10.5826/dpc.1302a92
Introduction: The diagnostic delay in nail melanoma (NM) has been repeatedly emphasized. It may be related to both clinical misinterpretations and to errors in the bioptic procedure.
Objectives: To assess the efficacy of histopathologic examination in different diagnostic biopsies in NM.
Methods: We retrospectively investigated the diagnostic procedures and histopathologic specimens referred to the Laboratory of Dermatopathology for the clinical suspicion of NM from 2006 to January 2016.
Results: Eighty-six nail histopathologic specimens were analysed consisting in 60 longitudinal, 23 punch and 3 tangential biopsies. A diagnosis of NM was performed in 20 cases, benign melanocytic activation in 51 cases and melanocytic nevi in 15 patients. Longitudinal and tangential biopsy were diagnostic in all cases, regardless of the clinical suspicion. Nail matrix punch biopsy instead was not diagnostic in most of the cases (13/23 specimens).
Conclusions:  In the presence of an NM clinical suspicion, longitudinal biopsy is recommended (lateral or median) because it provides exhaustive information on the characteristics of melanocytes’ morphology and distribution in all the components of the nail unit. Tangential biopsy, recently encouraged by expert authors due to the optimal surgical outcome, in our experience gives incomplete information on tumor extension. Punch matrix biopsy gives limited evidence in the diagnosis of NM.
text/xml
2160-9381
2686
en
Bianca Maria Piraccini
https://creativecommons.org/licenses/by-nc/4.0
Dermatology Practical & Conceptual
biopsy
The Histopathologic Evaluation of Diagnostic Procedures in Nail Melanoma
Text.Serial.Journal
https://dpcj.org/index.php/dpc
Original Article
2023-04-29
2022-07-06
2023-04-29
2023-05-31
e2023092
Dermatol Pract Concept
Introduction: The diagnostic delay in nail melanoma (NM) has been repeatedly emphasized. It may be related to both clinical misinterpretations and to errors in the bioptic procedure.
Objectives: To assess the efficacy of histopathologic examination in different diagnostic biopsies in NM.
Methods: We retrospectively investigated the diagnostic procedures and histopathologic specimens referred to the Laboratory of Dermatopathology for the clinical suspicion of NM from 2006 to January 2016.
Results: Eighty-six nail histopathologic specimens were analysed consisting in 60 longitudinal, 23 punch and 3 tangential biopsies. A diagnosis of NM was performed in 20 cases, benign melanocytic activation in 51 cases and melanocytic nevi in 15 patients. Longitudinal and tangential biopsy were diagnostic in all cases, regardless of the clinical suspicion. Nail matrix punch biopsy instead was not diagnostic in most of the cases (13/23 specimens).
Conclusions:  In the presence of an NM clinical suspicion, longitudinal biopsy is recommended (lateral or median) because it provides exhaustive information on the characteristics of melanocytes’ morphology and distribution in all the components of the nail unit. Tangential biopsy, recently encouraged by expert authors due to the optimal surgical outcome, in our experience gives incomplete information on tumor extension. Punch matrix biopsy gives limited evidence in the diagnosis of NM.
Bianca Maria Piraccini
2023/04/29
10.5826/dpc.1302a92
e2023092
Dermatology, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna
2160-9381
biopsy
en
e2023092
Kazi R, Moghaddam S, Chu P, Marghoob A. A Histologic Evidence of Melanocytes Isolated to the Nail Matrix. JAMA Dermatol. 2016;152(5):573–575. DOI:10.1001/jamadermatol.2015.5869. PMID: 26865087.
The Histopathologic Evaluation of Diagnostic Procedures in Nail Melanoma
https://dpcj.org/index.php/dpc/article/download/2686/2067
        The Histopathologic Evaluation of Diagnostic
                Procedures in Nail Melanoma
           Emi Dika1,2, Michela Starace1,2, Aurora Alessandrini1,2, Annalisa Patrizi1,2,
    Carlotta Baraldi1,2, Cosimo Misciali1,2, Pier Alessandro Fanti1,2, Anna Waśkiel-Burnat2,3,
                           Lidia Rudnicka2, Bianca Maria Piraccini1,2


