Liposarcoma occurs in the deep soft tissue of extremities and in the retroperitoneum. It is the most common soft tissue sarcoma and accounts for 20% of all mesenchymal tumors. They are typically large bulky tumors which tend to have multiple satellite lesions extending beyond the gross confines of the tumor. Patients usually note a deep seated mass in their soft tissue for tumors of the extremity. Only when the tumor is very large, do symptoms of pain or functional disturbances occur. Retroperitoneal tumors may present with signs of weight loss and emaciation and abdominal pain. These tumors may also compress the kidney or ureter leading to kidney failure.
Histological patterns vary from round cell, myxoid, well differentiated, and pleomorphic type. The round cell and pleomorphic types are the most aggressive with a relentless history of recurrences. The pathologist must differentiate this tumor from other soft tissue sarcomas, particularly malignant fibrous histiocytomas.
Epidemiology Disease Associations Pathogenesis Laboratory/Radiologic/Other Diagnostic Testing Gross Appearance and Clinical Variants Histopathological Features and Variants Special Stains/Immunoperoxidase Differential Diagnosis Prognosis and Treatment Commonly Used Terms Internet Links
EPIDEMIOLOGY CHARACTERIZATION INCIDENCE 9-16% of all soft tissue sarcomas AGE RANGE-MEDIAN
Retroperitoneal tumors are 5-10 years older than tumors of the extremities since they are detected later
SEX (M:F) Males 55-61%
May have slight female predominance in retroperitoneum
EPIDEMIOLOGIC ASSOCIATIONS CHARACTERIZATION Trauma Isolated case reports Postradiation Rare case Arising within a pre-existing lipoma Probably very rare
DISEASE ASSOCIATIONS CHARACTERIZATION EPIDERMAL
- Am J Dermatopathol. 2006 Aug;28(4):338-40 Abstract quote
Epidermal inclusion cysts are an exceedingly common entity seldom seen in association with a malignant tumor.
Herein, we report a unique case of an epithelial inclusion cyst seen in association with an atypical lipomatous tumor/well-differentiated liposarcoma. The epidermal inclusion cyst was delimited to the dermis and circumferentially enveloped by an atypical adipocyte tumor containing myxoid foci and comprised of lipoblasts.
This case underscores the importance of scrutinizing the entirety of cysts and other ostensibly trivial dermal entities to avoid the pitfall of misdiagnosing a potentially serious tumor.
PATHOGENESIS CHARACTERIZATION BETA-CATENIN
beta-Catenin Accumulation and Gene Mutation in Exon 3 in Dedifferentiated Liposarcoma and Malignant Fibrous Histiocytoma.
Sakamoto A, Oda Y, Adachi T, Saito T, Tamiya S, Iwamoto Y, Tsuneyoshi M.
Departments of Anatomic Pathology, Pathological Sciences (Drs Sakamoto, Oda, Adachi, Saito, Tamiya, and Tsuneyoshi), and Orthopaedic Surgery (Dr Iwamoto), Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Arch Pathol Lab Med 2002 Sep;126(9):1071-8 Abstract quote
Context.-beta-Catenin is an adhesion molecule that also plays a role in the Wnt signaling pathway.
Objective.-To analyze beta-catenin mutation and accumulation in a series of liposarcomas and malignant fibrous histiocytomas.
Design.-beta-Catenin mutation in exon 3 was studied using polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and direct sequencing analysis in 30 formalin-fixed, paraffin-embedded liposarcomas. The tumors included 12 dedifferentiated liposarcomas, characterized by both high-grade anaplastic components and well-differentiated liposarcoma components, plus 18 well-differentiated liposarcomas (10 lipoma-like and 8 sclerosing-type cases). The 2 components of dedifferentiated liposarcomas were analyzed independently. beta-Catenin accumulation in the nuclei or cytoplasm and Ki-67 expression (cell-proliferation marker, MIB-1 labeling index) were examined immunohistochemically. Nine storiform-pleomorphic-type malignant fibrous histiocytomas were also studied.
Results.-Dedifferentiated liposarcomas showed mutation in 2 cases (17%) and accumulation in 5 cases (42%). One of the 2 cases that showed mutations had a mutation in the well-differentiated component; this mutation was silent. The other case had mutations that differed between the 2 components. In well-differentiated liposarcomas, mutation was not seen in any of the cases (0/18; 0%); however, accumulation was seen frequently in the sclerosing-type cases (5/8; 63%), but not in the lipoma-like cases (0/10; 0%). Malignant fibrous histiocytomas showed mutation and accumulation in 5 (56%) and 4 (44%) cases, respectively, without any exact correlation between the cases. Cases with accumulation had a higher MIB-1 labeling index than those without, among both the sclerosing-type well-differentiated liposarcomas (P <.05) and the malignant fibrous histiocytomas.
Conclusions.-Our results suggest the possible involvement of beta-catenin activation caused by beta-catenin mutation in liposarcoma and malignant fibrous histiocytoma, but the contribution would seem to be different, depending on the tumor type. beta-Catenin accumulation is also thought to be related to cell proliferation in some of the cases.
Chromosomal abnormalities Not a feature of well-differentiated and pleomorphic liposarcomas MDM2-CDK4 AMPLIFICATION
- Detection of MDM2-CDK4 Amplification by Fluorescence In Situ Hybridization in 200 Paraffin-embedded Tumor Samples: Utility in Diagnosing Adipocytic Lesions and Comparison With Immunohistochemistry and Real-time PCR.
- Sirvent N, Coindre JM, Maire G, Hostein I, Keslair F, Guillou L, Ranchere-Vince D, Terrier P, Pedeutour F.
*Laboratory of Solid Tumors Genetics, CNRS UMR 6543 †Department of Pediatry, Nice University Hospital, Nice ‡Department of Pathology, Institut Bergonié and University Victor Ségalen, Bordeaux ∥Department of Pathology, Centre Léon Bérard, Lyon ¶Department of Pathology, Institut Gustave Roussy, Villejuif, France §Department of Pathology, University Institute of Pathology, Lausanne, Switzerland.
- Am J Surg Pathol. 2007 Oct;31(10):1476-1489. Abstract quote
Atypical lipomatous tumor/well-differentiated liposarcomas and dedifferentiated liposarcomas are characterized by the amplification of MDM2 and CDK4 genes.
To evaluate the accuracy of fluorescence in situ hybridization (FISH) analysis in the differential diagnosis of adipose tissue tumors, we investigated MDM2-CDK4 status by FISH, real-time polymerase chain reaction (PCR) [quantitative PCR (Q-PCR)] and immunohistochemistry (IHC) in a series of 200 adipose tumors.
First, we evaluated MDM2-CDK4 amplification and expression in a series of 94 well-defined adipose tissue tumors. Results showed that FISH was interpretable in 45 of 50 cases (90%), and was more specific and sensitive than Q-PCR and IHC. We then used the same techniques as complementary diagnostic tools in a series of 106 adipose and soft tissue tumors of unclear diagnosis to distinguish between (i) lipomas and atypical lipomatous tumor/well-differentiated liposarcomas, (ii) malignant undifferentiated tumors and dedifferentiated liposarcomas, and (iii) a variety of benign tumors and liposarcomas.
Our results indicate that although helpful, IHC alone is often insufficient to solve diagnostic problems. FISH and Q-PCR methods gave concordant results and were equally informative in most cases. However, the proportion of noninterpretable cases was slightly higher with FISH than with Q-PCR. When tumor cells represented a minor component of the tumor tissue, such as with inflammatory tumors, FISH was more powerful than Q-PCR by allowing visualization of individual cells.
In conclusion, we recommend that the evaluation of MDM2-CDK4 amplification using FISH or Q-PCR be used to supplement IHC analysis when diagnosis of adipose tissue tumors is not possible based on clinical and histologic information alone.
The 12q13-15 region encodes for important protooncogenes including MDM2, CDK4, HMGI-C, SAS, GLI, CHOP, OS1, and OS9 which play varying roles in oncogenesis
Myxoid and round cell liposarcomas share the same translocation which fuses the CHOP gene with the FUS or EWS gene
Pleomorphic tumors have complex rearrangements
Trisomy 8 H-ras oncogene mutation in dedifferentiated liposarcoma
Am J Clin Pathol 2001;115:235-242
Point mutations at codons 12 and 13 of the H-ras gene was studied in 34 liposarcomas, comprising 15 well-differentiated liposarcomas and 19 dedifferentiated liposarcomas, and in 8 storiform-pleomorphic type malignant fibrous histiocytomas (MFHs) using polymerase chain reaction–restriction fragment length polymorphism and direct sequencing analysis. The 2 components of dedifferentiated liposarcoma were analyzed independently
H- ras mutations were seen only in dedifferentiated liposarcomas (4/19 [21%]), 1 in WD components and 3 in HG components. The mutation was not seen in any of 15 cases of well-differentiated liposarcoma. MFHs showed an H-ras mutation in 1 (12%) of 8 cases
Results seem to suggest that the H-ras mutation is a relatively uncommon event in dedifferentiated liposarcoma, which may demonstrate an epiphenomenon of dedifferentiation in dedifferentiated liposarcoma
CHARACTERIZATION Radiographs Radiolucent tumors have little vascularity while radiopaque tumors such as myxoid, round cell, and pleomorphic types are richly vascular
Myxoid liposarcoma: magnetic resonance imaging appearances with clinical and histological correlation.
