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DERMATOPATHOLOGY: LECTURE 1 Cutaneous Tumors Normal Histology:

Mon. 09/13/10

3 main layers. Hair follicles, sebaceous glands, etc. within.

Many tumors originate from epidermis probably because it is the most superficial. Stratum corneum is outermost layer. Site of keratinocytes being continuously sloughed off keratinocytes have lost nuclei. S. granulosum cells are identifiable by bluish granules in the cytoplasm. S. spinosum can see web-like connections. Lamina densa = basement membrane. Attaches epidermis to dermis. Merkel cell involved in mediating reception of light touch. Melanocytes have dendritic processes. Melanin is involved in protecting keratinocyte DNA from damage. Parakeratosis Acanthosis

Definitions: Hyperkeratosis

Increase in stratum corneum (scale)

Abnormal keratinization characterized by retained nuclei in stratum corneum (scale)

Thickened epidermis

Papillomatosis
Acanthosis w/upward projections (wart; seborrheic keratosis)

Dysplasia
Cytologic atypia: 1) Variation in size and shape of nucleus (nuclear pleomorphism) 2) Variation in staining (hyperchromatism) 3) Increased and abnormal mitotic figures (cancer; precancer)

Solar Elastosis

Bluish discoloration of collagen in the dermis. Cutaneous Tumors Epithelial Epidermal tumors Adnexal tumors Melanocytic Nevi Melanoma Mesenchymal from fibroblasts in the dermis. Dermatofibroma benign. Dermatofibrosarcoma protuberans (DFSP) malignant. Hematopoietic Mycosis fungoides Langerhans cell histiocytosis Mastocytosis tumor of mast cells Seborrheic Keratosis Common Occur >30 years Trunk/face Rarely as paraneoplastic syndrome w/an internal malignancy. Sign of Leser-Trelat Papules raised. Smooth, rough, or greasy surface Light to dark brown Stuck on appearance People often scratch them off. Hyperkeratosis increased s. corneum Acanthosis (bland keratinocytes) Epidermal invaginations; keratin-filled pseudo-cysts
Test q: A 45y/o male develops multiple seborrheic keratosis over a period of a few months. He is diagnosed w/Leser-Trelat syndrome which is associated with: internal malignancy. Test q: A 56y/o farmer presents w/numerous macules and papules on his face. Biopsy shows hyperkeratosis, parakeratosis, and dysplasia in the lower dermis. Diagnosis: Seborrheic keratosis

Epidermal Tumors Benign Epithelial Tumors Seborrheic keratosis Premalignant/Malignant Epithelial Tumors Actinic keratosis Squamous cell carcinoma Basal cell carcinoma Keratoacanthoma (controversial) malignancy or not?

Irritation Inflammation

^ Solitary

^ Multiple

Above: Dermatosis Papulosis Nigra Multiple seborrheic keratoses.

Actinic Keratosis Fair-complexioned individuals (Irish/Anglo-Saxon heritage) Chronically sun-exposed areas Induced by ultraviolet radiation Course stable regress progress to squamous cell carcinoma Macules - flat Papules - raised Scale Hyperkeratosis (increased stratum corneum); parakeratosis Dysplasia of lower epidermis Solar elastosis

Test q: A 58y/o farmer has had a lesion on his face that has been enlarging for the past 3yr. This lesion is excised, and microscopic exam shows basal cell hyperplasia. Some of the basal cells show nuclear atypicality associated w/marked hyperkeratosis and parakeratosis. Solar elastosis is present. Which of the following lesions best accounts for these findings? Actinic keratosis. Test q: A 50y/o male presents w/a maculopapular scaly lesion on the back of his neck. A biopsy shows dysplasia of the keratinocytes in the lower epidermis and marked solar elastosis in the dermis. Diagnosis: actinic keratosis.

Squamous Cell Carcinoma Common: >200,000 cases/year May metastasize M>F; >70 years Head and neck Predisposing factors: Ultraviolet light exposure Industrial carcinogens (tars and oils) Chronic ulcers Immunosuppression; HIV infection Mutations in p53 common Flesh-colored to erythematous (red) Smooth or warty surface Ulceration Firm Hyperkeratosis; parakeratosis Acanthosis Dysplasia of entire epidermis large nuclei within the entire epidermis Extension of tumor into dermis Squamous pearls Solar elastosis Cells still make keratin result is keratin pearls. Have s. corneum but its trapped beneath rather than being at the surface of the skin.

