Benign tumors and reactive conditions
Lipoma
Definition
- •
A benign dermal or subcutaneous mesenchymal tumor composed of mature adult-type adipose tissue
Clinical features
Epidemiology
- •
The most commonly encountered mesenchymal tumor
- •
Majority of patients are adults
- •
No sex predilection
Presentation
- •
Most cases are asymptomatic
- •
Occasionally painful when compressing nerves
- •
Slowly growing, but size is variable
- •
Usually solitary
- •
Multiple lipomas may be associated with neurofibromatosis, multiple endocrine neoplasia syndromes, or Bannayan syndrome (hemangiomas and multiple lipomas)
Prognosis and treatment
- •
Treated mostly for aesthetic reasons
- •
Cured by conservative surgical excision
- •
Recur only if incompletely excised and then only rarely
- •
Not associated with progression to liposarcoma
Pathology
Histology
- •
Resemble normal adult-type adipose tissue
- •
Lobules of adipocytes bounded by thin fibrous septa
- •
Adipocytes have large single lipid vacuole in their cytoplasm and eccentrically located small nuclei
- •
May show areas of fat necrosis and increased fibrosis after trauma
- •
No atypia, pleomorphism, mitoses, or hyperchromasia
Immunohistochemistry/special stains
- •
Adipocytes express S100 protein
Genetic profile
- •
True neoplasms
- •
Translocation at 12q14 involving HMGA2 gene is the most common aberration, often with LPP (3q27)
- •
6p21-23 rearrangements involving HMG1B gene are also seen
Main differential diagnoses
- •
Normal adipose tissue
- •
Pseudolipomatosis cutis
- •
Atypical lipomatous tumor
Lipomatosis
Definition
- •
Diffuse overgrowth of mature adipose tissue
- •
The disease presents in two forms: multiple symmetric lipomatosis (Launois-Bensaude syndrome) and asymmetric lipomatosis
Clinical features
Epidemiology
- •
Rare disorder, commonly associated with obesity
- •
Some familial cases show evidence of autosomal-dominant mode of inheritance
- •
Common in children less than 2 years of age
- •
Adults can occasionally be affected
- •
Can present in trunk, head and neck, and extremities
Presentation
- •
Painless, diffuse enlargement of affected area due to fat accumulation
- •
Rapid growth is characteristic
Prognosis and treatment
- •
Recurrence after palliative surgical removal is common
- •
Usually cured by radical surgical excision
- •
Although benign, can be fatal due to laryngeal obstruction
Pathology
Histology
- •
Sheets and lobules of mature adipocytes
- •
No encapsulation
Immunohistochemistry/special stains
- •
The mature adipocytes strongly express S100 protein
Main differential diagnoses
- •
Intramuscular lipoma
- •
Atypical lipomatous tumor
Multiple symmetric lipomatosis (Launois-Bensaude syndrome)
- •
The most common form of lipomatosis characterized by symmetrical deposition of adipose tissue in the trunk and head and neck area
- •
Two variants exist: diffuse and localized
- •
The diffuse variant usually affects the trunk of male children
- •
The localized variant characteristically affects the cervical area of adult males and can present with laryngeal obstruction
- •
Patients can present with neuropathy
Asymmetric lipomatosis
- •
Asymmetric deposition of adipose tissue affecting any part of the body
- •
Less common than the symmetric form of lipomatosis
- •
Can present with macrodactyly or gigantism of affected body area
Lipomatosis of Nerve
Definition
- •
A rare hamartomatous condition characterized by fatty infiltration of epineurium of a major nerve
- •
Also known as fibrolipoma of nerve, fibrolipomatous hamartoma of nerve, macrodystrophia lipomatosa, perineural lipoma, and intraneural lipoma
Clinical features
Epidemiology
- •
Affected individuals are mostly newborns and young children
- •
Female predilection
Presentation
- •
The median nerve is the most common location, followed by the ulnar nerve
- •
Slowly growing masses or macrodactyly
- •