Sundaram M, Baran G, Merenda G, McDonald DJ.
Department of Radiology, St. Louis University Medical Center, Missouri 63110-0250.
Skeletal Radiol 1990;19(5):359-62 Abstract quote
Myxoid liposarcoma is the most common type of liposarcoma. The magnetic resonance imaging (MRI) features of this tumor were evaluated and correlated with its clinical and histological features in seven patients to determine under what circumstances the tumor should be considered in differential diagnosis and why its signal intensity differs from those of lipoma and lipoma-like (lipoblastic) liposarcoma.
In all patients the tumor presented in a lower extremity (5 thigh, 2 calf) as a painless, slowly growing mass which had been present for several months to several years. MRI examination revealed the tumors to be encapsulated, noninfiltrating, and usually septated. On T1-weighted sequences five of seven lesions (71%) showed lacy, amorphous, or linear foci of high signal within a low signal mass. These foci are believed to represent fat within the tumor and distinguish it from several other benign and malignant masses. If an indolent mass in a lower extremity demonstrates a predominantly low signal with a few amorphous or linear high signal foci on T1-weighted sequences, one should consider the possibility of myxoid liposarcoma even if it appears benign by all other criteria.
Histologic evaluation showed that myxoid liposarcomas contain less than 10% mature fat, which accounts for their low signal on T1-weighted sequences in contrast to the high signal of lipomas and lipoblastic liposarcomas.
Liposarcoma of soft tissue: MRI findings with pathologic correlation.
Arkun R, Memis A, Akalin T, Ustun EE, Sabah D, Kandiloglu G.
Department of Radiology, Hospital of Ege University, Bornova, Izmir, Turkey.
Skeletal Radiol 1997 Mar;26(3):167-72 Abstract quote
OBJECTIVE: To evaluate the MRI findings of liposarcomas of different histologic types and correlate these with the histopathologic features.
DESIGN: The MR images of seven liposarcomas were reviewed retrospectively to assess the tumor size, location, margination, signal characteristics and enhancement patterns in different histologic types.
PATIENTS: Seven liposarcomas comprising three well-differentiated, two myxoid and two pleomorphic types were evaluated.
RESULTS AND CONCLUSION: All tumors showed well-defined and mostly lobulated margins. The well-differentiated liposarcomas were composed mainly of fat with septations or nodules, were hyperintense on T2-weighted images, and demonstrated faint enhancement or no enhancement following intravenous contrast. Myxoid liposarcomas were homogeneous or mildly heterogeneous and a pseudocapsule was present in one case. Pleomorphic types showed a markedly heterogeneous internal structure. Both myxoid and pleomorphic lesions-showed moderate or marked heterogeneous enhancement after contrast administration. Well-differentiated liposarcomas may be differentiated from other types of the tumor by their largely lipomatous appearance. The malignancy grade increases in parallel with tumor heterogeneity and contrast enhancement.
Myxoid liposarcoma: appearance at MR imaging with histologic correlation.
Sung MS, Kang HS, Suh JS, Lee JH, Park JM, Kim JY, Lee HG.
Department of Radiology, Catholic University of Korea at Holy Family Hospital, Sosa-dong, Puchun, Korea.
Radiographics 2000 Jul-Aug;20(4):1007-19 Abstract quote
Although myxoid liposarcoma is a subtype of liposarcoma, it may be difficult to establish the correct diagnosis with magnetic resonance (MR) imaging due to the lack of fat signal intensity.
Without the administration of gadolinium contrast material, the tumor may even mimic a cystic tumor. A spectrum of MR imaging abnormalities occur in myxoid liposarcoma, depending on the amount of fat and myxoid material, the degree of cellularity and vascularity, and the presence of necrosis. Most myxoid liposarcomas have lacy or linear, amorphous foci of fat. Some myxoid liposarcomas appear to be cystic at nonenhanced MR imaging, although they enhance like other solid masses at contrast material-enhanced MR imaging. The enhancing areas within the tumor represent increased cellularity and vascularity; the nonenhancing areas represent necrosis, reduced cellularity, and accumulated mucinous material. Gadolinium-enhanced imaging is important in differentiating myxoid liposarcoma from benign cystic tumors.
Characterization of the tumor with MR imaging plays an important role in the management of myxoid liposarcoma.
Most measure between 5-10 cm but cases greater than 15 cm have been reported
Tend to be well circumscribed or encapsulated with a distinct lobular pattern-common to have small separate lobules forming satellite nodules extending beyond the surgical margins
Mucinous and gelatinous cut surface often with hemorrhage-tumors with less fatty differentiation have a white or gray surface
SITES Most common sites are the extremities and retroperitoneum LIVER
Arch Pathol LabMed 2001;125:410–412
The authors present the eighth case, which occurred in an adult female patient.
Liposarcoma is an absolute contraindication for liver transplantation
Department of Pathology, Brigham and Womenʼs Hospital and Harvard Medical School, Boston, MA.
- Am J Surg Pathol. 2007 Dec;31(12):1868-1874. Abstract quote
Liposarcomas are rare in the mediastinum. Here, we report the clinicopathologic features of 24 cases of mediastinal liposarcoma. Patients included 13 males and 11 females, with an age range of 3 to 72 years (median 58). Nine tumors were located in the anterior mediastinum, 7 in the posterior mediastinum, 1 in the superior mediastinum, and the precise location was not specified in 7 cases. Of the anterior mediastinal tumors, 3 appeared to arise from the thymus. Tumors were well-circumscribed, multinodular masses and ranged in size from 2.2 to 61 cm in greatest dimension (median 16 cm).
Histologic examination revealed that most of the cases were well-differentiated liposarcomas (10), followed by dedifferentiated liposarcomas (8), pleomorphic liposarcomas (4), and myxoid liposarcomas (2). Of the pleomorphic liposarcomas, 2 had areas that resembled myxofibrosarcoma with atypical hyperchromatic spindle cells in a myxoid stroma, but the focal presence of lipoblasts confirmed the diagnoses.
Clinical follow-up was obtained in 15 cases (range 1 to 59 mo; median 26). Complete surgical excision was attempted in 13 patients; however, local recurrence was common (5 cases), including 1 patient whose tumor recurred twice. Eleven patients were alive with no evidence of disease at last follow-up (5 well-differentiated, 5 dedifferentiated, and 1 myxoid liposarcoma). Two patients developed distant metastases (dedifferentiated and pleomorphic liposarcoma). One patient was alive with disease (pleomorphic liposarcoma), and 2 died of disease (pleomorphic and dedifferentiated liposarcoma).
Overall, mediastinal liposarcomas appear to be similar, in clinicopathologic terms, to liposarcomas arising in the retroperitoneum.
Liposarcomas/atypical lipomatous tumors of the oral cavity: A clinicopathologic study of 23 cases.
Nascimento AF, McMenamin ME, Fletcher CD.
Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
Ann Diagn Pathol 2002 Apr;6(2):83-93 Abstract quote
Liposarcomas in the oral cavity have rarely been described, with less than 50 reported cases to date and a purported predominance of the myxoid type.
We reviewed our experience with 23 atypical lipomatous tumors/liposarcomas of the oral cavity. Twelve patients were men, 10 were women, and gender was not stated in one case. Age at presentation ranged from 28 to 83 years (median, 49.5 years). The most commonly affected site was the tongue and most cases presented as a slowly growing, painless mass. The clinical impression was lipoma or fibroma in the majority of cases. Tumor size ranged from 0.6 to 8.0 cm (median, 1.5 cm). Five cases were well circumscribed, 5 cases were focally infiltrative, and 13 cases had markedly infiltrative margins. Twenty-one cases were classified as atypical lipomatous tumors (of which 10 showed spindle cell features), one as dedifferentiated liposarcoma, and one as myxoid liposarcoma. Follow-up data was available in 13 of the 23 cases. Five others were lost to follow-up after a short period. Eleven patients remained free of disease without local recurrence or metastasis during the period of follow-up that ranged from 10 months to 9 years (median, 24 months). Two patients had multiple local recurrences.
Our study shows that atypical lipomatous tumor is the most common type of malignant fatty tumor to arise in the oral cavity with an apparently low risk of recurrence if widely excised, although follow-up is relatively limited thus far.
