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. Malignant soft tissue lesions, i.e. cancerous soft tissue lesions, are usually sarcomas. Sarcomas are malignancies derived from mesenchymal tissue.

Introduction

WHO classification of soft tissue lesions/tumours

Morphologic grouping

These include:[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

These include:[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

Morphohistologic 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

  • Formally known as the grading system from the French Federation of Cancer Centres Sarcoma Group (FNCLCC).

Overview

Components - 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]

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.

Stage

Lymph node metastases in sarcomas

Sarcomas more likely to be found in the lymph nodes - mnemonic RACE For MS:[12]

DDx by history/site

Retroperiteum

  1. Liposarcoma.
  2. Undifferentiated pleomorphic sarcoma.
  3. Leiomyosarcoma.
  4. MPNST.

Note: Synovial sarcoma and fibrosarcoma are very rare in the retroperitoneum.

Young person - extremity sarcoma

  1. Epithelioid sarcoma.
  2. Synovial sarcoma.

Gross characteristics

  • Usually non-specific.
  • Most sarcomas have a pushing border.
    • If there is an infiltrative border think: (1) fibromatosis, (2) carcinoma.

Adipocytic tumours

This category includes:

  • Lipoma.
  • Liposarcoma.
  • Hibernoma.

Smooth muscle tumours

IHC markers: desmin, SMA, H-caldemsin (most specific).

Leiomyosarcoma

Microscopic

Features (summary):

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

Fibrohistiocytic tumours

Fibrohistiocytic refers (only) to the histomorphologic appearance and therefore may be written in quotation marks; these tumours are not derived from histiocytes (or tissue macrophages), as the name implies.[13]

Pleomorphic undifferentiated sarcoma

  • Abbreviated PUS.
  • AKA Undifferentiated pleomorphic sarcoma, abbreviated UPS.
  • Previously known as malignant fibrous histiocytoma, abbreviated MFH.[14]

General

  • Common sarcoma.
  • Usually deep tissue of the trunk and extremities.
  • A diagnosis of exclusion[15] / wastebasket for unclassifiable high grade sarcomas.

Microscopic

Features:[16]

  • 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.
  • Deep to skin - important.

Other findings:

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

Notes:

DDx:

Images:

Subclassification

Pleomorphic sarcoma (PS) is subclassified the following way:[17]

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

IHC

Exclusionary stains - should be negative:

  • AE1/AE3.
  • p63.
  • Myogenin.
  • S-100.
  • HMB-45.

Usually negative, may be positive:[18]

  • Desmin.
  • SMA.

Commonly positive:

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:[19]

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

Angiomatoid fibrous histiocytoma

General

  • Rarely metastasizes.
  • Children & young adults.

Microscopic

Features:[20]

  • Cystic spaces with blood - simulates a vascular neoplasm.[21]
  • Epithelioid to spindle cells
    • May have a histiocytic appearance.[22]
  • Inflammation.
    • Lymphoid cuff[23] - lymphocytes around periphery of lesion.
  • Hemorrhage.

Images:

IHC

Features:[20]

  • CD68 +ve.
  • CD57 +ve.
  • Desmin +ve.
  • Vimentin +ve.

Molecular

AFH has recurrent translocations:

  • t(12;16) FUS/ATF1.
  • t(12;22) EWS/ATF1.

Aggressive angiomyxoma

  • AKA deep aggressive angiomyxoma.

General

  • Classically a vulvar mass or (less commonly) a scrotal mass.
    • Case report of a thigh lesion.[24]
  • Benign - no metastatic potential.
  • "Aggressive" as it has a high recurrance.

Microscopic

Features:[25]

  1. Thick blood vessels that meld into the surrounding stroma - key feature.
  2. Myxoid stroma - key feature.
  3. Small stellate cell/spindle cells without significant nuclear atypia.

DDx:

Images:

IHC

Features:[25]

  • Desmin +ve.
  • Vimentin +ve.
  • ER +ve.
  • PR +ve.

Angiomyofibroblastoma

General

  • Uncommon.

Clinical DDx:

Microscopic

Features:[26]

  • Hypercellular zones and hypocellular edematous zones.
  • Small blood vessels (~20 micrometers) - no large blood vessels - key feature.
  • Myxoid stroma - key feature.
  • Small stellate cell/spindle cells without significant nuclear atypia.

DDx:

Images:

Extrarenal malignant rhabdoid tumour

General

Microscopic

Features:[27]

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

IHC

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

Ewing sarcoma/PNET

Epithelioid sarcoma

Sarcomas with an epithelioid morphology are covered in epithelioid sarcomas.

General

  • Rare.
  • Adolescents, young adults.

