Pathology of Skin - Common Disorders

Pathology of Skin - Common Disorders “ Life’s battles don’t go always to the stronger or faster man, sooner or later, the man who wins is the man who thinks he can ” Aim for the Moon… even if you miss, you will land among Stars…..!

3. DERMATOPATHOLOGY Acute, Chronic, Infections, Blistering, Neoplastic Dr. Shashi dhar Venkatesh Murthy Associate Prof. & Head of Pathology

4. Dermatopathology: MD3020 curriculum <ul><li>Acute Inflammations: </li></ul><ul><ul><li>Urticaria, </li></ul></ul><ul><ul><li>Acute Eczema, </li></ul></ul><ul><ul><li>Erythema Multiforme. </li></ul></ul><ul><li>Chronic Inflammations: </li></ul><ul><ul><li>Psoriasis, </li></ul></ul><ul><ul><li>Chronic Eczema, </li></ul></ul><ul><ul><li>Lichen planus. </li></ul></ul><ul><li>Infections </li></ul><ul><ul><li>Bacterial (Impetigo), </li></ul></ul><ul><ul><li>Fungal(tinea) & </li></ul></ul><ul><ul><li>Viral(warts). </li></ul></ul><ul><li>Blistering Diseases </li></ul><ul><ul><li>Pemphigus, </li></ul></ul><ul><ul><li>Pemphigoid, </li></ul></ul><ul><ul><li>Dermatitis herpetiformis. </li></ul></ul><ul><li>5. Neoplastic: </li></ul><ul><li>Benign: </li></ul><ul><ul><li>Nevi, </li></ul></ul><ul><ul><li>Actinic Keratosis, </li></ul></ul><ul><ul><li>Seborrheic Keratosis. </li></ul></ul><ul><li>Malignant: </li></ul><ul><ul><li>BCC, SCC, Melanoma. </li></ul></ul>

5. Normal Skin: (Thin)

6. Thick Skin: Prominent granular layer

7. Dermatopathology: MD3020 curriculum <ul><li>Acute Inflammations: </li></ul><ul><ul><li>Urticaria, </li></ul></ul><ul><ul><li>Acute Eczema, </li></ul></ul><ul><ul><li>Erythema Multiforme. </li></ul></ul><ul><li>Chronic Inflammations: </li></ul><ul><ul><li>Psoriasis, </li></ul></ul><ul><ul><li>Chronic Eczema, </li></ul></ul><ul><ul><li>Lichen planus. </li></ul></ul><ul><li>Infections </li></ul><ul><ul><li>Bacterial (Impetigo), </li></ul></ul><ul><ul><li>Fungal(tinea) & </li></ul></ul><ul><ul><li>Viral(warts). </li></ul></ul><ul><li>Blistering Diseases </li></ul><ul><ul><li>Pemphigus, </li></ul></ul><ul><ul><li>Pemphigoid, </li></ul></ul><ul><ul><li>Dermatitis herpetiformis. </li></ul></ul><ul><li>5. Neoplastic: </li></ul><ul><li>Benign: </li></ul><ul><ul><li>Nevi, </li></ul></ul><ul><ul><li>Actinic Keratosis, </li></ul></ul><ul><ul><li>Seborrheic Keratosis. </li></ul></ul><ul><li>Malignant: </li></ul><ul><ul><li>BCC, SCC, Melanoma. </li></ul></ul>

8. INFLAMMATORY disorders: Pathogenesis <ul><li>Urticaria Acute Chronic Lichen </li></ul><ul><li>Eczema Eczema Sclerosis </li></ul><ul><li>Dermal Infl Epidermal Infl Hyperplasia Hyperkeratosis </li></ul>Acute Inflam. Chronic Inflam. Ep. Hyperplasia

9. URTICARIA (Hives) <ul><li>Type I hypersensitivity – Allergy </li></ul><ul><li>All ages, more in 20 – 40y. </li></ul><ul><li>Erythematous papules and plaques </li></ul><ul><li>Individual lesions are transient, usually resolve in 24 hr, but entire episode may last for days. </li></ul><ul><li>Usually on trunk and extremities. </li></ul>

10. Urticaria (Hives)

11. URTICARIA – Histopathology Perivascular inflammatory infiltrate: lymphocytes, neutrophils, eosinophils. * Note lack of spongiosis or other epidermal changes.

