Liposarcoma With Hibernoma-like Histology: A Clinicopathologic Study of 16 Cases.

Hibernoma is an uncommon benign tumor of brown fat cells that consistently expresses uncoupling protein 1 (UCP1). Herein, we clinicopathologically characterized 16 liposarcomas, for which histology, at least focally, closely resembled that of hibernoma, including sheets of brown fat-like, finely multivacuolated-to-eosinophilic tumor cells with no or minimal nuclear atypia. The cohort consisted of 4 well-differentiated liposarcomas (WDLSs), 6 dedifferentiated liposarcomas with a concomitant WDLS component, and 6 myxoid liposarcomas (MLSs). For all dedifferentiated liposarcoma cases, hibernoma-like histology was present only in the WDLS component. All tumors presented as large, deep-seated masses. Hibernoma-like histology resembled the pale cell, mixed cell, eosinophilic cell, or spindle cell subtypes of hibernoma, and it was a focal observation, with conventional liposarcoma histology coexisting in all cases. However, a few biopsy samples were predominated by hibernoma-like patterns, and 1 case was initially interpreted as hibernoma. Hibernoma-like components in WDLS immunohistochemically coexpressed MDM2 and CDK4 in most cases and harbored MDM2 amplification in tested cases, whereas half of the cases expressed UCP1. The hibernoma-like components of MLS expressed DDIT3, and DDIT3 rearrangements were present in the tested cases, whereas only negative or equivocal UCP1 expression was observed. In summary, WDLS and MLS focally demonstrate hibernoma-like histology on rare occasions. These elements are neoplastic, and some such areas in WDLS likely represent true brown fat differentiation, as supported by UCP1 expression. This pattern requires recognition to avoid the misdiagnosis as hibernoma, especially in biopsies. A careful search for classic liposarcoma histology and additional work-ups for the MDM2/CDK4 or DDIT3 status will be helpful for an accurate diagnosis.

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.

Primary gastrointestinal liposarcoma-a clinicopathological study of 8 cases of a rare entity.

Primary gastrointestinal liposarcoma is rare, and information regarding this entity is largely based on single case studies. We report on 8 patients with primary liposarcoma of the gastrointestinal tract and review the pertinent literature. The cohort includes 6 men and 2 women who ranged in age from 51 to 81 years (median 68.5). Two tumors arose in the stomach, 4 in the small intestine, and 2 in the large intestine. Tumors ranged in size from 2.5 to 14.5 cm (median 7 cm), originated in the submucosa or muscularis propria of the intestinal wall, and frequently protruded into the bowel lumen, resulting in mucosal ulceration and luminal obstruction. Six tumors were dedifferentiated liposarcomas, and 2 were well-differentiated liposarcoma. Surgical excision was performed on all tumors except for 1 case of dedifferentiated liposarcoma. On follow-up, 1 patient with dedifferentiated liposarcoma developed a lytic sacral lesion suspicious for metastasis 4 months after resection of the primary, and another underwent marginal resection and presented with recurrence 4 years later, had tumor re-resection, and was considered disease-free at 6 weeks postsurgery. A third patient with dedifferentiated liposarcoma was alive with unknown disease status at 17 months following surgery, and another patient with dedifferentiated liposarcoma was alive without evidence of disease at 30 months following surgery. No follow-up information on the remaining patients is available. Overall, liposarcomas of the intestinal tract are most frequently high-grade dedifferentiated tumors that are biologically aggressive and require surgical excision with widely negative margins to help reduce the risk of local recurrence and dissemination. Important in the differential diagnosis is malignant gastrointestinal stromal tumor. Care must be taken not to misdiagnose one entity for the other because the correct diagnosis carries important therapeutic implications.

[Pathological significance of NY-ESO-1 expression in the diagnosis of myxoid liposarcoma].

