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• The melanoma staging system continues to evolve in parallel with our understanding of this complex disease
• Some key features of the 8th Edition staging system include:
  • Modifications to the T1 subcategory
  • More granular incorporation of:
    • Satellite, in-transit, and microsatellite disease into the N category
  • Refinement and expansion of the M1 subcategories
• T Category:
  • Breslow tumor thickness and tumor ulceration:
    • Remain the dominant prognostic factors in the T category
  • Breslow tumor thickness:
    • Measured in millimeters and reported to the nearest tenth of a millimeter in the 8th Edition:
      • Is determined by using an ocular micrometer to measure the total vertical height of the melanoma:
        • From the granular layer to the area of deepest penetration
    • Historically, Clark level of invasion:
      • Was determined by assessing the extent of penetration into the dermis
    • Prospective data support that measurement of Breslow tumor thickness:
      • Is more reproducible than measurement of Clark level and that Breslow tumor thickness is the more accurate predictor of outcome
    • The AJCC Melanoma Expert Panel:
      • Continues to use Breslow tumor thickness cut-points of:
        • 1 mm for the T categories
        • 2 mm for the T categories
        • 4 mm for the T categories
      • However, in the 8th Edition of the AJCC staging system:
        • A tumor thickness stratum of 0.8 mm plays a key prognostic role:
          • In subcategorizing T1 tumors:
            • In contrast to previous incorporation of mitoses (as a dichotomous variable only:
              • i.e., < 1 mitosis/mm² vs. at least 1 mitosis/mm²:
                • Contributed to the definition of T1a and T1b, respectively in the 7th Edition
        • Specifically, in the 8th Edition, primary melanomas:
          • With a tumor thickness < 0.8 mm without ulceration are:
            • Designated T1a
          • Whereas primary melanomas 0.8 to 1.0 mm or those < 0.8 mm with ulceration are:
            • Categorized as T1b
      • Despite its removal from the T category for thin melanomas:
      • The AJCC recognizes the prognostic importance of mitotic rate in all T1 to T4 lesions:
        • Notes that this important covariate should be recorded (as number of mitoses/mm²), as it will likely be included in the development of clinical tools and contemporary prognostic models
• Melanoma may also present as metastasis to a regional nodal basin, or even with distant metastatic disease:
  • Yet without evidence of a primary lesion:
    • When there is no evidence of a primary tumor (i.e., unknown primary or completely regressed melanoma) or when thickness cannot be assessed:
      • The AJCC (8th Ed.) categorizes these as T0 and TX, respectively
• Primary tumor ulceration:
  • Is histopathologically defined:
    • As the absence of an intact epidermis overlying a portion of the primary tumor
  • Importantly, ulcerated melanomas are associated with a:
    • Significantly worse prognosis than nonulcerated melanomas of the same thickness
  • In the T category of the AJCC staging system, ulcerated tumors are designated by b following the numerical T:
    • An exception to this rule is for a nonulcerated primary melanoma with a tumor thickness 0.8 to 1 mm:
      • It is also designated by a “b” (T1b)

