51: Porokeratosis

Question 1

What are the clinical characteristics of Porokeratosis of Mibelli?

Answer 1

Porokeratosis of Mibelli is characterized by:
- Onset: Begins during infancy or childhood, autosomal dominant.
- Appearance: Asymptomatic, small, brown to skin-colored, annular papules with a well-demarcated hyperkeratotic border usually more than 1 mm in height, featuring a characteristic longitudinal furrow.
- Center of Lesion: May be hyperpigmented, hypopigmented, depressed, atrophic, or anhidrotic.
- Size: Lesions range from millimeters to several centimeters, with giant lesions up to 20 cm being rare and predominantly occurring on the lower leg and foot, associated with higher malignant potential.
- Persistence: Lesions persist indefinitely.

Question 2

What is the epidemiology of Disseminated Superficial Actinic Porokeratosis (DSAP)?

Answer 2

Disseminated Superficial Actinic Porokeratosis (DSAP) is characterized by:
- Prevalence: Most common form of porokeratosis.
- Genetics: Autosomal dominant inheritance.
- Onset: Earliest onset at 7 years, fully penetrant by the third or fourth decade of life.
- Lesion Characteristics: Uniformly small, annular, asymptomatic, or mildly pruritic papules ranging from 2 to 5 mm in diameter, symmetrically distributed on the extremities.
- Location: More generalized than other forms, with >50 lesions predominantly in sun-exposed sites, sparing palms, soles, and mucous membranes.
- Progression: Older lesions become atrophic and anhidrotic.

Question 3

What distinguishes Disseminated Superficial Porokeratosis (DSP) from DSAP?

Answer 3

Disseminated Superficial Porokeratosis (DSP) is characterized by:
- Genetics: Autosomal dominant inheritance.
- Onset: Occurs in the 3rd to 4th decade of life.
- Morphology: Morphologically identical to DSAP, with lesions occurring on the extremities.
- Distribution: Typically distributed symmetrically but does not spare sun-protected areas as seen in DSAP.

Question 4

A patient with porokeratosis has lesions on sun-exposed areas but no history of immunosuppression. What type of porokeratosis is most likely?

Answer 4

The most likely type is Disseminated Superficial Actinic Porokeratosis (DSAP).

Question 5

What is the clinical significance of the cornoid lamella in porokeratosis?

Answer 5

The cornoid lamella is a histopathologic feature corresponding to the raised hyperkeratotic border evident clinically.

Question 6

A patient presents with porokeratosis lesions that are more generalized and involve non-sun-exposed areas. What type of porokeratosis is this?

Answer 6

This is Disseminated Superficial Porokeratosis (DSP).

Question 7

What is the gender distribution for Disseminated Superficial Actinic Porokeratosis (DSAP) and Porokeratosis Palmaris et Plantaris Disseminata?

Answer 7

DSAP is twice as likely to occur in women, while Porokeratosis Palmaris et Plantaris Disseminata affects males twice as often as females.

Question 8

What is the clinical course of Porokeratosis of Mibelli, and what is its malignant potential?

Answer 8

Porokeratosis of Mibelli persists indefinitely and has a higher malignant potential, especially in giant lesions.

Question 9

What are the clinical features of Disseminated Superficial Actinic Porokeratosis (DSAP)?

Answer 9

DSAP features small, annular, asymptomatic or mildly pruritic papules distributed symmetrically on sun-exposed extremities, sparing the palms, soles, and mucous membranes.

Question 10

A patient presents with hyperkeratotic papules surrounded by a threadlike elevated border that expands centrifugally. What is the most likely diagnosis, and what histological feature would confirm it?

Answer 10

The most likely diagnosis is porokeratosis. The histological feature that confirms it is the presence of a cornoid lamella, a thin column of parakeratotic cells extending through the stratum corneum.

Question 11

A 35-year-old woman presents with more than 50 small, annular, mildly pruritic papules on sun-exposed extremities. What is the most likely type of porokeratosis, and what is its inheritance pattern?

