Soft Tissue Tumours Notes

Soft Tissue Tumours General Features And Classification

Soft tissue tumours are a variety of mesenchymal tumours arising from tissues which are embryologically derived from mesoderm; however, it also includes tumours of peripheral nerve
which are ectoderm-derived.

Read And Learn More: Systemic Pathology Notes

Thus, the group includes tumours from adipocytes, fibroblasts and myofibroblasts, fibro histiocytic cells, chondro-osseous tissues, smooth and skeletal muscle, vessels and perivascular tissues, peripheral nerves, and tumours of some specialised soft tissues.

Soft Tissue Tumours Classification:

Depending upon the line of differentiation of tumour cells (adult tissue they resemble), the
WHO classification (2013) divides soft tissue tumours into 12 groups:

1. Adipocytic tumours,
2. Fibroblastic/myofibroblastic tumours,
3. So-called fibrohistiocytic tumours,
4. Smooth muscle tumours,
5. Pericytic (perivascular) tumours,
6. Skeletal muscle tumours,
7. Vascular tumours,
8. Gastrointestinal stromal tumours,
9. Nerve sheath tumours,
10. Chondroosseous tumours,
11. Tumours of uncertain differentiation, and
12. Undifferentiated/unclassified sarcomas.

Based on biological behaviour, soft tissue tumours are distributed generally into the following 4 categories:

Benign: These soft tissue tumours generally do not recur and are cured by complete excision. A common example is a lipoma.

Intermediate, locally aggressive: These tumours are locally destructive, and infiltrative and often recur but do not metastasise. Such tumours are generally treated by wide excision; for example desmoid tumours.

Intermediate, rarely metastasising: This category of tumours is also locally destructive, infiltrative and recurrent but in addition, about 2% of cases may have clinical metastasis which may not be predicted by morphology. A common example in this category is dermatofibrosarcoma protuberans.

Malignant: Tumours in this category are clearly malignant they are locally destructive and infiltrative and they metastasise in a high per cent of cases. The metastatic rate in low-grade sarcomas is about 2-10% and in high-grade sarcomas is 20-100%.

Soft Tissue Tumours Common Features:

• Benign soft tissue tumours are about 100 times more common than sarcomas. Sarcomas rarely arise from the malignant transformation of a pre-existing benign tumour. Instead, sarcomas originate from the primitive mesenchymal cells having the capacity to differentiate along different cell pathways.
• As discussed, soft tissue sarcomas metastasise most frequently by the haematogenous route and disseminate commonly to the lungs, liver, bone and brain. Lymph node metastases are often late and are associated with widespread dissemination of the tumour.
• Histologic differentiation and grading of soft tissue sarcomas are important because of varying clinical behaviour, prognosis and response to therapy.

The majority of soft tissue tumours have the following important general features:

1. Superficially-located tumours tend to be benign while deep-seated lesions are more likely to be malignant.
2. Large-sized tumours are generally more malignant than small ones.
3. Rapidly growing tumours often behave as malignant tumours more than those that develop slowly.
4. Malignant tumours have frequently increased vascularity while benign tumours are selectively avascular.
5. Although soft tissue tumours may arise anywhere in the body but in general more common locations are the lower extremity (40%), upper extremity (20%), trunk and retroperitoneum (30%) and head and neck (10%).
6. Generally, males are affected more commonly than females.
7. Approximately 15% of soft tissue tumours occur in children and include some specific examples of soft tissue sarcomas example rhabdomyosarcoma, and synovial sarcoma.

Soft Tissue Tumours Etiology And Pathogenesis:

The aetiology of soft tissue tumours remains largely unknown; however, a few common features in aetiology and pathogenesis apply to many soft tissue tumours:

1. Frequently there is a history of antecedent trauma which may bring the tumour to the 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 example translocations, various fusion genes etc.
3. Most soft tissue tumours occur sporadically; however, there are a few examples which are components of genetic syndromes example neurofibromatosis type 1, Li-Fraumeni syndrome, Osler-Weber-Rendu syndrome etc.
4. Oncogenic viruses such as Epstein-Barr virus are implicated in the development of smooth muscle tumours in patients with immunodeficiency syndromes.

