Melanoma histology involves examining melanoma tissue under a microscope. This study of tissue structure and cell characteristics is important in confirming a melanoma diagnosis. Understanding these microscopic details helps healthcare providers identify the disease precisely, which is an important step in managing the condition.
The Pathologist’s Process
A tissue sample’s process begins with a biopsy, where a small piece of suspicious skin is removed. Common biopsy types include excisional biopsies, which remove the entire lesion, or punch biopsies, which take a cylindrical core of tissue. A dermatologist or surgeon performs these procedures, sending the sample to a pathology laboratory for analysis.
At the lab, the tissue undergoes several standardized steps for microscopic examination. It is fixed in a formaldehyde solution to preserve cellular structure and prevent decomposition. The tissue is then dehydrated and embedded in paraffin wax, creating a solid block for slicing. These blocks are cut into thin sections, often just a few micrometers thick, using a microtome.
The thin tissue sections are mounted onto glass slides and stained to make cellular components visible. Hematoxylin and Eosin (H&E) staining is common, with hematoxylin staining cell nuclei blue and eosin staining the cytoplasm and extracellular matrix pink. A pathologist, a medical doctor specializing in diagnosing diseases by examining tissues and fluids, meticulously reviews these stained slides. Their role is to identify abnormal cells or architectural patterns indicating melanoma and differentiate it from benign conditions.
Microscopic Features and Diagnosis
Pathologists meticulously examine tissue samples for architectural and cytological features that distinguish melanoma from benign moles (nevi). Architectural features often include asymmetry in the lesion’s shape and a lack of clear boundaries, meaning tumor cells are not neatly contained. Melanoma cells frequently show irregular nesting, forming nests of varying sizes and shapes within the epidermis and dermis, unlike the uniform nests in benign moles. The upward migration of atypical melanocytes, known as pagetoid spread, where melanocytes scatter abnormally into the upper epidermis, is another architectural indicator.
Beyond tissue arrangement, individual cells exhibit specific cytological abnormalities. Melanoma cells typically have large, pleomorphic (variably shaped) nuclei that appear irregular and sometimes angulated. Prominent nucleoli, small, dense structures within the nucleus, are often observed and can be multiple or unusually large. The cytoplasm of these atypical melanocytes may show varied pigmentation, ranging from heavily pigmented to completely lacking pigment, unlike the more uniform pigmentation in benign melanocytes. These combined architectural disorganization and cellular irregularities are important for a precise melanoma diagnosis.
Understanding Melanoma Subtypes
Melanoma encompasses several subtypes, each with distinct histological features. Superficial Spreading Melanoma is the most common subtype and often shows a radial growth phase before invading deeper. Histologically, it is characterized by atypical melanocytes spreading individually or in small nests along the epidermal-dermal junction and often extending upward into the epidermis, exhibiting pagetoid spread.
Nodular Melanoma is known for its rapid vertical growth phase, often appearing as a raised, dark lesion. Under the microscope, it typically presents as a dense proliferation of atypical melanocytes forming a cohesive nodule within the dermis, with little or no radial growth component. The cells show high mitotic activity and can extend deeply into the skin layers.
Lentigo Maligna Melanoma usually develops on chronically sun-damaged skin, particularly on the face, and begins as a slow-growing, flat lesion. Histologically, it is characterized by an increase in atypical melanocytes mainly confined to the basal layer of the epidermis, often singly or in small nests, with solar elastosis (damage to elastic fibers) present in the underlying dermis. These cells spread laterally along the epidermis for an extended period.
Acral Lentiginous Melanoma is a less common subtype occurring on the palms, soles, and under the nails. Its microscopic appearance includes atypical melanocytes that proliferate along the basal layer of the epidermis, similar to lentigo maligna melanoma. These melanocytes often show a lentiginous pattern of growth, meaning they are arranged linearly along the epidermal ridges, and can be associated with epidermal thickening.
Histology’s Role in Prognosis and Treatment
Histological examination provides crucial information that directly influences melanoma prognosis and guides treatment. Breslow thickness, measured in millimeters from the granular layer of the epidermis to the deepest point of tumor invasion, is the single most important prognostic factor. Thicker melanomas are associated with a higher risk of metastasis and a less favorable outcome. For example, a melanoma less than 1.0 mm thick carries a low risk of spread, while those greater than 4.0 mm indicate a higher risk.
The presence or absence of ulceration, a break in the epidermis overlying the melanoma, also significantly impacts prognosis. Ulcerated melanomas, regardless of their thickness, are considered a more aggressive feature and are associated with a higher risk of disease progression. The mitotic rate, the number of actively dividing cancer cells per square millimeter, indicates tumor aggressiveness. A higher mitotic rate suggests faster tumor growth and a less favorable prognosis.
Historically, the Clark level of invasion was also used, which describes the anatomical depth of invasion into different layers of the skin. While still sometimes reported, its prognostic significance has largely been superseded by Breslow thickness, especially for thinner melanomas. The findings from the pathology report, including Breslow thickness, ulceration, and mitotic rate, determine the melanoma’s stage. This staging information informs management strategies, such as further surgery, sentinel lymph node biopsy, or systemic therapies.