Basal Cell Carcinoma Most Common malignant skin tumor: >700,000/year Locally invasive; rarely metastasize M>F; 60 years Head and neck Predisposing factors: Fair complexion Chronic sunlight exposure Immunosuppression Nevoid basal cell carcinoma syndrome

Test q: The most common cutaneous malignancy is: basal cell carcinoma

Nevoid Basal Cell Carcinoma Syndrome Autosomal dominant PTCH gene Receptor for SHH (sonic hedgehog) gene product PTCH mutation present in 30% of sporadic BCC
Test q: A 22y/o male develops more than a dozen basal cell carcinomas on his upper face. This syndrome is autosomal dominant and is associated w/mutation of which gene? PTCH. Test q: A 5y/o male presents w/a basal cell carcinoma on his forehead. The genetic basis for this disease is: PTCH.

Basal Cell Carcinoma Papules or nodules (nodules = big papules) Smooth surface (translucent; pearly) Telangiectasia dilated blood vessels within the lesion Central ulcer See peripheral palisading (below) cells lined up parallel to the periphery of the lobule.

Test q: A 66y/o female farmer has a pearly nodule on her forehead. The nodule is focally ulcerated and shows prominent dilated blood vessels. Histologically you would expect to see: peripheral palisading. Test q: All of the following regarding basal cell carcinoma are true except: Tumor exhibits full thickness atypia of the epidermis (Other choices Retraction spaces are seen around tumor lobules; Peripheral palisading is a feature; The nose is a frequent site; Sun exposure is a risk factor)

Keratoacanthoma Benign vs. malignant Rapidly growing tumor M>F Sun-exposed skin May spontaneously involute (regress) Rarely aggressive Cup-shape Keratin plug Glassy keratinocytes
Test q: A 70y/o man develops a keratoacanthoma on his nose. The lesion is cupshapes and filled w/glossy keratinocytes. The lesion can be expected to: Spontaneously regress. Test q: A 60y/o man has noted the appearance of a nodule on his ear during the past month. On phys exam, there is a 1.2cm flesh-colored, dome-shaped nodule on his right ear lobe. The nodule has a central keratin-filled crated surrounded by proliferating epithelium. The lesion regresses and disappears within 1mo. Which of the following is the most appropriate diagnosis of this lesion? Keratoacanthoma.

Adnexal Tumors Most benign Derived from adnexal structures including follicle, sebaceous gland, eccrine gland, apocrine gland Cylindroma Benign adnexal tumor, derived from eccrine glands Occurs on forehead and scalp Multiple lesions may coalesce into hat-like growth (turban tumor) Similar to basal cell carcinoma, but cells are a little more responsible try to make basement membrane (pink web) and ducts (eccrine glands).

Melanocytic Tumors: Melanocytic Nevi (Moles) Common Congenital (1% of population) Acquired (1-35 years) Trunk, extremities, face Acquired Melanocytic Nevi: - Macules and papules - Tan to black - Regular in shape and border - <5mm diameter

Nevus Nests of cells epidermis (junctional nevus) dermis (intradermal nevus) epidermis + dermis (compound nevus) Nevus cells round with oval nucleus variable melanin Summary of histologic features Symmetric Predominant nest pattern Cytologically bland melanocytes No dermal mitotic figures Maturation (nuclei get smaller with descent into dermis)
Test q: Characteristics of benign nevi include: maturation; smaller cells in dermis.

Congenital Melanocytic Nevi:

Dysplastic Nevi: Macules and papules Irregular: shape, border, color >5mm diameter Occur on sun-exposed and nonsun-exposed skin Clinical significance unclear: Isolated lesions: not very significant Multiple lesions: probably increased risk of melanoma (only very slightly) Dysplastic nevus syndrome (atypical mole syndrome) Autosomal dominant

Malignant Melanoma:

Very irregular in shape and color. Middle picture shows regression in the middle immune system attacks and partially destroys the melanoma.

