The content of these questions and answers are taken from the Galderma Pre-Board Seminar. The online version of the Galderma Pre-Board Seminar will be available starting April 15, 2015. To register, visit www.galdermausa.com/Our-Commitment/Resident-Education.aspx
1. Which statement concerning this condition is true?
a) Unscheduled DNA synthesis is markedly reduced in the variant group
b) Palmer pits are a cutaneous marker for the disease
c) It is caused by a defect in the type A gene on chromosome 5
d) Genetic heterogeneity can be demonstrated by complementation group analysis
e) Jaw cysts are present in up to 50% of affected individuals
2. Kamino bodies are found in the epidermis near the dermoepidermal junction. The most likely diagnosis is:
a) Spitz nevus
b) Nevus spilus
c) Giant congenital nevus
d) Dysplastic nevus
e) Malignant melanoma
3. This patient has an inherited syndrome consisting of multiple large bowel adenomatous polyps with a high incidence of malignant transformation. Histologically, the cystic lesions most closely resemble:
a) Trichilemmomas
b) Trichoepitheliomas
c) Trichofolliculomas
d) Neurilemmomas
e) Pilomatricomas
4. Cross-linkage of involucrin into the stratum corneum envelope results from the activity of which enzyme?
a) Steroid sulfatase
b) Epidermal transglutaminase
c) Gamma-glutamyl transpeptidase
d) Nuclease
e) Ornithine decarboxylase
To learn the answers, go to page 2
{{pagebreak}}
Answers
1. Xeroderma pigmentosum
1. Which statement concerning this condition is true?
d) Genetic heterogeneity can be demonstrated by complementation group analysis
Scheduled DNA synthesis = S phase DNA synthesis. Unscheduled DNA synthesis = non-S phase (repair) DNA synthesis. In cells from most patients with xeroderma pigmentosum (except those in the variant group), unscheduled DNA synthesis is markedly reduced. This is caused by a defect early in the nucleotide excision repair pathway. In the variant group, the defect may be present in the ligase step of excision repair, in post-replication repair or in some other pathway. Cockayne syndrome is caused by a defect in the type A gene on chromosome 5. Palmer pits and jaw cysts are associated with basal cell nevus syndrome. Patients with Rothmund-Thomson syndrome and Chediak-Higashi syndrome also may have ultraviolet sensitivity and reduced DNA repair capacity.
References
Hanawalt PC. The awakening of DNA repair at Yale. Yale J Biol Med. 2013;86(4):517-523.
Knoch J, Kamenisch Y, Kubisch C, Berneburg M. Rare hereditary diseases with defects in DNA-repair. Eur J Dermatol. 2012;22(4):443-455.
2. Spitz nevus
Kamino bodies are found in the epidermis near the dermoepidermal junction. The most likely diagnosis is:
a) Spitz nevus
Kamino bodies are eosinophilic globules found near the dermoepidermal junction in Spitz nevi; they are thought to result from increased proliferation of keratinocytes and melanocytes and sudden death byapoptosis of some of these cells. They have also been reported, but much less commonly, in malignant melanoma.
References
Ferrara G, Gianotti R, Cavicchini S, Salviato T, Zalaudek I, Argenziano G. Spitz nevus, Spitz tumor, and spitzoid melanoma: a comprehensive clinicopathologic overview. Dermatol Clin. 2013;31(4):589-598.
Metzger AT, Kane AA, Bayliss SJ. Differences in treatment of Spitz nevi and atypical Spitz tumors in pediatric patients among dermatologists and plastic surgeons. JAMA Dermatol. 2013;149(11):1348-1350.
Zayour M, Bolognia JL, Lazova R. Multiple Spitz nevi: a clinicopathologic study of 9 patients.
J Am Acad Dermatol. 2012;67(3):451-8, 458.e1-2.
Luo S, Sepehr A, Tsao H. Spitz nevi and other Spitzoid lesions part I. Background and diagnoses.
J Am Acad Dermatol. 2011;65(6):1073-1084.
Berlingeri-Ramos AC, Morales-Burgos A, Sánchez JL, Nogales EM. Spitz nevus in a Hispanic population: a clinicopathological study of 130 cases. Am J Dermatopathol. 2010;32(3):267-275.
Requena C, Requena L, Kutzner H, Sánchez Yus E. Spitz nevus: a clinicopathological study of 349 cases. Am J Dermatopathol. 2009;31(2):107-116.
3. Gardner’s syndrome
This patient has an inherited syndrome consisting of multiple large bowel adenomatous polyps with a high incidence of malignant transformation. Histologically, the cystic lesions most closely resemble:
e) Pilomatricomas
The multiple epidermoid cysts that are found in Gardner’s syndrome (familial adenomatous polyposis) are most common on the legs, face, scalp and arms; histologically, they demonstrate pilomatricoma-like changes. Besides the gastrointestinal polyps and tumors, other important manifestations include desmoid tumors, osteomas, dental abnormalities, pigmented lesions of the ocular fundus and other neoplasms. (The association of familial adenomatous polyposis with central nervous system tumors is called Turcot syndrome).
