Five Canadian and 18 US pathologists responded (total 23; see Acknowledgments and Supplement 1 for details; all supplemental materials can be found at American Journal of Clinical Pathology online).
Frequency of IOE of SLNs
Intraoperative consultation was requested on almost all SLNs in 10 (43.5%) institutions. In nine (39.1%) institutions, IOE of SLN was only requested in selected cases (such as patients undergoing mastectomy, post-neoadjuvant cases, patients who did not meet ACOSOG Z11 criteria) Figure 1A. In four (17.4%) institutions, three of which were Canadian, there were no requests for IOE of SLN.
A, Nearly half the institutions surveyed reported intraoperative consults only for selected cases. B-E, Demonstrates areas of dichotomy in pathology practice. B, Fat processing during intraoperative evaluation. C, Plane of sectioning. D, Permanent H&E levels. E, Keratin immunohistochemistry. F, Tumor in pericapsular lymphatic space. FS, frozen section; ITC, isolated tumor cell; LVI, lymphovascular invasion.
Comments. "The surgeons only freeze SLN for post neoadjuvant patients."
"Done in about 60% of cases. In other cases breast surgeons opt not to ask for frozen."
"Routinely done, even for patients meeting Z11 criteria, our surgeons are still requesting frozen, although we have a carepath that states there doesn't need to be an FS."
"We do NOT perform frozen on SLN if it is a clinically negative node and patient is having lumpectomy for invasive carcinoma. Inpatients with clinically positive nodes or known positive node; most get some type of neoadjuvant therapy and in those cases we do frozen on SLN. In patients with known positive nodes, as most have this biopsied and diagnosed before surgery, then there is no need for FS. For almost all patients with invasive carcinoma, or large DCIS [ductal carcinoma in situ] (generally over 5 cm) having mastectomy, we do FS on SLN. Our institution follows Z11 criteria. These are general principles but of course exceptions exist."
"FS is done for most DCIS patients undergoing mastectomy and for Alliance A011202 trial or similar patients (post-neoadjuvant chemotherapy with known axillary metastasis prior to therapy)."
"Only done in the setting of mastectomy for known ipsilateral invasive carcinoma without neoadjuvant chemotherapy."
"Our surgeons have not asked to implement this practice."
"Not anymore. Used to be by cytology touch prep. Rarely now for a large, suspicious node."
"Only perform for cases with clinically the node is felt to be grossly positive. If obviously positive only a representative section is frozen."
"Yes, for post neoadjuvant and mastectomy."
"Our surgeons never send sentinel lymph node for intraoperative consultation."
"Our surgeons feel comfortable waiting for final diagnosis on permanent sections."
"Mostly for mastectomy, after neoadjuvant, etc., not routinely done for BCS/Z11 patients."
Method of IOE
Of 19 institutions where intraoperative assessments are requested, the most common method of evaluation is using FS alone (13; 68.4%). In six institutions, FS and/or cytologic techniques are used (four imprints/touch preparation [TP], one smear, and one either, depending on pathologist preference). In one institution, the preference is for cytology (TP), except for post-neoadjuvant chemotherapy cases, where FS is used.
Comments. "FS, C [cytologic] or both—with recommendations from the breast service that frozens are preferred in post neoadjuvant cases, cases with scant atypical cells on touch prep or lobular cancers."
"Touch prep, except in NAC [neoadjuvant chemotherapy] treated patients where I prefer FS."
"Pathologist preference but predominantly FS > 95%."
Gross Evaluation of SLNs and Non-SLNs
During intraoperative evaluation, a sleeve of perinodal fat is retained (fat not completely trimmed) in nine (47.4%) institutions, for evaluation of extranodal extension Figure 1B and Figure 2. In eight (42.1%) institutions, the fat is completely trimmed. In two (10.5%) institutions, the practice is variable—trimmed fat is submitted for evaluation for extranodal extension for permanent sections in one institution. In 12 (52.2%) institutions, the entire node is submitted, usually sectioned at 2-mm intervals. Practice is variable in the others. The preferred plane of sectioning is perpendicular to the long axis in 12 (52.2%) institutions, parallel to the long axis in 8 (34.8%) institutions, and variable in 3 (13%) institutions Figure 1C and Figure 3. In all 23 institutions, non-SLNs are entirely processed at 2 mm.
Gross image. Lymph node with surrounding adipose tissue. Gross extranodal extension is generally an indication for axillary lymph node dissection.
Gross image. Two lymph nodes of near-equal size sectioned perpendicular to the long axis (left) and parallel to long axis (right).
Comments. "As much fat is trimmed as possible."
"Fat is trimmed as best as possible."
"As much fat as possible is trimmed away if peels off easily. If adherent and worrisome for extranodal extension, this is submitted. Any trimmed tissue is submitted for permanent sections."
"Fat is either trimmed or lipid is removed by gentle rolling the lymph node on a paper towel or similar material."
"Depends on the setting and size of node. Smaller nodes are bisected, larger ones breadloafed at 2 mm intervals perpendicular to long axis. Gross assessment is performed, if suspicious areas are seen, these are submitted, otherwise 1–2 of the largest sections are processed for FS and the remainder is fixed and processed routine FFPE [formalin-fixed, paraffin-embedded]."
"We freeze all nodes entirely when we do FS—typically bisected, freeze both halves, but if very large may need to try to trisect or serially section at 2 mm intervals etc. and if very small just put on whole."
"Bisected trisected or more—whatever necessary to freeze entirely, at least bisected unless tiny."
"Sections such that 2 mm intervals are used; if we can achieve that by bivalving that is preferred."
"For non-sentinel nodes, we always put in all nodal tissue but the way we section it depends on the node size—may breadloaf at 2 mm intervals or bisect—I do not think we have one set way of doing it other than to make sure all nodal tissue is submitted."
