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Intraoperative Margin Assessment in Head and Neck Cancer: A Case of Misuse and Abuse?

  • Proceeding of the North American Society of Head and Neck Pathology Companion Meeting, March 1, 2020, Los Angeles, California
  • Published:
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Abstract

Surgical removal with negative margins is the preferred management of oral squamous cell carcinomas. This review summarizes statements by professional organizations and data supporting the specimen-driven approach to margin assessment. Practical aspects of the intraoperative margin assessment, as guided by gross examination, are presented. The most cost- and time-efficient method of intraoperative margin assessment depends on desired margin clearance and likelihood of other adverse histologic factors, such as extranodal extension, perineural invasion, which are likelier in advanced carcinomas. Intraoperative surgeon-pathologist communication can be improved by reporting to surgical team gross distances to all or selected closest margins, before choosing margins for microscopic frozen examination. Case specific mitigation strategies to minimize the negative impact of tumor-bed driven margin assessment or of suboptimal margin revision are proposed. Based on size, shape, histology, size of carcinoma at the margin, and orientation of the additional tissue, margin revision may be judged as adequate (conversion of a positive margin into a negative one), inadequate (positive margin remains positive), or indeterminate. The significance of anatomic subsite based labeling, radial margin sampling from the main resection specimen, and the relationship between the distance to closest margin and local control are highlighted. The modern definition of safe margin would account for other parameters, such as perineural invasion. An updated approach to resolution of frozen versus permanent sampling issues is outlined. Future studies are needed to design and validate risk models that would help to determine for individual patient what represents a safe margin and how to judge the quality of margin revision.

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source paper illustrates curves for local recurrence, too. Model-derived estimated probability of 3-year locoregional recurrence-free survival is plotted against the distance to closest margin and perineural invasion status. The presented curve functions like a nomogram. For instance, a patient with a closest margin of about 1 mm and positive for perineural invasion would have an estimated probability of 3-year locoregional recurrence free survival of about 0.7 (probability of recurrence at 30%). Arrows illustrate how referencing for individual patients can be done. A black vertical arrow is drawn from the point corresponding to the distance to closest margin on axis “x” until the line crosses the orange Kaplan–Meier curve (with PNI). From this point on Kaplan–Meier curve, horizontal black arrow towards the “y” axis will point out the estimated probability of 3-year locoregional recurrence free survival

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References

  1. Sridharan S, Thompson LDR, Purgina B, et al. Early squamous cell carcinoma of the oral tongue with histologically benign lymph nodes: A model predicting local control and vetting of the eighth edition of the American Joint Committee on Cancer pathologic T stage. Cancer. 2019;125(18):3198–207.

    Article  Google Scholar 

  2. Chiosea SI. Intraoperative margin assessment in early oral squamous cell carcinoma. Surg Pathol Clin. 2017;10(1):1–14.

    Article  PubMed  Google Scholar 

  3. Anderson CR, Sisson K, Moncrieff M. A meta-analysis of margin size and local recurrence in oral squamous cell carcinoma. Oral Oncol. 2015;51(5):464–9.

    Article  PubMed  Google Scholar 

  4. Buchakjian MR, Tasche KK, Robinson RA, Pagedar NA, Sperry SM. Association of main specimen and tumor bed margin status with local recurrence and survival in oral cancer surgery. JAMA Otolaryngol Head Neck Surg. 2016;142(12):1191–8.

    Article  PubMed  Google Scholar 

  5. Liao CT, Chang JT, Wang HM, et al. Does adjuvant radiation therapy improve outcomes in pT1-3N0 oral cavity cancer with tumor-free margins and perineural invasion? Int J Radiat Oncol Biol Phys. 2008;71(2):371–6.

    Article  PubMed  Google Scholar 

  6. Liao CT, Chang JT, Wang HM, et al. Analysis of risk factors of predictive local tumor control in oral cavity cancer. Ann Surg Oncol. 2008;15(3):915–22.

    Article  PubMed  Google Scholar 

  7. Maxwell JH, Thompson LD, Brandwein-Gensler MS, et al. Early oral tongue squamous cell carcinoma: sampling of margins from tumor bed and worse local control. JAMA Otolaryngol Head Neck Surg. 2015;141(12):1104–10.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Duvvuri U, Seethala RR, Chiosea S. Margin assessment in oral squamous cell carcinoma. Cancer. 2014;120(3):452–3.

