Soft Tissue Lesions

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types of soft tissue lesions?

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*Mass-forming reactive processes
*Neoplasms
-Benign (-oma)
-Malignant (-sarcoma)

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Prefixes:
Fibrous tissue neoplasms (fibro-)
Fatty tissue neoplasms (lipo-)
Smooth muscle (leiomyo-)
Skeletal muscle (rhabdomyo-)

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Fibrous tissue neoplasms (fibro-)
Fatty tissue neoplasms (lipo-)
Smooth muscle (leiomyo-)
Skeletal muscle (rhabdomyo-)

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Analyzing soft tissue tumors: information to consider:

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*Age of patient
-Rhabdomyosarcoma in kids
-Synovial sarcoma in young adults
-Liposarcoma and MFH in older adults

*Location of lesion
-40% in lower extremity, especially in thigh
-Deep lesions generally worse than superficial

*What is the cell of origin?

*If malignant (sarcoma): what is the grade?
-Grade relates to prognosis
Grade I, low, well-differentiated
Grade II, moderate, moderately differentiated
Grade III, high, poorly differentiated
-Mitotic rate, necrosis especially important

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tl: adipose
tr: fibrous
bl: smooth muscle
br: skeletal muscle

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Significance of staging in soft tissue tumors:

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*Staging is important in prognosis

*Size is most important factor:
<5 cm sarcoma: 30% of cases will have metastasis
>20 cm sarcoma: 80% of cases will have metastasis

*Overall 10yr survival rate for sarcoma: 40%

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Fibrous tumor-like proliferations--list types:

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*Reactive processes which are not aggressive
Nodular fasciitis
Myositis ossificans

*Locally aggressive – ‘fibromatoses’
Superficial
Deep

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Nodular fasciitis:

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*Self-limited fibroblastic proliferation
*Presentation:
-Adults; volar forearm, chest, back
-Several weeks of solitary, rapidly growing, sometimes painful mass
-Preceding trauma noted in 10-15%
*Over time may spontaneously regress
*Rarely recur after excision

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What does Nodular fasciitis look like:

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*Gross: several cm in diameter, nodular, poorly defined margins

*Histology:
-very cellular with plump, immature fibroblasts (‘tissue-culture’ appearance)
-Myxoid stroma
-Often conspicuous nucleoli, mitoses present

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*note triangular fibroblast nucleus upper center
*background is myxoid, blue--a tipoff that this is NODULAR FASCIITIS

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Myositis ossificans:

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*Post-traumatic bony metaplasia
*Presentation:
-Athletic adolescents/young adults
-Proximal muscles of extremities
-Initially swollen/painful, evolves to painless, hard, well demarcated mass, bony on Xray
*Simple excision is curative

*Differential diagnosis: osteosarcoma

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Fibromatoses

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*Infiltrative fibroblastic proliferations
-May be locally aggressive
-May recur after excision

*Disfiguring, disturb function, +/- painful

*Two clinicopathologic groups
1) superficial and 2) deep
Histologically similar

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What do fibromatoses look like:

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*Gross: 1-15 cm size, gray-white, firm, rubbery, poorly demarcated

*Histology: cell of origin is myofibroblast
-Plump cells, broad sweeping fascicles
-Penetrate adjacent tissue
-Infrequent mitoses
-Early lesions cellular, later are less cellular with abundant collagen (esp. superficial ones)

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Fibromatoses!

*Histology: cell of origin is myofibroblast
-Plump cells, broad sweeping fascicles
-Penetrate adjacent tissue
-Infrequent mitoses
-Early lesions cellular, later are less cellular with abundant collagen (esp. superficial ones)

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superficial Fibromatoses:

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*Presentation:
M>F, present early, deformation of hand (often bilateral), foot, penis

*Eponyms
Palmar fibromatosis – Dupuytren’s contracture
Penile fibromatosis – Peyronie’s disease

*May stabilize, or resect +/- recurrence
*May show trisomy 3 or trisomy 8

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Palmar fibromatosis, aka Dupuytren’s contracture

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deep Fibromatoses:

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*Any age, but most frequent teens-30s
*Muscles of trunk or extremity
-Shoulder, thigh, chest wall, back

*Abdominal wall and abdominal cavity
-In abdomen, often called “desmoid tumor”
-Present with abdominal signs (abd or flank pain, bowel obstruction, hydronephrosis, etc.)

