Management of skin malignancy

Skin cancers in brief. Covering three most common type of skin cancers i.e basal cell carcinoma, squamous cell carcinoma and malignant melanoma.

1. Management of skin malignancy Dr Anil Gupta AIIMS, New Delhi

2. Introduction Skin is the largest organ of the body The layers of the epidermis from superficial to deep are Stratum corneum Stratum lucidum Stratum granulosum Stratum spinosum Stratum basale The dermis incorporates the adnexal structures (hair follicles, sebaceous glands, and sweat glands) and is made up of collagen, elastic tissue, and reticular fibers The subcutis is made up of adipose tissue.

3. Skin Malignancy Skin cancers are broadly divided into melanoma and nonmelanoma skin cancers (NMSC) NMSC includes 82 types with variable prognosis As per WHO classification (We’ll discuss) Keratinocytic /epidermal tumors- cSCC and BCC Melanocytic tumors Appendageal tumors Tumors of hematopoietic and lymphoid origin Soft tissue and neural tumors- Dermatofibrosarcoma Protuberans

4. Basal Cell Carcinoma (BCC) Is the most common type of skin cancer It arises from the basal keratinocytes of the epidermis (according to some authors, the tumor originates from the hair follicle epithelium) The most common presentation is a pink, pearly papule or plaque on sun exposed skin Risk factors - fair complexion, chronic sun exposure, and IR Patients > 40 years of age are more prone to BCC, although incidence is increasing in younger patients

5. It is a slow-growing skin cancer with an extremely low metastatic potential it does not develop on precursor lesions such as actinic keratosis, but it may arise on nevus sebaceous It does not metastasize through blood vessels or lymphatics in the great majority of cases. It progresses slowly in the absence of treatment and causes an irregular outgrowth toward adjacent tissue. Direct invasion of the tumor may be detected on fasciae, periosteum, perichondrium, and nerve sheaths. In neglected cases it may even penetrate bone

6. MC site- face, particularly the nose Patient may relay a history of a bump or blemish that never heals completely or bleeds easily Nodular Type Superficial Type Morphoeic (Sclerosing) Type Pigmented Type Basosquamous Type

7. AJCC STAGING

8. Treatment algorithm for BCC

9. Topical Treatments Photodynamic therapy (PDT), 5-FU, and imiquimod can be used in the management of premalignant lesions and superficial BCC. The data regarding use of PDT for superficial BCC and SCC in situ are relatively limited, though some treatment protocols have resulted in promising cure rates Imiquimod and 5-FU have been more recently approved by the FDA for the treatment of superficial BCC on the trunk and extremities. Cure rates- 50% to 90% depending on type of tumor, frequency of application, and duration of treatment course Not approved other subtype or site

10. Electrodesiccation and Curettage (ED&C) Most effective for the destruction of well-defined, superficial skin cancers

11. Excision

12. Mohs Micrographic Surgery Is a specialized technique of excision and margin examination that provides the highest cure rates and maximum conservation of normal tissue The cure rates associated with Mohs surgery for the treatment of BCC and SCC are well established and approach 99% The technique is particularly well suited for high-risk tumors Ensures both that 100% of the surgical margin is histologically examined and that only the malignant tissue – with a minimal margin of normal tissue – is removed

13. Radiotherapy The likelihood of cure is similar after surgery or RT for early-stage BCCs and SCCs Selection of one modality over another is based on other parameters such as function, cosmesis, age of the patient, convenience, cost, availability of appropriate RT equipment, and the wishes of the patient Patients with advanced cancers are often best treated with surgery and adjuvant RT if the cancer is resectable and the functional and cosmetic outcomes are acceptable to the patient Postoperative RT is added after surgery if pathologic examination of the surgical specimen reveals findings indicative of a high risk for local recurrence, such as close or positive margins and/or invasion of nerve, cartilage, or bone

14. RT Techniques External beam techniques Interstitial implant Combination with external beam techniques

15. Dose Per Fraction As high as 20 Gy Reason???

16. Squamous Cell Carcinoma (SCC) It is the second most common skin cancer Presents as slowly enlarging, irregular reddish patches Approximately 5% of cases develop an invasive component and of these up to 30% have metastatic potential Manifests predominantly in lighter skin and is most common in adulthood, with the highest incidence in patients older than 60 years

