Definition

• Cellular, pleomorphic sarcoma with lipoblasts

Diagnostic Criteria

• Pleomorphic, cellular sarcoma
  • Most show features of pleomorphic MFH
  • May show other patterns
    • Fibrosarcoma
    • Hemangiopericytoma
    • Rhabdoid tumor
    • Chondrosarcoma
    • Epithelioid differentiation
• Lipoblasts must be present
  • Cytoplasmic vacuole or vacuoles
    • Must be sharply defined
    • Must indent and distort nucleus
  • May be focal or widespread
  • S100 may highlight lipoblasts
  • May contain cytoplasmic eosinophilic globules
• Mature fat cells not present
  • Overrun fat at periphery must be excluded
• May have myxoid background
• Pleomorphic myxoid liposarcoma has been reported in young patients (Alaggio)
  • 12 of 82 liposarcomas age 22 and under
  • Typical myxoid pattern merging with hypercellular foci with marked pleomorphism and increased, atypical mitotic figures
  • 70% mortality within 36 months
  • Lacks CHOP translocations of usual myxoid type
  • Not clear if this should be considered a variant of myxoid type, pleomorphic type, a mixed type, or a separate type

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

Original posting: August 4, 2007
Updates: 4/20/08; 5/25/09, 12/25/12

Definition:

• Pleomorphic liposarcoma with prominent epithelioid features

Diagnostic Criteria for Epithelioid Variant

• Solid, cohesive sheets
  • Lack extracellular matrix
  • Separated by narrow vascular septa
• Epithelioid cells
  • At least focally with cytoplasmic vaculoles
  • Some cases with abundant clear to eosinophilic cytoplasm
• Nulcei generally round, uniform
  • Mitotic figures frequent (21-101/10 hpf)
  • Occasional pleomorphic nuclei
• Frequent necrosis
• Keratin positive in 5/11 cases
• Same clinical finding and anatomic distribution as other pleomorphic liposarcomas
• Poor prognosis (5/10 dead within one year)

Supplemental studies

Immunohistology

Conventional type

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

• No characteristic cytogenetic abnormalities
• Presence of giant ring chromosomes should suggest the possiblity of a dedifferentiated liposarcoma
• No cytogenetic data available for epithelioid variant

Differential Diagnosis

• Dedifferentiated liposarcoma
• Myxoid liposarcoma
• MFH and other pleomorphic non-lipogenic sarcoma
• Carcinoma (vs. epithelioid pleomorphic liposarcoma)

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).

Pleomorphic Liposarcoma is distinguished from MFH and other pleomorphic non-lipogenic sarcomas by the presence of lipoblasts in the former

Myxoid Liposarcoma does not demonstrate the degree of pleomorphism seen in Pleomorphic Liposarcoma

Epithelioid Variant Pleomorphic Liposarcoma	Carcinoma
Mucin negative large vacuoles	No large vacuoles unless mucin positive
EMA negative	Most are EMA positive
No glandular lumens	May have glandular lumens

Keratin, S100 and vimentin are not useful as both can stain for these markers

Clinical

• <5% of all liposarcomas
• Age: Most 50-70 years
  • Rare in children
• Site of involvement
  • Most in deep soft tissue
    • Extremeties and retroperitoneum most common
  • Rarely superficial
    • When superficial, recurrences are infrequent (4/24) and no metasatases reported (Gardner 2012)
• Prognosis
  • 5 year survival rate 40-63%

Grading / Staging / Report

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

French Federation of Cancer Centers System grading scheme for adult sarcomas

• Tumor differentiation score = 3 for pleomorphic 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

• 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.
• Hornick JL, Bosenberg MW, Mentzel T, McMenamin ME, Oliveira AM, Fletcher CD. Pleomorphic liposarcoma: clinicopathologic analysis of 57 cases. Am J Surg Pathol. 2004 Oct;28(10):1257-67.
• Panoussopoulos D, Theodoropoulos G, Lazaris AC, Papadimitriou K. Focal divergent chondrosarcomatous differentiation in a primary pleomorphic liposarcoma and expression of transforming growth factor beta. Int J Surg Pathol. 2004 Jan;12(1):79-85.
• Huang HY, Antonescu CR. Epithelioid variant of pleomorphic liposarcoma: a comparative immunohistochemical and ultrastructural analysis of six cases with emphasis on overlapping features with epithelial malignancies. Ultrastruct Pathol. 2002 Sep-Oct;26(5):299-308.
• Gebhard S, Coindre JM, Michels JJ, Terrier P, Bertrand G, Trassard M, Taylor S, Chateau MC, Marques B, Picot V, Guillou L. Pleomorphic liposarcoma: clinicopathologic, immunohistochemical, and follow-up analysis of 63 cases: a study from the French Federation of Cancer Centers Sarcoma Group. Am J Surg Pathol. 2002 May;26(5):601-16.
• Oliveira AM, Nascimento AG. Pleomorphic liposarcoma. Semin Diagn Pathol. 2001 Nov;18(4):274-85.
• Downes KA, Goldblum JR, Montgomery EA, Fisher C. Pleomorphic liposarcoma: a clinicopathologic analysis of 19 cases. Mod Pathol. 2001 Mar;14(3):179-84.
• Miettinen M, Enzinger FM. Epithelioid variant of pleomorphic liposarcoma: a study of 12 cases of a distinctive variant of high-grade liposarcoma. Mod Pathol. 1999 Jul;12(7):722-8.
• Castleberry RP, Kelly DR, Wilson ER, Cain WS, Salter MR. Childhood liposarcoma. Report of a case and review of the literature. Cancer. 1984 Aug 1;54(3):579-84.
• 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.
• Alaggio R, Coffin CM, Weiss SW, Bridge JA, Issakov J, Oliveira AM, Folpe AL. Liposarcomas in young patients: a study of 82 cases occurring in patients younger than 22 years of age. Am J Surg Pathol. 2009 May;33(5):645-58.
• Gardner JM, Dandekar M, Thomas D, Goldblum JR, Weiss SW, Billings SD, Lucas DR, McHugh JB, Patel RM. Cutaneous and subcutaneous pleomorphic liposarcoma: a clinicopathologic study of 29 cases with evaluation of MDM2 gene amplification in 26. Am J Surg Pathol. 2012 Jul;36(7):1047-51.