Soft tissue lesions

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Soft tissue lesions strike fear in many pathologists as they are uncommon and may be difficult to diagnose.

Introduction

WHO classification of soft tissue lesions/tumours

Morphologic grouping[1]

  1. Adipocytic tumours.
  2. Fibroblastic/myofibroblastic tumours.
  3. "Fibrohistiocytic" tumours.
  4. Smooth muscle tumours.
  5. Skeletal muscle tumours.
  6. Vascular tumours.
  7. Perivascular (pericytic) tumours.
  8. Chondro-osseous tumours.
  9. Tumours of uncertain differentiation.

Biologic potential grouping[2]

  1. Benign.
  2. Intermediate (locally aggressive).
  3. Intermediate (rarely metastasizing).
  4. Malignant.

Prevalence

  • All sarcomas are rare buggers.
    • As the classification has been changing over the past years (with more subtypes being recognized/identified) numbers are variable from study-to-study.
  • Once upon a time almost everything was called malignant fibrous histiocytoma; thus, it is listed as a common entity in some publications.

Most common:[3]

  • Liposarcoma.
  • Leiomyosarcoma.

Molecular testing

  • Molecular testing plays an important role in soft tissue pathology.
  • It is generally seen as an adjunct test that:[4]
    • Often is used to confirm the histomorphologic impression/quality control.
    • Frequently has some prognostic significance.
    • May directly affect treatment.

Translocations

Histologic patterns

Name Description DDx Image(s) Other
Storiform, AKA patternless pattern[5] whorled, cartwheel-like arrangement pleomorphic undifferentiated sarcoma, solitary fibrous tumour, dermatofibrosarcoma protuberans, dermatofibroma[6] intermed. mag., very high mag. other ?
Herring bone like herring bone (technique) for climbing a hill in cross country skiing; books on a shelf, where they have partially fallen over -- on the one shelf to the left and the one below to the right fibrosarcoma, synovial sarcoma, MPNST intermed. mag., high mag. other ?
Fasicular the long axis of the (spindle) cells are perpendicular to one another in adjacent bundles of cells leiomyoma, leiomyosarcoma intermed. mag., high mag. other ?
Biphasic nests of cells and stroma synovial sarcoma, DSRCT, alveolar RMS DSRCT - high mag. (WC) other ?

Notes:

  • Memory device: herring bone DDx MSF = MPNST, Synovial sarcoma, Fibrosarcoma.

Grading

  • Several systems exist.
  • The US-CAP advocates the use of the French system over the NCI system.
    • The French system is a better predictor metastases and mortality.[7]

French system

Overview:[7][8]

  1. Differentiation (score 1-3).
    • De facto, this is mostly the histologic type.
  2. Mitotic rate (score 1-3).
  3. Necrosis (score 0-2)

Obtaining a score:

  • Add all the points from the three components.

Scoring:

  • Grade 1 = 2-3.
  • Grade 2 = 4-5.
  • Grade 3 = 6-8.
Differentiation
  • Standardized for histologic types.
  • Most tumours = 3/3.

Exceptions:[8]

  • Well-differentiated liposarcoma = 1.
  • Myxoid liposarcoma = 2.
  • Conventional liposarcoma = 2.
  • Fibrosarcoma = 2.
  • Myxofibrosarcoma =2.

A group of tumours is not graded:[8]

Mitotic rate
  • 0-9 mitoses/10 HPF.
  • 10-19 mitoses/10 HPF.
  • >=20 mitoses/10 HPF.

Notes:

  • 1 HPF = 0.1734 mm^2.
    • Most resident microscopes have a field of view = 0.2376 mm^2.
      • Thus, ~7.3 HPFs on a resident microscope corresponds to 10 US-CAP HPFs.
Necrosis
  • None = score 0.
  • <=50% of tumour = score 1.
  • >50% of tumour = score 2.

System used by some at MSH

Some pathologists at MSH use the system advocated by Costa et al..[9]

Scoring

  • Grade 1 = 1 point.
  • Grade 2 = 2 points.
  • Grade 3 = 3-4 points.

Components

Points for each of the following:

  • Mitotic activity >= 6 / 10 HPF @ 40X - definition suffers from HPFitis.
  • Pleomorphism present.
  • Cellularity (cells/matrix) > 50%.
  • Necrosis >15% - microscopic (without targeting necrosis grossly) or grossly.

