Dermatopathology (Puthoff) Flashcards
What is the general structure of human skin?
Epidermis
Dermis
Subcutaneous tissue
What are different cell types within the epidermis?
Squamous epithelial cells (keratinocytes)
Melanocytes
Dendritic cells (Langerhans cells)
Merkel cells
What are different cell types in the dermis?
Lymphocytes Lymphatics Small blood vessels Afferent and sensory nerve fibers Adnexal components (hair shafts and sebaceous glands)
The bottom layer of the epidermis contains epidermal ridges called _______ ______. These will interconnect with the _______ _______ on the dermis.
Rete pegs
Dermal papillae
What are the 2 layers of the dermis?
Papillary layer (contains dermal papillae) Reticular layer
What are the layers of the epidermis (from superficial to deep)?
Stratum corneum Stratum lucidum Stratum granulosum Stratum spinosum Stratum basale
***Mnemonic = Come, Let’s Get Sun Burned
This layer of the epidermis is only in thick skin (soles and palms).
Stratum lucidum
Major proteins formed within keratinocytes are ________. These are intermediate filament proteins making up the cytoskeleton of the cells.
Keratins
Antibodies to various _________ are used in pathology to identify keratinocytes (ie, CK AE1/3).
Cytokeratins
These are structures that are derived from the skin and usually adjacent to it. Functionally this includes hair follicles, sebaceous and sweat glands. In a larger, macroscopic sense of the skin, it also includes specialized structures like nails of fingers and toes.
Skin adnexa (appendages)
What are the main disorders of pigmentation and melanocytes?
Freckle
Lentigo
Nevi
Melanoma
These are the most common pigmented lesions of childhood in lightly pigmented individuals. Also called an Ephelis.
Freckle
This is a benign, localized melanocytic hyperplasia.
Lentigo
This type of nevus (non-medical = mole) that can be caused by acquiring activating mutations in Ras signaling pathway.
Melanocytic/Pigmented Nevi
This type of nevus may be a direct precursor of melanoma.
Dysplastic Nevi
This type of nevus develops at the dermal/epidermal junction.
Junctional Nevi
A Junctional Nevus can become deeper and develop into this. This type of nevus is also at the junction but also nests into the reticular dermis.
Compound Nevi
This type of nevus is deep dermal and sometimes subcutaneous growth around adnexa, neuromuscular bundles, and blood vessel walls. It is present at birth, and large variants have increased melanoma risk.
Congenital Nevus
This type of nevus has non-nested dermal infiltration, often with associated fibrosis. It is a black-blue nodule, often confused with melanoma clinically. Highly dendritic, heavily pigmented and painful.
Blue Nevus
This type of nevus has fascicular growth, and consists of large, plump cells with pink-blue cytoplasm and fusiform cells. Common in children, red-pink nodule often confused with hemangioma clinically.
Spindle and Epithelioid cell (Spitz) Nevus
This type of nevus has lymphocytic infiltration surrounding the nevus cells. It is identical to ordinary acquired nevi, and there is a host immune response against nevus cells and surrounding normal melanocytes.
Halo Nevus
In Dysplastic nevi, an important feature is the presence of…
Cytologic atypia
This is the most deadly of all skin cancers. It is strongly linked to sun exposure and is inherently immunogenic.
Malignant melanoma
What is the ABCDE rule for melanoma?
A = Asymmetry B = Border C = Color D = Diameter (greater than 6 mm) E = Evolution
This measurement will look at the thickness of melanoma. Under 1 mm is a good prognosis.
Breslau Measurement
What are the types of benign epithelial tumors?
- Seborrheic keratoses
- Acanthosis nigricans
- Fibroepithelial polyp
- Epithelial inclusion cyst
This type of benign epithelial tumor can be pigmented or pale, also often irritated due to picking at it. Very common in older individuals, mostly on the trunk. Quite superficial/flat to round/coin-like, waxy exophytic lesions.
Seborrheic keratoses
This sign occurs when crops of Seborrheic keratoses suddenly appear. Can be a sign of cancer.
