Chondro-osseous tumours

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Chondro-osseous tumours occasionally cross the desk of the pathologist. They are grouped together as bone may develop from cartilage.

Primary bone tumours are rare; the most common bone tumour is metastases.[1]

Bone tumours occasionally are lumped with soft tissue tumours. Soft tissue tumours are dealt with in the soft tissue lesions article. An introduction to bone is found in the bone article. An introduction to cartilage is found in the cartilage article.

General

  • Diagnosis of a primary bone tumour should not be made without radiologic & clinical information!
  • Metastasis:primary bone tumours = >20:1.[1]

Common malignant

Epidemiology:[2]

  • Osteosarcoma -> 2nd decade.
  • Ewing's ->5-20 yrs.
  • Chondrosarcoma -> from enchondroma or osteochrondroma -- patients over 40 yrs.
  • Multiple myeloma -> most common primary bone tumour in adults.

Malignant bone tumours by age

Most common by age:[3]

Benign aggressive bone tumours

  • Giant cell tumours.
  • Osteoblastoma.
    • Thought to be related to osteoid osteoma.
    • If in long bones often diaphyseal.

Ref.:[4][5]

Summary tables

Bone tumours

Entity Key feature Other features Radiology / gross Clinical Stains / other Image
Osteoma normal bone (???) other features (???) radiology / gross (???) ? no stains / may be assoc. with FAP Image (???)
Osteoid osteoma osteoblastic rimming anastomosing bony trabeculae <= 1.5 cm painful, NSAIDs remove pain, young IHC / other low mag., high mag.
Osteoblastoma osteoblastic rimming anastomosing bony trabeculae > 1.5 cm not painful IHC / other low mag., high mag.
Ewing sarcoma small round blue cell tumour cytoplasmic clearing (due to glycogen) Radiology / gross pediatric PAS+, PASD- intermed. mag., high mag. - PAS
Osteosarcoma osteoid Other features Radiology / gross Clinical no stains; many subtypes very high mag.
Giant cell tumour of bone abundant giant cells nuclei of surrounding cells similar to those in giant cells Radiology / gross Clinical IHC / other high mag.

Cartilage tumours

Entity Key feature Other features Radiology / gross Clinical Stains / other Image
Chondroma ctyologically benign cells equally spaced nests Radiology / gross benign / DDx: chondroma, well-diff. chondrosarcoma IHC / bone marrow cavity chondroma = enchondroma very high mag.
Chondroblastoma abundant extracellular material, abundant eosinophilic cytoplasm calcifications surround cells nests ("chickenwire" appearance) - classic Radiology / gross DDx: giant cell tumour of bone S100+ve, vimentin +ve very high mag.
Chondrosarcoma cartilaginous appearance +/- nuclear atypia Other features Radiology / gross Clinical IHC / may be histologically benign looking high mag.

Other

Entity Key feature Other features Radiology / gross Clinical Stains / other Image
Osteochondroma Key feature Other features Radiology / gross Clinical IHC / other Image
Adamantinoma bisphasic - stroma & epithelium Other features Radiology / gross Clinical IHC / other Image
Diffuse tenosynovial giant-cell tumour (AKA PVNS) pigmented giant cells nodules Radiology / gross Clinical IHC / other Image
Brown tumour Key feature Other features Radiology / gross due to hypercalcemia; not a neoplasm IHC / other Image

Cartilage

Chondroma

General

  • Benign thingy.
  • Usual legs and feet.
  • May be difficult to separate from chondrosarcoma.
  • Multiple chondromas = enchondromatosis; three distinct syndromes.[6]
  • Enchondroma = chondroma in the marrow space.

Clinical:[6]

  • Pain.

Radiology

Features:[6]

  • Lytic lesion.
  • Usual close to a growth plate.

Microscopic

Features:

  • Ctyologically benign cells is spaced nests.

