Frozen Section Pathology for Decision Making in Parotid Surgery

Research

Original Investigation Frozen Section Pathology for Decision Making in Parotid Surgery

Kerry D. Olsen, MD; Eric J. Moore, MD; Jean E. Lewis, MD

IMPORTANCE For parotid lesions, the high accuracy and utility of intraoperative frozen section (FS) pathology, compared with permanent section pathology, facilitates intraoperative decision making about the extent of surgery required.

OBJECTIVE To demonstrate the accuracy and utility of FS pathology of parotid lesions as one factor in intraoperative decision making.

DESIGN, SETTING, AND PARTICIPANTS Retrospective review of patients undergoing parotidectomy at a tertiary care center.

INTERVENTIONS Evaluation of the accuracy of FS pathology for parotid surgery by comparing FS pathology results with those of permanent section.

MAIN OUTCOMES AND MEASURES Documented changes from FS to permanent section in 1339 parotidectomy pathology reports conducted from January 1, 2000, through December 31, 2009, included 693 benign and 268 primary and metastatic malignant tumors.

RESULTS Changes in diagnosis were found from benign to malignant (n = 11) and malignant to benign (n = 2). Sensitivity and specificity of a malignant diagnosis were 98.5% and 99.0%, respectively. Other changes were for lymphoma vs inflammation or lymphoma typing (n = 89) and for confirmation of or change in tumor type for benign (n = 36) or malignant (n = 69) tumors. No case changed from low- to high-grade malignant tumor. Only 4 cases that changed from FS to permanent section would have affected intraoperative decision making. Three patients underwent additional surgery 2 to 3 weeks later. Overall, only 1 Author Affiliations: Department of patient was overtreated (lymphoma initially deemed carcinoma). Otorhinolaryngology–Head and Neck Surgery, Mayo Clinic, Rochester, Minnesota (Olsen, Moore); Division CONCLUSIONS AND RELEVANCE Frozen section pathology for parotid lesions has high of Anatomic Pathology, Mayo Clinic, accuracy and utility in intraoperative decision making, facilitating timely complete Rochester, Minnesota (Lewis). procedures. Corresponding Author: Kerry D. Olsen, MD, Department of Otorhinolaryngology–Head and Neck JAMA Otolaryngol Head Neck Surg. 2013;139(12):1275-1278. doi:10.1001/jamaoto.2013.5217 Surgery, Mayo Clinic, 200 First St SW, Published online October 17, 2013. Rochester, MN 55905 (olsen.kerry @mayo.edu).

arotid neoplasms are uncommon tumors that present Many centers use preoperative FNA cytology to aid in di- unique challenges in diagnosis and effective treat- agnosis and management decision making. However, FNA cy- P ment planning. The patient’s history, examination find- tology of salivary gland lesions has a high false-negative rate ings, and imaging all contribute to an overall clinical assess- that limits its usefulness, so few surgeons are willing to com- ment. Operative decision making, including the amount of mit to a comprehensive or extended surgical procedure on the gland removed (partial, superficial, deep, or total), facial nerve result of this test alone. Physicians may use FNA cytology for resection (partial or total), and removal of parotid and re- an initial impression and delay any decisions on major sur- gional cervical nodes, is generally based on clinical and surgery or other treatment until permanent section pathology is gical findings, imaging results, and the pathologic diagnosis available. from fine-needle aspiration (FNA) cytology, frozen section (FS) Some medical centers also use FS pathology for parotid pa- pathology, or permanent section pathology (standard hema- thology and margin analysis. However, many pathologists do toxylin-eosin–stained sections). Accurate pathologic diagno- not because of the rarity of these neoplasms, the variety of tu- sis is challenging because of the rarity and variety of parotid mors, and the challenges in making an accurate diagnosis from tumors. FS pathology. Prior authors evaluating the value of FS pathol-

