Difference between revisions of "Soft tissue lesions"

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==Clear cell sarcoma==
==Clear cell sarcoma==
*Known among pathologists as "soft-tissue melanoma" and "melanoma of the soft parts", as it has a strong morphological resemblance.<ref name=pmid18300804>{{cite journal |author=Hisaoka M, Ishida T, Kuo TT, ''et al.'' |title=Clear cell sarcoma of soft tissue: a clinicopathologic, immunohistochemical, and molecular analysis of 33 cases |journal=Am. J. Surg. Pathol. |volume=32 |issue=3 |pages=452–60 |year=2008 |month=March |pmid=18300804 |doi=10.1097/PAS.0b013e31814b18fb |url=}}</ref>
{{Main|Clear cell sarcoma}}
*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.<ref name=pmid17227118>{{Cite journal  | last1 = Dim | first1 = DC. | last2 = Cooley | first2 = LD. | last3 = Miranda | first3 = RN. | title = Clear cell sarcoma of tendons and aponeuroses: a review. | journal = Arch Pathol Lab Med | volume = 131 | issue = 1 | pages = 152-6 | month = Jan | year = 2007 | doi = 10.1043/1543-2165(2007)131[152:CCSOTA]2.0.CO;2 | PMID = 17227118 }}</ref>
*Guarded prognosis.
*First described in 1965.<ref>URL: [http://www.informaworld.com/smpp/723576818-750600/ftinterface~db=all~content=a789166263~fulltext=713240928 http://www.informaworld.com/smpp/723576818-750600/ftinterface~db=all~content=a789166263~fulltext=713240928]. Accessed on: 5 May 2010.</ref>
 
===Microscopic===
Features:<ref name=pmid18300804/>
*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:
*[[Malignant melanoma]].
*[[PEComa]].
*Carcinoma.
 
====Images====
<gallery>
Image:Clear_cell_sarcoma_-_intermed_mag.jpg | Clear cell sarcoma - intermed. mag. (WC)
Image:Clear_cell_sarcoma_-_very_high_mag.jpg | Clear cell sarcoma - very high mag. (WC)
Image:Clear_cell_sarcoma.Image12.jpg | Clear cell sarcoma (WC/Gardner)
</gallery>
===IHC===
Features:<ref name=pmid18300804/>
*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).<ref name=pmid18300804/>
**Fusion transcripts:
***EWSR1-ATF1.
****Same translocation in: ''[[myxoid liposarcoma]]'',<ref name=pmid21115923>{{Cite journal  | last1 = Suzuki | first1 = K. | last2 = Matsui | first2 = Y. | last3 = Endo | first3 = K. | last4 = Kubo | first4 = T. | last5 = Hasegawa | first5 = T. | last6 = Kimura | first6 = T. | last7 = Ohtani | first7 = O. | last8 = Yasui | first8 = N. | title = Myxoid liposarcoma with EWS-CHOP type 1 fusion gene. | journal = Anticancer Res | volume = 30 | issue = 11 | pages = 4679-83 | month = Nov | year = 2010 | doi =  | PMID = 21115923 }}</ref> and ''[[hyalinizing clear cell carcinoma]]''.
***EWSR1-CREB1 (GI tract associated).


==Synovial sarcoma==
==Synovial sarcoma==

Revision as of 05:14, 23 September 2013

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)
Storiform, AKA patternless pattern[5] whorled, cartwheel-like arrangement pleomorphic undifferentiated sarcoma, solitary fibrous tumour, dermatofibrosarcoma protuberans, dermatofibroma[6]
Patternless pattern. (WC)
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
Herring bone. (WC)
Fasicular the long axis of the (spindle) cells are perpendicular to one another in adjacent bundles of cells leiomyoma, leiomyosarcoma
Fasicular pattern. (WC)
Biphasic nests of cells and stroma synovial sarcoma, DSRCT, alveolar RMS
DSRCT. (WC)

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.

Note:

  • The first impression may be that it is granulomatous inflammation; however, the cytoplasm doesn't fit (it isn't bubbly and it isn't sheet-like), and the nuclei aren't quite right (few footprint shaped nuclei).

