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

Main article: Molecular pathology
  • 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

Main article: Chromosomal 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, dermatofibroma[6] 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.[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

Main article: Adipocytic tumours

This category includes:

  • Lipoma.
  • Liposarcoma.
  • Hibernoma.

Smooth muscle tumours

Leiomyosarcoma

Main article: Leiomyosarcoma

Microscopy

Features:

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.

Microscopic

Features:[11]

  • 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:[12]

  • 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:[13][14]

  • 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:[15]

  • 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).[16]

Desmoid-type fibromatosis

  • AKA desmoid tumour.

General

Microscopic

Features:[18]

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

IHC

Features:[18]

  • 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 (?).[18]
  • May be benign or malignant; more commonly benign.[19][20]

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 (?).[18]
  • 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.[21]
  • Oncogenic osteomalacia - assoc. with hemangiopericytoma.[22]

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.[23]

Location

  • Usually extremities - femur or prox. tibial.[24]

Histology

Features:[25]

  • Hypervascular lesion - key diagnostic feature.[26]
    • 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:[18][26]

  • 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:[27]

  • EMA -ve.
  • S100 -ve.

DDx

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

Desmoplastic fibroblastoma

  • AKA collagenous fibroma.[28]
  • Benign lesion.
  • Classically found in shoulder region.

IHC

  • Beta-catenin -ve.[29]
    • Significance ???

Low-grade fibromyxoid sarcoma

  • AKA hyalinizing spindle cell tumour.

General

  • Deep soft tissue.

Microscopic

Features:[30]

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

Notes:

  • Few/absent mitoses.

Molecular pathology

t(7;16)(q33;p11)[31]

Perivascular tumours

This grouping includes only two:[32]

Vascular lesions

Main article: Vascular lesions

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

They include:

Skeletal muscle tumours

Rhabdomyoma

Main article: Rhabdomyoma

Rhabdomyosarcoma

  • Abbreviated RMS.
Main article: Rhabdomyosarcoma

Comes it two main flavours:

  • Alveolar rhabdomyosarcoma.
  • Embryonal rhabdomyosarcoma.

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

Chondro-osseous tumours

Main article: Chondro-osseous tumours

This grouping includes tumours derived from cartilage and bone.

Tumours of uncertain differentiation

Ewing sarcoma/PNET

Main article: Ewing sarcoma

Epithelioid sarcoma

General

  • Rare.
  • Adolescents, young adults.

Subclassification:[33]

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

Microscopic

Features:[34]

  • 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:[33]

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

DDx:

IHC

Features:[35]

  • INI1 (SMARCB1[36]) -ve.[37]
  • 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:[38]

  • 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).[39]

Desmoplastic small round cell tumour

  • Abbreviated DSRCT.

General

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

Microscopic

Features:[40]

  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.[43]
    • 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.[44]

Microscopy

Features:[43]

  • 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:[43]

  • 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).[43]
    • Fusion transcripts:
      • EWSR1-ATF1.
      • EWSR1-CREB1 (GI tract associated).

Synovial sarcoma

General

  • Does not arise from cartilage.[38]
    • Usually close to a joint.
  • Young adults or adolescents.

Microscopic

Comes in three (histologic) flavours:[38][45]

  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:[38]

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

Others:

Molecular pathology

Unique translocation:

  • t(X;18)(p11.2;q11.2).[48]

Other

Granulocytic sarcoma

  • AKA myeloid sarcoma, AKA chloroma.

General

  • Soft tissue manifestation of acute myeloid leukemia.

Microscopic

Features:

