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Abstract

To the Editor: We appreciate the comments of Fraser-Andrews et al relating to our manuscript,1.Breneman D.L. Raju U.S. Breneman J.C. Steele P.E. McFadden D.W. Cualing H.D. et al.Lymph node grading for staging of mycosis fungoides may benefit from examination of multiple excised lymph nodes.J Am Acad Dermatol. 2003; 43: 702-706Abstract Full Text Full Text PDF Scopus (9) Google Scholar and would like to address the points of their letter as follows. It is true that the existing staging system is not based on multiple lymph node assessment.2.Bunn P.A. Lamberg S.I. Report of the Committee on staging and classification of cutaneous T-cell lymphomas.Cancer Treat Rep. 1979; 63: 725-728PubMed Google Scholar However, this should not deter physicians from trying to better characterize the extent of disease by using additional procedures if indicated. Just because sampling multiple nodes is not incorporated into the existing staging system does not mean that such sampling may not have prognostic significance. Because the premise of the current system is that disease stage should be based on the highest identified grade in the sampled node (even if very focal), it might be very reasonably assumed that biopsying multiple nodes may decrease the chance of sampling errors and thus give a more accurate estimation of prognosis. In fact, this principle has been proven and incorporated as a standard of practice in the staging of other types of malignancies.3.Mathiesen O. Carl J. Bonderup O. Panduro J. Axillary sampling and the risk of erroneous staging of breast cancer: An analysis of 960 consecutive patients.Acta Oncol. 1990; 29: 721-725Crossref PubMed Scopus (100) Google Scholar, 4.Werner J.A. Dunn E.A.A. Ramaswamy A. Folz B.J. Lippert B.M. Moll R. et al.Sentinel node detection in No cancer of the pharynx and larynx.Br J Cancer. 2002; 87: 711-715Crossref PubMed Scopus (77) Google Scholar Our study does not aim to compare the utility of histologic lymph node grading to molecular studies looking for clonogenic T-cell populations. The role of genotypic studies as an independent prognostic indicator or even substitute for lymph node grading remains to be studied in large cohorts of patients with mycosis fungoides, and several potential pitfalls exist when attempting to apply this information in the clinic. First, the finding of T-cell clonality for highly sensitive polymerase chain reaction (PCR) assays is not limited to conditions that are clearly recognized as malignant. The magnitude of these false positive assays is unknown, but could potentially be significant. Second, genotypic studies traditionally assess simply whether or not a clonal T-cell population is present, reflecting possible tumor dissemination, but not necessarily tumor burden. This may be an important issue given the correlation between tumor burden and response to treatment seen in cutaneous and other types of lymphoma.5.Evans A.V. Wood B.P. Scarisbrick J.J. Fraser-Andrews E.A. Chinn S. Dean A. et al.Extracorporeal photopheresis in Sezary syndrome: Hematologic parameters as predictors of response.Blood. 2001; 98: 1298-1301Crossref PubMed Scopus (60) Google Scholar Finally, even if molecular studies are assumed to be of value in the clinical care of these patients, analyzing multiple lymph nodes may increase the sensitivity of PCR, as even these techniques are not immune to sampling errors. It is appropriate to raise the question of increased morbidity from sampling multiple lymph nodes. Our practice is to obtain the additional lymph nodes through the same incision as the first node, and a formal lymph node dissection is never carried out. Therefore, one would anticipate no additional morbidity from this approach, as was our experience in the reported series. We agree that our series of eight patients represents a limited sample, and the findings should not be construed as a recommendation for the routine use of multiple lymph node biopsies for the staging of mycosis fungoides. However, even this small series demonstrates the sampling error that can occur when evaluating a single lymph node. The clinical implications of this are at present unknown, but deserve further thought, regardless of the laboratory method used for pathologically evaluating the node.