DEFINITION AND PATHOGENESIS
- May be metastatic to soft tissue (or bone) or a primary cutaneous malignancy
- Classification based on radial growth phase
- Level I: confined to epidermis (in situ melanoma)
- Level II: tumor cells extend from the epidermis to unexpanded papillary dermis (10% in vertical growth phase)
- Level III: tumor nodule fills and expands the papillary dermis (usu >1mm thick)
- Level IV: tumor cells infiltrate reticular dermis collagen fibers
- (a): into superficial reticular dermis
- (b): into deep reticular dermis
- Level V: infiltration of tumor cells into subcutaneous fat (periosteum in subungual location)
- Histologic types
- Superficial spreading melanoma
- High incidence of precursor lesion (benign or dysplastic nevus)
- Most common histologic type in hand locations, even in subungual location
- Lentigo maligna melanoma
- Prevalent in Australia as "Hutchinson's melanotic freckle", occurring in lentigo maligna
- Acral and mucosal lentiginous melanoma
- Subungual melanoma is a subset of acral-lentiginous melanoma (thumb and great toe most common)
- "Hutchinsons' sign": pigmentation extends beyond cuticle involving skin (warrants prompt bx of nail bed)
- Melanoma with unclassified radial growth phase
- Nodular melanoma
- Other variants
- Desmoplastic and desmoplastic neurotropic
- Vertical growth phase--formation of a nodule, into, and out of the skin, with statistical chance for distant metastases (90% adjacent to region of radial growth)
- Rising incidence due to sun exposure with ? incidence in fair skinned individuals, those with multiple large nevi, and those with a family hx of skin cancer
- ?32,000 cases/?6,700 deaths/yr in the USA (most common cancer in F 25-29 yrs)
- About 5% of pts with melanoma have evident skeletal metastases, 50% at autopsy
- "ABCD(E)" criteria generally apply:
- Border irregularity
- Color variegation
- >95% white, <5% black
- Median age 46 (58 in subungual location)
- Subungual melanoma: massive destruction of the uderlying phalanx may occur
- Subungual and plantar lesions associated with a high rate of misdiagnoses
- Thumb, then MF most commonly involved
- ? ulceration (29/38)(poor prognosticator)
- Most common location of foot/ankle lesions is plantar surface of the foot
- Foot/ankle lesions generally have a poorer prognosis due to advanced stage (delay in dx)(esp plantar location)
- Soft tissue musculoskeletal metastases may occur without evidence of a primary lesion
- Radial and vertical growth phases are clinically evident
- TNM staging: Stage I-IV (PT=primary tumor, N=regional LN, M=distant metastases)
- Stage I: local disease
- Stage II: local disease
- Stage III: nodal/in-transit disease
- Stage IV: distant visceral metastases
- X-rays usually negative, except in subungual lesions which can reveal marked erosion of the distal phalanx
- Metastases: multiple bone lesions which are primarily lucent, although a solitary lesion may be present
- Lymphatic mapping using a lymphoscintigram to identify the sentinel lymph node
- Low-dose radiolabelled sulfur colloid intradermally injected near the primary and a mark made over the skin
- In the OR (the same day), isosulfan blue is injected intradermally or methylene blue topically near the primary and a cut down is performed at the previous mark to identify and remove the blue sentinel node (false - <1-2%)
- A hand held gamma detector is used to help locate the "hot" node
- Neoprobe (Neoprobe Corp, Dublin, OH)
- Usually >6mm in size
- Vertical growth phase area is usually raised above adjacent radial growth phase area
- Friable lesion within bone in metastatic disease
- Keratinocytes, lymphocytes, and melanocytes
- Thickness measured from top of the granular layer to the level of the deepest tumor cell
- Melanocytes uniform to pleomorphic, depending on morphology of tumor, arranged in a pagetoid pattern
- Histogenic types
- Acral lentiginous
- ? desmoplasia
- ? neurotropia
- + S-100
- + HMB-45 antibodies
- CAM 5.2, 903, for keratin
- Other stains:
- Common leukocyte antigen
- Abnormalities on chromosomes 1, 6, 7, 9
- Loss of P-selectin adhesion receptors (in tumor microvasculature) for infiltrating WBCs (no inflammatory infiltrate/tumor regression)