Melanoma is not in the overall top 10 reasons for cancer death, however, it is one of the most deadly skin cancers
Test q: In the US, the malignant tumor most commonly causing death in females is: Lung. Test q: The malignancies responsible for the most cancer deaths in women and men in the US (currently) is (are): Lung for both Test q: The most common cause of cancer-related mortality in US women aged 20-25 is: melanoma. (From 2005 test. Did he say that this year?)

Melanoma Sites

Malignant Melanoma In Blacks and Asians Soles Mucous membranes Palms Nail beds

Chest in men. Lower legs in females. Faces in both. Melanoma Risk Factors Light complexion, hair, eyes dont make as much melanin. History of blistering sunburn(s) Proximity to the equator Indoor occupation; outdoor hobbies more likely to get burnt. Family history of melanoma or dysplastic nevi Precursor lesions (congenital or dysplastic nevi) Xeroderma pigmentosa inhibits ability to repair DNA.
Test q: In the US, the highest incidence of melanoma can be found in: Texas (other choices: CA, ME, NC, IN. Proximity to equator) Test q: Malignant neoplasms develop in patients w/xeroderma pigmentosum because these patients: Lack an enzyme necessary for DNA repair.

Melanoma Not just a disease of older patients Most common cause of cancer-related mortality in young women Well documented pediatric cases Warning signs Change in pre-existing mole Itching/pain in pre-existing mole New pigmented lesion as adult ABCDs Malignant Melanoma: ABCDs A: Asymmetry B: Border C: Color D: Diameter anything over 10mm should be looked at more closely. Melanoma: Pathologic Concepts Radial and vertical growth phase RGP: intraepidermal growth +/- minimal involvement of dermis VGP: significant invasion into dermis Radial Growth Phase: Spread of melanoma cells within the epidermis and papillary dermis, often for a prolonged time. No capacity for metastasis. Vertical Growth Phase: Pattern of growth assumes a vertical component, the melanoma grows downward into the deeper dermis as an expansile mass. This correlates with the emergence of a clone of cells with true metastatic potential.

Depth of dermal involvement correlates with prognosis. Clarks level (anatomic location of tumor) Breslow level (quantitative measurement)
Test q: In melanoma, the single most important prognostic factor is: depth of invasion Test q: The Breslow measurement is used to: assess melanoma tumor stage and prognosis (as opposed to tumor grade and prognosis)

Vertical growing down into the dermis and subcutaneous fat.

Clarks Levels I tumor cells are confined to the epidermis (melanoma in situ) II superficial papillary dermis III filling papillary dermis IV in reticular dermis, where collagen fibers are thicker (distinguishes from papillary dermis) V has the greatest risk of metastasis.
Test q: A 37y/o red-haired female has a pigmented papule on her back that measures 0.8cm in diameter. On excisional biopsy, melanoma is diagnosed. The melanoma is confined entirely to the epidermis. The Breslow measurement is .75mm. This melanoma is most accurately described as: Melanoma in situ REPEATED x2 (once it was 1.0cm in diameter) Test q: A 39y/o woman has a nodule on her back that has become larger over the past 2mo. On phys exam, there is a 2.1cm pigmented lesion w/irregular borders and an irregular brown-black color. An excisional biopsy w/wide margins is performed and microscopic exam of the biopsy specimen shows a malignant melanoma composed of epithelioid cells that extends 3.5mm (one year, was 2mm) down to the reticular dermis. There is a band of lymphocytes beneath the melanoma. Which of the following statements is most appropriate to make to this patient regarding these findings? Metastases are probable. REPEATED x2 (One year, answer was The prognosis is poor. Other choices were the same both times: Her immune system will prevent metastases; Other family members are at risk for this condition; The primary site for this lesion is probably the eye; Nevi elsewhere on her body will become malignant.)

Breslow Level: Perpendicular distance from granular layer Measured in mm More reproducible

Melanoma can metastasize to various locations in the body, including axillary nodes, lung, and liver.

