Pathology: Soft Tissue Tumors Flashcards
Definition of soft-tissue tumors
Defined as mesenchymal proliferations that occur in the extraskeletal, nonepithelial tissues of the body, excluding organs, coverings of the brain, and lymphoreticular system.
Classification of soft-tissue tumors
the types of tissue that they recapitulate or differentiate to (e.g. fat, fibrous tissue, muscle, vessels, nerves). In each histogenetic category, they can be divided into benign and malignant (sarcoma) forms.
Soft-tissue tumor locations
Soft-tissue tumors can arise in any location; approximately 40% occur in the lower extremities, 20% in the upper extremities, 10% in the head and neck, and 30% in the trunk and retroperitoneum.
Benign vs malignant soft-tissue tumor prevalence
Benign soft-tissue tumors outnumber malignant soft-tissue tumors by 100:1. Sarcomas are relatively rare, accounting for 0.8% of all invasive malignancies, but 2% of all cancer deaths.
Soft-tissue malignancy metastasize pattern
In contrast to carcinomas, sarcomas usually metastasize via hematogenous routes (e.g. to lung and bone). - rare to lymphnodes
malignant soft-tissue tumor called
sarcoma
type of cell that give rise to soft-tissue tumors
Soft tissue tumors are believed to develop due to mutations in mesenchymal stem cells distributed throughout the body.
State the most common type of genetic abnormality in soft tissue tumors.
translocation –> fusion genes that encode chimeric transcription factors, leading to transcriptional deregulation (uncontrolled cell proliferation).
Other genetic abnormalities result in deregulation of kinase signaling.
Neurofibromatosis Type 1 –>
neurofibroma, malignant peripheral nerve sheath tumor
Gardner Syndrome –>
Fibromatosis
Osler-Weber-Rendu syndrome –>
telangiectasia
Environmental factors implicated in development of soft tissue tumors
Trauma, environmental agents, radiation therapy, viruses, chronic disease
dioxin –>
various sarcomas
vinyl chloride –>
hepatic angiosarocma
post-radiation –>
pleomorphic sarcoma/malignant fibrous histiocytoma, osteosarcoma
HHV8 –>
Kaposi sarcoma
Chronic lymphedema
Angiosarcoma
Some specific types of sarcoma tend to occur in certain _____. In general, incidence of sarcomas increases with ___.
Some specific types of sarcoma tend to occur in certain age groups. In general, incidence of sarcomas increases with age.
Factors that influence prognosis
Histologic classification Histologic grade Stage of tumor Superficial vs. deep Size
Initial morphologic assessment is based on the ____________ of the tumor cells as well as the _______________. Numerous immunohistochemical stains are used in the histologic assessment of some tumors. In some instances, genetic analysis for specific fusion genes can aid in diagnosis.
Initial morphologic assessment is based on the cytologic appearance of the tumor cells as well as the architectural pattern of growth. Numerous immunohistochemical stains are used in the histologic assessment of some tumors. In some instances, genetic analysis for specific fusion genes can aid in diagnosis.
Histologic grade is based on the ______, ___________, and amount of _________
Histologic grade is based on the tumor differentiation score, mitotic count, and amount of tumor necrosis
Staging of soft-tissue sarcomas is based on _________ presence or absence of ___________, and presence or absence of __________. Most sarcoma metastases are ____________.
Staging of soft-tissue sarcomas is based on tumor characteristics (superficial or deep, size less than or greater than 5 cm), presence or absence of lymph node metastases (although lymph node metastases are rare in sarcomas,), and presence or absence of distant metastases (so staging is a T,N,M classification). Most sarcoma metastases are hematogenous.
Tx benign soft-tisue tumors
surgery (simple excision)
soft tissue sarcoma tx
surgery, with radiation therapy and chemotherapy used in certain clinical situations. Sometimes radiation therapy and/or chemotherapy is done before surgical excision (preoperative or neoadjuvant therapy)
Imaging/lab and soft-tissue tumors
Imaging studies (such as MRI) are often used in the assessment of soft-tissue tumors. Needle biopsy is often used to obtain diagnosis and plan therapy for large tumors.
