this presentation was done during clinical rotation to department of plastic surgery.

1. Malignant Melanoma
Dr Gagan Adhikari
MS resident

2. Introduction
• Melanomas arise from the melanocyte that is a dendritic cell located in the basal layer of skin.
• These tumors primarily arise from melanocytes at the epidermal-dermal junction
• but may also originate from mucosal surfaces of the oropharynx, nasopharynx, eyes,
proximal esophagus, anorectum, and female genitalia.
• Melanocyte is responsible for producing the melanin pigment that gives the skin phenotypes.
• Melanocyte numbers are equal among all skin colors;
• however, the production of melanin varies.

3. Introduction
• Melanomas can grow in both a radial and vertical growth pattern.
• The radial pattern is usually in the epidermis and some melanomas can stay in this
radial growth pattern for a long time.
• In the vertical growth, the growth shifts down into the dermis and indicates a worse
prognosis.

4. Risk Factors: Host factors
• Physical attributes such as
• fair features,
• Fitzpatrick I–II skin types, and
• blue/ green eyes.
• Numerous common congenital nevi,
• atypical nevi, and
• giant nevi are all associated with increased risk.

5. Risk Factors: Host factors
• A personal history of melanoma is thought to confer a 5% lifetime risk of developing a
second melanoma.
• Finally, familial melanoma accounts for approximately 10% of all cases and
• is associated with mutations within
• the cyclin-dependent kinase inhibitor 2A locus (CDKN2A),
• cyclin-dependent kinase 4 (CDK4), and
• melanocortin 1 receptor (MC1R)

6. Risk Factors: environmental factors
• The most significant and modifiable environmental risk factor for melanoma is sun exposure,
particularly intermittent and intense exposure.
• UVA and UVB exposure are both strongly associated with melanoma.
• One or more blistering sunburns early in life or greater than five sunburns at any age increases
the lifetime risk of developing melanoma twofold.
• Regular broad spectrum sunscreen use may reduce the risk of developing invasive melanoma.

7. Risk Factors: environmental factors
• It is important to note that intense sun damage is not necessarily required for malignant
transformation,
• as a significant number of lesions arise in relatively sun-protected areas (soles of feet, anus, and vagina).
• There happens to be the complex multifactorial role of host and environmental factors in
melanoma pathogenesis.

8. Progression of Melanocytes to Cutaneous Melanoma

9. Clinical features
• Rapid growth of a long standing mole.
• Darker pigmentation, increased vascularity.
• Ulceration of the overlying skin epithelium.
• Gradual Invasion of the tumor cells into the surrounding skin to produce a
‘halo’ which indicates malignancy.
• Regional lymph nodal enlargement.
• Malignant melanoma is not painful bit it itches often.
• Symptoms: c/o lymph nodal enlargement, weight loss, dyspnoea or
jaundice.
• Occular melanomas are most non-cutaneous melanomas.

10. Spread
• Local extension:
• initial spread is by contiguity and continuity.
• Malignant melanoma has a tendency to form satellite skin nodules.
• Lymphatic spread:
• it is the commonest route of spread, reaching the regional lymph nodes by permeation and embolization.
• It is a/w poor prognosis.
• By the time regional lymph nodes are involved, 70-80% of patients will have developed distant mets.
• Hematogenous:
• it’s a late event. Can spread to skin, liver, lungs, bones and brains.
• However, lungs and liver are the most common sites.
• Melanoma is predilected for brain tissue probably due to its similar embryology.

11. Diagnosis
• ABCDE diagnostic tool was developed at the New York University Langone Medical Center to educate the public and
general healthcare practitioners, simplifying the decision to biopsy a suspicious lesion
• This tool utilizes five simple criteria for identifying pigmented lesions that are suspicious for melanoma:
• Asymmetry,
• Border Irregularity,
• Color Variegation,
• Diameter > 6 mm, and
• Evolution or change in the appearance of lesion over time.
• However a minority of lesions are atypical
• can be nonpigmented (5%),
• resemble other types of cutaneous malignancies (basal or squamous cell carcinoma),
• or be smaller than 6 mm in size.

