Breast malignant
Breast cancer
Sentinel lymph nodes


Topic Completed: 9 September 2019

Revised: 12 September 2019

Copyright: 2002-2019, PathologyOutlines.com, Inc.

PubMed Search: Sentinel lymph nodes[TI] breast cancer[TI] free full text[sb]

Sucheta Srivastava, M.D.
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Cite this page: Srivastava S. Sentinel lymph nodes. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/breastmalignantsentinel.html. Accessed December 7th, 2019.
Definition / general
  • Sentinel lymph node (SLN) is the first lymph node in a lymph node bed to receive lymphatic drainage and metastasis from a tumor
Essential features
  • Sentinel lymph node is the first lymph node in a lymph node bed to receive lymphatic drainage from a tumor
  • Preoperative axillary ultrasound or standard breast MRI helps surgeon to determine the involvement of axillary lymph nodes
  • Methylene blue dye or radioactive colloid is injected around tumor to identify the draining sentinel lymph node at the time of surgery
  • Intraoperative frozen section or intraoperative imprint cytology can be performed on the sentinel lymph node to determine need for axillary lymph node dissection at the time of surgery
  • Axillary lymph node metastases are classified into 3 groups: isolated tumor cell clusters, micrometastasis and macrometastasis
Terminology
  • At least 1 node with presence or absence of cancer documented by pathologic examination is required for pathologic N classification
  • When the number of sentinel and nonsentinel nodes removed is < 6 nodes, the AJCC "sn" modifier is used
ICD coding
  • IDC-10 code for axillary sentinel lymph node is C77.3
    • It became effective in 2019 edition of ICD-10-CM on October 1, 2018
  • CPT code for axillary sentinel lymph node:
Epidemiology
  • In experienced hands, SLN biopsy can be successfully performed in > 90% of eligible breast cancer patients
  • May be useful even after neoadjuvant (preoperative) chemotherapy (Acad Radiol 2009;16:551)
Sites and pathophysiology
  • Axillary lymph nodes are divided into 3 levels:
    1. Low axilla: lateral to the lateral border of the pectoralis minor muscle
    2. Mid axilla: between the medial and lateral borders of the pectoralis minor muscle and the interpectoral (Rotter) lymph nodes
    3. Apical axilla or infraclavicular nodes: medial to the medial margin of the pectoralis minor muscle and inferior to the clavicle
  • Usually sentinel lymph node is in level I but may be at level II or level III; rarely intramammary, interpectoral (Rotter) or internal mammary node (Eur J Surg Oncol 2009;35:252)
  • Intramammary nodes are present within breast tissue and are most commonly found in the upper outer quadrant
    • Intramammary nodes may rarely be sentinel lymph nodes
    • These nodes are included with axillary nodes for AJCC N classification
  • Internal mammary nodes, supraclavicular nodes and infraclavicular nodes are rarely removed for breast cancer staging
    • If metastases are present in these nodes, there are specific AJCC N categories
  • Tumor is more likely at inflow junction of afferent lymphatic vessel (Am J Surg Pathol 2003;27:385)
Clinical features
  • Frozen section had 60% sensitivity and 100% specificity in one study, with atypical cases usually negative on permanent sections (Mod Pathol 2005;18:58)
  • Concentrated smear technique is more sensitive than direct smears (Am J Clin Pathol 2004;122:944)
  • High risk (60%) of tumor in nonsentinel nodes if sentinel node has macroscopic tumor (≥ 2 mm) versus low risk (3%) if microscopic tumor (0.2 - 2 mm) (Mod Pathol 2005;18:762)
  • Memorial Sloan Kettering Cancer Center nomogram is useful to surgeons to predict likelihood of nonsentinel lymph node axillary metastases (Ann Surg Oncol 2003;10:1140, J Am Coll Surg 2009;208:229)
  • Minimal morbidity and high accuracy of SLN biopsy in breast cancer have been validated by multiple independent investigators and the data suggest that this surgical technique may eventually replace complete lymph node dissection as the preferred axillary procedure for the management of early stage disease
  • In one study, 8% (21 of 271) had negative SLN but positive axillary nodes (Br J Surg 2006;93:374)
    • Rate was not affected by patient's age, histological tumor type or grade, timing of radioisotope injection or visualization on preoperative lymphoscintigraphy
    • Rate was associated with multifocality, resulting in a recommendation in Sweden to not to include multifocal tumors when performing sentinel node biopsy as a single staging procedure (Br J Surg 2006;93:374)
Radiology description
  • Axillary ultrasound is a very useful tool to determine axillary lymph node status prior to surgery
    • When combined with fine needle aspiration, the specificity of this modality significantly increases (World J Surg 2012;36:46)
  • Evaluation of axillary nodal status on standard breast MRI is comparable to dedicated axillary ultrasound in breast cancer patients
    • In patients who underwent preoperative standard breast MRI, axillary ultrasound can then be done on those with suspicious nodal findings on MRI (Eur J Radiol 2016;85:2288)
  • Benefit of preoperative identification of axillary metastases is that it allows the surgeon to proceed directly to axillary lymph node dissection and to avoid an unnecessary sentinel lymph node biopsy and the need for a second surgical procedure involving the axillary nodes (Radiographics 2013;33:1589)
  • Important features noted on ultrasonography, such as cortical thickening, hilar effacement and nonhilar cortical blood flow, are more important than size criteria in the identification of metastases (Radiographics 2013;33:1589)
  • Magnetic resonance imaging is also useful, with the added benefit of providing a global view of both axillae
  • Preoperative axillary ultrasound and fine needle aspirate cytology are routine at many breast units, with a sensitivity of 56% (confidence interval: 47 - 64%) and specificity of 90% (84 - 93%) for ultrasound alone and 76% (61 - 87%) and 100% (65 - 100%) combined with fine needle aspirate cytology before sentinel lymph node biopsy significantly increases the identification rate and decreases the false negative rate (J BUON 2011;16:454)
Prognostic factors
  • If SLN are negative, other axillary nodes are negative in > 95% of cases and axillary recurrence rate is only 0.3% at median 34 months (Eur J Surg Oncol 2008;34:1277)
  • Considered a suitable replacement for axillary dissection for staging / diagnosis in T1 and T2 tumors, with reduced morbidity because fewer lymph nodes are removed (Ann Surg Oncol 2008;15:1996)
Treatment
  • Presence of micro or macrometastasis on frozen section is an indication for axillary lymph node dissection
  • Although the majority of breast cancer patients are clinically node negative (cN0) at diagnosis, 15 - 20% will have a positive SLN designated as pN1(sn)
  • In early breast cancers with clinically uninvolved lymph nodes, findings show that long term survival does not differ after axillary radiotherapy and axillary dissection (Breast Care (Basel) 2018;13:331)
  • Study by Schmidt-Hansen et al. showed no differences in survival or recurrence rates observed between SLN biopsy alone, SLN biopsy followed by axillary radiotherapy and SLN biopsy followed by completion axillary lymph node dissection (Springerplus 2016;5:85)
    • Morbidity, however, increases in the case of axillary radiotherapy and especially completion axillary lymph node dissection when compared to SLN biopsy alone
  • Even though adjuvant therapeutic strategies rely on ER and HER2, the number of involved lymph nodes is still important for clinical decision making (Ann Oncol 2018;29:2153)
  • ER+ / HER2- patients with limited involvement of axillary lymph nodes, for example, might be spared adjuvant chemotherapy if the tumor biology is favorable (Ann Oncol 2018;29:2153)
  • Conversely, in ER+ patients with limited involvement of lymph nodes but either an adverse tumor biology or > 3 involved axillary lymph nodes, adjuvant chemotherapy is indicated (Breast Care (Basel) 2018;13:331)
  • Regardless of the ER status, the number of involved lymph nodes is important to tailor chemotherapy appropriately (Breast Care (Basel) 2018;13:331)
  • From a radiation oncologist's perspective, there is currently a trend towards extending the indication of locoregional radiotherapy from patients with high nodal burden (> 3 positive lymph nodes) to patients with only 1 - 3 positive nodes (N Engl J Med 2015;373:317, N Engl J Med 2015;373:1878)
Clinical images

