Table of Contents
Definition / general | Essential features | Terminology | Epidemiology | Sites | Case reports | Prognosis and treatment | Clinical images | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Cytology description | Positive stains | Negative stains | Molecular / cytogenetics description | Molecular / cytogenetics images | Differential diagnosis | Additional references | Board review style question #1 | Board review style answer #1Cite this page: Clay M. Atypical lipomatous tumor / well differentiated liposarcoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/softtissuewdliposarcoma.html. Accessed August 14th, 2022.
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
Epidemiology
- Most common adipocytic malignancy (40 - 45% of all liposarcomas)
- Peak age in adults is between ages 40 - 60 years
- Very rare in children (Hum Pathol 2017 Jul 10, [Epub ahead of print]) but can be associated with Li-Fraumeni syndrome (Pediatr Dev Pathol 2010;13:218)
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
Case reports
- 36 year old woman with gluteal mass (World J Surg Oncol 2006;4:33)
- 43 year old woman with abdominal fullness and weight gain (Hinyokika Kiyo 2010;56:697)
- 73 year old man with mesenteric tumor (Case Rep Oncol 2011;4:178)
- Multiple cases of oral and salivary gland liposarcomas (Mod Pathol 2002;15:1020)
Prognosis and treatment
- Most important factor is anatomic location; surgical resection with widely negative margins is generally curative
- Tumors do not metastasize unless they dedifferentiate, which is associated with significantly shorter overall survival (Am J Surg Pathol 2007;31:1)
- 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)
- 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
Clinical images
Gross description
- Typically multilobulated and well circumscribed
- Rarely grossly infiltrative
- Marbled yellow cut surface in lipoma-like lesions, with more firm / fibrotic white areas grossly in lesions with less adipocytic differentiation
- Fat necrosis in large lesions, especially at the periphery
- Sample carefully to look for dedifferentiated component
- Dedifferentiated areas are nonlipogenic and can stand out as firm nodules or be more diffusely admixed with low grade areas
Gross images
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 contain 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 for nonlipogenic tumors
- Chronic inflammatory cells (B > T cells) with occasional lymphoid follicles scattered in a cellular fibrocollagenous stroma with sparse multinucleate 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)
- Lipoleiomyosarcoma:
- Lipoma-like subtype:
- 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 vs. 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 below)
- Lipomas do occur in the retroperitoneum (BMC Res Notes 2015;8:75) and the distinction with WDL may require molecular testing
- 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)
- Nuclei with sharply outlined vacuoles (Lochkern cells) are enlarged and can appear hyperchromatic but are normal adipocytes cut in cross section
Microscopic (histologic) images
Scroll to see all images:
Contributed by Michael Clay, M.D.
AFIP images
Morphologic variability:
Metaplastic change:
Images hosted on other servers:
Cytology description
- Large cells with multilobulated nuclei and mature appearing adipocytes
- May have bizarre tumor cells (Acta Cytol 2000;44:459)
Positive stains
- MDM2, CDK4 and p16 together have 71% sensitivity and 98% specificity for detecting WDL and DDL (Am J Surg Pathol 2012;36:462, Appl Immunohistochem Mol Morphol 2009;17:51)
- Pitfalls:
- MDM2 and CDK4 can falsely stain endothelial cells, foamy macrophages and multinucleated giant cells; this means fat necrosis may be positive
- Care should be taken in problematic well differentiated lipomatous tumors (lipoma-like WDL vs. lipoma), where sensitivity is particularly low (Am J Surg Pathol 2016;40:1647); in such cases FISH testing is preferred by some
- S100 (adipocytes in 2/3 of cases)
- CD34 (some spindle cells)
- Desmin (rare cells are often identified)
Negative stains
Molecular / cytogenetics description
- Ring or giant marker/rod chromosomes derived from 12q13-15 in almost all cases
- Amplifications of the 12q12-21 (Virchows Arch 2012;461:67)
- MDM2 and CDK4, by FISH or real time PCR, can differentiate from other sarcomas (Hum Pathol 2006;37:1123, Am J Surg Pathol 2007;31:1476)
- See Am J Surg Pathol 2015;39:1433 for recommendations on when to utilize FISH in well differentiated tumors
- Carboxypeptidase M amplification has also been reported (Mod Pathol 2009;22:1541)
- Other rearrangements include amplifications of 10p11-14 (Virchows Arch 2012;461:67) and complex rearrangements involving chromosomes 8 and 12 (Oncol Rep 2005;13:649)
Molecular / cytogenetics images
Differential diagnosis
- Inflammatory subtype of ALT / WDL
