for those with micromets or individual cytokeratin+ cells in their sentinel nodes...

[Lani]

Benign Cells in Sentinel Lymph Node Biopsies May Yield False-Positive Diagnosis

By Will Boggs, MD

NEW YORK (Reuters Health) Jun 12 - Displacement and transport of benign epithelial cells to axillary sentinel lymph nodes can result in a false-positive diagnosis of breast cancer, according to a report in the May 1 Journal of Clinical Oncology.

"Epithelial cell(s) in sentinel lymph nodes do not necessarily equate with metastasis," Dr. Ira J. Bleiweiss from Mount Sinai School of Medicine, New York told Reuters Health.

Dr. Bleiweiss and colleagues note that staining for cytokeratins is common in evaluating sentinel lymph nodes. They report 25 cases in which iatrogenic epithelial cell displacement and transport of benign breast epithelial cells into axillary lymph nodes probably resulted in falsely positive results.

Fifteen of the patients had intraductal carcinoma (DCIS) with no invasive carcinoma, nine had T1 invasive duct carcinomas, and one had a T2 invasive duct carcinoma separate from an area of DCIS, the authors report.

Displaced benign epithelial cells were seen in granulation tissue of the biopsy site in 17 cases, in lymphatic channels in one patient, and in adjacent ducts in one patient, the results indicate, and 22 of the patients' biopsy sites had intraductal papilloma.

In all but one case, the researchers note, epithelial cells were present only individually or in clusters in peripheral sinuses of sentinel lymph nodes, and in all cases the immunohistochemistry and/or the cytology of the epithelial cells differed from that of the DCIS or invasive tumor.

Similarly, the report indicates, epithelial cells in the sentinel lymph node were estrogen-receptor (ER) negative in all 13 cases with ER-positive tumors and Her-2/neu negative in 5 cases of high nuclear-grade DCIS that were Her-2/neu-positive.

"In the end, the presence of epithelial cells in sentinel lymph nodes must be evaluated carefully on a case by case basis with comparative histology and immunohistochemistry until a reliable metastasis specific marker can be developed," the authors conclude.

"In our view," they add, "until a patient has a histologically proven invasive tumor, sentinel lymph node dissection should not be a routine procedure, particularly in cases of intraductal carcinoma involving an intraductal papilloma."

Dr. Bleiweiss reinforced this advise, saying that it would be especially important to evaluate sentinel lymph node results that might be suspect in "any patient with DCIS only (no proven invasive carcinoma), particularly if there is anything described as papillary, or in patients with very small invasive tumors (less than 1 cm essentially) which are not poorly differentiated."

"The mere physical presence in the draining lymph node of groups of cells from the primary lesion must not be interpreted as established metastases with all its implications," write Dr. Beverley A. Carter from St. Clare's Mercy Hospital, St. John's, Newfoundland, Canada and Dr. David L. Page from Vanderbilt University, Nashville, Tennessee in a related editorial.

"We look forward to the future development of laboratory assays that will correctly differentiate small lymph node deposits that are truly metastatic (implicating greater likelihood of distant metastases than already indicated by size, grade, and other measures of the primary tumor) from those minimal deposits that are unlikely to have any significant impact on the patient and those deposits that have been benignly transported to the lymph node as a clean-up mechanism by the lymphatic system," the editorial concludes.

J Clin Oncol 2006;24:2013-2018,1978-1979.

[al from Canada]

What they say is this:
"...and in all cases the immunohistochemistry and/or the cytology of the epithelial cells differed from that of the DCIS or invasive tumor".

No one mentioned that they were normal. Are there shades of grey, meaning pre-cancerous or time-bombed cells?
I have some distrust for researchers because most of them are really left-brain, linear not divergent thinkers, better spellers than I am.... just a fact. Conclusions therefore may not reflect the big picture. Interesting stuff though.
Al

[RobinP]

How researchers vary in opinion. Note what is stated below on this topic. I had this bookmarked from the SABC 2005:[img]file:///C:/DOCUME%7E1/HP_OWNER/LOCALS%7E1/TEMP/moz-screenshot.jpg[/img][img]file:///C:/DOCUME%7E1/HP_OWNER/LOCALS%7E1/TEMP/moz-screenshot-1.jpg[/img][img]file:///C:/DOCUME%7E1/HP_OWNER/LOCALS%7E1/TEMP/moz-screenshot-2.jpg[/img][img]file:///C:/DOCUME%7E1/HP_OWNER/LOCALS%7E1/TEMP/moz-screenshot-3.jpg[/img][img]file:///C:/DOCUME%7E1/HP_OWNER/LOCALS%7E1/TEMP/moz-screenshot-4.jpg[/img]
Significance of sentinel lymph node micrometastasis on survival for patients with invasive breast cancer.

