PATHOLOGY OF SOFT TISSUE
TUMORS AND PSEUDOTUMOROUS LESIONS
-soft tissue tumours arise from any of the cells present in extraskeletal connective tissue, including fibroblast, adipocyte, neural derivates, endothelium, smooth muscle, skeletal muscle, fibrohistiocytic elements, and other mesenchymal cells
-benign soft tissue tumors are very common- lipomas and hemangiomas are among the most common neoplasms
-malignant soft tissue tumors are rare
-soft tissue neoplasms may occur almost at any site of the body- more commonly- extremities and the retroperitoneum based on their clinical behavior, soft tissue tumors may be classified to following major groups:
1. BENIGN SOFT TISSUE NEOPLASMS
-well circumscribed encapsulated nodular masses, that usually closely resemble the tissue of origin (lipoma- appears as a mass of mature adipose tissue encapsulated by fibrous capsule )
-local excision is curative
-rarely- mesenchymal neoplasm may be multiple and inherited as an autosomal dominant trait
-generalized neurofibromatosis (von Recklinghausen disease )
-generalized lipomatosis (Dercum´ s disease ) -rare
-benign mesenchymal neoplasms rarely undergo malignant transformation
2. LOCALLY AGGRESSIVE SOFT TISSUE NEOPLASMS
are intermediate in clinical behavior between benign and malignant
they are locally aggressive- tend to recur after surgery, but do not metastasise
are associated with locally aggressive and destructive growth pattern
they typically require wide excision with margins of normal tissue
DESMOID FIBROMATOSES- typical example
-abdominal desmoid- the rectus abdominis muscle- in women after pregnancy
3. RARELY METASTASIZING SOFT TISSUE NEOPLASMS
locally aggressive, but in addition they have ability to give rise to distant meta in rare cases, the risk is very low and not reliably predictable
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PLEXIFORM FIBROHISTIOCYTIC TUMOR, so-called ANGIOMATOID
MALIGNANT FIBROUS HISTIOCYTOMA-typical examples
- in addition, it has been shown recently, that typical benign neoplasm, such as cutaneous benign fibrous histiocytoma may very rarely metastasise!
4. MALIGNANT SOFT TISSUE NEOPLASMS (SARCOMA)
-sarcomas are malignant tumors derived from mesenchymal cells-
-much less common than carcinomas
-the most common types of sarcomas- liposarcoma, less commonly- rhabdomyosarcoma, fibrosarcoma, leiomyosarcoma, malignant neural neoplasms, angiosarcoma, etc.
-sarcomas usually present as soft tissue mass, large focally necrotic, with hemorrhages- most commonly- extremities and retroperitoneum biological behavior- extremely variable:
-HIGH GRADE SARCOMAS
-are highly cellular tumors, composed of poorly differentiated cells
-marked nuclear abnormalities, polymorphism, high mitotic rate- anaplasia- sometimes difficult to classify- recognition of cell of origin- immunohistochemistry, electron microscopy
-grow rapidly, may metastasize early through the bloodstream, lymphatic spread is uncommon
-poor prognosis, treatment is rarely successful
-LOW GRADE SARCOMAS
-better-differentiated, less cellular, tend to resemble more the tissue of origin, cytologic abnormalities less prominent, mitotic rate low
-slower growth rate, high risk of local recurrences, but lower tendency to metastasize
-long survival with repeated recurrences
the new WHO Classification of soft tissue tumours has been introduced in late
2002, it represents wide consensus view- it has gained a wide acceptance in the world
CLASSIFICATION OF SOFT TISSUE TUMOURS
1. Adipocytic tumours
Lipoma and liposarcoma
 -Lipomas- lipomas are the most frequent tumours, delicately encapsulated, small tumors, composed of mature adipose tissue, is benign tumour that can
