1. Dermatopathology
Dr. Amitabha Basu

3. The normal histologic appearance of the skin is shown here.

4. This is normal skin from a person with a dark complexion
This is normal skin from a person with a dark complexion. The amount of skin pigmentation varies among races and individuals.

5. Here are normal adnexal structures of the skin

6. The Pilosebaceous unit.
Here are sebaceous glands, located next to a hair shaft ,forming the pilosebaceous unit.

7. Terms user in Dermatopathology
MACROSCOPIC TERMS
MICROSCOPIC TERMS

8. MACROSCOPIC TERMS Macule Papule Plaque Nodule Vesicle Bulla, blister
Scale

9. Macroscopic Terms
Macule: A circumscribed change in skin color without elevation or depression.

10. Papule : A solid elevated lesion usually 5 mm or less in diameter.

11. Plaque : A raised flat topped lesion that has a greater than 5 mm across.

12. Nodule: A palpable solid lesion of varying size, greater than 5 mm in diameter, which may be present in the epidermis, dermis or subcutis.

13. Vesicle: A circumscribed elevated lesion which contains free fluid
Vesicle: A circumscribed elevated lesion which contains free fluid. Vesicles are 5 mm or less in diameter.

14. Bulla ( blister ) more than 5mm across.

15. Scale: Dry , horny plate like excrescence[ due to imperfect cornification].

16. MICROSCOPIC TERMS Hyperkeratosis Parakeratosis Acanthosis Dyskeratosis
Papillomatosis
Spongiosis

17. Hyperkeratosis Hyperplasia of the stratum Corneum
Hyperkeratosis Hyperplasia of the stratum Corneum. Qualitative abnormality of keratin.

18. Parakeratosis Keratinization characterized by retention of the nuclei.

19. Acanthosis Epidermal hyperplasia

20. Dyskeratosis Abnormal Keratinization occurring prematurely.

21. LOSS OF INTERCELLULAR CONNECTION RESULTING IN LOSS OF COHESION.
Acantholysis
LOSS OF INTERCELLULAR CONNECTION RESULTING IN LOSS OF COHESION.

22. Papillomatosis. Hyperplasia of the papillary dermis with elongation of the dermal papilla.

23. Spongiosis Intracellular edema of the epidermis.

24. Topic Benign Pigmented Lesion
Benign and Premalignant Epithelial Lesions
Malignant disease of skin
Acute inflammatory Dermatosis
Chronic inflammatory dermatosis
Bullous Disease

25. Pigment disorder Vitiligo
Depigmented multiple patches on skin.Mo melanocytes in effected area.
Characterized by loss of melanocytes.
It has to be differentiated from albinism.
Melasma
Blotch of hyperpigmented patches on face.
OCP use.“ Musk of pregnancy”
Freckles
Light brown macule in face.
Sunlight ecposure.
Linear melanocytic hyperplasia.

26. Characterized by patchy loss Autoimmune
In albinism:
this is melanocyte but no melanin formation
Characterized by patchy loss
of melanocytes.
Autoimmune

27. Benign Pigmented Lesion
Nevocellular Nevus
Melanocytic nevi (aka, "moles") are pigmented, benign neoplasms composed of modified melanocytes (nevus cells); they may be congenital or acquired lesions.

28. These are benign nevi. Small brown flat to slightly raised nevi
These are benign nevi. Small brown flat to slightly raised nevi. They are usually less than a centimeter in diameter.
IT IS A CONGENITAL LESION

29. This is a larger flat 4 cm long pigmented nevus on the upper back
This is a larger flat 4 cm long pigmented nevus on the upper back. Such larger nevi are often congenital.

30. Nevocellular Nevus
Nests of small blue nevus cells.

31. Histologically : Compound and Junctional Nevus.
Compound Nevus
Definition: A type of mole formed by groups of nevus cells found in the epidermis and dermis . 
Junctional Nevus.
Definition: A mole found in the junction (border) between the epidermis and dermis layers of the skin.

32. Compound Nevus

33. Junctional Nevus.

34. Congenital nevus
A nevus present at birth, may be pre-malignant depending on the size of the lesion .

35. Blue nevus
Raised, bluish lesion on his upper back.

36. Blue nevus : contain spindle cells

37. Potential precursor to malignant melanoma often more than 5 mm across.
Dysplastic Nevus
Potential precursor to malignant melanoma often more than 5 mm across.

38. Dysplastic Nevus
Tendency to occur in sun exposed as well as non-sun exposed body surfaces.
Dysplastic nevi generally develop in early adolescence or adulthood, and are present in large numbers.
Can occur in multiple members of the family and prone to develop melanoma.
[ Heritable Melanoma Syndrome]

39. Benign and Premalignant Epithelial Lesions.
SEBORIC KERATOSIS
KERATOACANTHOMA
ACTINIC KERATOSIS

40. SEBORIC KERATOSIS : usually a benign and indolent neoplasm.
If occur suddenly and Multiple in number you should suspect an internal malignancy
[Paraneoplastic Syndrome]

41. SK's are common over the face, neck, and upper trunk
SK's are common over the face, neck, and upper trunk. They are raised, rough-surfaced and brown coin-like plaques.