- Castleman disease:
- No well differentiated liposarcomatous component
- Absence of 12q13-15 amplification
- Hodgkin lymphoma:
- Inflammatory myofibroblastic tumor:
- No well differentiated liposarcomatous component
- Usually see a highly cellular proliferation of SMA positive myofibroblasts associated with a dense lymphoplasmacytic infiltrate
- Predilection for children and lack MDM2 gene amplification
- Nearly 1/2 are positive for ALK immunostaining secondary to ALK gene rearrangements (Mod Pathol 2001;14:569)
- Sclerosing mesenteritis or idiopathic retroperitoneal fibrosis:
- No well differentiated liposarcomatous component, lack MDM2 gene amplification
- Beware fat necrosis, which can give the false impression of liposarcoma in this setting
- Look for increased IgG4 positive plasma cells to evaluate for IgG4 related disease (Mod Pathol 2012;25:1181)
- Castleman disease:
- Lipoma-like subtype of ALT / WDL
- Lipoblastoma:
- Usually age 3 or younger, (Virchows Arch 2002;441:299)
- Lobular growth pattern with delicate branching vessels and myxoid change are characteristic
- Negative for 12q13-15 amplification
- Classic lipoma:
- Typically superficial, lack atypical nuclei
- Use FISH in deep seated lesions where atypia may be sparse
- Molecular confirmation is particularly useful (Am J Surg Pathol 2015;39:1433):
- Recurrent tumors
- Deep extremity lesions > 10 cm in patients over the age of 50
- Cases with equivocal cytologic atypia
- Lesions in the retroperitoneum, pelvis or abdomen
- Molecular confirmation is particularly useful (Am J Surg Pathol 2015;39:1433):
- Lipomatous angiomyolipoma:
- HMB45+ epithelioid cells, negative for 12q13-15 amplification (Pathol Int 2006;56:638)
- Massive localized lymphedema:
- Clinically very different, localized in the proximal thigh of morbidly obese individuals
- Fat separated by widened edematous fibrous septa, with no cytologic atypia
- Also see other areas of compromised lymphatic drainage such as lymphangiectasia in the overlying skin
- Lacks molecular findings of ALT / WDL (Am J Surg Pathol 1998;22:1277)
- Myxoid liposarcoma:
- Morphology may be similar but negative for 12q13-15 amplification (Mod Pathol 2009;22:223)
- Tends to have more lobular growth, delicate plexiform vasculature and signet ring lipoblasts
- Characterized by FUS gene rearrangements
- Paraffinoma:
- History of paraffin injection, no atypical nuclei, negative for 12q13-15 amplification (Br J Radiol 2003;76:264)
- Spindle cell / pleomorphic lipoma:
- Frequently seen in the head and neck or other superficial soft tissues, look for ropey collagen and absence of fibrillary stroma
- Have deletions of 16q / 13q and do not have amplification of 12q13-15 (Am J Surg Pathol 2012;36:1119)
- loss of RB1 by IHC staining (Am J Surg Pathol 2012;36:1119)
- Lipoblastoma:
- Sclerosing subtype of ALT / WDL
- Atypical spindle cell lipomatous tumor (Am J Surg Pathol 2017;41:234):
- Dedifferentiated liposarcoma:
- Nonlipogenic high grade sarcoma, that still retains molecular characteristics of WDL
- Typically shows abrupt transition between well differentiated and dedifferentiated components
- Rarely can have homologous lipoblastic differentiation where the dedifferentiated component morphologically resembles pleomorphic liposarcoma (Histopathology 2013;62:702)
- Concept of low grade dedifferentiation is controversial but generally has cellularity between that seen in WDL and DDL (Pathol Int 2001;51:392)
- Lipomatous hemangiopericytoma (solitary fibrous tumor with fatty differentiation) (Am J Surg Pathol 1999;23:1201):
- Morphologically distinct with the patternless pattern of growth, round to spindle cell morphology and characteristic hemangiopericytomatous vasculature
- Has NAB2-STAT6 gene fusions (diffuse STAT6 and CD34 IHC positivity) and negative for 12q13-15 amplification
Additional references
Board review style question #1
Which of the following is true about atypical lipomatous tumor / well differentiated liposarcomas (ALT / WDL)?
- Frequently present in the upper trunk / back of the neck in adults.
- Have genomic alterations at 8q11-13.
- Lack the ability to metastasize.
- Must contain lipoblasts.
- Show a predilection to metastasize to other soft tissue sites.
Board review style answer #1
C. Lack the ability to metastasize; ALT / WDL cannot metastasize unless it progresses to a dedifferentiated liposarcoma.
Comment Here
Reference: Atypical lipomatous tumor / well differentiated liposarcoma
- Incorrect, spindle cell lipomas show this predilection.
- Incorrect, lipoblastomas have PLAG1 gene fusions, which is located at 8q11-13.
- Incorrect, remember they neither need nor always have lipoblasts.
- Incorrect, myxoid liposarcoma shows the unusual predilection amongst fatty tumors to metastasize to other soft tissue sites.
Comment Here
Reference: Atypical lipomatous tumor / well differentiated liposarcoma