Soft tissue

Adipose tissue tumors

Liposarcoma

Atypical lipomatous tumor / well differentiated liposarcoma



Last author update: 5 May 2023
Last staff update: 5 May 2023

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PubMed Search: Atypical lipomatous tumor / well differentiated liposarcoma

Susan Potterveld, D.O., M.P.H.
Michael R. Clay, M.D.
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Cite this page: Potterveld S, Clay MR. Atypical lipomatous tumor / well differentiated liposarcoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/softtissuewdliposarcoma.html. Accessed February 22nd, 2024.
Definition / general
  • Locally aggressive mesenchymal tumor composed of mature adipocytes and stromal cells with at least focal cytologic atypia
  • Adipocytic component and background cellular constituents vary in concentration and lead to several recognizable morphologic subtypes
Essential features
  • Low grade lipogenic tumor with multiple morphologic subtypes and significant histologic variability
  • Molecularly characterized by ring or giant marker / rod chromosomes composed of material from 12q13-15
    • Results in localized amplification of several neighboring genes, including MDM2
  • Behavior is dependent upon location, with deep seated lesions having the ability to dedifferentiate and subsequently metastasize
  • Terminology is based on location (see Terminology)
  • Wide local excision with negative margins is often curative
Terminology
  • Use of the terminology atypical lipomatous tumor (ALT) and well differentiated liposarcoma (WDL) is based on a tumor's location in the body and primarily relates to resectability
    • Tumors are morphologically and genetically identical, with the variation in terminology intended to avoid both undertreatment and overtreatment
  • Tumors located in the periphery have no risk of metastasis
    • For such lesions, complete resection is generally curative
    • For these tumors, the designation as sarcoma is inappropriate and the term ALT is preferred
  • If the tumor is deep seated (retroperitoneum, mediastinum, spermatic cord), the chance of achieving negative margins is significantly diminished and the risk of local recurrence, dedifferentiation (DDL) and death are increased
    • Lesions are best regarded as true sarcomas and the terminology of well differentiated liposarcoma is more appropriate
  • Suggestion: use of atypical lipoma is not recommended
ICD coding
  • ICD-O:
    • 8850/1 - atypical lipomatous tumor
    • 8851/3 - liposarcoma, well differentiated
  • ICD-11:
    • 2F7C & XH0RW4 - neoplasms of uncertain behavior of connective or other soft tissue & atypical lipomatous tumor
    • 2B5H & XH7Y61 - well differentiated lipomatous tumor, primary site & liposarcoma, well differentiated
Epidemiology
Sites
  • Most common site is the deep thigh of the lower extremity, followed by retroperitoneum, trunk, head and neck region and spermatic cord
  • Numerous anatomic sites have been reported, including the subcutis and skin
Diagnosis
  • Diagnosis typically requires surgical resection to ensure adequate sampling, as diagnostic accuracy is limited by sampling bias on core needle biopsy (AJR Am J Roentgenol 2021;216:997)
Radiology description
  • Fat tissue density mass with thick or nodular enhancing septa on CT imaging
  • Mass of fat isointense signal in all sequences, thick septa or nodular nonlipomatous areas with contrast enhancement on MRI imaging
  • Retroperitoneal WDL typically shows fat with an abnormal appearance on MRI (stranding) that represents the thick fibrous bands
  • Reference: Radiographics 2005;25:1371
Prognostic factors
  • Most important factor is anatomic location
  • Tumors do not metastasize unless they dedifferentiate, which is associated with significantly shorter overall survival (Am J Surg Pathol 2007;31:1)
  • Subcutaneous or intramuscular tumors may recur but typically do not dedifferentiate or metastasize
  • Risk of dedifferentiation is directly related to location and duration of growth
Case reports
Treatment
  • Surgical resection with widely negative margins is generally curative
  • Retroperitoneal or central body site tumors are difficult to resect with a clear margin, frequently recur, can dedifferentiate and cause death (J Surg Res 2012;175:12)
  • Positive margin status and sclerosing subtype are associated with reduced local recurrence free survival (Ann Surg Oncol 2004;11:78)
Clinical images

