1. Premalignant Lesions of Skin Speaker Dr. Saikat Mandal
Moderator Dr. Sumit Ray
2. The Architecture of the Skin
3. Layers of epidermis Stratum basale (germinativum) Stratum
spinosum Stratum granulosum Stratum lucidum (may not be present)
Stratum corneum
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. Stratum spinosum Several cells thick Have cytoplasmic
processes (spines) Desmosomes
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. Stratum lucidum Present only in thick skin Cells in which
keratinization is advanced
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. 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. 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. 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. Actinic keratosis. Tall columns of parakeratotic keratin
alternate with bands of orthokeratotic keratin with moderate atypia
of the underlying keratinocytes
13. Actinic keratosis. Beneath a thick layer of parakeratotic
keratin the epidermis shows cytologic atypia.
14. Actinic keratoses are keratinocytic dysplasias or squamous
cell carcinomas in situ Types- I) Hypertrophic, II) Atrophic, III)
Bowenoid, IV) Acantholytic, V) Pigmented
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. 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. 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. 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. Actinic keratosis, Bowenoid type (squamous cell carcinoma
in situ). Low magnification. Beneath a thick layer of parakeratotic
keratin the epidermis shows cytologic atypia.
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. Actinic keratosis, Bowenoid type (squamous cell carcinoma
in situ). High magnification. Large atypical mitoses are prominent
in this Bowenoid actinic keratosis
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. 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. Actinic keratosis, acantholytic type. Medium magnification.
In the dermis, there is a dense lichenoid inflammatory infiltrate.
The keratosis shows focal acantholytic change
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. 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. 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. 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. 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. 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. Oral leukoplakia. In this example, the squamous epithelium
is hyperkeratotic and acanthotic but shows no evidence of
dysplasia.
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. 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. 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. Bowen's disease. The epidermis is irregularly thickened.
The normal maturation pattern is effaced
36. Bowen's disease. Throughout the epidermis, the cells lie in
disarray, with frequent large atypical mitoses
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. 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. 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. Bowenoid papulosis. Histologically, bowenoid papulosis is
essentially identical to carcinoma in situ
41. Bowenoid papulosis. Solitary or grouped papules with
full-thickness atypia and a retained maturation pattern
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. 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. 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. 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. Squamous cell carcinoma, well differentiated. (Low
magnification) in a case of Marjolins ulcer
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. 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. 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. 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. 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. 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. 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. 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. 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. Spitz nevus of spindle cell type. This example is
predominantly junctional in location.
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. Reed nevus. The tumor is heavily pigmented, in contrast to
the usual type of Spitz nevus.
59. Spitz nevus of the spindle cell type associated with
pseudoepitheliomatous hyperplasia.
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. 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. 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. Congenital nevus with central hyperpigmented area
64. Vascular involvement in congenital nevus.
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. 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. 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. A and B, Dysplastic nevus. There is dermal fibrosis,
inflammation, and a proliferation of melanocytes at the
dermoepidermal junction, with bridging of rete ridges.