Objective: To detect the expression of New York esophageal squamous cell carcinoma antigen 1 (NY-ESO-1) in common types of mesenchymal myxoid tumors, and to investigate its significance in the diagnosis and differential diagnosis of myxoid liposarcoma. Methods: A total of 43 formalin-fixed paraffin-embedded samples of mesenchymal myxoid tumors from the Affiliated Hospital of Qingdao University and Qingdao Municipal Hospital ranging between 2010 and 2017 were selected. NY-ESO-1 expression was detected by immunohistochemical staining. DDIT3 gene status was detected by fluorescence in situ hybridization (FISH). NY-ESO-1 mRNA was detected by reverse transcription-PCR (RT-PCR). Results: Histopathology and FISH results confirmed that there were 11 cases of myxoid liposarcoma and 32 other types (including 7 cases of well-differentiated liposarcoma, 1 dedifferentiated liposarcoma, 3 lipomas, 2 lipoblastomas and 19 non-adipocytic tumors). Immunohistochemical staining showed that the positive expression propotion of NY-ESO-1 in myxoid liposarcoma was 11/11, and the positive location was the cytoplasm and nucleus of lipoblast cells. The expression intensity is higher in regions with round cell differentiation. Among the 32 cases of other mesenchymal myxoid tumors, only one well-differentiated liposarcoma showed positive immunoreactivity for NY-ESO-1. RT-PCR confirmed that 7 cases of myxoid liposarcoma (7/11) and one well-differentiated liposarcoma (1/7) had NY-ESO-1 mRNA expression. Conclusions: NY-ESO-1 is positively expressed in myxoid liposarcoma. It can be served as a useful marker for the diagnosis and differential diagnosis of myxoid liposarcoma.

Dysplastic Lipoma: A Distinctive Atypical Lipomatous Neoplasm With Anisocytosis, Focal Nuclear Atypia, p53 Overexpression, and a Lack of MDM2 Gene Amplification by FISH; A Report of 66 Cases Demonstrating Occasional Multifocality and a Rare Association With Retinoblastoma.

In our routine and consultative pathology practices, we have repeatedly encountered an unusual subcutaneous fatty tumor with notable anisocytosis, single-cell fat necrosis, and patchy, often mild, adipocytic nuclear atypia. Because of the focal atypia, consultative cases have most often been received with concern for a diagnosis of atypical lipomatous tumor. Similar tumors have been described in small series under the designations "subcutaneous minimally atypical lipomatous tumors" and "anisometric cell lipoma." Sixty-six cases of this tumor type were collected and reviewed. Immunohistochemistry for p53, MDM2, CDK4, Retinoblastoma 1 (RB1) protein, CD34, S100, and CD163 was performed. Cases were tested for MDM2 gene amplification and RB1 gene deletion with fluorescence in situ hybridization (FISH) and for TP53 mutations by Sanger sequencing. Next-generation sequencing analysis using a panel of 271 cancer-related genes, including TP53, RB1, and MDM2, was also carried out. Our patient cohort included 57 male patients, 8 female patients, and 1 patient of unstated sex, who ranged in age from 22 to 87 years (mean: 51.2 y). All tumors were subcutaneous, with most examples occurring on the upper back, shoulders, or posterior neck (86.4%). Ten patients had multiple (2 to 5) lipomatous tumors, and the histology was confirmed to be similar in the different sites in 4 of them, including 1 patient who had a retinoblastoma diagnosed at age 1. The tumors were generally well circumscribed. At low magnification, there was notable adipocytic size variation with single-cell fat necrosis in the background associated with reactive histiocytes. Adipocytic nuclear atypia was typically patchy and characterized by chromatin coarsening, nuclear enlargement, and focal binucleation or multinucleation. Focal Lochkern change was frequent. In most instances, the degree of atypia was judged to be mild, but in 3 instances, it was more pronounced. Spindle cells were sparse or absent, and when present, cytologically bland. Thick ropy collagen bundles were absent. In all cases, p53 immunoexpression was noted (range: 2% to 20% of adipocytic nuclei), characteristically highlighting the most atypical cells. Twenty of 50 cases had MDM2 immunoreactivity, usually in <1% of the neoplastic cells, but in 4 cases, up to 10% of the cells were positive. Of 32 cases tested, 22 showed a near total loss of RB1 immunoexpression, and the remainder showed partial loss. Three of 13 cases showed RB1 gene deletion in >45% of the cells by FISH (our threshold value for reporting a positive result) with an additional 3 cases being very close to the required cutoff value. MDM2 gene amplification was absent in all 60 cases tested, including those with the greatest MDM2 immunoexpression and most pronounced atypia. All 5 tested cases showed no TP53 mutation with Sanger sequencing. Because of material quality issues, next-generation sequencing analysis could be performed in only 3 cases, and this did not reveal any recurrent mutations. All tumors were managed by simple local excision. Follow-up was available for 47 patients (range: 1 to 192 mo; mean: 27 mo) and revealed 2 local recurrences and no metastases. Dysplastic lipoma is a distinctive atypical fatty tumor variant that has p53 overexpression and RB1 gene abnormalities and lacks MDM2 gene amplification by FISH. These tumors have a strong male predominance and a notable tendency to involve the subcutaneous tissue of the shoulders, upper back and posterior neck. Multifocality is frequent (18.9% of patients with follow-up information), and there is a rare association with retinoblastoma. This tumor warrants separation from ordinary lipoma with fat necrosis, fat-rich spindle cell lipoma and the conventional form of atypical lipomatous tumor that features MDM2 gene amplification.

