| What is urticaria? | ➢ Common disorder mediated by localized mast cell degranulation, which leads to dermal microvascular hyperpermeability.
➢ Resulting erythematous, edematous, and pruritic plaques termed wheals (papules).
➢ Histologic features : usually a sparse superficial perivenular infiltrate of mononuclear cells, rare neutrophils, and sometimes eosinophils.
➢ Superficial dermal edema causes splaying of collagen bundles, making them appear to be more widely spaced than normal.
➢ Degranulation of mast cells, which reside around superficial dermal venules, is difficult to appreciate with routine hematoxylin-eosin (H&E) stains but can be highlighted using a Giemsa stain |
| What is acute eczematous dermatitis? | ➢ Eczema is a clinical term that embraces a number of conditions with varied underlying etiologies.
➢ New lesions take the form of erythematous papules, often with overlying vesicles, which ooze and become crusted.
➢ Pruritus is characteristic.
➢ With persistence, these lesions coalesce into raised, scaling plaques.
➢ The nature and degree of these changes vary among the clinical subtypes, which include the following:
Allergic contact dermatitis
Atopic dermatitis (genetic predisposition)
Drug-related eczematous dermatitis
Photoeczematous dermatitis |
| How is morphology of allergic contact dermatitis? | ➢ skin involvement in contact dermatitis is limited to sites of direct contact with the triggering agent
➢ whereas in other forms of eczema, lesions may be widely distributed.
➢ Spongiosis, or epidermal edema, characterizes all forms of acute eczematous dermatitis—hence the synonym spongiotic dermatitis.
➢ Edema fluid seeps into the epidermis, where it splays apart keratinocytes
➢ Intercellular bridges are stretched and become more prominent and are easier to visualize.
➢ These changes are accompanied by a superficial perivascular lymphocytic infiltrate, edema of dermal papillae, and mast cell degranulation.
➢ Eosinophils may be present and are especially prominent in spongiotic eruptions provoked by drugs, but in general the histologic features are similar regardless of cause, emphasizing the need for careful clinical correlation. |
| What is erythema multiforme? | ➢ Erythema multiforme is characterized by epithelial injury
mediated by skin-homing CD8+ cytotoxic T lymphocytes.
➢ It is an uncommon, usually self-limited disorder that appears to be a hypersensitivity response to certain infections and drugs.
➢ Antecedent infections include those caused by herpes simplex, mycoplasma, and some fungi
➢ Implicated drugs include sulfonamides, penicillin, salicylates, hydantoins, and anti-malarials.
➢ The cytotoxic T cell attack is focused on the basal cells of
cutaneous and mucosal epithelia, presumably due to
recognition of still unknown antigens. |
| How is morphology of erythema multiforme? | ➢ Affected individuals present with a wide array of lesions, which may include macules, papules, vesicles, and bullae (hence the term multiforme).
➢ Well-developed lesions have a characteristic “targetoid” appearance, Target like lesions consist of a pale central blister or zone of epidermal necrosis surrounded by macular erythema.
➢ Early lesions show
✓ a superficial perivascular lymphocytic infiltrate
✓ dermal edema
✓ margination of lymphocytes along the dermoepidermal junction in intimate association with apoptotic keratinocytes
➢ With time, discrete, confluent zones of basal epidermal necrosis appear, with concomitant blister formation. In a rarer and more severe form of this disease, toxic epidermal necrolysis, the necrosis extends through the full thickness of the epidermis |
| What are chronic inflammatory dermatoses? | ➢Psoriasis
➢Lichen Planus
➢Lichen Simplex Chronicus |
| What is psoriasis? | ➢ Psoriasis is a T cell-mediated inflammatory disease, presumed to be autoimmune in origin, although the antigens are not well described.
➢ It is unclear whether the inciting antigens are self-antigens, environmental antigens, or some combination of the two.
➢ Psoriatic lesions can be induced in susceptible individuals by local trauma (Koebner phenomenon), which may induce a local inflammatory response that promotes lesion development. |
| How is psoriasis morphology? | ➢ The typical lesion is a well-demarcated, pink to salmon colored plaque covered by loosely adherent silver-white scale
Histology
➢ Marked epidermal thickening (acanthosis), with regular downward elongation of the rete ridges.