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arise in any place in which fat is normally present- they arise in subcutaneous tissue- shoulder, neck, back,
-lipomas are single or multiple,
 diffuse lipomatosis- rare, it is a massive enlargement of limbs because of diffuse proliferation of mature adipose tissue in symmetric pattern
 morphologic variants of benign lipoma:
 fibrolipoma-characterized by mature adipose and fibrous tissue
 myxolipoma-tumor has myxoid change in stroma
 spindle cell lipoma-characterized by location in shoulder region of adult men, composed of admixture of mature lipocytes and mature spindle cell in fibrous and mucinous background
 pleomorphic lipoma-benign soft tissue adipose tumor that contains multinucleated tumor cells
 lipoblastoma/lipoblastomatosis- affects young children, grossly the lesion is soft and lobulated, histologically resembles fetal fat tissue, composed of lipoblasts, clinically benign
 Liposarcomas- are much less common than lipomas, liposarcoma is second most frequent soft tissue sarcoma in adults,
-liposarcomas are large tumors, more commonly located in deep soft tissues of extremities, and retroperitoneum, histologically the tumors are characterized by lipoblasts- mononuclear or multinuclear cell with one or more cytoplasmic fat vacuoles, nucleus may be pushed aside by one large fat vacuole resulting in signet ring appearance, or may remain centrally located with multiple small cytoplasmic vacuoles- resulting in appearance similar to mature sebaceous cell- scalloped
nuclear appearance
 four major variants of liposarcoma: myxoid, round cell type, well differentiated- better outcome
-pleomorphic, dedifferentiated- poor outcome
 myxoid liposarcoma-by far most common type of LS, microscopically characterized by prominent capillary anastomosing network, mucoid matrix and lipoblasts
 well-differentiated LS- previously called “atypical lipomatous tumor”, no meta potential, however if located within retroperitoneum- ultimately associated with uncontrolled growth, and significant tumor-related mortality!
2. FIBROBLASTIC/MYOFIBROBLASTIC TUMORS AND TUMOR-LIKE
LESIONS
Reactive pseudosarcomatous proliferations
 Nodular fasciitis
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- reactive, benign fibroproliferative lesion, more commonly mistaken for malignant tumor than any other non-neoplastic condition
-the lesion appears as palpable mass, most frequent in extremities
-rapid growth, in young patients
-morphologically- it is composed of spindled fibroblasts/myofibroblasts in a loose myxoid stroma
-does not recur, no potential to meta
 Myositis ossificans
-a variant of fasciitis, sometimes preceded by trauma, occurs most often in skeletal muscle
-favored site are extremities morphologically-circumscribed, unencapsulated mass composed of fibroblast/myofibroblast in myxoid stroma, the periphery has a rim of bone
-mature lesion are completely ossified
 FIBROMATOSES- the generic name ”fibromatoses” was given to a group of fibroproliferative lesions characterized by
proliferation of well differentiated fibroblasts and myofibroblasts, infiltrative growth pattern, presence of variable amount of collagen between cells, aggressive clinical behaviour characterized by repeated recurrences and lack of capacity to metastasize
grossly the lesions areoften large, firm in consistency, whitish in colour
microscopically- most proliferating cells have features between fibroblasts and myofibroblasts, mitotic figures are rare, admixture of variable amount of collagen, inlfammatory infiltrates at the advancing edges of the tumor
 Plantar, palmar, penile fibromatoses
-some forms of fibormatosis derive their names from their particular locations, such as palmar fibromatosis- Dupuytren contracture
-plantar f.- located on the foot- Lederhose c.