Hibernoma Mimicking Atypical Lipomatous Tumor: 64 Cases of a Morphologically Distinct Subset.

Hibernoma is a benign adipocytic tumor with predilection for subcutaneous tissue of the thigh, upper trunk, and neck of middle-aged adults. 11q13 rearrangement resulting in MEN1/AIP codeletion is characteristic. Hibernomas are composed, in varying proportions, of brown fat cells, mature adipocytes, and microvacuolated lipoblast-like cells. Examples containing predominantly multivacuolated lipoblast-like cells are uncommon and distinction from atypical lipomatous tumor (ALT) is important for clinical management. We herein present the clinicopathologic features of 64 hibernomas histologically mimicking ALT. MDM2 and CDK4 immunohistochemistry as well as MDM2 fluorescence in situ hybridization were performed in a subset of cases. Clinical and follow-up information were obtained from referring pathologists. Thirty-four patients were male and 30 female, with a median age of 43 years (range, 24 to 78 y). The tumors were well circumscribed and mostly deeply located (53/64 cases, 83%) with a median tumor size of 12.9 cm (range, 3.5 to 23 cm) and predilection for the thigh (42/64 cases, 66%). Histologically, large cells with prominent lipoblast-like cytoplasmic fatty vacuoles and small central nuclei were present to a prominent degree in all cases, along with mature univacuolated adipocytes and smaller numbers of large, finely vacuolated cells with eosinophilic granular cytoplasm. Nuclear atypia and mitoses were absent. None of the 39 cases tested showed CDK4 and MDM2 overexpression or MDM2 amplification. Follow-up, available for 16/64 cases (median, 47 mo; range, 1 to 165 mo), revealed no recurrences or metastases. Hibernoma mimicking ALT shows predilection for deep soft tissue, especially in the thigh. These tumors behave in a benign manner and MDM2/CDK4 negativity may be useful in excluding ALT.

[Clinicopathologic features of atypical spindle cell lipomatous tumor].