Leser-Trelat sign
This type of benign epithelial tumor consists of dark-thickened skin in creases or flexural areas. Has velvet-like texture.
Acanthosis nigricans
What percentage of Acanthosis nigricans is benign, and is acquired (obesity, DM, etc) or inherited (rare, AD inheritance)?
80%
What percentage of Acanthosis nigricans is associated with malignancy, most commonly GI carcinomas?
20%
This type of benign epithelial tumor is also known as a skin tag.
Fibroepithelial polyp
This type of benign epithelial tumor is very common, and are sebaceous cyst, or wen. These can rupture and the pus is very smelly. Have to excise with the capsule or they can reoccur.
Epithelial inclusion cyst
This category of cutaneous tumors can arise from hundreds of neoplasms.
Adnexal (appendage) tumors
What type of tumors are within the premalignant and malignant epidermal tumor category?
Premalignant = Actinic keratosis
Malignant = SCC and BCC
BCC can often present small red blood vessels, which is called…
Telangiectasis
In a normal cell, SHH will bind to ______ and dissociates ______. This allows activation of gene expression in normal development and tissue homeostasis. However, in BCC there is mutated _______, causing _______ to be permanently dissociated and active. This leads to unregulated cell division and abnormal growth.
PTCH
SMO
PTCH
SMO
What is the mnemonic and terms for so-called “painful” skin lesions?
GLENDAB
G = Glomus tumor (occurs under nail) L = Leiomyoma (angio-type) E = Eccrine spiradenoma N = Neurofibroma D = Dermatofibroma A = Angiolipoma B = Blue rubber bleb nevus
This type of tumor of the dermis refers to a heterogenous family of morphologically and histogenetically related benign dermal neoplasms of uncertain lineage. Usually seen in adults and often occur on legs of young and middle-aged women. Lesions are asymptomatic or tender and may increase or decrease in size over time.
Benign Fibrous Histiocytoma (Dermatofibroma)
What type of tumor of the dermis can often have a history of antecedent trauma? Suggesting an abnormal response to injury and inflammation (ie, like in a hypertrophic scar or keloid).
Benign Fibrous Histiocytoma (Dermatofibroma)
This tumor of the dermis is a well-differentiated, primary fibrosarcoma of the skin. They are slow-growing, and although they are locally aggressive and can recur, they rarely metastasize.
Dermatofibrosarcoma Protuberans
Describe the molecular hallmark of Dermatofibrosarcoma Protuberans.
Translocation involving the genes encoding collagen 1A1 (COL1A1) and platelet-derived growth factor-B (PDGFB). The resulting rearrangement juxtaposes the COL1A1 promoter sequences and the coding region of PDGFB and leads to over expression and increased secretion of PDGFB, which drives tumor cell growth through an autocrine loop.
What are the tumors of cellular migrants to the skin?
- Mycosis Fungoides (Cutaneous T-Cell Lymphoma)
- - Mastocytosis
The term _________ encompasses a spectrum of rare disorders characterized by increased numbers of mast cells in the skin and, in some instances, in other organs as well.
Mastocytosis
A cutaneous form of mastocytosis that affects predominantly children and accounts for more than 50% of all cases is termed ________ ________. The cutaneous lesions are usually multiple, although solitary mastocytomas may also occur in very young children.
Urticaria pigmentosa
About _______ of individuals with mast cell disease have systemic disease, with mast cell infiltration of many organs. These individuals are often adults, and unlike localized cutaneous disease, the prognosis may be poor.
10%
In mastocytosis, this term refers to a localized area of dermal edema and erythema (wheal) that occurs when lesions skin is rubbed.
Darier sign
In mastocytosis, _________ refers to an area of dermal edema resembling a hive that occurs as a result of localized stroking of apparently normal skin with a pointed instrument.
Dermatographism
In mastocytosis, ________ is caused by excessive histamine release in the marrow microenvironment and can be a clue to the diagnosis, particularly in premenopausal women and in men.