Images hosted on other servers:

Blue stained axillary node

Frozen section / intraoperative description
  • Axillary SLN are identified by the surgeon by determining uptake of radiotracer, blue dye or both
  • Procedure: blue dye or radioactive colloid is injected around tumor, which travels to and identifies the first draining SLN
    • The lymph node is then submitted for intraoperative evaluation
  • 99mTc injection is used for lymphatic mapping to assist in the localization of lymph nodes draining a primary tumor site in patients with breast cancer, which is followed by lymphoscintigraphy to evaluate lymphatic flow and SLN
  • Some surgeons also use methylene blue dye in addition to the 99mTc injection to determine SLN intraoperatively
  • In most cases, if metastases are present, the SLN will be involved; in rare cases, only nonsentinel nodes contain metastases
  • Metastasis to nonsentinel lymph node can occur if the true SLN is completely replaced by tumor (and therefore is not detected by radioactive tracer or dye), if there is unusual lymphatic drainage or if there is failure of the technique to identify the node
    • This finding should be included in the report
  • Often drainage to > 1 lymph node group and SLN is identified
  • Intraoperative evaluation of axillary SLN is standard of care for breast cancer
  • Intraoperative frozen section or imprint cytology is performed on the SLN to determine need for axillary lymph node dissection (World J Surg Oncol 2008;6:69, Eur J Surg Oncol 2009;35:16)
  • One study proposed that removal of multiple SLN can be avoided by removing all hot and blue nodes and correlating with findings on lymphoscintigraphy (Acta Chir Belg 2010;110:185)
Frozen section images

Contributed by Sucheta Srivastava, M.D.

