Dedifferentiated Liposarcoma

Definition

• 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)
      • None of the cases with only IMT in the dedifferentiated component metastasized, thus this does not appear to qualify
  • 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

• 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

Immunohistology

• MDM2 and CDK4 are markers amplified as a result of the supernumerary ring chromosomes described below

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

Differential Diagnosis

• Pleomorphic liposarcoma
• Lipomatous hemangiopericytoma
• Non-lipogenic sarcoma
• GI stromal tumor

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

Clinical

• 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

Lists

Lipogenic tumors

• Angiomyolipoma
• Hemosiderotic Fibrohistiocytic Lipomatous Lesion
• Hibernoma
• Lipofibromatosis
• Lipoma
• Lipomatosis
• Lipoblastoma / lipoblastomatosis
• Pleomorphic lipoma
• Spindle cell lipoma
• Atypical lipomatous tumor
• Liposarcoma
  • Dedifferentiated
  • Myxoid
  • Pleomorphic
  • Unclassified
• Atypical Spindle Cell Lipomatous Tumor

Bibliography

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• Weiss SW, Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors, 4th edition, 2001
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