    Article  PubMed  Google Scholar 

  9. Sperry SM, Varvares MA, Chiosea SI. Patients with revised surgical resection margins are best studied as a distinct group. Cancer. 2018;124(21):4262–3.

    Article  PubMed  Google Scholar 

  10. Chang AM, Kim SW, Duvvuri U, et al. Early squamous cell carcinoma of the oral tongue: comparing margins obtained from the glossectomy specimen to margins from the tumor bed. Oral Oncol. 2013;49(11):1077–82.

    Article  PubMed  Google Scholar 

  11. Duvvuri U, Johnson JT, Chiosea SI. Standardized Margin Assessment Is Needed Before Implementing Negative Margin as a Quality Measure. JAMA Otolaryngol Head Neck Surg. 2018;144(6):541–2.

    Article  PubMed  Google Scholar 

  12. Liao CT, Lin CY, Fan KH, et al. Identification of a high-risk group among patients with oral cavity squamous cell carcinoma and pT1-2N0 disease. Int J Radiat Oncol Biol Phys. 2012;82(1):284–90.

    Article  PubMed  Google Scholar 

  13. Johnson RE, Sigman JD, Funk GF, Robinson RA, Hoffman HT. Quantification of surgical margin shrinkage in the oral cavity. Head Neck. 1997;19(4):281–6.

    Article  CAS  PubMed  Google Scholar 

  14. Mistry RC, Qureshi SS, Kumaran C. Post-resection mucosal margin shrinkage in oral cancer: quantification and significance. J Surg Oncol. 2005;91(2):131–3.

    Article  PubMed  Google Scholar 

  15. George KS, Hyde NC, Wilson P, Smith GI. Does the method of resection affect the margins of tumours in the oral cavity? Prospective controlled study in pigs. Br J Oral Maxillofac Surg. 2013;51(7):600–3.

    Article  PubMed  Google Scholar 

  16. Weinstock YE, Alava I 3rd, Dierks EJ. Pitfalls in determining head and neck surgical margins. Oral Maxillofac Surg Clin North Am. 2014;26(2):151–62.

    Article  PubMed  Google Scholar 

  17. Kim S, Chiosea S. On challenges of disproving inferiority of tumor bed margins. Oral Dis. 2019;25(8):2040–1.

    Article  PubMed  Google Scholar 

  18. Gerber S, Gengler C, Gratz KW, Kruse AL. The impact of frozen sections on final surgical margins in squamous cell carcinoma of the oral cavity and lips: a retrospective analysis over an 11 years period. Head Neck oncology. 2011;3:56.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Gokavarapu S, Chandrasekhara Rao LM, Patnaik SC, Parvataneni N, Raju KV, Chander R. Prognostic value of frozen section in t1, t2 carcinoma of oral cavity. Indian J Otolaryngol Head Neck Surg. 2015;67(Suppl 1):86–90.

    Article  PubMed  Google Scholar 

  20. Chaturvedi P, Datta S, Nair S, et al. Gross examination by the surgeon as an alternative to frozen section for assessment of adequacy of surgical margin in head and neck squamous cell carcinoma. Head Neck. 2014;36(4):557–63.

    Article  PubMed  Google Scholar 

  21. DiNardo LJ, Lin J, Karageorge LS, Powers CN. Accuracy, utility, and cost of frozen section margins in head and neck cancer surgery. Laryngoscope. 2000;110(10 Pt 1):1773–6.

    Article  CAS  PubMed  Google Scholar 

  22. Datta S, Mishra A, Chaturvedi P, et al. Frozen section is not cost beneficial for the assessment of margins in oral cancer. Indian J Cancer. 2019;56(1):19–23.

    Article  PubMed  Google Scholar 

  23. Prabhu AV, Sturgis CD, Lai C, et al. Improving margin revision: Characterization of tumor bed margins in early oral tongue cancer. Oral Oncol. 2017;75:184–8.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Black C, Marotti J, Zarovnaya E, Paydarfar J. Critical evaluation of frozen section margins in head and neck cancer resections. Cancer. 2006;107(12):2792–800.

    Article  PubMed  Google Scholar 

  25. Kerawala CJ, Ong TK. Relocating the site of frozen sections–is there room for improvement? Head Neck. 2001;23(3):230–2.

    Article  CAS  PubMed  Google Scholar 

  26. van Lanschot CG, Mast H, Hardillo JA, et al. Relocation of inadequate resection margins in the wound bed during oral cavity oncological surgery: a feasibility study. Head Neck. 2019;41(7):2159–66.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Mair M, Nair D, Nair S, et al. Intraoperative gross examination vs frozen section for achievement of adequate margin in oral cancer surgery. Oral Surg Oral Med Oral Pathol Oral Radiol. 2017;123(5):544–9.

