Malignant Melanoma

pathology, investigations, staging and treatment options

1. Malignant Melanoma Clinical Features, Pathology and Management By Dr Madhu kumar Under guidance Dr PV Budha MS Dr Venkat Reddy MS Dr Sailajarani MS Dr Satyanaryana MS Dr Ayyapasrinivas MS

2. What is Melanoma Melanoma is a very serious form of skin cancer. Melanoma is cancer of the melanocytes . Melanocytes are located in the Stratum Basale and produce melanin.

3. Melanocytes When skin is exposed to sunlight, melanocytes produce more pigment, causing the skin to tan. Sometimes, clusters of melanocytes form noncancerous ( benign) growths called moles . Moles can be either flat or raised, round or oval, and are smaller than a pencil eraser. Generally harmless, but can become cancerous

4. Incidence Although melanoma accounts for only about 5% of all skin cancer cases, it causes most skin cancer-related deaths The incidence is rising by 3% a year

5. Causes of Melanoma 90% of all melanomas are linked to UV radiation. (Sun exposure) 8% are due to chromosomal abnormalities About 2% are unknown

6. Risk Factors Family history of melanoma Dysplastic nevi (noncancerous, but unusual- looking moles ) Previous melanoma Many nevi (ordinary moles ): more than 50 Severe, blistering sunburns Freckling tendency Fair skin Excessive use of tanning beds Genetic predisposition

7. Signs and symptoms of melanoma Melanoma can appear suddenly as a new mole , or it can develop slowly in or near an existing mole. In men, melanomas are often found between the shoulders and hips, or the head and neck area. In women, melanoma often develops on the lower legs as well as between the shoulders and hips. It may also appear under the fingernails or toenails or on the palms or soles

8. ABCDE of melanoma A is for Asymmetry: One half of a mole or birthmark does not match the other. B is for Border:   The edges are irregular, ragged, notched, or blurred. C is for Color:   The color is not the same all over and may include shades of brown or black, or sometimes with patches of pink, red, white, or blue. D is for Diameter:   The spot is larger than 6 millimeters across (about ¼ inch – the size of a pencil eraser), although melanomas can sometimes be smaller than this. E is for Evolving:   The mole is changing in size, shape, or color.

9. Biopsy Small and accessible lesions Excision with 1 cm margins in suspicious lesions Large lesions Incisional or punch biopsy ? Shave biopsy discouraged

10. Histomorhological types Superficial Spreading Melanoma Nodular Melanoma Lentigo Maligna Melanoma Acral Lentiginous Melanoma Amelanotic Melanoma

11. Superficial Spreading Melanoma Most common histologic type (70 %) Appear as a flat, pigmented lesion growing in the radial pattern

12. Nodular Melanoma Second most common type (15%) Vertical growth pattern Worst prognosis based on a higher average tumor thickness.

13. Lentigo Maligna Melanoma Sun-damaged skin Flat,darkly pigmented lesion with irregular borders and a history of slow development

14. Acral Lentiginous Melanoma Subungual areas and the glabrous skin of the palms and soles Seen in blacks

15. Amelanotic Melanoma Uncommon Difficult to diagnosis Lacks pigmentation

16. Antibodies for immunohistochemistry S - 100 HMB - 45 Mutations BRAF NRAS AKT

17. Stage (Clark’s level or Breslow Depth)

18. 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.

19. Breslow level of invasion Current stage system is based on depth of invasion Measured using ocular micrometer Currently Breslows level 0f < 1mm, 1 to 4mm and > 4 mm is used for TNM staging

20. Metastatic workup done for stage III onwards Chest x ray CT Chest and abdomen PET CT MRI brain

21. Treatment of Melanoma

22. Early stages: Wide local excision More advanced: Wide local excision plus sentinel node biopsy, Based on the pathology Lympadnectomy observation interferon Metastatic: Clinical trial Radiation and systemic therapy

23. Wide Excision Regardless of tumor depth or extension, surgical excision is the management of choice If the deep fascia is not involved fascia is left intact

24. SLN biopsy using TC 99

25. Elective lymph node dissection ( ELND) Use of prophylactic dissection (clinically negative nodes) is controversial No prospective, randomized studies have demonstrated that elective LN dissection improves survival in patients with intermediate-thickness melanomas By SLN biopsy micrometastasis is identified removed node sent for frozen-section examination, a complete LN dissection is performed

26. Dissection should be complete Groin dissection Deep (iliac) nodes must be removed along with the superficial (inguinal) nodes Axillary dissection All levels I, II, III should be removed Head and Neck Superficial parotidectomy to remove parotid nodes and a modified neck dissection

27. Complications Wound seroma Cellulitis lymphedema

28. In-transit disease (local disease in lymphatics ) 5 to 8% of melanoma patients with a high-risk primary melanoma (>1.5 mm) Hyperthermic regional perfusion Melphalan is the chemotherapeutic agent used

29. Melphalan generally is heated to an elevated temperature [up to 41.5°C, (106.7°F)] and perfused for 60 to 90 minutes Produce a high response rate (greater than 50 %) Complications neutropenia , amputation, death Tumor necrosis factor alpha or interferon- alfa along with melphalan regression rate 90%

30. Targeted therapies BRAF Inhibitor PLX4032( vemurafenib ) KIT Inhibitor Imantinib mesylate

31. Chemotherapy Dacarbazine is drug of choice Other drugs Cisplatine Paclitaxel Docetaxel Temozolomide

32. Immunotherapy Interlukin IL-2 and Interferon on high doses BCG Monoclonal antibodies Ipilmumab Tumour vaccine Polyvalent melanoma vaccine ( Canvaxin ) Allogenic melanoma cell lysate ( Melacin ) Detoxified endotoxin / myco bacterial cell wall skeleton (DETOX) Gp 100 DNA vaccine GM-CSF 2 nd generation oncolytic herpes virus vaccine

33. Radiation Used in some cases High doses Not so useful

34. Follow up Early melanomas Every 6 months for 2 yrs them annually Advanced melanomas Every 3-4 months for 3-4 yrs, every 6 months for 1 year, latter annually

35. Thank You