12. URTICARIA (Hives) <ul><li>Follows exposure to pollens, foods, drugs, pressure, temperature etc. </li></ul><ul><li>Ag  IgE  Mast cell Degranulation  Inflam. </li></ul><ul><li>perivascular inflammatory infiltrate: lymphocytes, neutrophils or eosinophils. </li></ul><ul><li>Hereditary angioneurotic edema  Congenital C1 esterase inhibitor deficiency causes uncontrolled complement activation and urticaria. </li></ul>

13. Urticaria – Microscopic features <ul><li>Superficial dermal edema (space between collagen) </li></ul><ul><li>Dilated blood vessels with perivascular inflammatory cells. </li></ul><ul><li>Normal Epidermis (no spongiosis or hyperplasia) </li></ul>1 3 2

14. Acute ECZEMA – Types <ul><li>Contact dermatitis </li></ul><ul><li>Atopic dermatitis </li></ul><ul><li>Drug eczema </li></ul><ul><li>Photoeczema </li></ul><ul><li>Primary irritant dermatitis </li></ul>Intraepidermal edema & blister

15. ECZEMA dry - (atopic)

16. My ear is dripping on my shirt…! <ul><li>A 36y Male, 12wk rash left ear. </li></ul><ul><li>Spreading and becoming increasingly irritating despite twice daily applications of Kenacomb Otic ointment. </li></ul><ul><li>he is otherwise in good health, with no history of serious illness, and there are no known allergies nor rashes anywhere else. </li></ul><ul><li>DD: contact dermatitis, fungal infection (Tinea), Imeptigo (bact), others. </li></ul>Drug induced Eczema

17. ECZEMA – histology <ul><li>Spongiosis (Intraepidermal) edema </li></ul><ul><li>Superficial perivascular lymphocytic infiltrate </li></ul>

18. ECZEMA – pathogenesis: <ul><li>Hypersensitivity Reaction: </li></ul><ul><li>Initial exposure to antigen: </li></ul><ul><ul><li>Antigen processed by Langerhans cells and presented to T cells in the lymph node  T cell activation  memory cells. </li></ul></ul><ul><li>Re-exposure to antigen: </li></ul><ul><ul><li>Quick (memory T cells) response  inflammation  urticaria, erythema, wet eczema </li></ul></ul><ul><li>Persistence of antigen stimulation: </li></ul><ul><ul><li>Chronic inflammation  Acanthosis, hyperkeratosis (lichenification) – dry eczema. </li></ul></ul>

19. ECZEMA (irritant)

20. ECZEMA (contact dermatitis)

21. ERYTHEMA MULTIFORME: <ul><li>Self limited Hypersensitivity response to, </li></ul><ul><ul><li>Infections : herpes simplex, Mycoplasma </li></ul></ul><ul><ul><li>Drugs : sulfonamides, penicillin barbiturates </li></ul></ul><ul><ul><li>Malignancy : carcinoma, lymphoma </li></ul></ul><ul><ul><li>Auto Immune dis: SLE, SS, dermatomyositis </li></ul></ul><ul><li>Multiple forms - papules, plaques, nodules, blisters, ulcers etc.. </li></ul><ul><li>Characteristic “targetoid” lesions. </li></ul><ul><ul><li>Central grey necrosis, Erythematous raised border. </li></ul></ul><ul><li>Mild to severe forms – spectrum </li></ul><ul><li>EM Minor, EM Major, Stevens-Johnsons syndrome and toxic epidermal necrolysis. </li></ul>

22. ERYTHEMA MULTIFORME Target Lesions

23. ERYTHEMA MULTIFORME - Microscopy <ul><li>Necrotic keratinocytes </li></ul><ul><li>Spongiosis (edema) </li></ul><ul><li>Epidermal lymphocytes </li></ul><ul><li>Superficial perivascular lymphocytes </li></ul>Note: destruction of basal epidermal layer.