Soft Tissue Tumours Diagnostic Criteria:

Accurate pathological diagnosis of soft tissue tumours is based on histogenesis which is important for determining the prognosis and can be made by the following plan:

1.  Cell Patterns: Several morphological patterns in which tumour cells are arranged are peculiar in different tumours example

• Smooth muscle tumours: interlacing fascicles of pink staining tumour cells.
• Fibrohistiocytic tumours: characteristically have a storiform pattern in which spindle tumour cells radiate from the centre in a spoke-wheel manner.
• Herringbone pattern: is seen in fibrosarcoma in which the tumour cells are arranged like the vertebral column of sea fish.
• Palisaded arrangement: is characteristically seen in schwannomas in which the nuclei of tumour cells are piled upon each other.
• Biphasic pattern: is the term used for a combination arrangement of two types—fascicles and epithelial-like examples in synovial sarcoma.

2. Cell Types: After looking at the pattern of cells described above, a preliminary categorisation of soft tissue tumours is done on the basis of cell types comprising the soft tissue tumour:

• Spindle cells These are the most common cell types in most sarcomas. However, there are
  subtle differences in different types of spindle cells example
  • Fibrogenic tumours have spindle cells with light pink cytoplasm and tapering-ended nuclei.
  • Neurogenic (Schwann cell) tumours have tumour cells similar to fibrogenic cells but have curved nuclei.
  • Leiomyomatous tumours have spindle cells with blunt-ended (cigar-shaped) nuclei and more intense eosinophilic cytoplasm.
  • Skeletal muscle tumours have spindle cells similar to leiomyomatous tumours but in addition, have cytoplasmic striations.
• Small round cells Some soft tissue sarcomas are characterised by the dominant presence of small round cells or blue cells and are given various names such as malignant small round cell tumours, round cell sarcomas, or blue cell tumours (due to the presence of lymphocyte-like round nuclear size and dense blue chromatin).
  • Examples of this group of soft tissue tumours include rhabdomyosarcoma (embryonal and alveolar types), Ewing’s sarcoma, malignant peripheral nerve sheath tumour (MPNST), desmoplastic small round cell tumour, etc.
  • A few epithelial tumours such as small cell carcinoma, malignant melanoma, sinonasal carcinoma, malignant carcinoid tumours, and other tumours such as malignant lymphoma, neuroblastoma, retinoblastoma etc, enter the differential diagnosis of small round cell tumours.
• Epithelioid cells Some soft tissue tumours have either epithelioid cells as the main cells (for example epithelioid sarcoma) or have epithelial-like cells as a part of a biphasic pattern of the tumour (for example synovial sarcoma).

3. Immunohistochemistry: Soft tissue tumours are distinguished by the application of immunohistochemical stains. Antibody stains are available against almost each cell constituent. Based on the differential diagnosis made on routine morphology, the panel of antibody stains is chosen for application on paraffin sections for staining. Some common examples are as under:

1. Smooth muscle actin (SMA): for smooth muscle tumours
2. Vimentin: a common marker to distinguish mesenchymal cells from the epithelium
3. Desmin: for skeletal muscle cells
4. S-100: for nerve fibres
5. Factor VIII: antigen for vascular endothelium
6. LCA (leucocyte common antigen): a common marker for lymphoid cells

4. Electron Microscopy: Em as such is mainly a research tool and does not have much diagnostic value in soft tissue tumours but can be applied sometimes to look for tonofilaments or cell organelles.

5. Cytogenetics: Many soft tissue tumours have specific genetic and chromosomal changes which can be analysed for determining histogenesis, or for diagnosis and prognosis. Some of the common cytogenetic aberrations in soft tissue tumours are listed.

