Arya. Skin Path Lab
Transcript of Arya. Skin Path Lab
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Skin Pathology – Laboratory
Dr. Savita Arya MD, DPB, MBBS
Associate Professor, Pathology, Ross University School of Medicine
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CASE HISTORY
• A 35-year-old woman has 17 pale tan-to dark brown lesions on her torso and upper extremities. They range from macules to small papules 2-6 mm in diameter. They have smooth borders and uniform pigmentation. The microscopic appearance of one of the lesions is shown. What is your diagnosis? Intradermal Nevus
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Dysplastic nevus
• Gross– Pigmented macule with variable pigmentation
and irregular borders
• Biopsy– Melanocytic proliferation with mild architectural
and cytologic atypia– Lamellar fibrosis
• Features– Larger than most acquired nevi– In non-sun-exposed areas– Risk of developing malignant melanoma– Dysplastic nevus syndrome
• Autosomal dominant condition• >100 nevi• Mutated CDKN2A gene
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CASE HISTORY
• A 51-year-old man sees his physician because of growth and change in color of an abdominal mole that, according to his statement, has been present since his birth. The mole has always had an oval shape with even, brown pigmentation.
• Recently, the patient noticed changes at the edge of the mole. The shape has become irregular, and some areas show dark discoloration. He denies pain or itching. This is the first time that he has seen a physician for this type of complaint.
• He has no family history of malignant melanoma.
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Clinical presentation
Lesion is irregular in pigmentation and contour, and very suspicious for a malignant melanoma.
D.D. Pigmented lesion1. Melanocytic lesions -
Melanocytic nevi, Dysplastic nevi, Malignant melanoma
2. Non-melanocytic lesions – Seborrheic keratosis, Basal cell carcinoma, Hemangioma, Kaposi sarcoma
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Skin biopsy
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Skin, malignant melanoma – High power
Hyper-chromatic and pleomorphic polygonal and spindle cells; nucleoli prominent; Cytoplasmic melanin granules may be seen
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Superficial spreading type Nodular melanoma
When the melanoma begins the vertical growth phase, metastases are more likely to occur.
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• Major risk factor– Exposure to uv light (UVB), inducing pyrimidine dimers
• Molecular alteration– Familial melanoma – Deletion of P16/INK4a gene encoding for
CDKN2 – Mutations involving CDK4 and BRAF genes
• Prognosis– Depends particularly on depth of invasion
• Lesions <0.75 mm deep– Good prognosis (>95% 5-yr survival)• Lesions > 0.75 mm deep– Poor prognosis (<50% 5-yr survival)
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CASE HISTORY
• A 55-year-old man sees his physician because of a firm, light brown papule on his back. The lesion is round, has a diameter of 14 mm, and a surface 3 mm above the surrounding skin level. The patient worries that he might have a malignant melanoma. There is no bleeding, itching, or pain.
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• Are these lesions benign or malignant? Malignant
• What would the appearance of many lesions suggest in a patient with an underlying malignancy?– Sign of Leser-Trélat
• Occurrence of multiple seborrheic keratoses over a short time
• Paraneoplastic syndrome
– Production of TGF-α by malignant cells.
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Low-power magnification - Thickened epidermis, elevating the lesion above surrounding skin
Thickened (acanthotic) epidermis composed of epithelial cells with scant cytoplasm resembling immature squamous cells of epidermal basal layer (basaloid cells). Small cyst-like structures containing lamellated pink keratin present within this proliferation (pseudohorn cysts).
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CASE HISTORY• A 67-year-old man comes to the outpatient clinic with a lesion on his left cheek. The nodular
lesion measures 12 mm in widest diameter and has a pearly color with clearly visible blood vessels and a small crust on top of it. It has been present for 3 months, and, despite the use of ointments prescribed by the patient's family physician, it has not disappeared. Nearly every morning while the patient is washing his face, the crust comes off and the lesion starts bleeding.
• Basal Cell carcinoma!
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The tumor is composed of basaloid cells. The cells forming the periphery of the tumor nodules tend to be arranged radially with their long axes in parallel alignment (palisading). A large cleft is visible
• The family physician finally sends the patient to see a dermatologist with this question: Is this non-resolving lesion a form of skin cancer? The dermatologist suspects basal cell carcinoma and takes a small biopsy specimen from the edge of the lesion. The biopsy results confirm the diagnosis, and the patient subsequently undergoes definitive therapy
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Solitary, 5 mm pearly pink papule with telangiectasias
Rounded nests of“basaloid” cells
Peripheral palisading
Cleft formation
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What are the risks of developing basal cell carcinomas?