Can be asymptomatic or associated with pain, paresthesia, or motor deficit
Prognosis and treatment
- •
Benign condition, but management can be challenging
- •
Surgical excision may result in permanent sensory and/or motor deficit
- •
Incomplete removal is associated with high rate of recurrence
Pathology
Histology
- •
Infiltration of epineurium and perineurium by mature adipose tissue admixed with fibrous tissue
- •
Metaplastic bone formation is rarely seen
Main differential diagnoses
- •
Intraneural lipoma
- •
Diffuse lipomatosis
- •
Traumatic neuroma
Adiposis Dolorosa
Definition
- •
A rare condition characterized by multiple painful plaques of accumulated subcutaneous fat
- •
Also known as Dercum disease
Clinical features
Epidemiology
- •
Rare disorder, commonly associated with obesity
- •
Affected individuals are mainly postmenopausal women
Presentation
- •
Painful and tender plaques
- •
Usually multiple
- •
Most cases are located in the lower extremities and pelvic area
Prognosis and treatment
- •
Benign condition cured by surgical excision
Pathology
Histology
- •
Subcutaneous lobules of mature adipocytes
- •
Fat necrosis can be seen
Immunohistochemistry/special stains
- •
The mature adipocytes strongly express S100 protein
Main differential diagnoses
- •
Lipoma
- •
Other forms of lipomatosis
Piezogenic Pedal Papules
Definition
- •
Multiple papules located at the internal aspects of the heels
Clinical features
Epidemiology
- •
Commonly affects athletes, particularly marathon runners
- •
Associated with Ehlers-Danlos and Prader-Willi syndromes as well as rheumatoid arthritis
- •
Rarely familial
Presentation
- •
Multiple asymptomatic skin-colored papules
- •
Lesions become more pronounced after prolonged standing
- •
Pressure may elicit pain
Prognosis and treatment
- •
Conservative management includes intralesional steroid and anesthetic injection or compression treatment
- •
Therapy outcome might not be satisfactory
- •
Surgical intervention is usually more effective
Pathology
Histology
- •
Mature adipose tissue herniating into the dermis
Immunohistochemistry/special stains
- •
The mature adipocytes strongly express S100 protein
Main differential diagnoses
- •
Intradermal lipoma
Fat Necrosis of the Morbidly Obese
Definition
- •
Necrosis of subcutaneous adipose tissue as a result of obesity
- •
It is thought to result from medial calcification of subcutaneous arterioles with subsequent ischemic necrosis of fat
Clinical features
Epidemiology
- •
Usually affects distal extremities
- •
Can affect thighs, abdomen, and other areas
- •
Associated with chronic renal failure and hyperphosphatemia
Presentation
- •
Painful induration and purplish discoloration of skin
- •
Associated skin necrosis can lead to ulcer formation
- •
Skin ulceration progresses rapidly as level of phosphate peaks
Prognosis and treatment
- •
High mortality rate due to development of secondary infection
Pathology
Histology
- •
Massive necrosis of subcutaneous adipose tissue with minimal inflammatory reaction
- •
Calcification of subcutaneous arterioles with luminal narrowing
Nevus Lipomatosus Superficialis
Definition
- •
A rare cutaneous hamartomatous lesion characterized by multiple small collections of adipocytes within the dermis
Clinical features
Epidemiology
- •
Affected individuals are children or adolescents
- •
Adults present with solitary variant
- •
No sex predilection
Presentation
- •
Multiple painless papules
- •
Size ranges from few millimeters up to 2 cm
- •
Most commonly affect the gluteal area, upper thighs, and lower back
Prognosis and treatment
- •
Cured by simple excision
Pathology
Histology
- •
Nonencapsulated lesion composed of variable number of fatty lobules deposited in the upper portion of the dermis
- •
The lobules condense around blood vessels and are interspersed by loose fibrous tissue
- •
Secondary changes include perifollicular fibrosis, follicular hyperkeratosis, and epidermal atrophy
