The first clue to the diagnosis of LM is an increased density of junctional melanocytes [1, 4], typically associated with a solar lentigo-like background, i.e. hyperpigmentation of basilar keratinocytes. The neoplastic melanocytes may be cytologically bland. Not uncommonly, however, there is some nuclear atypia [1] (Figs. 5.1 and 5.3), ranging from slight nuclear enlargement to two or three times the size of a normal melanocyte. Nuclear enlargement is often associated with hyperchromasia [1].

The density of junctional melanocytes varies. While in early lesions solitary units of melanocytes may be separated from each other by a few keratinocytes, in more developed lesions, melanocytes form strips or files and become confluent [1, 4], i.e. form junctional aggregates without interspaced keratinocytes. A conspicuous cytoplasmic fixation retraction artifact producing a clear halo may be present. Neoplastic melanocytes commonly extend into adnexal structures [15] (Figs. 5.1, 5.2, and 5.3). Adnexal involvement is most often first seen in the infundibular portion of the follicle. However, melanocytes may extend deeper to the level of the sebaceous gland and inferior portion of the follicle [4]. This may occasionally cause challenges in assessing dermal invasion and tumor thickness. Junctional tumor growth may lead to the formation of junctional nests. Melanocytes may also be found in the spinous layer [1].

The epidermis of LM is often atrophic with flattening of the rete ridges [12, 17] (Fig. 5.3). The dermis often contains a patchy or band-like lymphocytic infiltrate with melanophages (Fig. 5.2). Some authors suggest that the presence of melanophages is a helpful clue against reactive melanocytic hyperplasia of chronically sun-damaged skin [4]. However, this does not apply when one considers a lichenoid keratosis in the differential diagnosis, since melanophages are commonly seen in this benign condition, which may also be associated with a reactive melanocyte hyperplasia.

In more developed lesions of LM, the nuclear atypia of melanocytes may become more prominent characterized by an angulated or somewhat spindled shaped nucleus [1]. The nuclear chromatin pattern is typically dark (hyperchromatic) [1]. Some of the melanocytes are multinucleated with prominent dendritic processes, a phenomenon, which has been called “starburst giant cell” [18]. The greater the number of nuclei within a multinucleated giant cell, the more likely it is associated with LM [18]. However, the starburst giant cell is not specific for LM, but can also be seen in benign melanocytic nevi, including junctional nevi [19]. Additionally, some melanocytes, possibly already in initial stages of LM, show dendritic appearance, with thick dendrites reaching the upper spinous layer [4, 11].

Associated invasive melanoma may have many different appearances from amelanotic (common) to pigmented (uncommon), epithelioid, fusiform or mixed cell type [20]. A minor degree of stromal fibrosis is often a clue to early superficial invasion. Superficial invasion is often limited to a few isolated tumor cells or small cell aggregates in the papillary dermis. If they are cytologically bland and form nests, they may be difficult to distinguish from a small nevus remnant. Subtle invasive melanoma may at times only be located around follicular structures. Invasive melanoma is readily recognizable, if the tumor cells are pleomorphic, mitotically active and form a mass. Vertical growth phase melanoma is defined as cohesive nests, nodules or plaques larger than those within the epidermis and consisting of atypical tumor cells cytologically different from those in the radial growth phase. In lentigo maligna melanoma, the vertical growth phase often shows spindle cell morphology. Invasive tumors associated with LM may or may not display stromal desmoplasia and perineural invasion [20]. If desmoplasia is prominent, the tumor is designated “desmoplastic”. Up to two thirds of desmoplastic melanomas are associated with LM [21–23]. Neurotropism is rare in small superficial tumors, but not uncommon in more deeply invasive LMM [4]. While it is most often seen in association with fusiform cells, epithelioid melanoma may also be neurotropic.

Although the epidermis is typically atrophic, LM may also contain areas with elongated rather than attenuated rete ridges. This may be in some cases due to LM coinciding with a pigmented actinic keratosis, solar lentigo, or seborrheic keratosis [24]. Some authors describe these lesions as simulating a dysplastic nevus or a lentiginous nevus. Based on one study, dysplastic nevus–like areas, defined as having elongated and/or fused rete ridges and prominent medium to large nests of pleomorphic melanocytes with little or no pagetoid upward migration, predominated in as much as 43 % of LM/LMM [25]. Some authors have suggested a term lentiginous melanoma for lesions with features of LM but with preservation of rete ridges and absence of prominent solar elastosis [26]. It is important to recognize these variants, especially if examining a partial biopsy to avoid a pitfall of erroneous diagnosis of a dysplastic nevus or a lentiginous nevus.