Stanford School of Medicine

Surgical Pathology Criteria

 use browser back button to return

Dedifferentiated Liposarcoma


  • Biphasic neoplasm with one component of atypical lipomatous tumor and a second component of high grade sarcoma

Diagnostic Criteria

  • Biphasic neoplasm
    • Both components may be present in one specimen
      • Components may be adjacent or intermingled
      • Proposed size requirement for high grade component is one 10x objective field
    • May be temporally biphasic with a high grade non-lipogenic recurrence in a patient with an atypical lipomatous tumor
    • One component must be atypical lipomatous tumor
      • Mature fat and atypical cells
    • Other component must be high grade sarcoma
      • Mitotic rate at least 5/10 hpf
        • Cytologically obvious sarcoma does not have a required mitotic rate
      • Pleomorphic MFH pattern is most common
      • Many other types of sarcoma may be seen
        • Classically the sarcoma must be non-lipogenic
          • Recent studies describe cases that appear to represent dedifferentiation as pleomorphic liposarcoma (Boland 2010, Mariño-Enríquez 2010)
      • An inflammatory myofibroblastic tumor component has been proposed as dedifferentiation (Lucas, 2010)
    • A high grade sarcoma arising in a location typical of atypical lipomatous tumor (such as retroperitoneum) that is FISH positive for amplification of MDM2 may also be considered a dedifferentiated liposarcoma
  • Metastases contain only the high grade sarcoma component
  • By definition, may not occur following radiation of atypical lipomatous tumor
  • Low grade dedifferentiated liposarcoma has been proposed
    • Non-lipogenic component with features of fibromatosis, low grade fibrosarcoma or dermatofibrosarcoma protuberans
      • Mitotic rate <5/10 hpf
    • Survival is the same as atypical lipomatous tumor
      • All cases that metastasized had a local recurrence with a high grade component or were incompletely resected
    • We do not make this diagnosis
    • Cellular atypical lipomatous tumor (Evans 2007) is an acceptable term

Robert V Rouse MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342

Original posting/last update : 8/4/07, 4/16/12

Does inflammatory myofibroblastic tumor qualify as dedifferentiation?

  • Lucas 2010 reported a series of 6 patients with components of atypical lipomatous tumor and inflammatory myofibroblastic tumor (IMT)
    • 3 of 6 metastasized
      • However, of these three, two were not pure IMT in the dedifferentiated component, with the remainder being high grade sarcoma
      • The one pure case with metastasis is reported as to the inguinal region, where direct spread/recurrence through the inguinal canal appears to be a possibility
      • The histology of the metastases is not described
  • It is not clear from this report that IMT should be included in dedifferentiated liposarcoma

Supplemental studies


Stains on dedifferentiated component
Marker % of Tumors Reported Positive
p16 78-97%
MDM2 55-95%
CDK4 84-92%
CD34 25%
Desmin 44%
Smooth muscle actin 44%
Neurofilament 41%
S100 9%
Muscle specific actin 6%
Keratin 3%
  • MDM2 and CDK4 are markers amplified as a result of the supernumerary ring chromosomes described below
Immunohistochemistry of lipomatous tumors
  MDM2 CDK4 p16
Atypical lipomatous tumor 45-100% 84-92% 78-97%
Dedifferentiated liposarcoma 55-95 90-100 90
Myxoid / round cell liposarcoma 0-4 0-4 0
Pleomorphic liposarcoma 0 0 0
Lipoma 0-4 0-2 0
Spindle cell and pleomorphic lipoma 0-25 0-6 20
Angiomyolipoma 0 0  
Hibernoma 0 0 positive, variable
Lipoblastoma 0 (1 case) 0 (1 case) positive (1 case)

Genetic analysis

  • Frequently exhibits same findings as atypical lipomatous tumor
    • >60% have supernumerary ring chromosomes derived from 12q(13-15)
    • 16q13 abnormality rare
      • Common in spindle cell and pleomorphic lipomas
  • Karyotype is typically less complex than other non-fatty sarcomas
FISH/PCR of lipomatous tumors
Atypical lipomatous tumor 90-100% 72-100% 75-100% 69-100%
Dedifferentiated liposarcoma 100% 100% 100% 100%
Myxoid liposarcoma 20%      
Spindle cell / pleomorphic lipoma Negative Negative Negative Negative
Angiolipoma Negative      
Lipoma, NOS Negative Negative Negative Negative
Sarcomas 0-40% 0% 0% 0%
  • Spindle cell / pleomorphic lipoma showed 89% chromosome 12 polysomy
  • Differential Diagnosis

    Pleomorphic Liposarcoma Dedifferentiated Liposarcoma
    Cellular pleomorphic sarcoma throughout Atypical lipomatous areas present
    MDM2 and CDK4 negative MDM2 95% and CDK4 92%
    Classically, pleomorphic liposarcoma was not permitted as the dedifferentiated component, but it appears that it rarely occurs in this guise, associated with atypical lipomatous tumor and expressing MDM2 (see Boland 2010).

