Advances in Anatomic Pathology:
Letters to the Editor
*Department of Pathology and Laboratory Medicine, Vancouver General Hospital University of British Columbia Vancouver BC, Canada
†Department of Pathology and Laboratory Medicine, University of California Los Angeles, CA
The authors have no funding or conflicts of interest to disclose.
We would like to thank Dr Piscioli for his interest in our paper and his thought-provoking discussion. However, there are a few fundamental points raised by Dr Piscioli that require clarification.
The malignant potential of a tumor is a manifestation of its biological behavior. A nevus is considered a benign tumor because if its indolent clinical course, which is dictated by its biological and molecular properties. A melanoma, in contrast, is regarded as malignant because it can clinically cause disseminated disease and ultimately death.
As in all neoplastic systems, the biological potential of a given melanocytic neoplasm is encoded in its genome and epigenome and is revealed through its interactions with the host environment. The subsequent biological behavior of any particular melanocytic neoplasm is regulated by obscure mechanisms of stochastic probability. Thus, because of our inherent lack of understanding of tumor progression at the molecular level, the biological behavior and malignant potential of melanocytic neoplasms a priori remain largely inexplicable. For example, occasional microinvasive melanomas with thin Breslow measurements and seemingly favorable prognoses are sometimes rapidly fatal, and thick melanomas exist that despite all adverse prognostic indicators remain clinically indolent with long-term follow-up observation. In sum, “biological potential” and “malignant potential,” which are indications of genomic and epigenomic derangements are directly linked to one another.
The tumor group that we have designated as “melanocytic neoplasms with indeterminate biological potential” or “melanocytic tumor of uncertain malignant potential—MELTUMP” is exactly as its name states; these are lesions that do not quite fulfill the criteria for bona fide melanomas, yet they are too atypical for conventional nevi. This statement holds true with respect to both the morphologic and molecular properties of MELTUMP.
Recent long-term follow-up studies are beginning to reveal the biological behavior, and hence malignant potential, of this class of tumors. Retrospective analyses have shown that these tumors do not behave like nevi, nor do they behave like melanomas. Instead, they may frequently involve regional lymph nodes but rarely cause disseminated disease and death. The best studied entity within the MELTUMP category is the atypical Spitz tumor.1,2 As the longest follow-up period in the literature for these tumors is 83.5 months,3 almost all observers still maintain that this time interval is clearly not sufficient to establish the biological or malignant potential of this enigmatic class of tumors.
The biological potential of MELTUMP currently cannot be elucidated by molecular studies alone. Recent literature has shown that these lesions are proving difficult to characterize at the molecular level. Some tumors that metastasize to regional lymph nodes appear to demonstrate no apparent chromosomal aberrations or other genomic variations at all.4,5 This is an area of active research, and perhaps in the future we will be able to better explain the clinical behavior of many MELTUMPs in molecular terms.
For the foreseeable future, conventional microscopy will remain the gold standard for the categorization of this class of challenging melanocytic lesions. Pathologists can comment on the potential biological outcome of a tumor just based on haematoxylin-eosin morphology alone because retrospective analyses of these cases in the literature have shed light on how they might manifest within the patient.3,6,7 With additional data and longer follow-up periods, we might soon be able to reclassify some of these tumors with “indeterminate biological potential/uncertain malignant potential” as “low-grade malignant neoplasms.”
As in other areas of pathology, molecular information is ancillary data that should always be interpreted prudently together with histopathologic observations. The link between molecular aberrations and biological/malignant potential is still “indeterminate” for MELTUMP, and hence we remain “uncertain” about their malignant potential. As such, as “melanocytic neoplasms with indeterminate biological potential” or “melanocytic tumor of uncertain malignant potential—MELTUMP” is an appropriate provisional category until further scientific advances may potentially facilitate more precise classification of such neoplasms.
T. Hung, MD*
*Department of Pathology and Laboratory Medicine, Vancouver General Hospital, University of British Columbia, Vancouver, BC, Canada
Raymond L. Barnhill, MD†
†Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA
1. Ludgate MW, Fullen DR, Lee J, et al. The atypical Spitz tumor of uncertain biologic potential: a series of 67 patients from a single institution. Cancer. 2009;115:631–641
2. Sepehr A, Chao E, Trefrey B, et al. Long-term outcome of Spitz-type melanocytic tumors. Arch Dermatol. 2011;147:1173–1179
3. Cerroni L, Barnhill R, Elder D, et al. Melanocytic tumors of uncertain malignant potential: results of a tutorial held at the XXIX Symposium of the International Society of Dermatopathology in Graz, October 2008. Am J Surg Pathol. 2010;34:314–326
4. McCalmont T, Bastian B. An unconventional deep penetrating melanocytic nevus with microscopic involvement of regional lymph nodes. J Cutan Pathol. 2012;39:25–28
5. Raskin L, Ludgate M, Iyer R, et al. Copy number variations and clinical outcome in atypical Spitz tumors. Am J Surg Pathol. 2011;35:243–252
6. Spatz A, Calonje E, Handfield-Jones S, et al. Spitz tumors in children: a grading system for risk stratification. Arch Dermatol. 1999;135:282–289
7. Barnhill RL. The Spitzoid lesion: rethinking Spitz tumors, atypical variants, and risk assessment. Mod Pathol. 2006;19:S21–S33
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