Liposarcoma of the oral and salivary gland region: a clinicopathologic study of 18 cases with emphasis on specific sites, morphologic subtypes, and clinical outcome.
Fanburg-Smith JC, Furlong MA, Childers EL.
Departments of Soft Tissue (JCFS, MAF) and Oral and Maxillofacial Pathology (ELBC), The Armed Forces Institute of Pathology, Washington, DC.
Mod Pathol 2002 Oct;15(10):1020-31 Abstract quote
Liposarcoma is rare in the oral and salivary gland region (OSG), previously described in only case reports and two small series. Clinicopathologic features of a large series of these tumors were studied. Cases coded as "liposarcoma or lipoma" from 1970 to 2000 were searched for in our files. Inclusion required an OSG location and diagnosis by established soft tissue criteria. Dermal, other soft tissue, and intraosseous liposarcomas were excluded.
Clinical and pathologic material was reviewed and follow-up obtained. Eighteen liposarcomas were included: 10 from males and 8 from females. The median patient age was 51 years (range, 30-70 years). Specific anatomic locations included buccal mucosa (n = 7), tongue (n = 4), parotid gland (n = 3), soft tissue overlying the mandible (n = 2), and one each of palate and submandibular gland. The average tumor size was 4.2 cm (range, 1.5 to 6.0 cm). Histologically, most tumors were well differentiated, including one atypical lipoma (n = 10), followed by myxoid (n = 5) and dedifferentiated (n = 3). OSG liposarcomas of all subtypes had increased numbers of lipoblasts. All patients were treated with surgical excision alone.
Follow-up on 15 patients (83%) over a mean of 16.5 years (range, 2 to 53 years) revealed that three patients had between one and six local recurrences over periods of 18 months to 6 years. Twelve patients were without recurrence, with a mean follow-up of 12.8 years (range, 2-23 years).
No patients, including those with dedifferentiated liposarcoma, had metastases or died of disease. OSG liposarcomas are rare tumors of adults, occurring most commonly in the buccal mucosa, tongue, and then parotid gland. There were no pleomorphic liposarcomas in this series; well-differentiated liposarcoma was the most common subtype, which can locally recur but, even with high-grade dedifferentiation, does not necessarily predict poor outcome.
Therefore, OSG liposarcomas have better prognosis than liposarcoma in other soft-tissue locations, perhaps based on smaller size at presentation. Complete local excision and careful patient follow-up, without adjuvant therapy, appears to be the best treatment for OSG liposarcoma.
Primary liposarcoma of the orbit: A clinicopathologic study of seven cases
Yun-Cai Cai, MD
Máirín E. McMenamin, MB, MRCPI, MRCPath
Geoff Rose, MS, FRCOphth
Charles J. Sandy, FRCOphth
Ian A. Cree, MB, PhD, FRCPath
Christopher D.M. Fletcher, MD, FRCPath
Ann Diagn Pathol 2001;5:255-266 Abstract quote
Liposarcoma, the most common soft tissue sarcoma in adults, will rarely involve the orbit, either primarily or as a metastasis.
We describe seven primary orbital liposarcomas, representing the largest documented series of primary orbital liposarcoma to date. Affected patients were three males and four females ranging in age from 28 to 69 years (median, 51 years). Five patients presented with painless proptosis, one patient had painful proptosis, and no details of presenting symptoms are available in one case. The site distribution was retrobulbar (3 cases), lateral orbital wall (2 cases), medial wall (1 case), and unspecified (1 case). Radiologic impression included hemangioma, lipoma, and an inflammatory process. Lesional size ranged from 2.8 to 4 cm.
Five liposarcomas were purely well-differentiated, one was dedifferentiated, and one was pleomorphic in type. The well-differentiated cases comprised the following subtypes: spindle cell (2 cases), adipocytic (2 cases), and combined adipocytic/sclerosing/inflammatory (1 case). Five patients underwent orbital exenteration (one followed by radiation) and two had marginal/partial excision of their tumors. Follow-up was available for five patients, ranging from 13 to 204 months (median 65 months). Four patients showed no evidence of recurrence, including the patient with pleomorphic liposarcoma who had a long, disease-free survival (65 months) following marginal excision. One patient has had multiple recurrences following initial partial excision. One patient died of an unrelated cause with no clinical evidence of recurrence.
Despite the difficulty in obtaining wide surgical margins, the small tumor size at presentation and the apparent predominance of the well-differentiated type means that the prognosis for orbital liposarcoma is generally good.
In view of the various morphologic patterns that may occur, liposarcoma should be considered in the differential diagnosis of any histologically unusual mesenchymal lesion in the orbit.
Paratesticular liposarcoma: a clinicopathologic study.
Montgomery E, Fisher C.
Am J Surg Pathol 2003 Jan;27(1):40-7 Abstract quote
Paratesticular liposarcomas are rare and typically reported as isolated cases or as components of larger studies of liposarcomas.
We studied a series of these tumors. All cases of paratesticular liposarcomas were retrieved from the archives of the Royal Marsden Hospital and the Johns Hopkins Hospital. Slides were reviewed and clinical information obtained. There were 30 paratesticular liposarcomas from men aged 41-87 years (mean 63 years; median 65 years) that involved the spermatic cord (23, 76%), testicular tunics (6, 20%), and epididymis (1, 4%). Tumors ranged from 3 to 30 cm (mean 11.7 cm; median 10 cm). Nineteen were well-differentiated liposarcomas (WDLs) and 10 were dedifferentiated liposarcomas (DDLs, five with high-grade and five with low-grade dedifferentiation). One was a myxoid/round cell liposarcoma with 70% round cell areas.
All patients were treated by radical orchiectomy. One patient with WDL received radiation after his second recurrence and the myxoid/round cell liposarcoma received radiation and chemotherapy.
Follow-up information was available for 16 of the patients, including 10 WDLs (range 24-216 months, mean 106 months), 5 DDLs (14-30 months, median 24 months), and for the myxoid/round cell liposarcoma (14 months) (range for all cases 14 months to 22 years; mean 87 months, median 36 months). Six of the WDLs (60%) recurred at 2, 4, 6, 10, 18, and 21 years (median 8 years). The lesion that recurred at 18 years (case no. 6) displayed foci of high-grade dedifferentiation in the recurrence, although the patient was disease free at 19 years. One patient with WDL had two recurrences at 4 and 7 years, and another had six recurrences over a 17-year period. Only one example of DDL recurred, at 30 months; another patient, who refused therapy for 15 years, had a primary tumor 30 cm in diameter, displayed pulmonary metastases 1 month after excision, and died after 14 months. The patient with MRCL had abdominal metastases after 1 year and was alive at 14 months.
In summary, paratesticular WDL had a prolonged course with recurrences in more than half the cases, sometimes late. There were no metastases and the overall prognosis was good. One DDL recurred and only one of five (20%) developed metastases, but the mean follow-up for DDL was only 24 months.
Dedifferentiated liposarcoma of the pyriform sinus: report of a case and review of the literature.
Gonzalez-Lois C, Ibarrola C, Ballestin C, Martanez-Tello FJ.
Pathology Department, University Hospital "Doce de Octubre," Madrid, Spain.
Int J Surg Pathol 2002 Jan;10(1):75-9 Abstract quote
Laryngeal and hypopharyngeal liposarcomas are extraordinarily infrequent tumors.
To the best of our knowledge there are fewer than 40 well-documented cases reported to date. Almost all of them are well-differentiated liposarcomas, with only 2 laryngeal-hypopharyngeal dedifferentiated liposarcomas. Dedifferentiated liposarcoma is defined as a well-differentiated liposarcoma with areas of high-grade spindle cell nonlipogenic sarcoma. The well-differentiated areas may be of a lipoma-like, sclerosing, or mixed type, and the dedifferentiated areas most frequently are of malignant fibrous hystiocytoma-like type.
Despite its commonly pleomorphic histology, dedifferentiated liposarcoma does not behave as aggressively as most pleomorphic sarcomas of adulthood; however, it has the capacity to metastasize, in contrast to its well-differentiated counterpart. We present a case of dedifferentiated liposarcoma arising in the pyriform sinus, an event only twice reported previously in the literature.
Extremely rare, tends to occur in the scalp
Generally good prognosis which may be secondary to the relatively superficial location of the tumor
- Dedifferentiated liposarcoma of the cheek.
de la Roza G, Baredes S, Aisner SC.
Department of Pathology, State University of New York-Upstate Medical University, Syracuse 13203, USA.
Ann Diagn Pathol. 2004 Dec;8(6):352-7. Abstract quote
Liposarcomas of the head and neck region are rare; only a few cases have been reported to arise in the cheek or buccal mucosa. Dedifferentiated liposarcoma has rarely been reported in the head and neck region and, to the best of our knowledge, this is the first reported case of dedifferentiated liposarcoma of the cheek.