Objective: To investigate the clinicopathologic characteristics, immunophenotype, differential and diagnostic features of atypical spindle cell lipomatous tumor (ASLT). Methods: Three cases of ASLT were collected from January 2010 to March 2017 at Zhejiang Provincial People's Hospital. The clinical and imaging features, histomorphology, immunophenotype and prognosis were analyzed. Fluorescence in situ hybridization (FISH) was used to detect MDM2 gene amplification, and relevant literature was reviewed. Results: All three patients were adult males, aged 38, 43 and 54 years, respectively. One tumor originated in the subcutaneous soft tissue in the head and neck, one was located in the left primary bronchus and one in the latissimus dorsi muscle. Grossly, all three tumors were circumscribed and ranged from 4.0 to 5.8 cm in size. Microscopically, all showed a focally infiltrative front. These tumors were composed of variable proportions of spindle-shaped and adipocytic cells in a background of variable fibrous and edematous matrix. Scattered lipoblasts were easily seen. One tumor was composed predominately of spindle tumor cells, one of adipocytic cells, and one of equally mixed cell populations. The spindle tumor cells were generally bland-appearing with focal nuclear enlargement and hyperchromasia noted in one case. Mitosis was not seen in neither the spindle cells nor the adipocytic cells. By immunohistochemistry, diffuse and strong reactivity to CD34 of the spindle cells was noted in all cases, definite loss of Rb expression was noted in one of three cases, and S-100 protein was expressed only in the adipocytic cells. INI-1 was intact and Ki-67 index was 1% to 3%. All other markers including CDK4, MDM2, STAT6, SOX10, CD99, bcl-2, ß-catenin, CD117, GFAP, CK, EMA, SMA and desmin were negative. FISH of MDM2 was done in two cases, and both showed no amplification. The ASLT in the head and neck had two recurrences during 17 months of follow-up, whereas the tumor in the latissimus dorsi was free of disease during 33 months of follow-up. Conclusions: ASLT is a rare subtype of low-grade adipocytic neoplasm and is distinctive from atypical lipomatous tumor/well-differentiated liposarcoma. The histomorpholgy of ASLT has significant heterogeneity and forms a continuous spectrum. ASLT needs to be distinguished from a series of benign and malignant soft tissue tumors.

Clarifying the Distinction Between Malignant Peripheral Nerve Sheath Tumor and Dedifferentiated Liposarcoma: A Critical Reappraisal of the Diagnostic Utility of MDM2 and H3K27me3 Status.

Malignant peripheral nerve sheath tumor (MPNST) and dedifferentiated liposarcoma (DDLPS) are 2 major types of pleomorphic spindle cell sarcoma. The differentiation of MPNST and DDLPS by histomorphology alone can be problematic. Although MDM2 amplification and PRC2 alteration leading to H3K27me3 deficiency are genetic hallmarks of DDLPS and MPNST, respectively, a small number of MDM2-amplified MPNSTs and H3K27me3-deficient DDLPSs have been reported in the literature. We systematically compared MDM2 and H3K27me3 status in 68 MPNSTs and 47 DDLPSs. Of the 62 MPNSTs, 22 were immunopositive for MDM2, mostly in a weak and/or focal manner. Of the 21 MDM2-positive MPNSTs successfully tested by fluorescence in situ hybridization, high-level MDM2 amplification was observed in 1 case. In contrast, MDM2 staining and high-level MDM2 amplification were positive in all the DDLPS tested (28/28 and 20/20). Of the 68 MPNSTs, 42 cases (62%) exhibited complete loss of H3K27me3. All the 13 MPNSTs that showed heterologous differentiation were deficient in H3K27me3. Of the 47 DDLPSs, 3 cases (6%) had complete loss of H3K27me3, all of which exhibited heterologous differentiation. One case of H3K27me3-deficient DDLPS exhibited homozygous loss of EED according to targeted next-generation sequencing, whereas there were no alterations in NF1 and CDKN2A. In conclusion, high-level MDM2 amplification strongly suggests DDLPS over MPNST. Although a good marker for MPNST, H3K27me3 deficiency also uncommonly occurs in DDLPS in association with PRC2 mutational inactivation. Because both markers are imperfectly specific, rare sarcomas with dual features could be encountered, and their classification should integrate other parameters.

Lipoblasts in spindle cell and pleomorphic lipomas: a close scrutiny.

