Atypical Lipomatous Tumor

Differential Diagnosis

Lipoma	Atypical Lipomatous Tumor
Lacks atypical cells and lipoblasts	Atypical cells and frequently lipoblasts
MDM2, CDK4, p16 negative	MDM2, CDK4, p16 most positive

In the retroperitoneum, any tumor composed entirely of mature fat, even without atypia, historically has been considered atypical lipomatous tumor

Genetic analysis has demonstrated some examples of apparent true retroperitoneal lipomas (Macarenco)

The diagnosis of tumors composed of mature fat with atypia depends upon the location
- In 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

Hibernoma with predominant mature fat	Atypical Lipomatous Tumor
Small, central bland nuclei in vacuolated cells	Lipoblasts, if present, have atypical nuclei
Lacks atypical nuclei	Contains atypical nuclei
Frequently superifcial	Rarely superficial
MDM2, CDK4, p16 negative	MDM2, CDK4, p16 most positive

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

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

Dermatofibrosarcoma Protuberans	Spindle Cell Variant Atypical Lipomatous Tumor
No cytologic atypia	Mild to moderate atypia
Entrapped fat at periphery	Fat integral to lesion
No lipoblasts	Lipoblasts frequently present
CD34 may be extensive	CD34 only in scattered cells

Spindle Cell Atypical Lipomatous Tumor	Low Grade Fibromyxoid Sarcoma
Adult fat integral to lesion	No fat component
Lipoblasts may be present	No lipoblasts
Abnormal mitotic fibures may be present	No abnormal mitotic figures

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%)
- It has been suggested that some MFH that are positive for these markers represent dedifferentiated ALT (Chung)