6-1

Question 1

, is an autosomal dominant disorder characterized by diffuse hyperkeratosis of the palms and soles. It is caused by mutations in the gene encoding keratin 1

Answer 1

Diffuse nonepidermolytic palmoplantar keratoderma, otherwise known as Unna Thost type

Question 2

is clinically indistinguishable from the Unna-Thost type but histologically demonstrates epidermolytic hyperkeratosis. This disorder is inherited in an autosomal dominant fashion and is often associated with____ and ___. Mutation in ___

Answer 2

Diffuse epidermolytic palmoplantar keratoderma, otherwise known as the Vorner type,; hyperhidrosis and secondary bacterial infection.; mutations in keratin type 9

Question 3

is an autosomal dominant disorder associated with sensorineural deafness, severe mutilating PPK with a characteristic honeycomb pattern, and constrictions called pseudoainhum that may lead to auto-amputation. Hyperkeratotic starfish-like plaques are commonly observed on the knees, elbows, and dorsal hands.; mutation in ___

Answer 3

Vohwinkel syndrome ; It is caused by mutations in the GJB2 gene, which encodes connexin 26.

Question 4

is an autosomal recessive PPK with diffuse inflammatory keratoderma of the palms and soles that extends to involve the dorsal hands, feet, ankles, and wrists (referred to as___) ; mutations in___.

Answer 4

Mal de Meleda ; transgradiens involvement; SLURP1

Question 5

Like Mal de Meleda, Its distinguishing feature is_____,Both disorders have been localized to abnormalities in___

Answer 5

Papillon–Lefèvre syndrome; early-onset, severe periodontitis; cathepsin C

Question 6

is an autosomal dominant PPK characterized by mutilating keratoderma of the palms and soles, periorificial and often intertriginous inflammatory plaques, and alopecia that begins in infancy. Mutation in ___

Answer 6

Olmsted syndrome; TRPV3 gene,

Question 7

The histopathology for all of the diffuse PPKs except for____ is nonspecific, consisting of considerable ___and a sparse inflammatory infiltrate of lymphocytes in the upper dermis

Answer 7

diffuse epidermolytic palmoplantar keratoderma; hyperkeratosis, hypergranulosis, acanthosis,

Question 8

multiple discrete keratotic plugs on the palms and soles,

Answer 8

Keratosis Punctata Palmaris et Plantaris

Question 9

with depression of the underlying malpighian layer below the general level of the epidermis. There is an increase in the thickness of the granular layer. The dermis is free of inflammation

Answer 9

Keratosis Punctata Palmaris et Plantaris

Question 10

Keratosis Punctata Palmaris et Plantaris- mutation

Answer 10

AAGAB gene

Question 11

Pachyonychia Congenita (PC)
Is characterized by \_\_\_\_\_. Unlike other conditions associated with oral leukokeratoses, the mucosal changes in PC are benign and do not predispose to malignant degeneration

Answer 11

early-onset nail dystrophy followed by the development of focal painful palmoplantar keratoderma

Question 12

blisters that may be seen beneath and around the plantar callosities arise in the upper layers of the ____ through increasing intracellular edema and vacuolization; no areas of necrosis ; mutation in ___

Answer 12

stratum spinosum ; paired keratin genes 6a, 6b, 6c, 16, and 17

Question 13

congenital nail dystrophy that involves all nails is most likely to indicate ___mutations

Answer 13

keratin 6a or 17

Question 14

Childhood PPK with later development of associated features points toward ____and isolated focal nail involvement is rare but most likely to indicate underlying ____ mutations

Answer 14

keratin 16 mutations, ; keratin 6c

Question 15

is a rare condition characterized by shiny, firm, yellow-to-translucent, sometimes umbilicated papules, which develop at the periphery of the palms and soles with extension to the dorsa of the fingers and the sides of the feet

Answer 15

Acrokeratoelastoidosis

Question 16

_____ is the essential histologic feature of acrokeratoelastoidosis,

Answer 16

Elastorrhexis

Question 17

acrokeratoelastoidosis results from___ rather than from degeneration of elastic fibers. Formation of the discrete papules may result from___

