Squamous Cell Carcinoma

A detailed presentation on the clinical features, predisposing factors and treatment of skin cancers especially Squamous Cell Carcinoma. Pre - malignant conditions like Actinic keratosis, Bowen disease, Porokeratosis are also discussed. Also the presentation provides a detail of the various differential diagnoses of the skin cancers. Useful for medical students, post graduate trainees and nursing staff. Role of sunlight is also discussed.

1. SQUAMOUS CELL CARCINOMA & ITS PRECURSORS

2. PRECUROR LESIONS

3. PREMALIGNANT / PRECURSOR LESIONS Actinic keratosis Cutaneous horn Arsenical keratosis Post ioninzing radiation keratosis Disseminated superficial actinic porokeratosis Bowen’s disease / carcinoma in situ

4. ACTINIC KERATOSIS

5. ACTINIC KERATOSIS UV-induced  precancerous skin lesion  that may progress to skin cancer on chronically sun exposed areas affecting elderly males & females More common in white population & those with red hair & blue eyes . Relapsing-remitting lesions.

6. Initially : small lesion (macules or papules) with  rough surface →  coarse sandpaper-like   texture Usually asymptomatic Better appreciated by palpation May pass unnoticed by patient

7. Later: lesions grow and become  erythematous  and adherent hyperkeratotic scale - removed with difficulty and pain , revealing punctate bleeding points Presence of tenderness, induration , or a raised shoulder beyond disorganized scaling- malignant transformation.

8. 4 Clinical Variants Of Actinic Keratosis 1.Flat 2.Atrophic 3.Lichenoid 4.Pigmented

9. H/P - solar elastosis , -epithelial dysplasia restricted to basal layer -hyperkeratosis -parakeratosis -absent granular layer

10. HIGH RISK CLINICAL FEATURES OF AK -- EARLY INVASIVE SCC Multiple thick Aks Past history of NMSC Extensive actinic damage Immunocompromised state Tenderness, induration & enlarging lesion

11. T TREATMENT

12. Other Rx options Topical & oral retinoids Dermabrasions & chemical peels with trichloracetic acid Non ablative fractional resurfacing

13. CUTANEOUS HORN

14. CUTANEOUS HORN Benign c urved, hard, yellow-to-brown outgrowths composed of  keratin  - resembles a horn  & may develop from preexisting actinic and  seborrheic keratosis   or   warts UVR-induced on light exposed areas M ay  progress to  squamous cell carcinoma  ( SCC) ~ 40%

15. Keratotic lesion with a height of at least half the widest diameter of its base Dysplastic epidermal changes similar to AK Inflammation, induration & pain at the base suggests malignant transformation clinically – wide base or low height-to-weight ratio H/P – budding from basal layers in long established lesions

16. DIFFERENTIAL DIAGNOSIS Viral warts Actinic keratosis Seborrheic keratosis Keratoacanthoma Invasive SCC

17. MANAGEMENT Clinical appearance H/P of base to rule out malignancy Surgical excision – to obtain pathology & rule out malignany

18. ARSENICAL KERATOSIS

19. ARSENICAL KERATOSIS A corn like punctate keratosis caused by arsenic / a few years after exposure, mainly affecting the palms & soles. Hyperpigmentation –raindrop pattern , accompanied by hypopigmenated areas, and progression to generalized thickness of palms and soles . Smoking , nutritional deficiencies (retinol, Ca, iron, folate ,vitamin A,E,C)

20. H/P – epithelial dysplasia or hyperplasia. No typical microscopic feature. May progress to BCC, SCC or Bowen’s disease – induration , inflammation and ulceration become apparent. DIFFERNTIAL DIAGNOSIS Disseminated puntate keratoderma Darier’s disease Lichen planus Planter warts

21. MANAGEMENT Reduce arsenic exposure Well balanced diet 1 st line Solitary / few lesions – cryotherapy ,cautery or curettage. Multiple keratosis – oral retinoid in combination with keratolytics 2 nd line Imiquimod cream 5% OD for 6weeks or OD 3-5times per week

22. BOWEN’S DISEASE

23. BOWEN’S DISEASE S quamous cell carcinoma in situ   ( SCCIS) of the skin. UVR-induced damage in sun-exposed areas & non exposed areas, often associated with HPV Single, large, persistently non-elevated , well demarcated, erythematous plaque , with white-to-yellow scale – moist , reddened, granular surface on detachment with no bleeding point .

