< Current issue
Dermatopathology: Practical & Conceptual January - March 1997
New Concept: Melanocytic Dysplasia, Dysplastic Nevus, and Dysplastic Nevus Syndrome: Myth! Part IV
Daniela Massi, M.D.
Timothy Nielsen, M.D.
A. Bernard Ackerman, M.D.
From Seminars in Diagnostic Pathology
1. Terms and Phrases in the Title and the Abstract of the Article in Seminars in Diagnostic Pathology Not Yet Defined in Comprehensible, Repeatable Fashion
2. Critique of Positions of Clark
Changed Little or Not at All Since 1978
3. Critique of Positions of Clark
Changed Radically Since 1978
From the British Medical Bulletin
A. Examples of Impenetrable Language
B. Examples of Unsupported Speculations and Dizzying Definitions
C. A Critique of Positions of Clark
Changed Radically Since 1978
Two Articles by Clark
Summary of our Position Concerning DN and DNS as Elicited by A Series of Questions About Them
B. Examples of Unsupported Speculations and Dizzying Definitions
1) Clark et al.:
"The weakest link in the evolutionary chain of nevi is the junctional nevus.
Meticulous search of a large histologic collection of cutaneous pigmented lesions by one of us has shown but the rarest example of a junctional nevus with the histologic criteria given above (WHC). Further, a careful histologic systematist (Aldo Gonzales-Serva, personal communication, 1994) has told us that he has difficulty with the histologic diagnosis of a junctional nevus and rarely makes such a diagnosis, without qualification."
For practical purposes, all acquired melanocytic nevi begin with proliferation of mela-nocytes at the dermo-epidermal junction. Denying a junctional stage in the evolution of acquired melanocytic nevi is akin to averring, as Clark and co-workers have for more than 25 years, that so-called nodular melanoma does not begin as a macule made up of a proliferation of melanocytes at the dermo-epidermal junction, but, like Athena from the brow of Zeus, springs forth fully formed as a nodule composed of neoplastic melanocytes that extend well into the reticular dermis ("vertical growth phase from the outset").
These statements about junctional nevi and nodular melanomas, with or without qualification, defy belief. Why is it necessary for Clark, with his vast experience in the realm of melanocytic neoplasia and with a reputation himself for being "a careful histologic systematist" (whatever that means), feel compelled to defer to any other histopathologist in regard to the basic question of whether or not junctional nevus is real?
2) Clark et al.:
"Vertical growth phase melanoma refers to a stage in melanoma progression that is characterized by dermal invasion; the ability to grow in the dermis; and some metastatic capacity. Vertical growth phase is not a synonym for invasion. Vertical growth phase melanomas not only extend into the dermis, they grow there."
This statement makes no sense at all. Does it imply that the neoplastic melanocytes in the so-called radial phase have no capability to "grow" in the papillary dermis? Without capability of neoplastic melanocytes of melanomas to "grow" in the papillary dermis, the so-called vertical growth phase would never be attained. What is the distinction between extending into the dermis ("invasion") and "growing there"?
3) Clark et al.:
"A chronic problem with the terminology of the cells in nevi exists. . . . The intraepidermal melanocytes arrayed as single cells in nevi are difficult to distinguish from some melanocytes in the epidermis adjacent to the nevus. Consequently, many observers simply call this intraepidermal population of nevus cells, melanocytes. . . . Some authors call the cells in the dermis (and epidermis) nevomelanocytes. . . . We refer to the intraepidermal cells of nevi as melanocytes, either in single cell array or in nests. The cells in the dermis are termed dermal nevic cells."
What is the justification for this distinction? The cells under discussion in the epidermis and the dermis are all melanocytes; their cytoplasm either displays melanosomes or can be induced to generate melanosomes, e.g., by exposure to ultraviolet light. In short, so-called nevus cells, nevic cells, nevocytes, and nevomelanocytes are melanocytes, albeit abnormal ones.
4) Clark et al.:
"Common nevi clinical definitions. The following definition of a nevus is acceptably vague and comprehensive, but it lacks precision. A melanocytic nevus is a sharply circumscribed area where there is a great increase in the number of melanocytes and nevic cells in the surface epithelium, or in the dermis, or in both epidermis and dermis, when compared with the surrounding, unaffected skin."
This definition of melanocytic nevus is unacceptably vague because it pertains equally to melanoma. No usable definition can lack precision.