Dedifferentiated liposarcoma is a mixed histologic subtype defined by the association of an atypical lipomatous tumor or well-differentiated liposarcoma and a nonlipogenic sarcoma. The patient was a 61-year-old man who presented with a soft-tissue mass of the left cheek and a presumptive diagnosis of salivary neoplasm based on a fine needle aspiration. The tumor was excised and consisted histologically of an atypical lipomatous tumor/well-differentiated liposarcoma composed a well-differentiated lipomatous neoplasm with atypical cells and rare lipoblasts.
The tumor recurred in the same location 5 months after surgery. The recurrent tumor was primarily composed of a nonlipogenic spindle sarcoma with focal rhabdomyoblastic differentiation associated with areas of an atypical lipomatous tumor/well-differentiated liposarcoma.
Primary purely intradermal pleomorphic liposarcoma.
Val-Bernal JF, Gonzalez-Vela MC, Cuevas J.
Department of Anatomical Pathology, Marques de Valdecilla University Hospital, Medical Faculty, University of Cantabria, Santander, Spain.
J Cutan Pathol. 2003 Sep;30(8):516-20. Abstract quote
INTRODUCTION: Pleomorphic liposarcoma (PLPS) is a high-grade pleomorphic sarcoma, containing multivacuolated lipoblasts, which usually develops during late adult life. It usually occurs in the deep soft tissues and uncommonly arises in the subcutis, the dermis representing an exceedingly rare site of occurrence.
METHODS: We describe a case of PLPS arising in the dorsal aspect of the nose of a 75-year-old woman. Preoperative duration was 9 months.
RESULTS: The lesion was intradermal well-circumscribed, dome-shaped, measuring 1.2 cm. It fulfilled the histologic criteria for inclusion in the PLPS category. The tumor cells focally expressed calretinin. A review of the literature yielded four cases documented, to which we add the present report. All the patients were adults with a mean age of 67 (range 39-95) years, and three of five cases arose on the scalp. Local recurrence occurred in one patient, but no distant metastases or disease-related deaths were observed.
CONCLUSION: PLPS very rarely arises in the dermis. In spite of high-grade morphology, the intradermal tumor shows a relatively favorable prognosis. Diagnostic consideration includes pleomorphic lipoma, clear cell atypical fibroxanthoma, balloon cell melanoma, and metastatic clear cell carcinoma of renal origin. Recognition of this distinctive and rare type of liposarcoma is essential to avoid under- or misdiagnosis and inappropriate treatment.
HISTOLOGICAL TYPES CHARACTERIZATION GENERAL
The characteristic cell is the lipoblast although this is not required nor does it make the diagnosis
Characterized by a primitive cells with lipid droplets within the cytoplasm displacing the nucleus to the side:
Hyperchromatic indented or sharply scalloped nucleus
Lipid-rich (neutral fat) droplets in cytoplasm
Appropriate histological background
World Health Organization Classification 1994 Many investigators lump round and myxoid liposarcomas together Well differentiated liposarcoma
40-45% of all liposarcomas
Occurs equally in the retroperitoneum or limbs
Most common liposarcoma occurring in adults
Peak incidence of 6-7th decades
Although there are three classic histologic types, there are often transitional areas between the types
Oftentimes, lipoblasts are rare and diagnosis depends upon finding atypical stromal cells
Mainly mature lipocytes showing striking variation in size and shape with focal nuclear atypia and hyperchromasia
Sclerosing Occurs more frequently in the retroperitoneum and paratesticular region
Scattered bizarre stromal cells with rare lipoblasts
Inflammatory Polyphenotypic lymphocytes abundant with scattered lipoblasts DEDIFFERENTIATED
Transition from low grade to high grade nonlipogenic morphology within a well-differentiated liposarcoma occurs
Most common in retroperitoneum rather than extremities
Usually occurs within the primary tumor (90%) of time versus recurrences (10%)
Some have divided this into low grade and high grade dedifferentiation
Low grade: Bland spindle cells with a fascicular pattern with cellularity intermediate between well-differentiated sclerosing liposarcoma and usual high grade areas
Heterologous elements occur in 5-10% of cases usually with myogenic, osteo/chondrosarcomatous, or rarely angiosarcomatous
- Dedifferentiated Liposarcomas With Divergent Myosarcomatous Differentiation Developed in the Internal Trunk: A Study of 27 Cases and Comparison to Conventional Dedifferentiated Liposarcomas and Leiomyosarcomas.
*Department of Pathology, Institut Bergonié and Université Victor Segalen, Bordeaux †University Institute of Pathology, Lausanne, Switzerland ‡Department of Pathology, Institut Bergonié, Bordeaux §Department of Pathology, Val dʼAurelle Cancer Center, Montpellier ∥Department of Pathology, Georges-Francois Leclerc Cancer Center, Dijon ¶Unité INSERM U509, Institut Curie, Paris ♯Department of Oncology, Institut Bergonié **Department of Surgery, Institut Bergonié, Bordeaux, France.
- Am J Surg Pathol. 2007 Oct;31(10):1557-1566. Abstract quote
Dedifferentiated liposarcoma (DLPS) is one of the most frequent sarcomas of the retroperitoneum and represents most undifferentiated sarcomas of the internal trunk. In about 5% cases, the dedifferentiated component is an heterologous sarcoma such as leiomyosarcoma or rhabdomyosarcoma.
We reviewed a series of 65 sarcomas with a myogenic differentiation developed in the internal trunk for which initial diagnoses were leiomyosarcoma (37), rhabdomyosarcoma (6), malignant mesenchymoma (6), and DLPS (16). Immunostainings for MDM2, CDK4, alpha smooth actin, desmin, caldesmon, myogenin, c-kit, and progesterone receptor were performed. In 48 cases, the amplification status of MDM2 and CDK4 could be evaluated with quantitative polymerase chain reaction on paraffin-embedded tissues extracted DNAs.
After review of the cases, final diagnoses were leiomyosarcoma (35), rhabdomyosarcomatous (20) or leiomyosarcomatous (7) DLPS, probable DLPS (2), and malignant mesenchymoma (1). DLPS were bigger tumors (median: 18.2 cm) than leiomyosarcomas (median: 12 cm). They had a lower 5-year recurrence-free survival than leiomyosarcomas (45% vs. 71%) but a higher 5-year metastasis-free survival (73% vs. 39%). There was no significant difference in overall survival (57% vs. 34%).
Outcome of patients with a DLPS with a myosarcomatous component did not differ from conventional DLPS. In conclusion, most sarcomas with a rhabdomyosarcomatous differentiation occurring in the internal trunk of adults are DLPS. Moreover, DLPS with a myogenic component have a low metastatic potential, similar to conventional DLPS and significantly lower to the metastatic potential of leiomyosarcomas.
Mod Pathol. 2005 Nov;18(11):1461-70. Abstract quote
Dedifferentiated liposarcoma is a malignant adipocytic neoplasm containing a nonlipogenic sarcoma of variable histological grade that arises against the background of a pre-existing well-differentiated liposarcoma. The phenomenon of dedifferentiation is considered to be time-dependent, but the mechanism is not well known. The retinoblastoma protein, encoded by the RB1 gene located at 13q14, is a key regulator of proliferation, development, and differentiation of certain cell types, including adipocytes.
In the current study, we investigated the genetic alterations of the RB1 gene, such as mutation (the essential promoter region and the protein-binding pocket domain; exons 20-24) and methylation of the promoter region, in addition to pRB expression and loss of heterozygosity (LOH) status, in two morphologically distinct areas (nonlipogenic dedifferentiated and well-differentiated components) in 27 patients. As a control, 11 undifferentiated high-grade pleomorphic sarcoma/pleomorphic malignant fibrous histiocytoma samples and 11 well-differentiated liposarcoma samples were also evaluated. Dedifferentiated components showed LOH (15/25; 60%) and abnormal retinoblastoma protein expression (18/27; 66.7%) more frequently than noted in the well-differentiated components (3/24; 12.5% and 9/27; 33.3%, respectively). Five and four out of the 27 dedifferentiated components harbored mutations and promoter methylation, respectively, whereas none of these alterations were seen in the well-differentiated components.
These results suggest that retinoblastoma protein has a major role to play in dedifferentiation and that a 'two-hit' mechanism is involved in the altered retinoblastoma protein expression in dedifferentiated liposarcoma.
- Distant metastasis in retroperitoneal dedifferentiated
liposarcoma is rare and rapidly fatal: a clinicopathological
study with emphasis on the low-grade
myxofibrosarcoma-like pattern as an early
sign of dedifferentiation.
Huang HY, Brennan MF,
Singer S, Antonescu CR.