Images:

Chondroblastoma

General

  • Growth plate lesion.
  • Sclerotic margin.
  • "Young" = growth plates open.
  • Typically painful.[7]

Gross

  • Well-defined lesion.

Image:

Microscopic

Features:[8]

  • Abundant extracellular material - pink on H&E stain - looks vaguely like cartilage.
  • Chondroblasts:
    • Nuclear morphology variable: ovoid, folded or grooved.
    • Moderate-abundant eosinophilic cytoplasm.
  • +/-Calcification surrounds the cell nests ("chickenwire" appearance) - classic feature.
    • Cell nests have a thin pale blue rimming.
  • +/-Giant cells.

DDx:

Images:

IHC

Features:[8]

  • S100 +ve.
  • Vimentin +ve.[9]

Chondrosarcoma

General

  • Usually a good prognosis.

Clinical/epidemiologic features:[11]

  • Usually arise in a (benign) abnormality of cartilage (e.g. osteochondroma, enchondroma).
  • May be associated with a syndrome:
    • Olier disease (multiple enchondromatosis).
    • Maffucci syndrome (multiple enchondromas and hemangiomas).

Notes:

  • Review article (from oncology perspective): PMID 17545802.

Subtypes

Several subtypes exist:

  • Chondrosarcoma not otherwise specified (NOS).
  • Juxtacortical chondrosarcoma.
  • Myxoid chondrosarcoma.
  • Mesenchymal chondrosarcoma.
  • Clear cell chondrosarcoma.
  • Dedifferentiated chondrosarcoma.

Microscopic

Features:[12][13]

  • "Abnormal cartilage":
    • +/-Nuclear atypia - high grade lesions.
      • High grade lesions:
        • Nuclear clearing.
        • Nucleoli.
        • Hyperchromasia.
      • Low/intermediate grade lesions:
        • Bi-nucleation.
        • Hypochromatic enlarged nuclei.
        • Infiltration of lamellar bone ("invasion") - not common - diagnostic.
    • Increased cellularity.
      • More cellular than cartilage... but relatively paucicellular compared to other sarcomas.
    • Irregular spacing of chondrocytes.

Notes:

  • Low grade chondrosarcoma are not cytologically malignant; the diagnosis rests mostly on radiologic findings.
    • The exception is infiltration of lamellar bone -- this is diagnostic of chondrosarcoma.[14]

DDx:

Images:

Variants

Mesenchymal chondrosarcoma
  • Arise in soft tissue; this is where the name comes from.[15]
  • Rare variant of chondrosarcoma.

Microscopic: Features:

  • "White clouds in a blue sky".

Image:

Myxoid chondrosarcoma

Microscopic: Features:

  • Chordoma-like:
    • Myxoid background.
    • Small cells with eosinophilic cytoplasm.

DDx:

Extraskeletal myxoid chondrosarcoma
  • Originally thought to be a variant of myxoid chondrosarcoma of bone; however, may not be a chondrosarcoma at all.[17]
  • Characteristic chromosomal translocation: t(9;22) CHN-EWS.

DDx:

  • Chordoma.[17]
    • S-100 +ve (strong).
    • EMA +ve.

Image:

Dedifferentiated chondrosarcoma

Clinical:

  • Abysmal to poor prognosis.
    • In one series (22 patients) 5-year survival ~20%.[19]
    • All dead in two years in another series (25 patients).[20]

Features:[20]

  1. Poorly differentiated (mesenchymal) malignancy.
  2. Well-differentiated cartilaginous component.

Images:

Grading

Features:[21]

  • Grade I: mild-to-moderate increase of cellularity +/- binucleated cells.
  • Grade II: between Grade I and Grade III.
  • Grade III: nuclear pleomorphism, mitoses common.

IHC

  • S-100 -ve. (???)

Bone

Osteoma

General

Microscopic

Features:

  • Normal bone.

Osteoid osteoma

General

  • Benign bone lesion.

Clinical:[22]

  • Extremely painful.
    • Relieved by NSAIDS.