Soft Tissue Tumours Grading:

The number of pathological grades of soft tissue tumours may vary according to different grading systems: 2-grade system (grade 1,2 as a low and high grade), 3-grade system (grade 1,2,3 as a low, intermediate and high grade) and 4-grade system (grade 1,4). Pathological grading is based on the following 3 features:

Tumour differentiation or degree of cytologic atypia

1. Mitotic count
2. Tumour necrosis
3. Staging

Different staging systems for soft tissue sarcomas have been described but two of the most accepted staging systems are Enneking’s staging and American Joint Committee on Cancer (AJCC) staging system:

Enneking’s staging: This staging system is accepted by most oncologists and is based on the grade and location of the tumour as under:

• According to tumour location T1 (intracompartmental) and T2 (extra compartmental) tumours.
• According to tumour grade G1 (low grade) and G2 (high grade) tumours.
• Accordingly, the stages of soft tissue tumours vary from stage 1 to stage 3 as under:

Stage 1: G1 and T1-T2 tumours, but no metastases

Stage 2: G2 and T1-T2 tumours, but without metastases

Stage 3: G1 or G2, T1 or T2 tumours, but with metastases

AJCC staging This AJCC system of staging is similar to staging for other tumours. It is based on the TNM system in which the primary tumour (T), the status of lymph nodes (N) and the presence or absence of metastases (M) are taken into consideration for staging, besides the histologic grade of the tumour.

While a few groups of tumours and specific examples listed have been discussed in other related chapters, some important and common examples of soft tissue tumours are discussed in the following pages, taking care not to overburden the students.

Soft Tissue Tumours General Features and Classification:

• Soft tissue tumours are defined as tumours arising from non-epithelial extra-skeletal tissues of the body except the reticuloendothelial system, the glia and the supporting tissues of specific organs and viscera.
• Many of these tumours come to attention after trauma. Several of them have cytogenetic abnormalities. Most occur sporadically; others are part of genetic syndromes.
• Soft tissue tumours are divided into benign, intermediate (locally aggressive or rarely metastasising) and malignant. They are classified according to the line of cellular differentiation.
• They are classified according to the line of cellular differentiation.
• Their diagnosis rests on a few general common features: pattern of cells, cytologic features, and ancillary techniques (immunohistochemistry, EM and molecular profiling).
• Based on histologic features, they are graded into low-, intermediate- and high-grade.
• Staging of soft tissue tumours is based on either Enneking or AJCC method, taking TNM and histologic grade into consideration.

Fibroblastic And Myofibroblastic Tumours

Fibromas, nodular fasciitis, and myositis ossificans are all examples of benign tumours in this group. Intermediate group tumours are fibromatosis (superficial palmar/plantar, desmoid) as locally-aggressive, while dermatofibrosarcoma protuberans which has now been placed in this group as rarely-metastasising intermediate tumours. A common example of a malignant counterpart is fibrosarcoma.

Fibromas:

True fibromas are uncommon tumours in soft tissues and may occur on the tendon sheath. On the other hand, combinations of fibrous growth with other mesenchymal tissue elements are more frequent example neurofibroma, fibromyoma etc.

Three types of fibromas are distinguished:

1. Fibroma durum: a benign, often pedunculated and well-circumscribed tumour occurring on the body surfaces and mucous membranes. It is composed of fully matured and richly collagenous fibrous connective tissue.

2. Fibroma molle or fibro lipoma, also termed soft fibroma, is a similar type of benign growth composed of a mixture of mature fibrous connective tissue and adult-type fat.

3. Elastofibroma: this is a rare benign fibrous tumour located in the subscapular region. It is characterised by the association of collagen bundles and branching elastic fibres.

Nodular Fasciitis:

Nodular fasciitis, earlier called pseudosarcomatous fibromatosis, is a true benign tumour and not a reactive fibroblastic proliferation in which the growth extends from superficial fascia into the subcutaneous fat, and sometimes into the subjacent muscle.

