1. 1. Premalignant Lesions of Skin Speaker Dr. Saikat Mandal Moderator Dr. Sumit Ray
2. 2. The Architecture of the Skin
3. 3. Layers of epidermis Stratum basale (germinativum) Stratum spinosum Stratum granulosum Stratum lucidum (may not be present) Stratum corneum
4. 4. Stratum basale (germinativum) Single layer of cells on basal lamina Stem cells which give rise to keratinocytes Contain melanin transferred from melanocytes May see mitotic figures Desmosomes and hemidesmomes
5. 5. Stratum spinosum Several cells thick Have cytoplasmic processes (spines) Desmosomes
6. 6. Stratum granulosum 1 to 3 layers of fusiform shaped basophilic cells Keratohyalin granules contain cystine-rich and histidine-rich proteins that associate with keratin filaments
7. 7. Stratum lucidum Present only in thick skin Cells in which keratinization is advanced
8. 8. Stratum corneum Superifical keratinized layer Cells Almost filled with keratin Flattened, non nucleate Coated with extra-cellular lipids that form water barrier of skin Layer that varies most in thickness
9. 9. Actinic keratosis Seen as multiple lesions in sun-exposed areas Excessive exposure to sunlight over many years and inadequate protection against it are the essential predisposing factors Seen most commonly on the face and the dorsa of the hands and in the bald portions of the scalp in men
10. 10. lesions measure less than 1 cm in diameter erythematous, are often covered by adherent scales May pigmented and show peripheral spreading Occasionally, lesions show marked hyperkeratosis and then have the clinical aspect of cutaneous horns.
11. 11. Analogous lesion on the vermilion border of the lower lip as solar cheilitis and may show areas of erosion and hyperkeratosis Both can develop into squamous cell carcinoma Incidence of this transformation varies but It has been estimated that in 20% of patients have SCC in one or more of the lesions . SCC arising either in actinic keratoses or de novo in sun-damaged skin do not metastasize
12. 12. Actinic keratosis. Tall columns of parakeratotic keratin alternate with bands of orthokeratotic keratin with moderate atypia of the underlying keratinocytes
13. 13. Actinic keratosis. Beneath a thick layer of parakeratotic keratin the epidermis shows cytologic atypia.
14. 14. Actinic keratoses are keratinocytic dysplasias or squamous cell carcinomas in situ Types- I) Hypertrophic, II) Atrophic, III) Bowenoid, IV) Acantholytic, V) Pigmented
15. 15. Hypertrophic type of actinic keratosis Hyperkeratosis is pronounced and is usually intermingled with areas of parakeratosis Mild or moderate papillomatosis may be present The epidermis is thickened in most areas and shows irregular downward proliferation that is limited to the uppermost dermis and does not represent frank invasion Stratum malpighii show a loss of polarity and a disorderly arrangement Lichenoid actinic keratosis a well known variant
16. 16. Actinic keratosis, Hypertrophic type. The lesion shows hyperkeratosis and papillomatosis with prominent cytologic atypia. There is a moderate lymphocytic infiltrate in the underlying papillary dermis.
17. 17. Atrophic type of actinic keratosis Hyperkeratosis usually is slight Epidermis is thinned and devoid of rete ridges Atypicality of the cells is found predominantly in the basal cell layer Atypical basal layer may proliferate into the dermis as buds and duct-like structures
18. 18. Bowenoid type of actinic keratosis Histologically indistinguishable from Bowen's disease Also be referred to as squamous cell carcinoma in situ As in Bowen's disease, there is within the epidermis considerable disorder in the arrangement of the nuclei, as well as clumping of nuclei and dyskeratosis
19. 19. Actinic keratosis, Bowenoid type (squamous cell carcinoma in situ). Low magnification. Beneath a thick layer of parakeratotic keratin the epidermis shows cytologic atypia.
20. 20. Actinic keratosis, Bowenoid type (squamous cell carcinoma in situ). Medium magnification. Marked cellular and nuclear pleomorphism are present together with frequent and atypical mitoses
21. 21. Actinic keratosis, Bowenoid type (squamous cell carcinoma in situ). High magnification. Large atypical mitoses are prominent in this Bowenoid actinic keratosis
22. 22. Acantholytic type of actinic keratosis Immediately above the atypical cells composing the basal cell layer there are clefts or lacunae Result of anaplastic changes in the lowermost epidermis, resulting in dyskeratosis and loss of the intercellular bridges Above the acantholytic clefts, the epidermis shows varying degrees of atypicality but generally less atypicality than basal layer When atypia is full-thickness or high-grade, the term acantholytic squamous cell carcinoma in situ may be applied.