12. TYPES:
• Superficial spreading,
• Nodular ,
• Lentigo maligna,
• Acral lentiginous,
• Desmoplastic melanoma
• Amelanotic melanoma

13. Superficial spreading
• Presents as flat or slightly elevated lesion with variegate
pigmentation,
• most commonly occurring on the trunk in men and the legs in
women,
• in patients aged 30 to 50 years.
• the growth pattern is typically superficial and radial with
scattered atypical melanocytes in the epidermis.
• It is the most common subtype in the Caucasian population
• likely contributes significantly to the increasing incidence of
melanoma over the past 30 years.

14. Nodular melanoma
• Is the second most common growth pattern,
• which often lacks the classic features commonly identified
by the ABCDE melanoma screening tool.
• These lesions commonly present as a smooth, single colored
(black or brown) elevated nodule or an ulcerated mass on
examination, frequently affecting the legs or trunk.
• They are typically thicker and more advanced at the time of
diagnosis, largely due to a relatively short or lack of radial
growth phase.
• Both nodular and superficial spreading melanomas are
associated with increased sun exposure in fair-skinned
individuals.

15. Lentigo maligna melanoma
• is a slow growing lesion with radial spreading
• typically arises in longstanding pigmented lesion on chronically
sun-damaged anatomic sites (head and arms)
• in older patients, with an average age
• of diagnosis at 65 years
• Hypopigmented lesions are also possible within this subtype.
• It occurs most often in fair-skinned older individuals
• and is associated with solar elastosis of the surrounding skin.

16. Acral lentiginous melanoma
• affects only 2% to 8% of Caucasians, but accounts for up to 36%
of melanoma diagnosed in African Americans, making it the most
common subtype within this demographic.
• It commonly occurs on the palms of the hand, sole of the feet, or
beneath the nail plate (subungual)
• presents at a more advanced stage with an aggressive course
compared with the other subtypes.
• Subungual variants commonly present as a longitudinal line of
pigment extending the length of the nail plate,
• with the hallmark spread of the pigment to the proximal nail
fold referred to as Hutchinson sign.

17. Desmoplastic melanoma
• is a relatively uncommon subtype
• presents as an unremarkable plaque or nodule
• can easily be misdiagnosed at an early stage.
• It affects older patients (although not as old as lentigo maligna melanoma)
• most commonly in the head and neck
• occurs in men twice as often as in women.
• Desmoplastic melanoma is frequently associated with nerve invasion and spread along fascial planes and tends
to be thicker at the time of diagnosis.
• They are locally aggressive with a higher rate of local recurrence, but exhibit a low incidence of lymph node
involvement.

18. Amelanotic Melanoma
• is a type of skin cancer in which the cells do not make melanin.
• They can be pink, red, purple or of normal skin color, hence difficult to recognize
• It has an asymmetrical shape and an irregular faintly pigmented border
• Atypical appearance leads to delay in diagnosis, the prognosis is bad
• Recurrence rate is high

19. Investigations
• A full thickness excisional biopsy with a 1 to 2 mm margin of normal tissue is the
method of choice for suspicious lesions.
• In larger lesions located in areas where a complete excision may be technically difficult or
result in significant deformity (i.e., areas of the face),
• it may be necessary to perform an incisional biopsy or multiple punch biopsies.
• This should include the most raised area of the lesion.
• All patients diagnosed with cutaneous melanoma undergo
• a thorough skin assessment and
• clinical evaluation of the relevant nodal basins.

20. Investigations
• Further screening workup for newly diagnosed patients with invasive melanoma includes
• chest X-ray,
• complete blood count,
• liver function tests, and
• serum lactate dehydrogenase (LDH).
• Abnormal findings in the review of systems or these screening modalities should prompt further
imaging studies such as CT scan or PET scan
• Patients with head and neck primary tumors are likely to benefit from CT or PET imaging to
identify suspected nodal involvement.

21. Investigations
• Further metastatic workup includes
• serum alkaline phosphatase,
• serum creatinine,
• body CT imaging,
• MRI of the brain, and
• bone scan.
• Antibodies for immunohistochemistry
– S - 100
– HMB - 45

22. STAGING

24. STAGING
• Melanoma is characterized according to the American Joint Committee on Cancer (AJCC)
as
• localized disease (stage I and II),
• regional disease (stage III),
• or distant metastatic disease(stage IV).