• N Category:
  • The N category refers to melanoma metastases to:
    • Regional lymph node basins and other intralymphatic manifestations of melanoma metastasis (e.g., in-transit, satellite, and microsatellite disease)
  • Regional nodal tumor burden:
    • Is the most important predictor of survival in patients without distant disease
  • Overall, there is significant heterogeneity in prognosis among patients with regional disease
  • Multiple studies have demonstrated that the number of pathologically involved lymph nodes:
    • Is a dominant and independent predictor of outcome in patients with melanoma
  • The 8th Edition AJCC staging system N category continues to use:
    • 1, 2 to 3, and 4 or more regional lymph nodes to generate N subcategories
  • The presence of primary tumor ulceration has also been shown to be an independent adverse prognostic factor:
    • Among patients with regional nodal disease:
      • Leading to its continued incorporation into the melanoma staging system
  • In the 8th Edition:
    • Both primary tumor thickness and ulceration are used to define N stage groups
  • Aside from the number of tumor-involved lymph nodes:
    • It is important to distinguish the:
      • Burden of nodal disease as well as the presence or absence of in-transit, satellite, and/or microsatellite disease
    • Previous empiric definitions such a microscopic and macroscopic regional nodal disease:
      • Have been replaced by “clinically occult” or “clinically detected” regional nodal disease, respectively:
        • Patients who have clinically negative regional lymph nodes but pathologically documented nodal metastases (i.e., a positive sentinel node):
          • Are defined as having “clinically occult” nodal metastases:
            • Designated by the letter a in the N category
      • In contrast, patients with clinical evidence of regional nodal metastases that is confirmed on pathologic examination are defined as having “clinically detected” nodal metastases:
        • Designated by the letter b in the N category
          • Overall, survival for patients with clinically detected nodal disease is worse than for patients with clinically occult nodal disease
  • Additional components of the N category include:
    • Satellite, in-transit, or microsatellite disease
    • Presence of at least one of these types of metastasisis coded by a suffix “c” in the 8th Edition N category and further stratified according to the number of tumor-involved regional lymph nodes:
      • N1c, N2c, or N3c
    • Satellite and in-transit metastases are classically defined:
      • As skin or subcutaneous lesions:
        • Within 2 cm of the primary tumor or more than 2 cm from the primary melanoma, respectively:
          • But generally not beyond the regional nodal basin, and are types of non-nodal regional metastasis
    • Microsatellites are defined as:
      • Any foci of metastatic tumor cells adjacent or deep to, and discontinuous from the primary tumor
      • It is important that there be an element of normal interposition tissue, that is, if only fibrosis and/or inflammation separate a suspected microsatellite from its primary, one should query where this represents regression of this intervening region
      • Microsatellites are also included in the N category staging system

• M Category:
  • The M category refers to:
    • Melanoma distant metastasis and is classified as stage IV
  • Within the M category:
    • There is only one stage, M1
      • In contrast to the three M subcategories in the 7th Edition (M1a, M1b, and M1c)
    • There are four subcategories in the 8th Edition AJCC melanoma staging system
  • Distant metastases to the skin, subcutaneous tissue, or distant lymph nodes:
    • Are designated M1a:
      • They are associated with a better prognosis than metastases to other anatomical sites
  • Metastases to the lungs:
    • Are associated with an intermediate prognosis:
      • Are designated M1b
  • Visceral metastases are associated with a worse prognosis:
    • Are designated M1c
  • New to the 8th Edition is the addition of a subcategory for CNS metastasis (i.e., brain, spinal cord, and/or leptomeningeal disease):
    • Designated M1d
      • This category of disease is generally associated with worse survival compared to the other M categories
  • M1c now includes patients with non-CNS visceral metastasis
  • The subcategories reflect survival differences among patients with metastatic disease:
    • Depending on the anatomic sites of metastases.
  • Serum lactate dehydrogenase (LDH) level also continues to be included in the M category:
    • An elevated LDH has been shown to adversely influence survival across patients with stage IV disease
    • LDH level is denoted with:
      • The suffix (0) in patients without elevation, or (1) for those with an elevated LDH (i.e., M1a(1) …M1d(1))
    • In patients in whom LDH level is unknown or unspecified, no suffix is added

• Clinicopathologic Staging (c/pTNM)
  • Clinical staging includes:
    • Above-noted features of the primary tumor:
      • As well as lesions and clinical and/or radiologic studies
  • Pathological staging involves incorporating all variables of microstaging of the primary tumor:
    • As well as information from the surgical specimen, including treatment effect and margin status
    • Lymph node status is confirmed by both identification and quantification of sentinel and/or regional nodal basin involvement
    • Formal pathological staging is crucial to both proper classification and prognostication of patient outcome

