarcoma. Combination chemotherapy with pirarubicin and ifosfamide may be effective for treating vaginal dedifferentiated liposarcoma.

Dedifferentiated Liposarcoma With Meningothelial-Like Whorls: Five Additional Cases and Review of the Literature.

Background. Diagnosis of dedifferentiated liposarcoma (DDL) can sometimes be challenging due to a wide variety of histological features. "Meningothelial-like" whorl is an uncommon histological feature of DDL, which is also observed in neural tumors and follicular dendritic cell sarcoma. This feature is frequently associated with metaplastic bone formation. We conducted this study to describe the clinicopathological features of DDL with meningothelial-like whorls that would aid in establishing accurate diagnosis. Material and Methods. Microscopic glass slides of 5 cases of DDL with meningothelial-like whorls, diagnosed between January 2010 and December 2019, were reviewed. Results. Paratesticular region was the most common site. Whorls occupied 10% to 75% of tumor area and ranged in size from <0.1 cm to >2 cm. In 1 case, these whorls coalesced to form large areas of dedifferentiation. The cells forming whorls were spindle to epithelioid shaped and lacked significant nuclear pleomorphism and increased mitoses. Metaplastic bone formation was observed in 4 cases and cartilage formation in 3 cases. p16 and α-smooth muscle actin (α-SMA) immunohistochemical stains were positive in 2 cases, when performed. MDM2 gene amplification was observed in all cases by fluorescence in situ hybridization technique. These tumors showed aggressive behavior, similar to that of DDL without meningothelial-like whorls. Two patients died, 1 developed recurrence, 1 presented as recurrent tumor, and 1 developed metastasis. Conclusion. Meningothelial-like whorls in DDL most likely represent an early stage of dedifferentiation. Presence of well-differentiated liposarcoma areas, metaplastic bone formation, positive expressions for p16 and α-SMA immunohistochemical stains, and MDM2 gene amplification are useful diagnostic clues. These tumors have the potential to behave aggressively.

Analysis of Dedifferentiated Liposarcomas Emphasizing the Diagnostic Dilemmas

Abstract Introduction: Dedifferentiated liposarcoma (DDLPS) is defined as a progression of well-differentiated liposarcoma (WDLPS) to another nonlipogenic sarcoma. Since a variety of heterologous sarcomas can be encountered in dedifferentiation, clinical dilemmas arise. The present study analyzed the role of clinicopathologic and immunohistochemical (IHC) features in the diagnosis of DDLPS and its differentiation from mimics. Materials and Methods: A retrospective and prospective study was conducted wherein all cases of liposarcoma from 2012 to 2017 were reviewed. DDLPS cases were identified among pleomorphic lesions. Clinical and histopathological details for these cases were retrieved from medical records section and department archives. Histomorphology and immunohistochemistry (MDM2, S100, and Ki-67) were analyzed for these cases. Results: Among 37 cases of liposarcomas reviewed, DDLPS was diagnosed in 12 cases (32.4%). Mean age of the patients was 54.3 years with equal gender distribution (M:F =1:1.2). Two patients had recurrent tumors. Most were retroperitoneal (58.3%) with mean duration of symptoms being 8.7 months. Mean tumor dimension was 17.5 cm. High-grade dedifferentiated component was most common (83.3%) with only one case each (8.3%) of low-grade and homologous dedifferentiation. Undifferentiated pleomorphic sarcoma was the frequent nonlipogenic sarcoma. MDM2 overexpression was detected in 100%, focal S100 positivity seen in 66.6%, and mean Ki-67 labeling index was 24. Conclusion: DDLPS exhibits aggressive clinical behavior. Adequate sampling, correlation to clinical details, demonstration of transition from WDLPS to DDLPS aid in narrowing the differentials. Immunostaining with MDM2 helps in definite categorization and S100 highlights lipoblasts, when they are not easily identifiable. MDM2, CDK4, and p16 IHC panel is recommended in all cases and fluorescence in situ hybridization analysis where IHC is noncontributory.

Diagnostic Utility and Limitations of Immunohistochemistry of p16, CDK4, and MDM2 and Automated Dual-color In Situ Hybridization of MDM2 for the Diagnosis of Challenging Cases of Dedifferentiated Liposarcoma.