    Lipomatous Hemangiopericytoma Dedifferentiated Liposarcoma
    Cytologically bland High grade dedifferentiated areas
    No areas of atypical lipomatous tumor Areas or history of atypical lipomatous tumor
    Circumscribed Usually non-circumscribed

    Independently Arising Nono-lipogenic Sarcoma vs Atypical Lipomatous Tumor

    • Must be ruled out by adequate pathologic and surgical sampling
    • There should be a high level of suspicion for tumors arising in the retroperitoneum
    • Prior specimens should be examined
    • Radiographic evidence should be sought of a non-sampled fatty component
        MDM2 CDK4
      Dedifferentiated Liposarcoma 95% 92%
      MFH 11 3
      Myxofibrosarcoma 42 17
      Leiomyosarcoma 6 1
      Maligant peripheral nerve sheath tumor 64 12

    Dedifferentiated Liposarcoma GIST (spindled, cytologically malignant)
    Frequently markedly pleomorphic Pleomorphism infrequent, even in malignant lesions
    CD117, DOG1 negative CD117, DOG1 85-95%
    CD34 may be positive in both


    • Age: Most 50-70 years, all over 21 years old
    • Site of involvement
      • Same as atypical lipomatous tumor
        • Central body
          • Retroperitoneum, spermatic cord, mediastinum
          • Frequent recurrences, may be uncontrollable
          • Initial specimen or recurrences may exhibit dedifferentiation
        • Intramuscular / intermuscular
          • Thigh, arm, buttock
          • Frequent recurrences, rarely uncontrollable
          • Dedifferentiation rare
        • Subcutaneous
          • By definition does not occur in posterior neck, upper back or shoulders
          • Infrequent recurrences, never uncontrollable
          • Dedifferentiation very rare
        • Viscera
          • Larynx most common, other sites extremely rare
          • Recurrences frequent, never uncontrollable
          • Dedifferentiation very rare
    • Prognosis
      • Recurrence rate 40-50%
      • Metastatic rate 15-20%
        • Only dedifferentiated component can metastasize
        • Most common sites for metastases are lung, liver, bone
      • Median survival approximately 5 years from appearance of dedifferentiated component
      • Prognosis may be better than for patients with corrresponding pure high grade sarcoma in cases outside retroperitoneum and inguinal area

    Grading / Staging / Report

    According to the guidelines of the ADASP, dedifferentiated liposarcoma is considered high grade

    French Federation of Cancer Centers System grading scheme for adult sarcomas

    • Tumor differentiation score = 3 for dedifferentiated liposarcoma
    • Mitotic index
      • Score 1 0-9 mitoses per 10 hpf (0.1744 sq mm)
      • Score 2 10-19 mitoses per 10 hpf
      • Score 3 >19 mitoses per 10 hpf
    • Tumor cell necrosis
      • Score 0 No necrosis on any slide (one slide per 2 cm tumor diameter)
      • Score 1 <50% of tumor is necrotic on slides examined
      • Score 2 >50% of tumor is necrotic on slides examined
    • Final Grade (add the three scores above)
      • Grade 1 Sum of scores = 2 or 3
      • Grade 2 Sum of scores = 4 or 5
      • Grade 3 Sum of scores = 6 or more

    Use TNM Staging

    The surgical pathology report should contain or address the following:

    • Location
    • Type of resection or biopsy
    • Histologic diagnosis
    • Managerial category III (Local recurrence common; Metastasis occurs)
    • Extent of tumor cell necrosis
    • Grade
      • Percent poorly differentiated area
    • Stage
    • Size
    • Depth (dermis, subcutis, below fascia, body cavity)
    • Margins
      • Involved
      • Not involved
        • If under 2 cm give all such distances and sites
        • If over 2 cm give minimum distance and site
    • Results of supplementary studies if performed
    • Relationship to other specimens from the same patient


