Atypical Cellular Blue Nevi (Cellular Blue Nevi With Atypical Features): Lack of Consensus for Diagnosis and Distinction From Cellular Blue Nevi and Malignant Melanoma (“Malignant Blue Nevus”)

Abstract

The distinction of cellular blue nevi (CBN) with atypical features ["atypical" CBN (ACBN)] from conventional CBN and malignant melanomas related to or derived from CBN remains a difficult problem. Here, we report on the diagnosis of various cellular blue melanocytic neoplasms by 14 dermatopathologists who routinely examine melanocytic lesions. Three parameters were assessed: (1) for between rater analyses, we calculated interobserver agreement by the kappa statistic (regardless of whether the diagnosis was correct). (2) For each individual lesion, we reported whether a majority agreement (>50%) was reached and, if so, whether the majority agreed with the gold standard diagnosis, derived from standardized histopathologic criteria for melanoma, definitive outcome such as metastatic event or death of disease, or disease-free follow-up for > or =4 years. (3) For the individual pathologists, we calculated sensitivity and specificity for each type of lesion. The study set included 26 melanocytic lesions: (1) 6 malignant melanomas developing in or with attributes of CBN; (2) 11 CBN with atypical features and indeterminate biologic potential (ACBN); (3) 8 conventional CBN; and (4) 1 common BN. The kappa values for interrater agreement varied from 0.52 (95% confidence interval 0.45, 0.58) for melanoma to 0.02 (0.05, 0.08) for ACBN and 0.20 (0.13, 0.28) for CBN. The kappa for all lesions was 0.25 (0.22, 0.28). The pathologists' sensitivities were 68.6% (61.0%, 76.1%) for melanoma, 33.1% (21.0%, 45.2%) for ACBN, and 44.6% (29.0%, 60.3%) for CBN. The specificities were 65.7% (55.8%, 75.6%) for melanoma, 84.7% (77.3%, 92.2%) for ACBN, and 89.9% (82.7%, 97.1%) for CBN. Overall, greater than 50% of the pathologists agreed and were correct in their diagnosis 38.5% (10 lesions) of the time. There was a majority agreement, but with an incorrect diagnosis, another 26.9% (7 lesions) of the time. Six of the 7 majority agreements with an incorrect diagnosis were for ACBN lesions. In summary, the results of our study indicate that there is substantial confusion and disagreement among experienced histopathologists about the definitions and biologic nature of cellular blue melanocytic neoplasms particularly those thought to have atypical features ("atypical" CBN).

Oral Atypical Cellular Blue Nevus: An Infiltrative Melanocytic Proliferation

“…Some believe that this group represents low-grade tumors with potential for lymph node metastasis but rare distant metastasis [20]. The topic of ACBN has drawn considerable attention in the last several years given the struggle among experts to agree upon strict clinical and histologic criteria [18][19][20][21]. For instance, when 14 dermatopathologists used a defined set of criteria to discriminate CBN from ACBN and MBN only 18.2 % of the ACBN lesions were correctly identified by the majority of the pathologists [18].…”

“…The topic of ACBN has drawn considerable attention in the last several years given the struggle among experts to agree upon strict clinical and histologic criteria [18][19][20][21]. For instance, when 14 dermatopathologists used a defined set of criteria to discriminate CBN from ACBN and MBN only 18.2 % of the ACBN lesions were correctly identified by the majority of the pathologists [18]. The authors concluded that histologic overlap makes it difficult to define the ''limits of atypicality'' for a diagnosis of ACBN over CBN as well as to establish the minimal criteria to warrant a malignant diagnosis.…”

“…Cutoffs for distinguishing ACBN from CBN varies from [1-2 cm [17,18] to [2-3 cm [22] to [5 cm [3]. As the size increases from [3 cm [23] to [6 cm [3], melanoma is reported to be more likely.…”

“…However, multiple reports in recent decades of tumors with features intermediate between CBN and MBN prompted the controversial [15] designation of ''atypical blue nevus'' or ''atypical cellular blue nevus'' (ACBN) [16,17]. While similar clinically and apparently biologically to CBN [17], discrete histologic criteria for ACBN are currently under debate even among expert dermatopathologists [18][19][20][21][22]. The most often cited histologic criteria include asymmetry, a deeply infiltrative and irregular border, mild cytologic atypia, and mitotic activity [2 mm 2 [17,18,23].…”

“…While similar clinically and apparently biologically to CBN [17], discrete histologic criteria for ACBN are currently under debate even among expert dermatopathologists [18][19][20][21][22]. The most often cited histologic criteria include asymmetry, a deeply infiltrative and irregular border, mild cytologic atypia, and mitotic activity [2 mm 2 [17,18,23]. Herein we describe, to our knowledge, the first oral case of a CBN exhibiting atypical architectural features along with complementary molecular data.…”