1 Dermatology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna
2 Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy
3 Department of Dermatology, Medical University of Warsaw, Warsaw, Poland



Key words: nail melanoma, subungual melanoma, pathology, surgical excision, biopsy
Citation: Dika E, Starace M, Alessandrini A, et al. The Histopathologic Evaluation of Diagnostic Procedures in Nail Melanoma.
Dermatol Pract Concept. 2023;13(2):e2023092. DOI: https://doi.org/10.5826/dpc.1302a92
Accepted: September 25, 2022; Published: April 2023
Copyright: ©2023 Dika et al. This is an open-access article distributed under the terms of the Creative Commons Attribution-
NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use,
distribution, and reproduction in any medium, provided the original authors and source are credited.
Funding: None.
Competing Interests: None.
Authorship: All authors have contributed significantly to this publication.
Corresponding Author: Michela Starace, Dermatology, Department of Experimental, Diagnostic and Specialty Medicine, University of
Bologna, via Massarenti 1, 40138, Bologna, Italy. Tel +39051-6364867; Fax +39-0516364867; E-mail:michela.starace2@unibo.it




  ABSTRACT             Introduction: The diagnostic delay in nail melanoma (NM) has been repeatedly emphasized. It may
                       be related to both clinical misinterpretations and to errors in the bioptic procedure.
                       Objectives: To assess the efficacy of histopathologic examination in different diagnostic biopsies in NM.
                       Methods: We retrospectively investigated the diagnostic procedures and histopathologic specimens
                       referred to the Laboratory of Dermatopathology for the clinical suspicion of NM from January 2006
                       to January 2016.
                       Results: Eighty-six nail histopathologic specimens were analyzed consisting in 60 longitudinal,
                       23 punch and 3 tangential biopsies. A diagnosis of NM was performed in 20 cases, benign melanocyt-
                       ic activation in 51 cases and melanocytic nevi in 15 patients. Longitudinal and tangential biopsy were
                       diagnostic in all cases, regardless of the clinical suspicion. Nail matrix punch biopsy instead was not
                       diagnostic in most of the cases (13/23 specimens).
                       Conclusions: In the presence of an NM clinical suspicion, longitudinal biopsy is recommended (lateral
                       or median) because it provides exhaustive information on the characteristics of melanocytes morphol-
                       ogy and distribution in all the components of the nail unit. Tangential biopsy, recently encouraged by
                       expert authors due to the optimal surgical outcome, in our experience gives incomplete information on
                       tumor extension. Punch matrix biopsy gives limited evidence in the diagnosis of NM.




