Sentinel Node Pathologic Staging

The pathologic assessment of axillary lymph node dissection specimens is highly important in the prognostication and selection of adjuvant therapy in breast cancer patients.¹ Traditionally, studies of axillary lymph nodes were based on the histologic examination of one microscopic section per lymph node.

In sentinel lymph node (SLN) biopsy procedures, prognostic determinations and therapeutic decisions are based on the examination of a single lymph node rather than a full axillary dissection.

Attempts have been made to make the pathologic assessment of these nodes as accurate as possible. Much of the work performed on the pathology of SLNs has focused on the detection of micrometastases through such techniques as step sections, cytokeratin immunohistochemistry and reverse-transcriptase polymerase chain reaction (RT-PCR).

Studies clearly show that these special techniques can detect small groups of tumor cells not found in a standard, single histologic section. Obtaining multiple sections through the paraffin-embedded lymph node tissue, or step sections, has been associated with a 7 percent to 33 percent increase in micro-metastases detection.² Immunostaining for epithelial markers such as cytokeratin has yielded up to a 29 percent increase in nodal positivity.

Immunohistochemistry

When using immunohistochemistry to detect metastatic tumor cells, it is important to confirm that labeled cells show malignant cytologic features because lymph nodes may contain nonneoplastic cells -- such as interstitial reticulum cells and benign glandular inclusions -- that express epithelial markers.^3,4 Highly sensitive molecular techniques such as RT-PCR have been reported to have up to a 55 percent increased detection rate for occult metastasis. However, the specificity of this technique has been questioned because mRNA for such tumor markers as CEA, cytokeratin 19, GA733.² and MUC-1 has been found in many lymph nodes of control patients without carcinoma.

Because PCR techniques do not include the morphologic confirmation of malignant cells, the false-positive results possibly are the result of the expression of tumor markers by nonneoplastic cells in lymph nodes.

Another possibility is that tumor-associated products may be released from mammary epithelial cells and transported via lymphatics to the lymph nodes, where they are processed. Disassociated tumor markers such as the TAG-72 antigen previously have been identified in benign lymph nodes draining inflammatory processes of the colon.

Clinical impact

The clinical impact of micrometastases detected by these special techniques in breast cancer patients is uncertain. Only about half of the published studies have found a significant association between disease recurrence or patient survival and lymph node micrometastases.

It also is of interest that most studies have not shown a significant negative clinical impact for bone marrow micrometastases detected by immunohistochemistry in breast cancer patients. 7 For a clinically significant metastasis to occur, tumor cells must invade, avoid the host response, develop a blood supply and grow. It is possible that specialized techniques may detect small clusters of tumor cells that lack the ability to become clinically significant.

Currently, pathologic evaluation of axillary SLNs from breast cancer patients at Ellis Fischel Cancer Center is based on three histologic step sections of the entire lymph node. This process complies with the recent recommendations of the Association of Directors of Anatomic and Surgical Pathology. 9 More or less sensitive techniques may be recommended as we gain additional understanding of the significance of micrometastases.