(1)
Department of Pathology, University of Manitoba Max Rady College of Medicine, Winnipeg, MB, Canada
Keywords
AngiolipomaAtypical lipomatous tumor/well-differentiated liposarcomaHibernomaLipomatous tumorMyxoid liposarcomaPleomorphic liposarcomaSpindle cell lipoma
Fig. 4.1
Numerous adipocytes with abundant clear cytoplasm and eccentric inconspicuous nuclei
Fig. 4.2
Multiple lipoblasts in a pleomorphic liposarcoma (arrow). These cells contain one or more clear vacuoles that indent or displace the nuclei. These particular lipoblasts demonstrate substantial nuclear atypia consistent with their malignant nature
4.1 Lipoma
A lipoma rarely elicits much excitement in the clinic or at the microscope. However, many unusual or malignant soft tissue tumors are initially presumed to be a lipoma, and familiarity with this entity can prove useful when discussing an alternative diagnosis. Lipomas commonly occur as superficial subcutaneous masses in the shoulder, back, neck, abdomen, and extremities, often arising in the fifth to seventh decade of life [1, 2]. Less frequently, they present as larger and more deeply located masses in the muscles of the arm, thigh, or thorax [3].
Pathology
On gross examination, lipomas consist of yellow and translucent adipose tissue. Microscopic examination shows relatively unremarkable adipocytes with inconspicuous eccentrically located nuclei. Sometimes, focal areas of fat necrosis are present, but areas of significant nuclear atypia are generally not identified (Fig. 4.3).
Fig. 4.3
Unremarkable adipocytes in a lipoma with focal areas of fat necrosis
Ancillary Studies
Lipomas are positive for S100 immunohistochemical stain and often contain mutations involving the HMBA2 gene. However, these ancillary studies are not typically utilized for diagnosis.
Differential Diagnosis
Well-differentiated liposarcoma
Comments
- 1.
Because lipomas and well-differentiated liposarcomas can appear remarkably similar under the microscope, knowledge of the clinical presentation of a lipomatous lesion is helpful for a pathologist.
- 2.
Pathologists have increased suspicion for liposarcoma when confronted with adipocytic lesions that are large (greater than 10 cm) and recurrent, or have concerning radiologic features. Fatty tumors arising in the abdomen, pelvis, and retroperitoneum are highly suspicious for a well-differentiated liposarcoma [4].
- 3.
Well-differentiated liposarcoma can often be excluded by demonstrating the absence of MDM2 or CDK4 gene amplification by fluorescence in situ hybridization.
- 4.
Lipomas are benign, but can rarely recur, particularly if they are deeply located. Lipomas that are intimately associated with muscle (intramuscular lipomas ) have an increased risk for recurrence [5].
4.2 Angiolipoma
Angiolipomas are fatty tumors that arise as single or multiple subcutaneous nodules on the forearm, upper arm, or trunk. These often arise in young adult males and are painful. Approximately 5% of patients will have a family history of angiolipomas [2, 6].
Pathology
On gross examination, resected angiolipomas tend to appear as fatty tissue. Microscopic examination demonstrates bland-appearing adipose tissue with prominent blood vessels (Fig. 4.4a). Occasionally, this vascular network can be the predominant component of the lesion. At least a few of the vessels will contain fibrin thrombi (Fig. 4.4b) [7].
Fig. 4.4
(a) Angiolipoma with network of dilated vessels in association with benign-appearing adipose tissue. (b) Vessels of angiolipoma with fibrin thrombi (arrow)
Ancillary Studies
The vessels in an angiolipoma are highlighted by CD34, CD31, and ERG immunohistochemical stains.
Differential Diagnosis
Lipoma
Kaposi sarcoma
Intramuscular hemangioma
Spindle cell lipoma
Comments
- 1.
Lipomas contain scattered capillaries, but these are compressed and lack the intravascular thrombi seen in angiolipoma.
- 2.
Highly cellular angiolipomas can be mistaken for a more aggressive neoplasm such as Kaposi sarcoma. The endothelial tumor cells in Kaposi sarcoma are distinguished by positive HHV-8 staining.
- 3.
Sometimes hemangiomas in the muscle can have associated adipose tissue. However, the vessels in intramuscular hemangiomas are much larger than those seen in a subcutaneous angiolipoma [2].
- 4.
A cellular angiolipoma can have areas of vague spindling which can be confused for a spindle cell lipoma. While the cells in spindle cell lipoma will also stain with CD34, they lack more specific endothelial markers like CD31.
- 5.
Angiolipomas are benign lesions that are cured by complete excision and typically do not recur [5].
4.3 Spindle Cell/Pleomorphic Lipoma
Spindle cell/pleomorphic lipomas are benign lesions that arise in the subcutaneous tissue of the posterior neck, back, and shoulders of middle-aged to older adults. These occasionally can occur in other areas such as the head and extremities [8].