-when involves the penis- penile fibromatosis- Peyronie ´s disease these lesions are mainly in adults, they may recur after excision
 Musculoaponeurotic fibromatosis- desmoid (aggressive fibromatosis)
-this lesion is traditionally regarded as a neoplasm of the abdominal wall in women during and after pregnancy, it is however almost as common in men and in other locations, thus we can distinguish based on location:
-abdominal desmoid
-extraabdominal desmoid- affects men and women equally
-intra-abdominal desmoid- affects the intestine, mesenterium, etc. associated in Gardner syndrome (multiple colonic polyposis and multiple osteomas
-the lesions are potentially curable by excision, but they stubbornly recur
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 juvenile fibromatosis- is a term given to f. occurring in children, they have a greater propensity for local recurrences, there are three forms of fibromatosis in childhood with special clinical presentations
 congenital torticollis (fibromatosis coli)- is a type affecting the lower segment of m.sternocleidomastoideus, this condition requires surgical resection of the muscle
 infantile digital fibromatosis- is a form restricted to childhood, lesions are often multiple, located on fingers, this lesion has great tendency for local recurrence
 infantile myofibromatosis- presents as solitary or multiple nodules in the skin and soft tissues, most cases appear before 2 years of age, about 60% are congenital
 fibrosarcoma-are commonly tumor of adults, they arise from superficial and deep connective tissues
-histologically- composed of fibroblastic cells arranged in fascicles new entities:
 solitary fibrous tumor- formerly regarded as a mesothelial tumor, now known to arise from soft tissue anywhere
-the tumor is benign, composed of spindle cells in abundant collagenous stroma
 inflammatory myofibroblastic tumor- rarely metastasising category, most tu behave in bening fashion, rare cases (unpredictable which ones) can be aggressive
 myxofibrosarcoma- tendency to arise in ssuperficial subcutaneous tissue of the limbs
 mammary type myofibroblastoma- described in breast, but may occur in extramammary sites as well, benign, cytogenetic similarities with spindle cell lipoma
 angiomyofibroblastoma- predilection ot vulvovaginal region, benign lesion, well circumscribed, must be distinguished from aggressive angiomyxoma
 nuchal type fibroma- benign lesion in posterior neck or upper trunk of younger adult men, may be associated with diabetes mellitus, is characterized by a poorly marginated hypocellular collagenous stroma, with entrament of adipose tissue
 myxoinflammatory fibroblastic sarcoma- distal parts of extremities of young adults, high risk of local recurrences, only very low risk of distant meta
 sclerosing epithelioid fibrosarcoma- wide age range, predilection for low extremity, very aggressive tumor with high rate of meta
3. Fibrohistiocytic tumors
-this is a large group of tumours characterized by dual differentiation of neoplastic cells, both fibroblastic and histiocytic
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 Benign fibrous histiocytoma
-distinctive unencapsulated well demarcated tumour composed of a mixture of cells resembling fibroblasts, myofibroblast, histiocytes and primitive mesenchymal cells
-benign giant and foamy cells can be also found
 Dermatofibrosarcoma protuberans
Uncommon dermal/subcutaneous tumor,mostly encountered in adults (4 th decade), also observed in adolescents, children
is characterized by local aggressiveness, high tendency for recurrences, but metastases are extremely rare
this lesion is highly cellular, without capsule, high mitotic activity, storiform pattern of growth – this refers to a peculiar arrangement of cells around one point producing radiating fascicles grouped at right angles to each other.
pigmented variant of DP is called Bednar tumor- melanin
 giant cell fibroblastoma- juvenile variant of DFSP, GCF and DFSP share some chromosomal abnormalities, such as translocation of 17q22,
 hybrid tumors GCF and DFSP- exist
 Atypical fibroxanthoma- tumor with borderline malignancy, it typically presents as a small nodule in the sun-exposed skin of elderly patients
 Malignant fibrous histiocytoma- frankly malignant tumor, most cases occur in deep soft tissue of extremities, microscopically composed of polymorphic cells in storiform pattern, multinucleated cells and inflammatory infiltrate may be present
-the tumor is prone to local recurrence and may metastasise
-not so common as previously expected, most so-called pleomorphic MFH represent other entiies newly described…
4. Tumors of skeletal muscle
 Rhabdomyosarcoma- there are three major categories of RMS- pleomorphic, embryonal and alveolar
 pleomorphic RMS - is least common, it arises from deep skeletal muscle, mostyl lower extremity
 embryonal RMS- occurs mostly in children between 3 and 12 years of age, located in head and neck region, retroperiteoneum and urogenital tract, less commonly in soft parts
 alveolar RMS- most common locations are upper extremity, perineal and perirectal region, prognosis is worse than that of embryonal RMS,
Rhabdomyoma- heart
5. smooth muscle tumors
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smooth muscle tumors ave been traditionally subdivided in to benign and malignant category based on cytological atypia, mitotic activity and other criteria…
 Leiomyoma and leiomyosarcoma
-both occur predominantly in the female genital tract, they may occur at other site, such as skin and deep soft tissue
 cutaneous leiomyoma- arise from arrector pili smooth muscle elements, tumors are small, poorly circumscribed, benign, can recur if not removed completely
 angioleiomyoma- arise from the muscle of blood vessel, they are the most common smooth muscle tu of sft tissues, they are located in deep soft tissue of leg, or subcutaneous tissue, benign in most cases, rare- atypical mitotic activity-uncertain biological potential
 leiomyosarcoma of peripheral soft tissues- occur mainly in older adults in wide variety of anatomical sites, most are high grade sarcomas with poor prognosis, prognosis is related to size, depth and grade!