Subclassification:[28]

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

Microscopic

Features:[29]

  • 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:[28]

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

DDx:

Images:

IHC

Features:[30]

  • INI1 (SMARCB1[31]) -ve.[32]
  • 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).
  • CK7 +ve / CK20 -ve.[33]

Alveolar soft part sarcoma

  • Abbreviated ASPS.

General

  • Adolescents/young adults.
  • Children -- classically location: base of tongue and orbit.
  • Typical indolent initially - ultimately a poor prognosis.[34]

Microscopic

Features:[27]

  • 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.

DDx:

Images:

Stains

  • PAS +ve (cytoplasmic) - considered the most useful.[35]
  • PASD +ve (cytoplasmic).

IHC

  • TFE3 +ve -- suggestive of characteristic translocation.

Molecular

  • t(X;17)(p11.2;q25).[36]

Note:

EM

  • Distinctive membrane-bound intracytoplasmic crystal lattice with ~5 nm fibres spaced 10 nm apart.[34]

Image:

Desmoplastic small round cell tumour

  • Abbreviated DSRCT.

General

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

Microscopic

Features:[37]

  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.[40]
  • Not to be confused with clear cell sarcoma of the kidney.

General

  • Molecular changes and origin distinct from malignant melanoma.
  • Incidence: rare soft tissue tumour.

Clinical

  • Usually - deep soft tissue or extremities.
    • Classically associated with tendons and aponeuroses.[41]
  • Guarded prognosis.
  • First described in 1965.[42]

Microscopic

Features:[40]

  • Architecture: sheeting or fascicular (bundles) arrangement.
    • Fibrous septae - between tumour cells.
  • Tumour cells uniform (low pleomorphism) - spindle-shaped or epithelioid:
    • Classically have clear cytoplasm.
    • Prominent nucleoli - basophilic - key feature.
    • +/-Binucleation.

DDx:

Images:

IHC

Features:[40]

  • 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

Synovial sarcoma

  • Abbreviated SS.

General

  • Does not arise from cartilage.[27]
  • Young adults or adolescents.
    • Classic age: 30s.
  • Poor prognosis.

Clinical:[44]

  • Present with soft palpable mass - slow growing - often for years.
  • May present with pain.
    • Uncommon finding in sarcomas.

Gross

Location:

  • Usually close to a joint.
  • Usually distal extremity ~65% of cases.[44]
    • Upper extremity ~20% of cases.[44]

Appearance - often non-specific:

  • Solid often lobulated +/- cystic component.
  • Grey-yellow.
  • Pushing border to ill-defined border.

Images:

Microscopic

Comes in three (histologic) flavours:[27][46]

  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:

  • Herring bone or vesicular pattern - key feature.
  • Spindle cells.
  • +/-Glandular component - typically more pink.
  • +/-Calcification - uncommon.
    • Extensive calcification = better prognosis.[47]

DDx:

Images:

IHC

Features:[27]

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

Others:

  • Beta-catenin +ve ~30-70%.[48]
  • Cyclin D1 ~50%.[48][49]
  • TLE1 +ve nuclear staining; not specific for synovial sarcoma.[50][51]

Typically negative:[52]

  • CD34.
  • S100 ~30% +ve.
  • SMA.

Notes:

  • Synovial sarcoma & MPNST:
    • Both +ve: PGP9.5 (UCHL1[53]), S100, NGFR, CD56, CD99, vimentin.
    • Synovial +ve: EMA, keratin, BCL2, TLE1.
    • MPNST +ve: nestin, CD34.

Trivia:

  • PGP in PGP9.5 = protein gene product.[54]

EM

Features:[55]

  • Biphasic tumour have biphasic ultrastructural features (unlike spindle cell carcinoma and epithelioid sarcoma).
  • Epithelioid component is adenocarcinoma-like - they have:
  • Spindle cell component - mostly features less.
    • Poorly formed desmosomes.
    • No intermediate filaments, no myofilaments.

Molecular pathology

Associated translocation:

  • t(X;18)(p11.2;q11.2).[56]
    • SYT/SSX fusion gene.

Several SSX genes - cannot be differentiated with standard karyotyping:

  • SSX1.
  • SSX2 - better survival, rarely seen in biphasic tumours.[57]
  • SSX4 - uncommon.

Notes:

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

Other

Granulocytic sarcoma

  • Common alternate terms: myeloid sarcoma, chloroma.
  • Other terms:[58] myeloblastoma, chloromyeloma, chloromyelosarcoma, granulocytic leukosarcoma, or myelosarcoma.

General

  • Soft tissue manifestation of acute myeloid leukemia.[58]

Microscopic

Features:

Note:

Images:

See also

References

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