The Histopathological Diagnosis and Reporting of Melanoma: A New Look at an Old Challenge

Special Article - Melanoma Skin Cancer

Austin J Dermatolog. 2016; 3(1): 1044.

The Histopathological Diagnosis and Reporting of Melanoma: A New Look at an Old Challenge

Gerardo Ferrara1* and Giuseppina Improta2

1Department of Oncology, Gaetano Rummo General Hospital, Italy

2Laboratory of Clinical Research and Advanced Diagnostics, IRCCS - CROB Centro di Riferimento Oncologico della Basilicata, Italy

*Corresponding author: Gerardo Ferrara, Department of Oncology, Anatomic Pathology Unit, Gaetano Rummo General Hospital, Via dell’ Angelo 1, Benevento, Italy

Received: December 21, 2015; Accepted: January 19, 2016; Published: January 22, 2016


The goal of a standardized and reproducible histopathological diagnosis and reporting of melanoma is far from being fully achieved. Clark’s and McGovern’s historical classification into lentigo maligna melanoma, superficial spreading melanoma, nodular melanoma, and acral (and mucosal) lentiginous melanoma can be still kept as an acceptable startpoint. The WHO 2006 classification recognizes additional subtypes of melanoma but is still largely incomplete. The differential diagnosis of melanoma with benign melanocytic proliferations is one of the most difficult fields in Dermatopathology because it stems from the evaluation of a constellation of diagnostic criteria whose implementation, meaning, and relative weight considerably vary depending on the overall morphological context; thus the histopathological diagnosis of a melanocytic tumor is a mere assessment of probability, and is subject to considerable interobserver disagreement. Ancillary (Immunohistochemistry and molecular biology) techniques have been increasingly performed in order to assist the histopathological diagnosis; as a rule, however, no single information achieved with these techniques is expected to give clear-cut information for the differential diagnosis between nevus and melanoma. The histopathological reporting should include at least the following compulsory parameters: ulceration (absent vs present); mitotic rate (integer number/square millimeter); regression (if present); lymphovascular invasion (if present) perineurial invasion (if present); Breslow’s thickness; microsatellitosis (if present); status of the surgical margins (with microscopically measured distances between tumor and lateral or deep margins). Even is molecular techniques are expected to completely change our landscape of histopathology of melanoma within the next few years; these ‘classical’ histopathological parameters are still the cornerstone for the management of melanoma patients.

Keywords: Melanoma; Histopathology; Differential diagnosis; Immunohistochemistry; Molecular biology; Histopathological reporting


The histopathological diagnosis and classification of melanoma is probably the greatest conceptual and practical challenge in modern dermatopathology and is expected to rapidly evolve within the next few years [1]. For Clinicopathological purposes, it is still useful to refer to the time-honored classification proposed by Clark [2] in the United States and McGovern [3] in Australia, that is: lentigo maligna melanoma, superficial spreading melanoma, nodular melanoma, and acral (and mucosal) lentiginous melanoma. However, we preliminarily warn that the clinicopathologic prognostic implications of such a classification are not so sharp as originally thought [4]. It must be also underlined that such ‘classical’ categories are identified by the microscopic features of the intraepidermal component of the neoplasm. When such an intraepidermal component is not associated with an invasive dermal component (melanoma cells breeching the basal membrane at the dermoepidermal junction), melanoma is defined as ‘in situ’ (confined within its anatomic compartment of origin). It should be noted that in the context of a seemingly in situ melanoma, invasive tumor is sometimes found after serial sectioning and immunohistochemical studies: however, standardized histologic protocols for the search of any invasive component in a putative melanoma in situ are still lacking.