25. Depth of Invasion
• Breslow thickness is the depth of invasion measured from the granular layer of the epidermis to
the base of the lesion.

26. Clark Classification (Level of Invasion)
• Level I: Lesions involving only the epidermis (in situ
melanoma); not an invasive lesion.
• Level II: Invasion of the papillary dermis but does not
reach the papillary-reticular dermal interface.
• Level III: Invasion fills and expands the papillary dermis
but does not penetrate the reticular dermis.
• Level IV: Invasion into the reticular dermis but not into
the subcutaneous tissue.
• Level V: Invasion through the reticular dermis into the
subcutaneous tissue.

27. Prognostic Factors
• Depends most importantly on staging
• Depth of invasion (most important prognostic factor)
• Ulceration(presence of ulceration carries worst prognosis)
• Lymph node status
• Satellite lesion
• Distant metastasis

28. Management

29. Wide and Deep Excision
• Surgical excision is critical for establishing the diagnosis and also for the definitive management of
malignant melanoma.
• Historically, 5 cm margins were advocated for local tumor excision based on observations that
melanoma had a propensity to recur adjacent to the primary site.
• Over the past few decades, however, the guidelines for surgical margins have been redefined by several
randomized prospective clinical trials and are largely based on the thickness of the primary lesion.

30. Wide and Deep Excision
• In many cases, the primary tumor can be managed with a full thickness elliptical excision (down to the
level of deep muscular fascia) with primary closure.
• Challenging anatomic sites include the ear, face, hands, and feet.
• Melanoma of the ear is generally treated by full thickness wedge excision and primary closure
• due to the proximity of the underlying cartilage to the thin overlying skin.
• Primary lesions of the face can be particularly challenging, and every effort should be made to
excise the primary lesion with recommended margins.
• However, narrower margins in anatomically complex areas for intermediate thickness lesions (1 to 4
mm) may be considered
• there is a higher rate of local recurrence,
• but no significant impact on long-term survival.

31. Wide and Deep Excision
• Invasive melanoma of the fingers and toes often requires
amputation through the mid-phalanx proximal to the
primary lesion.
• In subungual melanoma of the index, middle, ring, or
little fingers, this requires amputation through the mid-
portion of the middle phalanx
• for the thumb, through the proximal phalanx

32. Wide and Deep Excision
• Likewise, for the great toe (most common site of digital melanoma) and remaining toes,
amputation through the mid-proximal phalanx is recommended.
• Palmar or plantar melanoma requires excision down to the palmar/plantar fascia with
primary closure or local tissue rearrangement.
• Dorsal lesions on the hands/feet or web-space lesions require soft tissue resection down
to the tendon or bone with skin grafting or local flap coverage.

33. Sentinel lymph node biopsy
• Sentinel lymph node is the first lymph node in the draining basin from the primary tumor site.
• Because this node is usually involved, if there is regional nodal metastasis it can be used as a selective
sample marker to see if the rest of the nodal basin is affected.
• Sentinel lymph node sampling is advocated
• in patients with stage I/II melanoma with tumor thickness 1.0 to 4.0 mm Breslow depth,
• or those with depth of 0.76 to 1.0 mm with other high-risk factors, including
• ulceration,
• lymphovascular invasion,
• significant vertical growth phase, and
• increased mitotic rate.
• Additionally patients with tumor >4.0 mm depth and clinically negative nodes also benefit from SLN biopsy.

34. Sentinel lymph node biopsy
• The SLNB technique involves
• preoperative lymphoscintigraphy with intradermal injections of technetium-sulfur colloid to
delineate lymphatic drainage and
• intraoperative intradermal injection of 1 mL of isosulfan or methylene blue dye near the tumor
or biopsy site.
• The radioactive tracer-dye combination allows the sentinel node to be identified in 98% of cases.

35. Sentinel lymph node biopsy
• An incision over the lymph node basin of interest allows nodes
to be excised and studied with
• hematoxylin and eosin and
• immunohistochemistry (S100, HMB45, and MART-
1/Melan-A) staining.
• Risks of this technique are uncommon
• but include skin necrosis near the site of injection,
anaphylactic shock, lymphedema, surgical site infections,
seromas, and hematomas.