Answer 11

The most likely type is Disseminated Superficial Actinic Porokeratosis (DSAP), which has an autosomal dominant inheritance pattern.

Question 12

A child develops asymptomatic, small, brown annular papules with a hyperkeratotic border on the lower leg. What type of porokeratosis is this, and what is its potential risk?

Answer 12

This is Porokeratosis of Mibelli, which has a potential risk of malignant transformation, especially in giant lesions.

Question 13

How does Disseminated Superficial Actinic Porokeratosis (DSAP) differ from other forms of porokeratosis in terms of clinical presentation and epidemiology?

Answer 13

• Epidemiology: Most common form of porokeratosis, occurs predominantly in fair-skinned individuals.
• Onset: Earliest onset at 7 years, fully penetrant by the third or fourth decade of life.
• Lesion Characteristics: Uniformly small, annular, asymptomatic, or mildly pruritic papules ranging from 2 to 5 mm in diameter.
• Distribution: Distributed symmetrically on the extremities, more generalized with >50 lesions in sun-exposed sites.
• Spare Areas: Typically spares palms, soles, and mucous membranes.
• Progression: Older lesions become atrophic and anhidrotic, with a subtle hyperkeratotic border.

Question 14

What are the key differences in the clinical presentation of Disseminated Superficial Porokeratosis (DSP) compared to Disseminated Superficial Actinic Porokeratosis (DSAP)?

Answer 14

Feature | Disseminated Superficial Actinic Porokeratosis (DSAP) | Disseminated Superficial Porokeratosis (DSP) |
|———|————————————————–|————————————————–|
| Onset | Earliest at 7 years, penetrant by 3rd or 4th decade | Onset at 3rd to 4th decade of life |
| Lesion Characteristics | Small, annular, asymptomatic, or mildly pruritic | Morphologically identical to DSAP |
| Distribution | Symmetrically on extremities, spares palms and soles | Occurs on extremities, does not spare sun-protected areas |
| Lesion Count | More generalized with >50 lesions | Similar distribution but not specified |
| Progression | Older lesions become atrophic and anhidrotic | Not specified |

Question 15

What are the characteristics and clinical implications of Disseminated Superficial Porokeratosis of Immunosuppression?

Answer 15

• Recognized after renal, hepatic, and cardiac transplantation, as well as after immunosuppressive chemotherapy and other treatments.
• Similar distribution and morphology to DSAP, but less evident history of sun exposure.
• Associated with conditions like HIV infection and Type 2 DM.
• Can occur after bone marrow transplantation without ongoing immunosuppressive therapy.

Question 16

What distinguishes Linear Porokeratosis from other types of porokeratosis?

Answer 16

• Traditionally seen as a separate entity, now recognized as a mosaic manifestation of other types.
• Two clinical variants: unilateral lesions following Blaschko lines and a rare generalized form affecting multiple extremities.
• Highest potential for malignant degeneration among porokeratoses, possibly due to allelic loss from a postzygotic mutation.

Question 17

What are the key features of Porokeratosis Palmaris et Plantaris Disseminata?

Answer 17

• An autosomal dominant genodermatosis characterized by small, uniform lesions on palms and soles.
• Lesions can spread to other body parts, including mucous membranes.
• Palmar and plantar lesions are hyperkeratotic with a pronounced longitudinal furrow.
• Typically appears during adolescence or early adulthood, affecting males more than females.

Question 18

How does Punctate Porokeratosis present and how is it differentiated from other conditions?

Answer 18

• Appears during adolescence or adulthood, often alongside other types of porokeratosis.
• Characterized by multiple minute, discrete, hyperkeratotic lesions with a thin, raised margin on palms and soles.
• Must be differentiated clinically and histologically from punctate keratoderma.

Question 19

What are the main phenotypic features of CDAGS Syndrome and its association with porokeratosis?

Answer 19

• Main features include craniosynostosis, clavicular hypoplasia, anal anomalies, and porokeratosis.
• An autosomal recessive trait possibly linked to chromosome band 22q12-1.
• Cutaneous manifestations include widespread porokeratotic papules from 1 month of age, primarily affecting the face and extremities, with photoaggravation of lesions.

