Historical Perspective: Barnhill et al., 1999

 
In 1999, Barnhill and co-workers74 again wrote about the difficulty of distinguishing melanomas from Spitz's nevi histopathologically. They sought to determine how accurate a panel of 10 expert dermatopathologists was in diagnosing 30 vexing cases in which the issue, fundamentally, was Spitz's nevus, melanoma, or neither. Barnhill et al. conducted this exercise utilizing certain criteria and employing particular diagnoses as follows:
 
"Each lesion was categorized by the observers as one of the following: (1) stereotypical Spitz nevus/tumor; (2) atypical Spitz nevus/tumor; (3) melanoma, whether Spitzoid (ie, with spindle and/or epithelioid cell features) or not; (4) tumor with unknown biologic potential; or (5) other unclassifiable melanocytic lesion. The only histological guidelines discussed before the review were the following: (1) criteria for stereotypical Spitz nevi/tumors were those conventionally described in the literature; (2) criteria for atypical Spitz nevi/tumors included significant deviation from those conventionally ascribed to typical Spitz nevi (while maintaining some of the customary criteria), for example, size larger than 1 cm, ulceration, extension into deep dermis or subcutis, prominently increased cellularity or confluence of growth, intradermal mitotic figures, lack of maturation toward the base, and so forth; (3) conventional criteria for melanoma; (4) tumors categorized as lesions of unknown biological potential were those for which there were insufficient criteria to confidently classify the lesions as either benign or malignant; and (5) those few lesions that were otherwise unclassifiable by the observers."
 
Table 2 of Barnhill and coworkers lists the 30 cases of "spitzoid lesions," six of them being in children, two of whom, ages 6 and 7, had metastases to regional lymph nodes. Another "child," whose age was not given, died of metastatic disease. Despite the fact that the melanoma in the 2-year -old girl metastasized, Barnhill and associates nonetheless referred to her neoplasm as an "atypical Spitz tumor." (Fig. 16) Eight of the panel of experts classified that neoplasm as a melanoma; one expert thought it was a "Spitz's nevus", and one considered it to be a lesion of "uncertain biological potential." None of the panel diagnosed it as an "atypical Spitz tumor," even though that was the diagnosis given to it by Barnhill et al. in the legend to their figure 4. Five experts classified the spitzoid lesion that metastasized in the 7-year-old boy as a melanoma, four as a lesion of "uncertain biological potential," and one as an "atypical Spitz nevus." The lesion in the child who already had died of metastatic melanoma was diagnosed as a "melanoma" by three of the experts, "atypical Spitz nevus" by three, "Spitz's nevus" by three, and a lesion of "uncertain biological potential" by one.

View Figure  
View Figure  		Fig. 16  Comment: The neoplasm shown by Barnhill et al. in their figure 4 came from a 2-year-old who they considered to have an "atypical Spitz tumor" that had metastasized. On the basis of both the architectural pattern and the cytologic features, this neoplasm can be judged to be a melanoma. Aggregations of neoplastic melanocytes vary substantially in size and shape, some have assumed bizarre geometric outlines, and many have become confluent to form a sheet. Although many of the melanocytes have a large nucleus, abundant cytoplasm, and polygonal shape, they cannot be those of Spitz's nevus because of the heterochromasia of nuclei, the prominent centrally located nucleolus, and the fact that some nuclei are small.
 
Another flaw that limited seriously the undertaking by Barnhill and coworkers was misapprehension concerning "conventional" criteria, as they are encountered in the literature, for diagnosis histopathologically of Spitz's nevi, atypical Spitz's nevi, and melanoma. In actuality, there are no agreed on criteria for any of them, and that is one of the reasons why panels of "expert" dermatopathologists never agree about diagnosis of melanocytic neoplasms that are unconventional.128–131 In the case of "atypical Spitz nevi/tumors," in particular, there is no reason to believe that it even exists, i.e., it can be identified with confidence by a majority of competent histopathologists. Barnhill et al. came to these positions in regard to what they referred to as "Spitz nevi/atypical Spitz tumors":
 
"Seventeen of the 30 lesions were classified by most of the observers as exhibiting some features of a Spitz nevus/tumor, but there was no consensus (ie, concordance of six or more pathologists) with respect to categorization as Spitz nevus, atypical Spitz tumor, melanoma, or tumor of unknown biological potential. In only one case did six of the observers concur in the diagnosis of a convential Spitz nevus (discussed later). In general, the lesions in this group were most often designated as either atypical Spitz nevus/tumor, melanoma, or tumor of unknown biologic potential."
 
For Barnhill and his fellow dermatopathology coauthors, among them, Argenyi, From, Glass, Maize, Marge, Mihm, Rabken, Ronan, W.L. White, and Piepkorn, the essence of the matter was distilled in these words:
 
"These results illustrate (1) substantial diagnostic difficulties posed by many Spitz tumors, especially those with atypical features, even among experts, and (2) the lack of objective criteria for their distinction from melanoma and for gauging their malignant potential. Nevertheless, our observations do suggest that a biological relationship exists between the Spitz nevus/tumor and melanoma."
 
The chaos that abounded in regard to diagnosis in the 30 challenging cases of Spitz's nevus and melanoma seems to have resulted directly from problems that pertain to criteria for diagnosis histopathologically of those two very different melanocytic neoplasms and to the language in which diagnoses of them was couched. For practical purposes, the diagnosis of these 30 cases was either Spitz's nevus or melanoma, but for the experts assembled by Barnhill, other diagnoses were proferred as legitimate, chief among them, "atypical Spitz tumor" and "lesion of uncertain biological potential." In order for the experts to have arrived at such disparate diagnoses, they had to be using very different criteria or, less likely, were utilizing the same criteria in very different fashion. In any event, the result of the exercise organized by Barnhill was even more confusion than before and, because there was unanimity among the experts about only six of the 30 cases, an embarrassment to pathology as a respected scientific discipline.