• EXTENT OF DISEASE EVALUATION
  • In addition to physical examination, several adjuncts are used to determine the extent of disease
  • The National Comprehensive Cancer Network (NCCN) provides guidelines to evaluate for possible metastatic melanoma with imaging
  • For melanoma in situ:
    • Imaging studies are not recommended
  • For stages I–II melanoma:
    • Imaging is recommended only if there are specific signs or symptoms that need evaluation
  • For stage III melanoma:
    • It is my general practice to obtain baseline imaging with a:
      • Chest x-ray, computed tomographic scan, PET/CT, and/or magnetic resonance imaging (MRI) of the brain
      • Ultrasonography with fine-needle aspiration of the associated lymph node basins may be useful in detecting metastatic disease in lymph nodes:
        • Excisional biopsy and/or formal resection of suspicious nodes solely for diagnostic purposes is discouraged
  • Patients who present with suspected stage IV are generally staged with:
    • Computed tomography (CT) of the chest, abdomen, and pelvis ± positron emission tomography (PET) as well as MRI of the brain:
      • Image-guided percutaneous biopsy of concerning lesions can be used to confirm disease
      • Excisional biopsy of suspected metastatic lesions is rarely indicated for diagnostic purposes

#Arrangoiz #CancerSurgeon #HeadandNeckSurgeon #SurgicalOncologist #MountSinaiMedical Center #MSMC #Melanoma #SkinCancer

• The molecular classification of melanoma, considering the increasing incidence rates projected for 2025 in the United States and the associated risk factors such as ultraviolet (UV) exposure, demographic changes, and genetic predispositions:
  • Is primarily based on the genetic alterations and the degree of cumulative sun damage (CSD)
• Low-CSD Melanomas:
  • These include superficial spreading melanomas and nodular melanomas:
    • Which are often characterized by BRAF mutations, particularly the BRAFV600E variant
  • These melanomas are typically associated with:
    • Intermittent, intense UV exposure
• High-CSD Melanomas:
  • These include lentigo maligna melanomas and desmoplastic melanomas
  • They often have a high mutation burden and can harbor:
    • NRAS mutations, TP53 mutations, and other non-V600E BRAF mutations
  • These melanomas are associated with chronic, cumulative UV exposure
    
• Non-CSD Melanomas:
  • These include acral lentiginous melanomas and mucosal melanomas:
    • Which usually do not show BRAF, NRAS, or NF1 mutations (triple wild-type)
    • However, they may have mutations in C-KIT, GNAQ, or GNA11 genes
  • These melanomas are not related to UV exposure
• Familial Melanomas:
  • These are often associated with germline mutations in genes such as:
    • CDKN2A and MC1R:
      • Which significantly increase melanoma risk
      • These genetic changes are inherited and present in all body cells
• The molecular classification of melanoma is crucial for guiding targeted therapies and improving patient outcomes:
  • For instance, BRAF inhibitors (e.g., vemurafenib, dabrafenib) and MEK inhibitors (e.g., trametinib):
    • Are effective in treating melanomas with BRAF mutations, while immune checkpoint inhibitors (e.g., nivolumab, pembrolizumab) have shown efficacy across various melanoma subtypes
• References:
  • Molecular Markers and Targets in Melanoma. Teixido C, Castillo P, Martinez-Vila C, Arance A, Alos L. Cells. 2021;10(9):2320. doi:10.3390/cells10092320.
  • Heterogeneous Pathogenesis of Melanoma: BRAF Mutations and Beyond. Colombino M, Casula M, Paliogiannis P, et al. Critical Reviews in Oncology/Hematology. 2024;201:104435. doi:10.1016/j.critrevonc.2024.104435.
    Melanoma. National Library of Medicine (MedlinePlus).
  • Melanoma. Schadendorf D, Fisher DE, Garbe C, et al. Nature Reviews. Disease Primers. 2015;1:15003. doi:10.1038/nrdp.2015.3.

