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Soft Tissue
Reviewers / Editors: Komal Arora, M.D., Jerad Gardner, M.D., Raul Gonzalez, M.D., David Lucas, M.D., Annie Simpson Morrison, M.D., Deepti Reddi, M.D., Vijay Shankar, M.D., Lauren N. Stuart M.D., M.B.A. (see Reviewers page)
Revised: 26 April 2012, update in progress
Copyright: (c) 2002-2012, PathologyOutlines.com, Inc.
Table of contents
General: primary references soft tissue-normal sarcomas-general approach to diagnosis architectural patterns cell types grading molecular staging syndromes
Infections, inflammation and hematoma: general granulomatous hematoma necrotizing fasciitis PVP granuloma tumoral calcinosis
Tumors
Adipose tissue: embryology & physiology white fat brown fat
lipoma and variants: lipoma angiolipoma chondroid fibrolipoma intramuscular lipoma arborescens lipoma of tendon sheath lipomatosis lipomatosis of nerve lumbosacral myolipoma myxoid nevus lipomatosus pelvic pleomorphic / spindle cell
other benign lesions: hemosiderotic fibrohistiocytic hibernoma lipoblastoma subconjunctival herniated orbital fat
liposarcoma: general atypical lipomatous tumor / well differentiated ( variants: inflammatory lipoleiomyosarcoma dedifferentiated ) myxoid-general myxoid-well differentiated myxoid-round cell pleomorphic mixed type sclerosing poorly differentiated
Extraskeletal bone tumors: aneurysmal bone cyst chondroma chondrosarcoma chordoma Ewing/PNET osteosarcoma parachordoma
Fibroblastic / myofibroblastic: general fibroblastic/myofibroblastic - normal angiomyofibroblastoma calcifying aponeurotic fibroma calcifying fibrous tumor cellular angiofibroma dermatofibrosarcoma protuberans desmoplastic fibroblastoma elastofibroma eosinophilic fasciitis fibroma of tendon sheath fibromatosis-general fibromatosis-superficial fibromatosis-deep fibromatosis colli fibrosarcoma-adult fibrosarcoma-infantile fibrous hamartoma of infancy focal myositis Gardner fibroma giant cell angiofibroma giant cell fibroblastoma hemangiopericytoma inclusion body fibromatosis inflammatory myofibroblastic tumor intranodal palisaded myofibroblastoma ischemic fasciitis juvenile hyaline fibromatosis lipofibromatosis low grade fibromyxoid sarcoma low grade myofibroblastic sarcoma mammary type myofibroblastoma myofibroma / myofibromatosis myositis ossificans myxofibrosarcoma myxoinflammatory fibroblastic sarcoma nodular fasciitis and related lesions nuchal fibrocartilaginous pseudotumor nuchal type fibroma ossifying fibromyxoid tumor pleomorphic fibroma proliferative fasciitis proliferative myositis proliferative peribursitis sclerosing epithelioid fibrosarcoma solitary fibrous tumor superficial acral fibromyxoma
Fibrohistiocytic:
benign fibrous histiocytoma and variants: superficial deep aneurysmal angiomatoid atypical cellular epithelioid juvenile xanthogranuloma
other benign lesions: general atypical
fibroxanthoma giant cell tumor of soft tissue giant cell tumor of tendon sheath-diffuse giant cell tumor of tendon sheath-localized MFH-giant cell MFH-inflammatory MFH-pleomorphic PHAT plexiform fibrohistiocytic tumor
Mesenchymal: hamartoma mesenchymoma phosphaturic mesenchymal tumor
Peripheral nerve:
neurofibroma: general pacinian pigmented plexiform neurofibromatosis type 1 type 2
other benign: normal myxopapillary ependymoma nerve sheath myxoma neuroma neurothekeoma perineurioma pigmented neuroectodermal tumor of infancy schwannoma
Perivascular epithelioid cell: PEComa-general abdominopelvic sarcoma falciform ligament / ligamentum teres
Skeletal Muscle: skeletal muscle-normal neuromuscular hamartoma myxoma
rhabdomyoma: adult fetal genital
rhabdomyosarcoma: general alveolar anaplastic embryonal pleomorphic sclerosing
Smooth Muscle: general angioleiomyoma EBV-related
leiomyoma: classic bizarre cutaneous epithelioid genital deep soft tissue
leiomyosarcoma: general cutaneous epithelioid myxoid pleomorphic rhabdoid features
Vascular:
normal/benign: normal bacillary angiomatosis glomus hemangioma-general -microvenular -symplastic intravascular papillary endothelial hyperplasia myopericytoma vascular ectasias
low/intermediate grade: giant cell angioblastoma hemangioendothelioma Kaposi sarcoma
high grade: angiosarcoma intimal sarcoma
Lymphangioma: -general -cystic -post-radiation lymphangiomatosis lymphangioendothelioma lymphangiomyoma lymphangiosarcoma
Other: alveolar soft part sarcoma clear cell sarcoma desmoplastic small round cell tumor epithelioid sarcoma granular cell tumor metastases myoepithelial carcinoma myospherulosis myxoma rhabdoid tumor sinus histiocytosis with massive lymphadenopathy synovial sarcoma teratoma
Index (table of contents in alphabetical order)
A-E: adipose: embryology &
physiology alveolar soft part sarcoma aneurysmal BFH angioleiomyoma angiolipoma angiomatoid BFH angiomyofibroblastoma angiosarcoma approach to diagnosis architectural patterns atypical BFH atypical
fibroxanthoma atypical lipomatous tumor / well differentiated bacillary angiomatosis benign fibrous histiocytoma (superficial) brown fat calcifying aponeurotic fibroma calcifying fibrous tumor cell types cellular angiofibroma cellular BFH chondroid lipoma clear cell sarcoma dedifferentiated liposarcoma deep
benign fibrous histiocytoma dermatofibrosarcoma protuberans desmoplastic fibroblastoma desmoplastic small round cell tumor EBV-related smooth muscle elastofibroma eosinophilic fasciitis epithelioid BFH epithelioid sarcoma extraskeletal aneurysmal bone cyst extraskeletal chondroma extraskeletal chondrosarcoma extraskeletal chordoma extraskeletal Ewing/PNET extraskeletal osteosarcoma