➢ The pattern of this downward growth has been likened to “test tubes in a rack.”
➢ Increased epidermal cell turnover and lack of maturation results in loss of the stratum granulosum and extensive parakeratotic scale.
➢ Also seen is thinning of the epidermal cell layer overlying the tips of dermal papillae (suprapapillary plates), and dilated and tortuous blood vessels within the papillae.
➢ These vessels bleed readily when the scale is removed, giving rise to multiple punctate bleeding points (Auspitz sign)
➢ Neutrophils form small aggregates within both the spongiotic superficial epidermis and the parakeratotic stratum corneum.
➢ Similar changes can be seen in superficial fungal infections, which need to be excluded with appropriate special stains |
| What are clinical features of psoriasis? | ➢ Psoriasis most frequently affects the skin of the elbows, knees, scalp, lumbosacral areas, intergluteal cleft, glans penis, and vulva.
➢ Nail changes on the fingers and toes occur in 30% of cases.
➢ In most cases psoriasis is limited in distribution, but it can be widespread and severe.
➢ Mild disease is treated topically with ointments containing corticosteroids or other immunomodulatory agents
➢ Whereas more severe disease is treated with phototherapy (which has immunosuppressive effects) or systemic therapy with immunosuppressive |
| What is lichen planus? | ➢ Pruritic, Purple, Polygonal, Planar Papules, and Plaques” are the tongue-twisting Ps that describe this disorder of skin and squamous mucosa.
➢ The lesions may result from a CD8+ T cell–mediated cytotoxic response against antigens in the basal cell layer and the dermoepidermal junction that are produced by unknown mechanisms, perhaps as a consequence of a viral infection or drug exposure |
| How is microscopy of lichen planus? | ➢ a prototypical interface dermatitis : so called because the
inflammation and damage are concentrated at the interface of the
squamous epithelium and papillary dermis.
➢ a dense, continuous infiltrate of lymphocytes along the
dermoepidermal junction.
➢ The lymphocytes are intimately associated with basal
keratinocytes, which often atrophy or become necrotic.
➢ Perhaps as a response to damage, the basal cells take on the
appearance of the more mature cells of the stratum spinosum.
➢ This pattern of inflammation causes the dermoepidermal
interface to assume an angulated, zigzag contour (sawtoothing).
➢ Anucleate, necrotic basal cells are seen in the inflamed papillary
dermis and are referred to as colloid bodies or Civatte bodies. |
| How is morphology of lichen planus? | ➢ Cutaneous lesions of lichen planus consist of pruritic,
violaceous, flat-topped papules that may coalesce focally to form plaques.
➢ These papules are highlighted by white dots or lines termed Wickham striae.
➢ Hyperpigmentation may result from melanin loss into the
dermis from damaged keratinocytes. |
| How is microscopy of lichen planus? | ➢ a prototypical interface dermatitis : so called because the inflammation and damage are concentrated at the interface of the squamous epithelium and papillary dermis.
➢ a dense, continuous infiltrate of lymphocytes along the
dermoepidermal junction.
➢ The lymphocytes are intimately associated with basal
keratinocytes, which often atrophy or become necrotic.
➢ Perhaps as a response to damage, the basal cells take on the appearance of the more mature cells of the stratum spinosum.
➢ This pattern of inflammation causes the dermoepidermal interface to assume an angulated, zigzag contour (sawtoothing).
➢ Anucleate, necrotic basal cells are seen in the inflamed papillary dermis and are referred to as colloid bodies or Civatte bodies. |
| How is presentation of lichen planus? | ➢ Although these changes bear some similarities to those in erythema multiforme (another type of interface dermatitis), lichen planus shows well-developed changes of chronicity, including epidermal hyperplasia, hypergranulosis, and hyperkeratosis.
➢ uncommon disorder that usually presents in middle-aged adults. The cutaneous lesions are multiple and are usually symmetrically distributed, particularly on the extremities, and often occur around
➢ the wrists and elbows and on the vulva and glans penis.
➢ Approximately 70% of cases also involve the oral mucosa, where the lesions manifest as white papules with a reticulate or netlike appearance.