Microscopic

Features:[22]

  • Anastomosing bony trabeculae with:
    • Variable mineralization.
      • Mineralization (calcium phosphate) = purple on H&E stain.
    • Osteoblasts rimming.
      • Cells line-up at edge of bone.

Note:

Images:

Osteoblastoma

General

  • Benign bone tumour.

Microscopic

Features:[22]

  • Anastomosing bony trabeculae with:
    • Osteoblasts rimming.
      • Cells line-up at edge of bone.

Notes:

  • Histomorphologically near identical/indistinguishable from osteoid osteoma.[23]
  • Must be greater 1.5 cm by definition.[23]

Images:

Ewing sarcoma

  • AKA EWS/pPNET, AKA (confusingly) EWS/PNET:
    • EWS = Ewing sarcoma.
    • pPNET = peripheral primitive neuroectodermal tumour.
  • EWS and pPNET were once thought to be different tumours.

Notes:

General

Clinical:

  • Painful.
  • Usually younger than 20 years.
  • Second most common malignant bone tumour in children.
    • Most common malignant bone tumour = osteosarcoma (AKA osteogenic sarcoma).

Poor prognostic factors:[24]

  • Age (18 years-old+).
  • Pelvis (extremity = good).
  • >8 cm.
  • Metastases.
  • EWS-FL1 fusion type 2.
  • >90% necrosis.

Etiology:

  • Unknown origin; hypothesis: Ewing sarcoma arises from mesenchymal stem cell.[25]

Radiology

Features:[26]

  • Long bones, diaphyses.
  • Destructive.
  • "Onion-skin" periosteal reaction.

Microscopic

Features:[27]

  • Scant clear cytoplasm (contain glycogen -- PAS +ve, PAS-D -ve) - key feature.
  • Round small nucleus.
    • Usu. lack nucleoli.
    • Usu. minimal-moderate size variation.
  • Mitoses (common).

Notes:

Images:

IHC

Features:[29]

  • CD99 +ve -- 1. diffuse, 2. plasma membrane staining; both required -- most specific.
  • FLI-1 +ve.[30]
  • CD45 -ve.
  • +/-Neural markers (NSE, synaptophysin, CD57 (??? CD56 ???), S100).
  • +/-Cytokeratins.
  • Caveolin-1 +ve in ~ 85% of EWS.[31]
  • WT-1 -ve.[32]

Notes:[33]

Molecular diagnostics

Common features:

  • EWS/FLI-1 fusion gene formation due to translocation: t(11;22)(q24;q12).[34][35]
    • Often detected by RT-PCR (with EWS 5' and FLI-1 3' primers).
    • Type 1 = EWS exon 7 + FLI-1 exon 6; good prognosis.
    • Type 2 = others; poor prognosis.

Notes:

  • The t(11;22)(q24;q12) is seen in ~90% of EWS/PNET... but also in:
  • Several other EWS translocations exist.[36]
    • ERG,[37] ETV1, E1AF and FEV.
  • Lack of molecular findings does not exclude Ewing sarcoma.
  • Testing:
    • A break apart probe for EWS is a common way to look for pathologic change, as it covers almost all variants.

Electron microscopy

  • Primitive cell junctions.
  • Clear zone (glycogen lakes).

Osteosarcoma

  • AKA osteogenic sarcoma.

General

Trivia:

  • Terry Fox was afflicited by this tumour.

Definition

  • Tumour that makes osteoid.
    • Osteoid = (extracellular) organic component of bone, normally produced by osteoblasts (cells which make bone matrix).

Microscopic

Features:

  • Cells with malignant features (e.g. nuclear membrane irregularities, marked nuclear size differences, mitoses) surrounded by delicate strands of osteoid.
    • Osteoid on H&E: pink, homogenous, "glassy".
    • Tumours typically very cellular - when compared to normal bone.
  • Large (multinucleated) osteoclast-like giant cells may be seen.[38]

Images:

Subtypes

  • Many subtypes exist.