Lipoma
most common soft tissue of tumor of adults (rare younger than 20)
Conventional lipoma
most common type, mature fat only
Angiolipoma
mature fat plus small vessel proliferation; can be painful
Spindle cell lipoma/Pleomorphic lipoma:
mature fat plus spindle cells/pleomorphic cells
Myolipoma
mature fat plus smooth muscle
Chondroid lipoma:
mature fat plus cartilage-like cells
Angiomyolipoma:
mature fat plus vessels plus smooth muscle (typically associated with the kidney, and 1/3 occur in patients with tuberous sclerosis)
Myelolipoma:
mature fat plus bone marrow elements (usually adrenal gland)
lipoma types that typically occur in a superficial location and are well circumscribed and encapsulated.
conventional lipoma, angiolipoma, myolipoma
Intramuscular lipoma:
infiltrating lipoma involving skeletal muscle
Lipoblastoma/Lipoblastomatosis:
refer to circumscribed (lipoblastoma) and diffuse (lipoblastomatosis) forms of fatty proliferation, usually occurring in infants
Liposarcoma
one of the most common sarcomas of adulthood and typically occurs in middle to older age adults. This tumor usually arises in the deep soft tissues of the proximal extremities and retroperitoneum.
Morphologic variants of liposarcoma
Well-differentiated liposarcoma (relatively indolent, local recurrence, but can be fatal when located in the retroperitoneum); when this tumor occurs in a location amenable to surgical excision (such as an extremity or on the trunk) it may be called an “atypical lipomatous tumor”
Myxoid/round cell liposarcoma (intermediate malignancy)
Pleomorphic liposarcoma (aggressive tumor, frequently metastasizes)
well circumscribed encapsulated mass of mature adipose tissue
conventional lipoma
longterm corticosteroid use –>
overgrowth of mature adipose tissue in the face (moon face) and on the back (buffalo hump), called “steroid lipomatosis”
________ are non-neoplastic, benign lesions that develop following local trauma/injury or are idiopathic. Clinically, they are worrisome as they grow rapidly and can have an infiltrative appearance. Two types.
Reactive pseudosarcomatous proliferations are non-neoplastic, benign lesions that develop following local trauma/injury or are idiopathic. Clinically, they are worrisome as they grow rapidly and can have an infiltrative appearance. Two types.
Two types reactive pseudosarcomatous proliferations
Nodular fasciitis, myositis ossificans
Usually on upper extremities (forearm) or trunk. At any age, usually young adults that present with a several week history of a solitary, rapidly growing, sometimes painful mass; history of previous trauma is present in 10-15%.
dermis, subcutis, or muscle
nodular, yet poorly marginated, cellular proliferation of immature fibroblasts and myofibroblasts in a myxoid stroma
Mitotic figures are numerous -can be confused with a true sarcoma.
Following excision, the lesion rarely recurs.
Nodular Fasciitis
athletic adolescents and young adults
follows episode of trauma in more than 50% of cases
typically found in muscles of the proximal extremities
often 3-6 cm in size.
Initially, lesion is cellular and consists of plump fibroblasts and myofibroblasts as seen in nodular fasciitis. Overtime, the outer margin of the lesion develops osteoblasts, which then deposit mineralized bone in the outermost layer (ossification). Eventually the lesion can become completely ossified. In the proliferative stage, the lesion can be confused with an extraskeletal osteosarcoma.
Myositis ossificans
Nodular Fasciitis:
Usually on ________. At any age, usually _______ that present with _______ ___________ mass. 10-15% hx of ____________.
Usually on upper extremities (forearm) or trunk. At any age, usually young adults that present with a several week history of a solitary, rapidly growing, sometimes painful mass; history of previous trauma is present in 10-15%.
Nodular Fasciitis:
____, _____, or _______
Circumscribed?
_________, cellular proliferation of immature ___ and ______ in a myxoid stroma
_____ figures are numerous -can be confused with a true _______.
Following excision, the lesion ____________.
dermis, subcutis, or muscle
nodular, yet poorly marginated, cellular proliferation of immature fibroblasts and myofibroblasts in a myxoid stroma
Mitotic figures are numerous -can be confused with a true sarcoma.
Following excision, the lesion rarely recurs.