• The American Joint Committee on Cancer (AJCC) staging system (8th Edition) for thin melanomas (less than or equal to 1 mm):
  • Includes both tumor thickness and ulceration as distinguishing features of a stage 1a and stage 1b melanoma
• The American Society of Clinical Oncology (ASCO) and the Society for Surgical Oncology (SSO) jointly developed evidence-based recommendations for the use of SLN biopsy for patients with melanoma:
  • The guidelines note that SLN biopsy is recommended for:
    • All patients with intermediate-thickness melanomas (between 1 and 4 mm):
      • Studies have shown that SLN biopsy is useful for identifying nodal metastases in these patients:
        • Who account for about one-third of all melanoma cases
      • SLN biopsy detects cancer in the sentinel nodes in about:
        • 18% to 26% of patients
    • The majority of melanomas are thin (1 mm thick) and usually can be cured simply by wide local excision of the primary tumor:
      • The incidence of tumor-positive SLN biopsy among patients with thin melanomas is approximately 5%
      • Although SLN biopsy is not necessary in most cases:
        • The guideline recommendations note that it should be discussed and considered for selected patients with:
          • Thin melanomas (0.8mm to 1mm)
          • Those with melanomas < 0.8mm and possess high-risk factors:
            • Such as:
              • Ulceration
              • A mitotic rate of 1/ mm2
• Wong et al:
  • Evaluated the results of SLN biopsy in 223 patients with thin melanomas and found nodal metastasis to be uncommon among patients with:
    • Melanomas less than 0.75 mm thick
    • Less than Clark level IV
• References:
  • Wong SL, Faries MB, Kennedy EB, et al. Sentinel lymph node biopsy and Management of Regional Lymph Nodes in Melanoma: American Society of Clinical Oncology and Society of Surgical Oncology Clinical Practice Guideline Update. J Clin Oncol. 2018;36:399-413.
  • Wong SL, Brady MS, Busam KJ, Coit DG. Results of sentinel lymph node biopsy in patients with thin melanoma. Ann Surg Oncol.;2006;13:302-309.

• A tumor bed boost has consistently been shown to reduce rates of local recurrence in patients undergoing breast-conserving surgery:
  • However, limited data have been available for patients with ductal carcinoma in situ (DCIS)
• Moran et al. retrospectively evaluated 4,131 patients with DCIS:
  • Finding that the addition of a tumor bed boost:
    • Reduced ipsilateral breast tumor recurrences, with the benefit being:
      • 0.8% at 5 years
      • 1.6% at 10 years
      • 3.6% at 15 years
• The American Society for Radiation Oncology (ASTRO) has published guidelines on the use of a tumor bed boost following whole-breast irradiation:
  • It is important to note that the range of boost doses depend on surgical margins following lumpectomy
• References
  • Bartelink H, Maingon P, Poortmans PM, et al. Whole-breast irradiation with or without a boost for patients treated with breast-conserving surgery for early breast cancer: 20-year follow-up of a randomised phase 3 trial. Lancet Oncol. 2015;16(1):47-56.
  • Romestaing P, Lehingue Y, Carrie C, et al. Role of a 10-Gy boost in the conservative treatment of early breast cancer: results of a randomized clinical trial in Lyon, France. J Clin Oncol. 1997;15(3):963-968.
  • Moran MS, Zhao Y, Ma S, et al. Association of radiotherapy boost for ductal carcinoma in situ with local control after whole-breast radiotherapy. JAMA Oncol.2017;3(8):1060-1068.
  • Smith BD, Bellon JR, Blitzblau R, et al. Radiation therapy for the whole breast: Executive summary of an American Society for Radiation Oncology (ASTRO) evidence-based guideline. Pract Radiat Oncol. 2018;8(3):145-152.
  • Morrow M, Van Zee KJ, Solin LJ, et al. Society of Surgical Oncology-American Society for Radiation Oncology-American Society of Clinical Oncology consensus guideline on margins for breast-conserving surgery with whole breast irradiation in ductal carcinoma in situ. Pract Radiat Oncol. 2016;6(5):287-295.