References
Shen Z, Hoffman JD, Hao F, Pier E. More than just skin deep: faciocutaneous clues to genetic syndromes with malignancies. Oncologist. 2012;17(7):930-936.
Thiers BH, Sahn RE, Callen JP. Cutaneous manifestations of internal malignancy. CA Cancer J Clin. 2009;59(2):73-98.
4. Stratum corneum
Cross-linkage of involucrin into the stratum corneum envelope results from the activity of which enzyme?
b) Epidermal transglutaminase
Enzymes can serve as markers for various stages of keratinization. Ornithine decarboxylase is a reliable marker for proliferative activity in epidermal cells, and is found primarily in the basal layer. Nucleases are most active in the immediate suprabasal region. Transpeptidases are found in the mid-epidermis. Transglutaminases in the stratum granulosum appear to cross-link precursor proteins (such as involucrin) in the process of forming the stratum corneum. Transglutaminase deficiency has been implicated in the pathogenesis of lamellar ichthyosis. Steroid sulfatase at the junction of the living epidermis and stratum corneum is responsible for the conversion of cholesterol sulfate to cholesterol. Steroid sulfatase deficiency appears to play a role in the pathogenesis of X-linked ichthyosis.
References
Aufenvenne K, Rice RH, Hausser I, et al. Long-term faithful recapitulation of transglutaminase 1-deficient lamellar ichthyosis in a skin-humanized mouse model, and insights from proteomic studies. J Invest Dermatol. 2012;132(7):1918-1921.
Hasegawa T, Shimada H, Uchiyama T, Ueda O, Nakashima M, Matsuoka Y. Dietary glucosylceramide enhances cornified envelope formation via transglutaminase expression and involucrin production. Lipids. 2011;46(6):529-535.
Bruce Thiers, MD, FAAD, is professor and chairman of the Department of Dermatology and Dermatologic Surgery at the Medical University of South Carolina in Charleston, SC.
The content of these questions and answers are taken from the Galderma Pre-Board Seminar. The online version of the Galderma Pre-Board Seminar will be available starting April 15, 2015. To register, visit www.galdermausa.com/Our-Commitment/Resident-Education.aspx
1. Which statement concerning this condition is true?
a) Unscheduled DNA synthesis is markedly reduced in the variant group
b) Palmer pits are a cutaneous marker for the disease
c) It is caused by a defect in the type A gene on chromosome 5
d) Genetic heterogeneity can be demonstrated by complementation group analysis
e) Jaw cysts are present in up to 50% of affected individuals
2. Kamino bodies are found in the epidermis near the dermoepidermal junction. The most likely diagnosis is:
a) Spitz nevus
b) Nevus spilus
c) Giant congenital nevus
d) Dysplastic nevus
e) Malignant melanoma
3. This patient has an inherited syndrome consisting of multiple large bowel adenomatous polyps with a high incidence of malignant transformation. Histologically, the cystic lesions most closely resemble:
a) Trichilemmomas
b) Trichoepitheliomas
c) Trichofolliculomas
d) Neurilemmomas
e) Pilomatricomas
4. Cross-linkage of involucrin into the stratum corneum envelope results from the activity of which enzyme?
a) Steroid sulfatase
b) Epidermal transglutaminase
c) Gamma-glutamyl transpeptidase
d) Nuclease
e) Ornithine decarboxylase
Answers
1. Xeroderma pigmentosum
1. Which statement concerning this condition is true?
d) Genetic heterogeneity can be demonstrated by complementation group analysis
Scheduled DNA synthesis = S phase DNA synthesis. Unscheduled DNA synthesis = non-S phase (repair) DNA synthesis. In cells from most patients with xeroderma pigmentosum (except those in the variant group), unscheduled DNA synthesis is markedly reduced. This is caused by a defect early in the nucleotide excision repair pathway. In the variant group, the defect may be present in the ligase step of excision repair, in post-replication repair or in some other pathway. Cockayne syndrome is caused by a defect in the type A gene on chromosome 5. Palmer pits and jaw cysts are associated with basal cell nevus syndrome. Patients with Rothmund-Thomson syndrome and Chediak-Higashi syndrome also may have ultraviolet sensitivity and reduced DNA repair capacity.
References
Hanawalt PC. The awakening of DNA repair at Yale. Yale J Biol Med. 2013;86(4):517-523.
Knoch J, Kamenisch Y, Kubisch C, Berneburg M. Rare hereditary diseases with defects in DNA-repair. Eur J Dermatol. 2012;22(4):443-455.