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ogy have determined that it offers greater accuracy and more and pathologic findings are all used to guide intraoperative and improved sensitivity than FNA cytology. Most studies, though, postoperative management. have examined only the accuracy of FS pathology in determining benign vs malignant disease and margin extent.1 At our institution, FNA cytology is rarely performed for pa- Methods rotid lesions. Instead, we rely on FS pathology to provide histopathologic intraoperative information to guide surgical man- Frozen section analysis of nearly all surgical specimens is stan- agement. The surgeon needs to know not only whether the dard practice at our institution. Approximately 20 patholo- tumor is benign or malignant but also whether it is lym- gists with general expertise participate in the FS laboratory. In phoma or carcinoma, whether it is low grade or high grade, the most cases, a final report is generated on the basis of the FS status of any intraparotid and extraparotid lymph nodes, and pathology result. However, in more complex cases, such as the margin analysis. The extent of parotid and neck surgery is those requiring immunostains and/or intradepartmental con- influenced by pathologic information. Operative surgical de- sultation, a preliminary FS report is issued, and the final re- cisions include whether a partial, superficial, deep, or total pa- port is deferred to permanent section. For every FS proce- rotidectomy should be performed. Margin analysis of an in- dure performed, a corresponding hematoxylin-eosin section volved nerve or adjacent structures also factors into the extent is prepared and reviewed the following day. of an operation. Finally, a decision regarding the removal of Approval from the Mayo Clinic Institutional Review Board regional neck nodes and deep lobe parotid nodes can be guided was obtained to review all FS and permanent section pathol- by the parotid tumor histology and/or involvement of the nodes ogy reports for all cases of parotid gland surgery in patients in the superficial lobe. Frozen section pathology can help in who had given written permission for the use of their medi- all of these decision points, especially the last one. cal records for research purposes. Any change in diagnosis on If FS pathology provides reliable information, patients the permanent section pathology report was noted, even if a could benefit by receiving all surgical procedures in a single preliminary FS pathology report stated that the diagnosis was operation. There would be no need to return later to the op- suspect or suspicious, and it was then confirmed on perma- erating room for an operation the surgeon would have per- nent section. When there was any change in the final pathol- formed if the correct diagnosis had been known at the time of ogy report, we reviewed it to determine whether the change the initial surgery or to rely instead on radiation therapy post- led to overtreatment or undertreatment surgically. All appli- operatively. Accurate FS pathology can provide the surgeon cable surgical records were then reviewed. with an important factor in planning a rational oncologic procedure that is based on knowledge of tumor behavior. However, if the information from FS parotid pathology is Results not accurate, it may increase the potential for performing the wrong operation and possibly harming the patient. The pa- During a 10-year period from January 1, 2000, through Decem- tient may undergo unnecessary surgery, return for another op- ber 31, 2009, a total of 1339 parotid surgical procedures were eration, or accept a nonsurgical treatment because surgeons conducted at Mayo Clinic, Rochester, Minnesota, with FS analy- may be reluctant to operate again in a parotid bed after prior sis performed on each case. Subsequent pathologic review led parotid surgery. to a permanent pathologic diagnosis for each case. There were For the patient with a parotid mass, we use FS evaluation 693 benign tumors and 268 primary and metastatic malig- of the lesion as a key factor to determine whether to proceed nant lesions. The remaining 378 cases included infections, si- with deep lobe removal or neck dissection during the initial aladenitis, and inflammatory nodes. operation. Frozen section pathology has been used for sev- No change was found in the pathology report from FS to eral decades in all parotid operations at Mayo Clinic. This in- permanent section in 1119 of the 1339 cases of parotid surgery traoperative diagnostic approach has potential value for our that underwent the FS procedure. The remaining 220 cases patients. If accurate, it could be cost-effective if it eliminated were studied in detail. The change from FS to permanent sec- the need for FNA, additional surgery, or radiotherapy. tion included both those cases for which the diagnosis was pre- This report is the largest series to date evaluating the ac- liminary and confirmed on permanent section and those cases curacy of FS pathology for parotid surgery. We sought to de- that were indeterminate or that had any substantive change termine whether the FS diagnosis of the pathologist, as con- made in diagnosis from FS to permanent section (Table). veyed to the surgeon, provided information that led to Of the 220 cases, 89 were suggestive of lymphoma or an overtreatment or undertreatment. We wanted to determine inflammatory process. The final diagnosis was confirmed or whether FS pathology results had a positive or negative ef- determined with additional pathologic study. There was only fect overall on surgical treatment decision making, beyond just 1 case of presumed lymphoma, which proved to be a carci- determining whether a tumor was malignant or benign. An FS noma (ie, Merkel cell carcinoma). In addition, only a single case pathology report of a high-grade malignant tumor with known of lymphoma was incorrectly identified on FS as high-grade potential for lymphatic spread or the pathologic finding of posi- carcinoma. tive superficial parotid nodes often leads to the decision at sur- Our review identified 69 cases of suspected malignant gery to proceed with a deep lobe parotidectomy and neck dis- tumor on FS that had some change in the final pathology section to remove potential metastatic cancer. Clinical, surgical, report. A specific suspected malignant tumor was confirmed