Myositis Ossificans: population - \_\_\_\_\_\_\_\_\_ and \_\_\_\_\_\_\_\_\_\_\_ follows \_\_\_\_\_\_\_\_\_\_ in more than 50% of cases typically found in \_\_\_\_\_\_\_\_ often\_\_\_\_\_\_\_\_\_ in size.
athletic adolescents and young adults
follows episode of trauma in more than 50% of cases
typically found in muscles of the proximal extremities
often 3-6 cm in size.
Myositis Ossificans:
Initially, lesion is ___ and consists of plump _________ and __________ as seen in __________. Overtime, the outer margin of the lesion develops _______, which then deposit _________ in the outermost layer (_________). Eventually the lesion can become completely _________. In the proliferative stage, the lesion can be confused with an ______________
Initially, lesion is cellular and consists of plump fibroblasts and myofibroblasts as seen in nodular fasciitis. Overtime, the outer margin of the lesion develops osteoblasts, which then deposit mineralized bone in the outermost layer (ossification). Eventually the lesion can become completely ossified. In the proliferative stage, the lesion can be confused with an extraskeletal osteosarcoma.
benign fibroblastic neoplasms involving the fascia or aponeuroses (broad tendons); lesions characterized by nodular or poorly defined broad fascicles of fibroblasts and myofibrobasts surrounded by abundant dense collagen. Many types exist, defined by location
Superficial fibromatoses
Superficial Fibromatoses: _____ fibroblastic neoplasms involving ______ or _________
lesions characterized by ____ or ____ ______ broad fascicles of _____ and _______ surrounded by abundant ________. Many types exist, defined by location
benign fibroblastic neoplasms involving the fascia or aponeuroses (broad tendons); lesions are characterized by nodular or poorly defined broad fascicles of fibroblasts and myofibrobasts surrounded by abundant dense collagen. Many types exist, defined by location
3 most common fibrous tumors and tumor-like lesions
Palmar fibromatosis (Dupuytren’s contracture), Plan, Penile (Peyronie)
These benign tumors consist of an infiltrative, poorly marginated proliferation of bland fibroblasts with collagen. While these lesions do not metastasize, they can recur if incompletely excised. They may occur at any age but are most frequent in the teens to 30’s, and some are associated with a history of previous trauma.
Deep-Seated Fibromatosis (Desmoid tumors)
Desmoid Tumors: ____ tumors consist of an ____, _____ proliferation of ____ with ______. While these lesions ___ metastasize, they ____ recur if incompletely excised. They may occur at any age but are most frequent in the ______, and some are associated with a history of ________.
These benign tumors consist of an infiltrative, poorly marginated proliferation of bland fibroblasts with collagen. While these lesions do not metastasize, they can recur if incompletely excised. They may occur at any age but are most frequent in the teens to 30’s, and some are associated with a history of previous trauma.
3 main types desmoid tumors
Abdominal fibromatosis
Extra-abdominal
Intra-abdominal
Typically occurs in the musculoaponeurotic structures of the anterior abdominal wall in women during or after pregnancy.
Abdominal fibromatosis
occurs in men and women with equal frequency and arises principally in the musculature of the shoulder, chest wall, back, and thigh
extra-abdominal fibromatosis
typically occurs in the mesentery or pelvic side walls, often in individuals having familial adenomatosis polyposis (Gardner syndrome)
Intra-abdominal fibromatosis
intra-abdominal fibromatosis associated with
familial adenomatosis polyposis (Gardner Syndrome)
Virtually all deep-seated fibromatoses have ________ or _________ gene mutations
Somatic beta-catenin or adenomatous polyposis coli (APC)
malignant, sarcomatous tumors of fibroblasts. These tumors can occur anywhere in the body, but are most common in the deep soft tissues of the extremities
Fibrosarcomas
Fibrosarcomas are _______ malignancies, recurring in ___ of cases and metastasizing in ____
Fibrosarcomas are aggressive malignancies, recurring in more than 50% of cases and metastasizing in more than 25%
Benign fibrous histiocytoma Very common, legs Dermal proliferation of histiocytes/fibrocytes Pinch test - indents Tan/brown papules - not scaly, relatively normal Etiology unknown (bug bites) PUNCH In dermis
dermatofibroma (benign fibrous histiocytoma)
Sarcoma of low malignant potential Usually younger adults/children (nodular usually) Rarely metastasize/locally aggressive Protuberant nodule within firmer plaque Dense proliferation in dermis PUNCH
dermatofibrosarcoma protuberans
contain cellular elements that resemble both fibroblasts and histiocytes (tissue macrophages). As the phenotype of the neoplastic cells most closely resemble fibroblasts, the term fibrohistiocytic should be regarded as a descriptive term, not one indicating the cell of origin.
