Soft Tissue - Adipocytic Tumours Flashcards
Adipocytic Tumours
Benign
* Lipoma
* Angiolipoma
* Chondroid Lipoma
* Pleomorphic Lipoma
* Hibernoma
* Lipoblastoma
Locally Aggressive
* Atypical lipomatous tumour/Well differentiated LPS
Malignant
* Dedifferentiated liposarcoma
* Myxoid liposarcoma
* Pleomorphic liposarcoma
* Liposarcoma NOS
Lipoma
- Benign tumor composed of mature adipocytes
- Most common soft tissue tumor
- Mostly subcutaneous, < 5 cm
- Radiologically, grossly and microscopically same as normal fat
- In large (> 10 cm) and deep seated / retroperitoneal tumors, exclusion of MDM2 amplification is required for diagnosis
- Painless, subcutaneous mass
- In special site, might have specific symptoms (i.e. gastrointestinal → melena)
- 5% multiple
- Associated with obesity
Syndromes
* Cowden syndrome
* Bannayan-Riley-Ruvalcaba syndrome
* Hamartoma Tumor Syndrome
IHC:
* S100
* Calretinin
Angiolipoma
- Benign, soft tissue tumor consisting of mature adipose tissue and clusters of thin walled vessels, often containing intraluminal fibrin thrombi
- Forearm, trunk and upper arm common sites
- Nodules are usually tender or painful
- Rare familial predilection (5%) with autosomal dominant inheritance
Micro:
* Consists of mature adipose tissue and branching capillary sized vessels
* Thin walled vessels often contain bright pink fibrin thrombi
* Vascularity is more prominent in the periphery
* Well formed capillaries often have a lobular arrangement
* Occasionally, few thin fibrous septae present
* Proportion of adipocytes and vessels varies
* No nuclear atypia in the adipocytic or vascular component
IHC
S100 protein (focal to diffuse positivity in adipocytes)
ERG (vascular component)
CD31 (vascular component)
CD34 (vascular component)
CD61 (platelet marker highlights thrombi
Chondroid lipoma
- Rare variant of lipoma with features of immature fat and immature cartilage
- Rare, slow going, painless mass in adult women
- Lobulated, circumscribed, deep seated tumor
- Mostly affects the proximal extremities and limb girdles of adult women
- Nests and cords of uni and multivacuolated lipoblasts with variable adipose tissue in a myxochondroid matrix
- Excision is curative
Micro:
* Encapsulated with occasional lobulations
* Lobulations are formed by fibrous septa
* Composed of 3 components arranged in nests, cords and sheets in variable proportion:
* Mature adipose tissue
* Cells displaying lipoblastic differentiation
* Myxohyaline chondroid matrix
* Mature adipocytes contain eccentrically placed nuclei and vacuolated cytoplasm
Molecular:
* Shows recurrent t(11;16)(q13;p13) translocation with resultant C11orf95 and MRTFB fusion
IHC
S100:
Positive in mature adipocytes (strong)
Lipoblasts (weak)
Negative in cells that do not show lipoblastic differentiation
Keratins: rarely positive
Spindle cell / pleomorphic lipoma
- Spindle cell lipoma and pleomorphic lipoma are benign adipocytic tumors, currently regarded as morphologic variants of a single neoplasm.
