The Spitzoid Lesion: The Importance of Atypical Variants and Risk Assessment

To the Editor: The following discourse is written in response to the letter of Dr. Urso and the recent responses of Drs. Cerroni, Piepkorn, and Ackerman appearing in the Journal. In 1910 Darier and Civatte described in some detail an unusual [Spitzoid] melanocytic tumor developing rapidly on the nose of a young child, and they were completely thwarted in their efforts to decipher whether the lesion was benign or malignant.1 One century later one can question whether pathologists have made any real progress in resolving this very same conundrum: the inability to accurately interpret many such Spitzoid lesions* histologically and to know their biological potential! Of course over these ensuing 95 years a certain amount of information has been collected about these lesions and guidelines have been proposed for distinguishing “Spitz nevi” from malignant melanoma.2-24 Because of these guidelines for diagnosis, many dermatopathologists may on the surface appear to be at ease or to have greater confidence in dealing with this problem. However the reality of the situation is that a large proportion of these lesions remain a daunting challenge to histopathological interpretation and the diagnosis rendered is in many instances tentative, probabilistic and often arbitrary. The aim of this letter is not to review exhaustively the evolution of knowledge and thinking about Spitzoid lesions over the past century but rather to make certain observations and to offer a philosophically practical approach to the difficult Spitzoid tumor. It is useful to revisit the historic paper published by Sophie Spitz in 1948.2 Her article was entitled “Melanomas of Childhood” indicating that Spitz did not consider these lesions as a group to be “unequivocally benign nev[i] of childhood” nor malignant melanomas of adults. Spitz also concluded that “differentiation histologically between the juvenile and adult melanomas could not be made with certainty in most cases”, and this was evidenced by fatal metastases developing in 1 of 13 cases reported by Spitz. The latter point is reinforced by recent experience. In 1999 we described one case [among 30 lesions studied] thought by consensus to be a “typical Spitz nevus” that ultimately resulted in death of the patient.25 Furthermore Spitz thought that the onset of puberty was a singularly important factor in the rise in mortality from melanoma noted with age and the extreme rarity of death from melanocytic lesions before puberty. It is noteworthy that both Spitz's and our fatal cases developed in 12-year-old females who undoubtedly were in puberty or were post pubertal. One is left with the distinct impression that Sophie Spitz remained unsettled by this group of lesions and did not at all consider them a variant of ordinary nevus. Over the past half century there has been the progressive trend to consider the Spitz tumor as simply a variant of benign melanocytic nevi quite distinct from melanoma and to utilize the terms “Spitz nevus, Spitz's nevus, or spindle and epithelioid cell nevus” to describe this lesion.3-24 This approach has come about from the reports of series of Spitzoid lesions and the promulgation of histological criteria from these series. As we have described various authors have reviewed their own series of “Spitz nevi” and accordingly formulated their “criteria” from these self-selected [and consequently biased] series of lesions.7,11,12,26 The inherent flaws resulting from this exercise involve circular reasoning, the cases in general have not been population-based, the number of cases have often been limited in number, and the cases have not had long-term follow-up (of 8 to 10 years) to know the outcomes.22,25,26 Following up on the observations that the vast majority of these Spitzoid lesions do not seem to recur or to metastasize, they have been lumped as a group in benign melanocytic nevi, even though some proportion of lesions seem impossible to distinguish from melanoma and or rare lesions behave aggressively. Thus the term “Spitz nevus” has become firmly entrenched in the medical literature. The author acknowledges without question that the most typical or banal Spitz tumors share particular features with conventional acquired melanocytic nevi. One can argue that this group of Spitz lesions (that do not appreciably deviate from this characterization of a benign melanocytic lesion) should be termed Spitz nevi. However the problem with the indiscriminate use of “nevus” is that it connotes a lesion that is completely benign and a priori presents no risk to the patient. Obviously this is not the case for some subset of Spitzoid lesions as has clearly been shown by Sophie Spitz herself (and many others)! It is neither rational nor