Osteoporosis
This is a group of inherited disorders of epidermal maturation that is apparent at or soon after birth. There are a few acquired variants that may be paraneoplastic manifestations of lymphoid or visceral malignancies. Have fissured, scaly appearance.
Ichthyosis
What are the types of acute inflammatory dermatoses?
- Urticaria (wheals)
- Acute eczematous dermatitis
- Erythema multiforme
What are the types of chronic inflammatory dermatoses?
- Psoriasis
- Seborrheic dermatitis
- Lichen planus
In dermatoses, (ACUTE/CHRONIC) lesions last from days to weeks and are characterized by inflammatory infiltrates (usually composed of lymphocytes and macrophages rather than neutrophils), edema, and variable degrees of epidermal, vascular, or subcutaneous injury.
Acute
In dermatoses, (ACUTE/CHRONIC) lesions persist for months to years and are often associated with epidermal changes (atrophy or hyperplasia) or dermal fibrosis.
Chronic
This is a firm edematous plaque resulting from infiltration of the dermis with fluid. They are transient and may last only a few hours.
Wheal (hive)
________ is a common disorder of the skin characterized by localized mast cell degranulation and resultant dermal microvascular hyperpermeability. This combination of effects produces pruritic edematous plaques called wheals.
Urticaria
Urticaria is closely related to _________ and is characterized by the edema of the deeper dermis and the subcutaneous fat.
Angioedema
Mast cells are widely distributed in CT and participate in both acute and chronic inflammatory reactions. Mast cells express on their surface the receptor _______ that binds the Fc portion of ______ antibody. In immediate hypersensitivity reactions, the bound cells will degranulate and release mediators such as histamine and prostaglandins.
FcERI
IgE
***Type I Hypersensitivity!
Acute eczematous dermatitis is one of the most common acute skin disorder manifestations and can be subdivided into what categories?
1) Allergic contact dermatitis
2) Atopic dermatitis
3) Drug-related eczematous dermatitis
4) Photoeczematous dermatitis
5) Primary irritant dermatitis
What is an example of primary irritant dermatitis?
Poison ivy
________ ________ is an uncommon self-limited hypersensitivity reaction to certain infections and drugs. It affects individuals of any age and is associated with:
1) Infections such as herpes simplex, mycoplasmal infections, histoplasmosis, coccidioidomycosis, typhoid and leprosy, etc.
2) Exposure to certain drugs
3) Cancer
4) Collagen vascular diseases (ie, SLE, dermatomyositis)
Erythema Multiforme
This is a chronic inflammatory dermatosis that appears to have an autoimmune basis. It is a common disorder, affecting as many as 1-2% of people in the United States. Persons of all ages may develop the disease.
Psoriasis
Approximately 15% of the patients with psoriasis have associated ________. This may be mild or may produce severe deformities resembling the joint changes seen in RA. Psoriasis can also be associated with myopathy, enteropathy, and AIDS.
Arthritis
Psoriasis most frequently affects the skin of the elbows, knees, scalp, lumbosacral areas, intergluteal cleft, and glans penis. The typical lesion looks like…
Pink to salmon-colored plaque covered by loosely adherent silver-white scale
In psoriasis, this is the term for the appearance of small bleeding points after successive layers of scale have been removed from the surface.
Auspitz sign
In psoriasis, this is the term for the appearance of new skin lesions on previously unaffected skin that is secondary to trauma (ie, bump a knee or hit shin).
Koebner phenomenon
Treatment with what has shown efficacy for psoriasis?
Anti-TNF
Anti-IL17
This is a chronic inflammatory dermatosis that is even more common than psoriasis, affecting up to 5% of the general population. It classically involves regions with a high density of sebaceous glands, such as the scalp (dandruff), forehead, external auditory canal, retroauricular area, nasolabial folds, and presternal area.
Seborrheic Dermatitis
***Despite its name, it is associated with inflammation of the epidermis and is not a disease of the sebaceous glands per se.