The presence and frequency of lipoblasts (LPB) in spindle cell lipomas (SCL) and pleomorphic lipomas (PL) has never been studied in detail on a histologically, immunohistochemically and molecular genetically validated set of tumors. The authors investigated this feature by reviewing 91 cases of SCL and 38 PL. When more than 3 unequivocal LPB were found, the case was regarded as positive for the presence of LPB. All positive cases were then stained with CD34 and retinoblastoma (Rb) protein antibodies and tested by fluorescence in situ hybridization for MDM2 and CDK4 amplifications and the FUS gene rearrangements. The patients with SCL and PL containing LPB were 14 women and 47 men, the rest were of unknown gender. The cases usually presented as superficial, well-circumscribed soft tissue masses and most commonly occurred in the upper back and neck. CD34 was expressed in all cases, while Rb protein was consistently absent in all. Molecular genetic results, when available, were in concordance with the morphological diagnosis of SCL/PL. LPB were found in 37 (41%) cases of SCL and 25 cases of PL (66%). While in many cases they are inconspicuous, in some others they constitute a very prominent component of the tumor. It is important to be aware of this fact in order to avoid misinterpretation as liposarcoma.

Differential diagnosis of atypical lipomatous tumor/well-differentiated liposarcoma and dedifferentiated liposarcoma: utility of p16 in combination with MDM2 and CDK4 immunohistochemistry.

The differential diagnosis between atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDLPS) and dedifferentiated liposarcoma (DDLPS) from their morphologic counterparts is challenging. Currently, the diagnosis is guided by MDM2 and CDK4 immunohistochemistry (IHC) and is confirmed by the amplification of the corresponding genes. Recently, p16 IHC has been proposed as a useful diagnostic biomarker. The objective was to assess the utility of p16 IHC in the differential diagnosis of ALT/WDLPS and DDLPS. Our series included 101 tumors that were previously analyzed using fluorescence in situ hybridization for MDM2 and CDK4 amplification. We compared sensitivity and specificity of p16 IHC to MDM2 and CDK4 IHC in the differential diagnosis of ALT-WDLPS (n=19) versus benign adipocytic tumors (n=44) and DDLPS (n=18) versus mimicking sarcomas (n=20). In the differential diagnosis of ALT-WDLPS, p16 had a sensitivity of 89.5% but a specificity of 68.2%, which was impaired by false-positive lipomas with secondary changes, especially in biopsies. Likewise, in the differential diagnosis of DDLPS, p16 had a sensitivity of 94.4% and a specificity of 70%, which hampered its use as a single marker. However, adding p16 to MDM2 and/or CDK4 increased diagnostic specificity. Indeed, MDM2+/p16+ tumors were all ALT-WDLPS, and MDM2-/p16- tumors were all benign adipocytic tumors. Moreover, all MDM2+/CDK4+/p16+ tumors were DDLPS, and the MDM2-/CDK4-/p16- tumor was an undifferentiated sarcoma. Although the use of p16 as a single immunohistochemical marker is limited by its specificity, its combination with MDM2 and CDK4 IHC may help discriminate ALT-WDLPS/DDLPS.

A subset of fat-predominant angiomyolipomas label for MDM2: a potential diagnostic pitfall.