The most common locations are the upper extremity, trunk and neck region of young adults. Local excision is generally curative. Less than 5% of cases may have a local recurrence.

Grossly, the lesion appears as a solitary well-circumscribed nodule (true to its name) in the superficial fascia. The size may vary from a centimetre to several centimetres in diameter.

Microscopically, various morphologic patterns may be seen but the most common is a whorled or S-shaped pattern of fibroblasts present in the oedematous background. The individual cells are spindle-shaped, plump fibroblasts showing mild nuclear atypia. Typical mitoses are frequent but atypical mitoses are not present.

Myositis Ossificans:

• Myositis ossificans is also considered a benign tumour, and not a tumour-like lesion, that is characterised by osteoid and heterotopic bone formation in the soft tissues. It is a misnomer since the lesion neither occurs exclusively in the skeletal muscle as the name leads one to believe, nor
  is inflammation or ossification always essential?
• Myositis ossificans is generally preceded by a history of antecedent trauma to a skeletal muscle or its tendon. The trauma may be a minor and repetitive example to the adductor muscles of the thigh of a horseman, or maybe a single injury followed by a haemorrhage into the muscle. The patient generally complains of pain, tenderness and swelling.
• Richly vascularised granulation tissue replaces the affected muscle or tendon. Then follows the development of osteoid and bone at the periphery, giving a characteristic X-ray appearance.

Grossly, the lesion appears as an unencapsulated, gritty mass replacing the muscle.

Histologically, the central region of the mass shows loosely-arranged fibroblasts having high mitotic activity. Towards the periphery, there is the presence of an osteoid matrix and the formation of woven mineralised bone with trapped skeletal muscle fibres and regenerating muscle (myogenic) giant cells.

The appearance is sufficiently atypical to suggest osteosarcoma but osteosarcoma lacks maturation phenomena seen in myositis ossificans. This is why the condition is also called pseudo malignant osseous tumour of the soft tissues.

Fibromatosis:

• ‘Fibromatosis’ is the term used for actively proliferating fibrous tissue into a tumour-like mass that may at times be difficult to differentiate from sarcomas.
• These tumours are regarded as non-metastasising fibroblastic tumours which tend to invade locally and recur after surgical excision.
• In addition, electron microscopy has shown that the cells comprising these lesions have features not only of fibroblasts but of both fibroblasts and smooth muscle cells, so-called myofibroblasts.
• Depending upon the anatomic locations and the age group affected, fibromatoses are broadly grouped as under:

1. 1. Infantile or juvenile fibromatoses These include fibrous hamartoma of infancy, fibromatosis colli, diffuse infantile fibromatosis, juvenile aponeurotic fibroma, juvenile nasopharyngeal angiofibroma and congenital (generalised and solitary) fibromatosis.
   2.  Adult type of fibromatoses These are: palmar (Dupuytren-like contractures) and plantar fibromatosis, irradiation fibromatosis, penile fibromatosis (Peyronie’s disease), abdominal and extra-abdominal desmoid fibromatosis, and retroperitoneal fibromatosis.

These are further categorised into superficial or deep-seated. One common example of superficial (plantar and palmar fibromatosis) and deep-seated (desmoid type fibromatosis) are described below.

Superficial (Palmar/Plantar) Fibromatosis:

These fibromatoses are the most common form of fibromatoses occurring superficially.

• Palmar fibromatosis is more common in elderly males occurring in the palmar fascia
  and leading to flexion contractures of the fingers (Dupuytren’s contracture). It appears as a
  painless, nodular or irregular, infiltrating, benign fibrous subcutaneous lesion. In almost half the cases, the lesions are bilateral.
• Plantar fibromatosis is a similar lesion occurring on the medial aspect of the plantar arch. However, plantar lesions are less common than the palmar type and do not cause contractures as frequently as palmar lesions.