Immunohistochemistry/special stains
- •
The mature adipocytes strongly express S100 protein
Main differential diagnoses
- •
Lipofibroma
- •
Fibroepithelial polyp
Fibrohistiocytic Lipoma
Definition
- •
A rare variant of lipoma characterized by the presence of fibrohistiocytic proliferation in addition to the conventional lipomatous component
Clinical features
Epidemiology
- •
Strong predilection for young adult males
- •
Anterior aspect of trunk is most commonly affected
Presentation
- •
Small, painless, subcutaneous lesions
- •
Usually solitary
Prognosis and treatment
- •
Cured by local excision
- •
No reports of recurrence or metastasis
Pathology
Histology
- •
Well-circumscribed subcutaneous lipomas with fibrohistiocytic foci
- •
Fibrohistiocytic foci depict slightly plump, bland-looking spindle cells arranged in fascicles in a collagenous stroma
- •
May exhibit minimal inflammation and/or hemosiderin deposition
Immunohistochemistry/special stains
- •
Tumor cells express CD34 and calponin
- •
Fibrohistiocytic component lacks S100 protein expression
Main differential diagnoses
- •
Benign fibrous histiocytoma
- •
Spindle cell lipoma
- •
Atypical lipomatous tumor
- •
Dermatofibrosarcoma protuberans
Lipofibromatosis
Definition
- •
A benign fibrofatty neoplasm presenting in childhood
Clinical features
Epidemiology
- •
More common in males
- •
Develops in infancy and childhood (mean age 1 year)
- •
Already present at birth in a substantial number of cases (about 15%)
Presentation
- •
Slowly growing and ill-defined painless mass
- •
Size of the lesion usually between 2 and 5 cm
- •
Wide anatomical distribution with predilection for hands and feet
Prognosis and treatment
- •
Benign proliferation, associated with high rate of nondestructive recurrence(s) (about 70%)
- •
Diffuse involvement of the limbs can result in deformities of the underlying bone
- •
Risk factors for local recurrence(s) include congenital onset, male gender, incomplete excision, and increased mitotic rate
- •
Complete surgical excision generally curative, but may be difficult to achieve
Pathology
Histology
- •
Poorly delineated proliferation in the subcutis and/or deep soft tissues
- •
Two main components are mature fat and fibroblastic spindle-shaped cells
- •
Adipose tissue component
- •
Integral part of the tumor
- •
Usually the predominant component
- •
Composed of mature adipocytes
- •
Variably sized and poorly demarcated lobules
- •
- •
Fibroblastic spindle cell component
- •
Formation of fascicles, typically growing along the fat septa
- •
Mild cytological atypia
- •
Mitoses absent or rare in the majority of cases
- •
Increased mitotic rate associated with increased likelihood of local recurrence
- •
Small to moderate amounts of collagen
- •
Focal myxoid change occasionally present
- •
- •
Univacuolated cells
- •
Usually encountered at the interface between the fibroblastic and adipocytic component
- •
Characterized by a single vacuole in the cytoplasm
- •
Likely represent degenerating adipocytes, lipid-rich fibroblasts, or transitional cells between fibroblast and adipocyte
- •
Seen in the majority of lesions
- •
- •
Entrapment of normal structures, including vessels, nerves, skin adnexa, and skeletal muscle within the tumor
- •
Pigmented melanocytic spindled or dendritic cells (similar to the ones found in Bednar tumor) exceptionally seen among the lesional cells
Immunohistochemistry/special stains
- •
Not contributory
- •
Focal S100 protein positivity in the spindle cell component occasionally detected
- •
β-catenin negative
Main differential diagnoses
- •
Juvenile hyaline fibromatosis
- •
Fibrous hamartoma of infancy
- •
Calcifying aponeurotic fibroma
- •
Lipoblastoma
Lipoblastoma/Lipoblastomatosis
Definition
- •
Lipoblastoma and lipoblastomatosis are lesions characterized by the presence of lobules of fetal-type adipose tissue