Macrometastasis

Micrometastasis

Macrometastasis

Microscopic (histologic) description / diagnostic criteria
  • See Staging of breast carcinoma
  • Size of the metastatic focus is measured from the largest contiguous cluster of tumor cells
  • Direct extension of primary tumor into a regional node is classified as node positive
    • Tumor nodule with a smooth contour in a regional node area is classified as a positive node
    • Size of the metastasis, not the size of the node, is used for the criterion for the N category
  • Cases with isolated tumor cells only in lymph nodes are classified as pN0(i+)
  • Dispersed pattern of lymph node metastasis can be difficult to categorize
    • Especially lobular carcinomas metastasize as single cells and do not form cohesive clusters
    • If > 200 tumor cells are present in 1 cross section of the node, then the category isolated tumor cells should not be used
    • If there is difficulty in assigning the N classification, it is recommended that the reason be provided in a note
  • Area of extracapsular extension is included in the overall size of the lymph node metastasis (if contiguous)
    • Size of the metastasis includes the tumor cells and the desmoplastic response (i.e. the cells do not need to be contiguous but the cells plus fibrosis should be contiguous)
    • Finding of extranodal invasion is also reported
  • Areas of carcinoma invading into the stroma in axillary adipose tissue, without residual nodal tissue, are considered to be positive lymph nodes
Microscopic (histologic) images

Contributed by Sucheta Srivastava, M.D.

Macrometastasis

Macrometastasis with extranodal extension

Micrometastasis


Isolated tumor cells, pancytokeratin

Status post neoadjuvant chemotherapy

Cytology description
  • Fine needle aspiration smears of positive axillary lymph node are characterized by crowded, disorganized groups of cells with enlarged nuclei, nuclear pleomorphism, irregular nuclear membranes, intracytoplasmic vacuoles with or without mucin
  • There may be necrosis or mucin in the background and single intact cells
  • Sensitivity of sentinel node biopsy cytology is reported between 40 - 90% and specificity ~100% in multiple studies (Am J Transl Res 2018;10:1860)
  • Factors that can affect the outcome of fine needle aspiration are size of the metastasis in the lymph node, experience of the person doing image guided fine needle aspiration, availability of the pathologist to evaluate sample for adequacy at the time of fine needle aspiration
Cytology images

Contributed by Sucheta Srivastava, M.D.

Touch prep

Diff-Quik

Papanicolaou

Cell block

Positive stains
Molecular / cytogenetics description
  • Recently, some studies have reported usefulness of molecular assays (J Clin Oncol 2008;26:3338)
  • Reverse transcriptase polymerase chain reaction (RT-PCR) has been developed as an alternative method for examining lymph nodes
    • Tissue used for this assay cannot be examined microscopically
    • Nodal tissue can only be used for other assays if all macrometastases can be identified by H&E examination (J Clin Oncol 2008;26:3338)
    • False positive and false negative results can occur with RT-PCR
    • Significance of a positive RT-PCR result for a histologically negative lymph node is unknown (J Clin Oncol 2008;26:3338)
    • Current AJCC cancer staging manual included positive molecular findings by RT-PCR; no isolated tumor cell clusters detected as pN0 (mol+)
Sample pathology report
  • Right axilla, sentinel lymph node #1, biopsy:
    • One lymph node negative for metastatic carcinoma (0/1)
  • Right axilla, sentinel lymph node #1, biopsy:
    • One lymph node with macrometastatic carcinoma (12 mm deposit) with extranodal extension (measuring 2 mm) (1/1)
Differential diagnosis
Additional references
Board review question #1
The finding in the image below of a pancytokeratin immunostain of an axillary sentinel lymph node from a breast cancer patient is best described as



  1. pN0(i+)
  2. pN1a
  3. pN1mi
  4. pNX
Board review answer #1
A. pN0(i+): isolated tumor cell clusters (malignant cell clusters ≤ 0.2 mm)

Reference: Sentinel lymph nodes

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Board review question #2
Which of the following is true for axillary sentinel lymph nodes?

  1. Cases with isolated tumor cell clusters only in lymph nodes are classified as pN1a
  2. Isolated tumor cell clusters are clusters of cells ≤ 0.2 mm and ≤ 200 cells in a single cross section
  3. Most commonly, sentinel lymph node is in level II
  4. Only 1 lymph node can be a sentinel lymph node
Board review answer #2
B. Isolated tumor cell clusters are clusters of cells ≤ 0.2 mm and ≤ 200 cells in a single cross section

Reference: Sentinel lymph nodes

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Board review question #3
Differential diagnosis of metastasis to axillary sentinel lymph node includes which of the following?

  1. Benign epithelial inclusions
  2. Endosalpingiosis
  3. Heterotopic breast tissue
  4. All of the above
Board review answer #3
D. All of the above

Reference: Sentinel lymph nodes

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