The diagnosis of dedifferentiated liposarcoma (DDLPS) is challenging when an atypical lipomatous tumor component is absent or obscure. To analyze the utility and limitations of ancillary techniques, we studied 11 cases of DDLPS in challenging conditions and 17 cases of nonlipogenic high-grade sarcomas with immunohistochemistry (IHC) for p16, CDK4, and MDM2 and automated dual-color in situ hybridization (DISH) for MDM2 amplification. All DDLPS specimens lacked clear lipogenic components and were immunoreactive for p16, CDK4, and MDM2. DISH analyses also revealed high-level amplification of MDM2 in all DDLPS. In contrast, among nonlipogenic sarcomas, p16, CDK4, and MDM2 were expressed in 8, 9, and 3 cases, respectively. MDM2 amplification was detected in 3 of 8 studied. The MDM2-amplified tumors were the same as the MDM2-immunoreactive tumors. After careful reevaluation of these 3 sarcomas, 2 were reclassified as DDLPS because small areas of lipogenic components were detected in the original specimens. The respective sensitivities and specificities of these markers were as follows: p16 IHC (100% and 60%), CDK4 IHC (100% and 53.3%), MDM2 IHC (100% and 93.3%), and MDM2 DISH (100% and 83.3%). The results of MDM2 IHC completely coincided with those of MDM2 DISH. The present study confirmed the substantial utility of MDM2 IHC and MDM2 DISH in the diagnosis of DDLPS, especially when lipogenic components were indistinct compared with IHC for p16 and CDK4. Furthermore, automated DISH was more practical than fluorescent in situ hybridization.

Primary cardiac dedifferentiated liposarcoma in a middle-aged female: a case report

BackgroundPrimary malignant cardiac tumors are extremely rare and can present with the same nonspecific characteristics as benign primary cardiac tumors. We herein describe a middle-aged female with an intracavitary, irregular atrial mass who experienced partial surgical resection. The atrial mass which was recognized as myxoma before surgery was finally diagnosed as dedifferentiated liposarcoma (DDLPS) by postoperative pathological examination.Case presentationThe patient, a 61-year-old female, presented to the emergency room because of progressive chest congestion and shortage of liberties for 6 months and orthopnoea and paroxysmal nocturnal dyspnea for 3 days. The laboratory examinations confirmed no abnormalities. The thoracic computed tomography (CT) scan showed massive hydropericardium, pleural effusion and left atrium occupying lesion. The transesophageal echocardiography (TEE) confirmed an intracavitary and irregular left atrial mass, limiting the mitral valve inflow and pulmonary venous blood reflux. The positron emission tomography/computed tomography (PET/CT) revealed high grade fluorodeoxyglucose uptake only in the intracavitary mass which near the mitral valve. According to operative exploration, the intracavitary mass had invaded the mitral annulus and posterior wall of left ventricle which cannot be resected completely, we did merely partial surgical resection to relieve the patient’s symptoms. Postoperative immunohistochemical stain confirmed the diagnosis of DDLPS. The patient was transferred to the oncology department for further therapy. Unfortunately, the patient was detected with brain metastasis 1 month later and died within 5 months after the surgery.ConclusionsPrimary cardiac DDLPS is an extremely rare histological subtype of undifferentiated pleomorphic sarcomas which present the same nonspecific characteristics as benign primary cardiac tumors. Even though surgical resection combined with chemotherapy or radiotherapy remains the mainstream treatment strategy, the prognosis of cardiac malignancy is poor with high mortality. Novel management strategies need to be further explored.

Diagnostic accuracy of percutaneous biopsy in retroperitoneal sarcoma.