Images

www:

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.

Gross

  • Poorly circumscribed.
  • "Rubbery" or "gelatinous".

Location:

  • Vulva - classic location.

Clinical DDx:

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

www:

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.
  • Serum CA-125 may be useful for following clinically.[28]

Subclassification:[29]

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

Microscopic

Features:[30]

  • 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:[29]

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

DDx:

Images

www:

IHC

Features:[31]

  • INI1 (SMARCB1[32]) -ve.[33]
  • 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.[34]
  • CA-125 +ve.[28][35]

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.[36]

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

www:

Stains

  • PAS +ve (cytoplasmic) - considered the most useful.[37]
  • PASD +ve (cytoplasmic).

IHC

  • TFE3 +ve -- suggestive of characteristic translocation.

Molecular

  • t(X;17)(p11.2;q25).[38]

Note:

EM

  • Distinctive membrane-bound intracytoplasmic crystal lattice with ~5 nm fibres spaced 10 nm apart.[36]

Image:

Desmoplastic small round cell tumour

  • Abbreviated DSRCT.

General

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

Microscopic

Features:[39]

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

Notes:

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

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.

Images

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

Synovial sarcoma

Other

Granulocytic sarcoma

  • Common alternate terms: myeloid sarcoma, chloroma.
  • Other terms:[42] myeloblastoma, chloromyeloma, chloromyelosarcoma, granulocytic leukosarcoma, or myelosarcoma.

General

  • Soft tissue manifestation of acute myeloid leukemia.[42]

Microscopic

Features:

Note:

Images

www:

See also

References

  1. Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 601-3. ISBN 978-0781765275.
  2. Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 598-604. ISBN 978-0781765275.
  3. Skubitz KM, D'Adamo DR (November 2007). "Sarcoma". Mayo Clin. Proc. 82 (11): 1409–32. PMID 17976362. http://www.mayoclinicproceedings.com/content/82/11/1409.long.
  4. Fletcher CD, Fletcher JA, Dal Cin P, Ladanyi M, Woodruff JM (July 2001). "Diagnostic gold standard for soft tissue tumours: morphology or molecular genetics?". Histopathology 39 (1): 100–3. PMID 11454050.
  5. Mangano WE, Cagle PT, Churg A, Vollmer RT, Roggli VL (August 1998). "The diagnosis of desmoplastic malignant mesothelioma and its distinction from fibrous pleurisy: a histologic and immunohistochemical analysis of 31 cases including p53 immunostaining". Am. J. Clin. Pathol. 110 (2): 191–9. PMID 9704618.
  6. Meister P, Höhne N, Konrad E, Eder M (July 1979). "Fibrous histiocytoma: an analysis of the storiform pattern". Virchows Arch A Pathol Anat Histol 383 (1): 31–41. PMID 224569.
  7. 7.0 7.1 Guillou L, Coindre JM, Bonichon F, et al. (January 1997). "Comparative study of the National Cancer Institute and French Federation of Cancer Centers Sarcoma Group grading systems in a population of 410 adult patients with soft tissue sarcoma". J. Clin. Oncol. 15 (1): 350–62. PMID 8996162.
  8. 8.0 8.1 8.2 URL: http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/SoftTissue_11protocol.pdf. Accessed on: 12 April 2011.
  9. Costa J, Wesley RA, Glatstein E, Rosenberg SA (February 1984). "The grading of soft tissue sarcomas. Results of a clinicohistopathologic correlation in a series of 163 cases". Cancer 53 (3): 530–41. PMID 6692258.
  10. 10.0 10.1 Fong, Y.; Coit, DG.; Woodruff, JM.; Brennan, MF. (Jan 1993). "Lymph node metastasis from soft tissue sarcoma in adults. Analysis of data from a prospective database of 1772 sarcoma patients.". Ann Surg 217 (1): 72-7. PMC 1242736. PMID 8424704. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1242736/.
  11. URL: http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/SoftTissue_11protocol.pdf. Accessed on: 28 March 2012.
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  18. 18.0 18.1 Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 613. ISBN 978-0781765275.
  19. Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 602. ISBN 978-0781765275.
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