Bone lesions – diagnostic approach using immunohistochemistry and molecular pathology

Czech version

Authors: Iva Staniczková Zambo ¹; Tetiana Shatokhina ¹
Authors‘ workplace: I. ústav patologie FN u sv. Anny a LF MU, Brno ¹
Published in: Čes.-slov. Patol., 57, 2021, No. 1, p. 30-39
Category: Reviews Article

Overview

Immunohistochemistry and molecular pathology play an essential role in the diagnosis of some focal bone lesions. These techniques may greatly help to distinguish primary bone tumors from metastatic diseases and allow a biologically important refinements in subclassification of round cell sarcomas.

Recently, the diagnostic accuracy of organ and tumor specific antibodies has improved significantly. Knowledge of new type of antibodies and their meaningful use enables an accurate classification of the most undifferentiated carcinomas of unknown primary. However, the interpretation of immunohistochemical stains and molecular genetic analysis can be difficult in bone biopsies due to previous decalcification.

This article summarizes the most important algorithmic approach to the diagnosis of bone tumors. It outlines the most frequently used tissue-specific antibodies. New advances in the understanding of bone tumorigenesis are also discussed.

Keywords:

decalcification – immunohistochemistry – Molecular pathology – round cell tumors – bone metastases – primary bone lymphomas

Sources

1. Conner JR and Hornick JL. Metastatic carcinoma of unknown primary: diagnostic approach using immunohistochemistry. Adv Anat Pathol 2015; 22(3): 149-167.

2. Gao Z, Kahn LB. The application of immunohistochemistry in the diagnosis of bone tumors and tumor-like lesions. Skeletal Radiol 2005; 34(12): 755-770.

3. Adámková Krákorová D et al. Sarkomy. Praha: Mladá fronta 2019; 244-252.

4. Lam SW, van IJzendoorn DGP, Cleton-Jansen AM et al. Molecular pathology of bone tumors. Journal Mol Diagn 2019; 21(2): 171-182.

5. Brown RS, Edwards J, Bartlett JW et al. Routine acid decalcification of bone marrow samples can preserve DNA for FISH and CGH studies in metastatic prostate cancer. J Histochem Cytochem 2002; 50(1):113-115.

6. Singh VM, Salunga RC, Huang RJ et al. Analysis of the effect of various decalcification agents on the quantity and quality of nucleic acid (DNA and RNA) recovered from bone biopsies. Ann Diagn Pathol 2013; 17(4): 322-326.

7. Bignell GR, Greenman CD, Davies H et al. Signatures of mutation and selection in the cancer genome. Nature 2010; 463(7283): 893-898.

8. Maher CA, Wilson RK. Chromothripsis and human disease: piecing together the shattering process. Cell 2012; 148(1-2): 29-32.

9. Sugita S and Hasegawa T. Practical use and utility of fluorescence in situ hybridization in the pathological diagnosis of soft tissue and bone tumors. J Orthop Sci 2017; 22(4): 601-612.

10. Antonescu CR, Owosho AA, Zhang L et. Al. Sarcomas with CIC-rearrangements are a distinct pathologic entity with aggressive outcome: A clinicopathologic and molecular study of 115 cases. Surg pathol 2017; 41(7): 941-949.

11. Franceschini N, Lam SW, Cleton-Jansen AM, Boveé JVMG. What´s new in bone forming tumors of the skeleton? Virchows Arch 2020; 476(1): 147-157.

12. Fletcher CDM, Bridge JA, Hogendoorn PCW et al. WHO classification of tumours of soft tissue and bone (4th edn). Lyon: IARC; 2013.

13. Seningen JL, Inwards CY. Small round cell tumors of bone. Surg Pathol Clin 2012; 5(1): 231-256.

14. Folpe AL, Hill CE, PArham DM et al. Immunohistochemical detection of FLI-1 protein expression: a study of 132 round cell tumors with emphasis on CD99-positive mimics of Ewing’s sarcoma/primitive neuroectodermal tumor. Am J Surg Pathol 2000; 24(12): 1657-1662.

15. Hung YP, Fletcher CD, Hornick JL. Evaluation on NKX2-2 expression in round cell sarcomas and other tumors with EWSR1 rearrangement: imperfect specificity for Ewing sarcoma. Mod Pathol 2016; 29(4): 370-380.

16. Sbaraglia M, Righi A, Gambarotti M, Dei Tos AP. Ewing sarcoma and Ewing-like tumors. Virchows Arch 2019; 476(1): 109-119.

17. Renzi S, Anderson ND, Light N, Gupta A. Ewing-like sarcoma: An emerging family of round cell sarcomas. J Cell Physiol 2019; 234(6): 7999-8007.