24. ~10-20% multiple lesions , either widely spread or sometimes close together . Slower growth rate and spontaneous partial regression at times. Can occur on perianal skin, subungal region, palms & soles -higher risk of invasion & recurrence. May progress to invasive squamous cell carcinoma. ~3-5% risk

25. Clinical Variants OF Bowen’s Disease 1.Psoriasiform 2.Atrophic 3.Verrocous 4.Papillated 5.Irregular

26. Histopathology F ull thickness epidermal dysplasia & disordered differentiation with loss of epithelial polarity. Parakeratosis & acanthosis. Large hyperchromatic nuclei Atypical mitosis and gaint cells.

27. DIFFERENTIAL DIAGNOSIS

28. MANAGEMENT

29. POST –IONIZING RADIATION KERATOSIS

30. POST –IONIZING RADIATION KERATOSIS An area of scarring following accidental exposure to radiation or after therapeutic radiotherapy or excessive fluoroscopy Relatively uncommon –after months to years following exposure On limbs mostly or covered body sites. Changes similar to AK , telangiectasia, vasculitis, radiation ulcers, hemangiomas, subcutaneous sclerosis of connective tissue.

31. D/D – Actinic Keratosis H/P – epidermal changes similar to AK. Dermis – much extensive replacement of collagen by scar and elastotic material MANAGEMENT Skin biopsy to confirm the diagnosis Immediate reduction to exposure Cryotherapy for individual lesions.

32. DISSEMINATED SUPERFICIAL ACTINIC POROKERATOSIS

33. DISSEMINATED SUPERFICIAL ACTINIC POROKERATOSIS Multiple enlarging rough hyperkeratotic papules surrounded by a thread like elevated border , on distal extermeties – usually around a follicle Skin within the ring is atrophic , erythematous or hyperpigmented. Hypopigmented ring just inside the ridge.

34. Prominent in summer & improve in winter. Very low chances of malignant transformation . H/P - cornoid lamella at the margins. - narrow column of altered keratin - dyskeratotic & vacuolated epidermal cells

35. Clinical varaints of P orokeratosis 1. Porokeratosis of Mibelli 2. linear porokeratosis 3. DSAK 4.Porokeratosis palmaris & plantaris diffusa 5. Punctate porokeratosis

36. DIFFERENTIAL DIAGNOSIS Actinic keratosis – esp if on face , but present on other sun exposed sites as well Bowen’s disease – on legs Superficial BCC

37. MANAGEMENT Good use of emollient & high factor broad spectrum sunscreen Cryotherapy with liquid nitrogen Topical diclofenac gel , vit D3 analogues , 5% 5-FU cream , 5% imiquimod cream Photodynamic therapy Erbium , CO2, Q-switch ruby laser, Nd:YAG –under successful trials.

38. SCC Older males Common type of Non Melanoma Skin Cancer ( NMSC ) It is derived from keratinocytes May develop de novo or from precursor AK or SCC in situ Mainly on sun exposed sites ( hairless scalp, upper part of face, lips ( Lowerlip ), ears (helices), dorsa of hands, forearms, lower legs) Size few milimeters to centimeters in diameter .

39. PATHOPHYSIOLOGY Common mutations (tumor suppressor genes ) p53 – UVB induced p16 – UVR induced Chromosomal abnormalities ( Genome-wide expression & SNP analysis) 3p, 8q, 9p, 11p, 13q, 17p and 18p

40. RISK FACTORS UVR – Major risk factor ( UVB > UVA, sunlight & artificial tanning lamps) F air-skinned individuals (Fitzpatrick skin type 1 and 2) Premalignant conditions Inherited predisposition Smoking (lower lip SCC)

41. ... cont Viral Infections (HPV-16,-18) – viral warts,genital warts, many mucosal SCCs. B-type of HPV > excess risk of SCC. Longstanding dermatosis longstanding leg ulcer, fistula tracts, chronic injury site, inflammation sec to Hidradenitis supparativa.Thermal scars – Marjolin’s ulcer that occurs on chronic wound or scar including scars from burn. Immunosuppression ( ciclosposrin , azathioprine , organ transplant recipients , haematological malignancies , HIV )

42. 1 st clinical sign – induration. Firm , tender , erythematous nodule or plaque with keratotic crust , verrucous, tumid E roded fungating mass – that shows easy bleeding Lesions that fail to heal – develop ulcers with everted edge , indurated base & necrotic floor Outline – mostly irregular , sometimes rounded.