practical and it is potentially harmful to patients and physicians alike (see below) to prospectively label virtually all Spitzoid lesions as nevi and then to have to redress the issue at some later date. This usually involves reclassifying some lesions as malignant or melanoma some time later after the development of metastases or death. It is obvious that this practice also leads to the self-correcting behavior of lowering the threshold for diagnosing melanoma in order to avoid a disastrous outcome of missing melanomas and metastasizing lesions. For the later reasons the author favors the term “Spitz or Spitz-like tumor” (equally acceptable terms might include Spitz, Spitz-like, or Spitzoid lesion, melanocytoma or neoplasm) and the use of an intermediate or third category lesions that are difficult to classify as clearly benign or malignant, i.e., Spitz tumors that are “atypical, controversial, or biologically indeterminate” (see below).27 It is apparent that one message stemming from the published work on Spitzoid lesions is that if one utilizes the “established criteria” one can very easily interpret a Spitzoid neoplasm as either: 1) Spitz's nevus or 2) malignant melanoma.28 Another trend has been to interpret almost all Spitzoid lesions in children as benign “Spitz nevi” and many Spitzoid lesions in adults (particularly beyond the age of 30 to 40 years) as malignant melanoma, almost without any attention to the histopathological features (RL Barnhill, personal observations, 2005). As mentioned above a corollary of the latter practice, a literal “dumbing-down of criteria”, has been to designate virtually all Spitzoid lesions as melanoma. While medical-legal concerns have understandably influenced the behavior of pathologists in this area, the latter practices often offer pathologists no better solution than that of “flipping a coin”, or literally abandoning the practice of histopathology. The author does not believe that this overly simplistic attempt to assign an often arbitrary diagnosis of either “Spitz's nevus” or malignant melanoma to every Spitzoid lesion28 serves patients well nor provides a realistic methodology for dealing prospectively with an often profoundly difficult problem. Such an exercise undoubtedly results in both the over-diagnosis and under-diagnosis of melanoma in a certain number of cases. Patients may unfairly suffer the psychological burden of a grave diagnosis and may undergo overly aggressive and potentially harmful therapies. At the same time some proportion of patients will have the false and unjustified assurances of a benign diagnosis and may not receive appropriate treatment and follow-up. Rather we must be honest with patients and above all try to do no harm. We must accept that we currently have a rather poor understanding of the biological nature of Spitzoid lesions and that current criteria for their diagnosis are wanting. We must adopt a pragmatic approach that attempts to avoid both the over-diagnosis of melanoma and inappropriate management of patients. Einstein's philosophy that one should try to “make things simpler but not too simple” is especially applicable here. Thus the rather arbitrary interpretation of all Spitzoid lesions as either “Spitz's nevus” or malignant melanoma is too simple, not realistic, and may be harmful to patients. As the author has previously suggested a more realistic solution is to employ a well-defined protocol (Table 1) for the systematic and rigorous evaluation of Spitzoid lesions utilizing all histopathological, clinical, and ancillary information available.25,27,29 Having collected this information one can then assign a given lesion to 1 of 3 categories (Table 2): (1) Spitz tumors without appreciable abnormality (Fig. 1); (2) Spitz tumors with one or more atypical features (atypical Spitz tumor) (Fig. 2) including those with indeterminate biological or malignant potential (Fig. 3), and (3) malignant melanoma. In effect this involves risk stratification of lesions, open and honest communication with patients, and rational decision-making for patient management that is neither harmful nor negligent. Given the imperfect state of current information the author acknowledges that this exercise still remains largely subjective and is dependent on the knowledge, experience, and common sense of the pathologist and other physicians involved in the care of the patient.TABLE 1: Protocol for Spitz TumorsTABLE 2: Categorization of Spitzoid Lesions According to Risk StratificationFIGURE 1: Compound Spitz tumor without significant atypicality. A 22-year-old male with lesion involving left upper arm. The lesion measures less than 10 mm in diameter and 0.61 mm in Breslow thickness. Other attributes: no asymmetry, sharp circumscription, no ulceration, only minimal focal pagetoid spread, and