18. Kinkor Z, Grossmann P, Dubová M, et al. Co nového v Ewing-like family aneb malobuněčné/kulatobuněčné sarkomy měkkých tkání a kostí s rearanží genů CIC a BCOR. Přehled problematiky a naše prvotní zkušenosti. Cesk Patol 2017; 53(4): 175‐180.

19. Le Loarer F, Pissaloux D, Coindre JM et al. Update on families of round cell sarcomas other than classical Ewing sarcomas. Surg Pathol Clin 2017; 10(3): 587-620.

20. Cohen-Gogo S, Cellier C, Coindre JM et al. Ewing-like sarcomas with BCOR-CCNB3 fusion transcript: A clinical, radiological and pathological retrospective study from the Societe Francaise des Cancers de L’Enfant. Pediatr Blood Cancer 2014; 61(12): 2191-2198.

21. Puls F, Niblett A, Marland G et al. BCOR-CCNB3 (Ewing-like) sarcoma: A clinicopathologic analysis of 10 cases, in comparison with conventional Ewing sarcoma. Am J Surg Pathol 2014; 38(10): 1307-1318.

22. Kinkor Z, Vaneček T, Švajdler M Jr, et al. Kde končí a začíná diagnóza Ewingova sarkomu - popis dvou neobvyklých kostních nádorů s translokací t(20;22)(EWSR1-NFATc2) Cesk Patol 2014; 50(2): 87‐91.

23. Righi A, Gambarotti M, Longo S et al. Small cell osteosarcoma: clinicopathologic, immunohistochemical, and molecular analysis of 36 cases. Am J Surg Pathol 2015; 39(5): 691-699.

24. Ozdemirli M, Fanburg-Smith JC, Hartmann DP et al. Differentiating lymphoblastic lymphoma and Ewing’s sarcoma: lymphocyte markers and gene rearrangement. Mod Pathol 2001; 14(11): 1175-1182.

25. Machado I, Navarro S, Picci P et al. The utility of SATB2 immunohistochemical expression in distinguishing between osteosarcomas and their malignant bone tumor mimickers, such as Ewing sarcomas and chondrosarcomas. Pathol Res Pract 2016; 212(9): 811-816.

26. Kerr DA, Lopez HU, Deshpande V et al. Molecular distinction of chondrosarcoma from chondroblastic osteosarcoma through IDH1/2 mutations. Am J Surg Pathol 2013; 37(6): 787-795.

27. Schaefer IM, Fletcher JA, Nielsen GP et al. Immunohistochemistry for histone H3G34W and H3K36M is highly specific for giant cell tumor of bone and chondroblastoma, respectively, in FNA and core needle biopsy. Cancer Cytopathol 2018; 126(8): 552-566.

28. Rehkämper J, Steinestel K, Jeiler B et al. Diagnostic tools in the differential diagnosis of giant cell-rich lesions of bone at biopsy. Oncotarget 2018; 9(53): 30106-30114.

29. Southam BR, Crawford AH, Billmire DA et al. Long-term follow-up of adamantinoma of the tibia complicated by metastases and second unrelated primary cancer: a case report and literature review. Case Rep Orthop 2018; 2018: 5493750.

30. Baranov E, McBride MJ, Bellizzi AM, et al. A novel SS18-SSX fusion-specific antibody for the diagnosis of synovial sarcoma. Am J Surg Pathol. In press 2020.

31. Miettinen M, Wang Z, Laosta J et al. Nuclear brachyury expression in consistent in chordoma, common in germ cell tumors and small cell carcinomas and rare in other carcinomas and sarcomas. An immunohistochemical study of 5229 cases. Am J Surg Pathol 2015; 39(10): 1305-1312.

32. Švajdler M, Mezencev R, Šašková B, Ondič O, Mukenšnábl P, Michal M. Triple marker composed of p16, CD56, and TTF1 shows higher sensitivity than INSM1 for diagnosis of pulmonary small cell carcinoma: proposal for a rational immunohistochemical algorithm for diagnosis of small cell carcinoma in small biopsy and cytology specimens. HumPathol 2019; 85: 58‐64.

33. Lin F, Liu H. Immunohistochemistry in undifferentiated neoplasm/tumor of uncertain origin. Arch Pathol Lab Med 2014; 138(12): 1583-1610.

34. Vincenzi B, Frezza AM, Schiavon G et al. Bone metastasis in soft tissue sarcomas: a survey of natural history, prognostic value and treatment options. Clin Sarcoma Res 2013; 3(1): 6.

35. Demircay E, Hornicek FJ, Mankon HJ and Degroot H. Malignant lymphoma of bone: a review of 119 patients. Clin Orthop Relat Res 2013; 471(8): 2684-2690.