What disease correlations are there with Seborrheic Dermatitis?
- HIV with low CD4 counts
- - Parkinson Disease
This disease is usually self-limited, most commonly resolving spontaneously 1 to 2 years after onset. Resolution often leaves a residuum of post inflammatory hyperpigmentation. Oral lesions, however, may persist for years.
Lichen Planus
Lichen Planus has “Six P’s” which are…
Pruritic Purple Polygonal Planar Papules Plaques
What type of cancer has been noted to occur in chronic mucosal and paramucosal lesions of lichen planus?
SCC
What are the types of inflammatory blistering disorders?
- Pemphigus (5 types)
- Bullous pemphigoid
- Dermatitis herpetiformis
What are the types of pemphigus?
- Vulgaris
- Vegetans
- Foliaceous
- Erythematosus
- Paraneoplastic
In subcorneal blisters, the stratum corneum forms the roof of the bulla, as in…
Pemphigus foliaceus
In a suprabasilar blister, a portion of the epidermis, including the stratum corneum, forms the roof as in…
Pemphigus vulgaris
In a subepidermal blister, the entire epidermis separates from the dermis, as in…
Bullous pemphigoid
Pemphigus is a blistering disorder caused by auto-Abs that result in the dissolution of intercellular attachments within the epidermis and mucosal epithelium. All forms of pemphigus are autoimmune diseases caused by ______ auto-Abs.
IgG
Pemphigus ________, by far the most common type (accounting for more than 80% of cases worldwide), involves the mucosa and skin, especially on the scalp, face, axilla, groin, trunk, and points of pressure. It may present as oral ulcers that may persist for months before skin involvement appears. Primary lesions are superfi- cial vesicles and bullae that rupture easily, leaving shallow erosions covered with dried serum and crust.
Vulgaris
Pemphigus ________ is a rare form that usually presents not with blisters but with large, moist, verrucous (wart- like), vegetating plaques studded with pustules on the groin, axillae, and flexural surfaces.
Vegetans
Pemphigus _________ is a more benign form that is endemic in Brazil (where it is called fogo selvagem) and occurs sporadically in other geographic regions. Sites of predilection are the scalp, face, chest, and back, and the mucous membranes are only rarely affected. Bullae are so superficial that they mainly present as areas of erythema and crusting; these represent superficial erosions at sites of previous blister rupture.
Foliaceus
Pemphigus _________ is considered to be a localized, less severe form of pemphigus foliaceus that may selectively involve the malar area of the face in a lupus erythematosus-like fashion.
Erythematosus
__________ pemphigus occurs in association with various malignancies, most commonly non-Hodgkin lymphoma.
Paraneoplastic
This blistering disease generally affects elderly individuals and is caused by IgG auto-Abs that bind to proteins that are required for adherence of basal keratinocytes to the basement membrane.
Bullous pemphigoid
This blistering disease is a rare disorder characterized by urticaria and grouped vesicles. It affects predominantly males, most often in 3rd and 4th decades of life. In some cases it occurs in association with celiac disease and responds to a gluten-free diet. Plaques and vesicles are extremely pruritic.
Dermatitis herpetiformis
In dermatitis herpetiformis, discontinuous granular deposits of ______ will selectively localize in the tips of dermal papillae.
IgA
What are the non-inflammatory blistering disorders?
- Epidermolysis bullosa
- - the Porphyrias
This type of blistering disorder is a blanket term for a group of disorders caused by inherited defects in structural proteins that lend mechanical stability to the skin. The common feature is a proclivity to form blisters at sites of pressure, rubbing, or trauma, at or soon after birth. There are 4 types, each with a different defect.
Epidermolysis bullosa
***Do NOT need to know specific types!
Porphyria refers to a group of uncommon inborn or acquired disturbances of porphyrin metabolism. Prophyrins are pigments that are normally present in ________, ________, and _______. The classification of porphyrias is based on both clinical and biochemical features. Cutaneous manifestations consist of urticaria and vesicles associated with scarring. Exacerbated by exposure to sunlight.