Fibrohistiocytic tumors
kinds of fibrohistiocytic tumors
dermatofibroma, dermatofibrosarcoma protuberans
Malignant fibrous histiocytoma (group)
**Getting split into other classifications (fibroblast neoplasm)
storiform
splindle-cells radiating out like spindles
benign tumor showing skeletal muscle differentiation, very rare (heart or other sites)
rhabdomyoma
most common soft-tissue sarcoma of childhood and adolescence - malignant tumor showing skeletal muscle differentiation
Rhabdomyosarcoma
3 main types of rhabdomyosarcoma
Embryonal rhabdomyosarcoma
Alveolar rhabdomyosarcoma
Pleomorphic rhabdomyosarcoma
most common subtype (60%) rhabdomyosarcoma. usually occurs in children age 10 years or younger, and often arises in the head and neck (e.g. nasal cavity, orbit, middle ear) and genitourinary tract.
botryoid subtype of embryonal rhabdomyosarcoma arises in the mucosal lining of hollow organs forming a polypoid, grape like growth (e.g. nasal cavity, urinary bladder, vagina).
Embryonal rhabdomyosarcoma
subtype rhabdomyosarcoma - tends to occur in early to middle adolescence, commonly arising in deep soft-tissues of the extremities, and represents 20% of rhabdomyosarcomas.
alveolar rhabdomyosarcoma
Genetic basis for prognosis w/ alveolar rhabdomyosarcoma
Specific cytogenetic abnormalities have been identified, some of which connote a worse prognosis. For example, patients with metastatic disease have a four year survival of 75% with a PAX7/FKHR fusion gene vs. only 8% with a PAX3/FKHR fusion gene.
the rarest of the three subtypes (rhabdomyosarcoma), this sarcoma usually arises in the deep soft-tissues of adults.
pleomorphic rhabdomyosarcoma
Rhabdomyosarcomas are______ malignancies, and are often treated with multimodal therapy (____ _____ _____). ______, _______, _______ and _______ influence survival, with the _____ subtype having the best chance of survival. ___ and ____ subtypes (especially with the _______) are more aggressive.
Rhabdomyosarcomas are very aggressive malignancies, and are often treated with multimodal therapy (surgery, chemotherapy, radiation therapy). Histologic subtype, size (smaller is better), patient age (infant/child better than adult), and location influence survival, with the botryoid subtype having the best chance of survival. Pleomorphic and alveolar subtypes (especially with the unfavorable genotype) are more aggressive.
The benign tumor showing smooth muscle differentiation
leiomyoma
most common places leiomyoma
They most commonly arise in the uterus, are present in 77% of women, and are often called “uterine fibroids.” They also arise from the arrector pili muscles in the skin, nipples, scrotum, and labia and less frequently develop in deep soft tissues and GI tract. Leiomyomas of the GI tract and uterus are usually well circumscribed tumors.
malignant tumor showing smooth muscle differentiation
leiomyosarcoma
leiomyosarcoma locations
They most frequently occur in the uterus or GI tract; soft tissue leiomyosarcomas occur in the retroperitoneum, skin, and deep soft tissues of the extremities.
Histology of smooth muscle tumors
Both tumors consist of spindle cells showing histologic and immunohistochemical features of smooth muscle, arranged in fascicles that tend to intersect at right angles. Leiomyosarcoma shows increased nuclear pleomorphism and increased mitotic activity compared to the leiomyoma.
Most leiomyomas NOT found in soft tissue - but in
uterus (uterine fibroids)
Benign tumor and tumor-like conditions of blood vessels and lymphatics examples
Hemangioma
Pyogenic granuloma (eruptive hemangioma)
Lymphangioma
most often occur in the skin, but any site is possible (e.g. liver); morphologically see various subtypes, such as capillary (skin), and cavernous (skin, deep tissues, liver, spleen).
