ADASP Committee
The Association of Directors of Anatomic and Surgical Pathology (ADASP) has published numerous documents with recommendations for reporting of Surgical Pathology specimens involving particular organ sites (for example, breast, pancreas, thyroid, etc.) However, the Association has not yet considered the generic question of dealing with lymph node specimens in which the intent is to search for and document the presence of metastatic disease. We are also unaware of guidelines for pathologists published by any other organization on this subject.
It is well known that different pathologists in different laboratories follow different protocols for the processing and examination of these specimens. There is also extensive literature (some of which is summarized on the References appended to the present report) on the likelihood of identifying metastases of varying sizes with different methods of preparation, as well as on the clinical significance of this identification, which varies not only from site to site but also from report to report on the same site. The Association has reviewed this literature as well as the personal experience of its own members to present a set of recommendations for lymph node biopsies, lymph node dissections, sentinel node biopsies, and lymph node fine needle aspiration (FNA) and core needle biopsies. It should be noted that these recommendations are intended specifically for lymph nodes being studied for metastatic neoplasms, and are not intended to apply to lymph nodes being evaluated for lymphoma, infections, and other disease processes. They are, however, formulated generically enough to apply regardless of whether the primary tumor is a carcinoma of the breast, carcinoma of the prostate, melanoma, or any other malignant, potentially metastasizing tumor.
A. Lymph Node Biopsies
-
1
In the presence of gross tumor in a biopsy of a single lymph node, one or several routine sections to demonstrate the tumor and its possible extranodal extension will suffice.
-
2
In the absence of gross tumor, the entire node should be submitted for microscopic examination, cut into 3 to 4 mm slices in the longitudinal or transverse plane. If the node is so small that it cannot be sliced in this manner, it may be submitted as one piece in toto. If the node is sliced, care should be taken to process different surfaces for microscopic examination. The Association recommends the examination of several levels of each slide, stained with hematoxylin and eosin (H&E) only.
B. Lymph Node Dissections
-
1
Processing and Staining
-
a
a. As mentioned above, the principles presented here are generic, and may vary by site or by institution.
-
b
b. Lymph node dissections are best processed fresh, although other techniques (such as fixation in Bouin’s solution) may be used.
-
c
c. No clearing of adipose tissue is necessary, although it may represent an institutional or individual preference.
-
d
d. Submit every node for microscopic examination.
-
e
e. Submit the entire nodes cut as described in Section A unless they contain grossly visible tumor, in which case fewer slices are required, or if they are grossly largely replaced by adipose tissue, in which case processing is optional.
-
f
f. Lymph node levels in a dissection specimen should be specified and submitted separately where clinically appropriate (for example, neck dissections, colectomy specimens).
-
g
g. The summary of sections in the Surgical Pathology report should include how many sections of how many nodes are submitted in each cassette. Different color inks may be used to distinguish different nodes submitted in a single cassette.
-
h
h. One H&E slide per cassette is recommended.
-
i
i. Immunohistochemistry and other specialized techniques may be used as part of a research study or for different diagnosis, but are not now considered mandatory.
-
a
-
2
Reporting
-
a
a. The number of lymph nodes positive for metastatic disease and the total number of lymph nodes examined microscopically should be reported, with specific levels mentioned when appropriate.
-
b
b. The size of the largest metastasis (measured on the slide) should be reported if clinically indicated.
-
c
c. The presence of extracapsular extension may be reported, depending upon the primary site and institutional preference.
-
d
d. If the only tumor seen is in extranodal vessels, this should be stated.
-
e
e. Deposits of tumor not associated with any structure recognizable as a lymph node should be separately designated.
-
f
f. In rare situations, the grading of nodal metastases may be important.
-
g
g. After preoperative chemotherapy and/or radiotherapy, notation of necrotic versus non-necrotic tumor is recommended.
-
a
C. Sentinel Node Biopsy
-
1
The adequacy of the sentinel node dissection depends upon the skill and experience of the surgeon. At the present time, clinical utility of this technique is still controversial. In many institutions, this is still considered an experimental procedure.
-
2
Where this factor has been studied, the level of radiation associated with sentinel node biopsy has not been demonstrated to pose any danger to pathologists or histotechnologists from radioactivity. However, protocols should conform to institutional and state guidelines.
-
3
Intraoperative examination, whether by frozen section or scrape/imprint cytology or both, is appropriate only in those clinical situations in which the results will influence immediate therapeutic management. Examination of the intraoperative specimen by other than routine (H&E) stains is experimental at the present time.
-
4
The number of nodes received and their sizes should be noted in the gross description of the report. Each node should be processed grossly as mentioned earlier under Dissections. If any portion of the sentinel node(s) is not submitted for routine sectioning, this should be specified.