F-J: fibroblastic/myofibroblastic - general fibroblastic/myofibroblastic - normal fibrohistiocytic-general fibrolipoma fibroma of tendon sheath fibromatosis colli fibromatosis-deep fibromatosis-general fibromatosis-superficial fibrosarcoma-adult fibrosarcoma-infantile fibrous hamartoma of infancy focal myositis Gardner fibroma giant cell angioblastoma giant cell angiofibroma giant cell fibroblastoma giant cell tumor of soft tissue giant cell tumor of tendon sheath-diffuse giant cell tumor of tendon sheath-localized glomus grading granular cell tumor granulomatous hemangioendothelioma hemangioma-general hemangioma-microvenular hemangioma-symplastic hemangiopericytoma hematoma hemosiderotic fibrohistiocytic lipomatous lesion hibernoma inclusion body fibromatosis infections-general inflammatory liposarcoma inflammatory myofibroblastic tumor intimal sarcoma intramuscular lipoma intranodal palisaded myofibroblastoma intravascular papillary endothelial hyperplasia ischemic fasciitis juvenile hyaline fibromatosis juvenile xanthogranuloma
K-O: Kaposi sarcoma leiomyoma-bizarre leiomyoma-classic leiomyoma-cutaneous leiomyoma-deep soft tissue leiomyoma-epithelioid leiomyoma-genital leiomyosarcoma-cutaneous leiomyosarcoma-epithelioid leiomyosarcoma-general leiomyosarcoma-myxoid leiomyosarcoma-pleomorphic leiomyosarcoma-rhabdoid features lipoblastoma lipofibromatosis lipoleiomyosarcoma lipoma lipoma arborescens lipoma of tendon sheath lipomatosis lipomatosis of nerve liposarcoma-general low grade fibromyxoid sarcoma low grade myofibroblastic sarcoma lumbosacral lipoma lymphoma mammary type myofibroblastoma mesenchymal hamartoma mesenchymoma metastases MFH-giant cell MFH-inflammatory MFH-pleomorphic mixed type liposarcoma molecular MPNST myoepithelial carcinoma myofibroma / myofibromatosis myolipoma myopericytoma myositis ossificans myospherulosis myxofibrosarcoma myxoid lipoma myxoid liposarcoma-general myxoid-round cell liposarcoma myxoid-well differentiated liposarcoma myxoinflammatory fibroblastic sarcoma myxoma myxopapillary ependymoma necrotizing fasciitis nerves-normal nerve sheath myxoma neurofibroma-general neurofibroma-pacinian neurofibroma-pigmented neurofibroma-plexiform neurofibromatosis type 1 neurofibromatosis type 2 neuroma neuromuscular hamartoma neurothekeoma nevus lipomatosus nodular fasciitis and related lesions nuchal fibrocartilaginous pseudotumor nuchal type fibroma ossifying fibromyxoid tumor
P-Z: parachordoma PEComa PEComa-abdominopelvic sarcoma PEComa-falciform ligament / ligamentum teres pelvic lipoma perineurioma phosphaturic mesenchymal tumor pigmented neuroectodermal tumor of infancy pleomorphic fibroma pleomorphic hyalinizing angiectatic tumor pleomorphic liposarcoma pleomorphic / spindle cell lipoma plexiform fibrohistiocytic tumor primary references proliferative fasciitis proliferative myositis proliferative peribursitis PVP granuloma rhabdoid tumor rhabdomyoma-adult rhabdomyoma-fetal rhabdomyoma-genital rhabdomyosarcoma-alveolar rhabdomyosarcoma-anaplastic rhabdomyosarcoma-embryonal rhabdomyosarcoma-general rhabdomyosarcoma-pleomorphic rhabdomyosarcoma-sclerosing sarcomas-general schwannoma sclerosing epithelioid fibrosarcoma sclerosing poorly differentiated liposarcoma sinus histiocytosis with massive lymphadenopathy skeletal muscle-normal smooth muscle general soft tissue-normal solitary fibrous tumor subconjunctival herniated orbital fat staging superficial acral fibromyxoma syndromes synovial sarcoma teratoma tumoral calcinosis vascular ectasias vasculature-normal white fat
top
AJCC Cancer Staging Manual (7th ed)
Weiss: Soft Tissue Tumors (5th edition, 2007)
Fletcher:
Pathology and Genetics of Tumours of Soft Tissue and Bone (AFIP 3rd Series, Vol 30), 2004
Fletcher:
Pathology and Genetics of Tumours of Soft Tissue and Bone (WHO, Vol 5), 2002, PDF
Websites with images: PathoPic USCAP (virtual slides) WebPathology.com
Fibroblastic / myofibroblastic tumors of soft tissue
Ischemic fasciitis of soft tissue
Definition: sarcoma-like fibroblastic proliferation, usually of soft tissue, overlying bony prominences
Also spelled ischaemic
First described in 1992 as atypical decubital fibroplasia (AJSP1992;16:708)
Epidemiology: occurs primarily in immobilized and elderly patients due to chronic pressure and impaired circulation, but also occurs in younger people not debilitated (Am J Surg Pathol 2008;32:1546) or with physical disabilities (Path Int 1998;48:160, Int J Gynecol Pathol 2004;23:65)
Sites: usually pressure points on shoulder, chest wall and sacrococcygeal region
Case reports: 45 year old woman with post-mastectomy axillary mass (The Internet Journal of Pathology 2008;7:1), 55 year old man with hip mass (Case of Week #64), 76 year old woman with thigh mass (Archives 2004;128:e139)
Treatment: local excision is curative, although may recur due to continuation of underlying ischemia and injury
Gross: usually 1 to 8 cm, poorly circumscribed, often myxoid; usually involves deep subcutis, may extend into adjacent skeletal muscle; ulceration is uncommon (i.e. overlying skin is intact)
Micro: zones of fibrinoid necrosis with uneven borders staining deep red/violet and prominent myxoid areas surrounded by ectatic, thin walled vessels and proliferating fibroblasts; endothelial cells may be atypical; fibroblasts have degenerative features of abundant, basophilic cytoplasm, enlarged nuclei with smudged chromatin and prominent nucleoli (resembling proliferating fasciitis or ganglion cells); may have frequent mitotic activity, but no atypical mitotic figures; fibrin thrombi are common within peripheral vessels, which may show fibrinoid necrosis and recanalization but no vasculitis; may have multivacuolated macrophages, but no lipoblasts; no primary vasculitis or myositis