43. Mobile structures like lip & Genitalia show early fissuring or small erosions or ulcers that fail to heal and bleeds recurrently. May be associated with other features of photodamage or premalignant lesions. Parestheisa , anesthesia, tenderness, pain particularly in perineural invasion Regional LN enlargement (later –hard & fixed)

44. Proliferation of Atypical Keratinocytes Typical SCC has nests of squamous epithelial cells arising from epidermis and invading into dermis

45. Malignant cell – large, abundant eosinophilic cytoplasm & large vesicular or hyperchromatic nucleus with pleomorphism & mitosis.

46. Variable keratinaization squamous eddies , keratin pearls (concentric layers of squamous cells with increasing keratinization towards the center ) Inflammatory infiltrates – varies considerably in intensity primarily lymphocytes & plasma cells

47. Grading of SCC Depends on how easy it is to recognize the characteristics of squamous epithelium ( e.g , intracellular bridges , keratinization ) , pleomorphism & mitotic activity The greater the degree of keratinization – the better differentiated tumor.

48. Well differentiated Poorly differentiated SCC SCC

49. METASTATIC SCC Upto 5% RISK OF METASTASIS Invasive SCC rarely metastasize and prove fetal. that r efers to growth into deeper layers of skin , the dermis. More difficult to treat than the original skin lesions . In 80% cases metastases develops from draining LN .

50. DIFFERENTIAL DIAGNOSIS

51. DIAGNOSIS DIFFERENTIATING POINTS Keratoacanthoma (KA ) Faster growth rate, involute to leave a scar. Classified as well differentiated SCC. No precursor lesion unlike SCC. Presents (initially) as firm, rounded flesh coloured papule (like MC) , (later) if keratotic > like a viral wart. More hyperkeratotic than AK Spontaneous resolution ~ 3months Actinic keratosis ( AK ) Sun exposed area. Multiple. Macules or papules with rough scaly surface & lack of dermal component on palpation. Asymptomatic. 10% chances of SCC Bowen’s disease / carcinoma in situ Solitary, larger, persistently non elevated, erythematous scaly plaque, with no bleeding on detachment. Slower growth rate and spont partial regression at times. Asymptoamtic

52. … cont Cutaneous horns Curved , hard, yellow to brown keratotic outgrowths with circumferential ridges. Mostly single. Inflammation, induration & pain at the base suggests malignant transformation. ~40%/usually SCC Warty leasion ( viral warts , seborrheic keratosis) Multiple , not indurated. SK have darker, raised & greasy warty surface. Basal cell carcinoma ( BCC ) Single , less hyperkeratotic than AK, irregular erythematous base. Arsenical keratosis Corn like , punctate keratosis caused by arsenic(years after exposure), mainly on palms and soles. Presents as hyperpigmentation of skin ,accompanied with hypopigmented areas. Progress over time with increase in numbers. High risk of developing BCC, SCC/ bowen’s disease .

53. INVESTIGATIONS

54. Skin biopsy - to confirm diagnosis MRI (in case of head and neck tumors and higher chances of mets ) CT scan(in case of nerve involvement ) USG combined with a guided fine needle aspiration or core biopsy (in case of LN involvement ) High resolution micro oil MRI / SPECT / PET – role in future. Reflectance confocal microscopy & high resolution optical coherence tomography – under trials.

55. Aim Remove primary tumor & prevent recurrence Rx Depends on clinical (size, location, number) & pathological features of tumor. Long term prognosis for adequately treated SCC is excellent. Larger / aggressive lesions need imaging before starting the treatment .

56. High Risk Clinical F eatures (HRCP) - diameter >20mm - immunosuppressive - site: ear, lip, scalp,eyelid - SCC arising in burns, scars, chronic ulceration , radiation damage. Bowen’s disease in non sun exposed skin , inflammatory conditions. High Risk Pathological F eatures (HRPF) - depth >4mm & diameter >20mm -poorly differentiated - perineural invasion - lymphovascular invasion -subtypes: desmoplastic , spindle cell, acantholytic , arising in B owen’s disease in non-sun-exposed skin

57. Rx Low Risk lesions Rx High risk lesions