2. Spitz nevus
Kamino bodies are found in the epidermis near the dermoepidermal junction. The most likely diagnosis is:
a) Spitz nevus
Kamino bodies are eosinophilic globules found near the dermoepidermal junction in Spitz nevi; they are thought to result from increased proliferation of keratinocytes and melanocytes and sudden death byapoptosis of some of these cells. They have also been reported, but much less commonly, in malignant melanoma.
References
Ferrara G, Gianotti R, Cavicchini S, Salviato T, Zalaudek I, Argenziano G. Spitz nevus, Spitz tumor, and spitzoid melanoma: a comprehensive clinicopathologic overview. Dermatol Clin. 2013;31(4):589-598.
Metzger AT, Kane AA, Bayliss SJ. Differences in treatment of Spitz nevi and atypical Spitz tumors in pediatric patients among dermatologists and plastic surgeons. JAMA Dermatol. 2013;149(11):1348-1350.
Zayour M, Bolognia JL, Lazova R. Multiple Spitz nevi: a clinicopathologic study of 9 patients.
J Am Acad Dermatol. 2012;67(3):451-8, 458.e1-2.
Luo S, Sepehr A, Tsao H. Spitz nevi and other Spitzoid lesions part I. Background and diagnoses.
J Am Acad Dermatol. 2011;65(6):1073-1084.
Berlingeri-Ramos AC, Morales-Burgos A, Sánchez JL, Nogales EM. Spitz nevus in a Hispanic population: a clinicopathological study of 130 cases. Am J Dermatopathol. 2010;32(3):267-275.
Requena C, Requena L, Kutzner H, Sánchez Yus E. Spitz nevus: a clinicopathological study of 349 cases. Am J Dermatopathol. 2009;31(2):107-116.
3. Gardner’s syndrome
This patient has an inherited syndrome consisting of multiple large bowel adenomatous polyps with a high incidence of malignant transformation. Histologically, the cystic lesions most closely resemble:
e) Pilomatricomas
The multiple epidermoid cysts that are found in Gardner’s syndrome (familial adenomatous polyposis) are most common on the legs, face, scalp and arms; histologically, they demonstrate pilomatricoma-like changes. Besides the gastrointestinal polyps and tumors, other important manifestations include desmoid tumors, osteomas, dental abnormalities, pigmented lesions of the ocular fundus and other neoplasms. (The association of familial adenomatous polyposis with central nervous system tumors is called Turcot syndrome).
References
Shen Z, Hoffman JD, Hao F, Pier E. More than just skin deep: faciocutaneous clues to genetic syndromes with malignancies. Oncologist. 2012;17(7):930-936.
Thiers BH, Sahn RE, Callen JP. Cutaneous manifestations of internal malignancy. CA Cancer J Clin. 2009;59(2):73-98.
4. Stratum corneum
Cross-linkage of involucrin into the stratum corneum envelope results from the activity of which enzyme?
b) Epidermal transglutaminase
Enzymes can serve as markers for various stages of keratinization. Ornithine decarboxylase is a reliable marker for proliferative activity in epidermal cells, and is found primarily in the basal layer. Nucleases are most active in the immediate suprabasal region. Transpeptidases are found in the mid-epidermis. Transglutaminases in the stratum granulosum appear to cross-link precursor proteins (such as involucrin) in the process of forming the stratum corneum. Transglutaminase deficiency has been implicated in the pathogenesis of lamellar ichthyosis. Steroid sulfatase at the junction of the living epidermis and stratum corneum is responsible for the conversion of cholesterol sulfate to cholesterol. Steroid sulfatase deficiency appears to play a role in the pathogenesis of X-linked ichthyosis.
References
Aufenvenne K, Rice RH, Hausser I, et al. Long-term faithful recapitulation of transglutaminase 1-deficient lamellar ichthyosis in a skin-humanized mouse model, and insights from proteomic studies. J Invest Dermatol. 2012;132(7):1918-1921.
Hasegawa T, Shimada H, Uchiyama T, Ueda O, Nakashima M, Matsuoka Y. Dietary glucosylceramide enhances cornified envelope formation via transglutaminase expression and involucrin production. Lipids. 2011;46(6):529-535.
Bruce Thiers, MD, FAAD, is professor and chairman of the Department of Dermatology and Dermatologic Surgery at the Medical University of South Carolina in Charleston, SC.