42. Broad bands of normal-appearing epidermal cells have large keratin-filled "horn cysts" within them.

43. Neoplasm that mimics Well Differentiated Squamous Cell Carcinoma
KERATOACANTHOMA
Flesh Coloured dome shaped nodule , with a central keratin filled plug.
Site: check, ear, nose.
Neoplasm that mimics Well Differentiated Squamous Cell Carcinoma

44. Keratoacanthoma: Neoplasm that mimics Well Differentiated Squamous Cell Carcinoma: heals spontaneously

46. Less than 1 cm in diameter and sandpaper like consistency.
ACTINIC KERATOSIS
Less than 1 cm in diameter and sandpaper like consistency.
It a dysplastic change and damage in the skin following Chronic Sun Exposure. Seen in Sun Exposed areas.

47. A premalignant Condition.
Actinic Keratosis
A premalignant Condition.

48. Actinic Keratosis Hyperkeratosis (increased amount of keratin)
Parakeratosis (presence of cell nuclei in the keratin layer, this is a sign of decreased turnover time of the epidermis)
Dysplasia (abnormal maturation of the epidermis; the cells have atypical morphology cytologically)
Solar elastosis (in which the dermis is stained blue rather than pink resembling the elastic tissue; this is a sign of sun damage)

49. Biopsy of the skin showing Solar Elastosis [ pale blue colored area, beneath the epidermis]

50. Major factor : Ultraviolet ray B
Lesions due to Sun exposure : Malignancy
Malignant melanoma
Squamous Cell Carcinoma
Basal Cell carcinoma
Major factor : Ultraviolet ray B

51. Malignant Melanoma Skin, Oral, anogenital, esophagus, meninges.
Metastasis: Regional Lynph node, lung, liver , brain. It can occur even after the surgical removal of the tumor.

52. Malignant Melanoma
Warning signs are A,B,C,D,E's of a Pigmented lesion.
Asymmetry,
Irregular Border,
Variegated Color,
larger than 5mm Diameter,
Elevation.

53. Compare a benign nevus and a melanoma ( right).

54. This is the microscopic appearance of a malignant melanoma.

55. Description
Large polygonal cells (or spindle cells in some cases) have very pleomorphic nuclei which contain prominent nucleoli.
The neoplasm is making brown melanin pigment.

57. Vertical Growth Phase.
There is a worse prognosis because the dermal invasion is apt to be deep at the time of initial presentation of the patient - resulting in an increased risk of metastases.

58. The neoplastic cells shown here stain positively with HMB-45, suggesting that the primary neoplasm is a melanoma.

59. Squamous cell Carcinoma

60. Risk Factor for SCCA
Besides sun exposure, risk factors for squamous cell carcinoma arising in skin include carcinogens such as
Tars,
Chronic ulcers,
Burn scars,
Arsenic poisoning, and
Radiation exposure.
XERODERMA PIGMENTOSA

61. SCCA : It actually arose in a draining sinus tract from chronic osteomyelitis of the humerus.

62. The neoplastic cells extend downward into the dermis.

63. Basal cell Carcinoma Occur in case of immunodeficiency
Xeroderma Pigmentosa [ Defect in DNA repair ]

64. Pearly lesion and telangiectasia in the surface in BCC

65. Rodent Ulcer-Ulcerated BCC

66. BCCA
These rarely metastasize, but are slow-growing and progressive over time.
Early detection and excision is a must.
A BCC can grow quite large and invade surrounding tissues, but it virtually never metastasizes.

67. The cells of a basal cell carcinoma are dark blue and oblong with scant cytoplasm: Mimic cells of basal layer.

68. The typical nest has a palisaded arrangement of cells around the periphery.

69. Basal Cell Carcinoma( Biological Behavior)
These neoplasms can be multifocal. Metastases are quite rare.
SO, PROGNOSIS IS GOOD.

70. MOLECULAR GENETIC OF SKIN CANCER
Nevoid basal cell carcinoma syndrome
PTCH/PTCH gene
DNA repair defect
Multiple BCCA
Autosomal dominant
Cowden syndrome
PTEN, MMAC1
Tumor of skin appendage and adenocarcinoma
Xeroderma
Pigmentosa
XPA/XPA gene
Skin cancer (SCCA, BCCA)

71. MOLECULAR GENETIC OF SKIN CANCER
SCCA
Sporadic: No inheritances, DNA damage and Immunosuppression by sunlight.
Mutation of p53 in actinic Keratosis induced SCCA is noted.
Melanoma
Occur in familiar setting(10-15%), In dysplastic nevus syndrome-it is associated with deletion of p16INK4A gene.
p16INK4A =Cyclin-dependent kinase inhibitor 2

72. Acute inflammatory Dermatosis
Urticaria (hives)
Acute Eczematous Dermatitis

73. Urticaria (hives) Caused due to Local mast cell Degranulation.
Occur in the areas exposed to the pressure, trunk, distal extremities, ears. This lesion will fade normally if no such exposure occur further

74. What are responsible antigens ?
Pollen
Food
Drugs(opiates)
Insect venom
Drug rash due to Cephalosporin

75. Acute Eczematous Dermatitis
Papulovesicular , oozing and crusted lesion
Contact reaction
to poison ivy,
laundry detergent.