• Lightly pigmented individuals with sun-damaged skin
• Immunosuppressed patients
• Inherited defects in DNA nucleotide excision repair (NER) pathway– Xeroderma pigmentosum
• Patients with Nevoid basal cell carcinoma syndrome – Gorlin syndrome – Germline mutation of
PTCH gene, which normally inactivates SMO transmembrane protein upregulating transcription factors
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Actinic Keratosis- precursor for cancer
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A
A
B
A. Cutaneous horn. B. Sandpaper-like plaques. C. Basal cell layer atypia with hyperkeratosis and parakeratosis. C
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Describe the histologic findings
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Small proliferative buds of cytologically atypical keratinocytes
Solarelastosis
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Parakeratosis
Solarelastosis
Atypical keratinocytes
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Scalp, squamous cell carcinoma – Clinical presentation
• Large actinic keratosis on the balding scalp of an elderly man.
• In the center, a non-healing ulcer is present consistent with superimposed squamous cell carcinoma.
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Skin, squamous cell carcinoma – Medium power
• Atypical squamous epithelial proliferation in the dermis surrounded by a lymphocytic infiltrate consistent with well-differentiated squamous cell carcinoma
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• Risk factors for squamous cell carcinoma– Sun exposure – Immuno-compromised (eg. transplant recipients)– Xeroderma pigmentosum – Multiple skin tumors;
mutation in DNA nucleotide excision repair (NER) genes
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CASE HISTORY
• A 55-year-old man requests removal of multiple skin tags around his neck. He is overweight and has diabetes and acanthosis nigricans. While some of his skin tags occasionally get caught on his clothing, he just doesn't like the way they look
Many skin tags and acanthosis nigricans on the neck of a man with diabetes
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• Skin tags, on histology, are characterized by acanthotic, flattened, or frond-like epithelium.
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Case History
• A 30-yr-old woman with recent onset of red, oozing area shown reports that by week’s end it has evolved to raised, scaling plaques.
• What is your diagnosis?
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• Eczema– General term for the acute appearance of red, oozing and
crusted lesions that in time become scaling plaques.
• Possible causes– Contact dermatitis– Atopic dermatitis– Insect bite– Drug reaction– Chemical exposure– Photosensitivity
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CASE HISTORY
• History of recent hike with some friends in a local wilderness area. The trail was quite overgrown.
• Poison ivy (Contact dermatitis)
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CASE HISTORY
• A 42-year-old man presents with an intensely itchy and blistering rash. Symptoms began one day before. The rash extends over his arms, hands, chest and face. The lesions are red and vesicular.
• On further discussion, the patient states that he has experiences these symptoms many times in the past, and attributes the rash to contact with poison ivy.
• The patient had been doing yard work the day prior to the onset of symptoms.
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Microscopic features of the rash
Allergic contact dermatitis (secondary to poison ivy exposure) • Epidermis
– Spongiosis– Lymphocytes
• Spongiotic vesicle
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CASE HISTORY
• A 25-year-old woman prescribed carbamazepine for a seizure disorder develops a papulo-vesicular skin rash with the microscopic appearance shown.
• What is the general term for the histologic appearance?
ACUTE ECZEMATOUS DERMATITIS
Epidermis shows marked edema with spongiosis
Spongiotic vesicles are filled with fluid
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CASE HISTORY
• An 18-year-old man visited the dermatologist after developing itchy, scaly, red papules on the skin of his elbows, scalp, and knees over several months. When the scale was lifted from one of the plaques, multiple minute bleeding points became visible.
Skin shows typical well-demarcated plaques covered by silver-white scales.
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Elongated rete ridgesParakeratotic scaleSuperficial perivascular infiltrate
Micro-abscess of neutrophils within parakeratosis
Biopsy performed at the edge of one of the lesions
confirmed the clinical impression.
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• Risk factors for psoriasis– Skin trauma (Koebner phenomenon)– Emotional stress, cigarette smoking, alcohol
consumption, drugs (NSAIDs)
• Associated nail changes– Yellow brown discoloration with pitting– Separation of nail plate (onycholysis)
• Associated joint disease– Psoriatic arthritis – distal inter-phalangeal
joints of hand and feet involved (similar to RA)
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Psoriasis
1. Parakeratosis2. Thin granular layer3. Thin supra-papillary
epidermis4. Elongated rete ridges
(acanthosis)5. Blood vessels in papillary
dermis6. Inflammation
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Psoriasis
Munro micro-abscesses
Neutrophil aggregates in epidermis
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• Salient histological features– Acanthosis with thinning of stratum granulsoum– Parakeratotic scale– Downward elongation of rete ridges– Dilated vessels in dermal papillae
• What is the pathogenesis?– TH1 immune response – Autoimmune reaction of Langerhans cells and CD4+ cells with
activation of CD8+ cells and release of cytokines like TNF– Increased rate of keratinocyte replication
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• Clinical course– Therapy resulted in partial remission of patient's
symptoms. – In the following years, the patient developed
involvement at other sites including the abdomen and inter-gluteal cleft.
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CASE HISTORY
• A 37-year-old woman presents with an itchy rash on her elbows and back since the last few months. Her mother has a history of similar lesions as well as a history of arthritis.
• On examination, the patient has a 4-cm sharply demarcated plaque on her left elbow. The lesion is scaly and has a silver sheen. A biopsy is performed.
