A Quantitative Immunohistochemical Evaluation of Lentigo Maligna and Pigmented Solar Keratosis

Abstract

Pigmented solar keratosis (PSK) is sometimes clinically indistinguishable from lentigo maligna, a form of malignant melanoma in situ. Occasionally histologic diagnosis is also difficult. Accurate diagnosis is essential, as the treatment and prognosis for each condition differs considerably. To determine whether there was a significant overlap in the number of melanocytes in these sun-damaged skin lesions, or whether immunohistochemistry might be helpful in the differential diagnosis, the authors examined skin biopsy specimens from 26 patients with obvious lentigo maligna and 15 patients with PSK using 3 monoclonal antibodies (HMB-45, NK1C3, and vimentin) and 1 polyclonal antibody (S-100 protein). Formalin-fixed paraffin sections were immunostained with each of the above antibodies, and immunopositive cells per mm2 of epidermis were counted. The difference between lentigo maligna and PSK counts was statistically significant at a level of P < .0001; furthermore, there was almost no overlap between the two groups. The sensitivity for the diagnosis of lentigo maligna was high with all antibodies. However, HMB-45 had the highest sensitivity and the lowest false-positive rate and was visually most pleasing. Using a cut-off count of 60 cells per mm2 of epidermis, HMB-45 had a sensitivity of 96% and a 0% false-positive rate. In this study, lentigo maligna was easily differentiated from PSK. The real value of immunohistochemistry in the differential diagnosis of these pigmented lesions should be tested in a prospective study using cases that are difficult to diagnose by routine light microscopy.

Spreading pigmented actinic keratosis: A review

“…However, recognition of atypical melanocytes that may be scant or lightly pigmented is sometimes difficult, and SPAK may contain vacuolated pigmented basal keratinocytes that can resemble melanocytes, making diagnosis difficult. 5 The differentiation between the two lesions also becomes difficult on sun-damaged skin. Hendi et al 26 proposed that melanocyte nesting, vertical stacking, or pagetoid spread must be identified to confidently diagnose MIS in this particular setting.…”

“…12 Several studies emphasize the importance of using other melanocytic markers such as S-100 and HMB-45 in addition to Melan-A and MART-1. 5,12,27,[29][30][31] One particular study looking at differences between MIS (lentigo maligna type) and SPAK cited HMB-45 counts of 60/mm 2 diagnostic of MIS with 96% sensitivity. However, the authors did admit that the number of positive cells in MIS (lentigo maligna type) varied from area to area within one piece of tissue and they selected only areas of greatest melanocyte density for study.…”

“…The histopathologic difficulty in distinguishing SPAK and melanoma in situ (MIS) (lentigo maligna type) occurs when it is not clear whether the pigmented atypical cells in the basal layer are keratinocytes or melanocytes. 4,5 This has obvious implications as the two conditions portend very different prognoses and levels of concern with MIS (lentigo maligna type) requiring total excision with histologic assessment and SPAK only requiring mild destructive therapy such as cryosurgery. 5 Other pigmented patches arising on sun-exposed skin that enter the differential diagnosis include: early seborrheic keratosis, melanocytic nevus, and solar lentigo.…”

“…4,5 This has obvious implications as the two conditions portend very different prognoses and levels of concern with MIS (lentigo maligna type) requiring total excision with histologic assessment and SPAK only requiring mild destructive therapy such as cryosurgery. 5 Other pigmented patches arising on sun-exposed skin that enter the differential diagnosis include: early seborrheic keratosis, melanocytic nevus, and solar lentigo. Management of the conditions remarkably and understandably differs as seborrheic keratosis and senile lentigo are banal requiring no further treatment whereas MIS (lentigo maligna type) and SPAK are evolving lesions toward melanoma and squamous cell carcinoma, respectively.…”

Management of lentigo maligna and lentigo maligna melanoma: Seminars in surgical oncology

“…Immunohistochemistry, with the markers HMB45 and Melan-A, is extremely valuable in making this distinction. HMB45 expression has a sensitivity for LM of 96% with a 0% false positive rate [35]. Melan-A (MART-1) is also a useful marker, but false-positive staining of melanin laden keratinocytes has been reported and therefore in pigmented epidermal lesions, Melan-A immunohistochemistry may overestimate melanocyte density.…”