Download SDL 16- Soft Tissue Tumors Soft Tissue: fibrous tissue, adipose

SDL 16- Soft Tissue Tumors
Soft Tissue: fibrous tissue, adipose tissue, skeletal muscle, smooth muscle
Usualy mesodermal (mesechymal) in origin
Classified according to the tissue they recapitulate (muscle, fat, and fibrous tissue)
Benign ST tumors > sarcomas by 100x
1/3 of benign ST tumors are lipomas, 1/3 are fibrohistocytic and fibrous tumors
Most common in thigh
Slight male predominance
Malignancies increase with age (median 65 years); ¾ are high grade (highly malignant)
Etiology generally unknown
Tumor-like lesions
Pigmented Villondular Synovitis (PVNS)
Benign disorder of uncertain etiology that affects synovial joints, bursae, and tendon sheaths
Locally aggressive but not metastasizing
Young adults in their third or fourth decades (30-40)
80% in knee (then ankle, hip, shoulder) monoarticular
Onset of symptoms: typically insidious
Nonspecific clinical symptoms: pain, swelling, localized tenderness, diminished ROM, locking, mass effect,
stiffness, snapping, or instability
Aspirations typically xanthochromic (yellowish discoloration) or serosanginous
2 forms: Nodular: most commonly in hands
Diffuse: most commonly in knee; thich, plush tan-brown synovium consisting of matted masses of villi and
synovial folds with sessile or pedunculated nodules. Brown appearance depends on content of hemosiderin
pigment
Microscopic: diffuse proliferation of mononuclear cells of synovial or histiocytic type accompanied by varying
proportions of multinucleated giant cells of osteoclastic type. Multinucleated giant cels, hemosiderin deposits,
inflammatory cells, mitotic figures are all common.
Chromosomal translocation t(1;2)(p13;q37) found in PVNS and giant cell tumors of tendon sheath
Treatment: complete synovectomy (recurrence common, malignancy rare)
Giant Cell Tumor of Tendon Sheath
Benign neoplasm of synoviocytes. Arises from a tendon sheath and is locally aggressive with capacity for local recurrence
Localized form of PVNS; more frequent than PVNS (30-50 years, female:male = 3:2)
Usually seen on palmar surface of digits (flexor digitorum); painless, nontender, slow-growing, firmly fixed mass
Morphology: well circumscribed with variegated color (white, yellow, brown). Neoplastic cells are ovoid to spindle with
vesicular nuclei forming a syncytium. numerous osteoclast-like giant cells; atypia/mitosis not common
Chromosomal translocation t(1;2)(p13;q37) found in PVNS and giant cell tumors of tendon sheath
Surgical removal is common, tendency to recur
SDL 16- Soft Tissue Tumors
Tumors of Adipose Tissue
Lipoma
Benign tumor of adipocytes, slow growing, lobulated soft mass enclosed by a thin fibrous capsule
Most common soft tissue tumors of adults (40-60 years)
Proximal extremities and trunk most commonly affected (superficial)
Intramuscular/ intermuscular (deep seated) uncommon
Painless soft tissue mass; well circumscribed, yellow masses enclosed by a thin fibrous capsule
Can have abundant fibrous tissue (fibroulipoma) or extensive vascularization (angiolipoma)
Exact etiology uncertain (55-75% have t(3;12) translocation (high motility group A2 (HMGA2) gene and the lipoma
preferred partner (LPP) gene fusion (this determines adipocytic differentiation)
Excellent prognosis, cured by simple excision
Liposarcoma
Malignant tumor of adipocytes (origin= adipoblast or lipoblast)
Avg onset 50 years (most common sarcoma of adulthood); males slightly > females
Deep soft tissue of the limbs (thigh) and retroperitoneum
Slowly enlarging, painless, non-ulcerated mass in a middle aged person
Well-circumsribed, not-encapsulated, large lobulated mass. Well differentiated resembles lipoma with pale-firm areas
4 variants:
Well-differentiated liposarcoma is composed of cells that appear as relatively mature adipocytes, but nuclear
atypia is evident. It represents 40-45% of all liposarcomas.
Myxoid liposarcoma is composed of neoplastic cells that mimic the structure of primitive mesenchyme but
contain cytoplasmic vacuoles of lipid.
Round-cell liposarcoma is composed of primitive round cells and no intervening stroma. Some of them contain
cytoplasmic vacuoles of fat.
