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Prognosis, Staging, and Reporting of Melanomas
Prognostic information is helpful for individual patients affected by melanoma to understand their likely clinical outcome. However, it is also important for clinicians to assist them in making management decisions and for the design, conduct, eligibility, and analysis of clinical trials. Approximately 90% of melanomas are diagnosed as primary tumors localized to the skin, with no evidence of metastatic disease at the time of diagnosis. The tumor-specific 10-year survival for such patients ranges from 75% to nearly 100%, depending on a combination of clinical and histopathologic parameters. Staging is a mechanism to assign patients to different risk category groups. Prognostic models and current staging system rely on a number of clinical and histopathologic factors. They are briefly described and discussed herein.
Clinical Parameters
Clinical parameters such as age, gender, skin color, pigmentation status of the tumor, and anatomic site are not only relevant for differences in the etiology and incidence of melanomas but play a role also for the outcome of patients. Advanced age, male gender, and head and neck location are prognostically disadvantageous. Some of the effects of clinical parameters on prognosis are indirect, having their effect by delayed diagnosis and treatment (e.g., an amelanotic subungual melanoma may only be biopsied at an advanced tumor stage), influencing surgical resectability (e.g., the increased local recurrence rate of melanomas of the head is in large part due to the difficulty in obtaining a wide and deep margin clearance in this anatomic region), or immune status (e.g., some of the adverse effect of increasing age on prognosis are likely related to age-related compromise of the immune system). Other issues, such as the survival advantage of women, are complex and multifactorial.
Histopathologic Parameters
Tumor Thickness
The pioneering work of Alexander Breslow, published in 1970, showed that the strongest predictor of clinical outcome for patients with localized primary cutaneous melanoma was tumor thickness as measured vertically from the top of the epidermal granular layer to the deepest invasive melanoma cells ( Fig. 32.1 ). Although prior studies showed that depth of invasion was related to prognosis in melanoma, the landmark publication by Breslow was the first to show that this was the most important prognostic factor. Since 1970, numerous other studies have confirmed the independent prognostic significance of tumor thickness. It remains the primary criterion on which patients with clinically localized primary melanoma are staged according to the eighth edition of the American Joint Committee on Cancer (AJCC) Melanoma Staging System.
Tumor thickness should be measured in millimeter units. According to AJCC guidelines the numerical value should be recorded to the precision of a single digit after the decimal (i.e., the nearest 0.1 mm). For example, both a melanoma measuring 0.95 mm or 1.04 mm in thickness should be rounded to 1.0 mm and reported as such. Assessing tumor thickness is a fairly reliable method. It is associated with excellent interobserver reproducibility among pathologists, if one accepts a range in the thickness value of ±10%.
However, there are pitfalls and difficulties in the assessment of tumor thickness. This may be due to partial sampling of the tumor, ulceration, epidermal hyperplasia, adnexotropism/periadnexal extension, lymphatic invasion, fragmentation and/or tangential sectioning, or other reasons.
Partial Biopsy.
When a partial biopsy of a melanoma is taken, the accuracy of tumor thickness from histopathologic examination of the biopsy depends on whether or not the thickest part of the tumor was biopsied and/or whether the entire depth of the tumor was captured by the procedure. When a melanoma is broadly transected at the base of a shave biopsy, only a minimum measurement can be provided, which may need to be modified upon review of the subsequent excision, depending on whether or not and how much residual tumor is found in the excision specimen. When melanoma only focally extends to the base of a biopsy, it is rare that additional measurable invasive tumor is found, unless the biopsy did not capture the area of greatest tumor thickness. When there is residual tumor in the subsequent excision, the question may arise whether or not and how much additional tumor depth may need to be added to the thickness value from the prior biopsy to obtain the most accurate final tumor thickness for prognosis. If invasive melanoma is present in an excision and located adjacent to a scar, the measured thickness of the prior biopsy is taken for staging purposes, if it exceeds the value of the excision; if the thickness of the excision exceeds the value from the prior biopsy, then the value from the excision is taken. If invasive melanoma is located underneath the scar from the prior biopsy, in which tumor was broadly transected at the base, it should be added. The value to be added to the tumor thickness of the prior biopsy is the distance of the most deeply located tumor cells from the base of the scar. It is understood that this is often not very precise, but a rough estimate is still better than ignoring a significant residual tumor component for prognostic purposes.
Ulceration.
When the area overlying the thickest invasive tumor component is ulcerated, the thickness is measured as the distance from the tissue base of the ulcer (excluding the fibrinous exudate) to the most deeply located tumor cell along a virtual vertical line ( Fig. 32.2 ). A large and deep ulcer may lead to underestimation of tumor thickness. However, for practical purposes, a minor inaccuracy in this setting is usually of little consequence for prognostic accuracy because most tumors with wide and deep ulcers are thick and display other high-risk features.
Epidermal Hyperplasia.
At most anatomic sites, the thickness of the epidermis measures approximately 0.1 to 0.2 mm. Variability in epidermal thickness has little impact on the value of Breslow tumor thickness of advanced melanomas, and there is a good correlation between thickness and actual stromal invasion. However, thickening of the epidermis, whether related to trauma/irritation (reactive hyperplasia), an associated verruca or keratosis, or anatomic site (palmar or plantar skin), can lead to a significant discordance between stromal invasion and measured tumor thickness in thin melanomas and lead to “overstaging.” For example, a melanoma may invade only minimally the papillary dermis to a depth of 0.2 mm, but if there was an overlying prurigo nodule with epidermal thickness of 0.8 mm, this would yield a pT1b melanoma, which in normal skin (unassociated with epidermal hyperplasia) would have been a pT1a melanoma.
Adnexotropism/Periadnexal Extension.
Some melanomas with adnexal involvement may invade the dermis from the epidermis and/or from within adnexal structures. When invasive melanomas are located both in the dermis underneath in situ melanoma and in perifadnexal stroma surrounding intraadnexal in situ melanoma, measuring tumor thickness precisely can be difficult. When the invasive tumor front underneath the epidermis is the thickest part of the entire lesion, this part is chosen for measuring Breslow thickness according to standard guidelines ( Fig. 32.3 ). When the largest or only invasive component of a melanoma is centered around a follicle (or sweat duct) with intraadnexal (in situ) melanoma and there is no or a much thinner melanoma population directly underlying the epidermis, we recommend measuring tumor thickness from the center of the adnexal structure to the outermost invasive tumor cells in the periadnexal stroma ( Fig. 32.4 ). This is a better approximation of tumor thickness than the distance from the granular cell layer of the epidermis overlying the dermal melanoma.
Lymphatic Invasion and/or Satellites.
For measuring tumor thickness, one should not include satellite lesions or lymphatic tumor emboli.
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