Melanoma

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Melanoma

  1. 1. Melanoma Presented by Dr. Sultan Tawfiq R5
  2. 2. incidence • The increasing rate of melanoma diagnoses is the highest of any cancer in the United States. • The age-adjusted incidence of invasive melanoma in the United States increased from approximately 4 to 18 per 100,000 white males between 1973 and 1998.73
  3. 3. pathogenesis • The pathogenesis of melanoma is complex and remains poorly understood to date. • Melanoma may arise from transformed melanocytes
  4. 4. • Although nevi (freckles) are benign melanocytic neoplasms found on the skin of many people, dysplastic nevi contain a histologically identifiable focus of atypical melanocytes. • These lesions are thought to represent an intermediate stage between benign nevus and true malignant melanoma.
  5. 5. Mole or melanoma ?
  6. 6. • Studies demonstrate increased relative risk of melanoma development based on increasing numbers of dysplastic nevi found on the patient. • a strong genetic component has been described • Up to 14% of malignant melanomas occur in a familial pattern
  7. 7. • family members of those with either dysplastic nevi or melanoma are at increased risk for tumor development.
  8. 8. •Once the melanocyte has transformed into the malignant phenotype, tumor growth occurs radially in the epidermal plane. •Even though microinvasion of the dermis may have occurred, metastases do not occur until these melanocytes form dermal nests.
  9. 9. • During the subsequent vertical growth phase, cells develop different cell-surface antigens and their malignant behavior becomes much more aggressive.
  10. 10. • 90% of melanomas are found on the skin • the eye and anus are notable sites • 4% of tumors are discovered as metastases without any identifiable primary site.
  11. 11. features suggestive of melanoma • • • • • pigmented lesion with an irregular border darkening coloration Ulceration raised surface recent changes in nevus appearance that may denote malignant transformation. • 5 to 10% of melanomas are nonpigmented.
  12. 12. Anal melanoma
  13. 13. Eye melanoma
  14. 14. Hard Palate melanoma
  15. 15. Types of melanoma • • • • 1- superficial spreading 2- nodular 3- lentigo maligna 4- acral lentiginous
  16. 16. superficial spreading • accounts for up to 70% of melanomas • occur anywhere on the skin except the hands and feet • typically flat and measure 1 to 2 cm in diameter at diagnosis. • a prolonged radial growth phase is characteristic of these lesions. • Typically of darker coloration and often raised
  17. 17. Nodular type • accounts for 15 to 30% of melanomas. • noted for their lack of radial growth • all nodular melanomas are in the vertical growth phase at diagnosis. • Although considered a more aggressive lesion, the prognosis for patients with nodular-type melanomas is similar to that for a patient with a superficial spreading lesion of the same depth.
  18. 18. Nodular melanoma
  19. 19. Lentigo maligna • accounts for 4 to 15% of melanomas • occurs most frequently on the neck, face, and hands of the elderly. • tend to be quite large at diagnosis, these lesions have the best prognosis because invasive growth occurs late. • Less than 5% of lentigo maligna are estimated to evolve into melanoma.
  20. 20. Acral lentiginous • Least common type • 2 to 8% of melanomas in white populations. • this type accounts for 29 to 72% of all melanomas in dark-skinned people (African Americans, Asians, and Hispanics). • Acral lentiginous melanoma most frequently is encountered on the palms, soles, and subungual regions.
  21. 21. • Most common on the great toe or thumb, subungual lesions appear as blue-black discolorations of the posterior nail fold. • The additional presence of pigmentation in the proximal or lateral nail folds (Hutchinson's sign) is diagnostic of subungual melanoma.
  22. 22. Prognostic indicators • Independent of histologic type and depth of invasion • lesions of the extremities have a better prognosis than patients with melanomas of the head, neck, or trunk (10-year survival rate of 82% for localized disease of the extremity compared to a 68% survival rate with a lesion of the face)
  23. 23. Lesion ulceration • Lesion ulceration carries a worse prognosis. The 10-year survival rate for patients with local disease (stage I) and an ulcerated melanoma was 50% compared to 78% for the same stage lesion without ulceration.
  24. 24. Lesion ulceration • Early studies identified that the incidence of ulceration increases with increasing thickness, from 12.5% in melanomas less than 0.75 mm to 72.5% in melanomas greater than 4.0 mm.74,76 Recent evidence suggests that tumors ulcerate as the result of increased angiogenesis.
  25. 25. Gender • females have an improved survival compared to males. • Women tend to acquire melanomas in more favorable anatomic sites • less likely to contain ulceration. • After correcting for thickness, age, and location, females continue to have a higher survival rate than men (10-year survival rate of 80% for women vs. 61% for men with stage I disease).
  26. 26. Prognosis • In general, there is no significant difference between different histologic tumor types in terms of prognosis, when matched for tumor thickness, gender, age, or other. • Nodular melanomas have the same prognosis as superficial spreading types when lesions are matched for depth of invasion.
  27. 27. • Lentigo maligna types have a better prognosis even after correcting for thickness • acral lentiginous lesions have a worse prognosis. • Even though the various types of melanoma have similar prognoses when controlled for the other prognostic factors, acral lentiginous melanoma has a shorter interval to recurrence.
  28. 28. Staging • Historically, the vertical thickness of the primary tumor (Breslow thickness) and the anatomic depth of invasion (Clark level) have represented the dominant factors in the T classification. • The T classification of lesions comes from the original observation by Clark that prognosis is directly related to the level of invasion of the skin by the melanoma.