Melanoma: Histologic features Asymmetric Irregular nests Single cell pattern Pagetoid spread upward spreading of melanocytes into the epidermis. Nuclear atypia Absence of maturation Dermal mitotic figures Pagetoid spread. Nuclei do not get smaller as they grow down. In the middle picture, see atypical cells. In the picture on the right, see mitotic figures. Melanoma Molecular mechanisms: Deletions of CDKN2A (INK4A) Deletion of p16 protein product leads to: Unrestricted phosphorylation of Rb (inactive Rb) Unrestricted cell growth Deletion of p14 (alternative protein product) leads to Decreased p53 function (via decreased function of MDM2) Enhanced growth of altered cells BRAF mutations Found in melanomas and nevi Part of RAS/RAF/MAP kinase pathway
Test q: A 20y/o man has a raised, irregular, pigmented lesion on his forearm that has increased in size and become more irregular in color over the past 4 months. An excisional biopsy specimen shows a malignant melanoma that extends into the reticular dermis. Family history indicates that the patients paternal uncle died of metastatic melanoma that spread to the liver after excision of a primary lesion on the foot. His grandfather required enucleation of the left eye because of a dark brown mass in the eyeball. Which of the following genes is most likely to have undergone mutation to produce these findings? p16 (cell cycle inhibition) REPEATED x2

Above: Pagetoid spread. Can see nests of melanocytes. Also single cells growing into the epidermis.

Mesenchymal Tumors: Benign Fibrous Histiocytoma(BFH)/Dermatofibroma (DF) Clinical Features: Solitary, slow-growing nodule, often red-brown in color Usually on extremities in dermis or superficial subcutis Presents in early or mid-adult life Spindled tumor cells Collagen trapping at the periphery of the tumor, the tumor cells interdigitate around preexisting collagen fibers of the reticular dermis
Test q: A pigmented skin lesion measures 1cm in diameter. Biopsy shows a proliferation of spindled cells in the dermis that appear to trap collagen. The epidermis is not involved. Mitoses are not identified. The subcutaneous fat is not involved. Diagnosis: Dermatofibroma Test q: A 50y/o male develops a slightly pigmented nodule on his forearm. On biopsy, one sees a proliferation of spindleshaped cells in the dermis. Collagen trapping is present, but fat-trapping is absent. There are no mitoses. Diagnosis? Dermatofibroma

Dermatofibroma. Large dark pink area = lesion. Proliferation induces acanthosis (thickening) of the overlying epidermis.

Dermatofibrosarcoma Protuberans (DFSP) Clinical Features: Slow-growing plaque, later nodular Usually occurs in mid-adult life Men > women Trunk, proximal extremities most common site Locally recurrent (very) Metastasis <5% cases DFSP: White spaces = what is left of the subcutaneous fat. Below: cells are a bit amorphic. Can see mitoses.

Hematopoietic Tumors: Mycosis Fungoides: Uncommon (<1% of lymphomas) Older adults Clinical progression in disease: patch plaque nodule Patch Stage: Scaly, reddish plaques that arise mainly on clothed areas of the body sun exposure actually acts as a treatment. T cell lymphoma uncommon relative to systemic lymphomas, but one of the most common skin lymphomas. Some people never progress through the disease. Cutaneous T-cell Lymphoma (Mycosis Fungoides)

Patch stage

Plaque stage

Plaque stage

Nodule (Tumor) Stage Not everyone evolves to this stage some people are in patch stage their whole life.

Sezary Syndrome (Erythrodermic Stage) Can evolve from patch stage to Sezary syndrome, but some people go straight to Sezary syndrome (involves peripheral blood). Mycosis Fungoides: Histologic Features Psoriasiform epidermal hyperplasia (acanthosis) looks like psoriasis Epidermotropism Lymphocytes in epidermis without spongiosis Pautriers microabscesses: collections of atypical lymphocytes in epidermis Cerebriform nuclei very convoluted lymphocyte nuclei
Above: Hyperkeratosis = increased s. corneum. See lymphocytes in the papillary dermis. Lymphocytes also in the epidermis (bigger, hyperchromatic).

Mycosis Fungoides: Atypical T-helper lymphocytes (CD4 positive) in dermis and epidermis
Test q: Mycosis fungoides is: a tumor of CD4+ T-cells.