23. 23. Actinic keratosis, acantholytic type. Low magnification. The epidermis is markedly hyperkeratotic. In the dermis, there is a dense lichenoid inflammatory infiltrate. The keratosis shows focal acantholytic change
24. 24. Actinic keratosis, acantholytic type. Medium magnification. In the dermis, there is a dense lichenoid inflammatory infiltrate. The keratosis shows focal acantholytic change
25. 25. Actinic keratosis, acantholytic type. High magnification. Keratinocytes in the basal layer are crowded, with an N:C ratio, and tend to become separated from one another and to adopt a rounded configuration
26. 26. Pigmented type of actinic keratosis Excessive amounts of melanin are present, especially in the basal cell layer Almost all the melanin is retained within the cell bodies and dendrites of the melanocytes, indicating some block in melanin transfer Numerous melanophages are seen in most cases in the superficial dermis
27. 27. In all five types of actinic keratosis, the upper dermis usually shows a fairly dense, chronic inflammatory infiltrate composed predominantly of lymphoid cells but often also containing plasma cells Solar cheilitis, more frequently than actinic keratosis of the skin, shows an inflammatory infiltrate in which plasma cells predominate
28. 28. ORAL LEUKOPLAKIA Leukoplakia carries no histologic connotation and is used only as a clinical description Defined as a white patch or plaque that will not rub off and that cannot be characterized clinically or histologically as any specific disease (e.g., lichen planus, lupus erythematosus, candidiasis, white sponge nevus) Chemical irritation through tobacco or mechanical irritation through dental stumps or ill-fitting dentures plays a role. Any leukoplakia that is growing or altering its appearance requires a repeat biopsy
29. 29. Clinically, lesions of leukoplakia on the oral mucosa consist of one or several white patches that may not be raised and that appear ill defined If slightly elevated, they appear sharply demarcated, with an irregular outline Frequently show C. albicans as a secondary invader, a finding that may give rise to an incorrect diagnosis of candidiasis Induced by papillomaviruses, especially by HPV-11 and HPV-16
30. 30. 80% of the lesions found to be benign Remaining 20% of the cases, 17% show varying degrees of dysplasia or in situ carcinoma, and 3% show infiltrating SCC Leukoplakias on the buccal mucosa were found to be benign in 96% of the cases; whereas on the floor of the mouth, only 32% of the leukoplakias were benign, 31% showed a carcinoma in situ, and 37% an invasive carcinoma
31. 31. Oral leukoplakia. In this example, the squamous epithelium is hyperkeratotic and acanthotic but shows no evidence of dysplasia.
32. 32. BOWEN'S DISEASE Solitary lesion May occur on exposed or on unexposed skin Exposed skin by exposure to the sun and on unexposed skin by the ingestion of arsenic Can form in lesions of epidermodysplasia verruciformis caused by HPV-5 Slowly enlarging erythematous patch of sharp but irregular outline, showing little or no infiltration. Within the patch are generally areas of scaling and crusting
33. 33. An intraepidermal squamous cell carcinoma referred to also as squamous cell carcinoma in situ Epidermis shows acanthosis with elongation and thickening of the rete ridges, Cells lie in complete disorder, resulting in a windblown appearance Horny layer usually is thickened and consists largely of parakeratotic cells with atypical, hyperchromatic nuclei
34. 34. Atypical individual cell keratinization Dyskeratotic cells are large and round and have a homogeneous, strongly eosinophilic cytoplasm and a hyperchromatic nucleus Border between the epidermis and dermis everywhere appears sharp, and the basement membrane remains intact Occasionally vacuolization of the cells, especially in the upper portion of the epidermis seen So long as Bowen's disease remains in its intraepidermal stage, metastases do not occur
35. 35. Bowen's disease. The epidermis is irregularly thickened. The normal maturation pattern is effaced
36. 36. Bowen's disease. Throughout the epidermis, the cells lie in disarray, with frequent large atypical mitoses
37. 37. ERYTHROPLASIA OF QUEYRAT Carcinoma in situ located on the glans penis Clinically and histologically, it is identical to Bowen's disease Seen almost exclusively in uncircumcised men Asymptomatic, sharply demarcated, bright red, shiny, very slightly infiltrated plaque on the glans penis, or less often, in the coronal sulcus or on the inner surface of the prepuce
38. 38. Role of HPV in causation Progression into an invasive squamous cell carcinoma has been observed in up to 30% of the patients , with metastases in about 20% Has a greater tendency toward invasion and metastasis than Bowen's disease of the skin
39. 39. BOWENOID PAPULOSIS Occurs in young adults Most commonly located on the penile shaft,usually multicentric Papules coalesce to form plaques that resemble condyloma acuminata An indolent clinical course Varying degrees of hyperkeratosis, parakeratosis, irregular acanthosis, and papillomatosis Viral(HPV),immunologic,hormonal, or chemical causes.