Hemangioma (blood vessel tumor)
typically occur in skin and subcutaneous soft tissue, look like a thin walled hemangioma without the red blood cells. Many of these occur in the neck or axilla of children. cystic hygroma (cavernous lymphangioma) of the neck in children can be associated with Turner syndrome
Lymphangioma
Lymphangioma associated w/
Turner syndrome (cavernous lymphangioma)
benign, typically painful tumor showing differentiation to the modified smooth muscle cells of the glomus body (arteriovenous structure involved in thermoregulation). These lesions arise most often in the distal digits.
Glomus tumor and glomangioma
Special types of vascular ectasias
Nevus flammeus (port wine stain one type of these)
Spider Angiomas
Hereditary Hemorrhagic Telangiectasia
Usually occur in head/neck of infant most regress. Port Wine Stain special type - does not regress. Those in trigeminal nerve can be associated w/ Sturge-Weber syndrome.
Nevus Flammeus.
Nevus Flammeus associated with
if in trigeminal nerve association - Sturge-Weber syndrome (MR, seizures, masses of leptomeninges)
skin spider-like vascular malformations seen in association w/ estrogen excess (pregnancy, cirrhosis)
Spider Angiomas
Spider angiomas seen in association w/
excess estrogen (pregnancy, cirrhosis)
autosomal dominant disorder with widely distributed vascular ectasias over the skin and oral mucous membranes, as well as in the respiratory, GI, and urinary tracts.
Hereditary Hemorrhagic Telangiectasia (Osler-Weber-Rendu Disease)
reactive vascular proliferation resulting from opportunistic infection from Bartonella bacteria in immunocompromised individuals. Lesions can occur anywhere in the body, and regress with successful antibiotic therapy.
bacillary angiomatosis
are aggressive, malignant sarcomas showing endothelial differentiation
Angiosarcoma
Angiosarcoma location
lesions occurring at any site but often involving skin (head and neck, especially the scalp), soft tissue, breast, and liver.
Angiosarcoma associated with
Patients with lymphedema following axillary lymph node resection for breast cancer can get an angiosarcoma which presumably arises in association with dilated lymphatics. Angiosarcomas can also be secondary to previous radiation therapy.
group of very rare malignant vascular tumors with clinical behavior less aggressive than angiosarcoma.
Hemangioendotheliomas
malignant vascular tumor with an infectious etiology, caused by human herpesvirus-8 (HHV-8). It is believed that the virus, in concert with a cofactor, results in endothelial cell proliferation.
Kaposi’s sarcoma
4 kinds of Kaposi’s Sarcoma
Chronic (classic), Lymphoadenopathic, Transplant-associated, AIDS-associated
occurs in older men of Eastern European (especially Ashkenazi Jews) or Mediterranean descent. While the tumor can be associated with a second malignancy or altered immunity, it is not associated with HIV infection. The lesions are typically found in the skin and subcutaneous tissues of the lower extremities, do not progress further, and are asymptomatic.
Kaposi sarcoma
Chronic KS (classic or European KS)
KS form - is endemic in Africa and afflicts young males and children, with involved lymph nodes and occasional organ involvement; this is an aggressive tumor.
Lymphadenopathic KS
KS occurs in the setting of solid organ transplant with long-term immunosuppression; this is an aggressive tumor
Transplant-Associated KS
KS - originally found in one-third of AIDS patients, incidence is now less than 1% due to the success of antiretroviral therapy. This tumor can involve lymph nodes and organs.
AIDS-associated KS
caused by repeated minor trauma, typically of the interdigital plantar nerve between the third and fourth toes. This results in a distorted nerve, with concentric perineural fibrosis.
Morton neuroma
when a peripheral nerve is severed or crushed, the proximal end regenerates. If the proximal end cannot reconnect with the distal end, a tangled mass of nerve fibers is produced.
Traumatic neuroma
from neural crest-derived Schwann cell, benign tumors, typically encapsulated, well circumscribed and arise adjacent to a nerve. Some schwannomas are associated with neurofibromatosis type 2 (NF2).