Langerhans Cell Histiocytosis (Histiocytosis X): Langerhans cell = APC typically found in epidermis Children > adults Solitary or multiple Papules, nodules or plaques Proliferation of Langerhans cells Langerhans Cell Histiocytosis: Histologic Features Proliferation of cells with reniform (bean-shaped) nuclei and eosinophilic cytoplasm Often involve epidermis (their origin) and dermis Eosinophils present in variable amounts Immunostains: CD1a and S100 positive EM: Birbeck granules look like tennis racket. Thought to be involved in antigen presentation.

Test q: A 13y/o male presents w/a solitary nodule on his forehead. Histologically, there is a proliferation of cells w/bean-shaped or reniform nuclei and eosinophilic cytoplasm. Malignant cells are present in both dermis and epidermis. Many eosinophils are present in the dermis. On immunohistochemistry you would expect: CD1a and S100 (+) REPEATED x2

Above: Langerhans cell histiocytosis: Kidney bean-shaped nuclei

Mastocytosis Spectrum of diseases Variety of clinical entities Urticaria pigmentosa 50% of cases Localized cutaneous disease Multiple red-brown papules Dariers sign traumatize/scratch mast cells degranulate, get a wheal. Systemic disease (multiple organs) 10 % Worse prognosis Pruritis, flushing, rhinorrhea, diarrhea, GI bleeding, bone pain

Above: Langerhans Cell Histiocytosis: CD1a Stain (CD1a immunostain is very sensitive and specific for Langerhans cells.)

Above: Mastocytosis. Non-descript cell type on H&E. Have granules in the cytoplasm. Blue stain granules are stained bright blue.

DERMATOPATHOLOGY: LECTURE 2 Inflammatory Dermatopathology

Tues. 09/14/10

General Principles: Thousands of inflammatory dermatoses Limited number of histologic reaction patterns Significant histologic overlap Correlation of histologic features with clinical presentation essential Dermatopathologist dependent on history and clinical description of lesions by dermatologist or family practitioner Histologic Classification: Based on pattern of inflammatory changes. Some patterns: Spongiotic (intraepidermal edema) ex: contact dermatitis/eczema Psoriasiform (epidermal acanthosis) ex: psoriasis Interface (damage to basal layer) Perivascular (inflammatory cells predominant ly around blood vessels) ex: erythema multiforme, lupus Lichenoid (inflammatory cells arranged as dense band beneath epidermis) ex: Lichen Planus Other patterns: Perivascular infiltrate (no epidermal changes) Interstitial infiltrate (inflammatory cells between collagen bundles) Bullous disease (blister) Intraepidermal blister within epidermis Subepidermal blister beneath epidermis Panniculitis (inflammation in subcutaneous fat) Miscellaneous Patterns: Represent starting point (defines category) Individual differentiating microscopic features Correlation with clinical features often necessary to make final diagnosis Spongiotic Dermatitis Primary feature: intraepidermal edema (ECF as a result of inflammation) Accumulation of edema fluid within epidermis Keratinocytes pull apart (easy to see intercellular bridges) May see intraepidermal vesicles May see some acanthosis thickening in older lesions (overlap with psoriasiform pattern) Red,papulovesicular, oozing and crusting Prototype: contact dermatitis Eczematous Dermatitis Histologic Features: Spongiotic dermatitis Intercellular edema in epidermis Small vesicles in epidermis due to edema fluid Inflammatory infiltrate in dermis (typically lymphocytes and eosinophils clue that its an allergic process) Pathogenesis of Contact Dermatitis Antigens processed by dendritic Langerhans cells Langerhans cells migrate to regional lymph nodes Antigen presentation stimulates naive T-cells Rash develops on re-exposure secondary to cytokine production from T-cells Psoriasiform Dermatitis Epidermal acanthosis most important feature Variable perivascular infiltrate Variable spongiosis Prototype: psoriasis

Test q: Allergic contact dermatitis is related to: Type IV hypersensitivity reaction. (Cell-mediated rather than antibody-mediated)

Psoriasis Chronic dermatitis Affects 1-3% of the population May develop at any age; genetic predisposition Psoriatic arthritis Overall incidence ~5% Usually seen in patients with severe skin disease HIV: psoriasis can be presenting sign Red plaques with loose silvery scale Pitted nails with yellow discoloration Frequent sites: extensor surfaces, scalp, lumbosacral region, gluteal cleft, glans penis Psoriasis: Histologic Features Uniform acanthosis Confluent parakeratosis (retained nuclei in stratum corneum mainly see neutrophils here.) Diminished to absent granular layer Thinned suprapapillary plate will see thickening of epidermis except this area. Parakeratotic scale with neutrophils Spongiform pustules in epidermis Dilated tortuous vessels in dermal papillae

Above: Psoriatic Arthritis (very disruptive).