Original Article | Dermatol Pract Concept. 2023;13(2):e2023092                                                                      1
Introduction                                                        Dermatopathology, University of Bologna, from January 2006
                                                                    to January 2016. Since our Laboratory is a referral center for
Nail melanoma (NM) prevalence in Caucasians is estimated            nail pathology, specimens are prevenient from our institution,
to range from 0.3 to 2.8 % of all melanomas. NM clinical            but also from other centers or private practices. The key words
presentation may be heterogeneous, and misdiagnoses are             for the database search were: “melanocytic activation”, “mela-
frequent [1-8].                                                     nocytic hyperplasia”, “melanoma” and “nevi”.
    The most frequent clinical misdiagnoses of NM are be-                  The histopathologic charts containing the selected key
nign inflammatory diseases or benign neoplasms that cause           words were reviewed for the following: 1) clinical query 2)
nail plate pigmentation. Non-pigmented NM, also called              the type of biopsy, and 3) histopathologic diagnosis.
amelanotic NM could be difficult to differentiate from squa-               The type of bioptic procedures assessed were: 1) punch
mous cell carcinoma of the nail (NSCC) or other conditions.         biopsy (PB) 2) longitudinal biopsy (LB) considering both
Misdiagnoses in NM may be also due to inappropriate surgi-          types lateral and median, and 3) tangential biopsy (TB).
cal sampling and subsequent difficulties in the interpretation             Transverse matrix biopsy was not considered among the
of histopathologic specimens.                                       evaluated procedures since it is not widely used in the surgi-
    Because of the particular anatomic location and the             cal practice in our institution and no cases were referred in
scarce number of cases in Caucasians, in the clinical suspi-        our laboratory (9).
cion of NM, no absolute consensus exists regarding the opti-               Finally, the appropriateness of the bioptic procedures was
mal diagnostic procedures.                                          evaluated in correlation to the final histopathologic responses.
    Bioptic techniques have been adequately described by            All NM histopathologic specimens were assessed by two der-
nail experts [9-23], but the two main problems in the correct       matopathologists (PAF and CM) respecting the American
choice and performance of the biopsy are probably related to        Joint Committee on Cancer (AJCC) guidelines [24].
the difficulty in performing surgery in the nail unit (insuffi-
cient familiarity with nail apparatus anatomy among derma-
tologic surgeons) and the risk of permanent nail dystrophy
                                                                    Results
when an excessive amount of nail matrix is excised.                 Eight-six cases were selected (54 females/32 males). Demo-
                                                                    graphic data are presented in Table 1.
Objectives                                                                 The most frequent queries from clinicians (first endpoint)
                                                                    were NM in 55 patients (64%); followed by NM versus me-
The aim of the study was to assess the efficacy of histopatho-      lanocytic nevus in 9 cases (10%) and NM versus friction/
logic examination in different diagnostic biopsies in NM.           post-traumatic melanonychia in 22 patients (26%).
                                                                           The second endpoint of the study was the evaluation of
                                                                    the bioptic procedures:
Methods
We retrospectively investigated the diagnostic procedures           a. LB was performed in 60 patients;
administered in patients referring for a clinical suspicion of      b. A 3 or 4 mm PB was performed in 23 cases;
NM. Histopathologic data were obtained from the archive of           c. A TB was performed in 3 cases.


              Table 1. Patients, clinical presentation and diagnostic procedures of the nail unit.
                           Gender           Age in years Site (hands/                  Clinical
 Diagnosis (cases)      (Female/ Male)       (median)        feet)                  presentation              Bioptic procedure
 Total (86)                  54/32               46               56/27         81 melanonychia/          60 longitudinal biopsy/ 23
                                                                                5 nodular neoplasms       punch biopsy/
                                                                                                          3 tangential biopsy
 Nail Melanoma                14/6               61               14/3          16 longitudinal           12 longitudinal biopsy/
 (20)                                                                           melanonychia/             5 punch biopsy/
                                                                                4 nodular neoplasms       3 tangential biopsy
 Benign melanocytic          33/18               52               32/19         50 nail pigmentation/ 34 longitudinal biopsy/
 activation (51)                                                                1 nodular mass of     17 punch biopsy
                                                                                the nail bed
 Nevus (15)                   8/7                25               10 / 3        15 nail                   14 longitudinal biopsy/
                                                                                pigmentations             1 punch biopsy