    Lipogenic tumors


    • Kempson RL, Fletcher CDM, Evans HL, Henrickson MR, Sibley RS. Tumors of the Soft Tissues, Atlas of Tumor Pathology, AFIP Third Series, Fascicle 30, 2001
    • Fletcher CDM, Unni KK, Mertens F. Pathology and Genetics of Tumours of Soft Tissue and Bone, World Health Organization Classification of Tumours 2002
    • Weiss SW, Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors, 4th edition, 2001
    • Azumi N, Curtis J, Kempson RL, Hendrickson MR. Atypical and malignant neoplasms showing lipomatous differentiation. A study of 111 cases. Am J Surg Pathol. 1987 Mar;11(3):161-83.
    • Weiss SW, Rao VK. Well-differentiated liposarcoma (atypical lipoma) of deep soft tissue of the extremities, retroperitoneum, and miscellaneous sites. A follow-up study of 92 cases with analysis of the incidence of "dedifferentiation". Am J Surg Pathol. 1992 Nov;16(11):1051-8.
    • Fanburg-Smith JC, Furlong MA, Childers EL. Liposarcoma of the oral and salivary gland region: a clinicopathologic study of 18 cases with emphasis on specific sites, morphologic subtypes, and clinical outcome. Mod Pathol. 2002 Oct;15(10):1020-31.
    • Rosai J, Akerman M, Dal Cin P, DeWever I, Fletcher CD, Mandahl N, Mertens F, Mitelman F, Rydholm A, Sciot R, Tallini G, Van den Berghe H, Van de Ven W, Vanni R, Willen H. Combined morphologic and karyotypic study of 59 atypical lipomatous tumors. Evaluation of their relationship and differential diagnosis with other adipose tissue tumors (a report of the CHAMP Study Group). Am J Surg Pathol. 1996 Oct;20(10):1182-9.
    • Rubin BP, Dal Cin P. The genetics of lipomatous tumors. Semin Diagn Pathol. 2001 Nov;18(4):286-93.
    • Pilotti S, Mezzelani A, Vergani B, Minoletti F, Cristofori E, Sozzi G, Pierotti MA. Morphologic-cytogenetic analysis of dedifferentiated liposarcomas with an extensive misleading leiomyosarcomatous component. Appl Immunohistochem Mol Morphol. 2000 Sep;8(3):216-21.
    • Henricks WH, Chu YC, Goldblum JR, Weiss SW. Dedifferentiated liposarcoma: a clinicopathological analysis of 155 cases with a proposal for an expanded definition of dedifferentiation. Am J Surg Pathol. 1997 Mar;21(3):271-81.
    • McCormick D, Mentzel T, Beham A, Fletcher CD. Dedifferentiated liposarcoma. Clinicopathologic analysis of 32 cases suggesting a better prognostic subgroup among pleomorphic sarcomas. Am J Surg Pathol. 1994 Dec;18(12):1213-23.
    • Hasegawa T, Seki K, Hasegawa F, Matsuno Y, Shimodo T, Hirose T, Sano T, Hirohashi S. Dedifferentiated liposarcoma of retroperitoneum and mesentery: varied growth patterns and histological grades--a clinicopathologic study of 32 cases. Hum Pathol. 2000 Jun;31(6):717-27.
    • Nascimento AG. Dedifferentiated liposarcoma. Semin Diagn Pathol. 2001 Nov;18(4):263-6.
    • Nascimento AG, Kurtin PJ, Guillou L, Fletcher CD. Dedifferentiated liposarcoma: a report of nine cases with a peculiar neurallike whorling pattern associated with metaplastic bone formation. Am J Surg Pathol. 1998 Aug;22(8):945-55.
    • Suster S, Fisher C. Immunoreactivity for the human hematopoietic progenitor cell antigen (CD34) in lipomatous tumors. Am J Surg Pathol. 1997 Feb;21(2):195-200.
    • Evans HL. Atypical lipomatous tumor, its variants, and its combined forms: a study of 61 cases, with a minimum follow-up of 10 years. Am J Surg Pathol. 2007 Jan;31(1):1-14.
    • Binh MB, Sastre-Garau X, Guillou L, de Pinieux G, Terrier P, Lagace R, Aurias A, Hostein I, Coindre JM. MDM2 and CDK4 immunostainings are useful adjuncts in diagnosing well-differentiated and dedifferentiated liposarcoma subtypes: a comparative analysis of 559 soft tissue neoplasms with genetic data. Am J Surg Pathol. 2005 Oct;29(10):1340-7.
    • Lucas DR, Shukla A, Thomas DG, Patel RM, Kubat AJ, McHugh JB. Dedifferentiated liposarcoma with inflammatory myofibroblastic tumor-like features. Am J Surg Pathol. 2010 Jun;34(6):844-51.
    • Boland JM, Weiss SW, Oliveira AM, Erickson-Johnson ML, Folpe AL. Liposarcomas with mixed well-differentiated and pleomorphic features: a clinicopathologic study of 12 cases. Am J Surg Pathol. 2010 Jun;34(6):837-43.
    • Mariño-Enríquez A, Fletcher CD, Dal Cin P, Hornick JL. Dedifferentiated liposarcoma with "homologous" lipoblastic (pleomorphic liposarcoma-like) differentiation: clinicopathologic and molecular analysis of a series suggesting revised diagnostic criteria. Am J Surg Pathol. 2010 Aug;34(8):1122-31
    • Thway K, Flora R, Shah C, Olmos D, Fisher C. Diagnostic utility of p16, CDK4, and MDM2 as an immunohistochemical panel in distinguishing well-differentiated and dedifferentiated liposarcomas from other adipocytic tumors. Am J Surg Pathol. 2012 Mar;36(3):462-9.
    Printed from Surgical Pathology Criteria:
    © 2005  Stanford University School of Medicine