Cox C, Vrcel V, Riker A, White L, Allred N, Ramos D, Myers M, Dupont E, King J, Cantor A, Diaz N. H. Lee Moffitt Cancer Center, Tampa, FL

OBJECTIVE: The overall objective of this study was to test the impact of micrometastatic carcinoma detected by sentinel lymph node (SLN) biopsy on survival in invasive breast cancer patients. To do so, we compared survival outcomes in such patients with a negative SLN biopsy and the outcomes of those with micrometastatic disease in a SLN.
METHODS: The charts of 2145 invasive breast cancer patients with pathology reports of SLN with either micrometastatic or no metastatic disease were reviewed. The SLN HE and immunostained (cytokeratin) slides of patients with the diagnosis of micrometastatic carcinoma were analyzed and reclassified according to the 6th edition of the AJCC Cancer Staging Manual. Tumor deposits > 0.2 mm but not > 2 mm were classified as N1mi. Patients with SLNs with isolated tumor cells not > 0.2 mm were classified as N0(i+). SLNs with no epithelial cells on either HE or immunostaining were classified as N0(i-). Kaplan Meier graphs of overall survival (OS) and disease free survival (DFS) were done.
RESULTS: Of the 2145 patients reviewed, 1854 (87%) were N0(i-). 291(13%) of our patients had single cells and/or small cell clusters or micrometastatic disease. 138 (6%) were reclassified as N1mi and 153 (7%) as N0(i+). OS and DFS of the patients with N1mi SLN differed significantly from patients with N0(i-) SLN (p=0.005 and 0.016 respectively; Figures 1 and 2).
CONCLUSIONS: The detection of micrometastatic carcinoma in the SLNs of invasive breast cancer patients, as presently defined by the AJCC, is a significant indicator of survival. Subset analysis of N0(i+) patients will be presented. Results of the ACOSOG Z0010 trial may validate the latter results and clarify the clinical significance of N0(i+) detected by SLN biopsy.

[Lani]

isolated tumor cells are found in SLNs and are considered "less than micromets"

when they are found in a her2+ patient they are not stained for her2 from what I have gathered. (technical problem, it seems)

Nevertheless, there is a technique to her2 stain isolated tumor cells when in bone marrow.

Until this is routinely done on her2 + patients lymph node micromets,"less than micromets" etc I don't think we will know the answer.

Also the type of biopsy done needs to be addressed--Needle biopsy and core biopsy and excisional biopsy after passing radioopaque wires are obviously more likely to dislodge tumor cells than excisional biopsies without wire passage when margins were clear from the get-go.

This is not a "sexy" area of research in breast cancer, so it may take a while to come up with the answers...

So for right now despite lots written and lots of talks (not all published) from meetings, we only know that we can detect even a few cells in a lymph node, but do not know if they are tumor cells and what their presence portends...

[RobinP]

Research is continuing via the Z0010 for less than .02mm. Dr. Borgen, from MSK, has done a lot of research, indicating that isolated tumor cells and clusters are real cancer cells and not just reactive epithelial cells so this is why the ZOO10 may be so important. The ZOO10 continues to see if these are prognostically significant and may define if they are true metastases or mechanically displaced cells orginating from the orginal tumor biopsy(s). When it comes to ITC or clusters, I think that the addition of positive LVI- lymphatic invasion may only heighten the concern of their orgin.

[al from Canada]

Just a comment or miro-met spread due to surgery; there are two schools of thought, one is the dislodging theory and for HER2, the growth factor theory (ie HER2 is a growth factor stimulated by surgical healing). There has been some recent and very successful work done with continuous 5-FU infusion as surgical prep; Continuous 5-FU during surgery and for days after, knowing that things may dislodge. There is very little evidence that fine needle biopsies dislodge.


Al