*APC gene (5q21-q22) mutation
*Beta-catenin gene overexpression

*Component of Gardner syndrome
-Autosomal dominant
-Germline mutation of APC gene
-Fibromatoses, intestinal adenomas, osteomas

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Do fibromatoses metastasize? How do you treat them?

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Do not metastasize

Treatment:
Some superficial ones may stabilize
Resection, but often recur, repeatedly
Some respond to tamoxifen
Others insensitive to chemo/radiation

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Fibrous/fibrohistiocytic tumors: types:

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*Benign
Fibroma
Benign fibrous histiocytoma (aka dermatofibroma)

*Malignant
Fibrosarcoma
Malignant fibrous histiocytoma

*‘histiocytic’ does not describe cell origin!

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Fibroma:

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*Rare, most often a small ovarian mass

*Gross: well-demarcated, round, firm, white nodule
*Histology: mature fibroblasts, copious collagen

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Benign fibrous histiocytoma:

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*Common benign lesion

*Presentation:
Adults, dermis or subcutis, firm nodule, <1 cm

*Histology:
Bland, mature fibroblasts with interlacing histiocyte-like cells

*Cured by simple excision

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Fibrosarcoma:

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*Presentation:
-Adults
-Deep tissue of thigh, knee, retroperitoneum
-Slow growth, present years once diagnosed

>50% recur locally after excision
Metastasize hematogenously (lungs)

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What do fibrosarcomas look like:

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Gross:
Soft, unencapsulated, infiltrative
Areas of hemorrhage and necrosis

Histology: varies, may be:
Bland, like a fibromatosis
Cellular, with herringbone pattern
Pleomorphic with many mitoses and necrosis

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think????

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fibrosarcoma- herringbone pattern

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fibrosarcoma

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fibrosarcoma

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Malignant fibrous histiocytoma:

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*Historically represented variety of sarcomas

*Histology:
Pleomorphic, bizarre giant cells
Storiform (swirling) architecture
Necrosis, hemorrhage, many mitoses

*Very aggressive behavior

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Malignant fibrous histiocytoma
-very pleomorphic and cellular

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Malignant fibrous histiocytoma:
pleomorphic, unspecific looking

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Diagnosing Malignant fibrous histiocytoma:

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*Currently MFH is a diagnosis of exclusion
aka pleomorphic sarcoma, NOS

*Immunohistochemistry:
-Doesn’t stain for:
S-100 (lipo)
Desmin (rhabdo, leio)
Smooth muscle actin (leio)
Myogenin or myoD1 (rhabdo)
Cytokeratin or EMA (synovial sarcoma)

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Tumors of fat (adipocytes)- types:

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Benign: Lipoma
Malignant: Liposarcoma

Immunohistochemistry: Usually positive for S-100

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Lipoma:

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*Most common soft tissue tumor of adults
*Presentation: Adults, usually solitary, slowly enlarging, mobile, painless mass

*Complete excision usually curative

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what do lipomas look like?

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Gross: soft, yellow, encapsulated
Histology: mature adipocytes

*May be subclassified by:
Other histologic features: conventional, myolipoma, spindle cell, myelolipoma, angiolipoma, pleomorphic
characteristic chromosomal rearrangements (don’t worry about these)

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lipoma
-there would be a thin fibous capsule around the edge of the lesion

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Liposarcoma:

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*Presentation:
Adult, 5th and 6th decades, mass or functional changes, in deep soft tissues or viscera

*Gross:
Fatty, may be TAN-WHITE, have hemorrhage or necrosis

*Histology:
Varies, type is prognostically important
Diagnostic cell is the lipoblast

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*Liposarcoma
*scalloped nucleus (LIPOBLAST) compressed by multiple little fat globs

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*Liposarcoma
*scalloped nucleus (LIPOBLAST) compressed by multiple little fat globs

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*Liposarcoma
*scalloped nucleus (LIPOBLAST) compressed by multiple little fat globs

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Liposarcoma, histology:

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*Well-differentiated:
Mature adipocytes with some lipoblasts

*Myxoid:
As above, but with a bluish, mucoid matrix, and chicken-wire vascular pattern

*Round cell:
Lipoblasts present, but majority are small, round cells

*Pleomorphic:
Significant pleomorphism

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Myxoid liposarcoma

Chicken wire vascular pattern

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Myxoid liposarcoma
Chicken wire vascular pattern
Note lipoblast on left center

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Why is important to be able to differentiate b/t types of liposarcoma based on their appearance?