36. After injection of radioactive technetium-99–
labeled sulfur colloid tracer at the primar cutaneous
melanoma site, sentinel lymph node basins are
identified.
A. Lymphoscintigraphy of 67-year-old male with a
malignant melanoma of the right heel; sentinel
lymph nodes in both the right popliteal fossa and
inguinal region.
B. Lymphoscintigraphy of 52-year-old male with a
malignant melanoma of the posterior right upper
arm; sentinel lymph node in the right axillary region.
C. Lymphoscintigraphy of 69-year-old male with a
facial melanoma; sentinel lymph nodes in the
submandibular region.

37. Lymphadenectomy
• Complete surgical lymphadenectomy is indicated in patients with clinically involved nodes diagnosed by
• examination,
• fine needle aspiration, and/or
• sentinel lymph node biopsy.
• Nodal status is the most important prognostic factor in staging malignant melanoma.
• Patients with only one positive node have a better prognosis than patient with multiple nodes.
• Some controversy exists, however, on the overall benefit of elective lymph node dissection in patients with
clinically uninvolved nodes.
• While multiple clinical trials have failed to show any benefit overall of non-selective elective lymph node
dissection,
• there may be some data to suggest that it may offer a survival benefit in select cases.

38. Lymphadenectomy
• While potentially therapeutic, a complete lymphadenectomy carries a significant risk for substantial
morbidity.
• Postoperative lymphedema is a major source of physical and psychological distress in patients
already coping with a diagnosis of melanoma.
• The rate of lymphedema following axillary and inguinal lymphadenectomy can be as high as
30% and 60%, respectively,
• compared with the incidence of lymphedema in patients who have only had a sentinel node
biopsy, which ranges from 3% to 7%.
• It is important to counsel patients that while the use of sentinel node biopsy significantly reduces
the risk of lymphedema, it does not eliminate it completely.

39. Surgery for Regional Metastasis
• Nonmetastatic, in-transit disease should undergo excision to clear margins when feasible.
• However, disease not amenable to complete excision derives benefit from isolated limb perfusion (ILP) and
isolated limb infusion (ILI).
• These two modalities are used to treat regional disease, and their purpose is to administer high doses of
chemotherapy, commonly melphalan, to an affected limb while avoiding systemic drug toxicity.
• ILI was shown to provide a 31% response rate in one study, while hyperthermic ILP provided a 63%
complete response rate in an independent study.

40. Surgery for Distant Metastasis
• The most common sites of distant metastasis are the lung and liver
• followed by the brain, gastrointestinal tract, distant skin, and subcutaneous tissue.
• A limited subset of patients with small-volume, limited distant metastases to the brain,
gastrointestinal tract, or distant skin
• will be cured with resection or gamma knife radiation.
• Liver metastases are better dealt without surgical resection
• unless they arise from an ocular primary.

41. Surgery for Distant Metastasis
• Adjuvant therapy after resection of metastatic lesions is not standard of care;
• however, there are ongoing clinical trials addressing whether drugs and vaccines will be
beneficial in this setting.
• Surgery may provide palliation for patients with gastrointestinal obstruction, gastrointestinal
hemorrhage, and non-gastrointestinal hemorrhage.
• Radiotherapy for symptomatic bony or brain metastases provides palliation in diffuse disease.

42. Adjuvant and Palliative Therapies
• Eastern Cooperative Oncology Group (ECOG) Trials 1684, 1690, and 1694
• were prospective randomized controlled trials
• that demonstrated disease free survival advantages in patients with melanoma thicker than 4
mm with or without lymph node involvement if they received adjuvant treatment with high-
dose interferon (IFN).
• A European Organization for Research and Treatment of Cancer (EORTC) trial
• also showed recurrence-free survival benefit with pegylated IFN

43. Adjuvant and Palliative Therapies
• Following drugs with/without vaccines have been shown in randomized studies
to provide survival benefit in metastatic disease:
• BRAF inhibitors (sorafenib),
• anti-PD1 antibodies,
• CTLA antibodies (ipilimumab),
• and high-dose interleukin-2 (IL-2)
• Despite the excitement of recent drugs, surgery will likely play an adjunct role in
treating individuals who develop resistance to these drugs over time.

45. Thank you