Percutaneous biopsy is recommended before surgery for suspected retroperitoneal sarcoma (RPS) to confirm the histological diagnosis and guide surgical strategy. The present study aimed to establish the diagnostic accuracy of percutaneous core biopsy with respect to histological diagnosis and tumour grade. Data on patients with suspected RPS who underwent percutaneous biopsy followed by surgical resection between 2005 and 2016 at one of two tertiary European sarcoma units were reviewed. Histological tumour type and tumour grade on biopsy were correlated with postoperative histology to evaluate diagnostic accuracy. A total of 239 patients underwent percutaneous core biopsy followed by surgical resection in Milan (163, 68·2 per cent) or Birmingham (76, 31·8 per cent). Diagnostic accuracy varied with histological diagnosis (P < 0·001), but demonstrated overall concordance with final pathology following resection in 67·2 per cent of biopsies (κ = 0·606). The majority of discrepancies occurred in dedifferentiated liposarcoma (DDLPS), owing to under-recognition of dedifferentiation in this group. Concordance between pathology on biopsy and resection improved to 81·1 per cent when DDLPS and well differentiated liposarcoma were grouped together as liposarcoma. Grade on biopsy was concordant with grade on resection specimen in 60·4 per cent of tumours (κ = 0·640). Diagnosis of high-grade tumours on biopsy had a high specificity (98 per cent), and moderate positive predictive value (85 per cent) and negative predictive value (78 per cent). A diagnosis of DDLPS or leiomyosarcoma on percutaneous biopsy is highly reliable. High-grade sarcomas can be identified with high specificity, which opens the door to a study on neoadjuvant therapy in these patients.

P16 Immunohistochemistry is Less Useful Than MDM2 and CDK4 to Distinguish Dedifferentiated Liposarcomas From Other Retroperitoneal Mimics.

Dedifferentiated liposarcoma (DDL) frequently involves the retroperitoneum. In the absence of a lipogenic component histologically, the differential diagnosis of a retroperitoneal DDL includes other sarcomas and, if the tumor has visceral involvement, sarcomatoid carcinoma. DDL demonstrates amplification of chromosome subregion 12q13-q15. Detection of the amplification itself, or the resulting overexpression of the MDM2 and CDK4 genes by genetic and immunohistochemical methods, is a useful ancillary test in the diagnosis of DDL. More recently, immunohistochemistry for p16, the product of the CDKN2A gene, was shown to be a useful adjunct in differentiating well-differentiated liposarcoma from benign adipocytic tumors. In the present study, we examined the utility of p16 immunohistochemistry to distinguish DDL (n=44) from other high-grade and low-grade retroperitoneal mimics (n=73). p16 positivity was observed in 43/44 (98%) DDLs, with the majority of these showing strong, diffuse, staining. The rate of p16 positivity in other retroperitoneal tumors was lower (37/73, 51%) and staining was not as consistently diffuse or intense. Furthermore, p16 positivity varied between the control sarcomas based on tumor type as follows: 11/11 leiomyosarcomas, 8/11 pleomorphic undifferentiated sarcomas, 9/39 sarcomatoid carcinomas, 7/7 desmoid tumors, 1/3 endometrial stromal sarcomas, and 1/2 malignant gastrointestinal stromal tumors. On the basis of these findings, we conclude that p16 is highly sensitive for retroperitoneal DDL. However, the lack of specificity limits the diagnostic utility compared with the more established markers MDM2 and CDK4.

Dedifferentiated Liposarcoma of Retroperitoneum With Extensive Osteosarcomatous Component

Dedifferentiated liposarcoma (DDLS) is a rare subtype of liposarcoma composed of 2 components: a well-differentiated liposarcoma (WDLS) and a nonlipogenic sarcoma (dedifferentiation component), represented in &amp;gt;90% of cases by a high grade undifferentiated pleomorphic sarcoma, in the form of both small microscopic foci and/or grossly recognizable nodular masses. The paper reports a rare case of a retroperitoneal DDLS, in which approximately half of a tumor mass is composed of a high-grade osteosarcoma. A 68-year-old Caucasian woman affected by abdominal discomfort. Clinical examination showed a large, hard and fixed abdominal mass. Computed tomography scan revealed a huge retroperitoneal mass composed of 2 distinct components: the upper part showed a hypodense tissue, while the lower part showed a higher density and coarse calcifications. Patient underwent to a challenging surgical resection of the mass that, at histological examination, resulted to be a DDLS, in which a WDLS coexisted with an osteosarcoma. Presurgical diagnosis of DDLS is difficult due to the great morphologic variability of the dedifferentiated component, ranging from low to high-grade nonlipogenic sarcoma. The present case contributes to widen the morphological spectrum of DDLS, emphasizing the possibility that a retroperitoneal mass with a dual tissue component, one of which containing extensive areas with coarse calcifications, is highly suspected to be a DDLS with an osteosarcomatous component. This pre-operative finding should alert the surgeon because it has a significant impact on prognosis, increasing the risk of local recurrence and of death by disease in a few months after diagnosis.