Micro images: AFIP - cellular, fibrin-rich proliferation centered on subcutaneous fibrous septum and extending into adjacent fat; hyalinized focus with large ganglion-like cells, suggestive of proliferative fasciitis; fibrin is adjacent to foci of ganglion-like cells in collagenous stroma
other - central area of ischemic fasciitis filled with fibrin and surrounded by proliferating vascular fibrous tissue; fibrinoid necrosis with few viable cells; spindle cells with large nuclei with prominent nucleoli resembling proliferative fasciitis; capillaries lined by plump endothelial cells and surrounded by large fibroblasts/myofibroblasts enmeshed in a loose collagenous stroma (figure 5); post-mastectomy axillary mass-various images
hip mass in 55 year old bedridden man - image #1; #2; #3; #4; #5; #6
Ischemic fasciitis of soft tissue (continued)
Cytology: spindled and ovoid cells with ample cytoplasm and occasional nuclear atypia (Acta Cytol 1997;41:598)
Positive stains: vimentin, actin, CD68; variable CD34 in enlarged fibroblasts, desmin
Negative stains: keratin, S100
Differential diagnosis:
▪ epithelioid sarcoma - young adults on distal extremities, more cellular with central necrosis, cells have eosinophilic cytoplasm, atypical mitotic figures, keratin+
▪ myxoid liposarcoma - prominent plexiform vasculature and lipoblasts
▪ myxofibrosarcoma - marked atypia, but no smudgy chromatin or fibrin thrombi; lacks zonation
▪ proliferative fasciitis - younger patients, lesions not associated with pressure; zonation, myofibroblasts and fibroblasts with tissue culture type growth, also large ganglion cells
References: Mod Path 1993;6:69, Stanford University
Lipofibromatosis of soft tissue
Definition: pediatric tumor with adipose tissue and fibroblasts in adipose septa and skeletal muscle
Also called infantile fibromatosis of nondesmoid type
First described in 2000 (AJSP 2000;24:1491)
Epidemiology: rare childhood tumor (first surgery usually at age 1), 2/3 male, often of distal extremities
Clinical: associated with macrodactyly of foot (Foot Ankle 1991;12:40)
Clinically resembles lymphatic malformation, lymphedema or lipedema
Recurs locally, no metastases
Case reports: foot of male infant (Skeletal Radiol 2008;37:555), forearm of 10 month old boy (Ups J Med Sci 2005;110:259)
Gross: white-tan or yellow, 1-3 cm
Micro: bland fibroblasts in septa of adipose tissue, may have minute small vacuolated cells between fibroblasts and adipose; no atypia, no/rare mitotic figures
Positive stains: spindle cells - CD34, CD99, smooth muscle actin; variable bcl2, S100, EMA and muscle specific actin
Negative stains: desmin, keratin, beta-catenin
Molecular/cytogenetics: three-way t(4;9;6) translocation in a 5-year-old boy (rare, Cancer Genet Cytogenet 2007;179:136)
Differential diagnosis:
▪ fibrous hamartoma of infancy - has primitive oval cell component
▪ fibromatosis - solid fibrous growth, no fat
References: Stanford University
Definition: focal intramuscular reparative lesion composed of cellular fibrous tissue and metaplastic bone
See also Bone chapter
Also called benign fibro-osseous lesion or heterotopic ossification (better terms since may not involve muscle or inflammation)
In subcutis, called panniculitis ossificans; in fascia or tendons, called fasciitis ossificans
Various forms: circumscripta (localized, either traumatic or atraumatic) or progressiva (also called fibrodysplasia ossificans progressiva, inherited disorder with increasing involving of muscle groups over time)
Epidemiology: usually physically active young males with rapid growth of mass; 60-75% have history of trauma in prior 4-6 weeks; may also occur after elective surgery, severe burns, neurological injury
Fibro-osseous pseudotumor of digits: similar entity that affects fingers of older adults with occupations that require repetitive manual use (Ann Diagn Pathol 2008;12:21), less likely to contain fibrinous material (Int J Surg Pathol 2003;11:187)
Sites: upper extremity flexors, quadriceps, thigh adductors, gluteal muscles, soft tissues of hand
Xray: periosteal reaction with eggshell calcification at periphery 3-6 weeks after injury; recommended to review Xrays before diagnosis
Case reports: 9 year old boy with thigh pain (UPMC Case #72), 10 year old girl with progressiva form (Internet Journal of Orthopedic Surgery 2009;12(1)), 11 year old boy with thigh mass (Eur J Pediatr 2009;168:523), 46 year old man with tumor of sternocleidomastoid muscle after clavicle fracture (Cases J 2008 Dec 22;1(1):413), multiple tumors at autopsy due to trauma (Leg Med (Tokyo) 2008;10:274)
Treatment: excision, although may regress without treatment; rarely recurs if incompletely excised
Gross: well circumscribed, soft center, gritty periphery, usually 3-5 cm
Gross images: bone fragment from abdominal wall; in muscle
Micro: cellular stroma with new bone, atypia and mitotic figures, rarely cartilage; zonation often present, although zones may be poorly demarcated
early lesions (3 weeks): inner cellular zone resembling nodular fasciitis or osteosarcoma, with short fascicles or haphazard fibroblasts that are uniform with faint eosinophilic cytoplasm, tapering processes, vesicular or finely granular nuclei and variable nucleoli, usually numerous mitotic figures but none atypical; stroma is vascular, myxoid or edematous with extravasated red blood cells, fibrin, scattered inflammatory cells and osteoclast-like giant cells; intermediate zone has osteoblasts depositing woven bone, and outer zone has mineralized trabeculae
later: bone matures with formation of marrow and myofibroblasts are less prominent