1Department of Pathology, Memorial Sloan-Kettering
Cancer Center, NY, USA.
Mod Pathol. 2005 Jul;18(7):976-84. Abstract quote
The metastatic incidence of retroperitoneal dedifferentiated liposarcoma is comparatively lower than other pleomorphic sarcomas, varying widely from 1 to 18%. Low-grade dedifferentiation resembling low-grade fibrosarcoma has been recently accepted as part of the morphologic spectrum of dedifferentiated liposarcoma and was reported to have similar metastatic and survival rates to its high-grade counterpart.
We sought to determine the metastatic incidence of retroperitoneal dedifferentiated liposarcoma, the clinicopathological features related to metastasis, and their postmetastatic behavior. Of all 354 retroperitoneal liposarcoma cases diagnosed at Memorial Sloan-Kettering Cancer Center during 1982-2003, we identified seven patients developing distant metastases, occurring in four females and three males, ranging from 35 to 73 years in age at presentation. They were all de novo dedifferentiated, while none of the well-differentiated liposarcoma or secondary dedifferentiated liposarcoma developed distant metastasis. Primary tumor sizes varied from 7.5 to 25 cm. All seven patients developing metastases contained >/=50% dedifferentiated elements in the primary tumor, with a predominant morphology resembling myxofibrosarcoma in five cases. The metastatic sites included the lung in four patients, somatic soft tissue in two, and liver in one. The median metastasis-free survival was 48 months, with only two patients experiencing local recurrences before developing metastasis. Six patients died of disease at median follow-up of 53 months after diagnosis and only 5 months after their first metastases.
In conclusion, retroperitoneal dedifferentiated liposarcoma have a low metastatic rate, which is strongly related to de novo dedifferentiated histology that usually constitutes a prominent component of the primary tumor. Irrespective of the grade dedifferentiated liposarcoma with myxofibrosarcoma-like features should be closely monitored. Once metastases occur, they tend to follow a rapidly fatal course.
with a paraganglioma-like
histologic pattern: a
case report and review of the literature.
Liu D, Quinonez G, Latosinsky S.
Department of Pathology, University of Manitoba, Winnipeg.
Arch Pathol Lab Med. 2004 Jul;128(7):788-91. Abstract quote
A 53-year-old man presented with a 4-month history of increasing abdominal discomfort and distension. A large retroperitoneal mass was found on imaging. Image-guided needle core biopsy demonstrated a poorly differentiated malignant neoplasm.
A 30 x 32 x 33-cm soft tissue mass was removed. Microscopically, the tumor consisted of predominantly epithelioid malignant cells arranged in a paraganglioma-like growth pattern. Immunohistochemically, these cells were strongly positive for neuron-specific enolase. Stains for synaptophysin and chromogranin, however, were negative. There was no ultrastructural evidence of neuroendocrine differentiation. Adjacent sarcomatous areas were composed of spindled cells arranged in storiform and fibrosarcoma-like growth patterns. A small area of well-differentiated liposarcoma was identified, and a diagnosis of dedifferentiated liposarcoma was established.
To the best of our knowledge, this represents the first reported case of dedifferentiated liposarcoma with a paraganglioma-like histologic pattern. A brief review focusing on the morphologic variations of dedifferentiated liposarcoma is also presented.
Myxoid and round cell liposarcomas are the two histologic ends of a similar tumor
Share a common tranlsocation t(12;16)(q13;p11)
Most common type with round cell, accounting for 45-55% of all liposarcomas
Preferentially in lower extremity in 75% of cases
Ages are younger ranging from 25-45 years
Pure tumors have a hypocellular spindle cell proliferation set in a myxoid background with mucin pooling resembling a pulmonary edema pattern
Pure round cell tumors are hypercellular with >80% composed of round cells with frequent transitions to myxoid areas
Lipoblasts are small
Plexiform (chicken wire) pattern of capillary sized blood vessels are frequent
Usually limbs of older patients
May resemble malignant fibrous histiocytoma with scattered lipoblasts or have a cellular spindle cell appearance with sheets of bizarre pleomorphic monovacuolated and multivacuolated lipoblasts
- Pleomorphic Liposarcoma: Clinicopathologic Analysis of 57 Cases.
Hornick JL, Bosenberg MW, Mentzel T, McMenamin ME, Oliveira AM, Fletcher CD.
*Department of Pathology, Brigham and Women's Hospital
and Harvard Medical School, Boston, MA; dagger
Department of Pathology, University of Vermont,
Burlington, VT; double dagger
Dermatohistopathologisches Gemeinschaftslabor, Friedrichshafen, Germany; and section signDepartment of Pathology, St. James's Hospital, Dublin, Ireland.
Am J Surg Pathol. 2004 Oct;28(10):1257-1267 Abstract quote
Pleomorphic liposarcoma is an uncommon form of liposarcoma that only recently has been properly characterized.
A series of 57 cases is presented. Patient age at presentation ranged from 27 to 95 years (median, 54 years), and there was a slight male predilection (male/female ratio = 1.2:1). Tumors most frequently involved the lower limb (47% of cases) or upper limb (18%). Other anatomic sites, including trunk (14%), retroperitoneum (7%), head and neck (5%), abdomen/pelvis (5%), and spermatic cord (4%), were less frequently involved. Tumor size ranged from 1.5 to 21 cm (median, 8 cm), with deep (subfascial) locations (39 cases) being more frequent than subcutaneous (11 cases) or dermal sites (5 cases). All lesions showed features of pleomorphic sarcoma and at least focally contained typical multivacuolated lipoblasts. Although there was considerable overlap, tumors fell into three broad categories: high-grade pleomorphic/spindle cell sarcoma with scattered lipoblasts or sheets of lipoblasts (60%), high-grade pleomorphic sarcoma with epithelioid areas and scattered lipoblasts (28%), and intermediate- to high-grade sarcoma predominantly resembling myxofibrosarcoma except for the presence of lipoblasts (12%).
Immunohistochemistry revealed focal staining for smooth muscle actin in 13 of 29 cases (45%), S-100 protein positivity in lipoblasts in 15 of 45 cases (33%), focal staining for keratin in 6 of 28 cases (21%), including 5 of 13 (38%) with epithelioid morphology, and focal staining for desmin in 4 of 30 cases (13%). Follow-up data, available in 50 patients (88%) (median, 33 months), showed local recurrence in 34% of patients, systemic metastases in 32%, and tumor-related death in 32%. Only 2 of the 16 superficial (dermal or subcutaneous) lesions metastasized. Five-year overall, local recurrence-free, metastasis-free, and disease-free survivals were 63%, 58%, 58%, and 39%, respectively. By univariate analysis, central (nonextremity) location, deep situation, tumor size â‰¥10 cm, mitotic rate â‰¥10 per 10 HPF, necrosis, and epithelioid morphology were associated with a worse prognosis. However, by multivariate analysis, only age â‰¥60 years, central location, tumor size, and mitotic rate remained independent predictors for an adverse outcome.
By multivariate analysis, wide local excision or amputation and postoperative radiotherapy protected against local recurrence.
Pleomorphic Liposarcoma: A Clinicopathologic Analysis Of 19 Cases
Katharine A. Downes, etal.
Modern Pathology 14:179-184 (2001) Abstract quote
Pleomorphic liposarcoma is a variant of liposarcoma defined morphologically by the presence of pleomorphic lipoblasts. Because of its rarity, there are limited studies with long-term follow-up information.
Nineteen pleomorphic liposarcomas were studied. Unequivocal pleomorphic lipoblasts were required for inclusion. In each case, the following features were noted: tumor site; tumor size; tumor depth; predominant histologic pattern (epithelioid or malignant fibrous histiocytoma [MFH]-like); extent of necrosis (absent, less than 15%, or at least 15%); mitotic counts; treatment and clinical follow-up.
Patients were 11 females and 8 males, aged 33–87 years (mean, 64.5 y; median, 70 y). Tumors involved the extremities (13 patients: intramuscular in 10, subcutaneous in 2, depth unknown in 1), retroperitoneum (4 patients), mediastinum (1 patient), and paratesticular region (1 patient). Size ranged from 4.5–31 cm (mean, 11.9 cm; median, 12.0 cm). Predominant pattern was epithelioid in 7 and MFH-like in 12. Necrosis was present in 15 (79%) and was extensive (36 15%) in 14 patients. Mitotic counts ranged from 0.2–3.4/10 high-power fields (mean, 1.4; median, 1.4) by the average-count method and from 1–6/10 high power fields by the highest count method (mean, 2.9; median, 3.0).