They are seen more often in adults and are infrequently multiple and bilateral. Essentially similar lesions occur in the shaft of the penis (penile fibromatosis or Peyronie’s disease) and in the soft tissues of the knuckles (knuckle pads).

Histologically, palmar and plantar fibromatoses have a similar appearance. The nodules are composed of fibrovascular tissue having plump, tightly-packed fibroblasts which have high mitotic rates. Ultrastructurally, some of the fibroblasts have features of myofibroblasts having contractile nature. The palmar lesions frequently extend into soft tissues causing contractures.

Both palmar and plantar lesions may remain stationary at the nodular stage, progress, or regress spontaneously. The recurrence rate after surgical excision in both forms is as high as 50-60%.

Deep-seated (Desmoid Type) Fibromatosis:

• Desmoid fibromatoses or musculo-aponeurotic fibromatoses, commonly referred to as desmoid tumours, are of 2 types: abdominal and extra-abdominal. Both types are, however, histologically similar.
• Clinically, both types behave aggressively and have to be distinguished from sarcomas. Recurrences are frequent and multiple.
• The pathogenesis of these lesions is not known but among the factors implicated are the role of antecedent trauma, genetic influences and relationship to oestrogen as observed by the occurrence of these lesions in pregnancy.
  • Abdominal desmoids are locally aggressive infiltrating tumour-like fibroblastic growths, often found in the musculoaponeurotic structures of the rectus muscle in the anterior abdominal wall in women during or after pregnancy.
  • Extra-abdominal desmoids, on the other hand, are more common in men and are widely distributed such as in the upper and lower extremities, chest wall, back, buttocks, and head and neck region.

• • Intra-abdominal desmoids present at the root of the small bowel mesentery are associated with Gardner’s syndrome (consisting of fibromatosis, familial intestinal polyposis, osteomas and epidermal cysts).

Grossly, desmoids are solitary, large, grey-white, firm and unencapsulated tumours infiltrating the muscle locally. The Cut surface is whorled and trabeculated.

Microscopically, their appearance is rather misleadingly bland in contrast with aggressive local behaviour. They are composed of uniform-looking fibroblasts arranged in bands and fascicles. Pleomorphism and mitoses are infrequent. The older regions of the tumour have hypocellular hyalinised collagen.

Dermatofibrosarcoma Protuberans:

Dermatofibrosarcoma protuberans has been reclassified from fibrohistiocytic group to the fibroblastic group due to its common genetic change (chromosomal rearrangement of chromosomes 17 and 22) in favour of the fibroblastic genotype. It is a low-grade malignant tumour of the intermediate category that recurs locally, and in rare instances gives rise to distant metastases. The most frequent location is the skin of the trunk.

Grossly, the tumour forms firm, solitary or multiple, satellite nodules extending into the subcutaneous fat and having thin and ulcerated skin surface.

Histologically, the tumour is highly cellular and is composed of fibroblasts arranged in bundles. The tumour cells have mild to moderate atypia.

Fibrosarcoma:

The number of soft tissue tumours diagnosed as fibrosarcoma has now dropped, partly because of the reclassification of fibromatoses which have aggressive and recurrent behaviour, and partly due to the reclassification of sarcomas into newer entities.

Fibrosarcoma is a slow-growing tumour, affecting adults between 4th and 7th decades of life. The most common locations are the lower extremity (especially thigh and around the knee), upper extremity, trunk, head and neck, and retroperitoneum. The tumour is capable of metastasis, chiefly via the bloodstream.

Grossly, fibrosarcoma is a grey-white, firm, lobulated and characteristically circumscribed mass. The cut surface of the tumour is soft, fish flesh-like, with foci of necrosis and haemorrhages.

Histologically, the tumour is composed of uniform, spindle-shaped fibroblasts arranged in intersecting fascicles. In well-differentiated tumours, such areas produce a ‘herring-bone pattern’ (herring-bone is a sea fish). Poorly-differentiated fibrosarcoma, however, has a highly pleomorphic appearance with frequent mitoses and bizarre cells.