➢ The cutaneous lesions of lichen planus usually resolve spontaneously within 1 to 2 years but the oral lesions may persist and be of sufficient severity to interfere with food intake. |
| What is lichen simplex chronicus? | ➢ manifests as roughening of the skin
➢ It is a response to local repetitive trauma, usually from rubbing or scratching.
➢ Nodular forms exist that are referred to as prurigo nodularis.
➢ The lesions often are raised, erythematous, and scaly and can be mistaken for keratinocytic neoplasms.
➢ can be superimposed on and mask another (often pruritic) dermatosis.
➢ It is therefore important to rule out an underlying cause while recognizing that the lesion may be entirely trauma-related. |
| How is morphology of lichen simplex chronicus? | ➢ Acanthosis, hyperkeratosis, and hypergranulosis.
➢ Also seen are elongation of the rete ridges
➢ fibrosis of the papillary dermis, and a dermal chronic
inflammatory infiltrate
➢ Of interest, these lesions are similar in appearance to normal volar (palms and soles) skin, in which skin thickening serves as an adaptation to repetitive mechanical stress. |
| What are bacterial infections dermatoses? | ➢ Numerous bacterial infections occur in skin.
➢ These range from :
Superficial infections known as impetigo
to deeper dermal abscesses associated with puncture
wounds that are caused by bacteria such as
Pseudomonas aeruginosa.
➢ The pathogenesis is similar to that for microbial
infections elsewhere |
| What is impetigo? | ➢ One of the most common bacterial infections of the skin, is seen primarily in children.
➢ The causative organism is usually Staphylococcus aureus or, less commonly, Streptococcus pyogenes
➢ Is typically acquired through direct contact with a source.
➢ Impetigo often begins as a single small macule, usually on the extremities or the face near the nose or the mouth, which rapidly evolves into a larger lesion often with a honey-colored crust of dried serum.
➢ Individuals who are colonized by S. aureus or S. pyogenes (usually nasal or anal) are more likely to be affected.
➢ A less common bullous form of childhood impetigo may mimic an autoimmune blistering disorder. |
| How is morphology of impetigo? | ➢ Impetigo is characterized by an accumulation of neutrophils beneath the stratum corneum that often produces a subcorneal pustule.
➢ Nonspecific reactive epidermal alternation and superficial dermal inflammation accompany these findings.
➢ Bacterial cocci in the superficial epidermis can be demonstrated by Gram stain. |
| What are fungal infections dermatoses? | ➢ Fungal infections are varied, ranging from superficial
infections with Tinea or Candida to life-threatening Aspergillus infections in immunosuppressed individuals.
➢ Fungal infections can be :
▪ Superficial (stratum corneum, hair, and nails)
▪ Deep (dermis or subcutis)
▪ Systemic : arising through hematogenous spread, often in an immunocompromised patient.\
➢ Superficial infections usually produce erythematous macules with superficial scale that can be pruritic
➢ While deeper infections such as those seen with Aspergillus are erythematous and often nodular and sometimes associated with local hemorrhage.
➢ Superficial fungal infections may have an annular appearance.
➢ However, they also may induce lesions that mimic other psoriasiform or eczematous dermatoses, so it is important to consider the possibility of fungal infection when these conditions are in the differential diagnosis. |
| How is morphology of fungal infection dermatoses? | ➢ The histologic appearance varies depending on :
the organism, The host response The degree of superinfection.
➢ Superficial infections are often associated with a neutrophilic infiltrate in the epidermis.
➢ Deep fungal infections produce greater tissue damage and often elicit a granulomatous response.
➢ Aspergillus can be angioinvasive.
➢ Periodic acid–Schiff (PAS) and Gomori methenamine silver stains are helpful in identifying the fungal organisms. |
| What are warts? | ➢ Verrucae are proliferative lesions of squamous epithelial cells that are caused by human papillomavirus (HPV).
➢ They are most common in children and adolescents, but may be encountered in any age group.
➢ HPV infection usually stems from direct contact with an
infected individual or autoinoculation.
➢ Verrucae generally are self-limited, most often regressing spontaneously within 6 months to 2 years.
➢ While some members of the HPV family are associated with preneoplastic and invasive cancers of the anogenital region cutaneous warts are mainly caused by low-risk HPV subtypes.