24. Stevens-Johnson Sy. (EM major) <ul><li>A 2y black male, who was started on Phenobarbital after his third febrile seizure. Seven days later, he developed erythematous lesions over his extremities, hands, face and trunk with high fever. Bullae, Erosion and crusting of mucosal surfaces. </li></ul><ul><li>May be caused by other drugs, infections, histology same as EM. </li></ul>

25. Toxic Epidermal Necrolysis (TENs): <ul><li>Larger body surface involvement (>40%) </li></ul><ul><li>Development of bullae & peeling of epidermis in sheets >3 cm & the skin becomes tender within 48 hours. </li></ul><ul><li>Extensive basal layer degeneration. </li></ul><ul><li>Serious complication of EM Major & TENs is conjunctival damage resulting in corneal drying and opacification (blindness). </li></ul>

26. "The gem cannot be polished without friction, nor man perfected without trials or problems (or exams) …!." --Chinese proverb

27. Dermatopathology: MD3020 curriculum <ul><li>Acute Inflammations: </li></ul><ul><ul><li>Urticaria, </li></ul></ul><ul><ul><li>Acute Eczema, </li></ul></ul><ul><ul><li>Erythema Multiforme. </li></ul></ul><ul><li>Chronic Inflammations: </li></ul><ul><ul><li>Chronic Eczema, </li></ul></ul><ul><ul><li>Psoriasis, </li></ul></ul><ul><ul><li>Lichen planus. </li></ul></ul><ul><li>Infections </li></ul><ul><ul><li>Bacterial (Impetigo), </li></ul></ul><ul><ul><li>Fungal(tinea) & </li></ul></ul><ul><ul><li>Viral(warts). </li></ul></ul><ul><li>Blistering Diseases </li></ul><ul><ul><li>Pemphigus, </li></ul></ul><ul><ul><li>Pemphigoid, </li></ul></ul><ul><ul><li>Dermatitis herpetiformis. </li></ul></ul><ul><li>5. Neoplastic: </li></ul><ul><li>Benign: </li></ul><ul><ul><li>Nevi, </li></ul></ul><ul><ul><li>Actinic Keratosis, </li></ul></ul><ul><ul><li>Seborrheic Keratosis. </li></ul></ul><ul><li>Malignant: </li></ul><ul><ul><li>BCC, SCC, Melanoma. </li></ul></ul>

28. PSORIASIS - pathophysiology <ul><li>Multifactorial: genetic and immune </li></ul><ul><li>strong association HLA-C (w⋆0602 allele) </li></ul><ul><li>Sensitized T cells infiltrate the skin and secrete cytokines and growth factors </li></ul><ul><ul><li>Inflammation, Increased cell turnover </li></ul></ul><ul><ul><li>Vascular proliferation angiogenesis </li></ul></ul><ul><ul><li>Trauma precipitates lesions – Koebner phen. </li></ul></ul><ul><li>Multi system disorder: </li></ul><ul><ul><li>Arthritis, myopathy, enteropathy, Immunodef. </li></ul></ul>

29. PSORIASIS - clinical <ul><li>Chronic, recurrent elbows, knee, scalp </li></ul><ul><li>well-demarcated, pink plaque covered with loosely adherent silvery scales. </li></ul><ul><li>Removal of scales  point bleeds – Auspitz sign. </li></ul>

30. PSORIASIS <ul><li>CLINICAL: </li></ul><ul><li>Pink Plaques </li></ul><ul><li>Silvery scales. </li></ul><ul><li>Koebner Phenomenon </li></ul><ul><li>Auspitz sign </li></ul><ul><li>Arthritis. </li></ul>

31. PSORIASIS – Nail changes <ul><li>“ Oil-slick” nail discoloration </li></ul><ul><li>Nail pitting </li></ul><ul><li>Onycholysis </li></ul>

32. PSORIASIS – Arthritis.

33. Psoriasis: Histopathology Acanthosis, Parakeratosis, neutrophilic microabscesses.

34. PSORIASIS - histology Parakeratosis Diminished granular layer Regular elongation of the rete ridges Tortuous papillary dermal vessels neutrophil abscess in epidermis

35. Lichen Planus: <ul><li>Pruritic, Purple, Polygonal, Planar, Papules and Plaques. </li></ul><ul><li>Skin & mucosa. Genitals, oral, </li></ul><ul><li>Self limited. 1-2 years. </li></ul><ul><li>Basal layer, Interface dermatitis. </li></ul><ul><li>Degenration, Squamatization </li></ul><ul><li>Anucleate dead epidermal cells in basal layer – Civatte bodies. </li></ul><ul><li>Similar to EM but chronic with hyperplasia, hyperkeratosis(scaling). </li></ul>