    Article  PubMed  Google Scholar 

  28. Guillemaud JP, Patel RS, Goldstein DP, Higgins KM, Enepekides DJ. Prognostic impact of intraoperative microscopic cut-through on frozen section in oral cavity squamous cell carcinoma. J Otolaryngol 2010;39(4):370–7.

  29. Jackel MC, Ambrosch P, Martin A, Steiner W. Impact of re-resection for inadequate margins on the prognosis of upper aerodigestive tract cancer treated by laser microsurgery. Laryngoscope. 2007;117(2):350–6.

    Article  PubMed  Google Scholar 

  30. Kwok P, Gleich O, Hubner G, Strutz J. Prognostic importance of "clear versus revised margins" in oral and pharyngeal cancer. Head Neck. 2010;32(11):1479–84.

    Article  PubMed  Google Scholar 

  31. Patel RS, Goldstein DP, Guillemaud J, et al. Impact of positive frozen section microscopic tumor cut-through revised to negative on oral carcinoma control and survival rates. Head Neck. 2010;32(11):1444–511.

    Article  PubMed  Google Scholar 

  32. Scholl P, Byers RM, Batsakis JG, Wolf P, Santini H. Microscopic cut-through of cancer in the surgical treatment of squamous carcinoma of the tongue. Prognostic and therapeutic implications. Am J Surg 1986;152(4):354–60.

  33. Bulbul MG, Tarabichi O, Sethi RK, Parikh AS, Varvares MA. Does clearance of positive margins improve local control in oral cavity cancer? A meta-analysis. Otolaryngol Head Neck Surg 2019. https://doi.org/10.1177/0194599819839006

  34. Buchakjian MR, Ginader T, Tasche KK, Pagedar NA, Smith BJ, Sperry SM. Independent predictors of prognosis based on oral cavity squamous cell carcinoma surgical margins. Otolaryngol Head Neck Surg 2018;154(4):675–82.

  35. Varvares MA, Poti S, Kenyon B, Christopher K, Walker RJ. Surgical margins and primary site resection in achieving local control in oral cancer resections. Laryngoscope. 2015;125(10):2298–307.

    Article  PubMed  Google Scholar 

  36. Tassone P, Savard C, Topf MC, et al. Association of positive initial margins with survival among patients with squamous cell carcinoma treated with total laryngectomy. JAMA Otolaryngol Head Neck Surg. 2018;144(11):1030–6.

  37. AJCC 8th Edition Updates and Corrections. In; 2019.

  38. Giurintano JP, Ha PK. Should margin sampling be obtained from the specimen or from the resection bed in oral cavity cancer? In: Difficult decisions in head and neck oncologic surgery. Berliin: Springer; 2019. p. 31–39.

  39. Network NCC. Head and Neck Cancers. In; 2019.

  40. Amit M, Na'ara S, Leider-Trejo L, et al. Improving the rate of negative margins after surgery for oral cavity squamous cell carcinoma: A prospective randomized controlled study. Head Neck. 2016;38(Suppl 1):E1803–E18091809.

    Article  PubMed  Google Scholar 

  41. Ettl T, El-Gindi A, Hautmann M, et al. Positive frozen section margins predict local recurrence in R0-resected squamous cell carcinoma of the head and neck. Oral Oncol. 2016;55:17–23.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Otolaryngology, Head and Neck Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

    Mark W. Kubik & Shaum Sridharan

  2. Department of Otolaryngology, Head and Neck Surgery, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, USA

    Mark A. Varvares

  3. Division of Hematology/Oncology, University of Pittsburgh Medical Center, Hillman Cancer Center, Pittsburgh, PA, USA

    Dan P. Zandberg

  4. Department of Radiation Oncology, UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Heath D. Skinner

  5. Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

    Raja R. Seethala & Simion I. Chiosea

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  1. Mark W. Kubik
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Correspondence to Simion I. Chiosea.

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Kubik, M.W., Sridharan, S., Varvares, M.A. et al. Intraoperative Margin Assessment in Head and Neck Cancer: A Case of Misuse and Abuse?. Head and Neck Pathol 14, 291–302 (2020). https://doi.org/10.1007/s12105-019-01121-2

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  • DOI: https://doi.org/10.1007/s12105-019-01121-2

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