- Mostly superficial, extremely rare in deep soft tissue
- 80% arise in the subcutaneous tissue of the posterior neck, back and shoulders
- 20% involve different sites, including face, oral cavity and trunk / extremities
- Commonly affects middle aged to elderly men (45 - 70 years)
Micro:
* Triad of mature adipocytes, bland spindle cells and hyalinized rope-like collagen fibers
* Multinucleated stromal giant cells and floret cells in pleomorphic lipoma
* Myxoid background with mast cells frequent
* Short and stubby spindle cells show occasional palisading
* Rare lipoblasts present in half of cases
* Infiltrative growth, necrosis, atypical spindle cells, pleomorphic lipoblasts and significant mitotic activity usually absent
Molecular:
* Characterized by partial or whole chromosome 13 or 16 deletions
* Breakpoints cluster around 13q14 where the RB1 gene resides
IHC:
* CD34, strong and diffuse
* Loss of nuclear RB1 protein expression
* Vimentin
Hibernoma
- Rare, benign, adipocytic tumor composed of variable proportions of brown fat cells admixed with white adipose tissue
- Mean age: 38 years, 60% presenting in third and fourth decades of life
- Most common site is the thigh (29%), followed by the shoulder (12%), back (10%), neck (9%) and chest wall (6%)
- Association with MEN type 1
Micro:
* Neoplastic lesion composed of polygonal brown fat cells with stromal cells in the background
* Large number of pale and eosinophilic brown fat cells with multivacuolated, eosinophilic granular cytoplasm and small central nucleus (about 70%) admixed with variable amount of univacuolated white cells
* Multivacuolations resemble lipoblasts
* Morphological variations or subtypes: typical, myxoid (9%), lipoma-like (7%), spindle cell (2%), thick bundles of collagen fibers, presence of mast cells and exclusively containing brown fat cells
Lipoblastoma
- Benign, rapidly growing neoplasm composed of embryonal white fat with variable degrees of myxoid changes
- Occurs predominantly in infancy, early childhood and very rarely in adulthood
- 80% boys
- Superficial, localized, well circumscribed; complete excision easy; common type
- Common in trunk and extremities
Micro:
* Lobulated sheets of adipocytes
* Myxoid areas with plexiform vascular network and primitive mesenchymal cells
* Fat cells revealing a spectrum of maturation, ranging from primitive stellate or spindled mesenchymal cells to multivacuolated or small signet ring cell lipoblasts
* Lobule zonation is defined by arrangement of immature myxoid cells at periphery near fibrous septa and mature adipocytes at center of the lobule
Molecular:
* Clonal rearrangements involving chromosomal region 8q11 > q13 (8q12) is the hallmark
* Oncogene PLAG1 (pleomorphic adenoma gene 1)
* Other rare fusion partners of PLAG1 are COL1A2 (7q21.3), HAS2 (8q24.13), RAD51B (14q24.1), COL3A1 (2q32.2), RAB2A (8q12.1-q12.2) and BOC (3q13.2)
IHC:
* Adipocytes: S100, CD34 and CD56
* Primitive mesenchymal cells: desmin
* Vascular endothelial cells: CD34
* Aberrant PLAG1 positivity (80%)
Liposarcoma
- Most frequent soft tissue sarcoma in adults
Areas:
* Lower extremities –> popliteal fossa and medial thigh
* Retroperitoneal
* Perirenal
* Mesenteric region
* Shoulder
Types:
* Well-Differentiated LPS/Atypical lipomatous tumour
* De-Differentiated LPS
* Pleomorphic LPS
* Myxoid/Round cell LPS
Well-Differentiated LPS/Atypical lipomatous tumour
- Locally aggressive mesenchymal tumor
- Composed of mature adipocytes and stromal cells with at least focal cytologic atypia
- Most common adipocytic malignancy (45%)
- Behavior is dependent upon location, with deep seated lesions having the ability to dedifferentiate and subsequently metastasize –> most important factor
Terminology:
* 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
Micro:
* 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
* Frequently contains lipoblasts –> multivacuolated cytoplasm in which vacuoles dent the atypical nucleus
* (Pseudolipoblasts –> Myxofibrosarcoma, Myxoinflammatory fibroblastic sarcoma)
Molecular:
* Ring or giant marker / rod chromosomes derived from 12q13-15 in almost all cases
* Amplifications of the 12q12-21
* MDM2 amplification
IHC:
MDM2
CDK4
p16
De-Differentiated LPS