2                                                                          Original Article | Dermatol Pract Concept. 2023;13(2):e2023092
    On histopathologic evaluation a diagnosis of NM was              Conclusions
performed in 20 cases, benign melanocytic activation in 51
patients and melanocytic nevi in 15 cases, respectively.             Misdiagnoses of NM are continuously reported in the scien-
    Regarding the final endpoint of the study, on the appro-         tific literature [25,26].
priateness of the bioptic procedure:                                     The most common clinical presentation of NM is longi-
                                                                     tudinal melanonychia, which is a brown to black band of the
a. 12/20 patients affected by NM had undergone a LB; 5/20            nail plate, starting from the proximal nail fold and extending
    a PB and 3/20 a TB.                                              to the distal margin of the nail. Nail plate pigmentation is
        LB was diagnostic in all cases. PB was diagnostic            due to melanin granules incorporated in the nail plate during
    only in 2/5 of melanoma cases. In both diagnosed cases           the process of nail matrix keratinization. In NM, both mel-
    of NM, PB was performed at the level of nail matrix. In          anin granules and atypical (pagetoid) melanocytes (Figure 1,
    the remaining 3 cases (in all them, PB was performed at          A and B) can be observed (authors experience).
    the nail bad), dermatopathologists had requested clinical            The process of keratinization in the nail unit is an evolving
    patient re-evaluation and a second LB was performed in           process. It initiates at the nail matrix level and is deduced clin-
    2 cases and en-block tumor excision in 1 case (the clini-        ically with the expansion of the plate. Melanocytes are present
    cal features were strongly suggestive of NM). The histo-         among matrix keratinocytes, but they are usually quiescent
    pathologic interpretation of TB was consistent with the          and not produce pigment. Melanin synthesis may occur in
    diagnosis of melanoma in all the 3 cases.                        benign and malignant conditions, and it is characterized by
b. A LB was diagnostic in 34/51 cases that were finally              incorporation of melanin in nail matrix keratinocytes during
    diagnosed with benign melanocytic activation and in              nail plate production. The pigmentation therefore initially
    the remaining 17 cases a PB was performed. PB was                starts in the proximal nail plate and occupies the whole length
    not diagnostic in 10/17 cases, all performed at the nail         of it during growth. This process is estimated to last from 4-6
    bed level. A second biopsy was requested in all cases            to 10-12 months (hands and feet). When we observe a pig-
    together with a clinical re-evaluation. The remaining            mented band, we therefore only see the degree and distribu-
    7 cases of PB were diagnostic and were performed at              tion of melanin within the nail plate and not the site of origin
    the nail matrix level.                                           of it, as the matrix lies below the proximal nail folds and only
c. A LB was performed in 14/15 cases that were diagnosed             its distal part, the lunula, is visible from the outside.
    as melanocytic nevi and a PB at the nail matrix level                Both technicians and dermatopathologists should be
    was performed in 1/15 cases. All cases were correctly            familiar with the nail anatomy to achieve an optimal pro-
    diagnosed.                                                       cessing of the specimens and to avoid diagnostic misinterpre-
                                                                     tations. But, most important, the surgeon should know that a
    All NM patients underwent therapeutic surgery (conser-           biopsy of melanonychia should excise the nail matrix, which
vative approach or phalanx disarticulation) and are still un-        is the source of the pigmentation.
dergoing regular clinical and instrumental controls. Patients            In the present study, two main issues were considered on
with a different diagnosis (nevi or benign melanocytic acti-         the suspicion of NM: 1) where to biopsy and 2) which type
vation) are undergoing clinical follow up where necessary.           of biopsy offers the best diagnostic approach.




     Figure 1. (A, B) Nail melanoma: histopathologic aspects of a nail matrix biopsy (H&E original magnification 10X; 25X) showing
     proliferation of atypical melanocytes in the basal and supra-basal layers of the nail matrix.




Original Article | Dermatol Pract Concept. 2023;13(2):e2023092                                                                        3
                 Figure 2. (A, B) Benign melanocytic activation: histopathologic aspects of a longitudinal nail biopsy (H&E
                 original magnification 20X; 25X) showing proliferation of melanocytes in the nail matrix and nail bed.


    In the nail unit, biopsies can be performed on four main            information on the characteristics of melanocytes morphol-
locations: the nail folds, bed, plate and matrix. In physiologic        ogy and distribution in all the components of the nail unit.
conditions, most melanocytes are located at the nail matrix
level, while very few or no melanocytes can be observed at              References
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Original Article | Dermatol Pract Concept. 2023;13(2):e2023092                                                                                5
