#dermpathJC August 2019:
Thursday, August 22nd, 9 pm EST
Article discussed: Is melanocyte density our last hope? Comparison of histologic features of photodamaged skin and melanoma in situ after staged surgical excision with concurrent scouting biopsies
Authors: Jodi Speiser, Joy Tao, Amanda Champlain, Lauren Moy, Monica Janeczek, Reeba Omman, Kumaran Mudaliar, Rebecca Tung
Temporary open access courtesy of Journal of Cutaneous Pathology at: https://doi.org/10.1111/cup.13462
Summary prepared by: Cacey Peters, M.D. (@caceypeters)
Journal Club Summary:
- Overlap between melanocytic hyperplasia (MH) and junctional lentiginous melanocytic proliferations (JLMP) and melanoma in situ (MIS) can be a significant diagnostic dilemma.
- Further complication arises from variability in diagnostic criteria among pathologists leading to over and under-diagnosis.
- Lentigo maligna (LM) is a subtype of MIS that grows on chronically photodamaged skin, predominantly on the head and neck.
- In an established lesion, LM is histologically defined as a junctional proliferation of confluent single cells and nests of large atypical melanocytes, which may demonstrate focal upward pagetoid spread.
- In contrast, the background nonlesional photodamaged skin displays melanocytic hyperplasia (MH) and cytologic enlargement and mild pleomorphism.
- This study used formalin-fixed paraffin-embedded staged mapped excision from a “slow Mohs” procedure in tandem with baseline scouting biopsies of adjacent non-lesional photodamaged skin to assist in determination of surgical margin clearance.
- The advantages for this technique include entire margin assessment and the need for specific additional excision, as well as better cosmetic outcomes.
- The lesional and photodamaged control biopsies from the same patient were compared using nuclear IHC stains to assess clinically relevant histologic criteria that may be used to distinguish photodamaged skin from JLMP and MIS.
- Inclusion criteria included patients (a) with a previous biopsy-confirmed JLMP or MIS (lentigo maligna or superficial spreading subtypes) in a cosmetically or surgically challenging location that was available for review, (b) whose biopsy included an IHC stain for MiTF or Sox-10 and (c) who were eligible for staged excision.
- Exclusion criteria included patients with previous biopsies that were unavailable for review or without IHC stain for MiTF or Sox-10, palpable areas within the lesion, cervical lymphadenopathy, an invasive component on initial biopsy or any contraindication for staged excision
- The combination of histologic and clinical features aid in differentiating benign melanocytic junctional proliferations from lesions described as AJMP include more advanced patient age, presence of background sun damage, lentiginous melanocyte clustering, increased melanocytic density, lack of upward spread, lack of definitive confluence (>3 consecutive melanocytes), and no/minimal nests.
- The clinical management of each entity has been highly debated.
- The NIH recommends a 5 mm margin on surgical excisions but has been had mixed success on proven adequacy.
- Staged excisions generally have high cure rates, with two studies reporting recurrence rates of 1.7% and 2.2%, respectively, although utilizing less specific IHC stains as this study.
- Creation of specific criteria and definitions of LM, JLMP/MIS have been revised over the decades, originating from Ackerman et al who were the first to propose a set of 12 criteria which included:
- Pagetoid spread (MIS) vs melanocytes situated at the dermal-epidermal junction (MH)
- Irregular MH (MIS) vs regular MH (MH)
- Deep adnexal involvement (MIS) vs superficial adnexal involvement (MH)
- Confluence of melanocytes (MIS) vs absence of confluence (MH)
- Presence of junctional nests (MIS) vs absence (MH)
- Uniform (MIS) vs nonuniform pigmentation (MH)
- Flat rete ridges (MIS) vs preserved rete ridges (MH)
- Pleomorphic melanocytic nuclei (MIS) vs uniform nuclei (MH)
- Prominent melanocytic dendrites (MIS) vs inconspicuous dendrites (MH)
- Markedly large and atypical nuclei (MIS) vs large but mildly atypical nuclei (MH)
- Collapse of cytoplasm around melanocytic nuclei (MIS) vs absence of this feature (MH)
- Abundant melanophages (MIS) vs few or no melanophages (MH)
- Subsequent criteria suggested in the literature were:
- Large, elliptical and irregular nuclei via nuclear morphometry
- 10% to 20% proliferating melanocytic cells by staining with PCNA or Ki-67/MIB-1
- Presence of HMB-45 positive melanocytes.
- Weyers et al evaluated the sensitivity and specificity of all the above criteria, establishing that the most valuable criteria for differentiation were:
- Presence of nests
- Irregular MH
- Deep adnexal extension of melanocytes
- Pleomorphism of melanocytes
- Pleomorphism of melanocytic nuclei
- IHC criteria have been proposed using Mart-1/Melan-A, MiTF and Sox-10 stains to evaluate LM, benign lesions on sun-damaged skin, and background sun damage.
- MiTF or Sox-10 (nuclear stains) are preferred as to avoid overestimation of melanocyte density with Mart-1/Melan-A (cytoplasmic stain)
- Photodamaged skin show many criteria originally used for MIS:
- Increased and irregular melanocyte density
- Melanocyte confluence
- Thèque formation
- Adnexal extension
- Suprabasilar scatter
- Most of these studies were cross-sectional analyses, comparing a variety of patients to each other, which made it impossible to control for factors such as geographic location, anatomic site, age, Fitzpatrick skin type, and history of sun exposure, all of which can influence baseline melanocytic density.
- The current study found a statistically significant difference in the following histopathologic findings:
- melanocyte density (per 1mm instead of 0.5 mm in previous studies)
- irregular melanocyte distribution
- clustering of melanocytes
- follicular infundibulum involvement
- Presence of nests
- This study was able to control for confounding factors, such as different baseline melanocytic densities, by comparing atypical/malignant biopsies with a sun-damaged control from the same patient.
- The photodamaged skin samples were taken at least 2 cm from the primary lesion in order to avoid any potential field effect.
- Although time consuming, assessment of melanocyte density may be an objective and reliable method for diagnosing these complex lesions.
- Digital imaging may eliminate the need for manual counting in the near future.
FIGURE 1 Clinical image showing clinical lentiginous lesion (after Wood’s lamp illumination) along with markings for scouting biopsies. FIGURE 2 Clinical image showing an additional peripheral surgical margin drawn approximately 5 mm away from the delineated clinical lesion. The margins are labeled like a clock face for orientation with the numbers 3, 6, 9, and 12. Two 3 mm scouting punch biopsies were taken at least 2 cm away from the original lesion.
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