Melanoma

Skip to end of metadata
Go to start of metadata

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)

IMPORTANCE

  • 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

CLINICAL FEATURES

  • "ABCD(E)" criteria generally apply:
    • Asymmetry
    • Border irregularity
    • Color variegation
    • Diameter
    • (Elevation)
  • >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

RADIOLOGIC FEATURES

  • 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)

GROSS PATHOLOGY

  • Usually >6mm in size
  • Vertical growth phase area is usually raised above adjacent radial growth phase area
  • Friable lesion within bone in metastatic disease

HISTOLOGIC/MOLECULAR FEATURES

  • 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
  • Desmoplastic
    • ? neurotropia
  • Nodular
    • Unclassified
  • + S-100
  • + HMB-45 antibodies
  • CAM 5.2, 903, for keratin
  • Other stains:
    • Common leukocyte antigen
    • Vimentin
  • Karyotyping
    • 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
  • "Misdiagnoses"
    • Benign nevus
    • Subungual hematoma
    • Blister
    • Chronic paronychia
    • Verrucae vulgaris
    • Pyogenic granuloma
    • Eccrine paroma
    • Dermatofibroma
    • Cysts

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

REFERENCES

Ackerman AB, Godomski J: Neurotropic malignant melanoma and other neurotropic neoplasms in the skin. Am J Dermatopathol 6(suppl):63- ,1984.
Barnes BC, Seigler HF, Saxby TS, Kocher MS, Harrelson JM: Melanoma of the foot. J Bone Joint Surg 76A:892-8,1994.
Boni R, Boni RA, Steinert H, Burg G, Buck A, Merincek B, Berthold T, Dummer R, Voollmy D, Ballmer B, : Staging of metastatic melanoma by whole-body positron emission tomography using 2-fluorine-18-fluoro-2-deoxy-D-glucose. Br J Dermatol 132:556-62,1995.
Bruijm JA, Mihm MC, Barnhill RL: Desmoplastic melanoma. Histopathology 20:197- ,1992.
Carlson JA, Dickersin GR, Sober AJ, Barnhill RJ: Desmoplastic neurotropic melanoma: a clinicopathologic analysis of 28 cases. Cancer 75:478-94,1995.
Conley J, Lattes R, Orr W: Desmoplastic malignant melanoma: a rare variant of spindle cell melanoma. Cancer 28:914- ,1971.
Czarnecki D, Meehan CJ: Is the incidence of malignant melanoma decreasing in young Australians? J Am Acad Dermatol 42:672-4,2000:
Dabbs DJ, Bolen JW: Superficial spreading malignant melanoma with neurosarcomatous metastasis. Am J Clin Pathol 82:109- ,1984.
Daly JM, Berlin R, Urmacher C: Subungual melanoma: a 25 yr review of cases. J Surg Oncol 35:107-12,1987.
Damian DL, Fulham MJ, Thompson E, Thompson JF: Positron emission tomography in the detection and management of metastatic melanoma. Melanoma Res 6:355-9,1996.
DeBoer DK, Schwartz JS, Thelman S, Reynolds VH: Heterogeneous Survival Rates for Isolated Skeletal Metastases From Melanoma. Clin. Orthop. 323:277-283, 1996.
DiMaio SM, Mackay B, Smith JL, : Neurosarcomatous transformation in malignant melanoma: an ultrastructural study. Cancer 50:2345- ,1982.
Egbert B, Kempson R, Sagebiel R: Desmoplastic malignant melanoma: a clinicopathologic study of 25 cases. Cancer 62:2033- ,1988.
Elder DE, Murphy GF: Malignant tumors (melanomas and related lesions). In Elder DE, Murphy GF, Atlas of Tumor Pathology. Melanocytic Tumors of the Skin. AFIP, Washington DC, 1991, pp 103-205.
Feibleman CE, Stoll H, Maize JC: Melanomas of the palm sole and nailbed: a clinicopathologic study. Cancer 46:2492-2504,1980.
Flørenes VA, Mælandsmo GM, Kerbel RS, Slingerland JM, Nesland JM, Holm R: Protein expression of the cell-cycle inhibitor p27KipI in malignant melanoma: inverse correlation with disease-ree survival. Am J Pathol 153:305-12,1998.
Fortin PT, Freilberg AA, Rees R, Sondak VK, Johnson TM: Malignant melanoma of the foot and ankle. J Bone Joint Surg 77A:1396-1403,1995.
Heaton KM, El Naggar A, Ensign LG, Ross MI, Balch CM: Surgical management and prognostic factors in patients with subungual melanoma. Ann Surg 219:197-204,1994.
Holder WD Jr, White RL Jr, Zugen JH, Easton EJ Jr, Greene FL: Effectiveness of positron emission tomography for the detection of melanoma metastases. Ann Surg 227:764-9,1998.
Hudson DA, Krige JEJ, Strover RM, King HS: Subungual melanoma of the hand. J Hand Surg 15B:288-90,1990.
Jain S, Allen PW: Desmoplastic malignant melanoma and its variants. Am J Surg Pathol 13:358- ,1989.
Klaase JM, Kroon BB, van Geel AN, : Prognostic factors for tumor response and limb recurrence-free interval in patients with advanced melanoma of the limbs treated with regional isolated perfusion with melphalan. Surg 115:39-45,1994.