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Well-differentiated and myxoid types are indolent

Round cell and pleomorphic types are aggressive, recur after excision, metastasize to lungs

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mutations associated with Liposarcomas:

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*Well-differentiated: amp 12q
-Increased transcription of MDM2 gene
-Product binds, inactivates p53 (tumor suppressor)

*All myxoid (and some round cell): t(12;16)
-CHOP gene (adipocyte differentiation) on 12q13
-FUS gene (transcription factor) on 16p

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Smooth muscle tumors:

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Benign: leiomyoma
Malignant: leiomyosarcoma

Immunohistochemistry:
Usually positive for vimentin, desmin, smooth muscle actin (SMA)

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Leiomyoma:

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*Most common presentation: uterine “fibroids”
Adult female with pelvic fullness, discomfort
Pregnancy and delivery complications

*Gross:
Very well-circumscribed masses
Tan-to-white WHORLED cut surfaces

*Histology:
Bands of smooth muscle cells with no mitotic activity

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-Leiomyoma in the uterus
-tan-white fibroids
-whorled pattern

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Low power of Leiomyoma

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High power of Leiomyoma
-bands of smooth muscle

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high power of Leiomyoma
-rounded nuclei
-kind of bland looking

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Leiomyosarcoma:

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*Presentation:
-Adults, female>male
-Skin: firm painless masses
-Deep tissue of extremities: mass, impaired function
-Retroperitoneum: abdominal symptoms

*Histology:
-spindle cells with cigar-shaped nuclei, +mitoses
interweaving fascicles

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Leiomyosarcoma
mitotic figure
elongated nucleoli

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Leiomyosarcoma
mitotic figure
elongated nucleoli

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treatment and prognosis in Leiomyosarcoma:

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Treatment: excision or radiation, or both

Prognosis:
Cutaneous/superficial: small, easy to treat
Retroperitoneal: large, difficult to excise, death by local extension and metastases

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Skeletal muscle tumors- types:

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Benign: rare: rhabdomyoma
Malignant: rhabdomyosarcoma

Immunohistochemistry:
Usually positive for vimentin, desmin, myogenin, MyoD1

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Rhabdomyosarcoma:

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*Kids and adolescents
-Most common soft tissue neoplasm
-Head/neck or genitourinary tract

*Gross: depends on location
-Hollow organs of GU: may be gelatinous, grape-like (sarcoma botryoides)
-In solid tissue: infiltrating mass

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*Rhabdomyosarcoma in a splayed open bladder.
*Sarcoma botryoides

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histological appearance of Rhabdomyosarcoma:

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*Histology: diagnostic cell: rhabdomyoblast
-Rich in thick and thin filaments
-May be elongated (tadpole cell or strap cell, cross striations may be visible) or round
-If very poorly differentiated, may look like small round blue cell, so immunohistochemistry needed

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Rhabdomyosarcoma
-rhabdomyoblasts full of thick/thin filaments

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Rhabdomyosarcoma
-rhabdomyoblasts full of thick/thin filaments
-"strap cells" are elongated rhabdomyoblasts

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Rhabdomyosarcoma- how does histology relate to prognosis?

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Histology: pattern variants are prognostic

Embryonic, pleomorphic, alveolar
(better  mid  worse prognosis)

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Mutations in Rhabdomyosarcoma:

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*Most cases have t(2;13)
-Chromosome 2: PAX3 gene, upstream of skeletal muscle differentiation gene
-Chromosome 13: FKHR gene
-Chimeric protein likely disregulates skeletal muscle differentiation

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synovial sarcoma:

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*"Other"
*Not comprised of synovial cells

*Presentation:
-Young adults; 20-40 y.o.
-Deep soft tissue around joints of extremities (60-70% around knee)

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appearance of synovial sarcoma:

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*Histology:
-Biphasic; spindle cells and epithelial-like cells
-Monophasic: entirely spindle cells
*May require immunohistochemistry
*Send for genetic studies!

*Immunohistochemistry: Both epithelial and spindle cells stain for cytokeratin

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*synovial sarcoma
*note the spindle cell in middle

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mutations in synovial sarcoma:

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*Most are t(X;18)
-leads to fusion product SSX/SYT
-Combines SYT gene (transcription factor) with SSX1 or
SSX2 gene (transcription inhibitors)

*Specific translocation relates to prognosis
-SSX1 involvement yields poorer prognosis

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treatment and prognosis in synovial sarcoma:

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*Treatment is aggressive
Limb-sparing surgery
Chemotherapy

*Metastasizes to lung, bone, lymph nodes

*Survival:
5 year: 25-62%
10 year: 10-30%