Subclassification:[39][40]

Giant cell tumour of bone

General

Features:[43]

  • Approximately 5% of primary bone tumours.
  • Typical age: 20-45 years.

Clinical

  • Location: growth plate of long bones.[44]
    • May present with joint pain, immobility.

Note:

Microscopic

Features:[45]

  • Giant cells with a large number of nuclei (usu. >10 in the plane of section).
    • Usu. have prominent nucleoli.
  • Mononuclear cells and small multinucleated cells with nuclei similar to those in the giant cells - key feature.

Notes:

  • Giant cells typically present in abundance.

DDx:

Images:

IHC

  • p63 +ve in scattered mononuclear cells.[46]
    • This seems to be contradicted by another paper.[47]

Other

This section collects stuff that doesn't neatly fit into the bone or cartilage category.

Osteochondroma

General

  • Benign.
  • Usually metaphyseal lesions.
  • Very common.
  • Abnormal outgrowth of bone and cartilage.

Microscopic

Features:

  • Normal bone and cartilage.

Images:

Diffuse tenosynovial giant-cell tumour

  • AKA tenosynovial giant-cell tumour, diffuse type.
  • Previously known as pigmented villonodular synovitis (PVNS).[48]

General

  • Course: benign.
  • Giant cell tumor of the tendon sheath is considered to be the soft-tissue counterpart of PVNS.[49]

Microscopic

Features:[50]

  • Subsynovial nodules composed of cells with:
    • Abundant cytoplasm.
    • Pale nuclei.
  • Multinucleated giant cells.
  • Hemosiderin-laden macrophages.
  • Foam cells.

Images:

Adamantinoma

Should not be confused with adenomatoid tumour.

General

Features:[26]

  • Rare: < 1% of bone tumours.
  • 25-35 years old.
  • Tibia, fibula.
  • Benign, may be locally aggressive.
  • Cousin of ameloblastoma. (???)

Radiology

  • Intracortical, radiolucent.

Microscopic

Features:

  • Biphasic tumour:
    1. Fibrous/spindle cell component.
    2. Epithelial component.

Images:

DDx:[52]

IHC

Features:[52]

  • CK14 +ve (HMWK).[53]
  • CK19 +ve (LMWK).
  • CK8/18 -ve (LMWK).

Brown tumour

General

  • Not a true neoplasm,[54] i.e. the name is a misnomer.
    • May (clinically) mimic a true neoplasm.
  • Due to hyperparathyroidism - usually parathyroid adenoma.
    • Usually secondary to chronic renal failure.

Hypercalcemia DDx

Mnemonic GRIMED:[55]

Microscopic

Features:

  • Fibrosis.
  • +/-Giant cells with round to oval nuclei and nucleoli.[56]
  • Bone unaffected by tumour - increased numbers of the following:
    • Multinucleated cells (osteoclasts).
    • Mononuclear cells around the bony trabeculae (osteoblasts).


DDx:

Images:

See also

References

  1. ↑ 1.0 1.1 Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 632. ISBN 978-0781765275.
  2. ↑ TN05 OR42.
  3. ↑ TN05 OR42.
  4. ↑ TN05 OR41.
  5. ↑ URL: http://www.emedicine.com/RADIO/topic494.htm.
  6. ↑ 6.0 6.1 6.2 URL: http://emedicine.medscape.com/article/389224-overview. Accessed on: 25 December 2010.
  7. ↑ Mitchell, Richard; Kumar, Vinay; Fausto, Nelson; Abbas, Abul K.; Aster, Jon (2011). Pocket Companion to Robbins & Cotran Pathologic Basis of Disease (8th ed.). Elsevier Saunders. pp. 625. ISBN 978-1416054542.
  8. ↑ 8.0 8.1 Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 642. ISBN 978-0781765275.
  9. ↑ 9.0 9.1 9.2 URL: http://emedicine.medscape.com/article/1254949-diagnosis. Accessed on: 31 December 2010.
  10. ↑ URL: http://path.upmc.edu/cases/case494.html. Accessed on: 24 January 2012.
  11. ↑ 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.
  12. ↑ IAV. 26 February 2009.
  13. ↑ Klatt, Edward C. (2006). Robbins and Cotran Atlas of Pathology (1st ed.). Saunders. pp. 417. ISBN 978-1416002741.
  14. ↑ BD. 28 April 2011.
  15. ↑ Dowling EA (June 1964). "Mesenchymal chondrosarcoma". J Bone Joint Surg Am 46: 747–54. PMID 14161087. http://www.ejbjs.org/cgi/reprint/46/4/747.pdf.
  16. ↑ Fisher C (May 2000). "Parachordoma exists--but what is it?". Adv Anat Pathol 7 (3): 141–8. PMID 10809219.
  17. ↑ 17.0 17.1 Aigner, T.; Oliveira, AM.; Nascimento, AG. (Feb 2004). "Extraskeletal myxoid chondrosarcomas do not show a chondrocytic phenotype.". Mod Pathol 17 (2): 214-21. doi:10.1038/modpathol.3800036. PMID 14657948.
  18. ↑ URL: http://www.cttr.org/cms/?p=736. Accessed on: 1 May 2011.
  19. ↑ Mitchell, AD.; Ayoub, K.; Mangham, DC.; Grimer, RJ.; Carter, SR.; Tillman, RM. (Jan 2000). "Experience in the treatment of dedifferentiated chondrosarcoma.". J Bone Joint Surg Br 82 (1): 55-61. PMID 10697315.
  20. ↑ 20.0 20.1 Sopta, J.; Dordević, A.; Tulić, G.; Mijucić, V. (Feb 2008). "Dedifferentiated chondrosarcoma: our clinico-pathological experience and dilemmas in 25 cases.". J Cancer Res Clin Oncol 134 (2): 147-52. doi:10.1007/s00432-007-0262-5. PMID 17653766.
  21. ↑ Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 643. ISBN 978-0781765275.
  22. ↑ 22.0 22.1 22.2 Mills, Stacey E; Carter, Darryl; Greenson, Joel K; Oberman, Harold A; Reuter, Victor E (2004). Sternberg's Diagnostic Surgical Pathology (4th ed.). Lippincott Williams & Wilkins. pp. 285. ISBN 978-0781740517.
  23. ↑ 23.0 23.1 23.2 Mills, Stacey E; Carter, Darryl; Greenson, Joel K; Oberman, Harold A; Reuter, Victor E (2004). Sternberg's Diagnostic Surgical Pathology (4th ed.). Lippincott Williams & Wilkins. pp. 286. ISBN 978-0781740517.
  24. ↑ PST. 14 February 2011.
  25. ↑ Lin PP, Wang Y, Lozano G (2011). "Mesenchymal Stem Cells and the Origin of Ewing's Sarcoma". Sarcoma 2011. doi:10.1155/2011/276463. PMC 2952797. PMID 20953407. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2952797/.
  26. ↑ 26.0 26.1 Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 650. ISBN 978-0781765275.
  27. ↑ PST. 22 February 2010.
  28. ↑ PST. 14 February 2011.
  29. ↑ Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 651. ISBN 978-0781765275.
  30. ↑ 30.0 30.1 Rossi S, Orvieto E, Furlanetto A, Laurino L, Ninfo V, Dei Tos AP (May 2004). "Utility of the immunohistochemical detection of FLI-1 expression in round cell and vascular neoplasm using a monoclonal antibody". Mod. Pathol. 17 (5): 547–52. doi:10.1038/modpathol.3800065. PMID 15001993. http://www.nature.com/modpathol/journal/v17/n5/full/3800065a.html.