Myositis ossificans (continued)
Micro images: AFIP - mature bone at periphery, fibrous tissue resembling nodular fasciitis at center, osteoid in between #1; #2; fibroblastic and myofibroblastic cells in center of lesion resemble nodular fasciitis, with nuclear uniformity #1; #2; osteoid is broader than in osteosarcoma; osteoblasts have large nuclei with prominent nucleoli, but clues to benign nature of lesion are reactive fibrous areas; osteoid deposition is uniform, and nuclei are enlarged but not pleomorphic; osteoid undergoing mineralization
other - bone and marrow elements; zonation; highly cellular deep focus resembles sarcoma; midportion shows osteoid formation by plump osteoblasts; peripheral zone shows well formed bone; image #1; #2; #3; various images (9 year old boy with thigh lesion); fig 8: central fibroblasts/myofibroblasts merge with woven bone at periphery, note the prominent osteoblastic rimming
Cytology images: hip mass with FNA showing crystals consistent with calcium
Virtual slides: myositis ossificans
Positive stains: fibroblasts and myofibroblasts express vimentin and variable actin and desmin, osteoclasts express vimentin
EM: fibroblasts and myofibroblasts have dilated rough endoplasmic reticulum and aggregates of cytoplasmic filaments variably associated with dense bodies; osteoblasts have numerous mitochondria and abundant dilated rough ER
Molecular: usually polyclonal (Virchows Arch 2005;446:438), but some cases have clonal USP6 rearrangements, and may be better classified as soft tissue aneurysmal bone cysts (Skeletal Radiol 2008;37:321, Cancer Res 2004;64:1920)
Progressiva variant due to mutations in ACVR1 and NOG genes (Genet Couns 2009;20:53)
Differential diagnosis:
▪ extraosseous osteosarcoma - rare, age 40+ years, different radiologic findings, malignant cytology, atypical mitotic figures, no or reverse zonation
▪ juxtacortical osteosarcoma - bone tumor, no zonation
▪ osseous muscle metastasis (AJR Am J Roentgenol 2001;176:1165)
References: eMedicine
Nodular fasciitis of soft tissue
Definition: highly cellular, reactive lesion of fibroblasts and myofibroblasts in myxoid stroma with granulation tissue-like vascular proliferation, lymphocytes and extravasated red blood cells, usually in young adults in fascia and subcutis, with rapid growth to 2-3 cm
Common lesion that typically presents as a rapidly growing mass on the flexor forearm, chest, back or elsewhere
Arises from superficial fascia, occasionally intramuscular or intravascular
May also develop within bladder (Hinyokika Kiyo 1994;40:427), breast (Breast 2005;14:384), cervix, intra-articular (AJSP 2006;30:237), prostate, vagina, vulva (Int J Gynecol Path 1997;16:117)
Epidemiology: peaks at age 40 years; prior trauma in 10% of cases
Benign behavior, but frequently misdiagnosed as sarcoma based on cellularity, mitotic figures and rapid growth
Case reports: 37 year old woman with wrist mass (Case of the Week #65), 44 year old man with shoulder mass (The Internet Journal of Plastic Surgery 2007;3(1)); regression after biopsy (J Craniofac Surg 2008;19:1167)
Treatment: excision (curative even if incomplete resection); recurs in 1% after incomplete excision but recurrence should suggest review of diagnosis; no metastases
Gross: tan-white-gray, myxoid appearance, usually 2 cm or less, relatively well circumscribed, no capsule; may be centered in subcutis, may grow into skeletal muscle
Gross images: scapular lesion; intraoperative mass within deltoid muscle
Micro: zonation effect with hypocellular central region and hypercellular periphery; composed of uniform, plump, immature fibroblasts or myofibroblasts without atypia, with a feathery, tissue-culture like growth pattern due to abundant ground substance; often with mucoid pools (microcysts); uniform elongated nuclei with prominent nucleoli; cellular areas may have storiform or fascicular patterns (S or C shaped); often frequent mitotic figures (but no atypical forms), lymphocytes and macrophages, red blood cell extravasation, bands of keloid-type collagen; vasculature is usually prominent; walls of small to medium sized vessels are involved by reactive process at periphery of lesion; may infiltrate adjacent fat; may have metaplastic bone, focal cystic areas, ganglion type cells but no cells with large, hyperchromatic, atypical nuclei; no/rare plasma cells and neutrophils; does not extend to skin except on face
Nodular fasciitis of soft tissue (continued)
Micro images: AFIP - subcutaneous tumor is partially circumscribed nodule infiltrating focally along fascial planes; focal infiltration into fat, with evenly distributed granulation tissue-like vessels throughout the lesion; gently curving C and S shaped fascicles of myofibroblastic cells exhibit a characteristic “torn Kleenex” pattern; focal storiform pattern is suggestive of fibrous histiocytoma; plump spindled myofibroblastic cells and extravasated red blood cells; mitotic figures but no abnormal forms; focally more collagenous stroma with skeletal muscle involvement; cystic degeneration #1; #2; osteoclastic giant cells are present in less collagenous areas, suggesting a variant of MFH; hyalinized variant resembles keloid or fibromatosis; vague zonation pattern with bone formation in lower right; island of new bone surrounded by myofibroblastic cells
other - leg lesion #1; #2; #3; #4; #5-resembles fibroblast culture; spindled fibroblasts and extravasated red blood cells in myxoid background, with giant cells (blue arrows) and mitotic figures (red arrows); myofibroblasts and staghorn blood vessels; small ill-defined lesion centered in subcutis; very cellular lesion; myxoid areas; keloid like collagen deposition; blood vessel involvement; figures 10A/B: H&E and CD68