- •
Lipoblastoma is localized while lipoblastomatosis is the diffuse form of the disease
Clinical features
Epidemiology
- •
Lipoblastoma/lipoblastomatosis are considered the fetal counterpart of the adult lipoma and lipomatosis, respectively
- •
Most patients are infants or young children less than 3 years of age
- •
Boys are much more commonly affected than girls
- •
The extremities are the most common location followed by the mediastinum, the trunk, the retroperitoneum, and the head and neck
Presentation
- •
Discrete or diffuse superficial, painless masses of fatty tissue
- •
Small lesions, usually measure 2 to 5 cm
Prognosis and treatment
- •
Benign condition
- •
Localized form of disease is readily cured by total resection
- •
Lipoblastomatosis may recur on some occasions mainly due to inability to completely excise the lesion
- •
Untreated cases may undergo maturation into an adult-type lipoma/lipomatosis
Pathology
Histology
- •
Lobules of mature adipocytes admixed with lipoblasts in varying stages of development
- •
Number of lipoblasts present in the tumor tends to decrease as the patient age increases
- •
Lipoblastomatosis is less lobulated and may infiltrate skeletal muscle tissue
- •
May have prominent fibrous septa and myxoid matrix
Genetic profile
- •
8q11~13 rearrangements resulting in HAS2 – PLAG1 or COL1A2 – PLAG1 fusion genes is common
- •
Gain of chromosome 8 seen in some cases
Main differential diagnoses
- •
Atypical lipomatous tumor
- •
Myxoid liposarcoma
- •
Lipofibromatosis
Lipoblastoma-Like Tumor of the Vulva
Definition
- •
An extremely rare mesenchymal neoplasm characterized by adipocytic differentiation
Clinical features
Epidemiology
- •
Adolescent and young adult females
Presentation
- •
Superficial, painless vulvar masses
- •
Can be cystic
- •
Can have mucoid consistency
Prognosis and treatment
- •
Cured with surgical resection
- •
Recurrences and metastases have not been reported
Pathology
Histology
- •
Well-circumscribed and lobulated
- •
Lobules are composed of uniform spindle cells showing slightly eosinophilic cytoplasm and elongated nuclei and variable number of lipoblasts separated by thin fibrous septa
- •
Lacks nuclear atypia and hyperchromasia
- •
Plexiform, “chicken-wire” vascular networks are commonly seen
Immunohistochemistry/special stains
- •
Fat cells express S100 protein
- •
No CD34 expression
Main differential diagnoses
- •
Lipoblastoma
- •
Myxoid liposarcoma
- •
Spindle cell lipoma
- •
Aggressive angiomyxoma
- •
Angiomyofibroblastoma
Angiolipoma
Definition
- •
A benign dermal or subcutaneous encapsulated mesenchymal tumor composed of mature adult-type adipose tissue and thin-walled small blood vessels
Clinical features
Epidemiology
- •
Mainly affects adolescents and young adults
- •
Predilection for females
- •
Familial in 5% of cases and shows autosomal-dominant mode of transmission
- •
Most commonly encountered in the upper limbs, trunk, and distal extremities
Presentation
- •
Many are painful
- •
Commonly multiple
- •
Size ranges from a few millimeters to 2 cm
Prognosis and treatment
- •
Cured by conservative, complete surgical excision
- •
No recurrence or metastasis reported
Pathology
Histology
- •
Encapsulated tumors composed of adipocytes and variable number of thin-walled small blood vessels
- •
Blood capillary vessels commonly show microthrombi
- •
No atypia, pleomorphism, mitoses, or hyperchromasia
- •
A rare cellular variant is recognized
- •
Older lesions can show increased fibrosis
Immunohistochemistry/special stains
- •
The adipocytes express S100 protein
- •
The endothelial cells are highlighted by CD34, CD31, and ERG
Genetic profile
- •
Low-level mutations of protein kinase D 2 have been demonstrated in 80% of cases
Main differential diagnoses
- •
Lipoma
- •
Hemangioma
- •
Kaposiform hemangioendothelioma
- •
Kaposi sarcoma
- •
Angiosarcoma