36. Lichen Planus: Mucosal involvement

38. Impetigo: Bacterial Infection <ul><li>Staph or Strep </li></ul><ul><li>Superficial, Bacterial </li></ul><ul><li>Oozing & crusting. </li></ul><ul><li>Spongiosis </li></ul><ul><li>Neutrophils. </li></ul>

39. Impetigo: Epithelium Ulcer + Inflam

40. Acne: Pathogenesis <ul><li>Inflammation of pilosebaceous units </li></ul><ul><li>Interplay of four factors </li></ul><ul><li>Excessive sebum - sebaceous gland hyperplasia </li></ul><ul><li>Hyperkeratinization – Microcomedo - Obstruct pores. </li></ul><ul><li>Lipids and cellular debris accumulate within the blocked follicle. </li></ul><ul><li>Colonization of Propionibacterium acnes (+ secondary infection) </li></ul><ul><li>Inflammation is further enhanced by follicular rupture and subsequent leakage of lipids, bacteria, and fatty acids into the dermis. </li></ul>

41. Acne: Hair fol. infection: Neutrophil Abscess Hair Follicle (infected) Hair Follicle (infected) Block  sebum  infection Harmonal, excess/drying/oily Comedo

42. Bacterial Skin Infections: Types

43. Viral Infections: <ul><li>Human papillomavirus: Warts (verrucae) </li></ul><ul><ul><li>Keratotic(hard) & condyloma (fleshy) </li></ul></ul><ul><li>Molluscum contagiosum: </li></ul><ul><li>Herpes – Zoster & Shingles. </li></ul><ul><li>HIV – Kaposi sarcoma (HHV 8) </li></ul>

44. Verruca Plana: <ul><li>HPV-3 or 10 </li></ul><ul><li>Face, young, flat </li></ul><ul><li>Small, hyperkeratotic </li></ul><ul><li>Koilocytic keratinocytes. </li></ul>

45. Palmoplantar warts: Myrmecia <ul><li>HPV-3 or 10 </li></ul><ul><li>Sole & Palms </li></ul><ul><li>Intradermal hard cyst. </li></ul><ul><li>Inward growth </li></ul><ul><li>Koilocytic keratinocytes. </li></ul>

46. Condyloma accuminatum: <ul><li>HPV-6, Genital warts </li></ul><ul><li>Fleshy growths </li></ul><ul><li>Acanthosis, papillomatosis </li></ul><ul><li>Koilocytes- perinuclear halo. – viral inclusions. </li></ul>Pap Smear Cervical Biopsy

47. Molluscum contagiosum: <ul><li>DNA pox virus </li></ul><ul><li>Grouped pearly hypopigmented flask like papules with central cupped scaly centre (arrow A). </li></ul><ul><li>Pink cytoplasmic viral inclusions “Molluscum body” (arrow B) </li></ul>B A

48. Fungal: Tineasis <ul><li>Ring worm, Round, scaly, itchy dermatitis – Trichophyton sp </li></ul><ul><li>Spreading out with Central clearing. </li></ul><ul><li>Lab: Scrapings in KOH solution </li></ul><ul><li>Tinea cruris. </li></ul><ul><li>Tinea capitis </li></ul><ul><li>Tinea versicolor – pale macules – </li></ul><ul><li>Pityrosporum . </li></ul>Fungus Fungus

49. Case Study: Painful, Itchy vesicles: <ul><li>A 32y man, itchy and painful rash on the back of his left leg </li></ul><ul><li>About 7 days ago, he began to feel an “ intense itching & burning pain ” behind his left knee. </li></ul><ul><li>“ small blisters” began to “pop up” over the area. </li></ul><ul><li>Not responding to antibiotic ointment and acetaminophen (Tylenol). </li></ul><ul><li>? likely diagnosis? </li></ul>*Intense, burning pain & blisters along nerve distribution Cutaneous Herpes - Shingles.

50. “ The worst thing in your life may contain seeds of the best. When you can see crisis as an opportunity, your life becomes not only easier, but more satisfying.” –Joe Kogel

Pathology of Skin - Common Disorders