Pre malignant lesions of skin

1. Premalignant Lesions of Skin
Speaker – Dr. Saikat Mandal
Moderator – Dr. Sumit Ray

2. The Architecture of the
Skin

4. Layers of epidermis
 Stratum basale
(germinativum)
 Stratum spinosum
 Stratum granulosum
 Stratum lucidum (may not
be present)
 Stratum corneum

6.  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

7.  Stratum spinosum
 Several cells thick
 Have cytoplasmic processes
(spines)
 Desmosomes

8. 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

9. Stratum lucidum
Present only in
thick skin
Cells in which
keratinization is
advanced

10. 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

11. 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

12.  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.

13.  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

16. Actinic keratosis. Tall columns of parakeratotic keratin alternate
with bands of orthokeratotic keratin with moderate atypia of the
underlying keratinocytes

17. Actinic keratosis. Beneath a thick layer of parakeratotic keratin
the epidermis shows cytologic atypia.

18.  Actinic keratoses are keratinocytic dysplasias or
squamous cell carcinomas in situ
 Types- I) Hypertrophic,
II) Atrophic,
III) Bowenoid,
IV) Acantholytic,
V) Pigmented

19. 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

20. 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.

21. 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

22. 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

23. Actinic keratosis, Bowenoid type (squamous cell carcinoma in situ). Low
magnification. Beneath a thick layer of parakeratotic keratin the epidermis
shows cytologic atypia.

24. Actinic keratosis, Bowenoid type (squamous cell carcinoma in situ).
Medium magnification. Marked cellular and nuclear pleomorphism are
present together with frequent and atypical mitoses

25. Actinic keratosis, Bowenoid type (squamous cell carcinoma in situ). High
magnification. Large atypical mitoses are prominent in this Bowenoid
actinic keratosis

26. 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.

27. 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

28. Actinic keratosis, acantholytic type. Medium magnification. In the dermis,
there is a dense lichenoid inflammatory infiltrate. The keratosis shows
focal acantholytic change

29. 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

30. 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

31.  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

32. 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

33.  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

34.  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

36. Oral leukoplakia. In this example, the squamous epithelium is
hyperkeratotic and acanthotic but shows no evidence of dysplasia.

37. 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

38.  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

39.  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

42. Bowen's disease. The epidermis is irregularly thickened. The
normal maturation pattern is effaced

43. Bowen's disease. Throughout the epidermis, the cells lie in disarray, with
frequent large atypical mitoses

44. 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

45.  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

47. 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.

48. Bowenoid papulosis. Histologically, bowenoid
papulosis is essentially identical to carcinoma in situ

49. Bowenoid papulosis. Solitary or grouped papules
with full-thickness atypia and a retained maturation
pattern

50. 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

51.  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

53. 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

54.  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 10–25 years later.
 Its edge is everted and not always raised.

56. Squamous cell carcinoma, well differentiated. (Low
magnification) in a case of Marjolin’s ulcer

57. 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

58.  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

60. 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.

61. 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

62. 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

63. 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

64.  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

66. 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.

67.  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 10–20
nuclei can be seen
 Mitoses are found in approximately half of the cases
 Pigmentation may occur(Reed Nevus)
 Variants – desmoplastic, pagetoid, plexiform, angiomatoid

69. Spitz nevus of spindle cell type. This example is predominantly
junctional in location.

70. 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

71. Reed nevus. The tumor is heavily pigmented, in contrast to the
usual type of Spitz nevus.

72. Spitz nevus of the spindle cell type associated with
pseudoepitheliomatous hyperplasia.

73. 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

74. 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

75.  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

76. Congenital nevus with central hyperpigmented area

79. Vascular involvement in congenital nevus.

80. 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

81.  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

82. 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

83. A and B, Dysplastic nevus. There is dermal fibrosis, inflammation,
and a proliferation of melanocytes at the dermoepidermal junction,
with bridging of rete ridges.