• An experienced dermatopathologist is an important member of the multidisciplinary melanoma team:
  • That contributes to the accurate diagnosis and staging of patients with melanoma
• It is my practice to have outside biopsies reviewed by our pathology staff upon referral to confirm diagnosis
• Although the pathologic analysis primarily consists of microscopic examination of hematoxylin- and eosin-stained tumor:
  • Several melanocytic cell markers may also be useful to confirm the diagnosis
  • Two antibodies that have been widely used in immunohistochemical evaluations are:
    • S-100 and HMB-45:
      • S-100 is expressed not only by more than 90% of melanomas:
        • But also by several other tumors and some normal tissues, including dendritic cells
      • In contrast, the monoclonal antibody HMB-45:
        • Is relatively specific (yet not as sensitive) for proliferative melanocytic cells and melanoma
        • It is therefore often used as a confirmatory stain when the diagnosis of melanoma is being considered
    • Anti–MART-1 staining has also been shown to be very useful in the diagnosis of melanoma:
      • Antityrosinase and Sox10 may also be used
    • The major histomorphologic components that should be included in a primary melanoma pathology report include:
      • Breslow thickness
      • Ulceration status
      • Peripheral and deep margin status
      • Mitotic rate:
        • Using the dermal hot spot approach with units of mitoses per mm²
      • Other features that are often also recorded include:
        • Presence of microsatellites
        • Histologic subtype
        • Lymphovascular invasion
        • Tumor-infiltrating lymphocytes (TIL)
        • Regression
        • Neurotropism
        • Growth phase
        • The absence of epidermal component:
          • As the latter may represent an uncommon dermal primary or a metastatic deposit
• The major histomorphologic types of melanoma:
  • Superficial spreading melanomas:
    • Constitute the majority of melanomas:
      • Approximately 70% of melanomas
    • Generally arise in a pre-existing nevus
• Nodular melanomas:
  • Are the second most common type:
    • 15% to 30% of melanoma
  • Nodular melanomas progress to invasiveness more quickly than other types:
    • However, when depth of the melanoma is controlled for:
      • Nodular melanomas are generally associated with the same prognosis as other lesions:
        • Although at least one recent study suggests that a thin (T1) nodular melanoma may be associated with worse prognosis than T1 superficial spreading-type melanoma
• Lentigo maligna melanomas:
  • Constitute a small percentage of melanomas:
    • 4% to 10%
  • These lesions occur in sun-exposed areas
  • Lentigo maligna melanomas are classically located on:
    • The faces of older white women
  • In general, lentigo maligna melanomas are:
    • Large (> 3 cm at diagnosis)
    • Flat lesions
    • Are uncommon in individuals younger than 50 years
  • Given their often-ill-defined appearance:
    • Margin control can sometimes be challenging at the time of wide excision
• Acral lentiginous melanomas:
  • Occur on the palms (palmar), soles (plantar), or beneath the nail beds (subungual):
    • Although not all palmar, plantar, and subungual melanomas:
      • Are acral lentiginous melanomas
  • These melanomas account for only 2% to 8% of melanomas in white patients:
    • But for a substantially higher proportion of melanomas (35% to 60%) in darker-skinned patients
  • They are often large:
    • With an average diameter of approximately 3 cm
  • Their clinical extent at the primary site may be difficult to define, and scouting biopsies are sometimes employed to facilitate clinical assessment of the extent of disease
• Amelanotic melanomas:
  • Are relatively uncommon melanomas that occur without pigmentation changes
  • They are often more difficult to diagnose because of their lack of pigmentation
  • Factors such as:
    • Change in size
    • Asymmetry
    • Irregular borders may suggest malignancy and prompt a biopsy, but delays in diagnosis may sometimes be observed
• While melanoma has been traditionally described using these categories:
  • Prognosis is more dependent upon staging than by these histomorphologic types

Boost radiation therapy is an additional dose of radiation delivered to the tumor bed after whole-breast irradiation (WBI) in patients who undergo breast-conserving surgery (BCS). The goal is to reduce local recurrence rates. The decision to give a boost is typically based on patient-specific risk factors.