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Table. Changes in Pathology Report From Frozen Section to Permanent Section in 220 of 1339 Patients Undergoing Parotid Surgery

Frozen Section Diagnosisa Lymphoma vs Nodal Status/ Permanent Section Inflammation Malignant Tumor Benign Tumor Margin Status Diagnosis (n = 89) (n = 69) (n = 53) (n=9) Lymphoma vs 88 1 (From high-grade car- 0… inflammation cinoma to lymphoma)b Malignant tumor 1 (From lymphoma 66 (No high grade to 11 (1 Case intermedi- 8 to Merkel cell)b low grade or vice versa) ate; others low grade)b Benign tumor … 2 42 … a Ellipses indicate data not applicable. Nodal status/ … … … 1 (From node negative b margin status to node positive)b Case for which an incorrect frozen section diagnosis would have Total 89 69 53 9 changed initial surgery (n = 4).

in 27 cases; in 40 of the other 42 cases, permanent section pathology proved it to be a Merkel cell carcinoma. The sec- pathology revealed a different final pathologic malignant ond case was initially believed to be a benign tumor, tumor. An example of the latter was adenocarcinoma on FS whereas permanent section pathology identified it as an evaluation identified as salivary duct–type carcinoma on the intermediate-grade mucoepidermoid cancer. The third case final pathology report. There were no cases of high-grade that required additional surgery was initially identified as cancer changed to low-grade cancer on the final pathology node-negative metastatic melanoma, whereas permanent report or vice versa. Only 2 cases were thought to be malig- section pathology found a parotid node that had been nant and instead proved to be benign on permanent section removed to be positive for metastasis. A neck dissection was pathology. Both were initially reported to be low-grade performed later. malignant tumors. Our review identified 53 cases of suspected benign tumor on FS pathology that had some change in the final pathology Discussion report. Thirty-six benign tumors had a pathologic classifica- tion on permanent section pathology that basically con- Most prior studies examining the accuracy and use of FS pa- firmed the presumed FS diagnosis. In the other 17 cases, the thology have compared it with FNA cytology and have docu- diagnosis was changed on permanent section pathology to an- mented improved accuracy of FS pathology over FNA other type of benign tumor, such as from monomorphic ad- cytology.1-3 Fine-needle aspiration cytology has been found to enoma to basal cell adenoma tumor (n = 6). A benign tumor have a high false-negative rate, up to 20%, that limits its suspected on FS proved to be a malignant tumor on perma- usefulness.1 nent pathology in only 11 cases. Ten of these 11 cases were ini- Reports to date of FS pathology as a diagnostic tool for pa- tially reported to the surgeon as benign tumors or as possible rotid surgery have largely focused on the ability to differenti- low-grade malignant tumors. One case proved to be an inter- ate a benign from a malignant tumor. One analysis of this fac- mediate-grade mucoepidermoid cancer. No cases were tor found the efficacy of FS pathology to be good, with changed to a high-grade cancer. specificity of 99% and sensitivity of 90%.2 Others have re- Finally, in 8 cases the number of involved nodes noted on ported 100% accuracy in both sensitivity and specificity.2 Our FS was different from the number identified on permanent sec- study found 98.5% sensitivity and 99.0% specificity for FS pa- tion pathology, and in 1 case several margins initially re- thology in detecting malignant tumors. ported as negative proved instead to be positive on perma- However, rather than just being a useful adjunct to intra- nent section pathology. operative decision making, FS pathology is most helpful if it Of all 220 cases, only 4 could be identified in which the can reliably determine more than whether a lesion is benign FS diagnosis would have altered intraoperative decision or malignant. It is important to know whether the tumor is lym- making if the final pathology report had been known. One phoma or carcinoma, whether it is a low-grade or a high- case involved a rapidly growing destructive lesion that was grade malignant tumor, and what the status is of the intrapa- replacing the parotid gland. Initial FS biopsy during surgery rotid nodes and peripheral margins. identified it as a high-grade carcinoma. A total parotidec- Our findings indicate that with experienced pathologists, tomy was performed. On permanent pathology, the case FS evaluation of the tumor and superficial parotid nodes can proved to be a high-grade lymphoma. This was the single be helpful in intraoperative decision making. Our patients un- case of overtreatment in the series. Three cases with FS dergoing parotid surgery are told that any tumor found with a pathology had the diagnosis changed on permanent section high likelihood of metastatic spread to the deep portion of the pathology such that the patient later returned to the operat- gland or neck nodes will be managed with deep lobe paroti- ing room for additional surgery. If the correct diagnosis had dectomy and select neck dissection during the same opera- been made initially, the additional operation would not have tion. In addition, FS pathology is helpful in evaluating mar- been necessary. Of these 3 cases, the first was initially gin status and aiding in determining the extent of surgery. It believed to be a lymphoma, whereas permanent section is one factor in decision making that is pertinent to sacrifice