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. ↑ URL: http://sarcomahelp.org/learning_center/mfh.html. Accessed on: 8 April 2011.
  11. ↑ 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.
  12. ↑ Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 613-4. ISBN 978-0781765275.
  13. ↑ Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 606. ISBN 978-0781765275.
  14. ↑ de Feraudy S, Fletcher CD (September 2010). "Intradermal nodular fasciitis: a rare lesion analyzed in a series of 24 cases". Am. J. Surg. Pathol. 34 (9): 1377–81. doi:10.1097/PAS.0b013e3181ed7374. PMID 20716998.
  15. ↑ BD. 26 April 2011.
  16. ↑ Velagaleti GV, Tapper JK, Panova NE, Miettinen M, Gatalica Z (March 2003). "Cytogenetic findings in a case of nodular fasciitis of subclavicular region". Cancer Genet. Cytogenet. 141 (2): 160–3. PMID 12606136.
  17. ↑ URL: http://www.dtrf.org/dtrf_aboutdesmoids.htm. Accessed on: 15 April 2011.
  18. ↑ 18.0 18.1 18.2 18.3 18.4 Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 609. ISBN 978-0781765275.
  19. ↑ URL: http://www.pathconsultddx.com/pathCon/diagnosis?pii=S1559-8675%2806%2970528-9. Accessed on: 25 June 2010.
  20. ↑ URL: http://wjso.com/content/6/1/86. Accessed on: 25 June 2010.
  21. ↑ URL: http://emedicine.medscape.com/article/1255879-overview. Accessed on: 2 May 2010.
  22. ↑ URL: http://emedicine.medscape.com/article/1255879-overview. Accessed on: 2 May 2010.
  23. ↑ URL: http://emedicine.medscape.com/article/1255879-diagnosis. Accessed on: 2 May 2010.
  24. ↑ URL: http://emedicine.medscape.com/article/1255879-overview. Accessed on: 2 May 2010.
  25. ↑ URL: http://emedicine.medscape.com/article/1255879-diagnosis. Accessed on: 2 May 2010.
  26. ↑ 26.0 26.1 Enzinger & Weiss's Soft Tissue Tumors. 4th Ed. PP.1007-13. ISBN 0-323-01200-0.
  27. ↑ Croul, SE. 8 November 2010.
  28. ↑ Watanabe, H.; Ishida, Y.; Nagashima, K.; Makino, T.; Norisugi, O.; Shimizu, T. (Feb 2008). "Desmoplastic fibroblastoma (collagenous fibroma).". J Dermatol 35 (2): 93-7. doi:10.1111/j.1346-8138.2008.00421.x. PMID 18271804.
  29. ↑ Takahara, M.; Ichikawa, R.; Oda, Y.; Uchi, H.; Takeuchi, S.; Moroi, Y.; Kiryu, H.; Furue, M. (Oct 2008). "Desmoplastic fibroblastoma: a case presenting as a protruding nodule in the dermis.". J Cutan Pathol 35 Suppl 1: 70-3. doi:10.1111/j.1600-0560.2007.00964.x. PMID 18544056.
  30. ↑ Vernon SE, Bejarano PA (September 2006). "Low-grade fibromyxoid sarcoma: a brief review". Arch. Pathol. Lab. Med. 130 (9): 1358–60. PMID 16948525.
  31. ↑ Panagopoulos I, Storlazzi CT, Fletcher CD, et al. (July 2004). "The chimeric FUS/CREB3l2 gene is specific for low-grade fibromyxoid sarcoma". Genes Chromosomes Cancer 40 (3): 218–28. doi:10.1002/gcc.20037. PMID 15139001.
  32. ↑ 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.
  33. ↑ 33.0 33.1 Guillou L, Wadden C, Coindre JM, Krausz T, Fletcher CD (February 1997). ""Proximal-type" epithelioid sarcoma, a distinctive aggressive neoplasm showing rhabdoid features. Clinicopathologic, immunohistochemical, and ultrastructural study of a series". Am. J. Surg. Pathol. 21 (2): 130–46. PMID 9042279.
  34. ↑ The International Agency for Research on Cancer (Editors: Fletcher, C.D.M.; Unni, K. Krishnan; Mertens, F.) (2006). Pathology and Genetics of Tumours of Soft Tissue and Bone (IARC WHO Classification of Tumours) (3rd ed.). World Health Organization. pp. 205. ISBN 978-9283224136.
  35. ↑ Miettinen M, Fanburg-Smith JC, Virolainen M, Shmookler BM, Fetsch JF (August 1999). "Epithelioid sarcoma: an immunohistochemical analysis of 112 classical and variant cases and a discussion of the differential diagnosis". Hum. Pathol. 30 (8): 934–42. PMID 10452506.
  36. ↑ Online 'Mendelian Inheritance in Man' (OMIM) 601607
  37. ↑ Mentzel T (March 2010). "[Epithelioid sarcoma: morphologic variants and differential diagnosis]" (in German). Pathologe 31 (2): 135–41. doi:10.1007/s00292-009-1250-0. PMID 19997734.
  38. ↑ 38.0 38.1 38.2 38.3 Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 627. ISBN 978-0781765275.
  39. ↑ Online 'Mendelian Inheritance in Man' (OMIM) 606243
  40. ↑ Pickhardt PJ, Fisher AJ, Balfe DM, Dehner LP, Huettner PC (March 1999). "Desmoplastic small round cell tumor of the abdomen: radiologic-histopathologic correlation". Radiology 210 (3): 633–8. PMID 10207460. http://radiology.rsna.org/content/210/3/633.full.
  41. ↑ Lee YS, Hsiao CH (October 2007). "Desmoplastic small round cell tumor: a clinicopathologic, immunohistochemical and molecular study of four patients". J. Formos. Med. Assoc. 106 (10): 854–60. doi:10.1016/S0929-6646(08)60051-0. PMID 17964965.
  42. ↑ Lal DR, Su WT, Wolden SL, Loh KC, Modak S, La Quaglia MP (January 2005). "Results of multimodal treatment for desmoplastic small round cell tumors". J. Pediatr. Surg. 40 (1): 251–5. doi:10.1016/j.jpedsurg.2004.09.046. PMID 15868593. http://www.dsrct.com/JPS%20Article.pdf.
  43. ↑ 43.0 43.1 43.2 43.3 Hisaoka M, Ishida T, Kuo TT, et al. (March 2008). "Clear cell sarcoma of soft tissue: a clinicopathologic, immunohistochemical, and molecular analysis of 33 cases". Am. J. Surg. Pathol. 32 (3): 452–60. doi:10.1097/PAS.0b013e31814b18fb. PMID 18300804.
  44. ↑ URL: http://www.informaworld.com/smpp/723576818-750600/ftinterface~db=all~content=a789166263~fulltext=713240928. Accessed on: 5 May 2010.
  45. ↑ Schaal CH, Navarro FC, Moraes Neto FA (2004). "Primary renal sarcoma with morphologic and immunohistochemical aspects compatible with synovial sarcoma". Int Braz J Urol 30 (3): 210–3. PMID 15689250. http://www.brazjurol.com.br/may_june_2004/Schaal_ing_210_213.htm.
  46. ↑ 46.0 46.1 Horvai AE, Kramer MJ, O'Donnell R (June 2006). "Beta-catenin nuclear expression correlates with cyclin D1 expression in primary and metastatic synovial sarcoma: a tissue microarray study". Arch. Pathol. Lab. Med. 130 (6): 792–8. PMID 16740029.
  47. ↑ Ng TL, Gown AM, Barry TS, et al. (January 2005). "Nuclear beta-catenin in mesenchymal tumors". Mod. Pathol. 18 (1): 68–74. doi:10.1038/modpathol.3800272. PMID 15375433.
  48. ↑ URL: http://www.ncbi.nlm.nih.gov/omim/300813. Accessed on: 30 May 2010.
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