Question 20

What genetic factors are associated with the etiology of porokeratosis?

Answer 20

• Genetically heterogeneous disorder with multiple loci identified.
• Splicing mutation in phosphomevalonate kinase (PMVK) linked to DSAP.
• The MVK gene on chromosome 12q24 identified as a causative gene in DSAP, involved in keratinocyte differentiation and protection against UV-induced apoptosis.

Question 21

What are the two clinical variants of Linear Porokeratosis, and which has a higher malignant potential?

Answer 21

The two variants are unilateral lesions confined to an extremity following Blaschko lines and a rare generalized form involving multiple extremities and the trunk. The linear variant has the highest malignant potential.

Question 22

What is the role of the MVK gene in the pathogenesis of porokeratosis?

Answer 22

The MVK gene regulates calcium-induced keratinocyte differentiation and protects against UVA-induced apoptosis.

Question 23

What are the main phenotypic features of CDAGS Syndrome?

Answer 23

The main features include craniosynostosis, clavicular hypoplasia, anal anomalies, genitourinary malformations, and porokeratosis.

Question 24

What is the clinical presentation of Punctate Porokeratosis, and how does it differ from other types?

Answer 24

Punctate Porokeratosis presents as multiple minute, discrete punctate hyperkeratotic lesions on the palms and soles. It differs by its punctate morphology and lack of malignant potential.

Question 25

What is the inheritance pattern of Porokeratosis Palmaris et Plantaris Disseminata, and when do lesions typically appear?

Answer 25

It has an autosomal dominant inheritance pattern, and lesions typically appear during adolescence or early adulthood.

Question 26

A patient with a history of renal transplantation develops porokeratosis-like lesions. What type of porokeratosis is most likely, and what is a distinguishing feature?

Answer 26

The most likely type is Disseminated Superficial Porokeratosis of Immunosuppression. A distinguishing feature is that a history of sun exposure is less evident compared to DSAP.

Question 27

A patient presents with unilateral lesions confined to an extremity following Blaschko lines. What type of porokeratosis is this, and what is its genetic basis?

Answer 27

This is Linear Porokeratosis, which is thought to result from allelic loss caused by a postzygotic mutation, representing a type 2 segmental manifestation of an autosomal dominant disorder.

Question 28

A male adolescent develops small, hyperkeratotic lesions on the palms and soles that spread to other body parts. What type of porokeratosis is this, and what is its inheritance pattern?

Answer 28

This is Porokeratosis Palmaris et Plantaris Disseminata, which has an autosomal dominant inheritance pattern.

Question 29

A patient presents with multiple minute, discrete punctate hyperkeratotic lesions on the palms and soles. What is the diagnosis, and what condition must it be differentiated from?

Answer 29

The diagnosis is Punctate Porokeratosis, and it must be differentiated from punctate keratoderma.

Question 30

A 1-month-old infant develops widespread porokeratotic papules predominantly on the face and extremities. What syndrome is this, and what are its genetic characteristics?

Answer 30

This is CDAGS Syndrome, an autosomal recessive trait possibly linked to chromosome band 22q12.

Question 31

What gene mutation has been identified as causative in Disseminated Superficial Actinic Porokeratosis (DSAP), and what is its role?

Answer 31

The mevalonate kinase (MVK) gene mutation on chromosome 12q24 is causative in DSAP.

Question 32

What syndrome is characterized by widespread porokeratotic papules in a 1-month-old infant?

Answer 32

This is CDAGS Syndrome, an autosomal recessive trait possibly linked to chromosome band 22q12.

Question 33

What gene mutation is causative in Disseminated Superficial Actinic Porokeratosis (DSAP)?

Answer 33

The mevalonate kinase (MVK) gene mutation on chromosome 12q24 is causative in DSAP. Its product regulates calcium-induced keratinocyte differentiation and protects against UVA-induced apoptosis.

Question 34

What is the genetic basis of Linear Porokeratosis?