Schwannoma
Schwannoma associated with
Neurofibromatosis type 2
benign tumor that presents as discrete localized masses – most commonly as a cutaneous form or in a peripheral nerve as a solitary form – or as an infiltrative lesion growing within and expanding a peripheral nerve (plexiform)
Neurofibroma
The presence of multiple neurofibromas or plexiform neurofibroma strongly suggests the diagnosis of ________. Plexiform neurofibromas may result in significant neurologic deficits and have a significant potential for malignant transformation.
neurofibromatosis type 1 (NF1)
highly malignant sarcomas usually arise in association with major nerve trunks → proximal portions of the upper and lower extremities and trunk.
Malignant peripheral nerve sheath tumor
MPNST associated with
NF1
Neurofibromatosis
___ ___ heredity w/ _____ expression
Autosomal dominant w/ variable expression
Neurofibromatosis
Affects males vs females
equally
Neurofibromatosis
Type 1 vs Type 2
prevalence, mutations
Type 1 - more common, chromosome 17 coding for neurofibromin (tumor suppressor)
Type 2 - less common, chromosome 22 coding for merlin (regulated membrane receptor signaling)
**Both act as growth suppressors
NF1 Associated w/
Café au lait spots: coffee-colored skin macules (can also occur in NF2 but usually quite infrequent); axillary and inquinal freckling
Optic gliomas, astrocytomas
Lisch nodules (pigmented hamartomas of the iris)
Osseous lytic lesions
Plexiform neurofibromas (do not occur in NF2), can get sarcomatous transformation as discussed previously
Cutaneous/subcutaneous neurofibromas
Association with pheochromocytoma, Wilm’s tumor, juvenile CML
Neurodevelopmental problems
NF2 associated w/
Bilateral acoustic schwannomas (cranial nerve VIII)
Meningiomas, spinal schwannomas, juvenile cataracts.
benign tumors that occur either as a localized or diffuse form, and have a characteristic fusion gene abnormality. Mixture of giant cells, round histiocytic cells, collagen, foam cells, hemosiderin.
Tenosynovial giant-cell tumor
solitary slow-growing painless mass, frequently involves tendon sheaths of fingers and wrists. Most common mesenchymal neoplasm of hand.
Localized, Giant cell tumor of tendon sheaths
usually in knee/ankle/foot, pignmented villonodular synovitis when involving joint space. Rare.
Diffuse form of tenosynovial giant-cell tumor
a misnomer, as this malignant tumor does not show synovial cell differentiation. Lesion uncommon in joint cavities, encountered in areas with no apparent relation to synovial structures. Primarily occurs in para-articular regions of the extremities in adolescents and young adults, and less commonly in the head and neck region.
Synovial sarcoma
Dx Synovial sarcoma
There are often calcifications within the tumor which can be seen radiographically. Immunohistochemistry is helpful in the diagnosis as these tumors show positivity for cytokeratin (an epithelial marker).
There is also a characteristic fusion gene abnormality (SYT-SSX fusion gene).
Two types synovial sarcoma
Microscopically, there are two types, a biphasic type with both epithelial and spindle cell components, and a monophasic type with spindle cell component only.
Myxomatous lesions
extracullar mucin accumulation with associated cellular proliferation
One myxoid lesion which is very common is the ________ which occurs as a cystic area of myxoid degeneration (not a neoplasm) in fibrous connective tissue, almost always located near a joint capsule or tendon sheath (wrist is the most common location).
ganglion cyst
On fingers, ganglion cysts known as
digital mucus cysts
Common benign mesenchymal/soft tissue tumors
lipomas, hemangiomas, fibrous histiocytoma (dermatofibroma), Dupuytren’s contracture, ganglion cyst, giant cell tumor of tendon sheath, leiomyomas (uterine)
Common adult sarcomas
undifferentiated pleomorphic sarcoma/MFH, liposarcoma, and various fibrosarcoma variants
Common childhood sarcomas
rhabdomyosarcoma, extraskeletal Ewings sarcoma/PNET, and neuroblastoma
Key clinical questions to ask regarding soft tissue neoplasm or tumor
1) what are the chances of local recurrence, and 2) what are the chances of distant metastases?