Case of Week #65 / tumor of wrist - image #1; #2; #3; #4; #5; #6
Cytology: markedly hypercellular smear with clusters of overlapping, relatively monomorphic spindle or epithelioid cells resembling sarcoma (AJCP 2005;123:388); also inflammatory cells, single mesenchymal cells, myxoid stroma (Acta Cytol 2004;48:473)
Positive stains: fibroblasts/myofibroblasts - smooth muscle actin (Ann Diagn Pathol 2002;6:94), muscle specific actin, vimentin and calponin (Am J Dermatopathol 2006;28:105); macrophages - CD68 (not specific for histiocytes-also fibroblasts that have acquired phagocytic properties)
Negative stains: S100, desmin, keratin and CD34 (AJSP 1993;17:1039); caldesmon, ALK, p53
EM: cells resemble myofibroblasts, are elongated with abundant, often dilated rough endoplasmic reticulum, may have cytoplasmic filaments with dense bodies, pinocytotic vesicles and cell junctions
Molecular/cytogenetics: diploid, no/few genetic aberrations (Am J Clin Pathol 2009;131:701)
Nodular fasciitis of soft tissue (continued)
Differential diagnosis:
▪ benign fibrous histiocytoma - based in dermis, storiform pattern, infiltrative borders, prominent xanthoma cells and often Touton giant cells, no microcysts
▪ fibromatosis - usually large tumor that infiltrates surrounding soft tissue, spindled cells are separated by abundant collagen, no loose tissue culture appearance
▪ inflammatory MFH - larger size, slower growth, more pleomorphic cells, presence of neutrophils, plasma cells, foam cells and atypical mitotic figures, no RBC extravasation, no keloid-type collagen
▪ inflammatory myofibroblastic tumor - no rapid growth, no zonation, no prominent myxoid stroma; larger tumor size, has mixed inflammatory infiltrate
▪ myositis ossificans (early) - centered in muscle, calcification
▪ myxofibrosarcoma - large, regularly arborizing vessels, atypia and pleomorphism
▪ other sarcoma - atypia is prominent
▪ reactive spindle cell nodules - post-biopsy
References: Stanford University
Cranial fasciitis
Definition: variant of nodular fasciitis that usually affects scalp and skull of infants or children < 2 years old
Rare; usually boys, erodes outer table of cranium and may infiltrate dura
Some cases show dysregulation of Wnt/beta-catenin pathway, and may be related to desmoid fibromatosis (Mod Pathol 2008;21:1330)
May be related to birth trauma, craniectomy or be spontaneous (J Neurosurg Pediatr 2008;2:370)
Grows quickly like nodular fasciitis, but same benign behavior (Cancer 1980;45:401)
Xray: lytic defect of skull with sclerotic rim
Case reports: 7 month old boy (AJNR Am J Neuroradiol 2003;24:1465), 3 year old girl with epidural mass (Pediatr Neurosurg 2008;44:148)
Gross: circumscribed, rubbery to firm; variably myxoid or cystic
Micro: fibroblasts, giant cells, myxoid matrix; may have osseous metaplasia
Positive stains: nuclear beta-catenin (some cases)
References: Hum Pathol 1999;30:87
Intravascular fasciitis
Definition: variant of nodular fasciitis that involves wall and lumen of small to medium-sized veins and arteries (AJSP 1981;5:29)
Usually subcutaneous
Rare; usually age 30 years or less
Slower growth than classic nodular fasciitis but same behavior
Case reports: pregnant woman with hand lesion (World J Surg Oncol 2007;5:7)
Gross: usually 2 cm or less; nodular or plexiform
Micro: resembles nodular fasciitis, often more prominent osteoclast-like giant cells; may be intra- or extravascular
Micro images: AFIP - large focus of nodular fasciitis protrudes into vascular space; cellular proliferation has edematous background characteristic of nodular fasciitis
other - intravascular proliferation of spindle cells #1; #2; #3
Proliferative funiculitis
Definition: pseudosarcomatous myofibroblastic proliferation of spermatic cord
Usually incidental at herniorrhaphy
Ages 52-76 years; may be due to ischemia, torsion or extension of vasitis
Resembles nodular fasciitis
Similar lesions in epididymis
Micro: may contain malignant appearing glandular structures composed of keratin+ mesothelial cells (Int J Surg Pathol 2008;16:48), rarely has proliferation of mast cells (Pathol Int 2003;53:897)
Positive stains: myofibroblasts - smooth muscle actin
References: AJSP 1992;16:448
Nuchal type fibroma of soft tissue
Definition: bundles of thick collagen fibers in posterior neck
Also called collagenosis nuchae
Nuchal: nape (posterior) of neck
Epidemiology: rare benign lesion of dermis and subcutis in posterior neck, upper back or other regions, more common in men, mean 40 years; associated with diabetes in 44% (Cancer 1999;85:156)
Case reports: associated with DFSP (J Cutan Pathol 2004;31:62)
Treatment: excision, recurs but does not metastasize
Gross: usually 3 cm or less, hard and white, unencapsulated, poorly circumscribed
Micro: no capsule, hypocellular, thick collagen fibers with delicate elastic fibers, entrapped adipose and entrapped nerves, resembling traumatic neuroma, may infiltrate into skeletal muscle, may have scattered lymphocytes
Micro images: AFIP - strands of acellular collagen mixed with fat; lesion is very hypocellular, differentiating it from fibromatosis
other - paucicellular with haphazard collagen fibers; central areas have collagen fibers organized in several planes of section, with criss crossing bundles often forming lobules; small entrapped islands of adipose are common; skeletal muscle involvement; often contains small nerves with haphazardly arranged fascicles, resembling traumatic neuroma; often contains delicate web of elastic fibers running parallel to collagen fibers; fibrous tissue replaces subcutaneous fat