Pleomorphic liposarcoma is composed of a few multi-vacuolated lipoblasts that proliferate on a background of
fascicles of spindle-shaped cells
Myxoid and round-cell have t(12;16) translocation CHOP/TLS results in FUS/CHOP oncoprotein
Well differentiated forms relatively indolent; nonmetastasizing but have recurring potential
Myxoid type is intermediate with malignant behavior
Round-cell and Pleomorphic types are aggressive and frequently metastasize
Tumors of Fibrous Tissue
Nodular Fascitis (subcutaneous pseudosarcomatous fibromatosis, pseudosarcomatous fibromatosis)
Often mistaken for a sarcoma because of its rapid growth (tender, develop over 2-3 week period)
Small, solitary mass with unknown etiology (10-15% cases there is preceeding trauma)
Myofibroblast origin: proliferation triggered by local injury or inflammation processes
Peak incidence between third and fourth decades
Upper extremities (flexors of forearms), trunk and neck
White nodular mass that is solid or rubbery: arises from superficial fascia (not encapsulated, has infiltration)
Spindle-shaped cells in wavy bundles and loose mucoid matrix (typical mitotic figures are common)
Ground substance shows loosely textured feathery appearance
Local excision advocated; recurrence after excision is rare
Myositis Ossificans
Abnormal bone formation within deep muscle (non-neoplastic lesion: hypercellular fibrous tissue and bone)
Young adults (mean 32 years); 50% preceding trauma
Anywhere in body, most common in musculature of proximal extremities (elbow, thigh, buttock, shoulder)
Hematoma followed by intramuscular ossification (painless, hard, well demarcated mass)
Well-delineated, ovoid mass with firm, gray-white, periphery and soft, glistening center
Early phase=numerous proliferating fibroblasts; 3-6 weeks= periphery differentiates to bone; center retains fibroblasts
X-ray: at 3-6 weeks dense calcifications form; radiolucent center in an eggshell fashion
Simple excision is curative, lesions may recur
SDL 16- Soft Tissue Tumors
Tumors of Fibrous Tissue (cont)
Superficial Fibromatosis
Wide spectrum of clincopathologic processes with proliferation of generally mature fibroblasts, mature collagen, and
infiltrative tendency/ local recurrence
Myofibroblast origin
Affects adults older than 30, men > women, rare in non-caucasians
Palmar (Dupuytren): hand (50% bilateral); thickening and pulling of fascia, involutional (active) stage has
palpable cord and contracture; residual (advanced) stage: no nodule, joint flexion contracture remains, nerve
compression can cause distal sensory disturbance
Small nodules with subcutaneous fat; gray-white surface
3 stages: proliferative phase; involutional phase (myofibroblasts align); residual phase (thick collagen)
30-70% report positive family history; 25% stabilize, 75% progress slowly (may recur after excision)
Plantar (Ledderhouse): plantar aponeurosis;
Penile (Peyronie): dorsolateral penis
Deep-Seated Fibromatosis (Desmoid Tumor)
Fibroblastic proliferations of deep ST (infiltrative growth)
Local recurrence but inability to metastasize
Myofibroblast origin (Less frequent than superficial fibromatosis)
Women 20-40 years
Extraabdominal: shoulder, chest wall, back
Abdominal: fascia, aponeurotic structures of the rectus and internal oblique
Intrabdominal: pelvic walls and mesentery
Firm, smooth, and mobile; adherent to surrounding structures- infiltrates and is poorly circumscribed
Familial adenomatous polyposis (Gardner syndrome) have desmoids intraabdominal fibromatosis
Mutation in APC of B-catenin genes
Cutable by surgical excision; recurrence is frequent; no metastatic potential
Fibrosarcoma
Malignant tumor of fibroblasts with variable collagen and herringbone architecture
Unknown cause, middle-aged and older adults
Deep seated (thigh, trunk, retroperitoneum) from CT like fascia, tendon, periosteum, and scar
Mass with or without pain
Unencapsulated, infiltrative, white (fish-flesh) mass firm in relation to collagen content
Monomorphic population of spindle cells arranged in fascicles that interact at acute angles= herringbone
Multiple chromosomal rearrangements
Aggressive with 50% recurrence; metastasis in 25% to lungs and bone
Fibrohistiocytic tumors
Contain cellular elements that resemble both fibroblasts and histiocytes (macrophages). Fibroblast origin.
Benign Fibrous Histiocytoma
Mesenchymal tumor with fibrohistiocytoid differentiation
Middle aged adult (fairly common)
Dermal location: skin of extremities (lower legs)
Solitary, slowly growing, asymptomatic pigmented nodule (overlying skin turn red/brown due to hemosiderin)
Unencapsulated and less than 1 sm
Spindle cell proliferation in the dermis in interlocking strand storiform pattern with histiocytes, giant cells, etc
No capsule with epidermis overlying with hyperplasia
Surgery is curative; recurrences are rare
SDL 16- Soft Tissue Tumors
Fibrohistiocytic tumors (cont)
Malignant Fibrous Histiocytoma
Malignant, undifferentiated, pleomorphic, stromal tumor with no definable differentiation.
