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Surgery FAQ Articles - Traumets by RJ Rosser, MD
© 2001 American Society for Clinical Oncology
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Safety of Sentinel Lymph Node Dissection and Significance of Cytokeratin
Micrometastases

by Robert J. Rosser, MD

Desert Regional Medical Center Desert Hospital Comprehensive Cancer, Palm
Springs, CA

To the Editor:

In the July 2000 issue of the Journal of Clinical Oncology, two
articles were published on the theme of sentinel lymph node dissection (SLND) as
a safe and effective alternative to full axillary dissection.1,2 I believe that there is
an unrecognized danger in the procedure that has not been adequately
considered.

Giuliano et al1 report that of the 124 patients with tumors smaller than 4 cm and
57 (46%) had pathologically positive nodes. Thirty-five patients (28%) had positive
lymph nodes detected by a traditional pathologic technique, whereas 22 (18%) had
clinically negative lymph nodes who successfully underwent the SLND procedure,
nodes detected only by cytokeratin immunohistochemistry (CK-IHC).

This additional 18% lymph node positivity is considered a favorable benefit of
being able to apply more sensitive pathologic techniques to the one or two lymph
nodes recovered by the SLND procedure while simultaneously reducing or
eliminating the morbidity associated with performance of a full axillary
dissection. Both Giuliano et al1 and McMasters et al2 consider the procedure
safe.

It is my contention that there has been no investigation as to the possible
causation of these CK-IHC–positive micrometastases by the SLND procedure
itself. Moreover, it is my contention that there is sufficient evidence that
CK-IHC–positive micrometastases are mechanical or traumatic in origin, are
the result of the SLND, and should be referred to as traumatic micrometastases
and more conveniently called traumets.

The evidence of this traumatic origin is overwhelming. Traumets have been
demonstrated in the sentinel lymph nodes of patients with ductal
carcinoma-in-situ as well as in a high percentage of cases of T1a infiltrating
breast cancers. Medical practitioners routinely massage the breast, sometimes
with heat, to increase flow of lymph, radioisotope, and blue dye to the axilla.
Scrub nurses massage the breast to prepare the skin for the surgical skin
incisions. Surgeons grasp breast tumors with clamps and forceps to retract them
while completing the tumor excision. It should not be surprising that
cellular fragments of less cohesive tumors are disrupted and are caught up in the
flow of lymph. The danger to the patient comes from those traumets that do not get
trapped in the sentinel lymph node but enter the systemic circulation.

I believe SLND is a commendable effort, but it should be done without massage or
any other attempt to hasten the flow of lymph. Moreover, the lesson from this
experience is that gentle manipulations of the breast with tumor in
breast-imaging centers and in operating rooms is indicated.

REFERENCES

Giuliano AE, Haigh PI, Brennan MB, et al: Prospective observational study of
sentinel lymphadenectomy without further axillary dissection in patients with
sentinel node negative breast cancer. J Clin Oncol 18: 2553-2559, 2000

McMasters KM, Tuttle TM, Carlson DJ, et al: Sentinel lymph node biopsy for breast
cancer: A suitable alternative to routine axillary dissection in
multi-institutional practice when optimal technique is used. J Clin Oncol 18:
2560-2566, 2000

Rosser RJ: A point of view: Trauma is the cause of occult micrometastic breast
cancer in sentinel axillary lymph nodes. The Breast J 6: 209-212, 2000

Response:
Armando Giuliano
John Wayne Cancer Center

Reply 1:The letter from Dr Rosser makes an excellent point concerning the
uncertain significance of small numbers of malignant cells detected only by
immunohistochemical (IHC) examination of sentinel nodes. Quite likely, breast
cells, benign and malignant, may be dislodged by manipulation. Such cells could
be taken up by the lymphatic system and could be detectable by highly sensitive
assays such as IHC or reverse transcriptase polymerase chain reaction. When we
undertook our prospective study in 1995,1 the concept of the sentinel node biopsy
was not well recognized. Using this technique without axillary dissection had not
been attempted. We were concerned about the safety of not removing lymph
nodes that may have micrometastases.

Consequently, our study was designed in the most
cautious manner so that patients who had IHC-detectable tumor cells in the lymph
nodes were subject to completion axillary dissection to assure removal of any
other involved nodes. I agree with Rosser that if these dislodged epithelial
cells are of no significance, axillary dissection is unnecessary and also more
aggressive adjuvant therapy may be unwarranted. Unfortunately, it is not clear
that we can establish which breast cancer cells in the sentinel node are
dislodged "traumets" of no significance and which cells have metastatic
potential. The current trial of the American College of Surgeons (Z0010)
mentioned in our article is designed to determine the clinical significance of
metastases detected by IHC. Once this trial is completed, we hope to understand
the biologic significance of such tumor cells in sentinel nodes.