- EM: melanosomes and ellipsoidal premelanosomes with cross striations
DIFFERENTIAL CLINICOPATHOLOGIC DIAGNOSIS
- Subungual lesions: infection, metastases (usu. squamous cell carcinoma of the lung), GCT of TS
- Lymphoma and spindle cell sarcomas in metastatic lesions to bone
- Benign nevus
- Subungual hematoma
- Chronic paronychia
- Verrucae vulgaris
- Pyogenic granuloma
- Eccrine paroma
DISEASE COURSE AND TREATMENT
- Punch (not shave) bx to preserve anatomic relationships for staging
- Survival (to 70-80%) due to earlier dx, esp if tx is during the radial growth phase, when cure is almost certain with prompt resection
- Survival related to thickness of the lesion (Breslow):
- <0.76mm thick lesions rarely metastasize (2% dead at 8 yrs) unless in the early vertical phase of growth (100% survival in radial growth phase lesions)
- LN dissection with conflicting results, but possibly of benefit in higher thickness lesions
- 0.77-1.50mm thick lesions have low-intermediate risk of LR/metastasis
- 1.51-3.99mm thick lesions have high-intermediate risk of LR/metastasis
- >4.00mm thick lesions have very high risk of LR/metastasis
- Level of invasion (more subjective)(Clark)
- Level I: in situ melanoma, epidermal confinement
- Level II: invasion of papillary dermis
- Level III: invasion of papillary/reticular dermal junction
- Level IV: invasion of reticular dermis
- Level V: invasion of subcutaneous fat (periosteum in subungual lesions)
- Other favorable prognosticators (in order of relative weight of importance):
- Low mitotic rate
- Tumor-infiltrating lymphocytes
- <1.70mm thick
- Location on an extremity (excluding volar or subungual regions)
- Female pts
- Absence of regression in the radial growth phase
- "Odds of survival" tables based on these factors
- Sentinel node mapping with techntium 99m-antimony sulfide colloid, blue dye mapping, and sentinel node bx (esp > 1.2mm thick lesions)
- LN resection if sentinel LN (based on lymphatic mapping) is + for tumor (on permanent sections--not on frozen)
- Tumors may regress spontaneously only to present as a metastasis later (with only a hx of a pigmented lesion)
- Resection margin 1-3cm based on thickness of tumor
- <1mm = 1cm
- 1-2mm = 1-2cm
- 2-4mm = 2cm
- >4mm = 3cm
- Amputation for digital lesions
- Neck of proximal phalanx for the thumb
- PIPJ level has been recommended for fingers
- LR may occur
- Lower rate of regional LN metastases at initial presentation for desmoplastic and desmoplastic neurotropic melanomas
- Loss of p27KipI protein expression in nodular (not superficial) melanomas a prognostic indicator of early relapse
- Skeletal involvement in 11-17% clinically detectable metastases, 23-49% of autopsy found metastases
- Isolated skeletal metastases (stage IV)
- Long latency indicates prognosis and appendicular locations warrant aggressive management
- Intramuscular metastases have been reported
- ? signal intensity on T1-weighted and STIR images
- Stage IV disease general prognosis is poor
- 10% may not have hx of primary lesion (spontaneous regression prior to metastasis)
- Hyperthermic isolation perfusion with melphalan with complete responses reported
- Metastatic disease is slowly and progressively fatal
- Median survival from the 1st skeletal metastasis is 2-11 mos (1-yr survival after brain, liver, or brain metastases @ 10%
- Better prognosis for a solitary appendicular lesion after a long NED period (no pts with axial metastases survive)
- Appears to be a better prognosis for pts whose initial lesion was <2mm in thickness
- Surgical resection must be considered for solitary metastases ? chemotx/XRT
- Immunotherapy including vaccine tx undergoing trials
SPECIAL CONSIDERATIONS (variants)
- Neurotropic (Desmoplastic) Melanoma
- Tend to migrate and spread along nerves, with desmoplastic properties, usually occurring in the head/neck region
- Has been reported along the ulnar nerve first arising from a subungual tumor
- Immunohistochemistry with + S-100 protein, + HMB-45, + nerve growth factor receptor
- Minimal deviation melanoma
- Malignant blue nevi and related lesions
- Unclassified vertical growth phase variants
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