Skip to main content
Log in

Confounders of intraoperative frozen section pathology during glioma surgery

  • Research
  • Published:
Neurosurgical Review Aims and scope Submit manuscript

Abstract

Although frozen section pathology (FSP) is commonly performed during surgery for glioma-suspicious lesions, confounders of accuracy are largely unknown. FSP and final diagnosis were compared in 398 surgeries for glioma-suspicious lesions. Diagnostic accuracy, risk factors for diagnostic shift from neoplastic to non-neoplastic tissue and vice versa according to the final diagnosis, and the impact on intraoperative and postoperative decision-making were analyzed. Diagnostic shift occurred in 70 cases (18%), and sensitivity, specificity, and the positive (PPV) and negative (NPV) predictive value of FSP were 82.5%, 77.8%, 99.4%, and 9.3%, respectively. No correlations between shift and patients‘ age and sex, sample fluorescence or volume, tumor location, correct information on the pathology form, final high- or low-grade histology, or molecular alterations were found (p > .05, each). Shift was more common after irradiation (25% vs 15%; p = .025) or chemotherapy (26% vs 15%; p = .022) than in treatment naïve cases and correlated with the type of surgery (p = .002). FSP altered intraoperative decision-making in 25 cases (6%). Postoperative shift led to repeated surgery in 12 patients (3%). In 45 cases, in which FSP and final diagnosis based on the same tissue, shift occurred in only 5 patients (11%), and sensitivity, specificity, PPV, and NPV for FSP were 77.4%, 78.6%, 88.9%, and 61.1%, respectively. No correlations between diagnostic shift and any of the analyzed variables were found (p > .05, each). Although accuracy of FSP during glioma surgery is sufficient, moderate NPV should be considered during intraoperative decision-making. While confounders are sparse, accuracy might be increased by repeated sampling. Diagnostic shift rarely alters postoperative treatment strategy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Data availability

Data can be provided by the corresponding author upon reasonable request.

References

  1. Lechago J (2005) The frozen section: pathology in the trenches. Arch Pathol Lab Med 129:1529–1531. https://doi.org/10.5858/2005-129-1529-TFSPIT

    Article  PubMed  Google Scholar 

  2. Kumar AS, Chander V, Parthasarathy J (2021) Diagnostic accuracy of intraoperative frozen section analysis in correlation with histopathological diagnosis of ovarian tumors in a tertiary care center—a retrospective study. Cancer Investig 39:153–158. https://doi.org/10.1080/07357907.2020.1865395

    Article  CAS  Google Scholar 

  3. Preisser F, Theissen L, Wild P, Bartelt K, Kluth L, Kollermann J, Graefen M, Steuber T, Huland H, Tilki D, Roos F, Becker A, Chun FK, Mandel P (2021) Implementation of intraoperative frozen section during radical prostatectomy: short-term results from a German tertiary-care center. Eur Urol Focus 7:95–101. https://doi.org/10.1016/j.euf.2019.03.007

    Article  PubMed  Google Scholar 

  4. Santoro A, Piermattei A, Inzani F, Angelico G, Valente M, Arciuolo D, Spadola S, Martini M, Fanfani F, Fagotti A, Gallotta V, Scambia G, Zannoni GF (2019) Frozen section accurately allows pathological characterization of endometrial cancer in patients with a preoperative ambiguous or inconclusive diagnoses: our experience. BMC Cancer 19:1096. https://doi.org/10.1186/s12885-019-6318-5

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Nanarng V, Jacob S, Mahapatra D, Mathew JE (2015) Intraoperative diagnosis of central nervous system lesions: comparison of squash smear, touch imprint, and frozen section. J Cytol 32:153–158. https://doi.org/10.4103/0970-9371.168835

    Article  PubMed  PubMed Central  Google Scholar 

  6. Plesec TP, Prayson RA (2007) Frozen section discrepancy in the evaluation of central nervous system tumors. Arch Pathol Lab Med 131:1532–1540. https://doi.org/10.5858/2007-131-1532-FSDITE

    Article  PubMed  Google Scholar 

  7. Zulkarnain S, Yunus N, Kandasamy R, Zun AB, Mat Zin AA (2020) Evaluation study of intraoperative cytology smear and frozen section of glioma. Asian Pac J Cancer Prev 21:3085–3091. https://doi.org/10.31557/APJCP.2020.21.10.3085