Fibroblastic and Myofibroblastic Tumours:

• True fibromas are uncommon benign tumours in fibrous tissues. Examples are fibroma durum, fibrolipoma and elastofibroma.
• Nodular fasciitis is a common lesion in fascia and subcutis that may superficially resemble pseudosarcoma.
• Myositis ossificans is a benign tumour consisting of osteoid and osseous tissue lying in proliferating fibrous tissue.
• A fibromatosis is a group of actively proliferating fibroblastic tissue that are locally aggressive tumours. Examples of superficial types are palmar (Dupuytren’s contracture) and plantar fibromatosis, and deep-seated desmoid fibromatosis.
• Dermatofibrosarcoma protuberans is a low-grade malignant soft tissue tumour, commonly in the skin that may rarely metastasise.
• Fibrosarcoma is the malignant counterpart which is generally a slow-growing tumour.

So-Called Fibrohistiocytic Tumours

The earlier prototype malignant tumour of this group, malignant fibrous histiocytoma (MFH), has been deleted from this group and has been reclassified in the current WHO classification under undifferentiated/unclassified sarcomas.

Thus, this group now has only benign tumours. As a group, these tumours are characterised by a cart-wheel or storiform pattern in which the spindle cells radiate outward from the central focus.

Benign Fibrous Histiocytomas:

Depending upon the location and predominant pattern, benign fibrous histiocytomas include a number of diverse entities such as dermatofibroma, sclerosing haemangioma, fibroxanthoma, xanthogranuloma, tenosynovial giant cell tumour (localised and diffuse-type giant cell tumour of the tendon sheath and pigmented villonodular synovitis).

All these tumours have a mixed composition of benign fibroblastic and histiocytic patterns of cells and have been described in relevant chapters already.

So-Called Fibrohistiocytic Tumours:

• Fibrohistiocytic tumours are characterised by the presence of cells with fibroblastic and histiocytic features in varying proportions and the identification of characteristic cart-wheel or storiform patterns.
• Benign fibrous histiocytomas include dermatofibroma, sclerosing haemangioma, fibroxanthoma, xanthogranuloma, giant cell tumour of the tendon sheath and pigmented villonodular synovitis.
• Malignant fibrous histiocytoma has been reclassified and renamed under undifferentiated/unclassified sarcomas.

Tumours Of Uncertain Differentiation

This group includes a long list of soft tissue tumours, mostly malignant, which do not have a clearly known line of differentiation. Many of them have distinctive morphological features. Common examples are described below.

Synovial Sarcoma (Malignant Synovioma):

• Whether true benign tumours of synovial tissue exist is controversial. Pigmented villonodular synovitis and giant cell tumours of tendon sheaths, both of which are tumour-like lesions of synovial tissues have been discussed already.
• Synovial sarcoma or malignant synovioma, on the other hand, is a distinctive soft tissue sarcoma arising from synovial tissues close to the large joints, tendon sheaths, bursae and joint capsule but almost never arising within joint cavities.
• The most common locations are the extremities, frequently the lower extremity. However, synovial sarcoma is also found in regions where synovial tissue is not present such as in the anterior abdominal wall, para-pharyngeal region and the pelvis.
• The tumour principally occurs in young adults, usually under 40 years of age. The tumour grows slowly as a painful mass but may metastasise via the bloodstream, chiefly to the lungs.
• The histogenesis of tumours is uncertain but is possibly derived from multipotent mesenchymal cells which may differentiate along different cell lines.

Grossly, the tumour is of variable size and is grey-white, round to multilobulated and encapsulated. The cut surface shows a fish flesh-like sarcomatous appearance with foci of calcification, cystic spaces and areas of haemorrhages and necrosis.

Microscopically, classic synovial sarcoma shows a characteristic biphasic cellular pattern composed of clefts or gland-like structures lined by cuboidal to columnar epithelial-like cells and plump to oval spindle cells.