Angiomyolipomas (AMLs) are typically benign mesenchymal tumors with variable histologic composition. Fat-predominant AMLs can mimic well-differentiated liposarcomas (WDLSs) both radiographically and histologically because of the abundance of fat with admixed atypical cells resembling lipoblasts. However, the treatment and prognosis of AMLs and WDLSs are vastly different. Immunohistochemistry for murine double minute 2 (MDM2) has been used to support a diagnosis of WDLS; however, MDM2 labeling has not been specifically evaluated in fat-predominant AMLs. Here, we evaluated MDM2 immunohistochemistry in 36 AMLs (including 14 conventional AMLs, 13 fat-predominant AMLs, 6 fat-rich AMLs, 3 epithelioid AMLs) and 10 WDLSs. In addition, we labeled cases for HMB45, calponin, or actin, which are immunostains traditionally used to label AML. We performed fluorescence in situ hybridization (FISH) for MDM2 amplification on selected cases. By immunohistochemistry, 14% (5/36) of AMLs were MDM2+, including 23% (3/13) of fat-predominant AMLs. All MDM2+ AMLs evaluated by FISH (n=4) were negative for MDM2 amplification. By immunohistochemistry, 90% of WDLSs were MDM2+, and both MDM2+ WDLSs evaluated by FISH (n=2) were MDM2 amplified. All 36 AMLs labeled with HMB45 and calponin or actin. No WDLS labeled with HMB45; however, 80% of WDLSs labeled with calponin or actin. Although uncommon, MDM2 labeling is seen in a subset of fat-predominant AMLs and is a potential diagnostic pitfall in the evaluation of fatty tumors of the retroperitoneum. HMB45 is more sensitive and specific for AML than calponin or actin, and an immunopanel containing both HMB45 and MDM2 may be warranted to distinguish between fat-predominant AML and WDLS in histologically ambiguous cases.

Pericytic mimicry in well-differentiated liposarcoma/atypical lipomatous tumor.

Pericytes are modified smooth muscle cells that closely enwrap small blood vessels, regulating and supporting the microvasculature through direct endothelial contact. Pericytes demonstrate a distinct immunohistochemical profile, including expression of smooth muscle actin, CD146, platelet-derived growth factor receptor ß, and regulator of G-protein signaling 5. Previously, pericyte-related antigens have been observed to be present among a group of soft tissue tumors with a perivascular growth pattern, including glomus tumor, myopericytoma, and angioleiomyoma. Similarly, malignant tumor cells have been shown to have a pericyte-like immunoprofile when present in a perivascular location, seen in malignant melanoma, glioblastoma, and adenocarcinoma. Here, we examine well-differentiated liposarcoma specimens, which showed some element of perivascular areas with the appearance of smooth muscle (n = 7 tumors). Immunohistochemical staining was performed for pericyte antigens, including smooth muscle actin, CD146, platelet-derived growth factor receptor ß, and regulator of G-protein signaling 5. Results showed consistent pericytic marker expression among liposarcoma tumor cells within a perivascular distribution. MDM2 immunohistochemistry and fluorescence in situ hybridization for MDM2 revealed that these perivascular cells were of tumor origin (7/7 tumors), whereas double immunohistochemical detection for CD31/CD146 ruled out an endothelial cell contribution. These findings further support the concept of pericytic mimicry, already established in diverse malignancies, and its presence in well-differentiated liposarcoma. The extent to which pericytic mimicry has prognostic significance in liposarcoma is as yet unknown.

Giant liposarcoma of the esophagus: A case report.

Liposarcomas rarely develop in the aerodigestive tract. Here, we present a primary esophageal liposarcoma that was discovered between the T3 and T7 levels of the esophagus during right pleural exploration of a 51-year-old male patient. The patient had presented with non-specific symptoms, including progressive dysphagia over the previous 6 mo, without complaints of chest or epigastric pain, regurgitation, or weight loss. A radical three-hole esophagectomy was performed. The tumor was extremely large (14 cm × 7.0 cm × 6.5 cm), but completely encapsulated. Upon histological examination, the tumor was diagnosed as a giant, well-differentiated esophageal liposarcoma with a dedifferentiated component. Non-specific radiological and endoscopic results during the clinical work-up delayed diagnosis until post-operative histology was performed. In this report, the clinical, radiological and endoscopic diagnostic challenges specific to the case are discussed, as well as the surgical and pathological findings.

Relationship of endothelial area with VEGF-A, COX-2, maspin, c-KIT, and DOG-1 immunoreactivity in liposarcomas versus non-lipomatous soft tissue tumors.