Images hosted on other servers:

Pelvic tumor during surgery

Intraoperative image of axillary tumor

Gross description
  • Typically multilobulated and well circumscribed
  • Rarely are grossly infiltrative
  • Marbled yellow cut surface in lipoma-like lesions, with more firm / fibrotic white areas grossly in lesions with less adipocytic differentiation (Semin Diagn Pathol 2019;36:112)
  • Fat necrosis in large lesions, especially at the periphery
  • Sample carefully to look for dedifferentiated components
    • Dedifferentiated areas are nonlipogenic and can stand out as firm nodules or be more diffusely admixed with low grade areas
Gross images

Images hosted on other servers:

Mesenteric tumor

Pelvic tumor

Retroperitoneal tumor

Dedifferentiated tumor in small bowel mesentery

Microscopic (histologic) description
  • Depends on subtype, generally composed of mature fat with variably sized adipocytes and bands of fibrotic stroma containing spindle cells with enlarged, hyperchromatic nuclei
  • Can be markedly atypical
  • Cellularity is low and mitotic figures are uncommon
  • Atypical cells are more commonly found in fibrous septa and in a perivascular distribution
  • Rarely display heterologous differentiation (Hinyokika Kiyo 2010;56:697)
  • There are 3 histologic subtypes that have limited clinical significance (Semin Diagn Pathol 2001;18:258, Ann Surg Oncol 2004;11:78)
    • Lipoma-like subtype
      • Most common subtype
      • Scattered atypical cells may be diffuse or exceedingly rare
      • Frequently contains lipoblasts
      • Grossly, can be indistinguishable from lipoma
    • Sclerosing subtype
      • Second most common subtype
      • Predilection for retroperitoneal or paratesticular location
      • Collagenous fibrous tissue with scattered adipocytes and atypical multinucleated stromal cells
      • Scant lipogenic component may be missed in small samples
    • Inflammatory subtype
      • Rare
      • Almost always in the retroperitoneum where it is confused with nonlipogenic tumors
      • Chronic inflammatory cells (B > T cells) with occasional lymphoid follicles scattered in a cellular fibrocollagenous stroma with sparse multinucleated atypical cells
      • May obscure adipocytes
  • Mixed subtype
    • Not uncommon to see an admixture of these subtypes with sufficient sampling
  • Rarest variants
    • Lipoleiomyosarcoma
      • Liposarcoma with leiomyosarcomatous differentiation
      • Both components are low grade
      • Variable amount of the smooth muscle component, which can be seen in association with large vascular walls
      • Similar biology and can dedifferentiate
    • ALT / WDL with low grade osteosarcoma-like areas
      • In contrast to osseous metaplasia, these lesions have foci reminiscent of parosteal osteosarcoma or low grade central osteosarcoma (Am J Surg Pathol 2010;34:1361)
  • Pitfalls and tips
    • Nuclei with sharply outlined vacuoles (Lochkern cells) are enlarged and can appear hyperchromatic but are normal adipocytes cut in cross section
      • These do not qualify for the diagnosis; the same goes for atrophic skeletal muscle fibers, which can simulate atypia on an otherwise typical lipoma
    • Histiocytes in areas of fat necrosis can simulate atypical cells
    • Lipoblasts are neither necessary nor sufficient for diagnosis
      • When present they are generally multivacuolated versus the signet ring lipoblasts commonly seen in myxoid liposarcoma
    • Fatty differentiation may be very focal and difficult to differentiate from background adipocytes; when in doubt test molecularly (see Molecular / cytogenetics description)
    • Lipomas do occur in the retroperitoneum and the distinction with WDL may require molecular testing (BMC Res Notes 2015;8:75)
      • Retroperitoneal WDL typically shows fat with an abnormal appearance on MRI (stranding) that represents the thick fibrous bands
    • Avoid using subtypes as diagnoses (i.e., inflammatory liposarcoma); the preferred terminology would be well differentiated liposarcoma, with the addition of inflammatory subtype (or that information conveyed in the comment)
Microscopic (histologic) images

