LAUSR

In this issue of the Journal of Cutaneous Pathology, Oh et al have examined the relationship of large cellular remnants of melanocytes (LCRMs) in the nail plate in patients with subungual melanoma and nail matrix nevi. Overall, the authors included 23 patients with subungual melanoma and eight patients with nail matrix nevi in this casecontrol study. The authors defined LCRM as melanocyte remnants that have a diameter equal to or larger than that of the neighboring corneocytes. The authors note that smaller cellular remnants of melanocytes are not easily distinguished from pigment in the nail plate. The key findings from this study include: both the number and linear density of the total LCRMs were significantly higher in the subungual melanoma samples than the nail matrix nevi samples, the LCRMs in subungual melanoma samples were more dorsally distributed in the nail plate than in the nail matrix nevi samples, and the LCRMs were more likely to be found in the dorsal part of the nail plate in invasive subungual melanoma as opposed to subungual melanoma in situ. Another important observation was made in this manuscript, which is the variability of HMB-45 and Melan-A staining of the LCRM in the nail plate in both subungual melanoma and nail matrix nevi specimens. Such variability of staining of melanocytic markers of melanocytes in the nail plate in nail clippings has been identified in the past. These prior reports have identified S-100 as a marker that may function better in highlighting melanocytes in the nail plate but, in our hands, even this marker can have variability in staining intensity between stain runs. We have discussed in the past that this variability in staining may be related to softening techniques which are employed to process specimens that include nail plate. Potentially, this variability in staining may also be related to antigen presentation variability as melanocytes exit the nail unit epithelium and traverse into the nail plate. Additionally, diagnostic antibodies that, in order to access the relevant antigens, must traverse the thicker nail plate (compared to more accessible regions of the nail unit epithelium) may also stain with variable intensity. A point of confusion remains why some cases will have good staining of the LCRM in the nail plate while others will not. This may relate to individual differences in the samples or individual patient characteristics. The important take-home point regarding this aspect of variable staining of LCRM is that negative staining does not exclude the presence of melanocytes or melanocyte remnants in the nail plate. When examining specimens with nail plate, the dermatopathologist must depend somewhat more on the features of the sections stained routinely with H&E when making a determination if melanocytes or their remnants are present. The authors have divided the appearance of LCRM into three subtypes. While these subtypes may find future research applications, we emphasize that the key use of the information presented is the recognition of the presence or absence of the LCRM within the nail plate, which is a much easier distinction for the workaday dermatopathologist to make. Identification of melanocytes in the nail plate at all is a concerning histopathologic feature, especially in an adult. It is well known that melanocytes may be found in the nail plate of nail unit melanocytic nevi in children, so evaluation of the nail plate while taking into account the patient's age is essential. The authors' data are clear that the total number and linear density of LCRM in the nail plate are higher in subungual melanoma than in nail matrix nevi, so the highest suspicion for a subungual melanoma would stem from the presence of many melanocytes or LCRM in the nail plate in an older adult patient. We emphasize to the readership that melanocytes or LCRM are in fact pagetoid spread of melanocytes from the nail matrix epithelium, and by their presence alone are a concerning histopathologic feature. The information presented by Oh et al opens up a wide range of applications for our readership to employ in their routine work. Nail clippings sent for histopathology have numerous diagnostic applications, and quantification and description of LCRM in them now can have some predictive value. However, it is important to note that the gold standard for diagnosis of nail unit pigmented lesions is through sampling of the nail matrix, so characterization of features of melanocytes or LCRM within the nail plate should prompt the dermatopathologist to recommend additional sampling, and not a specific diagnosis. As dermatopathologists, we are always concerned about the “wrong site” sampling for nail unit pigmented lesions, and this includes nail bed sampling for longitudinal melanonychia. However, with these new data presented by Oh et al, if LCRMs are found within the nail plate in a nail bed sample, this could also have some predictive value and justification for sampling of other anatomic areas (nail matrix) of the nail unit. Another sampling issue that may occur is when specimens taken for melanonychia evaluation are taken from the correct anatomic site of the nail matrix, but are too superficial. Such samples will often include pieces of nail plate and the superficial layers of matrix epithelium, but not the entire thickness of the matrix. Here too, if LCRMs are seen in the nail plate in such a sample, it could provide some predictive value and justification for additional, deeper sampling. We also present a final word of caution regarding the results presented by Oh et al. An important comparison was not included in Received: 3 January 2022 Revised: 6 January 2022 Accepted: 9 January 2022