Soft tissue tumors are rare tumors that show a heterogeneous structure; thus far, their molecular behavior has not been elucidated. The aim of our study was to define the relationship between microvessel density (MVD), evaluated with CD31, and other immunohistochemical markers, such as vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2), CD34, maspin, DOG-1, and c-KIT. Immunostains were done in 55 cases consisting of benign and malignant tumors, such as liposarcomas, dermatofibrosarcomas, and tumors with histiocytic differentiation. Renal tubes were used as external control for VEGF, maspin, and DOG-1. Although DOG-1 is considered a specific marker for gastrointestinal tumors (GISTs), its positivity, correlated with c-KIT and VEGF immunoexpression, was also shown by dermatofibrosarcomas and tumors with histiocytic and lipomatous differentiation, suggesting its possible pro-angiogenic role. Maspin expression was observed in adipose tissue tumors only. Regarding angiogenesis, 31 of the 55 cases were VEGF-positive, such positivity being directly correlated with COX-2 and CD34 positivity as evaluated in the tumor cells and also with MVD. Although no significant differences in angiogenic activity were found between benign and malignant non-lipomatous tumors, the MVD was directly correlated with the histological type/grade of liposarcomas. Based on these aspects, we conclude that VEGF/COX-2-induced angiogenesis is specific for non-lipomatous tumors, whereas liposarcomas are dependent on the VEGF/maspin angiogenic pathway. The DOG-1/c-KIT/VEGF target may be used for further personalized therapy of soft tissue sarcomas. No data about DOG-1 and maspin positivity in liposarcomas have been published to date.

Myogenic differentiation and histologic grading are major prognostic determinants in retroperitoneal liposarcoma.

The aim of the present work was to improve the understanding of the impact of malignancy grade and myogenic/rhabdomyoblastic differentiation on the natural course of retroperitoneal liposarcoma. All consecutive patients affected by primary well-differentiated (WD)/dedifferentiated (DD) retroperitoneal liposarcoma, surgically treated at our institution between January 2002 and December 2011, were retrospectively evaluated. Tumors were stained for mdm2 and 5 myogenic markers (smooth muscle actin-α, h-caldesmon, calponin, desmin, myogenin). The French National Federation of the Centers for the Fight Against Cancer (FNCLCC) grading system was applied. Overall survival, crude cumulative incidence of local recurrence, and distant metastases were calculated. Multivariable analyses were carried out. A total of 144 patients were identified. Median follow-up was 68 months (interquartile range: 46 to 104 mo). Fifty-two patients were affected by WD/G1 and 92 by DD liposarcoma. Among the latter, 60 were grade G2 and 32 G3. Myogenic differentiation was present in 54 cases (8/52 WD/G1, 27/60 DD/G2, 18/32 DD/G3). Seven cases had a rhabdomyoblastic DD component (1/60 DD/G2 and 6/32 DD/G3). Five-year overall survival rates were 93%, 57%, and 21% for WD/G1 liposarcoma, G2 DD, and G3 DD liposarcoma, respectively, and 75%, 42%, and 29% for liposarcoma without myogenic differentiation, with myogenic differentiation, with rhabdomyoblastic differentiation, respectively (P<0.001). Of note, 5/6 patients affected by G3 DD liposarcoma with a rhabdomyoblastic component died within 8 months. FNCLCC grade and myogenic differentiation significantly predicted the outcome of retroperitoneal liposarcoma. These should be factored into treatment decision-making and possibly used to stratify patients in clinical trials.

[Dedifferentiated Liposarcoma with Peculiar Meningothelial-Like Whorling and Metaplastic Bone Formation, Case Report]. / Meningotelyal Benzeri Girdapsi Yapilar ve Metaplastik Kemik Yapimi ile Karakterli Dediferansiye Liposarkom Olgusu.