40. 40. Bowenoid papulosis. Histologically, bowenoid papulosis is essentially identical to carcinoma in situ
41. 41. Bowenoid papulosis. Solitary or grouped papules with full-thickness atypia and a retained maturation pattern
42. 42. ARSENICAL KERATOSIS Careless handling of industrial wastes Arsenical keratoses of the palms and soles, consisting of verrucous papules without surrounding inflammation Cutaneous carcinomas following arsenic ingestion are usually multiple, and about three- fourths of them are located on the trunk Erythematous, scaling, occasionally crusted patches that slowly increase in size
43. 43. Avg latency between the beginning of arsenic intake and the onset of carcinoma about 18 yrs Visceral carcinoma -most common locations bronchi and the genitourinary system Commonly hyperkeratosis and acanthosis without evidence of nuclear atypicality but deeper sections show atypicality may become apparent Cutaneous carcinoma that follows arsenic ingestion can be either squamous cell carcinoma or basal cell carcinoma
44. 44. Marjolin's ulcer An aggressive ulcerating squamous cell carcinoma presenting in an area of previously traumatized chronically inflamed, or scarred skin Commonly present in the context of chronic wounds including burn injuries , venous ulcers, ulcers from osteomyelitis and post radiotherapy scars. Slow growth, painlessness (as the ulcer is usually not associated with nerve tissue), and absence of lymphatic spread due to local destruction of lymphatic channels
45. 45. Histologically the tumour is a well-diffrentiated squamous cell carcinoma. This carcinoma is aggressive in nature, spreads locally and is associated with a poor prognosis 40% occur on the lower limb and the malignant change is usually painless. This malignant change of the wound happens a long time after initial trauma, usually 1025 years later. Its edge is everted and not always raised.
46. 46. Squamous cell carcinoma, well differentiated. (Low magnification) in a case of Marjolins ulcer
47. 47. PAGET'S DISEASE Paget's disease of the breast occurs almost exclusively in women In the male breast after treatment of a carcinoma of the prostate with estrogen Begins either on the nipple or the areola of the breast and extends slowly to the surrounding skin Always unilateral and consists of a sharply defined, slightly infiltrated area of erythema showing scaling, oozing, and crusting. There may or may not be ulceration or retraction of the nipple
48. 48. Nearly always associated with carcinoma of the breast Paget cell - They are large, rounded cells that are devoid of intercellular bridges and contain a large nucleus and ample cytoplasm. The cytoplasm of these cells stains much lighter than that of the adjacent squamous cells The dermis shows a moderately severe chronic inflammatory reaction. Although Paget cells do not invade the dermis from the epidermis, may be seen extending from the epidermis into the epithelium of hair follicles
49. 49. Paget's disease. The epidermis is permeated with numerous Paget cells lying singly and in groups. There is no invasion of the dermis by Paget cells.
50. 50. Paget's disease. High magnification. Paget cells are scattered through the epidermis. They are large rounded cells devoid of intercellular bridges, with ample pale-staining cytoplasm
51. 51. EXTRAMAMMARY PAGET'S DISEASE Most commonly affects the vulva , less commonly the male genital area, or the perianal area,and rarely the axillae, the region of the ceruminal glands or that of Moll's glands Clinical picture shows a slowly enlarging reddish patch with oozing and crusting. The patch resembles an eczematous lesion, but has a sharp, irregular border In contrast to the mammary type, itching is common. Prognosis generally is better than that of mammary Paget's disease
52. 52. XERODERMA PIGMENTOSUM An autosomal recessive disorder Neucleotide excision repair enzymes are mutated Lesions occur chiefly in areas of the skin habitually exposed to sunlight Three stages I) Diffuse erythema is associated with scaling II) Atrophy of the skin, mottled pigmentation, and telangiectases III) Various types of malignant tumors of the skin appear, often causing death
53. 53. Hyperkeratosis, thinning of the stratum malpighii with atrophy of some of the rete ridges Squamous cell carcinoma, basal cell epithelioma, and, rarely, fibrosarcoma and malignant melanoma
54. 54. Spitz Nevus Benign juvenile melanoma & spindle and epithelioid cell nevus. Solitary and is seen most commonly on the lower extremities and face Dome-shaped, hairless, small pink nodule Microscopically, most Spitz nevi are of the compound type, with a prominent intraepidermal component Composed of spindle cells, epithelioid cells, or an admixture of both.