Pathology
Spindle cell lipomas contain bland adipose tissue that is traversed by a vaguely organized population of benign-appearing spindle cells. These spindle cells are usually associated with thick and dense collagen fibers (Fig. 4.5a). The more pleomorphic forms of this neoplasm will contain cells with multiple peripherally arranged nuclei that are referred to as “floret cells ” (Fig. 4.5b) [8, 9].
Fig. 4.5
(a) Spindle cell/pleomorphic lipoma with dense collagen and scattered spindle cells (arrow). (b) Occasional multinucleated “floret cell” in a spindle cell/pleomorphic lipoma
Ancillary Studies
Although not specific, spindle cell lipomas are positive for a CD34 immunohistochemical stain [10].
Differential Diagnosis
Neurofibroma
Solitary fibrous tumor
Well-differentiated liposarcoma
Comments
- 1.
Unlike neurofibroma, most spindle cell lipomas are negative for S100.
- 2.
Solitary fibrous tumor can be distinguished from spindle cell lipomas by positive staining with STAT6.
- 3.
More atypical forms of spindle cell/pleomorphic lipoma can be confused for well-differentiated liposarcoma. Well-differentiated liposarcomas only rarely occur in the subcutaneous tissue and do not typically exhibit ropey collagen fibers.
- 4.
If the microscopic features are particularly concerning, negative FISH studies for MDM2 gene amplification can help exclude well-differentiated liposarcoma [2].
4.4 Hibernoma
Hibernomas are benign adipocytic tumors that are similar to lipomas, except that the cells resemble the adipocytes seen in brown fat . These neoplasms occur over a broad age range, with the average age of occurrence being 38 years-old. Frequent locations include the thigh, shoulder, back, neck, chest, and arm, among others. Clinically, these present as progressively and slowly enlarging masses [11].
Pathology
The neoplasm is composed of adipocytes with eosinophilic granular or vacuolated cytoplasm (Fig. 4.6). Varying amounts of usual appearing adipocytes with clear cytoplasm can also be interspersed among these cells [5].
Fig. 4.6
Hibernoma with numerous adipocytes containing vacuolated and eosinophilic cytoplasm
Ancillary Studies
Ancillary studies are not typically utilized to diagnose a hibernoma.
Differential Diagnosis
Rhabdomyoma
Granular cell tumor
Well-differentiated liposarcoma or myxoid liposarcoma with hibernomatous cells
Comment
- 1.
Rhabdomyoma can be distinguished from hibernoma by cross striations in the cytoplasm and positive skeletal muscle markers.
- 2.
A granular cell tumor also has neoplastic cells with eosinophilic cytoplasm, but the cytoplasmic granules are much finer than seen in rhabdomyoma [2].
- 3.
Well-differentiated liposarcoma and myxoid liposarcoma can rarely contain fat cells with hibernoma-like changes. A careful eye for other malignant features and molecular cytogenetics can identify these more ominous entities.
- 4.
Hibernomas are benign lesions that do not recur.
4.5 Lipoblastoma
Lipoblastomas are benign lipomatous neoplasms of infants and young children. These occur as superficial soft tissue masses in the upper and lower extremities, head and neck, or trunk. Although benign, lipoblastomas have been associated with disorders such as autism, seizures, congenital anomalies, developmental delay, Sturge-Weber syndrome, or a family history of lipomas [12, 13].
Pathology
Grossly, these lesions appear to be yellow or tan in color, and myxoid areas are frequently present. In lesions that have a less “mature” appearance, microscopic examination shows immature adipocytes and occasional lipoblasts that are partitioned by fibrous septa to form a lobulated architecture (Fig. 4.7). Myxomatous areas and a delicate capillary architecture can be identified [14].
Fig. 4.7
Lipoblastoma with immature adipocytes and myxoid changes
Ancillary Studies
Lipoblastomas exhibit mutations involving the PLAG gene on chromosome 8.
These tumors are negative for genetic mutations involving the DDIT3 gene on chromosome 12.
Differential Diagnosis
Myxoid liposarcoma
Comment
- 1.
“Immature lipoblastomas” can look almost identical to a myxoid liposarcoma, since both can have a myxoid background, lipoblasts, and a delicate network of capillaries.
- 2.
While pediatric myxoid liposarcomas rarely occur, these usually only do so in the second decade of life and should be cautiously diagnosed only after molecular confirmation [15].
- 3.
Myxoid liposarcomas can be distinguished by their genetic translocations involving the DDIT3 gene.
- 4.
Lipoblastomas are benign, but they can recur. Patients with diffuse lesions that are incompletely excised are particularly at risk for recurrence [2].
4.6 Atypical Lipomatous Tumor/Well-Differentiated Liposarcoma
Atypical lipomatous tumor/well-differentiated liposarcoma represents almost half of adipocytic malignancies and has a predilection for deep locations, such as the retroperitoneum and deep proximal extremities. Other sites of occurrence include the mediastinum or spermatic cord . Superficial locations, such as subcutaneous tissue, are extraordinarily rare. Clinically, these arise as painless and slowly enlarging masses that can grow quite large prior to discovery. The diagnosis can sometimes be suspected from the size, location, and appearance of prominent fibrous septations on imaging [16–18].
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