Differential Diagnosis
Benign lipomatous tumors
Malignant lipomatous tumors
Other lesions containing prominent fat
Spindle cell lesions that may be confused with spindle cell variant of ALT
Other tumors containing atypical cells resembling those of ALT
Lipoma vs Atypical Lipomatous Tumor
Diagnosis and behavior depends to a great extent on location
Dermis and subcutis of posterior neck, shoulders and upper back
Virtually all are lipomas
Dermis and subcutis of all other sites
The vast majority are ordinary lipomas or angiolipomas
Rare mature fatty neoplasms with cytologic atypia or lipoblasts are seen in these locations
Infrequent recurrences
Dedifferentiation is very rare
Natural (untreated) history is unknown
We designate such neoplasms as atypical lipomatous tumors but with a comment that aggressive behavior is rare in tumors arising in those sites
Deep soft tissues
Intramuscular , intermuscular and periosteal
Lipomas are well described in these locations
Must not have cytologic atypia or lipoblasts
Intramuscular lipoma may recur if incompletely excised
Rare large intramuscular lipomas have recurred with features of atypical lipomatous tumor
Genetic study for MDM2 amplification may be indicated in large or aggressively recurring intramuscular lipomas even in the absence of atypia
Atypical lipomatous tumor can occur in these locations
Infiltration is not relevant to the diagnosis
Requires cytologic atypia or lipoblasts
Frequent recurrences, rarely uncontrollable
Dedifferentiation rare
Retroperitoneum, spermatic cord, mediastinum
Vast majority of mature fatty neoplasms are atypical lipomatous tumors
(Most cord “lipomas” are merely pre-peritoneal fat squeezed through the inguinal ring, and not neoplasms)
Frequent recurrences, may be uncontrollable
May dedifferentiate and metastasize
Rare lipomas have been documented in the retroperitoneum (Macarenco)
Requires extensive sampling to exclude cytologic atypia and lipoblasts
Immunohistochemical and/or genetic studies are recommended before making this diagnosis
Myelolipoma frequently occurs in or around the adrenal
Megakaryocytes should not be confused with atypical cells of ALT
We consider atypical lipomatous tumor and well differentiated liposarcoma to be equivalent terms and primarily use the former, although both are acceptable (see discussion of these terms )
Some use WDL for deep central tumors and ALT for those in other sites
Immunohistochemistry and/or in situ hybridization may be of use at any site
Lipomas are reported to be MDM2, CDK4, p16 negative
ALT are generally MDM2, CDK4, p16 positive
See subtypes of lipomas for specific differential diagnoses
Pleomorphic Lipoma vs Atypical Lipomatous Tumor
The diagnosis of tumors composed of mature fat with atypia depends upon the locationIn the dermis and subcutis of the posterior neck, upper back or shoulders, it is considered pleomorphic lipoma
In all other locations, it is considered atypical lipomatous tumor
Pleomorphic lipoma MDM2 and CDK4 negative, while most ALT are positive
Ropey collagen and extensive CD34 staining support pleomorphic lipoma
Myxoid Liposarcoma Atypical Lipomatous Tumor
No large atypical nuclei
Large atypical nuclei present
Prominent "chicken wire" vascular pattern
Lacks "chicken wire" vascular pattern
Rare as a primary lesion in retroperitoneum
Frequently occurs in retroperitoneum
MDM2 and CDK4 4% by immunohistology but 1/5 MDM2 by FISH
MDM2 and CDK4 most positive
Fat Necrosis
Atypical Lipomatous Tumor
Small central nuclei
Large eccentric nuclei
Nuclei not indented by vacuoles
Vacuoles indent nuclei in lipoblasts
Foamy cells frequently fill spaces of dead lipocytes
Lipoblasts scattered
Angiomyolipoma
Atypical Lipomatous Tumor
Large atypical blood vessels
No large vascular component
Large epithelioid cells
No large epithelioid cells
HMB45 positive
HMB4 negative
MDM2 and CDK4 negative
MDM2 and CDK4 most positive
Awareness of the clinical situation should make the diagnosis apparent
Spindle Cell Lipoma Spindle Cell Variant Atypical Lipomatous Tumor
Restricted to back of neck, upper back, shoulders
Various locations
Bland spindle cells
Mild to moderate atypia of spindle cells
Ropy collagen bundles
No ropy collagen
Circumscribed
May be infiltrative
Uniformly strong CD34
CD34 only occasionally reactive
MDM2 0-12% and CDK4 0-6%
MDM2 and CDK4 most positive
No areas of usual ALT pattern
Areas of usual ALT pattern
MDM2 and CDK4 figures given for usual ALT as no data for spindle cell variant
Neurofibroma
Spindle Cell Variant Atypical Lipomatous Tumor
Hypocellular
Moderated cullularity
No mitotic figures
Occasional mitotic figures
No nuclear pleomorphism
Mild to moderate atypia
S100 positive
Spindle cells S100 negative
Areas may be histologically identical
Low Grade Myxofibrosarcoma
Spindle Cell Variant Atypical Lipomatous Tumor
No lipoblasts
Lipoblasts frequently present
Hypocellular
Moderate cellularity
Perivascular grouping of cells
No perivascular pattern
May have atypical mitotic figures
No atypical mitotic figures
May have marked pleomorphism
Mild to moderate atypia
MFH and other pleomorphic sarcomas vs Atypical Lipomatous Tumor
Various neoplasms may have atypical cells resembling those of ALT
The diagnosis of ALT is made by identifying mature fat integral to the lesion
This requires appropriate surgical and pathological sampling of fatty areas
Fatty areas of neoplasm may be confused grossly with normal fat if the level of suspicion is not high
ALT is positive for MDM2 and CDK4 while MFH is infrequently positive (11 and 3%)