76. This is contact dermatitis, a form of type IV hypersensitivity reaction that is localized.
Other forms: Atopic and Drug (penicillin) related dermatitis.

77. Histology: Dermatitis
Spongiosis (edema) of epidermis.

78. Erythema Multiforme
The classic "target" lesion has a central vesicle surrounded by a zone of erythema.

79. Erythema Multiforme
These lesions are "multiform" because macules, papules, vesicles, and bullae may be seen grossly.
Sites : Lip, oral cavity, conjunctiva, urethra, anogenital Region.

80. Erythema Multiforme Etiology: A hypersensitivity reaction to
Infection,
Drugs,
Neoplasia, or
Collagen vascular diseases.

81. Erythema Multiforme Infection: Mycoplasma, leprosy, Typhoid
Drug: sulphonamide, barbiturate, salicylates
Malignancy: Carcinoma and lymphoma
Collagen disorder: Lupus erythematous.

82. Chronic inflammatory dermatosis
Psoriasis
Lichen Planus

83. Lichen Planus : p3 Pruritic, purple, polygonal papules.
White lines: Wickham Striae

84. Civatte Body in Lichen Planus and sawtoothing of epidermis
It is an anucleated necrotic Basal cells.

85. Psoriasis

86. Psoriasis : It is a common Inflammatory Dermatosis.
This is psoriasis. The thick, silvery, scaling lesions are most often found over bony prominences, scalp, genitalia, and hands.

87. Psoriasis
It occurs when there is abnormal proliferation of epithelial cells.
Sensitize T cell mediated tissue damage.
It will bleed if you scraped off this!- auspitz sign.

88. Nail Change : Onycholysis
The scalp, elbows, and knees are the most common sites for psoriasis

89. Psoriasis Psoriasis is an autoimmune disease.
Genetic and immune factors involved.

90. Munro microabscess
Munro microabscess. Important microscopic features.

91. Bullous Disease Secondary phenomenon of infections , dermatitis.
Bulla ( blister ) more than 5mm across.

92. Subcorneal Bulla

93. Supra basal Bulla

94. Subepidermal Bulla

95. Pemphigus Rare autoimmune blistering disorder
( Type II hypersensitivity reaction)
Age : middle age
Sex : Women : Men :: 1:1
Cause of Bulla formation : Acantholysis.
Type of Bulla: Supra basal Bulla.

96. Site: Scalp, face, axilla and also in the point of pressure.
Pemphigus
Pemphigus vulgaris [ most common]
Site: Scalp, face, axilla and also in the point of pressure.

97. Pemphigus vulgaris [ bulla rupture easily and will be covered by dried serum and crust.]

98. Pemphigus vulgaris [ Suparabasal bulla ]

99. Deposition of IgG and Complement along the cell membrane, giving a Fish Net appearance.

100. Pemphigus vulgaris
Sera of the patient contains IgG antibody to desmogleins [ intercellular cement substance] .

101. Bullous pemphigoid.
Seen in adult
Do not rupture easily unlike pemphigus
Heal without scarring.
The target antigen is hemidesmosome. Autoantibody produces against this protein.

102. There is a large, tense bulla at the center and a small bulla at the left.

103. Sites : Inner aspect of thigh, forearm axilla, groin and Mucosa

104. Bullous pemphigoid : Subepidermal Bulla

105. IgG and complement staining pattern in Bullous pemphigoid
IgG and complement staining pattern in Bullous pemphigoid. [ Linear Deposit ]

106. Dermatitis herpetiformis
Urticaria and grouped (herpetiform vesicles.

107. Site; extensor surface elbow, knees upper back.

108. Dermatitis herpetiformis : Subepidermal Blisters
It can occur in association to intestinal celiac disease and respond to a gluten free diet.

109. The inflammatory cells within the vesicle are PMN's
The inflammatory cells within the vesicle are PMN's. Slight basophilia is seen in the partly necrotic dermal papilla.

110. IgA granular basement membrane zone with stippling in dermal papillae (40x)

111. Kaposi's sarcoma
Late Lesion Early lesion

112. The lesions can start as small reddish to red-purple plaques or patches. Over time, the lesions become nodular and larger and more numerous. If the HIV test is positive, then KS is diagnostic of AIDS

114. End of Dermatopathology
Thank You .