➢ Because the growth of warts is normally halted by the immune response, immunodeficiency is associated with more numerous and larger verrucae |
| How is morphology of warts? | ➢ Different kinds of warts are identified on the basis of their gross appearance and location and generally are caused by distinct HPV subtypes.
➢ Verruca vulgaris :most common type, can occur anywhere but most frequent on the hands (dorsal surfaces and periungual areas) It appears as a gray-white to tan, flat to convex, 0.1- to 1-cm papule with a rough, pebble like surface.
➢ Verruca plana, or flat wart : common on the face or dorsal surfaces of the hands. These warts are flat, smooth, tan macules.
➢ Verruca plantaris and verruca palmaris : occur on the soles and palms, respectively. These rough, scaly lesions can reach 1 to 2 cm in diameter and may coalesce to form a surface that can be confused with ordinary calluses |
| How is morphology of condyloma acuminatum? | Occurson the penis, female genitalia, urethra, and perianal areas
➢ Histologic features common to verrucae include :
▪ Epidermal hyperplasia : often undulant in character (so-called verrucous or papillomatous epidermal hyperplasia)
▪ Cytoplasmic vacuolization (koilocytosis) : preferentially
involves the more superficial epidermal layers, producing halos of pallor surrounding infected nuclei.
▪ Infected cells also may demonstrate prominent keratohyalin granules and jagged eosinophilic intracytoplasmic protein aggregates as a result of impaired maturation |
| What are bullous disorders? | ➢ Although vesicles and bullae (blisters) occur as secondary phenomena in several unrelated conditions (e.g., herpesvirus infection, spongiotic dermatitis)
➢ there is a group of disorders in which blisters are the primary and most distinctive feature.
➢ Blistering in these diseases tends to occur at specific levels within the skin, a morphologic distinction that is critical for diagnosis.
➢ These disorders are classified based on the level of the
epidermis that is affected.
➢ often caused by autoantibodies specific for epithelial or basement membrane proteins that lead to unmooring of keratinocytes (acantholysis). |
| What is pemiphigus? | ➢ Pemphigus is an uncommon autoimmune blistering disorder resulting from loss of normal intercellular attachments within the epidermis and the squamous mucosal epithelium.
➢ There are three major variants:
• Pemphigus vulgaris (the most common type)
• Pemphigus foliaceus
• Paraneoplastic pemphigus
➢ Autoimmune diseases caused by antibody-mediated (type II) hypersensitivity reactions.
➢ The pathogenic antibodies are IgG autoantibodies that bind to intercellular desmosomal proteins found in the skin and mucous membranes.
➢ The antibodies disrupt the intercellular adhesive function of desmosomes and may activate intercellular proteases as well |
| How is morphology of pemphigus? | ➢ Pemphigus vulgaris involves both mucosa and skin
➢ Especially : scalp, face, axillae, groin, trunk, and points of pressure.
➢ The lesions are superficial flaccid vesicles and bullae that
rupture easily, leaving deep and often extensive erosions
covered with a serum crust .
➢ Pemphigus foliaceus, a rare, milder form of pemphigus, results in bullae that are mainly confined to the skin, with only infrequent involvement of mucous membranes.
➢ The blisters in this disorder are superficial, such that more
limited zones of erythema and crusting of ruptured blisters are seen. |
| How is acantholysis? | ➢ The common histologic denominator in all forms of pemphigusis acantholysis, lysis of the intercellular adhesive junctions between neighboring squamous epithelial cells that results in the rounding up of detached cells.
▪ In pemphigus vulgaris, acantholysis selectively involves the layer of cells immediately above the basal cell layer, giving rise to a suprabasal acantholytic blister.
▪ In pemphigus foliaceus, acantholysis selectively involves the superficial epidermis at the level of the stratum granulosum
➢ Variable superficial dermal infiltrates composed of lc,MP, eosinophils, accompany all forms of pemphigus.
➢ By direct IF study, lesional sites show a characteristic fishnetlike pattern of intercellular IgG deposits |
| What is bullous pemphigoid? | ➢ distinctive acquired blistering disorder with an autoimmune basis
➢ Blistering in BP is triggered by the linear deposition of
autoreactive IgG antibodies and complement in the epidermal basement membrane
➢ The proteins that are recognized by the autoantibodies have structural roles in dermoepidermal adhesion.