55. 55. The spindle cell variant is characterized by cigar-shaped cells with large nuclei and prominent nucleoli Epithelioid type have similar nuclei and a large, polygonal cytoplasm with distinct borders Multinucleated giant melanocyte containing up to 1020 nuclei can be seen Mitoses are found in approximately half of the cases Pigmentation may occur(Reed Nevus) Variants desmoplastic, pagetoid, plexiform, angiomatoid
56. 56. Spitz nevus of spindle cell type. This example is predominantly junctional in location.
57. 57. A and B, Spitz nevus of epithelioid type. The tumor cells feature large size, polygonal shape, occasional multinucleation, and a strongly eosinophilic cytoplasm. A and B, Spitz nevus of epithelioid type. The tumor cells feature large size, polygonal shape, occasional multinucleation, and a strongly eosinophilic cytoplasm
58. 58. Reed nevus. The tumor is heavily pigmented, in contrast to the usual type of Spitz nevus.
59. 59. Spitz nevus of the spindle cell type associated with pseudoepitheliomatous hyperplasia.
60. 60. MELTUMPS Melanocytic tumor of uncertain malignant potential Heterogeneous group of melanocytic tumors that exhibit some features indicative of possible malignancy, such as nuclear atypia, macronucleoli, mitotic activity, necrosis, or ulceration, but in number or degree insufficient to justify a malignant diagnosis Quite bulky neoplasms of the order of several millimeters in diameter and thickness, composed of pigmented often spindle-shaped cells cellularity, atypical mitosis or focal necrosis may be seen
61. 61. Giant Congenital Nevus Variant of congenital nevus characterized by its extensive size, its surface area being by definition 144 cm2 or larger Also been defined as a nevus that measures more than 20 cm in diameter in an adult, or that occupies 20% or more of the body surface area Distribute along a dermatome and often has a bathing trunk or garment configuration Also referred to as giant pigmented nevus and giant hairy nevus May involve a whole extremity, the entire scalp, and most of the trunk and even extend into the placenta
62. 62. Commonly show BRAF mutation Sometimes associated with meningeal or cerebral melanosis (neurocutaneous melanosis or melanocytosis) May give rise to malignant melanoma of the skin or central nervous system and to related malignant neuroectodermal tumors with a variety of patterns, including malignant peripheral nerve sheath tumor, (cutaneous malignant melanotic neurocristic tumor) rhabdomyosarcoma, liposarcoma, and round cell or spindle cell undifferentiated forms
63. 63. Congenital nevus with central hyperpigmented area
64. 64. Vascular involvement in congenital nevus.
65. 65. Dysplastic Nevus Occurs as a genetically determined syndrome in families prone to develop malignant melanoma (dysplastic nevus syndrome) Appear in adolescence and continue to develop in adult life Clinically atypical, with a relatively large size (>5 mm), irregular outline, and variegated Compound nevi exhibiting marked lentiginous proliferation of melanocytes at the dermoepidermal junction, with or without theques
66. 66. Dermis shows eosinophilic and lamellar fibroplasia, focal perivascular lymphocytic infiltrate, and vascular dialation. Collectively referred to as architectural atypia, are usually matched by a mild to moderate degree of cytologic atypia, manifested by nuclear hyperchromasia, prominent nucleoli, and dusty melanin pigment
67. 67. A and B, Clinical appearance of dysplastic nevi in patient with the dysplastic nevus syndrome. These nevi are large, have an irregular outline, and feature a variegated appearance
68. 68. A and B, Dysplastic nevus. There is dermal fibrosis, inflammation, and a proliferation of melanocytes at the dermoepidermal junction, with bridging of rete ridges.