there are no mitoses in the small dermal component. This lesion requires complete excision and the patient follow-up examinations at least once a year for example. A, Scanning magnification shows a slightly raised tumor with general symmetry. The lesion with and small dermal component. The lesion shows focal pagetoid and of of spindle and epithelioid in 2: Compound Spitz tumor with atypical A with lesion from The tumor measures less than 10 mm in diameter and at least mm in Breslow thickness. Other attributes: asymmetry, circumscription, no ulceration, no pagetoid of and of in and This lesion in the for conventional melanoma. Such a lesion requires with of about 1 and follow-up at least every may be at some but has no A, Scanning magnification shows a raised tumor with the general of Spitz tumor and of of dermal component. The lesion of but no pagetoid The of and is no at the of the melanoma metastasizing Spitz A with lesion from left as atypical Spitz nevus at The tumor measures mm in diameter and at least mm in Breslow thickness. Other attributes: asymmetry, circumscription, no ulceration, no pagetoid no and of and The lesion after the in a of At the time of complete excision large of an atypical melanocytic tumor. follow-up will be to if there is or A, Scanning magnification shows a large raised tumor with The of the tumor is by of of at with large large of of of the paper will on this of Spitz tumors with particular on the of atypical Spitz the group of melanomas Spitz or will be and whether their from atypical Spitz tumors is at The obvious of developing criteria for any tumor is to be to lesions that are behave or have other from those that are biologically or no to the patient. We to the as to whether the “criteria” for Spitz nevi lesions from aggressive or malignant lesions in a paper published in The latter involved a review of melanocytic lesions features of Spitz nevus cases “typical Spitz Spitz tumors with atypical biologically indeterminate Spitz-like lesions, and by 10 The outcome of the that this of pathologists could not consensus about diagnosing such Spitz lesions or distinguishing them from melanoma the conventional criteria from the As has been mentioned one of the cases thought by consensus to be a typical “Spitz nevus” resulted in death of the patient. we concluded that even the published guidelines for the of Spitz nevi from melanoma were The latter work has been the for the and of criteria for and risk stratification of Spitzoid lesions 3 and for Spitz of Spitz in and for Risk for The term Spitz tumor” was in the the in by and in a Spitz tumor a that from conventional Spitz nevi by and of spindle that and their In a of cases the term and epithelioid cell nevus with and Spitz (see below) to describe a series of Spitz-like melanocytic tumors by large ulceration, with of greater than that for a “Spitz nevus” and significant of mitoses to in a and focal tumors developed in young age years and years of and virtually all were on the and and patients were also to have metastases with of the and by tumor to the According to the authors there was no of long-term follow-up of these patients has not been were no features that the development of The author has reported a series of atypical Spitz-like melanocytic tumors in children and were 3 tumors as the cases that were with metastases and the death of one patient. of the latter patients had only metastases and have been with long-term follow-up. The latter tumors also potentially could be described as Spitz In general all tumors were by many of the same features as reported by large ulceration, significant of a but often and and the reports above it is apparent that there is a not only an but also a for criteria for Spitzoid lesions with features and that these potentially may have for risk stratification (and the rational for an intermediate category of Spitzoid (Table on information from the cases to we have developed the protocol in to in the of risk of Spitz tumors with features in children and In an evaluation of 30 atypical Spitz-like melanocytic tumors an resulted in greater risk for the development of A Spitzoid lesion should be to whether an obvious melanoma is melanoma can be Spitz-like tumors should be with the following histopathological, clinical, and ancillary (Table in The diameter of the lesion in mm is typical Spitz tumors 10 mm and to beyond 10 mm is This is a and there are to this in mm and of the are is as in all melanocytic is However is by in almost all will The most banal Spitz tumors to be at their atypical lesions are often less This with and other may be not in Spitz However such pagetoid should be limited to the half of should not should be only and (Fig. pagetoid involving the upper half of the a large of the lesion least one and in a or small is may