Indications for Boost Radiation after BCS

1. Age < 50 years (especially < 40 years)

Data: The EORTC 22881–10882 trial (Bartelink et al., 2001; 2007 update) Population: 5,318 women with stage I/II breast cancer who received BCS + WBI (50 Gy) ± boost (16 Gy). Results: 10-year local recurrence (LR): Without boost: 10.2% With boost: 6.2% (Absolute reduction: 4%, p < 0.0001) Age stratification: < 40 years: LR reduced from 24% to 14% with boost (10% absolute benefit) 41–50 years: LR reduced from 11.7% to 6.4% (5.3% absolute benefit) 50 years: Less pronounced benefit

2. Positive or Close Surgical Margins

Rationale: Tumor cells may remain near the excision cavity, increasing recurrence risk. Guideline Support: NCCN recommends a boost for positive margins (even if re-excised) or if final margins are close, particularly in young patients.

3. High-Grade Tumors (Grade 3)

Data: High-grade tumors are more biologically aggressive and associated with higher LR rates. Boost helps reduce recurrence in these patients, especially when combined with other risk factors (young age, close margins).

4. Lymphovascular Invasion (LVI)

LVI is a marker for higher local and regional recurrence risk. While not an absolute indication, it adds weight to the decision in a patient with other risk factors.

5. Extensive Intraductal Component (EIC)

Especially in younger patients, an EIC increases the risk of residual disease and LR.

6. Triple-negative or HER2-positive subtypes (in younger patients)

While molecular subtype alone isn’t a formal indication for boost, aggressive biology may influence the decision when combined with other features (e.g., young age, LVI, close margins).

Guidelines

ASTRO 2016: Endorses boost in patients <50 years or with high-risk features. NCCN 2024: Recommends consideration of boost based on age, margin status, histology, grade, and LVI.

Clinical Takeaway

Boost radiation significantly reduces local recurrence in high-risk patients following breast-conserving surgery. The greatest benefit is seen in younger women and those with adverse pathological features.

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• The choice of biopsy technique:
  • Varies according to the anatomical site as well as the size and shape of the lesion
• Particular attention should be placed on the impact of the biopsy:
  • On definitive surgical treatment
• Either an excisional biopsy or an incisional biopsy using a scalpel or punch is acceptable
• Punch biopsies can be performed for most lesions:
  • They should generally be performed at the most raised or darkest area of the lesion to sample the most aggressive area of the potential melanoma
• Full-thickness biopsy into the subcutaneous tissue:
  • Should be performed to ensure accurate staging of the lesion
• An excisional biopsy allows the pathologist to accurately determine the thickness of the lesion, since the entire lesion is available for evaluation:
  • Excisional biopsies should be performed when the lesion is too large for a punch:
    • But still can be removed without excessive surgical intervention
  • For excisional biopsies, a narrow margin of normal-appearing skin (1 to 2 mm) is generally taken with the specimen:
    • An elliptical incision is often used to facilitate closure
    • The biopsy incision should be oriented to facilitate later wide excision (e.g., axially on extremities) and minimize the need for a skin graft to provide wound closure at the time of wide excision
• Shave biopsy:
  • Is generally discouraged if a diagnosis of melanoma is being considered since incomplete assessment of tumor thickness may result if the deep margin is not cleared
  • If a shave biopsy is performed, a deep shave /saucerization is preferable to obtain full-thickness biopsy of the suspect lesion
• In general, I submit all pigmented lesions for permanent section examination and perform definitive surgery later
• I generally prefer image-guided fine-needle aspiration or core biopsy as an initial diagnostic maneuver to document nodal or other melanoma metastases, but not to diagnose primary melanomas