MUNRO’S MICRO-ABSCESS
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CASE HISTORY
• A 35-year-old woman who recently returned from Africa presents to the clinic with complaints of a rash. During her trip, she developed an itchy rash on both arms. She has an unremarkable medical history. Medications recently taken include chloroquine for malaria prophylaxis. Examination discloses multiple small violaceous papules on the flexor surfaces of the arms. The lesions have angular borders and flat tops. Some of the lesions have minute white streaks on surface, barely visible to the naked eye.
Flat-topped papulesConfluent papulesLichen planus presents with pruritic, purple, polygonal papules
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• Elevated flat-topped appearance of papule– Dense array of lymphocytes in
superficial dermis
• Wickham’s striae – Whitish discoloration– Chronic inflammation and
hyperkeratosis of cornified layer of epidermis
• Biopsy– Mainly lymphocytic inflammatory
infiltrate with hyperkeratosis, increased granular layer and liquefaction of basal cell layer
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1. Thicker granular layer2. Acanthosis3. Saw-tooth rete ridges4. Lymphoid infiltrate of
papillary dermis
Civatte Bodies
12 3
4
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CASE HISTORY
• A 35-year-old man treated with cephalosporin for an URTI develops the lesions shown over the extensor surfaces of his extremities, palms, neck and face. They subside in 3 weeks. What is your diagnosis?
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• Erythema multiforme– Classic targetoid lesions – central pale vesicle surrounded by a zone of erythema.– Macules, papules, vesicles, and bullae.
• What is the immunological basis for this condition?– Delayed type hypersensitivity reaction typically against an agent that haptenates
self proteins and elicits an inflammatory response
• What can precede the development of these lesions?– Herpes simplex infection– Mycoplasma, many bacteria and fungi– Drugs – Antibiotics, anticonvulsants, antipyretics, and anti-tuberculous agents– Underlying carcinoma or lymphoma– Collagen vascular disease - SLE
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CASE HISTORY
• A 47-year-old woman treated with sulfonamide for a fever and sore throat develops symmetric erythematous skin lesions on her face and torso 2 days later, which progress to flaccid bullae that slough. Biopsy is shown below.
• What is your diagnosis?
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• TEN– Necrosis of epidermal keratinocytes– Separation of epidermis at DEJ– Most severe variant of EM– Usually associated with prior drug therapy Mortality rate – up to 40%
• Steven Johnson syndrome– Mucosal involvement (Oral cavity, conjunctiva, urethra,
genital and perianal regions– Mortality rate – 5%
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CASE HISTORY
• A 62-year-old man visits his physician with painful lesions on his soft palate. On inspection, there are multiple red areas of ulceration. The oral lesions prevented the patient from eating normally. A mouthwash is initially prescribed. The lesions do not disappear, and after a few weeks, round to oval vesicles and bullae also appear scattered on the patient's face, chest, and groin.
Axilla shows large areas of ulceration. On the inner side of upper arm, few intact blisters are visible
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• A biopsy is performed• Immunofluorescence shows immunoglobulin deposition along cell
membranes of epidermal keratinocytes in a fishnet-like pattern. • Patient is subsequently treated with a combination of corticosteroids
and azathioprine resulting in disappearance of his skin lesions.
Blister roofBlister baseAcantholytic cellsRow of tombstone
Fish netlike pattern
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• What does the autoantibody in this disease recognize?– Desmoglein 3 (component of desmosomes that hold
keratinocytes together in stratum spinosum
• How do blisters form?– Bound antibody on the surface of keratinocytes activates
them to release a urokinase-like plasminogen activator (serine protease) that degrades desmosome junctions
– Epidermal cells lose adhesion --- acantholysis– Blister is formed above the basal layer
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CASE HISTORY
• An 80-year-old man presents with recent onset of blisters on his legs and arms.
• Physical examination - Large, tense blisters on medial thighs and flexor aspect of forearm.
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Microscopy
• Blister– Sub-epidermal– Roof – Intact, entire epidermis (including
stratum basalis)– Content- Inflammatory cells, fibrin, fluid
• Edematous papillary dermis
Direct Immunofluorescence
• Linear deposition of IgG along dermo-epidermal junction
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• What is the immune mechanism involved?– IgG autoantibodies are directed against
hemidesmosome proteins at the DEJ (eg. BPAg2 – type XVII collagen, a transmembranous protein with a collagenous extracellular domain)
• How do the bullae form?– Immune-mediated BM damage (via complement
activation and through the activity of Fc receptor-bearing inflammatory cells) leads to hemidesmosome degradation and subepidermal separation.
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THANK YOU!References
• Kumar: Robbins and Cotran Pathologic Basis of Disease, 8th ed., Elselvier Saunders Company, 2010
• Rubin R, Strayer DS. Rubin’s Pathology: Clinico-pathologic Foundations of Medicine, 5th edition, Lippincott Williams & Wilkins, 2008
• Webpath.: The Internet Pathology Laboratory for Pathology Education.