Positive stains: vimentin, CD34, CD99
Negative stains: actin, desmin
Differential diagnosis:
▪ fibrolipoma - circumscribed, different location
▪ fibromatosis - deep soft tissue, not back of neck, more cellular
▪ solitary fibrous tumor - patternless pattern, more cellular, staghorn type vessels
References: AJSP 1995;19:313, Stanford University
Ossifying fibromyxoid tumor of soft tissue
Definition: uncommon fibromyxoid soft tissue tumor of uncertain lineage, usually with peripheral bone present
First described in 1989 (AJSP 1989;13:817), now 300+ cases reported (Am J Surg Pathol 2008;32:996)
Epidemiology: median age 49 years, range 14-83 years, usually men with small painless mass in trunk or proximal extremities
Usually histologically benign with benign clinical course; local recurrences in 17%, malignant behavior in 5%
May have neuroectodermal origin due to CD56+, CD99+ (Int J Surg Pathol 2007;15:437)
Poor prognostic factors: high cellularity, high nuclear grade, > 2 mitotic figures/50 HPF (AJSP 2003;27:421)
Case reports: 21 year old woman with gingival mass (J Periodontol 2009;80:687), invasive spinal tumor (Skeletal Radiol 2008;37:1137)
Treatment: excision
Gross: well circumscribed, median 4 cm, usually involves deep soft tissue, also cutaneous (Am J Dermatopathol 2007;29:156) or subcutaneous (J Cutan Pathol 2006;33:749)
Micro: nests/cords of round/oval cells with indistinct cytoplasm in myxoid matrix with fibrosis and osteoid formation; lobulated at low power; surrounded by partial capsule of lamellar and woven bone; usually minimal atypia and minimal mitotic figures, but may have necrosis, vascular invasion or high nuclear grade
Micro images: tumor cells are bordered by metaplastic bone; moderately atypical cells in hyaline matrix
Cytology: clusters, cords or small aggregates of round, polygonal or spindle cells in myxoid background with osteoid-like material (Diagn Cytopathol 2004;30:41); malignant cases may show significant nuclear pleomorphism with coarse chromatin, irregular contours and 1-2 distinct nucleoli (Acta Cytol 2001;45:745)
Positive stains: vimentin, S100 (60%) (94% in tumors with conventional histology, Am J Surg Pathol 2008;32:996), Leu7/CD57 (focal), GFAP (focal), desmin (focal)
Negative stains: keratin, EMA; alpha smooth muscle actin (usually, may be weak, J Laryngol Otol 1993;107:75)
EM: complex cell processes, reduplicated basal lamina (Ultrastruct Pathol 2007;31:233)
Cytogenetics: may have complex aberrations (Cancer Genet Cytogenet 2007;176:156, Cancer Genet Cytogenet 2002;133:124)
References: Stanford University
Pleomorphic fibroma of skin - Soft Tissue Tumor chapter
Definition: polypoid or dome-shaped cutaneous nodule with sparse cellularity and cytologic atypia of fibroblasts
Not a WHO diagnosis
First described in 1989 (AJSP 1989;13:107)
Usually trunk, extremity or head (Clin Exp Dermatol 1998;23:22)
Case reports: 38 year old woman (Arch Pathol Lab Med 2005;129:e21), 66 year old woman with subungual tumor (J Cutan Pathol 2003;30:569)
Micro: resembles fibroepithelial polyp but with enlarged, bizarre, smudged, hyperchromatic nuclei, thick collagen bundles and rare mitotic figures; may be sclerotic (Am J Dermatopathol 2002;24:54) or have myxoid foci (Am J Dermatopathol 1998;20:502)
Micro images - AFIP - large pleomorphic cells separated by collagen; atypical cells have smudged chromatin, mitoses are absent/rare, compare to sarcomas with abnormal (but not degenerative) nuclei and frequent mitotic figures, some atypical; anal skin;
other - stromal cells have atypical nuclei; various images
Positive stains: vimentin, actin, CD34
Negative stains: S100
Differential diagnosis:
▪ atypical fibrous histiocytoma - storiform pattern, more cellular, foam cells, hemosiderin laden macrophages (Am J Dermatopathol 1999;21:414)
▪ atypical fibroxanthoma - more cellular, more mitotic figures
▪ giant cell fibroblastoma - young children
▪ angiofibroma - pleomorphic cells are similar, but have marked vascularity
Proliferative fasciitis - Soft Tissue Tumor chapter
Definition: subcutaneous or fascial proliferation similar to nodular fasciitis, but with large basophilic cells resembling ganglion cells
Similar to proliferative myositis
Epidemiology: usually adults (mean age 50 years); forearm is most common location, also trunk or proximal extremities, rare in patients under 15 years old (but see childhood variant below)
Rapid growth but benign behavior
Case reports: with rapid involution (Skeletal Radiol 2004;33:300)
Treatment: local excision
Gross: usually 3 cm or less, poorly circumscribed deep tissue mass that may extend horizontally along fascia
Micro: resembles nodular fasciitis due to zonation effect, tissue culture type growth and plump fibroblastic and myofibroblastic spindle cells, but has large ganglion type cells with abundant amphophilic to basophilic cytoplasm, round vesicular nuclei (occasionally 2-3 nuclei) and prominent nucleoli; stroma is collagenous or myxoid, often arborizing vascular pattern; variable mitotic figures but no atypical ones; ill defined margins
Micro images: AFIP - prominent hemorrhage and vague centering of cellular proliferation on interlobar septa of subcutaneous fat; mixture of ganglion-like cells, myofibroblasts and inflammatory cells; ganglion cells have abundant amphophilic cytoplasm and prominent nucleoli; ganglion cells mixed with inflammatory cells within myxohyaline matrix; condensed around thin walled vascular channel
other - myofibroblasts and fibroblasts with tissue culture appearance; ganglion-like cells #1 (figure 2); #2; #3; #4
stains - van Gieson stain; Alcian blue-PAS