5) Clark et al.:
"In other neoplastic systems dysplasia designated a class of lesions having considerable propensity for progression to overt cancer."
In general pathology, the term "dysplasia" does not simply designate "lesions having considerable propensity for progression to overt cancer." In fact, "dysplasia" is applied to a host of wholly unrelated pathologic processes. In the gastrointestinal tract, bladder, larynx and oral cavity, histopathologic "dysplasias" are generally regarded as potential "premalignancies" and "severe dysplasia" is considered to be synonymous with carcinoma in situ. In cervical pathology, "dysplasia" refers to all those disturbances in differentiation of squamous epithelium that may be encountered in acute inflammatory conditions (e.g., alterations induced by herpesvirus), chronic inflammatory processes (e.g., longstanding cervicitis), and neoplasms (e.g., the spectrum of "cervical intraepithelial neoplasia"). "Mild cervical dysplasias," and even some of the "severe dysplasias," may regress in the absence of treatment. In the cardiovascular system, "fibromuscular dysplasia" is thought to be a non-arteriosclerotic vascular disease of renal, carotid, axillary, and mesenteric arteries that results in distortion and obstruction of lumina. It has been described as "a disordered proliferation of the cellular and extracellular elements of the wall."
In bone and joint pathology, "fibrous dysplasia" is considered to be a defect in maturation in formation of bone characterized by thinning of the cortex and replacement of the marrow by fibrous tissue containing misshaped bony trabeculae.12 In eye pathology, "retinal dysplasia" is a congenital anomaly that may occur as part of other systemic defects and that represents "disturbed differentiation of neural ectoderm."
In breast pathology, "mammary dysplasia" was used in times past to describe fibrocystic disease that nowadays is thought to be an exaggeration of a physiological phenomenon.
Ectodermal dysplasias are a group of abnormalities in development that have in common the involvement of tissues of ectodermal origin, i.e., central nervous system, eye, and skin. In sum, the term "dysplasia" during the past 150 years has been used differently by pathologists of different periods, of different countries, and of different organs of specialization, as well as by pathologists of the same period, same country, and same organ of special interest.
6) Clark et al.:
"Clinically atypical nevi have a body site distribution that differs from common nevi. They are uncommon on the arms when compared with common nevi, while clinically atypical nevi are more frequent on the buttocks than common nevi. We also noted clinically atypical nevi and dysplastic nevi (histological dysplasia) commonly on the covered area of the female breast and in the scalp."
In the last sentence quoted, Clark and associates make a clear distinction between "clinically atypical nevi" and "DN," yet in 1993, he and co-workers, in their article in Seminars in Diagnostic Pathology, made no such distinction. On the contrary, they used those terms synonymously, e.g., when they wrote that "Clinical features of atypical (dysplastic) nevi discussed in early reports summarized in the 1983 Consensus Statement include considerations of size, profile, border, and color variegation." In short, until 1995, Clark and associates constantly contrasted DN with CAN and consistently employed atypical nevus as a synonym for DN. In 1995, however, they changed all that by adding a third type of nevus, namely, clinically atypical nevus. No effort was made to clarify the differences among them. In the same sentence, Clark et al. also indicate that "histopathological dysplasia" is a synonym for DN.
7) Clark et al.:
"Dysplasia may arise concomitantly with the development of a common nevus. This histogenetic proposal suggests that a common nevus develops and concomitantly shows dysplasia somewhere within the lesion. . . . we have photographically documented the development of a nevus that was both common and dysplastic . . . When excised the central elevated portion of the lesion was a compound nevus and the periphery of the lesion dysplastic. One cannot prove that the common nevus and the dysplastic nevus arose simultaneously, but, in this instance, the two certainly formed a continuum. Such histogenesis implies that the combination of common nevus and dysplastic nevus develop simultaneously and, in all likelihood, the inductive mechanisms for both forms of nevi were present at the same time."
Clark and collaborators continue to contend that a "DN" consists of two different components, to wit, a central "CAN" and a peripheral zone (shoulders) of "melanocytic dysplasia." We see it differently: DN is one type of CAN and the entire nevus is a single, integrated structure. As an aside, "shoulders" are seen episodically in other types of melanocytic nevi, such as compound Spitz's nevi, where they, too, represent an integral part of the entire structure. Parenthetically, we have yet to encounter a single melanoma that developed in association with any of the tens of thousands of compound Spitz's nevi we have examined by microscopy.
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