➢ Bullous pemphigoid and
➢ pemphigus vulgaris are thus caused by similar pathogenic mechanisms, but differ in their clinical presentation and course due to variation in the location of the target antigen |
| How is bullous pemphigoid morphology? | ➢ Bullous pemphigoid is associated with tense subepidermal bullae filled with clear fluid
➢ The overlying epidermis characteristically lacks acantholysis.
➢ Early lesions show variable numbers of eosinophils at the
dermal-epidermal junction, occasional neutrophils, superficial dermal edema, and associated basal cell layer vacuolization.
➢ The vacuolated basal cell layer eventually gives rise to a fluidfilled blister
➢ The blister roof consists of full-thickness epidermis with intact intercellular junctions, a key distinction from the blisters seen in pemphigus. |
| What is dermatitis herpetiformis? | ➢ Dermatitis herpetiformis is an autoimmune blistering disorder associated with gluten sensitivity that is characterized by extremely pruritic grouped vesicles and papules.
➢ The disease affects predominantly males, often in the third and fourth decades of life.
➢ Up to 80% of cases are associated with celiac disease;
➢ conversely, only a small fraction of patients with celiac disease develop dermatitis herpetiformis.
➢ Like celiac disease, dermatitis herpetiformis responds to a gluten-free diet.
➢ Genetically predisposed individuals develop IgA antibodies to dietary gluten as well as IgA autoantibodies that cross-react with endomysium and tissue transglutaminases, including epidermal transglutaminase expressed by keratinocytes.
➢ By direct immunofluorescence, the skin shows discontinuous, granular deposits of IgA selectively localized in the tips of dermal papillae |
| How is morphology of dermatitis herpatiformis? | ➢ The lesions are bilateral, symmetric, and grouped and preferentially involve the extensor surfaces, elbows, knees, upper back, and buttocks
➢ Initially, neutrophils accumulate selectively at the tips of dermal papillae, forming small microabscesses
➢ The basal cells overlying these microabscesses show vacuolization and focal dermoepidermal separation that ultimately coalesce to form a true |
| What is seborrheic keratosis? | ➢ SK are common pigmented epidermal tumors occur most
frequently in middle-age or older individuals.
➢ They arise spontaneously and are particularly numerous on the trunk, although the extremities, head, and neck also may be sites of involvement.
➢ Except for cosmetic concerns, SK are usually of little clinical importance.
➢ However, in rare patients hundreds of lesions may appear suddenlyas a paraneoplastic syndrome (sign of Leser-Trelat).
➢ Patients with this presentation may harbor internal malignancies, most commonly gastrointestinal tract carcinomas, which produce growth factors that stimulate epidermal proliferation |
| How is morphology of seborrheic keratosis? | ➢ Round, exophytic, coinlike plaques that vary in diameter from millimeters to centimeters and have a “stuck-on” appearance
➢ They are tan to dark brown and have a velvety- to granularappearing surface.
➢ Occasionally, their dark color is suggestive of melanoma, leading to surgical removal.
➢ Microscopically, composed of monotonous sheets of small cells that resemble the basal cells of the normal epidermis
➢ Variable melanin pigmentation is present within these basaloid cells, accounting for the brown coloration seen grossly.
➢ Hyperkeratosis occurs at the surface, and the presence of small keratin-filled cysts (horn cysts) and downgrowth of keratin into the main tumor mass (pseudo–horn cysts) are characteristic features. |
| What is actinic keratosis? | ➢ Premalignant lesion
➢ Because such lesions usually are the result of chronic exposure to sunlight and are associated with hyperkeratosis, they are called actinic (sun-related) keratoses.
➢ The rate of progression to squamous cell carcinoma is small, varying from 0.1% to 2.6% per year.
➢ Most regress or remain stable.
➢ increase in incidence with age and sun exposure |
| How is actinic keratosis morphology? | ➢ usually <1 cm in diameter, tanbrown or red, and rough
(sandpaper-like) to the touch
➢ Microscopically, lower portions of the epidermis show
cytologic atypia, often associated with hyperplasia of basal
cells or with atrophy and diffuse thinning of the epidermal
surface.