Answer 34

Linear Porokeratosis is caused by allelic loss due to a postzygotic mutation and manifests as unilateral lesions following Blaschko lines or a generalized form involving multiple extremities.

Question 35

What are the clinical implications of the female predominance in disseminated forms of porokeratosis?

Answer 35

The female predominance (2:1) in disseminated forms of porokeratosis suggests potential hormonal or genetic factors influencing the disease's manifestation, impacting screening and treatment approaches.

Question 36

How does Linear Porokeratosis present in its common and rare forms?

Answer 36

Linear Porokeratosis presents as: 1. Common form: Unilateral lesions following Blaschko lines. 2. Rare generalized form: Multiple lesions affecting several extremities and possibly the trunk.

Question 37

What are the distinguishing features of Punctate Porokeratosis?

Answer 37

Punctate Porokeratosis is characterized by multiple minute, discrete, hyperkeratotic lesions with a thin, raised margin on the palms and soles.

Question 38

What are the main phenotypic features of CDAGS Syndrome?

Answer 38

CDAGS Syndrome is characterized by craniosynostosis, clavicular hypoplasia, anal anomalies, and porokeratosis with widespread papules.

Question 39

What genetic mutations are associated with Disseminated Superficial Porokeratosis (DSP)?

Answer 39

DSP is associated with splicing mutations in the phosphomevalonate kinase (PMVK) gene and the mevalonate kinase (MVK) gene.

Question 40

What are the common histopathological features of porokeratosis?

Answer 40

Common features include hyperkeratosis of the stratum corneum, presence of the cornoid lamella, and a granular layer that may be absent or reduced.

Question 41

What are the treatment options for problematic porokeratosis lesions?

Answer 41

Treatment options include topical steroids, keratolytics, topical retinoids, 5-fluorouracil, imiquimod, cryotherapy, and laser therapies.

Question 42

What is the prognosis for patients with porokeratosis?

Answer 42

The prognosis varies; generally benign but malignant degeneration may occur in 7% to 11% of individuals.

Question 43

What are the differential diagnoses for localized lesions similar to porokeratosis?

Answer 43

Differential diagnoses include granuloma annulare, actinic keratosis, and viral warts.

Question 44

What is the malignant potential of porokeratosis?

Answer 44

Malignancy occurs in 7% to 11% of cases, with squamous cell carcinoma being the most frequently associated tumor.

Question 45

What is the recommended clinical approach for suspicious lesions in giant porokeratosis?

Answer 45

Closer disease surveillance and a lower threshold for biopsy of suspicious lesions are recommended.

Question 46

What is the significance of p53 and pRb overexpression in porokeratosis lesions?

Answer 46

Overexpression indicates dysplastic potential and a risk for malignant transformation.

Question 47

What is the role of disease surveillance in managing porokeratosis?

Answer 47

Disease surveillance is crucial for monitoring lesion progression and identifying malignant transformation early.

Question 48

What treatment options are available for squamous cell carcinomas associated with porokeratosis?

Answer 48

Treatment options include electrochemotherapy with intralesional bleomycin and surgical interventions.

Question 49

What are the histopathological features observed in porokeratosis?

Answer 49

Histopathological features of porokeratosis include: 1. **Hyperkeratosis** of the stratum corneum with a thin column of poorly staining parakeratotic cells. 2. Presence of the **cornoid lamella** running through surrounding normal-staining cells. 3. The granular layer beneath the cornoid lamella may be **absent or markedly reduced**. 4. The epidermis in the central portion may be **normal, hyperplastic, or atrophic**. 5. The cornoid lamella is not pathognomonic and can be found in other conditions such as **viral warts** and **ichthyoses**.

Question 50

What treatment options are available for porokeratosis, and when is intervention necessary?

Answer 50

Treatment options for porokeratosis include: **Topical**: Potent topical steroids, keratolytics, topical retinoids, topical 5-fluorouracil, imiquimod 5%, calcipotriol, anthralin, cryotherapy, carbon dioxide laser, pulsed dye laser, Nd:YAG laser; **Systemic**: Oral retinoids; **Surgical**: Curettage, excision, dermabrasion. Intervention is usually unnecessary, and **disease surveillance** is standard unless lesions are problematic or cosmetically unacceptable.