  31. ↑ PST. 14 February 2011.
  32. ↑ Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 286. ISBN 978-0781765275.
  33. ↑ PST. 22 February 2010.
  34. ↑ URL: http://atlasgeneticsoncology.org/Tumors/Ewing5010.html. Accessed on: 23 February 2010.
  35. ↑ Turc-Carel C, Aurias A, Mugneret F, et al. (June 1988). "Chromosomes in Ewing's sarcoma. I. An evaluation of 85 cases of remarkable consistency of t(11;22)(q24;q12)". Cancer Genet. Cytogenet. 32 (2): 229–38. PMID 3163261.
  36. ↑ URL: http://www.cancerindex.org/geneweb/EWSR1.htm. Accessed on: 20 November 2011.
  37. ↑ Online 'Mendelian Inheritance in Man' (OMIM) 165080
  38. ↑ Papalas JA, Balmer NN, Wallace C, Sangueeza OP (June 2009). "Ossifying dermatofibroma with osteoclast-like giant cells: report of a case and literature review". Am J Dermatopathol 31 (4): 379-83. doi:10.1097/DAD.0b013e3181966747. PMID 19461244.
  39. ↑ Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 638. ISBN 978-0781765275.
  40. ↑ URL: http://bestpractice.bmj.com/best-practice/monograph/780/basics/classification.html. Accessed on: 7 April 2011.
  41. ↑ 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. 279. ISBN 978-9283224136.
  42. ↑ URL: http://www.rsna.org/REG/publications/rg/afip/privateM/1997/0017/0005/1205/6.htm. Accessed on: 8 April 2011.
  43. ↑ Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 648. ISBN 978-0781765275.
  44. ↑ Wülling, M.; Engels, C.; Jesse, N.; Werner, M.; Delling, G.; Kaiser, E. (Aug 2001). "The nature of giant cell tumor of bone.". J Cancer Res Clin Oncol 127 (8): 467-74. PMID 11501745.
  45. ↑ Klatt, Edward C. (2006). Robbins and Cotran Atlas of Pathology (1st ed.). Saunders. pp. 420. ISBN 978-1416002741.
  46. ↑ Dickson BC, Li SQ, Wunder JS, et al. (April 2008). "Giant cell tumor of bone express p63". Mod. Pathol. 21 (4): 369–75. doi:10.1038/modpathol.2008.29. PMID 18311114.
  47. ↑ Alberghini M, Kliskey K, Krenacs T, et al. (January 2010). "Morphological and immunophenotypic features of primary and metastatic giant cell tumour of bone". Virchows Arch. 456 (1): 97–103. doi:10.1007/s00428-009-0863-2. PMID 20012988.
  48. ↑ Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson; Aster, Jon (2009). Robbins and Cotran pathologic basis of disease (8th ed.). Elsevier Saunders. pp. 1247. ISBN 978-1416031215.
  49. ↑ URL: http://emedicine.medscape.com/article/1253223-overview. Accessed on: 6 January 2011.
  50. ↑ URL: http://www.wheelessonline.com/ortho/pigmented_villonodular_synovitis.
  51. ↑ URL: http://southbaypath.org/CaseImages/sb5260/sb5260.htm. Accessed on: 7 December 2010.
  52. ↑ 52.0 52.1 URL: http://www.pathconsultddx.com/pathCon/diagnosis?pii=S1559-8675%2806%2970057-2. Accessed on: 28 April 2011.
  53. ↑ URL: http://www.nordiqc.org/Epitopes/Cytokeratins/cytokeratins.htm. Accessed on: 28 April 2011.
  54. ↑ Meydan N, Barutca S, Guney E, et al. (June 2006). "Brown tumors mimicking bone metastases". J Natl Med Assoc 98 (6): 950–3. PMC 2569361. PMID 16775919. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2569361/?page=1.
  55. ↑ TN06 Emerg.
  56. ↑ URL: http://path.upmc.edu/cases/case139/micro.html. Accessed on: 6 January 2012.

External links

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