➢ The dermis contains thickened, blue-gray elastic fibers (solar elastosis), the result of chronic sun damage.
➢ The stratum corneum is thickened and shows abnormal
retention of nuclei (parakeratosis).
➢ Uncommonly, full-thickness epidermal atypia is seen; such lesions are considered squamous cell carcinoma in situ |
| What is squamous cell carcinoma? | ➢ Cutaneous squamous cell carcinoma is mainly caused by UV light exposure, which leads to widespread DNA damage and extremely high mutational loads
➢ Patients with the rare disorder xeroderma pigmentosum, which disrupts repair of UV-induced DNA damage, are at an exceptionally high risk.
➢ Immunosuppression, particularly in organ transplant recipients, is associated with an increased incidence of cutaneous squamous cell carcinomas that are likely to be associated with HPV infection.
➢ Other predisposing factors include industrial carcinogens (tars and oils), chronic nonhealing ulcers, old burn scars, ingestion of arsenicals, and ionizing radiation. |
| How is morphology of squamous cell carcinoma? | ➢ Squamous cell carcinomas in situ appear as sharply defined, red, scaling plaques; some appear to arise in association with prior actinic keratoses.
➢ Microscopically, squamous cell carcinoma in situ is
characterized by highly atypical cells at all levels of the
epidermis, with nuclear crowding and disorganization.
➢ More advanced, invasive squamous cell carcinomas are
nodular, often scaly lesions that may undergo ulceration.
➢ Such tumors show variable degrees of differentiation, ranging from tumors with cells arranged in orderly lobules that exhibit extensive keratinization to neoplasms consisting of highly anaplastic cells with foci of necrosis and only abortive, singlecell keratinization (dyskeratosis) |
| How are clinical features of squamous cell carcinoma? | ➢ Invasive squamous cell carcinomas of the skin often are
discovered while small and resectable (<1% will have metastatic lymph nodes at diagnosis).
➢ The metastasis risk is related to the thickness of the lesion and degree of invasion into the subcutis.
➢ Tumors arising from actinic keratoses may be locally aggressive but generally metastasize only after long periods of time
➢ Those arising in burn scars, ulcers, and non–sun-expose skin often behave more aggressively.
➢ Squamous cell carcinomas arising at internal sites are generally invasive and aggressive, possibly because (unlike in the skin) early lesions go unrecognized. |
| What is basal cell carcinoma? | ➢ common slow-growing cancer that rarely metastasizes.
➢ It tends to occur at sites subject to chronic sun exposure and in lightly pigmented individuals.
➢ Basal cell carcinomas manifest as pearly papules, often with prominent, dilated subepidermal blood vessels (telangiectasia).
➢ Some tumors contain melanin pigment and can have an
appearance similar to melanocytic nevi or melanomas.
➢ Microscopically, the tumor cells resemble the normal
epidermal basal cell layer or follicular germinative elements.
➢ Because they arise from either the epidermis or the follicular epithelium, they are not encountered on mucosal surfaces. |
| What are patterns of basal cell carcinoma? | ➢ Two common patterns are seen:
• multifocal superficial growths, originating from the epidermis,
• nodular lesions growing downward into the dermis as cords and islands of variably basophilic cells with hyperchromatic nuclei, embedded in a fibrotic or mucinous stromal matrix.
➢ Peripheral tumor cell nuclei align in the outermost layer (a pattern termed palisading), which often separates from the stroma, creating a characteristic cleft
➢ By far the most important risk factor is cumulative sun
exposure;
➢ Advanced lesions may ulcerate, and extensive local invasion of bone or facial sinuses may occur if the lesions are neglected.
➢ Metastasis is exceedingly rare. |
| What is melanocytic nevi? | ➢ Strictly speaking, the term nevus denotes any congenital lesion of the skin.
➢ Melanocytic nevus, however, refers to any benign congenital or acquired neoplasm of melanocytes.
➢ Commonly tan-to-brown, uniformly pigmented, small papules (5 mm or less across) with well-defined, rounded borders.
➢ Early lesions are composed of round to oval cells that grow in "nests” along the dermoepidermal junction.
➢ Nuclei are uniform and round, and contain inconspicuous nucleoli with little or no mitotic activity.
