College of American Pathologists
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  Q & A





cap today

July 2003

Richard A. Savage, MD

Q. My colleagues and I are seeking information about assessing micrometastases and submicrometastases in sentinel lymph nodes examined for breast cancer. The recent revisions to the American Joint Committee on Cancer staging system define isolated tumor cells as deposits no larger than 0.2 mm in diameter and micrometastases as deposits ranging from 0.2 to 2.0 mm in diameter. When assessing single nodes with multiple small deposits, should these be classified based on the largest single metastatic focus or the aggregate dimension?

A. The largest contiguous focus is used to determine the N category. The AJCC Cancer Staging Manual1 defines isolated tumor cells as cellular clusters no larger than 0.2 mm in largest dimension [italics added]. Similarly, micrometastases are larger than 0.2 mm but not larger than 2.0 mm in largest dimension [italics added]. While not explicitly stated, there is no provision in the AJCC system for combining the sizes of multiple cellular clusters into a single aggregate dimension.

A sentinel lymph node containing three clusters of tumor cells measuring 0.9 mm, 0.7 mm, and 0.6 mm would be reported as pN1mi (sn) (largest focus, 0.9 mm), while a node with three clusters each measuring 0.1 mm would be reported as pN0 (sn) (largest focus, 0.1 mm). We recommend including a comment in the report describing the number of separate
foci found.

On occasion, these staging rules do not adequately describe the pathologic findings. For instance, invasive lobular carcinoma may show extensive nodal involvement by individually dispersed cells without forming discrete cellular nests. Classifying such cases as isolated tumor cells might be considered technically correct but would be an inaccurate characterization of the pathologic findings. In such cases, you must select staging categories that more accurately reflect the findings—that is, pN1mi, pN1, or pN2—based on the number of nodes involved and the extent of nodal involvement.

When faced with a deviation from the usual staging rules, pathologists should include a comment in their report describing why they chose a specific N category.


1. Greene FL, Page DL, Fleming ID, et al, eds. AJCC Cancer Staging Manual. 6th ed. New York, NY: Springer; 2002.

Patrick L. Fitzgibbons, MD
St. Jude Medical Center
Fullerton, Calif.
Advisor, CAP Surgical
Pathology Committee

Donald L. Weaver, MD
Fletcher Allen Health Care
University of Vermont
College of Medicine
Burlington, VT
Member, AJCC Breast Task Force

Q. Why is there disparity among the experts regarding separating malignant melanoma into Clark levels III and IV?

A. Level III is a tumor that fills the papillary dermis without extending into the reticular dermis. Level IV melanomas involve the reticular dermis. Disparity among consultants exists for the following reasons:

  • The reticular dermis is not well delineated in normal skin.
  • Tumor involving the dermis may obliterate the landmarks delineating the beginning of the reticular dermis, making it even more difficult to select the proper level.
  • Inflammation may obscure the delineation between the end of the papillary dermis and the beginning of the reticular dermis.

For these reasons, Breslow measurements remain the best approach to depth related to prognosis. Even Breslow measurements, however, have issues, including the subjectivity of deciding whether a cell is part of a nevus, melanoma cell, or inflammatory cell. If there is ulceration, one can only estimate the location of the granular layer. If blocks are step sectioned, the level may change by an average of 0.14 mm in depth.

Paul Bozzo, MD
Medical Director
PBC Laboratory
Professor, Clinical Pathology
University of Arizona