Adipocytic tumours

This category includes:

  • Lipoma.
  • Liposarcoma.
  • Hibernoma.

Smooth muscle tumours

Leiomyosarcoma

Microscopic

Features (summary):

  • Fasicular cellular spindle cell lesion with:
    • Nuclear atypia.
    • Necrosis.
    • High mitotic rate.

Fibrohistiocytic tumours

Pleomorphic undifferentiated sarcoma

  • Abbreviated PUS.
  • AKA Undifferentiated pleomorphic sarcoma.
  • Previously known as malignant fibrous histiocytoma, abbreviated MFH.[10]

General

  • Common sarcoma.
  • Usu. deep tissue of the trunk and extremities.
  • A diagnosis of exclusion[11] / wastebasket for unclassifiable high grade sarcomas.

Microscopic

Features:[12]

  • Storiform pattern (AKA patternless pattern) - key feature.
  • Marked nuclear pleomorphism key feature.
    • Variation is nuclear size, nuclear shape and nuclear staining (esp. hyperchromasia).
  • Mitoses - abundant; atypical mitoses common.
  • Necrosis (common).
  • Mix of spindle cells and epithelioid cells.

Other findings:

  • +/-Giant cells (see subclassification).
  • +/-Inflammation (see subclassification).
    • Neutrophils.
    • Eosinophils.

Image:

Subclassification

Pleomorphic sarcoma (PS) is subclassified the following way:[13]

  • PS with giant cells.
  • PS with inflammation.
  • PUS (not otherwise specified) - wastebasket diagnosis; if neither of the above two apply.

Fibroblastic/myofibroblastic tumours

This is a very large and important group of soft tissue lesions. It is covered in a separate article.

The grouping includes:

Perivascular tumours

This grouping includes only two:[14]

Vascular lesions

Vascular lesions are "too red"; they have too many RBCs.

They include:

Skeletal muscle tumours

Rhabdomyoma

Rhabdomyosarcoma

  • Abbreviated RMS.

Comes it two main flavours:

  • Alveolar rhabdomyosarcoma.
  • Embryonal rhabdomyosarcoma.

The histology may be that of a small round cell tumour.

Chondro-osseous tumours

This grouping includes tumours derived from cartilage and bone.

Tumours of uncertain differentiation

Extrarenal malignant rhabdoid tumour

  • Essentially identical to renal malignant rhabdoid tumour.[15]

General

Microscopic

Features:[15]

  • Variable architecture.
  • Round cells.
  • Eccentric vesicular nucleus.
  • Prominent nucleolus -- key feature.

IHC

  • INI1 (SMARCB1) -ve.
    • AKA BAF47.

Ewing sarcoma/PNET

Epithelioid sarcoma

General

  • Rare.
  • Adolescents, young adults.

Subclassification:[16]

  • Proximal type:
    • More aggressive.
  • Distal type:

Microscopic

Features:[17]

  • Epithelioid morphology and spindle morphology - which predominates is dependent on location (see subclassification).
  • +/-Prominent nucleolus - distinctive feature.
  • Zonal necrosis with irregular border.
    • Descriptors: "Garland necrosis", necrosis with "scalloped border" = necrotic regions with irregular border.

Subclassification:[16]

  • Proximal-type (proximal location):
    • More epithelioid.
  • Distal-type (distal location):
    • More spindled.
    • Granuloma-like pattern.

DDx:

IHC

Features:[18]

  • INI1 (SMARCB1[19]) -ve.[20]
  • Vimentin +ve.
  • Various keratins +ve.
    • Keratin 8, Keratin 19 +ve.
    • 34betaE12 +ve/-ve.
  • CD34 +ve.
    • Malignant rhabdoid tumour -ve.

Others:

  • S100 -ve (r/o melanoma).

Alveolar soft part sarcoma

  • Abbreviated ASPS.

General

  • Adolescents/young adults.
  • Children -- classically location: base of tongue and orbit.

Microscopic

Features:[15]

  • Arranged in nest/separated by thin septa; vaguely resembles alveoli (at low power).
  • Large cells (~30-50 μm) with abundant eosinophilic cytoplasm.
  • An eccentric nucleus.
  • +/-Nucleolus.