All patients were treated surgically; 10 patients received adjuvant chemotherapy and/or radiation therapy. On follow-up of 18 patients (range, 2–129 mo; mean, 35.4 mo; median, 23 mo) nine (50%) were dead of disease (range, 2–48 mo; mean, 20.1 mo; median, 12 mo), one died of other causes 2 months after diagnosis, two were alive with disease, five were disease free, and one was alive at 129 months (tumor status unknown). Five had recurrences (range, 3–28 mo; mean, 14.4 mo; median, 8 mo), and four of five (80%) with recurrences were dead of disease. Metastases developed in eight patients (range, 4–48 mo; mean, 19.5 mo; median, 11.5 mo), most commonly to the lungs.
In conclusion, pleomorphic liposarcoma is a rare tumor of adulthood that occurs most commonly in the deep, soft tissues of the extremities. It behaves as a high-grade sarcoma that frequently metastasizes, most commonly to the lungs. Although this tumor has a wide range of histologic appearances, no clinical or pathologic feature is predictive of a more aggressive clinical course.
Pleomorphic Liposarcoma: Clinicopathologic, Immunohistochemical, and Follow-up Analysis of 63 Cases: A Study From the French Federation of Cancer Centers Sarcoma Group.
Gebhard S, Coindre JM, Michels JJ, Terrier P, Bertrand G, Trassard M, Taylor S, Chateau MC, Marques B, Picot V, Guillou L.
University Institute of Pathology (S.G., L.G.), Lausanne, and Department of Pathology (S.T.), University Hospital, Geneva, Switzerland.
Am J Surg Pathol 2002 May;26(5):601-16 Abstract quote
The clinicopathologic and immunohistochemical features of 63 pleomorphic liposarcomas are presented. There were 35 men and 28 women (median age 63 years; range 18-93 years). Tumor size ranged from 2 to 23 cm (median 10 cm).
Tumor locations included lower extremity (36.5%), especially the thigh (28.5%), limb girdles (17.5%), upper extremity (16%), thoracoabdominal wall (9.5%), and internal trunk (20.5%). A total of 75% were deep seated and/or extracompartmental. Histologically, lesions show a varying combination of lipogenic and nonlipogenic areas characterized by malignant fibrous histiocytoma-like, round cell liposarcoma-like, and/or epithelioid/carcinoma-like features. A pericytic pattern was focally present in 15 (24%) tumors. Eighteen (29%) lesions were grade 2, and 45 (71%) were grade 3 sarcomas. Tumor necrosis was observed in 51 (81%) cases, vascular invasion in three, and mitotic counts ranged from 3 to 124 per 10 high power fields (median 25). Lipogenic areas were S-100 protein immunoreactive, at least focally, in 20 of 42 (48%) cases. Nonlipogenic areas showed focal reactivity for smooth muscle actin (24 of 49; 49%), desmin (9 of 48; 19%), CD34 (18 of 45; 40%), S-100 protein (5 of 49, 10%), CD68 (6 of 46, 13%), and epithelial membrane antigen (13 of 49, 26.5%). Epithelioid areas showed epithelial membrane antigen (4 of 11; 36%) but not cytokeratin (0 of 11) reactivity.
Treatment procedures in 51 patients consisted of simple tumorectomy (16) and wide excision (33). Five and 31 patients received neoadjuvant and adjuvant chemotherapy and/or radiation therapy, respectively. Follow-up (48 patients, range 7-276 months; median 38 months) showed a 45% local recurrence rate and a 42.5% metastasis rate, metastases occurring mostly in lungs and pleura. Seventeen patients (35%) died of disease, of whom none was metastatic at diagnosis. Five-year overall, metastasis-free, and local recurrence-free survivals were 57%, 50%, and 48%, respectively. Patient age >/=60 years, truncal tumor location, deep situation, tumor size >5 cm, vascular invasion, and incomplete tumor excision were significant adverse prognostic factors. Tumor grade and histology did not affect patient outcome.
In conclusion, pleomorphic liposarcoma is a rare, often deep-seated and limb-based aggressive and metastasizing neoplasm of late adulthood. It shows a wide range of morphologic appearances, but tumor grade and histology have no effect on patient outcome.
OTHER VARIANTS ATYPICAL LIPOMATOUS TUMORS
Controversial term with no consensus for which tumor the term is applied
Current thought is well differentiated liposarcomas are equivalent to this term
- Atypical Lipomatous Tumor, its Variants, and its Combined Forms: A Study of 61 Cases, With a Minimum Follow-up of 10 Years.
Department of Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030.
- Am J Surg Pathol. 2007 Jan;31(1):1-14. Abstract quote
Sixty-one cases of neoplasms composed wholly or in part of atypical lipomatous tumor were reviewed. Minimum follow-up was 10 years. The cases were divided into 4 groups based on the findings in the initial excision specimen: conventional atypical lipomatous tumor (n=15), cellular atypical lipomatous tumor (n=21), dedifferentiated liposarcoma (n=24), and atypical lipomatous tumor with a pleomorphic liposarcomalike component (n=1).
The term "cellular atypical lipomatous tumor" was applied to atypical lipomatous tumors having areas of increased cellularity that when nonlipogenic lacked the 5 mitotic figures per 10 high-power fields (maximal rate) required for a dedifferentiated component and when lipogenic fell short of being truly pleomorphic liposarcomalike. Myxoid regions within this spectrum sometimes had prominent or even plexiform vascularity, creating a resemblance to myxoid liposarcoma especially when interspersed small fat cells were present. The most important prognostic factor was tumor location, as none of the 12 patients with a subcutaneous or intramuscular neoplasm died of tumor. Among the 49 patients with neoplasms of central body sites (mostly retroperitoneum), those with dedifferentiated liposarcoma had significantly shorter survival (median 77 mo) than those with cellular (median 142 mo) or conventional (median 209 mo) atypical lipomatous tumor, whereas there was no statistically significant difference between the latter 2 categories.
Patients with atypical lipomatous tumor (either cellular or conventional) in central body sites had significantly shorter survival if the tumor transformed into dedifferentiated liposarcoma in recurrence, and, conversely, those with central body site dedifferentiated liposarcoma had significantly longer survival if it recurred as atypical lipomatous tumor. Metastasis (7 cases) occurred only when the initial specimen or a recurrence demonstrated dedifferentiated liposarcoma.
Lipoleiomyosarcoma (well-differentiated liposarcoma with leiomyosarcomatous differentiation): a clinicopathologic study of nine cases including one with dedifferentiation.
Folpe AL, Weiss SW.
Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia, U.S.A
Am J Surg Pathol 2002 Jun;26(6):742-9 Abstract quote
Leiomyosarcomatous (LMS) differentiation is a rare event in liposarcoma (LPS) and may consist of either well-differentiated liposarcoma (WDL) with an intrinsic smooth muscle component, so-called "lipoleiomyosarcoma," (L-LMS) or dedifferentiated liposarcoma having smooth muscle differentiation in the dedifferentiated zones. The latter are high-grade sarcomas, whereas the behavior of the former group is uncertain. Specifically, it is not clear whether the presence of LMS negatively affects the prognosis.
We present our experience with nine cases, the largest to date. The patients (seven male, two female) ranged in age from 42 to 65 years (mean 54 years). The tumors were usually large (2 to >40 cm [mean 17 cm]) tumors in the retroperitoneum (two cases), paratesticular-inguinal region (three cases), mediastinum (one case), lung (one case), abdomen (one case), and popliteal fossa (one case). The nine cases qualified as L-LMS and showed typical WDL with a multifocal, gradual transition into smooth muscle areas. The latter areas accounted for a variable portion of the lesions (range 5-90%) and were of low cellularity, mild to moderate nuclear atypia, and low mitotic activity. These areas seemed to arise from or blend with the smooth muscle in the walls of large vessels within the tumor. One case showed areas of dedifferentiation consisting of actin and desmin-negative, high-grade sarcoma. Follow-up in seven cases (range 26-312 months; mean 119 months) showed multiple local recurrences in seven patients and no metastases. Three patients are currently without evidence of disease (follow-up duration 26-312 months; mean 144 months) and four patients are alive with progressive disease (follow-up duration 60-132 months; mean 99 months).
Our study suggests that L-LMS is a dual lineage sarcoma as evidenced by the fact that the smooth muscle component is often multifocal, not necessarily found in close association with the atypical changes in fat, and seemingly originates from atypical ("in situ") changes in the vessel wall. The LMS component, which is typically low grade, does not adversely affect the overall behavior of the tumor, which is similar to that of conventional WDL. LMS in L-LMS should not be misconstrued as evidence of low-grade dedifferentiation, a phenomenon that identifies a more unstable and potentially metastasizing lesion.
MYXOID MFH AREAS
Retroperitoneal liposarcoma with combined well-differentiated and myxoid malignant fibrous histiocytoma-like myxoid areas.
Hisaoka M, Morimitsu Y, Hashimoto H, Ishida T, Mukai H, Satoh H, Motoi T, Machinami R.
