135 U.Akanksha: PATHOLOGY ASSIGNMENT

SOFT TISSUE TUMORS

(Roll no 135-139)

135-UMR.AKANKSHA

(WHO classification of soft tissue tumours)

136-DEDEEPYA VEMURI

(Etiopaghogenesis of soft tissue tumours)

137-UJWALA

(Gross features of soft tissue tumours)

138-VAGISHA RANI

(Microscopy of soft tissue tumours)

139-VAMSHITHA

(Genetics of soft tissue tumours)

Topic-1

World Health Organization classification of soft-tissue tumors

The World Health Organization (WHO) issued an updated classification of soft-tissue tumors that divided them into the following categories.

Adipocytic tumors
Fibroblastic/myofibroblastic tumors
So-called fibrohistiocytic tumors
Smooth-muscle tumors
Pericytic (perivascular) tumors
Skeletal-muscle tumors
Vascular tumors
Chondro-osseous tumors
Gastrointestinal stromal tumors
Nerve-sheath tumors
Tumors of uncertain differentiation
Undifferentiated/unclassified sarcomas

In addition, as part of this classification, soft tissue tumors were divided into the following four categories as appropriate:

Benign
Intermediate (locally aggressive)
Intermediate (rarely metastasizing)
Malignant

This terminology should not be confused with the grading system mentioned above, in which grade 2 may be regarded as intermediate.

Adipocytic tumors

Benign adipocytic tumors include the following:

Lipoma
Lipomatosis
Lipomatosis of nerve
Lipoblastoma/lipoblastomatosis
Angiolipoma
Myolipoma
Chondroid lipoma
Extrarenal angiomyolipoma
Extra-adrenal myelolipoma
Spindle cell/pleomorphic lipoma
Hibernoma

Intermediate (locally aggressive) adipocytic tumors include the following:

Atypical lipomatous tumor/well-differentiated liposarcoma

Malignant adipocytic tumors include the following:

Dedifferentiated liposarcoma
Myxoid liposarcoma
Pleomorphic liposarcoma
Liposarcoma, not otherwise specified

Fibroblastic/myofibroblastic tumors

Benign fibroblastic/myofibroblastic tumors include the following:

Nodular fasciitis
Proliferative fasciitis
Proliferative myositis
Myositis ossificans
Fibro-osseous pseudotumor of digits
Ischemic fasciitis
Elastofibroma
Fibrous hamartoma of infancy
Fibromatosis colli
Juvenile hyaline fibromatosis
Inclusion body fibromatosis
Fibroma of tendon sheath
Desmoplastic fibroblastoma
Mammary-type myofibroblastoma
Calcifying aponeurotic fibroma
Angiomyofibroblastoma
Cellular angiofibroma
Nuchal-type fibroma
Gardner fibroma
Calcifying fibrous tumor

Intermediate (locally aggressive) fibroblastic/myofibroblastic tumors include the following:

Superficial fibromatoses - Palmar/plantar
Desmoid-type fibromatoses
Lipofibromatosis
Giant cell fibroblastoma

Intermediate (rarely metastasizing) fibroblastic/myofibroblastic tumors include the following:

Dermatofibrosarcoma protuberans - Fibrosarcomatous, pigmented
Solitary fibrous tumor - Solitary fibrous tumor, malignant
Inflammatory myofibroblastic tumor
Low-grade myofibroblastic sarcoma
Myxoinflammatory fibroblastic sarcoma/atypical myxoinflammatory fibroblastic tumor
Infantile fibrosarcoma

Malignant fibroblastic/myofibroblastic tumors include the following:

Adult fibrosarcoma
Myxofibrosarcoma
Low-grade fibromyxoid sarcoma
Sclerosing epithelioid fibrosarcoma

So-called fibrohistiocytic tumors

Benign tumors of this type include the following:

Tenosynovial giant cell tumor - Localized, diffuse, malignant
Deep benign fibrous histiocytoma

Intermediate (rarely metastasizing) tumors of this type include the following:

Plexiform fibrohistiocytic tumor
Giant cell tumor of soft tissues

Smooth-muscle tumors

These tumors include the following:

Benign - Leiomyoma of deep soft tissue
Malignant - Leiomyosarcoma (excluding skin)

Pericytic (perivascular) tumors

These tumors include the following:

Glomus tumor (and variants) - Glomangiomatosis, malignant glomus tumor
Myopericytoma - Myofibroma, myofibromatosis
Angioleiomyoma

Skeletal-muscle tumors

These tumors include the following:

Rhabdomyoma
Embryonal rhabdomyosarcoma
Alveolar rhabdomyosarcoma
Pleomorphic rhabdomyosarcoma
Spindle cell/sclerosing rhabdomyosarcoma

Vascular tumors

Benign vascular tumors include the following:

Hemangioma - Synovial, venous, arteriovenous hemagnioma/malformation
Epithelioid hemangioma
Angiomatosis
Lymphangioma

Intermediate (locally aggressive) vascular tumors include the following:

Kaposiform hemangioendothelioma

Intermediate (rarely metastasizing) vascular tumors include the following:

Retiform hemangioendothelioma
Papillary intralymphatic angioendothelioma
Composite hemangioendothelioma
Pseudomyogenic (epithelioid sarcoma-like) hemangioendothelioma
Kaposi sarcoma

Malignant vascular tumors include the following:

Epithelioid hemangioendothelioma
Angiosarcoma of soft tissue

Chondro-osseous tumors

These tumors include the following:

Soft-tissue chondroma
Mesenchymal chondrosarcoma
Extraskeletal osteosarcoma

Gastrointestinal stromal tumors

Gastrointestinal stromal tumors (GISTs) include the following:

Benign GIST
GIST of uncertain malignant potential
Malignant GIST

Nerve-sheath tumors

Benign nerve-sheath tumors include the following:

Schwannoma (including variants)
Melanotic schwannoma
Neurofibroma (including variants) - Plexiform neurofibroma
Perineurioma - Malignant perineurioma
Granular cell tumor
Dermal nerve sheath myxoma
Solitary circumscribed neuroma
Ectopic meningioma
Nasal glial heterotopia
Benign Triton tumor
Hybrid nerve-sheath tumors

Malignant nerve-sheath tumors include the following:

Malignant peripheral nerve sheath tumor
Epithelioid malignant nerve sheath tumor
Malignant Triton tumor
Malignant granular cell tumor
Ectomesenchymoma

Tumors of uncertain differentiation

Benign tumors of uncertain differentiation include the following:

Acral fibromyxoma
Intramuscular myxoma (including cellular variant)
Juxta-articular myxoma
Deep ("aggressive") angiomyxoma
Pleomorphic hyalinizing angiectatic tumor
Ectopic hamartomatous thymoma

Intermediate (locally aggressive) tumors of uncertain differentiation include the following:

Hemosiderotic fibrolipomatous tumor

Intermediate (rarely metastasizing) tumors of uncertain differentiation include the following:

Atypical fibroxanthoma
Angiomatoid fibrous histiocytoma
Ossifying fibromyxoid tumor - Including malignant
Mixed tumor NOS - Including malignant
Myoepithelioma
Myoepithelial carcinoma
Phosphaturic mesenchymal tumor - Benign, malignant

Malignant tumors of uncertain differentiation include the following:

Synovial sarcoma NOS - Spindle cell, biphasic
Epithelioid sarcoma
Alveolar soft-part sarcoma
Clear cell sarcoma of soft tissue
Extraskeletal myxoid chondrosarcoma
Extraskeletal Ewing sarcoma
Desmoplastic small round cell tumor
Extrarenal rhabdoid tumor
Neoplasms with perivascular epithelioid cell differentiation (PEComa)
Intimal sarcoma

Undifferentiated/unclassified sarcomas

These tumorsinclude the following:

Undifferentiated spindle cell sarcoma
Undifferentiated pleomorphic sarcoma
Undifferentiated round cell sarcoma
Undifferentiated epithelioid sarcoma
Undifferentiated sarcoma NOS

Benign vs intermediate vs malignant tumors

Benign soft-tissue tumors usually do not recur locally, and if they do, the recurrence is nondestructive and almost always readily curable by complete local excision. Morphologically benign lesions, which are extremely rare, may give rise to distant metastases, which cannot be predicted on the basis of routine, contemporary histologic evaluation. This is best documented in rare, cutaneous benign fibrous histiocytoma.

Intermediate (locally aggressive) soft-tissue tumors show an infiltrative and locally destructive growth pattern. However, although they may recur locally, they do not metastasize. They usually require excision with a wide margin of normal tissue for better local control. The example in this category is desmoid (fibromatosis).

Intermediate (rarely metastasizing) soft-tissue tumors are often locally aggressive, but in some cases, they also have a tendency to produce distant metastases (usually in a lymph node or lung). This risk is low (< 2%), but histomorphologically, it is not reproducibly predictable. The classic examples in this group are plexiform fibrohistiocytic tumor and angiomatoid fibrous histiocytoma.

Malignant soft-tissue sarcomas are locally destructive with the potential to recur. The risk of distant metastasis is significant. (Depending on histologic type and grade, the potential ranges from 20% to almost 100%). Histologically low-grade sarcomas have a lower chance of metastasis (only 2-10%).However, the recurrences of such tumors may advance in grade and attain a higher risk of metastatic potential similar to that associated with myxofibrosarcoma and leiomyosarcoma.

TOPIC-2

ETIOPATHOGENESIS OF SOFT TISSUE TUMORS

Most sarcomas are sporadic and have no known predisposing cause.

A small minority are associated with germline mutations in tumor suppressor genes.

Others are linked to environmental exposures such as radiation, burns, or toxins.

Etiology of soft tissue tumours remains largely unknown.

1. Frequently there is history of antecedent trauma which may bring the tumour to attention of the patient.

2. Molecular and cytogenetic studies in many soft tissue tumours reveal chromosomal abnormalities and mutations in genes which can be used as a marker for diagnosis and histogenesis e.g. translocations, various fusion genes etc.

3. Most of the soft tissue tumours occur sporadically;however, there are a few examples which are components of syndromes e.g. neurofibromatosis type 1, Li-Fraumeni syndrome, Osler-Weber-Rendu syndrome etc.

The genetics of tumorogenesis are heterogenous, but some generilizations can be made based on karyotypic complexity:

SIMPLE KARYOTYPE(20%): Like many luekemias and lymphomas, sarcomas are occasionally euploid tumors with a single or limited number of chromosomal changes that ocuur early in tumorigenesis and are specific enough to serve as diagnostic markers. Commonly arise in younger individuals.

COMPLEX KARYOTYPE(80%):These tumors are usually aneuploid or polyploid and demonstrate multiple chromosomal gains and losses, a feature that suggests an underlying abnormality producing genomic abnormality.Such tumors are common in adults.