Question 51

What is the prognosis for patients with porokeratosis, particularly in relation to malignant degeneration?

Answer 51

The prognosis for patients with porokeratosis varies: Typically, the disease progresses over **decades** in **PM** (Porokeratosis Mibelli) but may be rapid in **DSAP** (Disseminated Superficial Actinic Porokeratosis), especially after sun exposure. The disease is generally considered **benign**, but malignant degeneration may occur in **7% to 11%** of individuals. **SCC** (squamous cell carcinoma) is the most frequently associated tumor and may be invasive, with reports of **Bowen disease** and **basal cell carcinoma** as well. **Spontaneous resolution** of lesions has been reported, although it is exceptionally rare.

Question 52

What are the inheritance patterns and risk factors associated with the different subtypes of porokeratosis?

Answer 52

| Subtype | Inheritance and Risk Factors | |---------|-----------------------------| | Porokeratosis of Mibelli | Autosomal dominant | | Disseminated superficial actinic porokeratosis (DSAP) | Autosomal dominant | | Disseminated superficial porokeratosis | Autosomal dominant | | Disseminated superficial porokeratosis of immunosuppression | Immunosuppression after organ transplantation, drugs, or infections | | Linear porokeratosis | Mosaic manifestation of other porokeratosis variants | | Porokeratosis palmaris et plantaris disseminata | Autosomal dominant | | Punctate porokeratosis | Concomitant occurrence with other forms of porokeratosis |

Question 53

What are the clinical findings associated with disseminated superficial actinic porokeratosis (DSAP)?

Answer 53

- Uniform, small, annular papules from 2-5 mm - Symmetrical distribution on photoexposed extremities - Asymptomatic or mildly pruritic

Question 54

What are the special concerns related to the different subtypes of porokeratosis?

Answer 54

| Subtype | Special Concerns | |---------|------------------| | Porokeratosis of Mibelli | Large lesions have malignant potential | | Disseminated superficial actinic porokeratosis (DSAP) | — | | Disseminated superficial porokeratosis | — | | Disseminated superficial porokeratosis of immunosuppression | — | | Linear porokeratosis | Highest potential for malignant degeneration | | Porokeratosis palmaris et plantaris disseminata | — | | Punctate porokeratosis | — |

Question 55

What are the clinical findings associated with Porokeratosis of Mibelli and how do they differ from those of disseminated superficial actinic porokeratosis (DSAP)?

Answer 55

**Porokeratosis of Mibelli:** - Asymptomatic, small, brown to skin-colored annular papules with an annular border. **Disseminated Superficial Actinic Porokeratosis (DSAP):** - Uniform, small, annular papules (2-5 mm) with symmetrical distribution on photoexposed extremities; asymptomatic or mildly pruritic.

Question 56

How does the inheritance pattern of disseminated superficial porokeratosis compare to that of linear porokeratosis?

Answer 56

**Disseminated Superficial Porokeratosis:** - Inheritance: Autosomal dominant. - Onset: Onset by third to fourth decade of life; female predominance. **Linear Porokeratosis:** - Inheritance: Mosaic manifestation of other porokeratosis variants. - Onset: Uncommon; presents in early childhood.

Question 57

What special concerns are associated with the clinical variant of porokeratosis known as punctate porokeratosis?

Answer 57

Punctate porokeratosis is characterized by multiple discrete punctate hyperkeratotic lesions that may aggregate to form plaques. It appears during adolescence or adulthood and has no specific special concerns noted in the table.

Question 58

What are the epidemiological characteristics of disseminated superficial actinic porokeratosis (DSAP) and how do they inform clinical practice?

Answer 58

**Epidemiological Characteristics of DSAP:** - Most common porokeratosis; onset as early as childhood. - Often present by the third to fourth decade of life with female predominance. **Clinical Implications:** - Awareness of early onset can aid in timely diagnosis and management, especially in females who may present with symptoms in later decades.