Proliferative fasciitis - Soft Tissue Tumor chapter (continued)
Cytology: cellular smear with spindle cells and large cells with abundant cytoplasm, one to two eccentric nuclei and macronucleoli (Acta Cytol 1985;29:882)
Positive stains: spindle cells-smooth muscle actin, muscle specific actin; ganglion-like cells-vimentin, actin
Negative stains: keratin, S100, desmin
Differential diagnosis:
▪ nodular fasciitis - no ganglion-type cells
▪ proliferative myositis - identical but intramuscular
▪ ganglioneuroma - different stroma, ganglion cells are positive for neural markers
▪ rhabdomyosarcoma - cross striations in ganglion-type cells, desmin+
▪ sarcoma - large mass, actual pleomorphism not just dual cell population, nuclear chromatin and membrane abnormalities, atypical mitotic figures
References: Cancer 1975;36:1450, Stanford University
Childhood variant
Gross: circumscribed mass
Micro: more cellular and lobulated than classic form with more prominent ganglion-like cells resembling rhabdomyoblasts and more mitotic figures; may have acute inflammatory cells and focal necrosis; often no/minimal fibroblasts
DD: rhabdomyosarcoma
References: AJSP 1992;16:364
Proliferative myositis of soft tissue
Definition: intramuscular mass similar to nodular fasciitis, but with large basophilic cells resembling ganglion cells
Affects skeletal muscle, usually of shoulder, chest or thigh
Children or adults
Treatment: conservative surgery is curative, may have spontaneous resolution (Head Neck 2007;29:416), recurrence suggests diagnostic error
Gross: poorly circumscribed, scar-like induration of muscle, usually 3-4 cm
Gross images: ill defined white material between skeletal muscle fibers
Micro: cellular with plump fibroblasts and myofibroblasts surrounding individual muscle fibers creating a checkerboard pattern; also large ganglion-like cells with abundant amphophilic to basophilic cytoplasm, vesicular nuclei and prominent nucleoli; stroma is collagenous or myxoid; variable mitotic figures but no atypical ones; ill defined margins; may have metaplastic bone
Micro images: AFIP - characteristic checkerboard pattern is produced by reactive proliferation expanding spaces between muscle bundles and individual muscle fibers #1; #2; with metaplastic bone, resembling myositis ossificans; large ganglion cells with crowding and molding resembling carcinoma; cells have abundant amphophilic cytoplasm and prominent nucleoli
other - checkerboard pattern; ganglion cells #1; #2; #3; #4 (figure 3)
spindle cell sarcoma resembling proliferative fasciitis - AFIP - checkerboard pattern produced by infiltration of tumor cells between muscle bundles without myocyte necrosis; cellular proliferation of atypical spindle cells differs from bland spindle cells of proliferative myositis
Proliferative myositis of soft tissue (continued)
Cytology: loose clusters of uniform fibroblast-like spindle cells and large, ganglion-like cells with eccentric nuclei, prominent nucleoli and abundant cytoplasm (Acta Cytol 1995;39:535)
Positive stains: vimentin, smooth muscle actin, muscle specific actin
Negative stains: keratin, S100, desmin
EM: fibroblasts and myofibroblasts, ganglion-like cells are fibroblasts or myofibroblasts with abundant dilated rough endoplasmic reticulum but no neuronal characteristics (AJSP 1991;15:654)
Differential diagnosis:
▪ sarcoma - large mass, marked atypia
▪ proliferative fasciitis - not in muscle
▪ nodular fasciitis - completely obliterates muscle, no ganglion-type cells
▪ desmoid fibromatosis - 3 cm or larger, completely replaces muscle, no ganglion-type cells; stroma is collagenous, skeletal muscle at periphery is injured
References: Stanford University
Proliferative peribursitis of soft tissue
Definition: angiomyxoid tumor-like mass near joints and ligaments
Not a WHO diagnosis
No PubMed references identified
Associated with prior joint disease, dislocation or trauma
Micro: separate vascular and nonvascular regions; vascular region has cluster of thick vessels with pericyte cuff in myxoid substance; high power shows evenly disbursed spindle cells with bipolar and stellate cells, occasional lymphocytes and histiocytes; histiocytes may contain vacuoles and resemble lipoblasts; may have cysts with or without ganglion cells, synovial lining, dense scar
Positive stains: actin (spindle cells)
Differential diagnosis:
▪ myxoma - stellate cells only; no prominent vasculature
▪ myxoid liposarcoma - uniform appearance of lipoblasts, no stellate myofibroblasts
Sclerosing epithelioid fibrosarcoma of soft tissue
Definition: rare, slow growing, intermediate-grade sarcoma of deep soft tissue with epithelioid tumor cells in nests and cords and hyalinized fibrous stroma
First described in 1995 (AJSP 1995;19:979)
Epidemiology: usually age 20+ years, no gender preference
Sites: limb/limb girdle, head and neck, back/chest wall, base of penis, cranium
50% have persistent disease or local recurrence; 43-86% develop distant metastases (lung, bone and soft tissue, breast, pericardium, brain), 25-57% die of disease within 16-86 months (AJSP 2001;25:699)
Case reports: 29 year old man with tumor related ascites (J Med Case Reports 2008 Jul 25;2:248), 30 year old man with metastatic disease (Sarcoma 2009;2009:953750), 48 year old woman with sacral tumor (J Clin Path 2004;57:90), 62 year old Chernobyl cleanup worker with cecal tumor (Archives 2007;131:1825), 90 year old woman with ankle mass (Case of Week #3)
Gross: mean 9 cm, range 4-22 cm, appears circumscribed but is not; firm, gray-white cut surface, may invade bone; usually no necrosis
Gross images: gray-white tumor