Interface Dermatitis Key feature: damage to basal layer of epidermis, usually by lymphocytes Damage to basal layer of epidermis with perivascular inflammation Erythema Multiforme Toxic Epidermal Necrolysis (TEN) Lupus Erythematosus Damage to basal layer of epidermis with lichenoid inflammation (dead span of lymphocytes underneath the epidermis) Lichen Planus Interface Dermatitis w/perivascular Inflammation: Erythema Multiforme: Spectrum of disease (EM, TEN) EM = less severe end of the spectrum TEN = toxic epidermal necrolitis (most severe end of the spectrum) Dramatic hypersensitivity response with a wide range of possible causes Infections: HSV, mycoplasma, histoplasmosis, coccidiomycosis, typhoid, leprosy Drugs: Sulfa drugs, PCN, barbiturates, salicylates, hydantoins, antimalarials Malignancies: carcinomas and lymphomas Collagen vascular disease: Lupus erythematosus, dermatomyositis, periarteritis nodosa Idiopathic ~ 50% of cases Clinical lesions variable (multiple forms) Papules Targetoid lesion (most characteristic) Vesicles Bullae

Rapid onset of red papules:

Target lesions:

Above: Central area = necrosis of the epidermis

Test q: A 25y/o female had a child in daycare that develops diarrhea which the patient also developed. Both were treated w/trimethaprim sulfa methoxazole (Septra). The mother develops a targetoid rash w/vesicles and bullae. You suspect: Erythema multiforme. Test q: A 40y/o male AIDS patient is treated w/Septra (trimethaprim sulfamethoxazole) for Pneumocystis pneumonia. His CD4 count is <200. He develops a papular rash which eventually shows a targetoid pattern. A biopsy shows full thickness necrosis of keratinocytes. The most likely diagnosis is: Erythema multiforme. Test q: A 28y/o AIDS patient suffers from Histoplasmosis and Nocardiosis. He is treated w/Itraconazole and Trimethiprim Sulfamethoxazole. He develops vesicles and target-shaped red skin papules. This history is consistent with: Erythema multiforme.

Stevens-Johnson Syndrome Extensive disease with oral and ocular involvement Fever Children more than adults Drugs are most common cause Get mucosal involvement. Very severe.

Toxic Epidermal Necrolysis (TEN) Widespread epidermal necrosis Extensive sloughing Resembles burns

Erythema Multiforme: Histologic Features Degeneration and necrosis of keratinocytes leading to full thickness necrosis Superficial perivascular lymphocytic infiltrate, usually mild in nature Prominent edema of papillary dermis

Figure: Erythema Multiforme/TEN: Mild (left); severe (right) Whole epidermis is necrotic Can see necrotic, apoptotic cells distinguish by small, darkened nucleus and orange cytoplasm See lymphocytes around blood vessels

Lupus Erythematosus (Interface Dermatitis w/perivascular inflammation) Acute Lupus Erythematosus: Subacute Lupus Erythematosus:
Annular, polycyclic, blanchable erythema Mild systemic involvement (arthralgias, fever, malaise) Illness is intermediate in severity between ALE and CLE Blanchable erythema Photo-distribution Malar rash Systemic symptoms: Circulating antibodies; immunoglobulin deposition in the skin and other organs 15% progress to acute LE

Chronic Lupus Erythematosus (aka discoid LE)

Figure: Damage to basal layer of epidermis can see vacuoles within basal keratinocytes as a result of damage. Can see dramatically thickened basement membrane here.

Discoid Lupus much more skin limitied. Very rarely progresses to systemic disease. See post-inflammatory hypopigmentation.

Perivascular lymphocytes

Above: Mucin production collagen bundles here are separated by mucin.


