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 Other
Storiform, AKA patternless pattern[5] whorled, cartwheel-like arrangement pleomorphic undifferentiated sarcoma, solitary fibrous tumour, dermatofibrosarcoma protuberans image ? 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 image ? other ?
Fasicular the long axis of the (spindle) cells are perpendicular to one another in adjacent bundles of cells leiomyoma image ? other ?
Biphasic nests of cells and stroma synovial sarcoma, DSRCT, alveolar RMS image ? other ?

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.[6]

French system

Overview:[6][7]

  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:[7]

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

A group of tumours is not graded:[7]

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..[8]

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

Microscopy

Features:

Fibrohistiocytic tumours

Pleomorphic undifferentiated sarcoma

  • Abbreviated PUS.
  • AKA Undifferentiated pleomorphic sarcoma.
  • Previously known as malignant fibrous histiocytoma, abbreviated MFH.[9]

General

  • Common sarcoma.
  • Usu. deep tissue of the trunk and extremities.

Microscopic

Features:[10]

  • 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:[11]

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

Fibroblastic/myofibroblastic tumours

Nodular fasciitis

General

  • Benign.
  • All age groups.
  • Associated with trauma.

Microscopic

Features:[12][13]

  • Usu. well-circumscribed.
  • Clusters of (non-pleomorphic) spindle cells.
  • Inflammation (lymphocytes).
  • Microcysts in cellular regions - uncommon - discriminatory.
  • Mitoses - common.
  • Extravasated RBCs.

The BD feature list:[14]

  • Tissue culture-like/CNS-like morphology.
  • Thick (keloid-like) collagen bundles - key feature.
  • Extravasated RBCs.
  • Inflammation.
  • +/-Giant cells.

Notes:

  • No significant nuclear atypia.
  • No atypical mitoses.
  • May be cellular.

Images:

IHC

Routine spindle cell panel:

  • CD34 -ve.
  • Desmin -ve..
  • SMA -ve.
  • S100 -ve.
  • AE1/AE3 -ve.

Others:

  • H-caldesmon -ve.
  • EMA -ve.
  • Vimentin +ve.

Molecular

  • Evolving - case reports.
    • t(15;15)(q13;q25).[15]

Desmoid-type fibromatosis

  • AKA desmoid tumour.

General

Microscopic

Features:[17]

  • Abundant fibroblasts.
    • Arranged in bundles or fascicles.
  • +/-Collagen.

IHC

Features:[17]

  • Beta-catenin +ve.
  • SMA +ve ~50% of lesions.

Proliferative fasciitis

  • Need to write something here.

Solitary fibrous tumour

General

  • Grouped with hemangiopericytoma in the WHO classification; possibly the same tumour (?).[17]
  • May be benign or malignant; more commonly benign.[18][19]

Microscopic

Features:

  • Well-circumscribed.
  • Fibroblast-like cells (spindle cells).
  • Hemangiopericytoma-like area (staghorn vessels) - not seen on image.
  • Keloid-like collagen bundles.

Images:

IHC

  • CD34 ~90% +ve.
  • CD99 ~70% +ve.
  • BCL2 ~50% +ve.

Hemangiopericytoma

General

  • Grouped with solitary fibrous tumour in the WHO classification; possibly the same tumour (?).[17]
  • Arises from the pericyte, a connective tissue cell of small vessels that is thought to be involved in flow regulation.
  • Hematologic spread most common - to lungs.[20]
  • Oncogenic osteomalacia - assoc. with hemangiopericytoma.[21]

Presentation

  • Usually painless mass, slow enlargement.

Radiology

  • Intramedullary lytic mass.
  • May be well-circumscribed.
  • +/-Periosteal reaction.
  • +/-Sclerotic border.

May be worked-up with angiography to distinguish from a vascular malformation.[22]

Location

  • Usually extremities - femur or prox. tibial.[23]

Histology

Features:[24]

  • Hypervascular lesion - key diagnostic feature.[25]
    • Abundant thin-walled branching small vessels of variable size.
      • May be described as "staghorn vessels" or "antler-like" vasculature.
      • Cells may "onion-skin" around thin blood vessels.
  • Spindle or ovoid shaped cells in nests or sheets.

IHC

Features:[17][25]

  • Vimentin +ve (usually).
  • Desmin -ve (typical).
  • Factor VIII -ve (marks endothelium).
  • CD34 +ve.
    • CD34 usu. -ve in synovial sarcoma.
  • CD31 -ve (marks benign endothelium).
  • vWF (von Willebrand factor) -ve.

May be in the DDx for meningioma:[26]

  • EMA -ve.
  • S100 -ve.

DDx

  • Other vascular tumours.
  • Vascular malformations.
  • Synovial sarcoma.

Desmoplastic fibroblastoma

  • AKA collagenous fibroma.[27]
  • Benign lesion.
  • Classically found in shoulder region.

IHC

  • Beta-catenin -ve.[28]
    • Significance ???

Low-grade fibromyxoid sarcoma

  • AKA hyalinizing spindle cell tumour.

General

  • Deep soft tissue.

Microscopic

Features:[29]

  • Myoid stroma - key feature.
  • Low cellularity.
  • Spindle cells.

Notes:

  • Few/absent mitoses.

Molecular pathology

t(7;16)(q33;p11)[30]

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

Epithelioid sarcoma

General

  • Rare.
  • Adolescents, young adults.

Microscopic

Features:[31]

  • Epithelioid morphology and spindle morphology.
  • Prominent nucleolus - key feature.
  • Zonal necrosis with irregular border.
    • Descriptors: "Garland necrosis", necrosis with "scalloped border" = necrotic regions with irregular border.

DDx:

Microscopic

Features:[32]

  • INI1 +ve.
  • 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:[33]

  • 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).[34]

Desmoplastic small round cell tumour

  • Abbreviated DSRCT.

General

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

Microscopic

Features:[35]

  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:

IHC

Features:

  • AE1/AE3 +ve.
  • Desmin +ve.
  • EMA +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.[38]
    • 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.[39]

Microscopy

Features:[38]

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

Image:

IHC

Features:[38]

  • 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).[38]
    • Fusion transcripts:
      • EWSR1-ATF1.
      • EWSR1-CREB1 (GI tract associated).

Synovial sarcoma

General

  • Does not arise from cartilage.[33]
    • Usually close to a joint.
  • Young adults or adolescents.

Microscopic

Comes in three (histologic) flavours:[33][40]

  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. Primative round cell type.

Images:

IHC

Features:[33]

  • Vimentin +ve + cytokeratin and/or EMA +ve.
  • CD99 +ve.

Others:

Molecular pathology

Unique translocation:

  • t(X;18)(p11.2;q11.2).[43]

Other

Granulocytic sarcoma

  • AKA myeloid sarcoma, AKA chloroma.

General

  • Soft tissue manifestation of acute myeloid leukemia.

Microscopic

Features:

See also

References

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