Most common sarcoma over 40 years (40-70); male: female is 2:1
Deep soft tissues of the limbs
Large, deep-seated mass that enlarges slowly but progressively
Most are well circumscribed with no capsule present
Pale fibrous and fleshy areas
Pleomorphic type is the most frequent and is composed of a mixture of fibroblasts and histiocytic-like cells. Fibroblastic
component is the basic, storiform pattern. The other component is composed of rounded histiocyte-like cells
and bizarre multinucleate cells. There are also varying numbers of inflammatory cells, foam cells, and
siderophages.
Aggressive tumors, their metastatic rate 30-50%. The recurrence rate is high.
Tumors of Skeletal Muscle
Rhabdoyosarcoma
Malignant mesenchymal rumor that recapitulates features of skeletal muscle. Cell of origin is rhabdomyoblast
Most common soft tissue sarcoma in children aged 1-5
½ from head and neck; 28% from GU system
Noticable lump on child’s body; clinical symptoms related to mass effect, obstruction, location
Poorly circumscribed and fleshy mass of pale-tan color that impinges other structures.
Embryonal rhabdomyosarcoma: The embryonal type is composed of primitive rhabdomyoblasts in various stages of
myogenesis. The most primitive end of this spectrum is the stellate cells with central oval nuclei. As these cells
differentiate they acquire more eosinophilic cytoplasm and elongate shapes, manifested in descriptive terms such as
“tadpole”, “strap” and “spider cell”. With the terminal differentiation cells become myotubes with multiple nuclei and
cross striations. The botryoid variant of embryonal rhabdomyosarcoma (sarcoma botryoides) contains aggregates of
tumor cells (known as cambium layer) that tightly abut an epithelial surface. As sarcoma botryoides grows in a polypoid
fashion, it protrudes into a hollow structure such as the bladder, producing the appearance of a cluster of grapes.
Alveolar rhabdomyosarcoma: Alveolar rhabdomyosarcoma is composed of aggregates of small round cells (primitive
rhabdomyoblasts) which are separated from the neighboring aggregates by fibrous septae. As the central cells
degenerate and drop out, a crude resemblance to pulmonary alveolae is created.
Pleomorphic rhabdomyosarcoma: bizarre polygonal, round and spindle cells which display evidence of muscle cell
differentiation.
Embryonal and alveolar rhabdomyosarcoma are two distinct entities genetically
Alveolar subtype: t(2;13) translocation (fusion of Pax3 and FKHR) Pax3 gain-of-function; reduce FKHR activity
Aggressive
Surgery and chemotherapy with/without radiation. Prognosis determined by stage, histological dx, age, site of origin.
Botrryoid rhabdomyosarcoma has better prognosis and alveolar is worst.
The younger the patient with prognosis the better
Tumors of Smooth Muscle
Leiomyoma of Deep Soft Tissues
Benign neoplasms of smooth muscle (distinct from uterine leiomyoma)
Deep soft tissues of extremities and retroperitoneum
Rare, middle aged-adults (37 yo) Retroperitoneal leiomyomas are exclusively in women around menopause (44)
Painful mass; gray-white and well circumscribed
Fascicles of mature smooth muscle cells with blunt end nuclei arranged in oblique or perpendicular planes (muscle cells
lack nuclear atypia and mitotic activity is extremely low)
Complete excision is curative
SDL 16- Soft Tissue Tumors
Leiomyosarcoma
Malignant mesenchymal tumor with predominant smooth muscle differentiation
Rare, affects middle-aged and elderly
Any site; most commonly in deep ST of extremities and walls of arteries and veins
Painless firm mass that obstructs vessels and organs
Fleshy masses from grey to white to tan with tendency for fresh tumor necrosis and cyctic degeneration
Spindle cells in interweaving fascicles, cigar shaped nuclei, blunt-ended, nuclear pleomorphism, hyperchromatism
Many chromosomal aberrations are id’d but none consistent
Simple enucleation virtually gurantees local recurrence. Majority have distal metastases
Tumors of Uncertain Histogenesis
Synovial Sarcoma
Cell of origin is unclear
Not associated with synovial joints; actually malignant mesenchymal tumors with variable dual, epithelial and
mesenchymal spindle cell differentiation. Rename carcinosarcoma?
Most common in patients 15-45 yo.
70% in deep ST of extremities, especially around knee and thigh in close association to tendon sheaths, bursae,
ligaments or fascial structures
Grows slowly with or without pain
Circumscribed or infiltrative soft, tan, grey (lack fibrous stroma)
Biphasic: epithelial and mesenchymal components in varying proportions (mesenchymal alone=monophasic synovial)
Stromal collagen is usually scanty
More than 90% of patients have t(X:18) translocation mutation that is not associated with other sarcomas
SYT gene on chromosome 18 (SS18) and SSX1 or SSX2 gene on the x chromosome
Aggressive (50% recur, 40% metastasize to lung and bone)
Surgical excision is the cornerstone of treatment: postoperatice radiation needed
Recurrance in first 2 years common (5y survival 25% to 62%)