Answer 17

failed secretion of elastin from fibroblasts,; filaggrin aggregation

Question 18

The term “porokeratosis” refers to a group of disorders characterized by a distinct “thread-like” peripheral hyperkeratotic ridge that histologically corresponds to___ arising from an invagination of the epidermis

Answer 18

the cornoid lamella, a column of parakeratosis

Question 19

One or more annular, hyperkeratotic plaques that develop in childhood and subsequently enlarge from the periphery over years characterize ___

Answer 19

classic porokeratosis of Mibelli.

Question 20

the most common of the porokeratoses; Multiple (>50) atrophic circinate plaques with a thread-like border occur most commonly on sun-exposed surfaces

Answer 20

Disseminated superficial actinic porokeratosis (DSAP)

Question 21

The main risk factors for DSAP include:

Answer 21

sun exposure, genetic susceptibility, and immunosuppression, presumably because of reduced immune surveillance

Question 22

T/F: Immunosuppressed patients with DSAP do not appear at greater risk for malignant transformation than other patients, in spite of a higher risk of de novo skin cancers

Answer 22

T

Question 23

Mutation in DSAP

Answer 23

Mutations in the mevalonate kinase (MVK) gene

Question 24

form of type II mosaicism, reflecting loss of heterozygosity in early development with proliferation of a single-cell clone ; typically follows Blaschko’s lines

Answer 24

Linear porokeratosis

Question 25

The development of ___ within lesions of porokeratosis is well documented, with {increased/decreased) found in some cases

Answer 25

nonmelanoma skin cancers (predominantly squamous cell carcinoma or Bowen disease) ; increase p53 expression

Question 26

____ representing the most characteristic feature of porokeratosis

Answer 26

the cornoid lamella,

Question 27

Typically, the site at which the parakeratotic column arises lacks a__ layer,

Answer 27

granular

Question 28

In porokeratosis, It is important that the biopsy specimen include the __

Answer 28

peripheral, raised, hyperkeratotic ridge.

Question 29

refers to the EB subtypes demonstrating

intra-epidermal bulla formati

Answer 29

Epidermolysis bullosa simplex (EBS)

Question 30

presents with cleavage through the lamina lucida and therefore heals with scarring

Answer 30

Junctional EB (JEB)

Question 31

Widespread ulceration is often seen in the most severe variant

Answer 31

Herlitz-JEB

Question 32

T/f . Patients with JEB have an especially high risk of highly aggressive squamous cell carcinomas

Answer 32

T

Question 33

Periorificial blistering is particularly prominent in JEB with excessive granulation tissue noted in variants associated with ___

Answer 33

laminin 332 mutation

Question 34

Subepidermal blistering and ulceration is seen in___ ; acral predilection

Answer 34

dystrophic EB

Question 35

present with trauma-induced blistering most predominately in acral locations

Answer 35

Kindler Syndrome ;

Question 36

biopsy is best taken from an __

Answer 36

Induced blister

Question 37

has traditionally been the standard criterion for diagnosis of EB subtypes,

Answer 37

Transmission electron microscopic examination;

Question 38

In EB simplex, the primary separation in induced blisters occurs within the __. Spontaneously arising blisters may be found __

Answer 38

basal cell layer; subepidermally

Question 39

In JEB, the trauma of having a specimen taken for biopsy generally is sufficient to induce separation. This separation is located between

Answer 39

the epidermis and the dermis

Question 40

T/F: There are morphologic and enzymatic abnormalities that can help distinguish the atrophic benign form of JEB from Herlitz–JEB.

Answer 40

F; none

Question 41

The histology of Kindler syndrome depends on the characteristics of the lesion that is biopsied. A skin biopsy from an area of poikiloderma will show ___; A biopsy of a bullous area shows the cleavage plane on different levels.

Answer 41

epidermal atrophy and loss of the rete ridges.