Labrecque P, Hu C, Winkelman RK: On the nature of desmoplastic melanoma. Cancer 38:1025- ,1976.
Lejeune FJ, Deloof T, Ewalenko P, : Objective regression of unexcised melanoma in-transit metastases after hyperthermic isolation perfusion of the limbs with melphalan: recent results. Cancer Res 86:268-76,1983.
Longacre TA, Egbert BM, Rouse RV: Desmoplastic and spindle cell malignant melanoma: an immunohistochemical study. Am J Surg Pathol 20:1489- ,1996.
Macfarlane DJ, Sondak V, Johnson T, Wahl RL: Prospective evaluation of 2-[18F]-2-deoxy-D-glucose positron emission tomography in staging of regional lymph nodes in patients with cutaneous malignant melanoma. J Clin Oncol 16:1770-6,1998.
Marghoob AA, Slade J, Salopek TG, : Basal cell and squamous cell carcinomas are important risk factors for cutaneous malignant melanoma. Cancer 75:707-14,1995.
Minor DR, Allen RE, Alberts D, : A clinical and pharmacokinetic study of isolated limb perfusion with heat and melphalan for melanoma. Cancer 55:2638-44,1985.
Nooijen PTGA, Westphal JR, Eggermont AMM, Schalkwijk C, Max R, de Waal RMW, Ruiter DJ: Endothelial P-selectin expression is reduced in advanced primary melanoma and melanoma metastasis. Am J Pathol 152:679-82,1998.
Ogose A, Emura I, Iwabuchi Y, Hotta T, Inoue Y, Sito H: Malignant melanoma extending along the ulnar, median, and musculocutaneous nerves: a case report. J Hand Surg 23A:875-8,1998.
Papachristou DN, Fortner JG: Melanoma arising under the nail. J Surg Oncol 21:219-22,1982.
Quinn MJ, Thompson JE, Crotty K, McCarthy WH, Caates AS: Subungual melanoma of the hand. J Hand Surg 21A:506-11,1996.
Quinn MJ, Wikramanayake R, Thompson JF, McCarthy WH: Non-subungual melanomas of the hand. J Hand Surg 17B:433-6,1992.
Reed PJ, Leonard DD: Neurotropic melanoma: a variant of desmoplastic melanoma. Am J Surg Pathol 3:301- ,1979.
Rigel DS, Carucci JA: Malignant melanoma: Prevention, early detection and treatment in the 21st century. CA Cancer J Clin 50:215-36,2000.
Rinne D, Baum RP, Hor G, Kaufmann R: Primary staging and follow-up of high risk melanoma patients with whole-body 18F-fluorodeoxyglucose positron emission tomography: results of a prospective study of 100 patients. Cancer 82:1664-71,1998.
Saida T, Ohshima Y: Clinical and histopathological characteristics of early lesions of subungual malignant melanoma. Cancer 63:556-60,1989.
Slingluff CL, Jr, Vollmer R, Seigler HF: Acral melanoma: a review of 185 patients with identification of prognositic variables. J Surg Oncol 45:91-8,1990.
Valensi Q: Desmoplastic malignant melanoma: a light and electron microscopic study of two cases. Cancer 43:1148- ,1979.
Warner TFCS, Hafez GR, Finch RE, : Schwann cell features in neurotropic melanoma. J Cutan Pathol 8:177- ,1981.
Warner TFCS, Lloyd RV, Hafez GR, : Immunocytochemistry of neurotropic melanoma. Cancer 53:254- ,1984.
Warso M, Gray T, Gonzalez M: Melanoma of the hand. J Hand Surg 22A:354-60,1997.
Weinstock MA: Sunscreens for melanoma prevention. Photodermatol Photoimmunol Photomed 15:209-11,1999.
Xerri L, Grob JJ, Gattyani Z: NM23 expression in metastasis of malignant melanoma is a predictive prognostic parameter correlated with survival. Brit J Cancer 70:1224-8,1994.
Yoshioka H, Itai Y, Niitsu M, Fujiwara M, Watanabe T, Satomi H, Otsuka F: Intramuscular metastasis from malignant melanoma: MR findings. Skeletal Radiol 28:714-6,1999.

Unknown macro: {corr}
Unknown macro: {springerlink}
Unknown macro: {panel}

Internet resources validated by OrthopaedicWebLinks.com

Unknown macro: {cache}
Unknown macro: {report-on}
Error formatting macro: rss: java.lang.IllegalArgumentException: Invalid uri 'http://www.orthopaedicweblinks.com/cgi-bin/owl/search.cgi?query=%content:title > url encode%&xml_feed=1': Invalid query
Unknown macro: {panel-related}
Unknown macro: {rate}
Cite this page
Unknown macro: {div}

. *

Unknown macro: {page-info}

*. _

Unknown macro: {builder-spacetitle}

. _In: OrthopaedicsOne - The Orthopaedic Knowledge Network. Created

Unknown macro: {page-info}

. Last modified

Unknown macro: {page-info}

ver.

Unknown macro: {page-info}

. Retrieved

Unknown macro: {report-info}

, from

Unknown macro: {page-info}

.

Unknown macro: {builder-hide}
Page contributions
Unknown macro: {div}

The following individuals have contributed to this page:

Unknown macro: {contributors-summary}