Hemoglobin
Myoglobin
Cytochromes
What are disorders of epidermal appendages, that are also considered chronic inflammatory disorders?
- Acne vulgaris
- - Rosacea
Acne vulgaris can result from hormonal fluctuations, androgens, obstructive effects, and chronic inflammation. What organism is involved in the pathogenesis of acne?
Proprionibacterium acnes
What helps treat acne vulgaris?
Antibiotics + retinoic acids (Vit. A derivatives)
What is another name for open and closed comedones?
Open comedone = Black head
Closed comedone = White head
This is a disorder that is not well understood and treatment for which is not well-defined. Seems to be associated with chronic inflammation that may be difficult to control. Can present with persistent erythema through pustules and even development of rhinophyma (markedly enlarged nose).
Rosacea
Rosacea is associated with an increased/abnormal endogenous anti-microbial proteins, such as…
Catheliciden peptides
This is the term for the inflammation of the subcutaneous layer of fat.
Panniculitis
What are the types of panniculitis?
Erythema nodosum
Erythema induratum
Describe Erythema nodosum via its mnemonic.
NODOSUM
NO = No cause found in 60% of cases D = Drugs (antibiotics) O = Oral contraceptives S = Sarcoidosis or Lofgren's syndrome U = Ulcerative colitis, crohns, bechet's M = Micro (TB -- viral, bacterial, parasitic)
***Also consists of nodular, deep and painful lesions.
This is an uncommon form of panniculitis that tends to affect adolescents and menopausal women. May be a primary vasculitis of deep vessels supplying fat lobes of the subcutaneous skin. Tends to exhibit an erythematous nodule that goes on to ulcerate.
Erythema induratum
This is a type of panniculitis that is VERY uncommon. It is a rare form of T-cell lymphoma and can present in SLE.
Weber-Christian disease (aka relapsing febrile nodular panniculitis)
What are the types of infections discussed in this lecture?
- Verrucae (warts)
- Molluscum Contagiosum
- Impetigo
- Superficial Fungal Infections
These are squamoproliferative disorders caused by HPV.
Verrucae (warts)
_________ ________ is a common, self-limited viral disease of the skin caused by a poxvirus. The virus is char- acteristically brick shaped, has a dumbbell-shaped DNA core, and measures 300 nm in maximal dimension, and thus represents the largest pathogenic poxvirus in humans and one of the largest viruses in nature. Infection is usually spread by direct contact, particularly among children and young adults.
Molluscum Contagiosum
________ is a common superficial bacterial infection of skin. It is highly contagious and is frequently seen in otherwise healthy children as well as occasionally in adults in poor health. The infection usually involves exposed skin, particularly that of the face and hands. Two forms exist, that only differ by the size of their pustules.
Impetigo
As opposed to deep fungal infections of the skin, where the dermis or subcutis is primarily involved, superficial fungal infections of the skin are confined to the _______ _______, and are caused primarily by dermatophytes. These organisms grow in the soil and on animals and produce a number of diverse lesions with characteristic distributions
Stratum corneum
What are the types of superficial fungal infections?
Tinea capitisn – affects children’s scalp
Tinea barbae – affects men’s beards
Tinea corporis – common, affects all ages
Tinea cruris – inguinal areas of obese men
Tinea pedis – athlete’s foot
Tinea versicolor – caused by yeast on upper trunk with different colored macules
These are severe adverse cutaneous drug reactions that predominantly involve the skin and mucous membranes. Both are rare but are considered medical emergencies as they are potentially fatal. Characterized by mucocutaneous tenderness and typically hemorrhagic erosions, erythema and more or less severe epidermal detachment presenting as blisters and areas of denuded skin.
Toxic Epidermal Necrolysis (TEN) – more severe epidermal detachment (>30%)
Stevens Johnson Syndrome (SJS) – less severe epidermal detachment (<10%)
***There is an SJS-TEN overlap where the detachment is mild (10-30%)