Images:

Molecular

  • t(X;17)(p11.2;q25).[21]

Desmoplastic small round cell tumour

  • Abbreviated DSRCT.

General

  • Males > females.
  • Usu. affects young adults.
  • Typically retroperitoneal.
  • Poor prognosis.

Microscopic

Features:[22]

  1. Broad bands of paucicellular fibrous stroma with:
  2. Small round cells in nests with an undulating sharp border.

Notes:

  • Usu. abundant mitoses.
  • +/-Necrosis.

Images:

DDx:

  • Metastatic germ cell tumour (DDx of location and age).
  • Embryonal RMS.
    • It should be noted that DSRCT, like embryonal RMS, is +ve for desmin!
  • Solid variant of alveolar RMS.
    • Nests in alveolar RMS have round edges.

IHC

Features:

  • AE1/AE3 +ve.
  • Desmin +ve.
  • EMA +ve.
  • Actin -ve.
  • WT1 (N-terminal) -ve.
  • WT1 (C-terminal) +ve.
  • CD57 +ve.

Molecular

Clear cell sarcoma

  • Known among pathologists as "soft-tissue melanoma" and "melanoma of the soft parts", as it has a strong morphological resemblance.[25]
    • Molecular changes and origin distinct from melanoma.
  • Incidence: rare soft tissue tumour.

Clinical

  • Usually - deep soft tissue or extremities.
  • Guarded prognosis.
  • First described in 1965.[26]

Microscopy

Features:[25]

  • Architecture: sheets or fascicular (bundles) arrangement.
  • Cells: Spindle cells or epithelioid cells.
  • Prominent nucleoli - basophilic - key feature.
  • Fibrous septae.
  • Uniform.
  • +/-Binucleation.

DDx:

Image:

IHC

Features:[25]

  • S100 +ve.
  • HMB-45 +ve.
  • Melan A (MART-1) +ve; sometimes -ve.
  • BCL2 +ve.
  • CD57 +ve (usually).

Keratins:

  • EMA may be +ve.
  • CAM5.2 -ve.
  • AE1/AE3 -ve.

Molecular studies

  • Chromosomal translocation t(12;22)(q13;q12).[25]
    • Fusion transcripts:
      • EWSR1-ATF1.
      • EWSR1-CREB1 (GI tract associated).

Synovial sarcoma

General

  • Does not arise from cartilage.[15]
    • Usually close to a joint.
    • Usually distal extremity.
  • Young adults or adolescents.
  • Poor prognosis.

Microscopic

Comes in three (histologic) flavours:[15][27]

  1. Spindle cell sarcoma with features of hemangiopericytoma, i.e. staghorn vessels.
  2. Biphasic synovial sarcoma:
    1. Spindle cells with features of hemangiopericytoma.
    2. Epitheliod glands or nests.
  3. Primitive round cell type.

Features:

DDx:

Images:

IHC

Features:[15]

  • Vimentin +ve.
  • EMA +ve.
  • BCL2 +ve.
  • CD99 +ve.

Others:

  • Beta-catenin +ve ~30-70%.[28]
  • Cyclin D1 ~50%.[28][29]
  • TLE1 +ve nuclear staining; not specific for synovial sarcoma.[30][31]

Notes:

  • Synovial sarcoma & MPNST:
    • Both +ve: PGP9.5 (UCHL1[32]), S100, NGFR, CD56, CD99, vimentin.
    • Synovial +ve: EMA, keratin, BCL2, TLE1.
    • MPNST +ve: nestin, CD34.

Trivia:

  • PGP in PGP9.5 = protein gene product.[33]

Molecular pathology

Associated translocation:

  • t(X;18)(p11.2;q11.2).[34]
    • SYT/SSX fusion gene.

Several SSX genes:

  • SSX1.
  • SSX2 - better survival
  • SSX4 - uncommon.

Notes:

  • At HSC t(X,18) = synovial sarcoma.

Other

Granulocytic sarcoma

  • Common alternate terms: myeloid sarcoma, chloroma.
  • Other terms:[35] myeloblastoma, chloromyeloma, chloromyelosarcoma, granulocytic leukosarcoma, or myelosarcoma.

General

  • Soft tissue manifestation of acute myeloid leukemia.[35]

Microscopic

Features:

Note:

Images:

See also

References

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