-
5
ADASP recommends that more than one section be performed on each block in these cases, if the node or nodes are not positive grossly or at intraoperative pathologic consultation. However, it is not currently clear how many sections (and from what levels of the block) are optimal. It is also unclear whether immunostains add clinically relevant information and whether they may be substituted for additional H&E-stained sections. It should be remembered that false positive immunostains occur, and these stains should be interpreted in the context of standard histopathology.
-
6
If metastases are identified only by immunostains, this should be stated in the final report. Other statements on reporting provided in Section B (2) of this document are also applicable.
D. Fine Needle Aspiration and Core Needle Biopsy
-
1
A negative result for tumor does not definitely exclude the presence of a metastatic tumor. Results should be correlated with the clinical situation.
-
2
If only FNA is performed, a cell block may be useful for special studies in positive cases.
-
3
If only a core needle biopsy is performed, all tissue should be submitted. The number of cores received should be specified in the gross description, and should be correlated with the slides received and examined.
-
4
In many cases, it may not be possible to document on an FNA or core needle biopsy specimen that a metastatic tumor is indeed within a lymph node. In such a situation, a comment should be made to that effect. (1, 2, 3, 4, 5, 6, 7, 8, 9, 10) (11, 12, 13, 14, 15, 16, 17, 18, 19, 20) (21, 22, 23, 24, 25, 26, 27, 28, 29, 30) (31, 32, 33, 34, 35, 36)
References
Ambrosch P, Kron M, Fischer G, Brinck U . Micrometastases in carcinoma of the upper aerodigestive tract: detection, risk of metastasizing, and prognostic value of depth of invasion. Head Neck 1995; 17: 473–479.
Anderson TJ . The challenge of sentinel lymph node biopsy. Histopathology 1999; 35: 82–84.
Calaluce R, Miedema BW, Yesus YW . Micrometastases in colorectal carcinoma: a review. J Surg Oncol 1998; 67: 194–202.
Carnino F, Fuda G, Ciccone G, Iskra L, Guercio E, Dadone D . Significance of lymph node sampling in epithelial carcinoma of the ovary. Gynecol Oncol 1997; 65: 467–472.
Cibull ML . Handling sentinel lymph node biopsy specimens. A work in progress. Arch Pathol Lab Med 1999; 123: 620–621.
Cochran AJ . Surgical pathology remains pivotal in the evaluation of “sentinel” lymph nodes. Am J Surg Pathol 1999; 23: 1169–1172.
Cox DE, Pendas S, Cox JM, Joseph E, Shons AR, Yeatman T, et al. Guidelines for sentinel node biopsy and lymphatic mapping of patients with breast cancer. Ann Surg 1998; 227: 645–651.
Demeure MJ, Doffek KM, Komorowski RA, Wilson SD . Adenocarcinoma of the pancreas: detection of occult metastases in regional lymph nodes by a polymerase chain reaction-based assay. Cancer 1998; 83: 1328–1334.
Dobashi K, Sugio K, Osaki T, Oka T, Yasumoto K . Micrometastatic p53-positive cells in the lymph nodes of non-small-cell lung cancer: prognostic significance. J Thorac Cardiovasc Surg 1997; 114: 339–346.
Dowlathshahi K, Fan M, Snide HC, Habib FA . Lymph node micrometastases from breast carcinoma: reviewing the dilemma. Cancer 1997; 80: 1188–1197.
Giuliano AE, Jones RC, Brennan M, Statman R . Sentinel lymphadenectomy in breast cancer. J Clin Oncol 1997; 15: 2345–2350.
Hermanek P, Hutter RVP, Sobin LH, Wittekind C . Communication from the International Union Against Cancer. Classification of isolated tumor cells and micrometastasis. Cancer 1999; 86: 2668–2673.
Ishida K, Katsuyama T, Sugiyama A, Kawasaki S . Immunohistochemical evaluation of lymph node micrometastases from gastric carcinomas. Cancer 1997; 79: 1069–1076.
Jannink I, Fan M, Nagy S, Rayudu G, Dowlatshahi K . Serial sectioning of sentinel nodes in patients with breast cancer: a pilot study. Ann Surg Oncol 1998; 5: 310–314.
Krag D, Weaver D, Ashikaga T, Moffat F, Klimberg VS, Shriver C, et al. The sentinel node in breast cancer—a multicenter validation study. N Engl J Med 1998; 339: 941–946.
Liberman L . Pathologic analysis of sentinel lymph nodes in breast carcinoma. Cancer 2000; 88: 971–977.
Liefers GJ, Cleton-Jansen AM, van de Velde CJH, Hermans J, van Krieken JH, Cornelisse CJ, et al. Micrometastases and survival in stage II colorectal cancer. N Engl J Med 1998; 339: 223–228.
Lockett MA, Baron PL, O’Brien PH, Elliott BM, Robison JG, Maitre N, et al. Detection of occult breast cancer micrometastases in axillary lymph nodes using a multimarker reverse transcriptase-polymerase chain reaction panel. J Am Coll Surg 1998; 187: 9–16.