Classical (Clark’s And McGovern’s) Subtypes of Melanoma

Lentigo maligna: This is the intraepidermal precursor/ component of lentigo maligna melanoma. It typically occurs in chronically sun-exposed areas of elderly white patients and can be therefore considered as the melanocytic analog of actinic keratosis [4]. Microscopically, it s characterized by a lentiginous (that is: mainly a single cell) proliferation, mostly along the basal layer of the epidermis, with deep involvement of the adnexal structures; neoplastic melanocytes are mainly spindle and usually show an obvious nuclear pleomorphism. The proliferation of melanocytes in the depth of the adnexa may mimic invasion [5]. The dermis always shows severe solar elastosis (the histologic hallmark of severe and chronic sun damage); the epidermis is commonly atrophic. It has to be underlined that some exceptions to these rules do occur. It was emphasized that long-standing lesions of lentigo maligna may show a ‘nested’ architecture, [6] a nest being defined as an aggregate of at least three melanocytes. In our experience, the correlation between the age and the architecture of the neoplasm is not absolute; as a matter of fact, 43% of lentigo maligna cases have at least focal dysplastic nevuslike features, typified by nests arranged at the tips of elongated rete ridges [7]. Also based on Clinicopathological correlation, we have suggested that ‘junctional atypical nevi’ of the head-neck area in the elderly are indeed examples of ‘nested lentigo maligna’ and must be cautiously managed as such [8]. Once a dysplastic nevus has been excuded also on the basis of the Clinicopathological correlation, the main differential diagnosis of lentigo maligna is with subacute/ chronic melanocytic photo activation, in which melanocytes are commonly epithelioid and monotonously atypical and show no nesting and no pigmentation (the latter being present in a cap-like fashion in the supranuclear region of the nearby keratinocytes) [9]. In recent years, also based on a careful Clinicopathological approach, a very slow-growing melanoma of the trunk, lentiginous melanoma, has been identified as the counterpart of lentigo maligna on non-chronically sun-damaged skin [10]. The neoplasm is usually very large; with a relatively regular ret form (dysplastic nevus-like) epidermal hyperplasia and a striking predominance of tightly packed single melanocytes at the junction [10].

Superficial spreading melanoma: is the most common subtype of melanoma and can occur anywhere in the body: [4] this means that the anatomic site of the neoplasm does not automatically identify the subtype. The equivalent term ‘pagetoid melanoma’[3] elucidates the histopathologic hallmark of the intraepidermal component of the tumor, that is: the presence of melanocytes at all levels of the epidermis (pagetoid pattern); neoplastic cells are most often epithelioid (rather than spindle as in lentigo maligna and in acral lentiginous melanoma), and sometimes show a hypercromatic nucleus and an abundant pale cytoplasm with ‘dusty’ melanin (pagetoid cells): these features impart a ‘shotgun appearance’ to the epidermis. In some instances, however, the pagetoid configuration is made by relatively small cells and is at risk to being overlooked on histopathologic examination. It must be emphasized that pagetoid configuration is not invariably found in melanoma and is not pathognomonic of melanoma. A more or less prominent pagetoid scatter may be found in vulvar/genital nevi, acral nevi, recurrent/persistent nevi, Spitz/Reed nevi, in nevi of the childhood, and in several non-melanocytic tumors (Paget’s disease, pagetoid Bowen’s disease, tricholemmal carcinoma, epiderotropic T cell lymphoma, Merkel cell carcinoma, Langerhans cell histiocytosis). For a melanocytic tumor, in favor of a diagnosis of superficial spreading melanoma is the widespread pagetoid configuration, the pagetoid configuration at the edges of the tumor, and the cytologic atypia [11]. Epidermotropic metastasis of melanoma is also difficult to be differentiated from primary superficial spreading melanoma: [12] the anamnestic data and the Clinicopathological correlation are the mainstay for such a differential diagnosis.

Nodular melanoma: is defined by an intraepidermal neoplastic component which involves less than three rete ridges at the edges of a dermal tumor mass. Neoplastic melanocytes may be epithelioid or spindle; in addition, also nevoid melanoma and spitzoid melanoma (see below) should have, by definition, the typical architectural features of nodular melanoma. If identified according to strict Clinicopathological criteria, nodular melanoma is quite rare: [13] moreover, some cases fulfilling the criteria for nodular melanoma represent a bona fide advanced nodular phase of another subtype of melanoma; and some other cases labeled as nodular melanoma are possibly primary dermal melanomas [14]. The differential diagnosis between primary nodular melanoma and metastatic melanoma can be very difficult: in favour of primary nodular melanoma are the prominent involvement of the epidermis, the association with a nevus, and the presence of an epidermal ‘collarette’ at the edges of the neoplastic nodule.

Acral (and mucosal) lentiginous melanoma: It is characterized by an intraepidermal component of the lentiginous type with a striking predominance of spindle melanocytes with hypercromatic nuclei, mainly arranged in single units at the junction with variable (not always prominent) pagetoid spread [15]. The epithelium is typically hyperplastic, usually with thin and very elongated rete ridges; inflammation is often evident even in very early lesions as collections of lymphocytes at the tips of the rete ridges [16]. Tumors showing these features have been described in the volar skin, in the nail matrix, in the oral and nasal cavity, in the vulva, and in the anus [4]. Black and Orientals are most commonly affected by this subtype of melanoma in the skin.

Other Subtypes of Melanoma

The WHO 2006 classification of melanoma [17] (Table 1) encompasses, along with the ‘classical’ subtypes, the below specified entities.