17. The etiology is possibly multifactorial including particularly solar radiation, arsenic exposure, and HPV infection It may involve any area of the body but most frequently occurs on sun-exposed areas such as the face, neck, arms, and lower legs The incidence of cSCC and other carcinomas of the skin varies globally, but is thought to be increasing overall since the 1960s at a rate of 3–8% per year from the epidermal keratinocytes of the skin and mucous membranes

18. Difference between BCC and cSCC BCC occurs more frequently around the central portion of the face Appearance- keratotic papules/plaques has a low incidence of lymphatic spread rarely produce metastases Histology- basaloid epithelium typically forms a palisade cSCC more often on the ears, preauricular and temporal area, scalp, and skin of the neck Rodent ulcer estimated to be at least 10% to 15% may develop distant metastases nests of squamous  epithelial  cells with   keratinisation  ( keratin  pearls)

19. Treatment algorithm for cSCC

20. Primary Cutaneous Malignant Melanoma Is the third most common type of skin cancer It is the leading cause of death due to skin cancer Can arise in many organs, the most common form, cutaneous melanoma, arises from the melanocytes Site- 91.2% of melanomas are cutaneous, 5.3% are ocular, 1.3% are mucosal, and 2.2% other Often presents as an irregularly bordered, pigmented macule with numerous shades of colors , ranging from tan to brown to jet-black, but they can also be evenly colored . Should be considered a systemic disease and remains a serious life-threatening entity

21. The most common sites in males are on the back and in the head and neck regions. In women, the most common sites are in the lower extremities, commonly below the knee Several immunostains that can be used on frozen sections have been studied extensively, including MART-1, S-100, MEL-5, Melan-A (A-103), and HMB-45 The classic appearance of primary cutaneous melanoma is summarized as ABCD for a symmetry b order irregularity c olor variation d iameter >6 mm

22. Amelanotic Melanoma Amelanotic Melanoma Superficial spreading Melanoma Superficial Melanoma Superficial spreading Melanoma with satellite nodules Acra l lentiginous Melanoma Lentigo Melanoma Nodular Melanoma Types of Primary Cutaneous Malignant Melanoma The classic appearance of primary cutaneous melanoma is summarized by the mnemonic ABCD for a symmetry, b order irregularity, c olor variation, and d iameter > 6 mm

23. Workup Biopsy-full-thickness biopsy of the entire lesion, with a narrow (1 to 2 mm) margin of grossly normal skin sentinel node biopsy Metastatic workup- chest radiography, and CT or MRI scanning, positron emission tomography (PET) Serum LDH

24. Breslow depth A standardized method to measure melanoma depth. It requires an optical micrometer fitted to the ocular position of a standard microscope The most important prognostic factor for localized melanomas is tumor thickness ≤1.0 mm (melanoma in situ and thin invasive tumors) 1.01–2.0 mm 2.01–4.0 mm ≥4.0 mm

25. Clark level Refers to penetration of the melanoma through the layers of the skin. Level I: Melanoma cells confined to the epidermis (melanoma in situ) Level II: penetrates the basement membrane into the papillary dermis Level III: fills the papillary dermis and encroaches on the reticular dermis Level IV: invades the reticular dermis Level V: into the subcutaneous fat is less reproducible among pathologists and does not reflect prognosis as accurately as tumor thickness

26. Tumor-infiltrating Lymphocytes (TILs) Lymphocytes that infiltrate and disrupt tumor nests and/or directly oppose tumor cells- Absent TIL infiltrate Non brisk TIL infiltrate Brisk TIL infiltrate TIL infiltration in primary cutaneous melanoma is a favourable prognostic factor

27. Neurotropism Presence of melanoma cells abutting nerve sheaths Usually circumferentially- perineural invasion Within nerves - intraneural invasion Tumor itself may form neuroid structures- neural transformation Associated with an increased local recurrence rate