Contributed by Michael Clay, M.D. and AFIP

Inflammatory ALT

Lipoma-like ALT

Recurrent ALT with ropey collagen


Recurrent ALT with ropey collagen

Sclerotic ALT

Sclerotic ALT



Morphologic variability:

Enlarged, dense irregular nuclei

Bizarre shaped cells

Lipoblasts are multivacuolated with atypical nuclei


Atypical cells within fibrous tissue

Lochkern cells with sharply outlined nuclear vacuoles

Floret cells


Thick collagen fibers

Thin collagen fibers

Moderately cellular (but not dedifferentiated)

Atypical cells within blood vessel walls



Metaplastic change:

Metaplastic bone

Metaplastic smooth muscle

Inflammatory subtype

Cytology description
  • Large cells with multilobulated nuclei and mature appearing adipocytes
  • May have bizarre tumor cells (Acta Cytol 2000;44:459)
Positive stains
Negative stains
Molecular / cytogenetics description
Molecular / cytogenetics images

Images hosted on other servers:

Giant ring or rod marker chromosome

Videos

Well differentiated liposarcoma / atypical lipomatous tumor mimicking lipoma

Well differentiated liposarcoma / atypical lipomatous tumor

Sample pathology report
  • Retroperitoneal mass, resection:
    • Well differentiated liposarcoma (7.5 cm) (see comment)
    • No evidence of dedifferentiation
    • Peripheral resection margins are positive for tumor
    • Comment: Histologic sections of this retroperitoneal mass show a well differentiated fatty neoplasm with fibrotic bands containing rare enlarged, hyperchromatic cells. The malignant cells show strong nuclear expression of MDM2 by immunohistochemistry, supporting the diagnosis.
Differential diagnosis
Board review style question #1

A retroperitoneal tumor is surgically resected and the microscopic image provided is representative of the entire lesion. Ancillary FISH testing is positive for MDM2 amplification. What is the diagnosis?

  1. Lipoma
  2. Myxofibrosarcoma
  3. Myxoid liposarcoma
  4. Pleomorphic lipoma
  5. Well differentiated liposarcoma
Board review style answer #1
E. Well differentiated liposarcoma. Given the findings of a retroperitoneal mass composed of a proliferation of variably sized adipocytes intermixed with rare atypical cells characterized by enlarged, hyperchromatic nuclei, the best diagnosis is well differentiated liposarcoma. Evidence of MDM2 amplification by FISH testing supports the diagnosis. A is incorrect, since although deep seated and large lipomas can occur, these lesions lack atypical nuclei and do not have 12q13-15 amplification. B is incorrect because myxofibrosarcomas are extremely rare in the retroperitoneum and although low grade lesions have scattered cells with enlarged, hyperchromatic nuclei, they do not have 12q13-15 amplification. C is incorrect because myxoid liposarcoma tumor cells lack significant atypia, are typically evenly distributed in a prominent myxoid stroma with delicate branching vasculature and do not have 12q13-15 amplification. D is incorrect because pleomorphic lipomas are most frequently seen in the head and neck region and do not have 12q13-15 amplification.

Comment Here

Reference: Atypical lipomatous tumor / well differentiated liposarcoma
Board review style question #2
Which of the following is true about atypical lipomatous tumor / well differentiated liposarcomas (ALT / WDL)?

  1. Frequently present in the upper trunk / back of the neck in adults
  2. Have genomic alterations at 8q11-13
  3. Lack the ability to metastasize
  4. Must contain lipoblasts
  5. Show a predilection to metastasize to other soft tissue sites
Board review style answer #2
C. Lack the ability to metastasize. ALT / WDL cannot metastasize unless it progresses to a dedifferentiated liposarcoma. A is incorrect because spindle cell lipomas show this predilection. B is incorrect because lipoblastomas have PLAG1 gene fusions, which is located at 8q11-13. D is incorrect since ALT / WDL neither need nor always have lipoblasts. E is incorrect because myxoid liposarcoma shows the unusual predilection among fatty tumors to metastasize to other soft tissue sites.

Comment Here

Reference: Atypical lipomatous tumor / well differentiated liposarcoma
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