- Well differentiated liposarcoma (WDL) with transition, either in the primary tumor or as a recurrence to a sarcoma that is typically nonlipogenic
- Most cases are intermediate to high grade; the existence of low grade dedifferentiated liposarcoma, although now officially recognized, has been controversial
- Typically occurs in older adults, with a slight predilection for men
- Occurs in up to 10% of well differentiated liposarcomas, with more frequent dedifferentiation noted in retroperitoneal primaries
- Most common site is the retroperitoneum, followed by the extremities
- Other frequent sites include the spermatic cord
Micro:
* Well differentiated and dedifferentiated components are often both present and can have abrupt or gradual transitions
* Dedifferentiated component is a cellular and typically a nonlipogenic sarcoma with significant pleomorphism
* Heterologous elements in 5 - 10% of cases
* Heterologous elements can easily mislead pathologists in poorly sampled cases, especially in metastatic sites
* Can manifest as neural differentiation, leiomyosarcoma, osteosarcoma / chondrosarcoma, rhabdomyosarcoma or pleomorphic liposarcoma (homologous lipoblastic dedifferentiation)
* Rhabdomyoblastic differentiation has been associated with worse outcomes
Molecular:
* 12q14 amplification, often due to supernumerary ring or giant chromosome derived from 12q13-15 region
* Degree of copy number change has been correlated with progression to higher grade tumors
IHC:
* MDM2 and CDK4 are more sensitive in dedifferentiated liposarcoma than in well differentiated tumors given how cellular they are
* Addition of p16 to the stains above may increase sensitivity and specificity
Prognosis:
* Better than other high grade pleomorphic sarcomas
* Retroperitoneal dedifferentiation –> higher rates of local recurrence
Pleomorphic LPS
- Pleomorphic, high grade sarcoma with variable numbers of pleomorphic lipoblasts
- Without areas that resemble atypical lipomatous tumor / well differentiated liposarcoma (or other lines of differentiation)
- Absence of MDM2 gene alterations by cytogenetic and molecular studies
- 66% cases occur on the extremities
Micro:
* Varying proportion of pleomorphic lipoblasts in a background of a high grade, usually pleomorphic, undifferentiated sarcoma
* Well circumscribed but nonencapsulated with infiltrative borders
* Cytologically, tumors are composed of high grade cells with varying numbers of pleomorphic and often bizarre, multinucleated tumor cells
* These tumor cells will often show subtle to prominent cytoplasmic vacuolization with some forms appearing as classic lipoblasts with scalloped nuclei
* Signet ring lipoblasts may also be scattered throughout tumor in association with malignant cells
* Epithelioid morphology is seen in about 25% of cases
Molecular:
* No pathognomonic recurrent molecular alterations have been identified
* Most important negative finding is identification of the absence of supernumerary ring chromosomes with amplification of MDM2 / CDK4, as this excludes a high grade dedifferentiated liposarcoma with pleomorphic features
IHC:
* MDM2 and CDK4 are typically negative
Myxoid liposarcoma
- Malignant tumor
- Composed of primitive nonlipogenic mesenchymal cells, signet ring lipoblasts and prominent myxoid stroma with a highly characteristic branching vascular pattern
- Usually in the extremities, proximal thigh is quite common
- Has an unusual propensity to present with a first metastasis to another soft tissue or bony site (such as from one leg to the contralateral leg or to the retroperitoneum or spine)
- Mets can occur decades later.
Micro:
Low grade
* Paucicellular with monomorphic, stellate or fusiform shaped cells without atypia; striking in their blandness, so much so that any significant pleomorphism should cause one to pause
* Prominent plexiform vasculature (delicate thin walled arborizing and curving capillaries that form a network reminiscent of chicken wire fencing)
* These are striking because of the overall background paucicellularity and are still present in high grade tumors but are much less obvious
High grade
* Hypercellular solid sheets of back to back cells with round cell or primitive cytomorphology in > 5% of the sampled tumor
Molecular:
* t(12;16)(q13;p11.2) FUS::DDIT3 in most cases
IHC:
Vimentin, S100
DDIT3
SOX11