Department of Pathology and Oncology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
Am J Surg Pathol 1999 Dec;23(12):1480-92 Abstract quote
To broaden the knowledge of myxoid morphology in liposarcoma, eight cases of unusual liposarcoma with combined well-differentiated and myxoid malignant fibrous histiocytoma (MFH)-like myxoid areas are reported.
The tumors arose as huge retroperitoneal masses in elderly patients, except for one that occurred in the spermatic cord. Three cases had local recurrences, and one of the seven patients who were followed up had died of the tumor.
Grossly, the tumors were mostly confluent and multinodular and showed a glistening myxoid appearance in variable proportions, which merged gradually into or were juxtaposed to yellow fatty or sclerotic whitish areas.
Microscopically, in addition to areas of well-differentiated lipoma-like or sclerosing liposarcoma, all the tumors contained myxoid portions characterized by scattered multinucleated or bizarre giant cells and a prominent plexiform vascular pattern that resembled myxoid MFH or myxofibrosarcoma. The myxoid areas were associated with discernible lipogenesis. High-grade dedifferentiation was present in one tumor.
Cytogenetically, in one case, the myxoid lesion had nonrandom chromosomal aberrations, such as ring and marker chromosomes, characteristic of a well-differentiated variant of liposarcoma. In a nested reverse transcription-polymerase chain reaction analysis using archival paraffin-embedded tissue, it was seen that none of the eight tumors with myxoid MFH-like features had TLS/FUS-CHOP fusion transcripts characteristic of myxoid and round cell liposarcomas.
These clinicopathologic and molecular features suggest that the current myxoid tumors are more closely related to well-differentiated liposarcoma rather than to ordinary myxoid liposarcoma despite their unequivocal myxoid morphology. Missense point mutations of the p53 gene were detected in two (25%) cases by single-strand conformation polymorphism and sequence analyses. Immunohistochemical expressions of p53 and mdm2 were observed in 75% of the cases, in which immunoreactive tumor cells were seen more often in the myxoid MFH-like areas.
Thus, altered p53 pathways, such as p53 gene mutation and mdm2-mediated inactivation of p53, may play a pathogenetic role in this form of tumor progression showing myxoid MFH-like morphology in liposarcoma, as has been suggested in dedifferentiated liposarcoma.
Spindle cell liposarcoma, a hitherto unrecognized variant of liposarcoma. Analysis of six cases.
Dei Tos AP, Mentzel T, Newman PL, Fletcher CD.
Department of Histopathology, St. Thomas's Hospital, London, U.K.
Am J Surg Pathol 1994 Sep;18(9):913-21 Abstract quote
A series of six cases of a previously unrecognized variant of liposarcoma characterized by a prominent spindle cell component is reported herein.
Clinically, all of the tumors arose in adults and developed around the shoulder girdle or upper limbs; all but one arose in subcutaneous tissue. Three patients developed multiple local recurrences over a period of 4-20 years. Recurrences in one case were purely lipoma-like. Following dedifferentiation in a recurrence, one patient developed distant metastases and eventually died, 46 months after the primary excision. Grossly, these lesions are characterized by multinodularity, and microscopically they show a relatively bland spindle cell proliferation arranged in fascicles and whorls and set in a variably myxoid stroma. The spindle cell areas are accompanied by an adipocytic component, which exhibits the morphologic features required for inclusion in the well-differentiated liposarcoma-atypical lipoma group, including definite lipoblasts.
Main differential diagnoses include benign lesions such as spindle cell lipoma and diffuse neurofibroma, as well as dermatofibrosarcoma protuberans and other malignancies such as sclerosing liposarcoma, low-grade myxofibrosarcoma, low-grade malignant peripheral nerve sheath tumor, and low-grade fibromyxoid sarcoma.
In view of their distinctive histologic appearance, and because aggressive clinical behavior was observed despite their superficial location, we propose that these lesions be regarded as spindle cell variants of well-differentiated liposarcoma.
CHARACTERIZATION Fat In general, not helpful but stains such as oil red O may be used to identify fat Alcian blue, hyaluronidase sensitive Stroma in myxoid liposarcomas are hyaluronidase acid-rich S100 Positive in fat cells and lipoblasts
Leptin and Leptin Receptor mRNA are Widely Expressed in Tumors of Adipocytic Differentiation
Andre M. Oliveira, M.D., Antonio G. Nascimento, M.D. and Ricardo V. Lloyd, M.D., Ph.D.
Department of Laboratory Medicine and Pathology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota Correspondence: Address reprint requests to: Ricardo V. Lloyd, M.D., Ph.D., Department of Laboratory Medicine and Pathology, Mayo Clinic
Mod Pathol 2001;14:549-555 Abstract quote
Adipose tissue is the principal source of leptin, a cytokine-like peptide with many biologic functions. Leptin binds to the leptin receptor, present in the hypothalamus and in many other tissues, and modulates energy balance and maintenance of body weight. The expression of leptin and leptin receptor in tumors of adipocytic differentiation has not been previously examined. Because normal adipose tissue is the principal source of leptin and expresses leptin receptor, we hypothesized that tumors of adipose tissue differentiation may also express leptin and/or the long functional form of the leptin receptor (OB-Rb).
Leptin and OB-Rb were analyzed by immunohistochemistry, in situ hybridization, RT-PCR, and western blotting in 21 lipomas, 2 hibernomas, and 16 liposarcomas.
Immunostaining and in situ hybridization showed leptin and OB-Rb mRNA expression in all cases of lipomas, hibernomas, and liposarcomas, including dedifferentiated and pleomorphic liposarcomas. RT-PCR analysis showed leptin and OB-Rb mRNA in both lipomas (n = 5) and liposarcomas (n = 5). Western blotting identified the 16 kDa leptin protein in a lipoma and a liposarcoma. No important difference in the expression of leptin and OB-Rb mRNA was found between lipomas and liposarcomas, although the level of leptin protein was higher in a lipoma than a liposarcoma by western blotting.
These results show for the first time that leptin and OB-Rb mRNA are expressed in lipomas, hibernomas, and liposarcomas. The presence of leptin and its receptor may provide new insights into the pathobiology of these tumors.
J Clin Pathol 1995;48:950
Antibodies have identified prelipoblasts
TLS/EWS-CHOP CHIMERIC ONCOPROTEIN
- Generation of the Novel Monoclonal Antibody Against TLS/EWS-CHOP Chimeric Oncoproteins That Is Applicable to One of the Most Sensitive Assays for Myxoid and Round Cell Liposarcomas.
Oikawa K, Ishida T, Imamura T, Yoshida K, Takanashi M, Hattori H, Ishikawa A, Fujita K, Yamamoto K, Matsubayashi J, Kuroda M, Mukai K.
*Departments of Pathology double daggerOrthopedic Surgery paragraph signDiagnostic Pathology, Tokyo Medical University, Tokyo, Japan daggerDepartment of Pathology, Kanto Medical Center NTT-EC, Tokyo, Japan section signNational Research Institute for Child Health and Development, Tokyo, Japan perpendicularDepartment of Surgical Pathology, Faculty of Medicine, Teikyo University, Tokyo, Japan.
Am J Surg Pathol. 2006 Mar;30(3):351-356. Abstract quote
The fusion oncoproteins, TLS-CHOP and EWS-CHOP, are characteristic markers for myxoid and round cell liposarcomas (MLS/RCLS). Especially, the peptide sequence of 26 amino acids corresponding to the normally untranslated CHOP exon 2 and parts of exon 3 (5'-UTR) is a unique structure for these chimeric proteins.
In this report, we have generated monoclonal antibodies against the unique peptide sequence of TLS/EWS-CHOP oncoproteins. These antibodies reacted with TLS-CHOP fusion protein, but not reacted with normal TLS and CHOP proteins by Western blot analysis. In addition, one of the antibodies also recognized the chimeric oncoprotein in archival paraffin-embedded tissue samples of MLS/RCLS. The oncoprotein was detectable by the antibody even in the paraffin-embedded tissue samples whose mRNAs were too degraded to be detected by a nested reverse transcription-polymerase chain reaction-based assay.
Thus, the molecular assay using the novel antibody is expected to be one of the most sensitive diagnostic assays for MLS/RCLS.