• The choice of biopsy technique:
  • Varies according to the anatomical site as well as the size and shape of the lesion
• Particular attention should be placed on the impact of the biopsy on definitive surgical treatment
• Either an excisional biopsy or an incisional biopsy using a scalpel or punch is acceptable
• Entire removal of the lesion is generally preferred to allow for accurate pathologic evaluation
• Punch biopsies:
  • Can be performed for most lesions:
    • Generally, they can be performed when lesions are located on areas where maximum preservation of surrounding skin is important, or can be completely excised with a punch
  • Punch biopsies:
    • Should be performed at the most raised or darkest area of the lesion to sample the most aggressive area of the potential melanoma
• Full-thickness biopsy:
  • Into the subcutaneous tissue should be performed to ensure accurate staging of the lesion
• An excisional biopsy:
  • Allows the pathologist to accurately determine the thickness of the lesion, since the entire lesion is available for evaluation
• Excisional biopsies:
  • Should be performed when the lesion is too large for a punch but still can be removed without excessive surgical intervention
• For excisional biopsies:
  • A narrow margin of normal-appearing skin (1 to 3 mm) is taken with the specimen
• An elliptical incision:
  • Is often used to facilitate closure
• The biopsy incision should be oriented to facilitate later wide excision (e.g., axially on extremities) and minimize the need for a skin graft to provide wound closure at the time of wide excision
• Shave biopsy:
  • Is generally discouraged if a diagnosis of melanoma is being considered since incomplete assessment of tumor thickness may result if the deep margin is not cleared
  • If a shave biopsy is performed:
    • A deep shave is preferable
• In general, I submit all pigmented lesions for permanent section examination and perform definitive surgery at a later time
• I generally prefer image-guided fine-needle aspiration biopsy as an initial diagnostic maneuver to document nodal or other melanoma metastases:
  • But not to diagnose primary melanomas

#Arrangoiz #CancerSurgeon #Teacher #HeadandNeckSurgeon #SurgicalOncologist #SkinCaner #Melanoma #PunchBiospy #MSMC #Mount SinaiMedicalCenter

• Clinical features of melanoma often include:
  • Variegated color
  • Irregular raised surface
  • Irregular perimeter
• A biopsy should be performed on a:
  • Pigmented lesion that changes in size, configuration, or color
• The so-called ABCDEs are a mnemonic device to help clinicians and laypersons remember potential early signs of melanoma:
  • A denotes lesion asymmetry
  • B border / surface irregularity
  • C color variegation
  • D diameter greater than 6 mm
  • E a lesion that is elevating, evolving, or enlarging
• When a patient presents with a lesion suggestive of melanoma, in addition to biopsy:
  • A thorough physical examination must be performed:
    • With particular emphasis on the skin (including the scalp, interdigit webspace, and intertriginous areas), nodal basins, and subcutaneous tissues
• Clinical Features:
  • Appearance:
    • Melanomas typically present as pigmented lesions, often with irregular borders and color variations
    • They can be black, brown, tan, or even red, white, or blue
    • Amelanotic melanomas:
      • Which lack pigment, can appear pink or flesh-colored, making them more challenging to diagnose
  • ABCDE Criteria:
    • The American Cancer Society recommends using the ABCDE criteria for early detection:
      • Asymmetry:
        • One half of the mole does not match the other
      • Border:
        • Edges are irregular, ragged, notched, or blurred
      • Color:
        • Color is not uniform and may include shades of brown, black, pink, red, white, or blue
      • Diameter:
        • The spot is larger than 6 mm across (about the size of a pencil eraser), although melanomas can be smaller
      • Evolving:
        • The mole is changing in size, shape, or color
• References:
  • Cutaneous Melanoma. Long GV, Swetter SM, Menzies AM, Gershenwald JE, Scolyer RA. Lancet (London, England). 2023;402(10400):485-502. doi:10.1016/S0140-6736(23)00821-8.
  • Cutaneous Melanoma: A Review of Multifactorial Pathogenesis, Immunohistochemistry, and Emerging Biomarkers for Early Detection and Management. Gosman LM, Țăpoi DA, Costache M. International Journal of Molecular Sciences. 2023;24(21):15881. doi:10.3390/ijms242115881.
  • Melanoma Epidemiology and Sun Exposure. Raimondi S, Suppa M, Gandini S. Acta Dermato-Venereologica. 2020;100(11):adv00136. doi:10.2340/00015555-3491.
    Melanoma. National Library of Medicine (MedlinePlus).