➢ Such early-stage lesions are called junctional nevi. |
| What is dysplastic nevus? | ➢ Dysplastic nevi may be sporadic or familial.
➢ The latter are important clinically because they identify
individuals who have an increased risk of developing
melanoma.
➢ As with conventional melanocytic nevi, activating RAS or
BRAF mutations are commonly found in dysplastic nevi and
are believed to have a pathogenic role.
➢ larger than most acquired nevi (often more than 5 mm across) and may number in the hundreds.
➢ flat macules to slightly raised plaques, with a “pebbly” surface
➢ They usually have variable pigmentation (variegation) and irregular borders |
| How is morphology of dysplastic nevus? | ➢ Microscopically, dysplastic nevi are mostly compound nevi that exhibit both architectural and cytologic evidence of
abnormal growth.
➢ Nevus cell nests within the epidermis may be enlarged and exhibit abnormal fusion or coalescence with adjacent nests (bridging).
➢ As part of this process, single nevus cells begin to replace the normal basal cell layer along the dermo epidermal junction, producing so-called “lentiginous hyperplasia”.
➢ Cytologic atypia consisting of irregular, often angulated,
nuclear contours and hyperchromasia is frequently observed |
| What is melanoma? | ➢ Melanoma is less common but much more deadly than basal or squamous cell carcinoma.
➢ The incidence of these lesions has increased dramatically over the past several decades, at least in part as a result of increasing sun exposure and/or higher detection rates resulting from vigorous surveillance.
➢ Mainly caused by UV light–induced DNA damage that leads to the stepwise acquisition of driver mutations.
➢ Hereditary predisposition also plays a role in an estimated 5% to 10% of cases.
➢ Key phases of melanoma development are marked by
➢ radial and vertical growth. |
| How is natural hx of melanoma? | ➢ The earliest recognizable phase of melanoma development is proposed to consist of lateral expansion of melanocytes along the dermoepidermal junction (lentiginous hyperplasia and lentiginous compound nevus;)
➢ This then progresses to the phase of melanoma in situ, which is marked by radial growth within the epidermis, often for a prolonged period.
➢ During this stage, melanoma cells do not have the capacity to invade and metastasize.
➢ With time, a vertical growth phase supervenes, in which the tumor grows downward into the deeper dermal layers as an expansile mass lacking cellular maturation
➢ This event often is heralded by the development of a nodule in a previously flat lesion and correlates with the emergence of metastatic |
| How is molecular pathogenesis of melanoma? | ➢ Note that no melanocytic nevus precursor is identified in most cases of melanoma.
➢ They are believed to arise de novo, perhaps all using the same pathway.
➢ The initiating event appears to be an activating mutation in BRAF or (less commonly) RAS.
➢ This, usually, produces only a benign nevus unless other
mutations are superimposed.
➢ Sequencing of nevi with “atypical” morphologic features
suggestive of melanoma as well as melanomas in the radial
phase of growth (melanoma in situ) has shown that they
commonly harbor mutations that activate the expression of
telomerase. |
| What are clinical features of melanoma? | ➢ Melanoma of the skin usually is asymptomatic, although pruritus may be an early manifestation.
➢ The most important clinical sign is a change in the color or size of a pigmented lesion.
➢ The main clinical warning signs are as follows:
1. Rapid enlargement of a preexisting nevus
2. Itching or pain in a lesion
3. Development of a new pigmented lesion during adult life
4. Irregularity of the borders of a pigmented lesion
5. Variegation of color within a pigmented lesion
➢ These principles are expressed in the so-called “ABCs” of
melanoma: asymmetry, border, color, diameter, and evolution |
| How is morphology of melanoma? | ➢ Unlike benign nevi, melanomas often exhibit striking variations in pigmentation, including shades of black, brown, red, dark blue, and gray
➢ The borders are irregular and often “notched.”
➢ Microscopically, malignant cells grow as poorly formed nests or as individual cells at all levels of the epidermis (pagetoid spread) and in expansile dermal nodules;
➢ These constitute the radial and vertical growth phases,
respectively
➢ Of note, superficial spreading melanomas are often associated with a brisk lymphocytic infiltrate a feature that may reflect a host response to tumor-specific antigens. |