  29. 29. • Whereas Clark used the histologic level [I, superficial to basement membrane (in situ); II, papillary dermis; III, papillary/reticular dermal junction; IV, reticular dermis; and V, subcutaneous fat] • Breslow modified the approach to obtain a more reproducible measure of invasion by the use of an ocular micrometer.
  30. 30. Breslow thickness • The lesions were measured from the granular layer of the epidermis or the base of the ulcer to the greatest depth of the tumor (I, 0.75 mm or less; II, 0.76 to 1.5 mm; III, 1.51 to 4.0 mm; IV, 4.0 mm or more). • These levels of invasion have been subsequently modified and incorporated in the AJCC staging system.
  31. 31. American Joint Committee on Cancer (AJCC) • The most current staging system • contains the best method of interpreting clinical information in regard to prognosis of this disease • The new staging system has largely replaced the Clark level with another histologic feature, ulceration, based on analysis of large databases available to the AJCC Melanoma Committee.
  32. 32. Staging
  33. 33. • Evidence of tumor in regional LNs is a poor prognostic sign associated with a steep drop in survival at 15-year follow-up. • Positive node status will advance any stage 1 or 2 to stage 3 • Identification of distant metastasis is the worst prognostic sign and is classified as stage IV disease.
  34. 34. Metastatic disease • Although occasional survival for several years has been noted, median survival ranges from 2 to 7 months depending on the number and site of metastases.
  35. 35. How to diagnose • History - Physical examination • Biopsy :• Diagnosis of melanoma typically requires excisional biopsy • A 1-mm margin of normal skin is taken if the wound can be closed primarily. • In large lesions incisional biopsy • Special stains and markers (sp-100), vimentin
  36. 36. Treatment of melanoma • surgical excision • Lymphadenectomy • immunotherapy
  37. 37. surgical excision • surgical excision is the management of choice. • Lesions 1 mm or less in thickness can be treated with a 1-cm margin. • For lesions 1 mm to 4 mm thick, a 2-cm margin is recommended. • Lesions of greater than 4 mm may be treated with 3-cm margins.
  38. 38. • The surrounding tissue should be removed down to the fascia to remove all lymphatic channels. • If the deep fascia is not involved by the tumor, removing it does not affect recurrence or survival rates, so the fascia is left intact.
  39. 39. Treatment of regional LNs • Treatment of regional LNs that do not obviously contain tumor in patients without evidence of metastasis is an area of continued debate. • If < 1 mm depth no LN treatment needed • With lesions deeper than 4 mm most likely has distant mets so local LN is not beneficial no effect on survival (most die of dist mets )
  40. 40. Metastatic melanoma
  41. 41. The controversy • In patients with intermediate-thickness tumors (T2 and T3, 1 to 4.0 mm) and no clinical evidence of nodal or metastatic disease, the use of prophylactic dissection (elective LN dissection on clinically negative nodes) is controversial. • To date, no prospective, randomized studies have demonstrated that elective LN dissection improves survival in patients with intermediate-thickness melanomas.
  42. 42. • However, 25 to 50% of LN specimens contain micrometastases in these cases and recurrence may be decreased with LN dissection. • Sentinel lymphadenectomy for malignant melanoma is gaining acceptance
  43. 43. ELND = elective lymph node dissection; IFN-a2b = interferon alfa-2b; LAD = lymphadenopathy; LN = lymph node; SLND = sentinel lymph node dissection .
  44. 44. Metastatic melanoma • Once melanoma has spread to a distant site, median survival is 7 to 8 months and the 5year survival rate is less than 5%. • Solitary lesions in the brain, GI tract, or skin that are symptomatic should be excised when possible. (cure is very rare but asymptomatic survival prolonged ) • A decision to operate on metastatic lesions must be made after careful deliberation with the patient and the treating oncologist.
  45. 45. Local recurrence • Locally recurrent, lymphatic-invading, or tumors unamenable to surgical excision present a significant management challenge. • local disease in lymphatics) develops in 5 to 8% of melanoma patients with a high-risk primary melanoma (>1.5 mm). • Hyperthermic ( 42 c) regional perfusion with a chemotherapeutic agent (e.g., melphalan) is presently the treatment of choice.
  46. 46. • Difficult to perform • Associated with complications (neutropenia, amputation, death) • it does produce a high response rate (greater than 50%) • Addition of tumor necrosis factor alpha or interferon- ϒ with melphalan results in the regression of more than 90% of cutaneous intransit metastases.
  47. 47. Extensive disease
  48. 48. Radiation • Use of radiation in under investigation • High dose per-fraction radiation produces a better response rate than low dose • the treatment of choice for patients with symptomatic multiple brain metastases • radiation therapy produced measurable improvement in tumor size, symptomatology, or performance status in 70% of treated patients.
  49. 49. • Interferon alfa-2b is the only Food and Drug Administration approved adjuvant treatment for AJCC stages IIB/III melanoma. • Side effects were common and frequently severe • majority of the patients required modification of the initial dosage and 24% discontinued treatment.
  50. 50. Future treatments • Immunotherapy also continues to be a field of great promise. • Vaccines have been developed with the hope of stimulating the body's own immune system against the tumor. • Melanoma cells contain a number of distinctly different cell-surface antigens, and monoclonal antibodies have been raised against these antigens.
  51. 51. References • Schwartz principles of surgery 9 e
  52. 52. Thank you

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