Test q: Histologic features of Lupus Erythematosus include: interface vacuoles and focal epidermal atrophy

Interface Dermatitis w/lichenoid (band-like) inflammation Lichen Planus Chronic but self-limiting disease Multiple, symmetric lesions on extremities (especially wrists) Pruritic, purple, polygonal papules Oral mucosal involvement common (see right) oral lesions have lacy, white pattern. Dense band-like lymphocytic infiltrate hugs epidermis Epidermal changes: Hyperkeratosis Wedge-shaped hypergranulosis

Saw-toothed basal layer Thickening of granular layer Individual necrotic keratinocytes (circled)

Test q: A 40y/o woman goes to her dentist who notes that she has 0.2 to 1.5cm scattered, white, reticulated areas on the buccal mucosa. The woman says that these lesions have been present for one year. She also has some 0.3-cm purple, pruritic papules on each elbow. A biopsy specimen of a skin lesion shows a bandlike infiltrate of lymphocytes at the dermalepidermal junction as well as degeneration of basal keratinocytes. The most likely diagnosis is: Lichen planus.

Above: Lichen Planus Interface dermatitis, so damage to the basal layer of keratinocytes due to attack by lymphocytes. Circle necrotic keratinocytes. See band-like infiltrate of lymphocytes. Thickening of epidermis increase in granular layer.

Bullous Dermatosis: Bullae and vesicles are primary clinical manifestations Bullae = large blisters; vesicles = tiny blisters Diagnostic categories based on level of split in epidermis Subcorneal (beneath SC), intraepidermal or subepidermal Diseases caused by Ig deposition i.e. autoimmune diseases Pemphigus Vulgaris: Presents in the 4th-6th decades, M=F Autoimmune blistering disease IgG against desmoglein 3 in desmosomes Desmosomes hold epithelial cells together loss of cell adhesion within the epidermis
Test q: In pemphigus vulgaris, IgG autoantibodies are directed against: Desmosomes REPEATED x2

Variants: pemphigus vegetans and foliaceus Flaccid, fragile bullae Oral mucosa involvement (typically ruptures before you see it clinically)

Pemphigus vulgaris.
Intraepidermal, suprabasilar blister with tombstone basal layer Mixed dermal inflammatory infiltrate, often with eosinophils Intraepidermal: looks like this blister is under the whole epidermis, but note the one layer of cells left underneath. The rest makes up the roof of the blister.

Above: In the base of the blister is one layer of the epidermis. The rest makes up the roof of the blister.

Above: Pemphigus Vulgaris Immunofluoresence

Bullous Pemphigoid: Generally affects elderly patients Bullae on extremities, intertriginous areas, abdomen and oral mucosa (1/3 pts) Autoimmune disease IgG against hemidesmosome proteins Hemidesmosomes bind epidermis to basement membrane Subepidermal blistering process blisters have more strength because of more material in the roof. Blisters are tense and stay intact longer (as compared to fragile blisters of PV, described above). Tense bullae

Above: Bullous Pemphigoid. Subepidermal blister without tombstones or acantholysis. No epidermis in the base of the blister.

Above: Blister contains edema fluid and eosinophils.

Bullous Pemphigoid: Immunofluorescence. IgG bound to hemidesmosome located in basement membrane.

Dermatitis Herpetiformis Vesicular dermatosis not bullous rd th 3 and 4 decades, M>F Pruritic, burning vesicles, especially on extensor surfaces of extremities Strongly associated with celiac disease everyone w/DH either has Celiac disease or sub-clinical Celiac disease. Responds to gluten free diet (like celiac) IgA deposited in dermal papillae of skin

Incredibly itchy patients will scratch blisters before you ever see them in clinic.

