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"Nevus/melanocytoma/ melanoma": that which we call a rose by any other name would smell as sweet.

To the Editor.--In the article "Nevus /Melanocytoma/Melanoma: An Emerging Paradigm for Classification of Melanocytic Neoplasms?" (1) the authors suggested expansion of the dichotomous classification scheme of melanocytic neoplasms, currently including entirely benign and entirely malignant, to include a third, intermediate, diagnostic category and proposed the term melanocytoma.We agree with the overall notion that some subclasses of melanocytic tumors demonstrate low metastatic/ fatality rates. Although the proposal by Zembowicz and Scolyer is timely in introducing a preliminary foundation for intellectual debate, we believe, in its current format, it suffers from a paucity of data and introduces nonspecific terminology.

Malignancy versus benignancy may often be decided based on 4 phases: malignant transformation of the target cell, growth of the transformed cells, local invasion, and metastasis. (2) The so-called melanocytoma would be classified as malignant because it harbors transformation of melanocytes into atypical cells, demonstrates tumor growth, has (low) potential to locally invade, and shows the possibility of metastasis. The mere presence of all of the above factors and not their quantification designates a tumor malignant. In this paradigm, basal cell carcinoma cannot be renamed basal cell keratinocytoma because of its low rates of metastasis. A prostatic adenocarcinoma with a Gleason score of 3 + 3 is still considered an adenocarcinoma--not a glandular epithelioma--regardless of a 5-year survival of 100% even after regional lymph node metastasis. (3)

The tumor grade and stage integrate the histopathologic attributes into an accepted system for prediction of prognosis more efficiently than any new, single (and sometimes controversial) terminology. Histopathology is just another predictor among other known prognosticators of complex malignancies like melanoma. Hypothetically, a 0.2 mm, classic, superficial spreading type melanoma with no ulcer or mitoses in a 19-year-old, black man might have less chance of metastasis than an ulcerated, 5-mm-thick "severely atypical Spitz tumor" with 9 mitoses/[mm.sup.2] in an 80-year-old white man. One could argue the latter has a higher metastatic potential or fatality rate; labeling the second tumor as melanocytoma introduces inaccuracy regarding the tumor's behavior. Before any reevaluation of the predictive value of different histopathologic variants (eg, melanocytoma, Spitzoid, among others), large-scale studies with longterm follow-up data and well-defined endpoints (eg, stage IV disease), adjusted for other prognosticators, should be launched.

The proposed terminology also lacks specificity. Zembowicz et al (4) had previously promulgated the term melanocytoma for what they perceived as a specific entity with chromosome 17q22-24 loss of heterozygosity, no PRKAR1A mutations, and loss of expression of R1[alpha]. Ironically, the new proposal now recycles the term melanocytoma for a more heterogeneous group of melanocytic tumors with low metastatic or fatality rates, including atypical Spitz tumors, with an entirely different clinical, demographic, and most important, molecular signature, including HRAS aberrations and the gain of chromosome arm 11p. Interestingly, in their original study on melanocytomas, they used 10 Spitz tumors as control.

The lexicon of melanocytic tumors entails dozens of other terms for a similar notion. (5) Proposing new concepts has been an ever-intriguing exercise; however, we believe coining new terms should be avoided until rigorous clinicopathologic and biologic studies with long-term follow-up could shed light on the natural course of any real "new entity."



Department of Pathology

Beth Israel Deaconess Medical Center

Harvard Medical School

Boston, MA 02215


(1.) Zembowicz A, Scolyer RA. Nevus/melanocytoma/melanoma: an emerging paradigm for classification of melanocytic neoplasms? Arch Pathol Lab Med. 2011; 135(3):300-306.

(2.) Kumar V, Abbas, AK, Fausto N, eds. Robbins and Cotran Pathologic Basis of Disease. 7th ed. Philadelphia, PA: Saunders Elsevier; 2004:272.

(3.) National Cancer Institute, US National Institutes of Health. Surveillance, epidemiology, and end results (SEER) program. statfacts. Accessed April 28, 2011.

(4.) Zembowicz A, Knoepp SM, Bei T, et al. Loss of expression of protein kinase a regulatory subunit 1a in pigmented epithelioid melanocytoma but not in melanoma or other melanocytic lesions. Am J Surg Pathol. 2007; 31(11):1764-1775.

(5.) Crowson AN, Magro CM, Mihm MC Jr, eds. The Melanocytic Proliferations. New York, NY: Wiley-Liss; 2001:477-500.

The authors have no relevant financial interest in the products or companies described in this article.

doi: 10.5858/arpa.2011-0148-LE
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Title Annotation:Letters to the Editor
Author:Sepehr, Alireza; Tahan, Steven R.
Publication:Archives of Pathology & Laboratory Medicine
Article Type:Letter to the editor
Date:Feb 1, 2012
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