• WHO Melanoma Trial No. 10 (1988):
  • Citation:
    • WHO Melanoma Programme. Lancet. 1988
  • Population:
    • 612 patients with melanomas ≤ 2 mm
  • Arms:
    • 1 cm vs 3 cm surgical excision margins
  • Results:
    • No significant difference in:
      • Local recurrence (LR):
        • ~ 2.3% (1 cm) vs ~2.2 % (3 cm)
      • Overall survival (OS):
        • Similar in both groups
      • Complication rates:
        • Similar
  • Conclusion:
    • 1 cm margins are safe and adequate for melanomas ≤ 1 mm in thickness
    • Wider excisions did not improve outcomes
• Swedish Melanoma Study Group Trial (1996):
  • Citation:
    • Ringborg U, et al. Cancer. 1996.
  • Population:
    • 989 patients with melanomas 0.8 to 2.0 mm
      • Arms:
    • 2 cm vs 5 cm margins
    • Results:
      • No significant difference in:
        
        • LR:
          • 3.8% (2 cm) vs 3.6% (5 cm)
        • OS:
          • 65% (2 cm) vs 68% (5 cm) at 10 years
            
      • Higher rates of skin grafting and wound complications in the 5 cm group
    • Conclusion:
      • 2 cm margins are sufficient
      • 5 cm excision is excessive, with no survival benefit but increased morbidity
• UK Melanoma Study Group Trial (2004):
  • Citation:
    • Thomas JM, et al. Lancet. 2004.
  • Population:
    • 900 patients with melanomas > 2 mm
  • Arms:
    • 1 cm vs 3 cm margins
  • Results:
    • Local recurrence:
      • 4.6% (1 cm) vs 1.2% (3 cm), p < 0.01
    • 5-year melanoma-specific survival:
      • 65% (1 cm) vs 69% (3 cm), not statistically significant
    • More wound closure problems and skin grafts in the 3 cm group
  • Conclusion:
    • 1 cm margins are inadequate for thick melanomas (> 2 mm)
    • 3 cm margins reduce local recurrence, but without a survival benefit
• French Cooperative Group Trial (2002, updated 2007):
  • Citation:
    • Veronesi U, et al. NEJM. 2002; Gallardo A, et al. J Clin Oncol. 2007.
  • Population:
    • 742 patients with melanomas > 2 mm
  • Arms:
    • 2 cm vs 5 cm margins
  • Results:
    • LR:
      • 3.7% (2 cm) vs 3.3% (5 cm)
    • Melanoma-specific survival at 10 years:
      • 67% (2 cm) vs 65% (5 cm)
    • Skin grafting more frequent in the 5 cm group
  • Conclusion:
    • 2 cm margins are equivalent to 5 cm margins for thick melanomas
    • 5 cm offers no additional benefit but increases morbidity
• Intergroup Melanoma Surgical Trial (US, 2001):
  • Citation:
    • Balch CM, et al. Ann Surg Oncol. 2001
  • Population:
    • 740 patients with melanomas 1 to 4 mm thick
    • Arms:
      • 2 cm vs 4 cm margins
    • Results:
      • LR:
        • 1.3% (2 cm) vs 0.9% (4 cm), not significant
      • DFS and OS:
        • No significant difference
      • More skin grafting and delayed healing in the 4 cm group
  • Conclusion:
    • 2 cm margins are sufficient for melanomas 1 to 4 mm in thickness
    • 4 cm margins do not improve outcomes and increase surgical morbidity
• MelMarT Pilot Trial (2016; Full Results Pending)
  • Citation:
    • Haydu L, et al. Ann Surg. 2016
  • Population:
    • 400 patients with melanomas > 1 mm (pilot phase)
    • Arms:
      • 1 cm vs 2 cm margins
    • Results (pilot):
      • LR, DFS, OS not significantly different (short follow-up)
    • Fewer complications in the 1 cm group
  • Conclusion (preliminary):
    • The 1 cm margin may be sufficient for select patients with intermediate-thickness melanomas
    • Full results from the larger trial (~2,000 patients) are pending and may influence future guidelines