28. An Electronic Prediction Tool Based on the Melanoma http://www.lifemath.net/cancer/melanoma/nodal/index.php

29. Treatment of Melanoma Surgical excision of the primary tumor is the standard treatment for invasive melanoma Sentinel lymph node biopsy should be considered in cases of invasive melanoma with a Breslow thickness greater than 1.0 mm Moh's surgery is generally considered inappropriate for definitive treatment of a invasive melanoma SLNB If positive for nodal disease, a complete nodal basin excision would ordinarily be performed

30. Adequate margins

31. The key prognostic factor for predicting the metastatic potential of a given primary tumor is its Breslow thickness Likewise, the key prognostic factor for predicting overall survival in a given patient is sentinel lymph node status Other key prognostic factors identified by stratified analyses included ulceration, lesion site, and patient age Paradox- There is a greater risk of lymph node metastasis in young patients at the time of SNBx especially for patients younger than age 35 years, but the melanoma-associated mortality risk increases with age for all thickness ranges

32. Radiotherapy in Malignant Melanoma Postoperative adjuvant radiation may be delivered with 2- to 3-cm margins around the resected lesion if margins are inadequate, or following resection of a locally recurrent lesion Neurotropic melanomas of the head and neck have a propensity to recur at the skull base by tracking along cranial nerves, and postoperative adjuvant radiation including the resection bed and the cranial nerve pathway should be considered for this variant Large unresectable primary lesions should be considered for palliative radiation therapy

33. Patients with positive SNBx or palpable regional nodal metastases (stage III disease) are treated with therapeutic inguinal, axillary, or cervical lymph node dissections Several large retrospective studies have identified lymph node extracapsular extension, large lymph nodes (≥3 cm in diameter), four or more involved lymph nodes, or recurrent disease after previous lymph node dissection as adverse risk factors that increase the risk for nodal basin recurrence following therapeutic nodal dissection to 30% to 50%

34. METASTATIC MELANOMA (STAGE IV) RT- brain metastases, vertebral mets Abscopal effect

35. Dermatofibrosarcoma Protuberans (DFSP) Most common type of cutaneous sarcoma DFSP is a dermal neoplasm that almost always extends into the subcutis Is a locally aggressive cutaneous tumor with low to intermediate grade malignant potential The tumor is composed of fairly uniform spindled cells with elongated nuclei Presents as a slow-growing, solitary or multiple, polypoid nodular lesion that ranges in size from 0.5 cm to 10 cm It has predilection for the trunk and proximal extremities of young and middle-aged adults, with slight male predominance

36. Local recurrence is common and the risk of metastases is rare (<0.5% of cases, usually to the lungs) Usually, metastatic disease is preceded by multiple local recurrences and appears to be associated with fibrosarcomatous transformation Is characterized by a reciprocal translocation, t(17;22)(q22;q13) (COL1A1 and PDGFB genes) IHC: The tumor cells are strongly positive for CD34 and negative for factor XIIIa , S-100 protein, and CD117 . CD99 is also positive in some cases Cause is unknown

37. A wide surgical excision with adequate margins or Mohs technique are used Minimal margin of at least 3 cm of surrounding skin, including the underlying fascia, without elective lymph node dissection Radiation therapy may be recommended for patients with positive/inadequate margins or in recurrence The complete radiation therapy dose ranges from 50-70 Gy Imatinib mesylate is indicated for the treatment of adult patients with unresectable, recurrent, and/or metastatic DFSP The recommended oral dose is 800 mg/d

38. Conclusion Basal cell ca (BCC), cutaneous squamous cell ca( cSCC ) and dermatofibrisarcoma protuberans (DFSP) has good prognosis as compared to cutaneous malignant melanoma ( cMM ) BCC has lower lymphatic spread and distant metastases as compared to cCC Surgery with adequate resection margin is the mainstay of cSCC , BCC, cMM and DFSP Radiotherapy is alternative treatment which is used in adjuvant setting in cSCC , BCC, cMM and DFSP with high risk features. It can used as upfront treatment in unresectable cSCC , BCC, cMM and DFSP

39. THANK YOU