Question 42

Mutations of keratin genes for ___ on chromosome 12 and 17, respectively, have been demonstrated in EBS

Answer 42

KRT5 and KRT14

Question 43

Rarer subtypes of EBS have identified mutations in ___, resulting in poor integration of keratin filaments into hemidesmosomes

Answer 43

in α6β4 integrin and plectin

Question 44

Intraepidermal cleavage is seen in subtypes caused by___. EM examination demonstrates perinuclear retraction of keratin filaments

Answer 44

plakophillin and desmoplakin deficiency

Question 45

In JEB, __ is present mainly on the blister roof but type IV collagen and laminin on the floor

Answer 45

Bullous pemphigoid antigen

Question 46

Mutations in the gene encoding___ located at chromosome band 3p21 have been reported to cause these abnormal findings in the dystrophic forms of EB

Answer 46

type VII collagen (COL 7A1)

Question 47

In both dominant dystrophic EB and in localized recessive dystrophic EB, Immunofluorescence mapping shows all three basement membrane zone constituents—____—on top of the cleavage (119).

Answer 47

bullous pemphigoid antigen, laminin, and type IV collagen

Question 48

Kindler syndrome is unique among EB subtypes in that the layer of separation is variable.___, which is mutated, has important roles in keratinocyte migration, adhesion, and proliferation

Answer 48

The FERMT1 gene

Question 49

is characterized by a localized, recurrent eruption of small vesicles, erosions, and crusted plaques in the intertriginous areas.

Answer 49

Familial Benign Pemphigus (Hailey–Hailey Disease)

Question 50

While early lesions may show small suprabasal separations, so-called__, ; Many cells of the detached stratum malpighii show loss of their intercellular bridges with acantholysis; shows only slight separation from one another because a few intact intercellular bridges still hold them loosely together, leading to the so-called “dilapidated brick wall” appearance of the disease.

Answer 50

lacunae

Question 51

Hailey hailey; mutations to the ___on chromosome 3q, This locus encodes the ___ leads to decreased calcium content in the usually calcium-rich basal keratinocytes

Answer 51

ATP2C1 gene ; SPCA pumps

Question 52

autosomal dominant genodermatosis characterized by progressive hyperkeratotic or crusted papules in a seborrheic distribution; peak age at __

Answer 52

Keratosis Follicularis (Darier Disease); puberty

Question 53

Nails show___ in the nail plate secondary to nail fragility. These nail findings are sometimes referred to as “candy cane nails.”

Answer 53

longitudinal erythronychia, longitudinal leukonychia, and distal v- shaped nicks

Question 54

mutations in found in segmental darier specimens suggest that this is a form of mosaic Darier disease

Answer 54

ATP2A2

Question 55

The characteristic changes in Darier disease include the following:

Answer 55

a specific pattern of dyskeratosis resulting in the formation of corps ronds and grains; suprabasal acantholysis resulting in suprabasal clefts or lacunae; and irregular upward proliferation into the lacunae of papillae lined with a single layer of basal cells, so-called villi

Question 56

The corps ronds occur in the upper stratum malpighii, particularly in the___. Grains are found in the ___and as acantholytic cells within the lacunae

Answer 56

granular and horny layers; horny layer

Question 57

Darier disease is due to mutations in the ATP2A2 gene, which encodes ___ . Diminished functioning of this ubiquitous protein leads to decreased calcium content in

Answer 57

SERCA2 ; The stratum basalis

Question 58

T/F In the familial benign pemphigus, dyskeratosis is much more pronounced than in darier disease,

Answer 58

F; more prounouned in darier

Question 59

The __on electron microscopic examination, are characterized by extensive cytoplasmic vacuolization. ___ are seen to consist of nuclear remnants surrounded by dyskeratotic bundles of tonofilaments.