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or preservation of the facial nerve. However, most decisions We believe that the histopathologic information pro- concerning the facial nerve rest equally on intraoperative find- vided by the pathologist is valuable in guiding the extent of ings, and a preoperative functioning facial nerve is almost al- treatment and the management of metastatic nodal disease. ways preserved. Most low-grade malignant tumors and be- Decisions made at the time of surgery include proceeding with nign tumors are generally treated the same. deep lobe removal, performing neck dissection, or extending Cost is an important consideration with the routine use the initial resection for management of adjacent structures and of FS pathology. Because FNA cytology is rarely performed the facial nerve.5 in our practice and FS pathology helps some patients avoid Frozen section pathology for parotid lesions can be quite returning at a later date to the operating room, the cost of FS accurate. In parotid surgery, the pathologist remains one of the pathology may be justified. Its use in guiding appropriate most important members of the surgical team. The routine use surgery also helps avoid postoperative radiotherapy in some of FS pathology for parotid pathology is valuable in that it can cases. provide information that may alter surgical management and Intraoperative parotid surgical decision making as a ben- add to patient safety, efficacy of treatment, and improved out- efit to the use of FS pathology has been described by other comes. Frozen section pathology for parotid tumors can in- authors.4 Reports have documented its value in making a di- form the surgeon of more than just whether the tumors are be- agnosis, delineating margins, and determining whether the fa- nign or malignant. It is accurate in distinguishing carcinoma cial nerve or neck nodes are involved. Its main value has been from lymphoma, high-grade from low-grade tumors, and the discussed in margin analysis and in differentiation of benign involvement of parotid nodes. This information can be valu- from malignant tumors.2 able in surgical and nonsurgical management.

ARTICLE INFORMATION intellectual content: All authors. 2. Arabi Mianroodi AA, Sigston EA, Vallance NA. Submitted for Publication: April 1, 2013; final Administrative, technical, and material support: Frozen section for parotid surgery: should it revision received July 3, 2013; accepted August 5, Olsen, Lewis. become routine? ANZ J Surg. 2006;76(8):736-739. 2013. Study supervision: Olsen. 3. Megerian CA, Maniglia AJ. Parotidectomy: a ten Published Online: October 17, 2013. Conflict of Interest Disclosures: None reported. year experience with fine needle aspiration and doi:10.1001/jamaoto.2013.5217. Previous Presentation: Presented at the Eighth frozen section biopsy correlation. Ear Nose Throat J. 1994;73(6):377-380. Author Contributions: Drs Olsen and Lewis had full International Conference on Head and Neck access to all of the data in the study and take Cancer; July 23, 2012; Toronto, Ontario, Canada. 4. Hillel AD, Fee WE Jr. Evaluation of frozen section responsibility for the integrity of the data and the in parotid gland surgery. Arch Otolaryngol. accuracy of the data analysis. REFERENCES 1983;109(4):230-232. Study concept and design: All authors. 1. Schmidt RL, Hunt JP, Hall BJ, Wilson AR, Layfield 5. Olsen KD, Moore EJ. Deep lobe parotidectomy: Acquisition of data: Olsen, Moore. LJ. A systematic review and meta-analysis of the clinical rationale in the management of primary and Analysis and interpretation of data: All authors. diagnostic accuracy of frozen section for parotid metastatic cancer [published online ahead of print Drafting of the manuscript: Olsen, Moore. gland lesions. Am J Clin Pathol. 2011;136(5): July 6, 2013]. Eur Arch Otorhinolaryngol.2013. Critical revision of the manuscript for important 729-738. doi:10.1007/s00405-013-2616-8.

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