DH Histologic Features- Subepidermal vesicles

Neutrophilic microabscess

Test q: A 35y/o female presents w/small vesicles on extremeties. The rash is extremely pruritic. She also has been diagnosed w/celiac disease. Diagnosis: Dermatitis herpetiformis REPEATED x2 Test q: A person w/dermatitis herpetiformis should avoid what food substance: gluten. Test q: A 35y/o man has had an outbreak of pruritic lesions over the extensor surface of the elbows and knees during the past month/ He has a history of malabsorption that requires him to eat a special diet, but he has had no previous skin problems. On phys exam, the lesions are 0.4-0.7cm vesicles. A 3mm punch biopsy of one of the lesions over the elbow is performed. Microscopic exam of the biopsy specimen shows accumulation of neutrophils at the tips of dermal papillae and formation of small blisters due to separation at the dermo-epidermal junction. Immunofluorescence studies performed on this specimen show granular deposits of IgA localized to tips of dermal papillae. Lab studies show serum anti-gliadin antibodies. Which of the following is the most likely diagnosis? Dermatitis herpetiformis.

DH Immunofluorescence. IgA deposits recruit in neutrophils.

Test q: Neutrophilic microabscesses and fluffy IgA deposits on basement membrane anchoring febrils are characteristic of: Dermatitis herpetiformis.

Infections and Infestations: Dermatophytosis: AKA: Tinea (capitis scalp, corporis body, barbae beard area, cruris groin, pedis foot), ringworm Dermatophytes infect outer keratin layer of skin

Dermatophytosis

Above: Tinea corporis expanding, annular, erythematous plaque w/elevated, scaly border. Annular because dermatophytes start in a small area and grow outwards = ring.

Dermatophyte Infection: Histologic Features: Hyperkeratosis Parakeratosis Neutrophils in keratin Hyphae in keratin Difficult to see on H&E Organisms grow in the stratum corneum do not go down into epidermis at all.
Test q: Neutrophils in the stratum corneum are a common feature in: Psoriasis and dermatophytosis. Test q: A 25y/o male joins a gym and works out regularly. He develops a pruritic rash on his feet which shows white centers w/a red, scaly border. A diagnostic stain would be: PAS stain.

PAS stain demonstrating hyphae


Shows fungal hyphae/spores very clearly but only in s. corneum.

Warts (verrucae): Benign neoplasms caused by human papillomavirus (HPV) >60 subtypes Certain subsets associated w/squamous cell carcinoma Common Common wart (verruca vulgaris) Plantar/palmar wart - caused by diff HPV subtypes Genital wart (condyloma acuminatum) Flat wart Occur at any age Self-limited Verruca Vulgaris: Histologic Features Histology similar across all the different subtypes. Papillomatosis projections of epidermis Acanthosis thickening of epidermis Tortuous vessels within papillae KEY FEATURE = Koilocytes. Have clear area within cytoplasm due to viral particles present.

Molluscum Contagiosum: Common especially in children Dome-shaped papules with a central keratinfilled crater Easily spread through contact DNA poxvirus Histologic Features: large, bright pink viral inclusions. Molluscum body: eosinophilic cytoplasmic inclusion in upper layers of epidermis.

Test q: A 35y/o man has noted a bump on his upper trunk for the past 6wk. On phys exam, there is a solitary 0.4cm flesh-colored nodule on the upper trunk. The dome-shaped lesion is umbilicated, and a curd-like material can be expressed from the center. This material is smeared on a slide, and Giemsa stain shows many pink, homogenous, cytoplasmic inclusions. The lesion regresses over the next 2mo. Which of the following infectious agents most likely produced this lesion? Molluscum contagiosum

Impetigo: Common superficial infection Staphylococcus or streptococcus Exposed surfaces Characteristic honey-colored crust Histologic Feature: Subcorneal pustule A lot of neutrophils in the stratum corneum can see gram positive cocci here.

Infestations: Scabies (Sarcoptes scabiei)

Above: The scabies mite.

Scabies feces.

Linear burrows.

Scabies like to burrow underneath the stratum corneum. Find them on the penis and web spaces of the fingers. Figure: Scabies organism underneath the stratum corneum. Scabies feces underneath?

Herpesvirus infections: HSV-1 Cold sores, fever blisters Oral infection most common Cutaneous blistering eruption, usually linear HSV-2 Genital herpes VZV varicella zoster Chicken pox
Figure: Germline mutation: born w/one mutated allele and one wildtype allele. During life, youll have hits from viruses, chemicals, other environmental factors and you will lose the wildtype allele. Called LOH (loss of heterozygosity) uncontrolled proliferation.

Figure: Herpes infects keratinocytes see multinucleated cells (circled one has 10-15 nuclei)