The early steps in the development and progression of primary malignant melanoma include proliferation of transformed epidermal melanocytes and their subsequent invasion into papillary dermis, a condition also known by the term “nontumorigenic radial growth phase”; this can be followed by the “tumorigenic vertical growth phase,” a progression step able to metastasize, characterized by the invasion of the reticular dermis and beyond.1 , 2 Following these histogenetic concepts, thin melanoma may be classified into three subtypes, correlated with different recommendations for sentinel lymph node biopsy, as follows:
- Nontumorigenic in situ or microinvasive radial growth phase thin melanoma: this lesion requires wide local excision for the removal of any small cellular nest eventually present at a distance from the main lesion.2 , 3 All of the cells must be removed because they could give rise to a tumorigenic vertical growth phase clone over time.2 , 3 However, sentinel lymph node biopsy is not recommended, because the growth lacks metastatic potential.4 Generally, the thickness of this subtype is less than or equal to 0.8 mm.
- Tumorigenic early vertical growth phase thin melanoma: this lesion is characterized by the presence of a cluster of cells in the dermis that is larger than the largest cluster in the epidermis (tumorigenicity) and/or by the presence of dermal mitoses (mitogenicity).2 , 3 These two features suggest that thin melanoma has acquired the capacity of growth not only in the epidermis and superficial dermis, but also in the deep dermis. This subtype is associated with a statistical chance for distant metastases; thus, enlargement biopsy and sentinel lymph node biopsy must be performed.4 Generally, the tumor thickness is greater than 0.8 mm and less than or equal to 1 mm.
- Uncertain tumorigenic thin melanoma: this lesion is associated with a significant risk for metastases because of the presence of extensive regression, which could contain a vertical growth phase clone.5 , 6 Wide local excision and sentinel lymph node biopsy are recommended.4
In practice, patients with tumorigenic and mitogenic early vertical growth phase thin melanoma or uncertain tumorigenic thin melanoma should be considered for sentinel lymph node biopsy. The recommendations of our histogenetic classification are in agreement with the conclusions of Appleton and colleagues.1 The authors have performed a meta-analysis of 35,276 patients with thin melanoma, and sentinel lymph node biopsy has yielded a positive result in 5.1 percent of these cases.1 Appleton et al. have concluded that the vertical growth phase had a strong association with sentinel lymph node biopsy positivity.1 In the eight edition of the American Joint Committee on Cancer Staging Manual, the melanoma expert panel has also noted that the subcategorization of thin melanoma beyond the Breslow thickness cutoff of 0.8 mm (pT1a ≤ 0.8 mm; pT1b > 0.8 mm) has clinical relevance for the role of sentinel lymph node biopsy regardless of ulceration.7 , 8 Sentinel lymph node metastases are very infrequent (<5 percent) in thin melanomas less than or equal to 0.8 mm, but they occur in 5 to 12 percent of thin melanoma cases deeper than 0.8 mm and less than or equal to 1 mm; consensus guidelines have recommended that sentinel lymph node biopsy should be considered in this second group of patients, particularly when other adverse prognostic indicators are present.7 We believe that this discrepancy is attributable to the greater incidence of early vertical growth phase inside 0.8 to 1.0 mm thin melanomas, well explainable through the histogenetic model of malignant melanoma progression here illustrated.
DISCLOSURE
Neither author has a financial interest to declare in relation to the content of this communication.
Luca Roncati, M.D., Ph.D.
Francesco Piscioli, M.D., Ph.D.
Department of Diagnostic and Clinical Medicine and of
Public Health
Institute of Pathology
University Hospital of Modena
Modena, Italy
REFERENCES
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2. Piscioli F, Pusiol T, Roncati L. Histopathological determination of thin melanomas at risk for metastasis. Melanoma Res. 2016;26:635.
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4. Piscioli F, Pusiol T, Roncati L. Wisely choosing thin melanomas for sentinel lymph node biopsy. J Am Acad Dermatol. 2017;76:e25.
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