DIFFERENTIAL DIAGNOSIS CHARACTERIZATION Normal fat with lockhern Normal fat cells sectioned in tangential sections may display a characteristic central vacuole
Common in thicker sections
Fat necrosis Macrophages are uniform size with small, evenly dispersed vacuoles that do not indent the nucleus Fatty atrophy Loss of intracellular lipid shrinks the cell assuming an epithelioid appearance with prominence of the nuclei
Cells are uniform in size and maintaing lobular arrangement
Localized massive lymphedema Develop in mobidly obese individuals
Changes of lymphedema with expanded connective tissue septa containing mildly atypical fibroblasts and delicate collagen fibrils separated by edema
May have vascular proliferation interfacing between connective tissue septa and fat lobules
Silicone reaction Inflammation with giant cell reaction and large cyst with eosinophilic borders Diffuse lipomatosis Spindle cell lipma/pleomorphic lipoma Myolipoma Cellular angiomyolipoma Lipomatous hemangiopericytoma Myxoid Liposarcoma DDX Myxoma Angiomyxoma Myxoid DFSP Myxoid chondrosarcoma Myxoid MFH
PROGNOSIS AND TREATMENT CHARACTERIZATION PROGNOSIS
Hypercellularity or round cell differentiation associated with worse prognosis
Increased recurrences, poorer prognosis
Retroperitoneal tumors poorer prognosis with 41% overall 5 year survival
Lung, visceral organs, and bone
Myxoid tumors tend to produce secondary lesions on the the serosal surfaces of the pleura, pericardium, and diaphragm and may metastasize to other soft tissue sites, unlike the other histological variants
Interval between mets may be as short as a few months or as long as 30 years
Well differentiated 30% local recurrence but no potential for metastasis unless there is dedifferentiation Dedifferentiated 15-20% metastases Pleomorphic 30% metastases MYXOID LIPOSARCOMA
Overall, there is good correlation between the percentage of round cell differentiation and clinical outcome
Did not have correlation with ploidy by as most tumors were diploid
Round cell population % Metastasis 0-5 11/48 (23%) 5-10 5/14 (35%) >25% 14/24 (58%) CHROMOSOMAL ALTERATIONS
- Gains of 13q are correlated with a poor prognosis in liposarcoma.
Schmidt H, Bartel F, Kappler M, Wurl P, Lange H, Bache M, Holzhausen HJ, Taubert H.
1Institute of Pathology, Martin Luther University Halle-Wittenberg, Halle, Germany.
Mod Pathol. 2005;18:638-644 Abstract quote
Liposarcomas are a phenotypical heterogenous group of tumors divided into four main subtypes: well-differentiated, dedifferentiated, myxoid/round cell, and pleomorphic. The aim of this study was to compare DNA sequence copy number changes of these subtypes as investigated by comparative genomic hybridization in 36 patients. Comparative genomic hybridization revealed genomic imbalances in tumors of 27 patients (mean 5.6 imbalances per tumor). The most frequent gains were within single regions of 1q, 12q, and 13q.
We found a significant correlation of poor overall survival and gain of 13q21 (P=0.0221), 13q22 (P=0.0341), 13q31 (P=0.0410), and 13q32 (P=0.0074). The univariate Cox regression analysis revealed an increased risk of tumor-related death for patients whose liposarcomas possess with gains of 13q21 and 13q32 simultaneously (P=0.010; RR=7.1; 95% CI 1.6-31.7). Furthermore, 12 high-level amplifications were found in tumors of seven patients. In four cases 12q14-q15 and in two cases 13q32-q33 were amplified. We identified in different liposarcoma subtypes characteristic genomic changes: Gains and high-level amplifications of 12q occurred in all 11 investigated well-differentiated liposarcomas, and these changes were often present simultaneously with gains of 1q (mean 5.5 changes). In the two dedifferentiated liposarcomas, gains of 1q in both liposarcomas, and a high-level amplification of 13q were striking. Only eight of the 17 patients with myxoid/round cell liposarcomas showed changes in DNA copy number (mean 3.4 imbalances). In four of these eight cases gains of 13q occurred. The six pleomorphic liposarcomas possessed the most frequent genomic imbalances (mean number 16.3) of all liposarcoma subtypes investigated. These imbalances were in almost all chromosomal regions detected predominantly as over-representations of chromosomes 1, 5p, 13q, and 22q.
Summarizing, all subtypes but well-differentiated liposarcomas showed gains of 13q, which were associated with a poor prognosis.
Prognostic Impact of P53 Status, TLS-CHOP Fusion Transcript Structure, and Histological Grade in Myxoid Liposarcoma: A Molecular and Clinicopathologic Study of 82 Cases.
Antonescu CR, Tschernyavsky SJ, Decuseara R, Leung DH, Woodruff JM, Brennan MF, Bridge JA, Neff JR, Goldblum JR, Ladanyi M.
Departments of Pathology [C. R. A., S. J. T., R. D., J. M. W., M. L.], Biostatistics [D. H. L.], and Surgery [M. F. B.] Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
Clin Cancer Res 2001 Dec;7(12):3977-87 Abstract quote
PURPOSE: A specific TLS-CHOP fusion gene resulting from the t(12;16) is present in at least 95% of myxoid liposarcomas (MLS). Three common forms of the TLS-CHOP fusion have been described, differing by the presence or absence of TLS exons 6-8 in the fusion product. Type 5-2 (also known as type II) consists of TLS exons 1-5 fused to CHOP exon 2; type 7-2 (also known as type I) also includes TLS exons 6 and 7 in the fusion, whereas type 8-2 (also known as type III) fuses TLS exons 1-8 to CHOP exon 2. We sought to determine the impact of TLS-CHOP fusion transcript structure on clinical outcome in a group of well-characterized MLS cases. We also analyzed P53 status, because this parameter has been found to have a significant prognostic impact in other sarcomas with chromosomal translocations.
METHODS: We analyzed TLS-CHOP fusion transcripts by reverse-transcription PCR using RNA extracted from frozen tissue in 82 MLS confirmed previously to harbor a CHOP rearrangement either by Southern blotting or by cytogenetic detection of the t(12;16). Parameters analyzed included age, location, size, percentage of round cell (RC) component, areas of increased cellularity, necrosis, and surgical margins. In 71 (87%) cases, adequate tumor tissue was available for immunohistochemical analysis of P53 status, using DO7 antibody. The Kaplan-Meier method, log-rank, and Cox regression tests were used for survival analyses.
RESULTS: Most MLS were >10 cm (73%), arising in the thigh (70%), and localized at presentation (89%). RC component was <5% in 47 (57%) cases and >/=5% in 35 (43%). The TLS-CHOP fusion transcript was type 5-2 in 55 (67%), type 7-2 in 16 cases (20%), and type 8-2 in 8 (10%). One tumor had a unique variant fusion, between exon 6 TLS and exon 2 CHOP. Two other cases (2%) showed an EWS-CHOP fusion transcript. Overexpression of P53 (defined as >/=10% nuclear staining) was detected in 12 (17%) cases. High histological grade (defined as >/=5% RC; P < 0.01), presence of necrosis (>/=5% of tumor mass; P < 0.05), and overexpression of P53 (P < 0.001) correlated with reduced metastatic disease-free survival in localized tumors. The presence of negative surgical margins (P < 0.01) and extremity location (P = 0.02) were found to be significant in predicting local recurrence in the entire group as well as localized cases by univariate and multivariate analysis. Although there was no significant correlation between TLS-CHOP transcript type and histological grade or disease-specific survival, an association was found between the P53 status and type 5-2 fusion (P < 0.01).
CONCLUSION: In contrast to some other translocation-associated sarcomas, the molecular variability of TLS-CHOP fusion transcript structure does not appear to have a significant impact on clinical outcome in MLS. Instead, high histological grade (>/=5% RC), presence of necrosis, and P53 overexpression are predictors of unfavorable outcome in localized MLS.
Varies according to site and tumor type but ranges from 46-57%
Multiple recurrences more common with myxoid and well differentiated types
SURVIVAL 5 Year Survival Overall varies from 59-70% 10 Year Survival Overall varies from 45-53% Well differentiated 100% survival Dedifferentiated
Am J Surg Pathol 1997;21:271
Survival follows fully malignant sarcomas except if dedifferentiation is limited to a small focus
41% with local recurrence
28% die of disease
Most patients die from local effects of the disease rather than metastasis
Tumors in retroperitoneum have worse prognosis
Myxoid 70% Round cell 20% Pleomorphic Overall 40% mortality Myxoid/Round cell
Age (years) <45 5YRS 88% 10YRS 80% >45 5YRS 72% 10YRS 50% Necrosis Yes 5YRS 25% 10YRS 0% No 5YRS 90% 10YRS 70% Round cell (%) <25% 5YRS 89% 10YRS 66% >25% 5YRS 79% 10YRS 40% TREATMENT
Radical local excision because of multiple satellite nodules
May follow with postoperative radiation
Ann Diagn Pathol 2000;4:252-266
Macpherson and Pincus. Clinical Diagnosis and Management by Laboratory Methods. Twentyfirst Edition. WB Saunders. 2006.
Rosai J. Ackerman's Surgical Pathology. Ninth Edition. Mosby 2004.
Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 6th Edition. McGraw-Hill. 2003.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.
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