The real point is not that sentinel lymph node dissection should be done without
massage, but that we should complete the research necessary to understand the
significance of isolated tumor cells. The occurrence of these cells was
recognized long before sentinel node dissection was performed. The breast with a
malignancy is inevitably subject to external pressure, such as mammography,
needle biopsies, surgical biopsies, and even an incidental bump or hug. Cells may
be dislodged. It will take large studies to determine the clinical relevance of
these dislodged cells and more work to learn how to distinguish a "traumet" from
a "real met."

REFERENCES


Giuliano AE, Haigh PI, Brennan MB, et al: Prospective observational study of
sentinel lymphadenectomy without further axillary dissection in patients with
sentinel node negative breast cancer. J Clin Oncol 18: 2553-2559, 2000
[Abstract/Free Full Text]
Response
Kelly McMasters
University of LouisvilleJ. Graham Brown Cancer CenterLouisville, KY 40202

Reply 2:Dr Rosser takes issue with the safety of sentinel lymph node biopsy for
breast cancer, citing evidence that he believes breast cancer cells or clusters
of cells detected by analysis of sentinel nodes by cytokeratin
immunohistochemistry (CK-IHC) are related to traumatic dislodgment of tumor cells
into the lymphatic system. Such cells in the sentinel node are referred to as
"traumets." While this phenomenon is controversial and by no means universally
accepted, we too are troubled by the finding of sentinel node metastases in as
high as 12% of patients with ductal carcinoma-in-situ (DCIS) (without
microinvasion) when CK-IHC is used.1 In many cases, these patients are then
subjected to axillary lymph node dissection and even chemotherapy. This simply
does not match the clinical reality of this disease, with a 98% or better
long-term disease-specific survival rate when treated by simple mastectomy or
breast-conserving therapy. Therefore, CK-IHC seems to detect the presence of
cells in the sentinel nodes that may not have clinical significance.

Because the significance of breast cancer micrometastases detected by CK-IHC is
very controversial, a consensus panel involving pathologists and surgeons has
recently agreed that CK-IHC should not be performed routinely for identification
of nodal micrometastases. We agree wholeheartedly with this position and have
recently ceased to perform CK-IHC at our center. We also corresponded with the
more than 250 surgeons involved in our multi-institutional study of breast cancer
sentinel lymph node biopsy2 encouraging them to discontinue the use of CK-IHC
for
clinical decision making. However, we continue to participate in the American
College of Surgeons Oncology Group Trial Z0010, in which CK-IHC of sentinel
nodes is performed at a central site, the investigators are blinded to the results,
and the prognostic significance of CK-IHC–positive sentinel nodes will be
prospectively evaluated in a large cohort of patients. A similar investigation is
underway in the National Surgical Adjuvant Breast and Bowel Project B-32 trial as
well. We believe that these important studies will answer the question of the
significance of CK-IHC–detected micrometastases once and for all.

Rosser implies that because CK-IHC may find evidence of breast cancer cells that
are not prognostically significant, sentinel lymph node biopsy is not safe. The
logic behind this contention, however, is flawed. First, there is no evidence
that patients who undergo sentinel lymph node biopsy are at any greater risk of
locoregional or systemic recurrence compared with patients who undergo
standard axillary dissection. In fact, there is some evidence that cancer cells can
be detected in the peripheral blood of early-stage breast cancer patients
routinely.3,4 The development of metastases is a complex multistep process that
involves more than just escape of cells from the primary tumor. Furthermore,
Rosser implies that the sentinel lymph node biopsy procedure is responsible for
the presence of so-called "traumets." There are many other interventions that
could result in breast cancer cells being traumatically dislodged (assuming this
theory is correct), including mammography, breast examination, and breast biopsy
by a variety of techniques. Surely Dr Rosser does not suggest that we forego any
of these potentially traumatic, but important, diagnostic maneuvers. Therefore,
sentinel lymph node biopsy is yet another diagnostic test that necessarily
involves manipulation of the breast, and it should be no less dangerous than
other procedures for diagnosis and treatment of breast cancer. Therefore, we
believe that sentinel lymph node biopsy, when performed properly and in
experienced hands, is a safe and accurate alternative to routine axillary
dissection for breast cancer.

REFERENCES


Klauber-DeMore N, Tan LK, Liberman L, et al: Sentinel lymph node biopsy: Is it
indicated in patients with high-risk ductal carcinoma-in-situ and ductal
carcinoma-in-situ with microinvasion? Ann Surg Oncol 7: 636-642, 2000[Abstract]
McMasters KM, Tuttle TM, Carlson DJ, et al: Sentinel lymph node biopsy for breast
cancer: A suitable alternative to routine axillary dissection in
multi-institutional practice when optimal technique is used. J Clin Oncol 18:
2560-2566, 2000 [Abstract/Free Full Text]
Racila E, Enhus D, Weiss AJ, et al: Detection and characterization of carcinoma
cells in the blood. Proc Natl Acad Sci U S A 95: 4589-4594, 1998 [Abstract/Free
Full Text]
Krag DN, Ashikaga T, Moss TJ, et al: Breast cancer cells in the blood: A pilot
study. Breast J 5: 354-358, 1999[Medline]

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