PEDIATRIC MALIGNANT SMALL ROUND CELL TUMORS: AN IMMUNOHISTOCHEMICAL ANALYSIS
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Keywords
Malignant small round cell tumors; pediatric neoplasms; immunohistochemistry; diagnostic algorithm; lineage‑defining markers
Abstract
Background: Malignant small round cell tumors (MSRCTs) of childhood pose diagnostic challenges due to overlapping morphology but divergent prognoses and treatments. Immunohistochemistry (IHC) is essential for accurate subclassification, yet standardized algorithms are lacking in many resource‑limited settings. Aim: To evaluate the IHC profile of 11 markers in 100 pediatric MSRCTs, determine diagnostic utility (sensitivity, specificity, predictive values), and propose a practical diagnostic algorithm. Methods: A prospective study of 100 consecutive MSRCTs (≤15 years) was conducted. An IHC panel comprising CD45, CD99, vimentin, desmin, myogenin, NSE, chromogranin, synaptophysin, cytokeratin, EMA, and WT1 was applied. Positivity was defined as >10% tumor cells with moderate‑to‑strong staining. Sensitivity, specificity, PPV, NPV, and p‑values (Fisher’s exact test) were calculated. Results: Myogenin, chromogranin, and CD45 were 100% sensitive and specific for embryonal rhabdomyosarcoma, neuroblastoma, and lymphoblastic lymphoma, respectively (p<0.0001). CD99 was 100% sensitive for Ewing sarcoma/PNET but only 70.6% specific due to positivity in lymphoblastic lymphoma (100%) and 29% of embryonal rhabdomyosarcomas. WT1 showed nuclear positivity in all Wilms tumours and cytoplasmic staining in 50% of DSRCTs. Desmin was positive in both embryonal rhabdomyosarcoma and DSRCT, resolved by myogenin and cytokeratin. Conclusion: A carefully chosen set of immunohistochemistry markers can correctly diagnose childhood small round cell tumors. Myogenin, chromogranin, and CD45 are the best markers for their respective tumors. CD99 must be used together with other markers. We recommend a stepwise approach starting with CD45, then myogenin, then chromogranin, and finally CD99 with WT1.
References
2. Jabeen S, Haque M, Islam MJ, Talukder MH. Profile of Paediatric Malignancies: A Five Year Study. Dhaka Med Coll. 2010;19(1):33 38.
3. Shah HJ, Soomro IN, Siddiqui MS, Pervez S, Hassan SH. Immunohistochemical Evaluation Of Small Round Cell Tumors of Childhood. J Pak Med Assoc. 1999;49(4):87 89.
4. Wick MR. Immunohistochemical Approaches To The Diagnosis Of Undifferentiated Malignant Tumors. Ann Diagn Pathol. 2008;12:72–84.
5. Patel MM, Dhandha ZB, Italiya SL, Shah MB, Kaptan KR, Mansuri BM. Role of Immunohistochemistry In Differential Diagnosis Of Round Cell Tumor. 2013;3(5).
6. Rajwanshi A, Srinivas R, Upasana G. Malignant Small Round Cell Tumors. J Cytol. 2009;26(1):1–10.
7. Folpe AL, Goldblum JR, Rubin BP, Shehata BM, Liu W, Dei Tos AP, Weiss SW. Morphologic and immunophenotypic diversity in Ewing family tumors: a study of 66 genetically confirmed cases. Am J Surg Pathol. 2005;29(8):1025 33.
8. Lucas DR, Bentley G, Dan ME, Tabaczka P, Poulik JM, Mott MP. Ewing Sarcoma vs Lymphoblastic Lymphoma: A Comparative Immunohistochemical Study. Am J Clin Pathol. 2001;115:11 17.
9. Ordóñez NG. Desmoplastic small round cell tumor: II: an ultrastructural and immunohistochemical study with emphasis on new immunohistochemical markers. Am J Surg Pathol. 1998;22(11):1314 27.
10. Miettinen M, Rapola J. Synaptophysin – an immunohistochemical marker for childhood neuroblastoma. Acta Pathol Microbiol Immunol Scand A. 1987;95(4):167 70.
11. Hirose T, Scheithauer BW, Lopes MB, et al. Olfactory Neuroblastoma: An Immunohistochemical, Ultrastructural, and Flow Cytometric Study. Cancer. 1995;76(1):1 16.
12. Barnoud R, Sabourin JC, Pasquier D, Ranchère D, Bailly C, Terrier Lacombe MJ, Pasquier B. Immunohistochemical expression of WT1 by desmoplastic small round cell tumor: a comparative study with other small round cell tumors. Am J Surg Pathol. 2000;24(6):830 6.
13. Devoe K, Weidner N. Immunohistochemistry of small round cell tumors. Semin Diagn Pathol. 2000;17:216 224.
14. Kodet R. Rhabdomyosarcoma in childhood. An immunohistological analysis with myoglobin, desmin and vimentin. Pathol Res Pract. 1989;185(2):207 13.
15. Wang NP, Marx J, McNutt MA, Rutledge JC, Gown AM. Expression of Myogenic Regulatory Proteins (Myogenin and MyoD1) in Small Blue Round Cell Tumors. Am J Pathol. 1995;147(6).
16. Fellinger EJ, Garin Chesa P, Glasser DB, Huvos AG, Rettig WJ. Comparison of cell surface antigen HBA71 (p30/32MIC2), neuron specific enolase, and vimentin in the immunohistochemical analysis of Ewing's sarcoma of bone. Am J Surg Pathol. 1992;16(8):746 55.
17. Sebire NJ, Gibson S, Rampling D, William S, Malone M, Ramsay AD. Immunohistochemical findings in embryonal small round cell tumors with molecular diagnostic confirmation. Appl Immunohistochem Mol Morphol. 2005;13(1):1 5.
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Dr. Afrin
Final Year Post Graduate Resident, Department of Pathology, National Institute of Medical Sciences and Research, NIMS University, Jaipur, India.
Dr. Sima Chauhan
Professor and Head, Department of Pathology, Department of Pathology, National Institute of Medical Sciences and Research, NIMS University, Jaipur, India.