 Retroperitoneal smooth muscle tumors- retroperitoneal leiomymomas reported only in middle aged women- “uterine type leiomyoma”- ER/PR positive, may be nvery large
 Leiomyomatosis peritonealis disseminata- refers ot uncommon occurrence of multiple benign leiomy proliferations
 Retroperitoneal leiomyosarcoma- common in old age, in women usually large tumors, poor prognosis
6. Tumors of peripheral nervous system
 schwannoma, neurofibroma, malignant peripheral nerve sheath tumor, perineurioma, nerve sheath myxoma
7. Vascular tumors
 hemangioma capillary and cavernous, spindle cell hemangioendothelioma –benign lesions
 group of intermediate vascular lesions: now subcategorised to
 locally aggressive: kaposiform hemangioendothelioma-new entity, rare affecting infants and children, mainly in retroperitoneum and skin these lesion may be very large, with consumption coagulopathy
(Kasabach-Merritt syndrome)
 rarely metastasising lesions: papillary intralymphatic angiendothelioma,
retiform hemangioendothelioma- described earlier as Dabska tumor- extremities of young adults
 malignant category includes: epithelioid hemangioendothelioma- 20-30% give rise to distant meta
 Kaposi sarcoma was moved to intermediate category of rarely meta sarcomas
8.SPECIAL TYPES OF SOFT TISSUE SARCOMAS
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 SYNOVIAL SARCOMA
-is a rare malignant soft tissue tumor of young adults that is unrelated to synovium and can occur in almost any part of the body, the designation synovial
sarcoma has become established, but it is known to be incorrect- the tumor has no relationship to synovium
-there is slight male preponderance, between 5-10% of soft tissue sarcomas are synovial sarcomas symptoms of synovial sarcoma: it grows slowly, and presents as a deep-seated mass with or without local pain or tenderness
-approximately 90% of cases occur in the extremities with 30% around knee, origin within a joint or bursa represent less than 5% of cases, most tumors are parasynovial or adjacent to joint capsule, tendon sheaths or bursae, distinct region of involvement is head and neck region, including face and tonsils
-90% of cases occur before the age of 50 years
Grossly: the typical synovial sarcoma is 3 to 10 cm in diameter and multinodular, slowly growing tumor may be circumscribed, but is not encapsulated, it infiltrates irregularly to the adjacent tissue histology: two distinctive variants can be distinguished:
 biphasic SS has an epithelial and spindle cell components often in equal proportions
 spindle cell component may predominate or occur alone- monophasic SS
–this is highly cellular tumor composed of spindled malignant cells
 poorly differentiated SS- numerous mitoses, focal necroses, high cellularity, this form is associated with worse prognosis clinical behavior: high grade sarcoma- there is local recurrence in up to 50% of cases, usually within 2 years after diagnosis, metastases are typically blood-borne to lungs and bone, they can also involve lymph nodes in up to 20% of cases the older literature reported gloomy prognosis with survival rates 25-50% after 5 years and 0-15% after 10 years- local control has been improved, prognosis a little better treatment includes adequate excision, irradiation and chemotherapy
 EXTRASKELETAL CHONDROSARCOMA
-most these tumors occur in extremities of adult patients, they are less aggressive than skeletal CHS, composed of strands and cords of small acidophilic cells embedded in abundant myxoid matrix
 ALVEOLAR SOFT PART SARCOMA-
highly malignant soft tissue tumor, mostly localised in thigh and leg, composed of large cells with granular cytoplasm and vesicular nuclei, the cells are arranged in well defined nests,
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 EPITHELIOID SARCOMA- affects usually adolescents and young adults, the extremities are most common location, particularly fingers and hands, the tumor tends to be superficially located
 OSSIFYING FIBROMYXOID TUMOR – is a newly described soft tissue neoplasm, it presents in adult patients, as well circumscribed nodule in subcutaneous tissue of extremities, the behaviour of this tumor is indolent, local recurences develop in 25% of cases