Answer 59

corps ronds, the grains

Question 60

histologically a distinction between Darier disease and familial benign pemphigus is generally possible, with___ being the predominating factor in Darier disease and ___ in familial benign pemphigus,

Answer 60

dyskeratosis; acantholysis

Question 61

there is slight papillomatosis, which is frequently but not always associated with circumscribed elevations of the epidermis resembling church spires

Answer 61

acrokeratosis verruciformis (AKV)

Question 62

T/F: AKV shows mutations in ATP2A2

Answer 62

T

Question 63

Urticaria pigmentosa is most commonly a sporadic childhood disorder and are associated with __mutations.

Answer 63

c-kit

Question 64

In ____ the cutaneous lesions often improve or even clear at puberty. Systemic involvement is typically absent.

Answer 64

classic childhood urticaria pigmentosa,

Question 65

T/F: In urticaria pigmentosa arising later, in adolescence or adult life, systemic disease is unlikely to be present

Answer 65

F: More likely

Question 66

most common type of urticaria pigmentosa. It consists of dozens or even hundreds of brown lesions that urticate on stroking___ The individual lesions often have a so-called peau d’orange texture.

Answer 66

The first is the maculopapular type, ; (Darier sign)

Question 67

typically occurs in adults and consists of an extensive eruption of brownish red macules showing fine telangiectasias, with little or no urtication on stroking.

Answer 67

telangiectasia macularis eruptiva perstans (TMEP),

Question 68

Systemic involvement occurs most commonly in the__ and ___ types and consists of bone marrow involvement or hepatosplenomegaly

Answer 68

erythrodermic and nodular

Question 69

all types of UP lesions, the histologic picture shows an infiltrate composed chiefly of mast cells, which are characterized by __

Answer 69

the presence of metachromatic granules in their cytoplasm.

Question 70

Mast cell’s granules can be seen well afte staining w/

Answer 70

Giemsa stain or with toluidine blue.

Leder’s method, makes mast cell granules appear red and thus quite conspicuous.

Question 71

In the maculopapular type and in TMEP, the mast cells are limited to ___ and are generally located around capillaries.

Answer 71

the upper third of the dermis

Question 72

In ____ a dense, band-like infiltrate of mast cells with a rather uniform appearance showing round to oval nuclei and a distinctly outlined cytoplasm is observed in the upper dermis.

Answer 72

the diffuse, erythrodermic type,

Question 73

if a biopsy is taken shortly after the lesion has been stroked, an increased number of____ are observed, which is an indication that granules have been released by the cells.

Answer 73

eosinophils and extracellular mast cell granules

Question 74

In contrast with Langerhans cell histiocytosis, the cells of urticaria pigmentosa have _

Answer 74

no tendency to invade the epidermis.

Question 75

Group I EDs are due to defects in___. Mutations have been identified in several important pathways. The prototypical group I ED is __

Answer 75

epithelial mesenchymal interactions; hypohidrotic ED.

Question 76

Group II EDs are due to____ affecting cell adhesion or communication. The prototypical group II ED is__

Answer 76

functional defects in structural proteins,; hidrotic ED.

Question 77

hypoplasia of the hair and the sebaceous glands. There is a variable degree of reduction in their number, size, and degree of maturation

Answer 77

Both the hidrotic and the anhidrotic forms ED

Question 78

The most common form of hypohidrotic ED is an X-linked recessive disorder caused by mutations in the genes for___. Autosomal dominant and autosomal recessive forms are caused by mutations in the___

Answer 78

ectodysplasin (EDA) ; ectodysplasin receptor (EDAR), or mediating proteins (EDARADD)

Question 79

patients with hypohidrotic ED with immunodeficiency have hypomorphic mutations in the____

Answer 79

NF-κB essential modulator (NEMO)

Question 80

Mutations in___ have been identified in the spectrum of disorders with abnormalities of the ectoderm, limb, and orofacial development such as AEC and EEC.

Answer 80

p63

Question 81

mutated gene____ on chromosome 13q12, which encodes ___ is implicated in hidrotic ectodermal dysplasia

Answer 81

gap junction protein beta-6 (GJB6); connexin 30,