be a factor to pagetoid in benign lesions. of and are and are the most important criteria for melanocytic lesions. these are subjective and difficult to and are also often to or (see or of and with in the dermal the and without are also atypical and Breslow may of such dermal One is the of such in Spitz tumors of young children may on less in the latter of and to the to often in typical Spitz (Fig. is the of of and of to and with The latter in most developed state involves a of and of to with with the of of a lesion from to and the of and of potentially aggressive and or this may be in both Spitz tumors and the of of may be a a more conventional Spitz The of the dermal is one of the most important for Spitzoid lesions to with of aggressive behavior or Furthermore this is in the of the dermal or the also seem to have greater than more are no for the of and the author any for the interpretation of a lesion as It is important in almost all instances to have to lesion must be on a case by case In any case beyond mitoses for that may the of 1) developing Spitz tumors may be in a and may have less (RL Barnhill, personal observations, 2) Spitz tumors in very young may have and and significant may be to The of such as has on for the of malignant As a the use of and may information beyond that of on the of Spitzoid more for may be useful in risk stratification of Spitz For have shown that atypical Spitz tumors have a of to in ordinary nevi, in conventional Spitz and in conventional melanomas (Table that a less than favors a conventional Spitz one greater than melanoma, and between and are the such may an atypical Spitz tumor and potentially one that is biologically The of with as with also with and less atypical of Spitz and as to and The of is of but remains subjective and features a more atypical Spitzoid lesion and melanoma include of cell the lesion, in an or or the of Spitz of or with of a large proportion of with and the of large The vast majority of Spitz tumors in young the age of 10 to The the especially beyond the age of to 30 the greater the of As a general threshold for diagnosing melanoma in such lesions should with the age of the patient a threshold for very young and a threshold for has guidelines for the diagnosis of Spitzoid lesions The author has noted that Spitz tumors may with greater in adults than has been to the of many pathologists to a priori interpret them as melanoma (RL Barnhill, personal observations, 2005). Other Other such as the of the of recent in a lesion, and of melanoma should be Spitz tumors involve the and The of atypical tumors on less involved by Spitz such as the is also factor of the lesion for melanoma. Spitzoid lesions have been with a of melanocytic and both Spitz tumors and melanoma in to the of and other the of Spitz In there is a of with of the dermal and in Spitz Spitz tumors also appear to of and to may also in distinguishing atypical Spitz tumors from melanoma (Table For to ordinary nevi conventional Spitz tumors atypical Spitz tumors and melanomas with many of the latter are of they rigorous with greater of cases and long-term follow-up in order if they have any in the evaluation of Spitzoid lesions. and In The majority of Spitz tumors by have had no the other of has been in a subset of cases and was to with Spitz tumors that were often in had in and dermal of Spitz tumors with of has shown an in number of and in the by in The latter do not usually in melanoma and consequently the authors have suggested that such (and the of in most Spitz may in the of Spitz tumors from melanoma. Other from the latter were that Spitz tumors are the majority of are with some large and Spitz tumors may be distinct from of have of on with in of and of “Spitz The latter for the between Spitz tumors and melanoma. of work has shown that a series of conventional Spitz tumors and Spitzoid melanomas metastasizing Spitz in children to any in the or The general of in Spitzoid lesions with a of to in conventional and to in melanocytic and a and to be for Spitzoid lesions. The recent of the to atypical Spitz-like tumors provides a of more information about the biological of such lesions. Spitz-like tumors may have in the or of in general the of tumor in is for melanoma, only the of of cases with long-term follow-up will the to know the biological of such with atypical Spitz if they are from conventional and if they potentially have better large and are almost of the of small is and requires more all for atypical Spitz tumors with have to any In the latter patients have had no with follow-up of to Spitz tumor in may have a or than metastases from conventional melanoma. remain to be about the of by atypical Spitz may have to the of Spitz tumor” as some of these patients have remained with long-term follow-up of up to years or the