• Reticulin fibres are present around spindle cells but absent within the epithelial foci. The spindle cell areas form interlacing bands similar to those seen in fibrosarcoma. Myxoid matrix, calcification and hyalinisation are frequently present in the stroma.
• Mitoses and multinucleate giant cells are infrequent. Immunohistochemically, both types of tumour cells are positive for cytokeratin.
• An uncommon variant of synovial sarcoma is a monophasic pattern in which the epithelial component is exceedingly rare and thus the tumour may be difficult to distinguish from fibrosarcoma.

Translocation t(X;18)(p11;q11) and SS18-SSX1 fusion gene help in differentiating biphasic from the monophasic form of synovial sarcoma.

Epithelioid Sarcoma:

This soft tissue sarcoma occurring in young adults is peculiar in that it presents as an ulcer with sinuses, often located on the skin and subcutaneous tissues as a small swelling. The tumour is
slow-growing but metastasising.

Grossly, the tumour is somewhat circumscribed and has a nodular appearance with central necrosis.

Microscopically, the tumour cells comprising the nodules have an epithelioid appearance by having abundant pink cytoplasm and the centres of nodules show necrosis and thus can be mistaken for a granuloma.

Alveolar Soft Part Sarcoma:

Alveolar soft part sarcoma is a histologically distinct, slow-growing malignant tumour of uncertain histogenesis. The tumour may occur at any age but affects children and young adults more often. Most alveolar soft part sarcomas occur in the deep tissues of the extremities, along the musculofascial planes, or within the skeletal muscles.

Grossly, the tumour is well-demarcated, yellowish and firm.

Microscopically, the tumour shows a characteristic alveolar pattern. Organoid masses of tumour cells are separated by fibrovascular septa. The tumour cells are large and regular and contain abundant, eosinophilic, granular cytoplasm which contains diastase-resistant PAS-positive material. This feature distinguishes the tumour from paraganglioma, which it closely resembles.

Translocation t(X;17)(p11;q25) and genetic abnormality TFE3-ASPL fusion gene are seen in a large proportion of cases and are helpful in confirming the diagnosis.

Clear Cell Sarcoma:

Clear cell sarcoma, first described by Enginzer, is seen in skin and subcutaneous tissues, especially in hands and feet.

Microscopically, it closely resembles malignant melanoma and is therefore also called melanoma of the soft tissues.

Clear cell sarcoma can be further distinguished from cutaneous melanoma by translocation t(12;22)(q13;q12) and the EWSR1-ATF1 fusion gene.

Desmoplastic Small Round Cell Tumour:

Desmoplastic small round cell tumour (DSRCT) is a rare and highly malignant tumour occurring more commonly in male children and juveniles under 2nd decade of life. The cell of origin is not clear. Some of the common locations are the abdomen, para-testicular region, ovaries, parotid, brain and thorax.

Grossly, the tumour appears as multiple soft to firm masses.

Microscopically, characteristic small and round tumour cells have epithelial, mesenchymal and neural differentiation.

The tumour spreads rapidly to regional lymph nodes and other sites. DSRCT with translocation t(11;22)(p13;q12) and EWSR1-WT1 fusion gene have a particularly poor prognosis.

Rhabdoid Tumour:

This is a tumour of uncertain histogenesis that occurs as renal and extra-renal soft tissue tumours. It is more common in children and young adults.

Microscopically, the tumour cells are arranged as solid sheets. The tumour cells are large with abundant eosinophilic cytoplasm, large pleomorphic nuclei containing nucleoli, resembling skeletal muscle cells and hence the name. Background may show myxoid change or hyalinised
stroma.

Rhabdoid tumour is a highly aggressive malignant tumour having early metastases to the lungs and liver.

Pecoma:

PEComa is a neoplasm with perivascular epithelioid cell differentiation but with unknown histogenesis. The tumour cells express myogenic (actin) and melanoma markers (HMB45). PEComa may occur at any age and may have varying biological behaviour ranging from benign to metastasising high-grade sarcoma.