Micro: nests or cords of small to medium sized, round to ovoid, relatively uniform epithelioid cells, often with clear cytoplasm and uniform bland nuclei embedded in a hyalinized fibrous stroma; hypo- and hypercellular areas; tumor cells are often in single file pattern resembling carcinoma; bone invasion and tumor necrosis are present; has areas resembling fibroma, low grade fibromyxoid sarcoma, conventional fibrosarcoma; 4 MF/10 HPF; may have hemangiopericytoma-like vasculature, vascular invasion
grade I: cell nuclei slightly larger and more abnormal than fibromatosis, no necrosis or hemorrhage
grade III: closely packed cells with markedly dense chromatin and no/minimal collagenous stroma, numerous mitotic figures
grade II: intermediate between grade I and III
Micro images: ankle mass; cecal tumor; sacral tumor; single file pattern; keratin MNF 116
Sclerosing epithelioid fibrosarcoma of soft tissue (continued)
Positive stains: vimentin, p53, bcl2; variable EMA, S100 and keratin
Negative stains: CD34, CD45, HMB45, desmin, alpha smooth muscle actin; low Ki-67
EM: fibroblastic features of parallel arrays of rough endoplasmic reticulum and prominent networks of intermediate filaments that may form perinuclear whorls
Molecular: may be related to low grade fibromyxoid sarcoma as same FUS-CREB3L2 translocation is detectable in some cases (Am J Surg Pathol 2007;31:1387)
Differential diagnosis:
▪ low-grade fibromyxoid sarcoma - monotonous and hypocellular, with alternating myxoid and collagenous stroma, only focal epithelioid cells
▪ synovial sarcoma - no large areas of sclerotic collagen
▪ sclerosing lymphoma - positive for lymphocytic markers
▪ poorly differentiated carcinoma - positive for keratin
▪ lobular breast carcinoma - single file pattern, but cells are low grade; usually ER+, PR+, keratin+
References: Histopathology 1998;33:354, Stanford University
Solitary fibrous tumor (extrapleural) of soft tissue
Definition: fibroblast like cells with patternless pattern, thin strip-like bands of collagen and gaping vessels
Similar to pleural tumor
Distinction from hemangiopericytoma has become increasingly blurred
See also discussion in Bladder, CNS, Ear, Eye, Kidney-Tumor, Liver-Tumor, Nasal Cavity, Oral Cavity, Pleura, Prostate and Thyroid gland chapters
See also related lesions - giant cell angiofibroma, hemangiopericytoma
Epidemiology: usually adults (median age 50 years)
Wide anatomic distribution; derives from pleura and various serosa or sites without any serosa
Rarely causes paraneoplastic hypoglycemia due to insulin-like growth factor production
Slow growing painless mass, usually benign; histologically malignant tumors may be grossly infiltrative and up to 50% may metastasize
Poor prognostic factors: size > 10 cm, >4 MF/10 HPF, cellular atypia, positive margins, malignant histology (Cancer 2002;94:1057), although histology has less significance in retroperitoneum (Urol Oncol 2008;26:254)
Case reports: 33 year old woman with mass in check (Case of Week #29 (dermal tumor), 63 year old woman with thigh tumor (Diagn Pathol 2007;2:19)
Treatment: excision, but behavior may be unpredictable (AJSP 1998;22:1501)
Gross: well circumscribed, partially encapsulated, up to 25 cm with multinodular, white, firm, whorled cut surface; necrosis and infiltrative margins are associated with locally aggressive or malignant tumors
Gross images: well circumscribed tan-white tumor with focal necrosis; tumor of omentum #1; #2; pleural tumor
Micro: patternless architecture of hypo- and hypercellular areas separated by thick, hyalinized collagen with cracking artifact and hemangiopericytoma-like vessels; bland and uniform spindle cells are dispersed along thin parallel collagen strands, cells have minimal cytoplasm, small elongated nuclei and indistinct nucleoli; some have myxoid change (Virchows Arch 2009;454:189), mast cells, adipose tissue or multinucleated giant cells; minimal pleomorphism; no atypia, no/rare mitotic figures
malignant SFT - hypercellular, moderate to marked atypia and pleomorphism, tumor cell necrosis, 4+ mitotic figures/10 HPF, infiltrative margins
Solitary fibrous tumor (extrapleural) of soft tissue (continued)
Micro images: AFIP - moderately cellular fibroblastic appearance; parallel arrays of collagen are separated by fibroblastic nuclei; cellular variant has cells with scant cytoplasm and uniform spindled nuclei, note the thin bands of intercellular collagen;
other - patternless pattern and collagenous stroma; patternless and myxoid patterns with hemangiopericytoma-like vessels; fibroblastic cells in fibrous, partly hyalinized matrix with hemangiopericytoma-like blood vessels; thick bands of keloid-type collagen; hemangiopericytoma-like vascular pattern; tumors without (fig A/B) and with (fig C/D) malignant components; comparison of immunostains with GIST; ear-H&E, CD34, CD99 and bcl2; larynx-H&E, CD34, CD99; thigh-H&E, CD34, bcl2; H&E, CD34, beta-catenin
Virtual slides: malignant tumor
Positive stains: CD34 (90%), CD99 (60-70%, myxoid-Mod Path 1999;12:463, oral soft tissue-AJSP 2001;25:900); variable bcl-2, EMA and actin (Mod Path 1997;10:443)
Negative stains: desmin, keratin, S100, CD117, CD31 (Hum Path 1995;26:440); vessels are D2-40 negative (Virchows Arch 2006;448:459)
EM: myofibroblasts, fibroblasts
Molecular/cytogenetics: cytogenetic abnormalities in most tumors 10 cm or larger
Differential diagnosis:
▪ synovial sarcoma - usually no thick collagen bands; keratin+, CD34-
▪ smooth muscle tumors - fascicles of cells with more abundant cytoplasm, blunted nuclei, desmin+, actin+
▪ benign neural tumors - S100+
References: Mod Path 2002;15:324, Mod Path 1997;10:1028
End of Soft Tissue chapter