 Extraskeletal Ewing sarcoma/PNET- the tumor is indistinguishable from skeletal E. sarcoma, most patients are young adults, is composed of small undifferentiated uniform cells with high mitotic activity, prognosis is poor
NON-NEOPLASTIC LESIONS OF SOFT TISSUES
Autoimmune Connective Tissue Diseases (Collagen Disease)
-is a group of disease characterized by
1) involvement of multiple sites
2) evidence of autoimmune cause
3) presence of serum anti-nuclear antibodies
4) inflammatory lesions of small vessels connective tissue diseases include- lupus erythematodes
- progressive systemic sclerosis
-polymyositis-dermatomyositis
-polyarteriitis nodosa and rheumatoid arthritis and rhematic fever- have also some features of “collagen disease”
LUPUS ERYTHEMATODES
-is a connective tissue disease- exists in two different clinical forms:
1. systemic lupus erythematodes (SLE) - progressive severe condition involving multiple organs
2. discoid lupus erythematodes- with skin involvement as only clinical presentation
SLE is more common in women, age at onset is 20-40 years etiology: unknown, it is mediated by an abnormal immune response associated with presence of anti-nuclear antibodies and immune complexes (formed by nuclear antigens and anti-nuclear antibodies) in serum, SLE is a complement mediated immune complex disease pathology:
-at the sites of immune complex depositions - evidence of tissue necrosis and acute inflammation of blood vessel walls- presenting features of the disease are variable- they depend on the site of injury
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-small vessel vasculitis-immune complex injury of arterioles-fibrinoid necrosis of the media and infiltration of the wall and perivascular tissue- mixed inflammatory infiltrate, thrombosis, results in tissue ischaemia and necrosis
-hyperplasia of the lymphoid system- enlargement of lymph nodes with follicular hyperplasia, splenomegaly
-skin- immune complex deposition occurs in basement membranes of the skin- skin rash of the face patients with discoid LE present with skin lesions only, immune complex deposition is restricted to the area of rash
-joint- in 90 % of patients- joint inflammation
-heart- include pericarditis, myocarditis, Libman-Sachs endocarditis clinical course: is variable, rarely -severe acute ilness that is refractory to treatment most patients persue a chronic course
PROGRESSIVE SYSTEMIC SCLEROSIS
-also called sclerodermia, is an uncommon connective tissue disease characterized by vasculitis affecting small vessels- with widespread deposition of collagen
-more commonly in females, onset most frequently from 20 to 50 years
-probably autoimmune disease closely related to SLE pathology: include vasculitis and marked fibrosis of connective tissue clinical features: in many patients- disease is restricted to the skin, in more severe cases involvement of internal organs, such as GIT, kidneys and lungs
-skin- fingers and face
-fibrosis of the dermis and extending to subcutaneous tissue, epidermis becomes thin, adnexal organs become atrophic, there are trophic ulcerations, dystrophic calcification gastrointestinal tract- esophagus, and small intestine usually show the most severe changes-fibrosis and sclerosis of connective tissue- dysphagia, deficient peristalsis, malabsorption
-kidneys: glomerular changes resulting from immune complex deposits- basement membrane thickening and mesangial hypercellularity
-lungs- progressive fibrosis and interstitial pneumonitis- honeycomb lung and respiratory failure clinical course is chronic and progressive, treatment with immunosuppressive drugs of limited value
POLYMYOSITIS-DERMATOMYOSITIS
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-uncommon connective tissue disease, affecting more commonly females, onset between 40 and 60
-patients are in increased risk of malignant tumours- carcinoma of the lung, breast, stomach, uterus, etc. clinical features: chronic disease characterized by increasing disability from muscle wasting
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