Maruyama R, Sugio K, Mitsudomi T, Saitoh G, Ishida T, Sugimachi K . Relationship between early recurrence and micrometastases in the lymph nodes of patients with stage 1 non-small-cell lung cancer. J Thorac Cardiovasc Surg 1997; 114: 535–543.
Natsugoe S, Mueller J, Stein HJ, Feith M, Hofler H, Siewert JR . Micrometastasis and tumor cell microinvolvement of lymph nodes from esophageal squamous cell carcinoma: frequency, associated tumor characteristics, and impact on prognosis. Cancer 1998; 83: 858–866.
Niemann TH, Yilmaz AG, Marsh WL Jr, Lucas JG . A half a node or a whole node: a comparison of methods for submitting lymph nodes. Am J Clin Pathol 1998; 109: 571–576.
Oberg A, Stenling R, Tavelin B, Lindmark G . Are lymph node micrometastases of any clinical significance in Dukes Stages A and B colorectal cancer? Dis Colon Rectum 1998; 41: 1244–1249.
Page DL, Anderson TJ, Carter B . Minimal solid tumor involvement of regional and distant sites. Cancer 1999; 86: 2589–2592.
Pelkey TJ, Frierson HF Jr, Bruns DE . Molecular and immunological detection of circulating tumor cells and micrometastases from solid tumors. Clin Chem 1996; 42: 1369–1381.
Pfeifer JD . Sentinel lymph node biopsy. Am J Clin Pathol 1999; 112: 599–602.
Reintgen D . More rational and conservative surgical strategies for malignant melanoma using lymphatic mapping and sentinel node biopsy techniques. Curr Opin Oncol 1996; 8: 152–158.
Reintgen D, Shivers D . Sentinel lymph node micrometastasis from melanoma. Proven methodology and evolving significance. Cancer 1999; 86: 551–552.
Shigaki S, Ohtake K, Nomura T, Nakajima T . The value of single versus multiple sections for detection of lymph node metastasis. J Oral Maxillofac Surg 1991; 49: 461–463.
Turner RR, Chu KU, Qi K, Botnick LE, Hansen NM, Glass EC, et al. Pathologic features associated with nonsentinel lymph node metastases in patients with metastatic breast carcinoma in a sentinel lymph node. Cancer 2000; 89: 574–581.
Van De Brekel MW, van der Waal I, Meijer CJLM, Free-man JL, Castelijns JA, Snow GB . The incidence of micrometastases in neck dissection specimens obtained from elective neck dissections. Laryngoscope 1996; 106: 987–991.
Weaver DL, Krag DN, Ashikaga T, Harlow SP, O’Connell M . Pathologic analysis of sentinel and nonsentinel lymph nodes in breast carcinoma. A multicenter study. Cancer 2000; 88: 1099–1107.
Wilkinson EJ, Hause L . Probability in lymph node sectioning. Cancer 1974; 33: 1269–1274.
Yamamoto N, Kato Y, Yanagisawa A, Ohta H, Takahashi T, Kitagawa T . Predictive value of genetic diagnosis for cancer micrometastasis; histologic and experimental appraisal. Cancer 1997; 80: 1391–1398.
Yu LL, Flotte TJ, Tanabe KK, Gadd MA, Cosimi AB, Sober AJ . Detection of microscopic melanoma metastases in sentinel lymph nodes. Cancer 1999; 86: 617–627.
Yu K, Merrie AEH, Gunn J, Phillips LV, McCall JL . Keratin 20 is a specific marker of submicroscopic lymph node metastases in colorectal cancer: validation by K-RAS mutations. J Pathol 2000; 191: 21–26.
Zhang PJ, Reisner RM, Nangia R, Edge SB, Broods JJ . Effectiveness of multiple-level sectioning in detecting axillary nodal micrometastases in breast cancer: a retrospective study with immunohistochemical analysis. Arch Pathol Lab Med 1998; 122: 687–690.
Additional information
This document was prepared by an ADASP Committee consisting of Drs. Steven G. Silverberg (Chair), James L. Conolly, David Dabbs, Carlos A. Muro-Cacho, David L. Page, Mukunda B. Ray, and Mark R. Wick.
Address reprint requests to: W. Dwayne Lawrence, M.D., Department of Pathology, Hutzel Hospital, 4707 St. Antoine Boulevard, Detroit, MI 48201.
Rights and permissions
About this article
Cite this article
ADASP Recommendations for Processing and Reporting of Lymph Node Specimens Submitted for Evaluation of Metastatic Disease. Mod Pathol 14, 629–632 (2001). https://doi.org/10.1038/modpathol.3880362
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/modpathol.3880362
This article is cited by
-
Integrated analysis of 18F-FDG PET/CT improves preoperative lymph node staging for patients with invasive bladder cancer
European Radiology (2019)
-
Frozen section evaluation of breast carcinoma sentinel lymph nodes: a retrospective review of 1,940 cases
Breast Cancer Research and Treatment (2014)