limited number of cases by such Spitzoid tumors have not had the of ulceration, of as such tumors resulting in Spitzoid it can be that some proportion of melanomas Spitz tumors and the the term Spitzoid melanoma if at all should be for melanomas that have a to Spitz The term a rare group of tumors often developing in young that are only as melanoma in i.e., after the development of metastases and an aggressive Given the of distinguishing some Spitz tumors from melanoma, the author the use of term Spitzoid melanoma it may in the indiscriminate of a group of lesions including benign Spitz lesions that are biologically conventional and also the rare group of tumors mentioned Spitz The latter group of lesions some that have given rise to metastases without on long-term follow-up. It be that as a group all of these unusual Spitz-like tumors more as to their biological The diagnosis of a melanoma as as mentioned above is on the and to a Spitz Thus such features potentially include any of the or or no about of of or some of or and especially a of epithelioid with or for histopathological, clinical, and ancillary criteria must be in the interpretation of a Spitzoid we and the or of the various features mentioned has not been However at the interpretation of a Spitzoid lesion remains almost histopathological with important given to all other have not been as to have any significant on the However some such as the the of of such as or and may useful information in the about a In the such ancillary may on greater may point that such an approach to many Spitz tumors In the of Spitz tumors common sense must and one must in that one is most dealing with a biological with many Spitz tumors at the or of the is question that as these various in number and the of an aggressive or melanoma It is apparent that certain on more than aggressive tumors or melanomas often have large to often may have significant distinct poor of more of without pagetoid including and significant melanocytic and and the of or or with The of or of cell to of the tumor be as a melanoma. the of a tumor to progressive of to and to in the of the lesion also melanoma. with is the of and and of in a Spitz the to the latter should of melanoma. features melanoma include that are a distinct from is acceptable for a Spitz As the greater the and number of the more one has melanoma. mitoses and melanoma but are not the is of It is obvious that a lesion with the features melanoma A lesion over or for a lesion that is over many years melanoma. that this diagnosis is the most difficult one in melanoma there are that make it even more if not In particular and significant response often features such as asymmetry, and abnormality the greater of melanoma. The author that all Spitz tumors be in order to complete histopathological and also to the risk of Spitz tumors excision for the same reasons but with greater to 1 in order to even greater that they are The reasons for excision with of the tumor are that (1) have at least one Spitz tumor not completely that at the same and in metastases and and (2) some Spitz tumors may be more atypical than the lesions and even more difficult to distinguish from of the latter tumors have resulted in Barnhill, personal observations, 2005). It is the that Spitz-like melanocytic tumors an indeterminate biological potential of 1 this is the of care for melanoma. The author acknowledges that there are currently no on the issue of for melanocytic lesions in of may be for lesions mm in Patients should be by examinations for (and in the case of atypical Spitz patients should be on an and efforts made to avoid both overly aggressive and management The author has to accurately the current state of the Spitzoid lesions, their and of remains to be about these lesions, there is that they may be a of melanocytic neoplasm distinct from conventional melanocytic nevi and malignant melanoma. the nature of Spitzoid lesions the author the term Spitz tumor rather than “Spitz nevus” and the term more information is to such a The author has also rational that patients are by the evaluation of Spitzoid lesions and their 3 (1) Spitz tumor without significant (2) Spitz tumors with one or more atypical features (atypical Spitz including those to have indeterminate biological and (3) malignant melanoma, rather than the categories of “Spitz nevus” and melanoma. Such an approach our current of knowledge about many of these lesions and over diagnosis of melanoma and of potentially aggressive The author has a protocol for this of histopathological, clinical, and ancillary and risk In only rigorous characterization of of Spitzoid lesions and long-term follow-up of will we be to have information about these lesions. Such to guidelines for the care of patients with these lesions. Barnhill, of and of of