Tumours of Uncertain Differentiation

• Synovial sarcoma arises from synovial tissues close to the large joints, tendon sheaths, bursae and joint capsule. Classic synovial sarcoma shows a biphasic cellular pattern of cuboidal to columnar epithelial-like cells and plump to oval spindle cells.
• Epithelioid sarcoma presents with sinus or soft tissue nodules having the epithelioid appearance of tumour cells.
• Alveolar soft part sarcoma occurs in the deep tissues of the extremities, along the musculofascial planes, or within the skeletal muscles.
• Clear cell sarcoma occurring in the subcutaneous soft tissues has some similarities with cutaneous melanoma.
• Desmoplastic small round cell tumour is a rare and highly malignant tumour occurring in male children and juveniles, most often in the abdomen.
• Rhabdoid tumour is a renal and extrarenal highly malignant tumour.
• PEComa is a tumour having perivascular epithelioid cell differentiation. Its behaviour may be benign or high-grade sarcoma.

Undifferentiated/Unclassified Sarcomas

This is a new group of malignant soft tissue tumours in the WHO classification which includes
those sarcomas which cannot be classified into any of the other categories. The common example is discussed below.

Undifferentiated/Unclassified Sarcomas (Previously: Malignant Fibrous Histiocytoma, Mfh):

• This group was previously included under fibrohistiocytic tumours. Thus, variations in morphologic patterns of MFH are reclassified in this group as undifferentiated sarcomas of spindle cell, pleomorphic, round cell, and epithelioid cell type.
• The overall incidence of the undifferentiated/unclassified group is ~20% of all soft tissue sarcomas, out of which about a quarter of cases are radiation-associated sarcomas.
• These sarcomas occur more commonly in males and more frequently in the age group of the 5th to 7th decades. The most common locations are the lower and upper extremities and retroperitoneum. It begins as a painless, enlarging mass, generally in relation to skeletal muscle, deep fascia or subcutaneous tissue.

Grossly, the tumour is a multilobulated, well-circumscribed, firm or fleshy mass, 5-10 cm in diameter. The Cut surface is grey-white, soft and myxoid.

Histologically, there is marked variation in appearance from area to area within the same tumour. Accordingly, spindle cell, pleomorphic, round cell, and epithelioid cell types of undifferentiated/unclassified sarcoma have been categorised:

1. In general, there is the admixture of spindle-shaped fibroblast-like cells and mononuclear round to oval histiocyte-like cells which may show phagocytic function.
2. There is a tendency for the spindle-shaped cells to be arranged in a characteristic cart-wheeler storiform pattern.
3. The tumour cells show varying degrees of pleomorphism, hyperchromatism, mitotic activity and the presence of multinucleate bizarre tumour giant cells.
4. Usually, there are numerous blood vessels and some scattered lymphocytes and plasma cells.

Important immunohistochemical markers include vimentin, α-chymotrypsin, CD68 and factor VIII-a.

The prognosis of undifferentiated/unclassified sarcoma is determined by 2 parameters:

• depth of location, and
• size of the tumour.

Deep-seated and large tumours such as in the retroperitoneum have poorer prognosis than those small in size and located superficially which come to attention earlier. Metastases are frequent, most often in the lungs and regional lymph nodes. The five-year survival rate is approximately 30-50%.

Undifferentiated/Unclassified Sarcomas:

• This is a group of sarcomas which cannot be classified into any of the other categories.
• They were previously included under fibrohistiocytic tumours having cells with fibroblastic and histiocytic features in varying proportion and identification of characteristic cart-wheel or storiform patterns.
• Undifferentiated sarcomas may have various morphologic patterns: spindle cell, pleomorphic, round cell and epithelioid type.
• These tumours comprise about 20% of all soft tissue sarcomas and a quarter of these cases are radiation-associated.
• Their prognosis depends upon the depth of location and size of the tumour. Generally, these tumours have a poor prognosis.