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Jaafar H (2006) Intra-operative frozen section consultation: concepts, applications and limitations. Malays J Med Sci 13:4–12

    PubMed  PubMed Central  Google Scholar 

  9. Khoddami M, Akbarzadeh A, Mordai A, Bidari-Zerehpoush F, Alipour H, Samadzadeh S, Alipour B (2015) Diagnostic accuracy of frozen section of central nervous system lesions: a 10-year study. Iran J Child Neurol 9:25–30

    PubMed  PubMed Central  Google Scholar 

  10. Leroy HA, Guerin L, Lecomte F, Baert G, Vignion AS, Mordon S, Reyns N (2021) Is interstitial photodynamic therapy for brain tumors ready for clinical practice? A systematic review. Photodiagn Photodyn Ther 36:102492. https://doi.org/10.1016/j.pdpdt.2021.102492

    Article  CAS  Google Scholar 

  11. Schipmann S, Muther M, Stogbauer L, Zimmer S, Brokinkel B, Holling M, Grauer O, Suero Molina E, Warneke N, Stummer W (2020) Combination of ALA-induced fluorescence-guided resection and intraoperative open photodynamic therapy for recurrent glioblastoma: case series on a promising dual strategy for local tumor control. J Neurosurg:1–11. https://doi.org/10.3171/2019.11.JNS192443

  12. Haybaeck J, von Campe G, Hainfellner JA (2012) Rapid frozen sections in neuropathology. Pathologe 33:379–388. https://doi.org/10.1007/s00292-012-1604-x

    Article  PubMed  CAS  Google Scholar 

  13. Rao S, Rajkumar A, Ehtesham MD, Duvuru P (2009) Challenges in neurosurgical intraoperative consultation. Neurol India 57:464–468. https://doi.org/10.4103/0028-3886.55598

    Article  PubMed  Google Scholar 

  14. Reuss DE (2023) Updates on the WHO diagnosis of IDH-mutant glioma. J Neuro-Oncol. https://doi.org/10.1007/s11060-023-04250-5

  15. Torp SH, Solheim O, Skjulsvik AJ (2022) The WHO 2021 Classification of Central Nervous System tumours: a practical update on what neurosurgeons need to know-a minireview. Acta Neurochir 164:2453–2464. https://doi.org/10.1007/s00701-022-05301-y

    Article  PubMed  Google Scholar 

  16. Berzero G, Di Stefano AL, Ronchi S, Bielle F, Villa C, Guillerm E, Capelle L, Mathon B, Laurenge A, Giry M, Schmitt Y, Marie Y, Idbaih A, Hoang-Xuan K, Delattre JY, Mokhtari K, Sanson M (2021) IDH-wildtype lower-grade diffuse gliomas: the importance of histological grade and molecular assessment for prognostic stratification. Neuro-Oncology 23:955–966. https://doi.org/10.1093/neuonc/noaa258

    Article  PubMed  CAS  Google Scholar 

  17. Reifenberger G, Wirsching HG, Knobbe-Thomsen CB, Weller M (2017) Advances in the molecular genetics of gliomas—implications for classification and therapy. Nat Rev Clin Oncol 14:434–452. https://doi.org/10.1038/nrclinonc.2016.204

    Article  PubMed  CAS  Google Scholar 

  18. Shankar GM, Francis JM, Rinne ML, Ramkissoon SH, Huang FW, Venteicher AS, Akama-Garren EH, Kang YJ, Lelic N, Kim JC, Brown LE, Charbonneau SK, Golby AJ, Sekhar Pedamallu C, Hoang MP, Sullivan RJ, Cherniack AD, Garraway LA, Stemmer-Rachamimov A et al (2015) Rapid intraoperative molecular characterization of glioma. JAMA Oncol 1:662–667. https://doi.org/10.1001/jamaoncol.2015.0917

    Article  PubMed  PubMed Central  Google Scholar 

  19. Mohamed A, Hassan MM, Zhong W, Kousar A, Takeda K, Donthi D, Rizvi A, Majeed M, Younes AI, Ali A, Sutton A, Murray G, Thayyil A, Fallon J, Geisinger K (2022) A quantitative and qualitative assessment of frozen section diagnosis accuracy and deferral rate across organ systems. Am J Clin Pathol 158:692–701. https://doi.org/10.1093/ajcp/aqac115