"Bisect and submit both halves, unless too big, then serial section and submit at 2 mm intervals."
"We process half and save half for permanents. We serially section/breadloaf the node at 2 mm intervals, inspect for any grossly suspicious areas, and submit half of the node for frozen section (to include any grossly suspicious areas), and then submit remainder for permanents."
"Usually the node is sampled in toto at 2 mm intervals but not for gross metastatic disease were representative section is submitted."
In 11 (47.8%) academic institutions, only a single H&E slide is obtained from the FFPE block. In 12 (52.2%) institutions, multilevel evaluation is performed Figure 1D. Two H&E levels appear to be the most common practice (seven institutions). In four institutions, three H&E levels are obtained, and in one institution, four H&E levels are obtained. In six institutions, the levels are between 1 and 10 μm deep. The levels are between 10 and 15 μm deep in three institutions and between 100 and 200 μm deep in two institutions. In one institution, the depth of evaluation was not specified.
Comments. "Single H&E levels, with additional levels on an as-needed basis, typically 2 or 3 levels with all levels stained."
"We do not perform intraoperative consult on sentinel lymph nodes. We assess an initial H&E first. After assessing it, 3 H&E and CAM 5.2 and AE1/AE3 are requested if there is no obvious tumor."
"Microns may very between levels. We do not have a set guideline for our histotechs."
Use of Immunohistochemistry
In 12 (52.2%) institutions, a cytokeratin immunohistochemical stain is obtained if necessary on a case-by-case basis (if suspicious cells identified, lobular morphology noted, or following neoadjuvant therapy). Routine keratin immunohistochemistry is obtained in 11 (47.8%) academic institutions Figure 1E. In three institutions, routine immunohistochemistry is only obtained in cases of lobular carcinoma and/or following neoadjuvant therapy and in two institutions only if the frozen section is negative for carcinoma. Cytokeratin AE1/AE3 is the favored immunostain (18 institutions, 78.3%). In three institutions, both cytokeratin AE1/AE3 and CAM 5.2 are evaluated.
Comments. "Cytokeratin immunostain is obtained on the case-by-case basis at the discretion of the pathologist."
"Pathologists order on or lobular carcinoma and neoadjuvant cases when no mets are seen on the initial section."
"Yes, routinely unless the node was positive on FS, then no cytokeratin."
"We almost never obtain cytokeratin stains. If needed to evaluate atypical cells we do it."
"Only if suspicious cells are seen that are not obviously carcinoma—usually if treatment effect present and deciding if histiocytes or carcinoma, sometimes do with lobular cases if questionable cells present."
"I know a lot of institutions in the New York City area are not doing routine cytokeratins on SLN and I understand the rationale in many instances is because the significance of detection of ITC [isolated tumor cell] has not been clearly demonstrated. We however continue to do them and the clinicians do factor this information into the decision making in some cases."
"Very rarely, only in very few post neoadjuvant cases with treatment effect and rare atypical cells or histiocytoid invasive lobular carcinoma."
"Cytokeratin is only routinely performed on sentinel lymph node for invasive lobular carcinoma."
Challenges in Interpretation
Twenty-one (91.3%) pathologists document the extent of extranodal extension (two qualitatively) Figure 4. Thirteen (56.5%) pathologists would interpret tumor cells in the pericapsular lymphatic space as lymphovascular invasion, and 10 (43.5%) would interpret them as isolated tumor cells Figure 1F and Figure 5.
Extent of extranodal extension (H&E, ×6). Extranodal extension is emerging as a predictor of non–sentinel lymph node involvement and may be an indication for axillary lymph node dissection.
Tumor cells in pericapsular lymphatic spaces are variably interpreted as lymphovascular invasion or isolated tumor cells (H&E, ×20).
Comments. "Extranodal extension. We will usually make a comment if it is focal."
"Extranodal extension. Just state present or absent."
"Extranodal extension. Only to note if 'focal' or 'extensive' but no set criteria for each."
"Extranodal extension. Yes, but only qualitatively as 'focal' or 'extensive' per request of radiation oncologists."
"Provide #mm of greatest extent."
"Isolated tumor cells. This is still unclear to me, but per CAP [College of American Pathologists] guidelines, I classified these as metastatic. I will perform levels to see if tumor cells show up in the parenchyma but most of the time this does not help."
"If tumor is in cap/pseudosubcapsular or extends into cap from outside I considered a positive node and based on size it is ITC, micromet, etc. If all tumor is entirely in a lymphatic space which does not enter any part of the node, I consider it LVI [lymphovascular invasion]."
"I consider it as ITC, but I know some other pathologists in my institute consider it as LVI."
"It depends, if within the lymph node capsule, consider isolated tumor cells. But if outside the lymph node capsule in the perinodal adipose tissue consider LVI."
Other Comments. "We have tried to standardize across a healthcare system so that lymph nodes removed in hospital 'Y' will be handled the same way as lymph nodes removed in hospital 'Z.' Not perfect, but more standardized than we were 3 years ago."
"Most of the frozens are for post-NAC patients that are clinically node-negative after chemo (no longer palpable). Our surgeons submit at least 3 lymph nodes in post-NAC patients. We also mention if treatment effect is present, if clearly present."
"Our surgeons still ask for a lot of intraoperative consultation. It would be great if there were consensus guidelines that we could point to when this is clearly indicated. The main point of intraoperative consultation in this setting is to find obviously positive lymph nodes at this point (not detect micromets or ITCs)—so even moving to gross evaluation with TP or frozen on suspicious nodes may be a relevant way to go. We need more data on what to do post neoadjuvant though."
Am J Clin Pathol. 2021;156(6):980-988. © 2021 American Society for Clinical Pathology