HomeThe PCMC Journalvol. 21 no. 1 (2025)

Cyclin D1 immunohistochemical stain as adjunct immunomarker in CD99 positive malignant small round blue cell tumors with primary consideration of primitive neuroectodermal tumor/ewing sarcoma (PNET/EWS) in a pediatric tertiary hospital

Marie Janina Gail B. Co | Ivy Marie Viola-Cruz

Discipline: medicine by specialism

 

Abstract:

OBJECTIVE: To evaluate the diagnostic accuracy of Cyclin D1 as an adjunct immunomarker in CD99 positive small round cell neoplasms with primary consideration of PNET/EWS. MATERIALS AND METHODS: Tissue from 2017 to 2023 with a histopathologic diagnosis of CD99 positive small round blue cell tumors with primary consideration of Primitive Neuroectodermal Tumor (PNET)/Ewing Sarcoma were retrieved and Cyclin D1 immunohistochemical staining was done. Diagnostic accuracy of Cyclin D1 immunostaining was determined by calculating the sensitivity, specificity, positive predictive value, and negative predictive value. RESULTS: Cyclin D1 immunohistochemical staining was performed in 19 specimens, of which 13 yielded a positive result. Of these, 8 had a final histopathologic diagnosis of CD99 positive small round blue cell tumor with primary consideration of PNET/Ewing Sarcoma, resulting in sensitivity of 61.54%, specificity of 100%, positive predictive value of 100% and negative predictive value of 50.0%. The overall accuracy is 72.2%. CONCLUSION: Cyclin D1 can be used as an adjunct immunomarker to aid in the diagnosis of CD99 positive round cell tumor with primary consideration of PNET/ Ewing Sarcoma specifically in resource limited settings where molecular testing is not readily available. Given the high specificity of Cyclin D1 in such cases, it can be used to rule out other small round blue cell tumors that can also stain positive for CD99 such as Rhabdomyosarcoma. However, interpretation must be done in conjunction with the results of other immunohistochemical stains in order to increase its diagnostic accuracy.



References:

  1. WHO Classification of Tumours Editorial Board. Soft tissue and bone tumours [Internet]. [cited 2024 June 5]. Available from: https://publications.iarc.fr/588. Page 3.
  2. Magro G, Salvatorelli L, Alaggio R, D’Agata V, Nicoletti F, Di Cataldo A, et al. Diagnostic utility of cyclin D1 in the diagnosis of small round blue cell tumors in children and adolescents. Human                Pathology. 2017 Feb; 60:58 65. doi:10.1016/j.humpath.2016.07.038. Page 3,10
  3. Nahid MS., Begum F., Jinnah MS. et. al.  Evaluation of Cyclin D1 Expression in Paediatric Common Solid Small Round Cell Tumour [Internet]. [cited 2024 June 5]. Available from: https://www.bapath.org/wp-content/uploads/2019/03/jhc_2017_1_v1_n1_p38_mosarrat.pdf. Page 3,10
  4. Marino MT, Grilli A, Baricordi C, Manara MC, Ventura S, Pinca RS, et al. Prognostic significance of mir-34a in Ewing sarcoma is associated with cyclin D1 and Ki-67 expression. Annals of Oncology. 2014 Oct; 25(10):2080–6. doi:10.1093/annonc/mdu249
  5. Kowalewski AA, Randall RL, Lessnick SL. Cell cycle deregulation in Ewing’s sarcoma pathogenesis. Sarcoma. 2011; 2011:1–10. doi:10.1155/2011/598704. Page 3
  6. Murthy SS, Fonseca D, Challa S, Kodandapani S, Arya SS, Gundimeda SD, et al. Sensitivity and specificity of cluster differentiation and friend leukemia integration1 for the diagnosis in a series of molecularly confirmed Ewing Sarcoma family of tumors. Oncology Journal of India. 2021 May; 5(2):55–9. doi:10.4103/oji.oji_8_21. Page 9
  7. Magro G, Brancato F, Musumeci G, Alaggio R, Parenti R, Salvatorelli L. Cyclin D1 is a useful marker for soft tissue Ewing’s sarcoma/peripheral primitive neuroectodermal tumor in children and adolescents: A comparative Immunohistochemical study with rhabdomyosarcoma. Acta Histochemica. 2015 May;117(4–5):460–7. doi:10.1016/j.acthis.2015.01.005. Page 9
  8. Tina Shooshtarizadeh T, Fereidooni L, Motevalli D. Cyclin D1 as a Useful Marker for the Differentiation of Ewing’s Sarcoma from Rhabdomyosarcoma [Internet]. [cited 2024 Oct 5]. Available from: https://mejc.sums.ac.ir/article_46715_2bba86542fa041430334496a6d00be2b.pdf. Page 10.
  9. Mahapatra S. Neuroblastoma [Internet]. U.S. National Library of Medicine; 2023 [cited 2024 Oct 6]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK448111/. Page 10.
  10. Tu J, Huo Z, Gingold J, Zhao R, Shen J, Lee D-F. The histogenesis of Ewing Sarcoma. Cancer Reports and Reviews. 2017; 1(2). doi: 10.15761/crr.. 1000111. Page 10.