    Article  PubMed  Google Scholar 

  20. Obeidat FN, Awad HA, Mansour AT, Hajeer MH, Al-Jalabi MA, Abudalu LE (2019) Accuracy of frozen-section diagnosis of brain tumors: an 11-year experience from a tertiary care center. Turk Neurosurg 29:242–246. https://doi.org/10.5137/1019-5149.JTN.23220-18.2

    Article  PubMed  Google Scholar 

  21. Amraei R, Moradi A, Zham H, Ahadi M, Baikpour M, Rakhshan A (2017) A comparison between the diagnostic accuracy of frozen section and permanent section analyses in central nervous system. Asian Pac J Cancer Prev 18:659–666. https://doi.org/10.22034/APJCP.2017.18.3.659

    Article  PubMed  PubMed Central  Google Scholar 

  22. Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, Ohgaki H, Wiestler OD, Kleihues P, Ellison DW (2016) The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol 131:803–820. https://doi.org/10.1007/s00401-016-1545-1

    Article  PubMed  Google Scholar 

  23. Gitas G, Proppe L, Alkatout I, Rody A, Kotanidis C, Tsolakidis D, Baum S (2019) Accuracy of frozen section at early clinical stage of endometrioid endometrial cancer: a retrospective analysis in Germany. Arch Gynecol Obstet 300:169–174. https://doi.org/10.1007/s00404-019-05158-0

    Article  PubMed  CAS  Google Scholar 

  24. Khonglah Y, Lyngdoh BS, Kakati A, Mishra J, Al Aman MM, Phukan P (2021) Intraoperative diagnosis of central nervous system tumors: challenges, errors, lessons learned, and the surgeon's perspective. Cureus 13:e17823. https://doi.org/10.7759/cureus.17823

    Article  PubMed  PubMed Central  Google Scholar 

  25. Kurdi M, Baeesa S, Maghrabi Y, Bardeesi A, Saeedi R, Al-Sinani T, Samkari A, Lary A, Hakamy S (2022) Diagnostic discrepancies between intraoperative frozen section and permanent histopathological diagnosis of brain tumors. Turk Patoloji Derg 38:34–39. https://doi.org/10.5146/tjpath.2021.01551

    Article  PubMed  PubMed Central  Google Scholar 

  26. Park JY, Lee SH, Kim KR, Kim YT, Nam JH (2019) Accuracy of frozen section diagnosis and factors associated with final pathological diagnosis upgrade of mucinous ovarian tumors. J Gynecol Oncol 30:e95. https://doi.org/10.3802/jgo.2019.30.e95

    Article  PubMed  PubMed Central  Google Scholar 

  27. Bryski MG, Frenzel-Sulyok LG, Delikatny EJ, Deshpande C, Litzky LA, Singhal S (2021) Molecular imaging can identify the location to perform a frozen biopsy during intraoperative frozen section consultation. PLoS One 16:e0252731. https://doi.org/10.1371/journal.pone.0252731

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Cotter JA, Szymanski LJ, Pawel BR, Judkins AR (2022) Intraoperative diagnosis for pediatric brain tumors. Pediatr Dev Pathol 25:10–22. https://doi.org/10.1177/10935266211018932

    Article  PubMed  Google Scholar 

  29. Haapala I, Kondratev A, Roine A, Makela M, Kontunen A, Karjalainen M, Laakso A, Koroknay-Pal P, Nordfors K, Haapasalo H, Oksala N, Vehkaoja A, Haapasalo J (2022) Method for the Intraoperative detection of IDH mutation in gliomas with differential mobility spectrometry. Curr Oncol 29:3252–3258. https://doi.org/10.3390/curroncol29050265

    Article  PubMed  PubMed Central  Google Scholar 

  30. Della Pepa GM, Menna G, Olivi A (2023) Technical pearls to effectively use 5-ALA in fluorescence-guided tumor resection-5 lessons from the operating room. Brain Sci 13. https://doi.org/10.3390/brainsci13030411