Dedifferentiated liposarcoma represents a both morphologically and biologically fascinating lesion in which transition from low-grade to high-grade nonlipogenic morphology within a well-differentiated liposarcoma is observed. A peculiar form of dedifferentiated liposarcoma characterized by a nonlipogenic component with a meningothelial- like whorling pattern of growth and metaplastic bone formation has been described. A 59-year-old man presented with a pelvic retroperitoneal mass measuring 13x10x8 cm. Histopathologically the mass consisted almost entirely of a dedifferentiated nonlipogenic component with meningothelial-like whorling pattern, metaplastic cartilage and bone. Dedifferentiated liposarcoma with meningothelial- like whorling pattern has rarely been encountered. Here, we report this case because of the problems in differential diagnosis especially for cases that have an extensive dedifferentiated component and the uncertainty of the biological behavior of these tumors.

Retroperitoneal liposarcoma with colonic involvement: a case report.

A 72-year-old male visited a local hospital on presentation of melena. Colonoscopy revealed a protruded lesion in the ascending colon, and computed tomography revealed a 20 cm retroperitoneal tumor. Biopsy failed to provide a definitive diagnosis of the colonic lesion. He was diagnosed as having a retroperitoneal liposarcoma and an ascending colon tumor using computed tomography, and referred to our hospital. Biopsy of the ascending colon lesion showed spindle cells with fibrosis. On immunohistochemical staining, tumor cells were positive for cyclin-dependent kinase 4 and murine double minute 2, and the lesion was diagnosed as a well-differentiated or dedifferentiated liposarcoma. The retroperitoneal liposarcoma, which had infiltrated the ascending colon, was resected along with the right colon and the right kidney. Macroscopically, the tumor had infiltrated the ascending colon, forming a multinodular solid mass in the lumen and the right kidney. Microscopic finding of the main tumor revealed a well-differentiated liposarcoma, and that of the colonic lesion revealed a dedifferentiated liposarcoma with nuclei of different sizes and shapes and increased spindle cell morphology. The right kidney and ureter were surrounded by tumor cells but were not infiltrated, and there was no lymph node involvement. The diagnosis of retroperitoneal liposarcoma is often difficult because symptoms appear only after the tumor becomes very large. Some retroperitoneal liposarcomas are found on computed tomography by chance. The clinical course of this case was very rare because of the presentation of melena as the first symptom and the detection of an invasive mass in the ascending colon using colonoscopy.

Are peripheral purely undifferentiated pleomorphic sarcomas with MDM2 amplification dedifferentiated liposarcomas?

Dedifferentiated liposarcoma (DDLPS) has been defined as a tumor composed of well-differentiated liposarcoma associated with a nonlipogenic undifferentiated sarcoma and is genetically characterized by a 12q13-15 amplicon with MDM2 amplification. Some peripheral (extremities, trunk wall, head/neck) undifferentiated pleomorphic sarcomas (UPS) without areas of well-differentiated liposarcoma present an MDM2 amplification. We addressed whether they are true DDLPS or not. We compared the clinical data, histologic data, MDM2 status (immunohistochemistry [IHC], fluorescence in situ hybridization [FISH]), genomic profile (array comparative genomic hybridization), and follow-up of 19 patients with peripheral UPS with MDM2 amplification and 62 with peripheral conventional DDLPS retrieved from the French sarcoma network (RRePS) and the Conticabase (Connective Tissue Cancer Network database). For a control cohort, we described 153 patients from the Conticabase, with peripheral UPS without expression of MDM2 by IHC. By IHC, tumor cells were positive for MDM2 in 59 conventional DDLPS and in all UPS with MDM2 amplification. FISH analysis and/or quantitative polymerase chain reaction showed amplification of MDM2 in 54 conventional DDLPS and in all UPS with MDM2 amplification. The 2-year overall survival rates of UPS with MDM2 amplification, conventional DDLPS, and UPS without expression of MDM2 were 93.3%, 90.7%, and 73.9%, respectively. Such similarities in the clinical characteristics, morphology, genomic profile, and follow-up of peripheral UPS with MDM2 amplification and peripheral conventional DDLPS strongly suggest that peripheral UPS with MDM2 amplification are in fact DDLPS. Faced with histologic diagnosis of UPS, a systematic IHC evaluation of MDM2 allows a selection of cases for FISH analysis permitting the diagnosis of DDLPS.