  31. Ji SY, Kim JW, Park CK (2019) Experience profiling of fluorescence-guided surgery II: non-glioma pathologies, Brain Tumor Res Treat. 7:105–111. https://doi.org/10.14791/btrt.2019.7.e39

  32. La Rocca G, Sabatino G, Menna G, Altieri R, Ius T, Marchese E, Olivi A, Barresi V, Della Pepa GM (2020) 5-Aminolevulinic acid false positives in cerebral neuro-oncology: not all that is fluorescent is tumor. A case-based update and literature review. World Neurosurg 137:187–193. https://doi.org/10.1016/j.wneu.2020.01.238

    Article  PubMed  Google Scholar 

  33. Mangesius J, Mangesius S, Demetz M, Uprimny C, Di Santo G, Galijasevic M, Minasch D, Gizewski ER, Ganswindt U, Virgolini I, Thome C, Freyschlag CF, Kerschbaumer J (2022) A multi-disciplinary approach to diagnosis and treatment of radionecrosis in malignant gliomas and cerebral metastases. Cancers (Basel) 14. https://doi.org/10.3390/cancers14246264

  34. Mair F, Erickson JR, Frutoso M, Konecny AJ, Greene E, Voillet V, Maurice NJ, Rongvaux A, Dixon D, Barber B, Gottardo R, Prlic M (2022) Extricating human tumour immune alterations from tissue inflammation. Nature 605:728–735. https://doi.org/10.1038/s41586-022-04718-w

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Han S, Liu Y, Cai SJ, Qian M, Ding J, Larion M, Gilbert MR, Yang C (2020) IDH mutation in glioma: molecular mechanisms and potential therapeutic targets. Br J Cancer 122:1580–1589. https://doi.org/10.1038/s41416-020-0814-x

    Article  PubMed  PubMed Central  Google Scholar 

  36. Pirozzi CJ, Yan H (2021) The implications of IDH mutations for cancer development and therapy. Nat Rev Clin Oncol 18:645–661. https://doi.org/10.1038/s41571-021-00521-0

    Article  PubMed  CAS  Google Scholar 

  37. Wirsching HG, Weller M (2016) The role of molecular diagnostics in the management of patients with gliomas. Curr Treat Options in Oncol 17:51. https://doi.org/10.1007/s11864-016-0430-4

    Article  Google Scholar 

  38. Howanitz PJ, Hoffman GG, Zarbo RJ (1990) The accuracy of frozen-section diagnoses in 34 hospitals. Arch Pathol Lab Med 114:355–359

    PubMed  CAS  Google Scholar 

  39. Jutte H, Tannapfel A (2020) Intraoperative rapid frozen section-when meaningful, when necessary? Chirurg 91:456–460. https://doi.org/10.1007/s00104-020-01115-9

    Article  PubMed  CAS  Google Scholar 

  40. Geramizadeh B, Larijani TR, Owji SM, Attaran SY, Torabinejad S, Aslani FS, Monabati A, Kumar PV, Tabei SZ (2010) Accuracy of intra-operative frozen section consultation in south of Iran during four years. Indian J Pathol Microbiol 53:414–417. https://doi.org/10.4103/0377-4929.68250

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Contributions

JWAH: data collection, manuscript draft, statistical analyses, and interpretation of the results; EMSS: data acquisition and manuscript draft; NMK: data acquisition and manuscript draft; CT: manuscript draft and interpretation of the results; OG: manuscript draft and interpretation of the results; MÖ: data collection; manuscript draft, and interpretation of the results; HTE: manuscript draft and interpretation of the results; WS: conception and manuscript draft; WP: manuscript draft; BB: statistical analyses, manuscript draft, and conception.

Corresponding author

Correspondence to Benjamin Brokinkel.

Ethics declarations

Ethics approval

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethikkommission der Ärztekammer Westfalen-Lippe und der Westfälischen Wilhelms-Universität, Az.: 2021-733-f-S.

Consent to participate

Informed consent was obtained from all individual participants included in this study.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

ESM 1

(DOCX 32 kb)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Harms, J.W.A., Streckert, E.M.S., Kiolbassa, N.M. et al. Confounders of intraoperative frozen section pathology during glioma surgery. Neurosurg Rev 46, 286 (2023). https://doi.org/10.1007/s10143-023-02169-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s10143-023-02169-z

Keywords

Navigation