The content of these questions and answers are taken from the Galderma Pre-Board Seminar. The online version of the Galderma Pre-Board Seminar will be available starting April 15, 2015. To register, visit www.galdermausa.com/Our-Commitment/Resident-Education.aspx
1. Which statement concerning this condition is true?
a) Unscheduled DNA synthesis is markedly reduced in the variant group
b) Palmer pits are a cutaneous marker for the disease
c) It is caused by a defect in the type A gene on chromosome 5
d) Genetic heterogeneity can be demonstrated by complementation group analysis
e) Jaw cysts are present in up to 50% of affected individuals
2. Kamino bodies are found in the epidermis near the dermoepidermal junction. The most likely diagnosis is:
a) Spitz nevus
b) Nevus spilus
c) Giant congenital nevus
d) Dysplastic nevus
e) Malignant melanoma
3. This patient has an inherited syndrome consisting of multiple large bowel adenomatous polyps with a high incidence of malignant transformation. Histologically, the cystic lesions most closely resemble:
a) Trichilemmomas
b) Trichoepitheliomas
c) Trichofolliculomas
d) Neurilemmomas
e) Pilomatricomas
4. Cross-linkage of involucrin into the stratum corneum envelope results from the activity of which enzyme?
a) Steroid sulfatase
b) Epidermal transglutaminase
c) Gamma-glutamyl transpeptidase
d) Nuclease
e) Ornithine decarboxylase
,
The content of these questions and answers are taken from the Galderma Pre-Board Seminar. The online version of the Galderma Pre-Board Seminar will be available starting April 15, 2015. To register, visit www.galdermausa.com/Our-Commitment/Resident-Education.aspx
1. Which statement concerning this condition is true?
a) Unscheduled DNA synthesis is markedly reduced in the variant group
b) Palmer pits are a cutaneous marker for the disease
c) It is caused by a defect in the type A gene on chromosome 5
d) Genetic heterogeneity can be demonstrated by complementation group analysis
e) Jaw cysts are present in up to 50% of affected individuals
2. Kamino bodies are found in the epidermis near the dermoepidermal junction. The most likely diagnosis is:
a) Spitz nevus
b) Nevus spilus
c) Giant congenital nevus
d) Dysplastic nevus
e) Malignant melanoma
3. This patient has an inherited syndrome consisting of multiple large bowel adenomatous polyps with a high incidence of malignant transformation. Histologically, the cystic lesions most closely resemble:
a) Trichilemmomas
b) Trichoepitheliomas
c) Trichofolliculomas
d) Neurilemmomas
e) Pilomatricomas
4. Cross-linkage of involucrin into the stratum corneum envelope results from the activity of which enzyme?
a) Steroid sulfatase
b) Epidermal transglutaminase
c) Gamma-glutamyl transpeptidase
d) Nuclease
e) Ornithine decarboxylase
To learn the answers, go to page 2
{{pagebreak}}
Answers
1. Xeroderma pigmentosum
1. Which statement concerning this condition is true?
d) Genetic heterogeneity can be demonstrated by complementation group analysis
Scheduled DNA synthesis = S phase DNA synthesis. Unscheduled DNA synthesis = non-S phase (repair) DNA synthesis. In cells from most patients with xeroderma pigmentosum (except those in the variant group), unscheduled DNA synthesis is markedly reduced. This is caused by a defect early in the nucleotide excision repair pathway. In the variant group, the defect may be present in the ligase step of excision repair, in post-replication repair or in some other pathway. Cockayne syndrome is caused by a defect in the type A gene on chromosome 5. Palmer pits and jaw cysts are associated with basal cell nevus syndrome. Patients with Rothmund-Thomson syndrome and Chediak-Higashi syndrome also may have ultraviolet sensitivity and reduced DNA repair capacity.
References
Hanawalt PC. The awakening of DNA repair at Yale. Yale J Biol Med. 2013;86(4):517-523.
Knoch J, Kamenisch Y, Kubisch C, Berneburg M. Rare hereditary diseases with defects in DNA-repair. Eur J Dermatol. 2012;22(4):443-455.
2. Spitz nevus
Kamino bodies are found in the epidermis near the dermoepidermal junction. The most likely diagnosis is:
a) Spitz nevus
Kamino bodies are eosinophilic globules found near the dermoepidermal junction in Spitz nevi; they are thought to result from increased proliferation of keratinocytes and melanocytes and sudden death byapoptosis of some of these cells. They have also been reported, but much less commonly, in malignant melanoma.
References
Ferrara G, Gianotti R, Cavicchini S, Salviato T, Zalaudek I, Argenziano G. Spitz nevus, Spitz tumor, and spitzoid melanoma: a comprehensive clinicopathologic overview. Dermatol Clin. 2013;31(4):589-598.
Metzger AT, Kane AA, Bayliss SJ. Differences in treatment of Spitz nevi and atypical Spitz tumors in pediatric patients among dermatologists and plastic surgeons. JAMA Dermatol. 2013;149(11):1348-1350.
Zayour M, Bolognia JL, Lazova R. Multiple Spitz nevi: a clinicopathologic study of 9 patients.
J Am Acad Dermatol. 2012;67(3):451-8, 458.e1-2.
Luo S, Sepehr A, Tsao H. Spitz nevi and other Spitzoid lesions part I. Background and diagnoses.
J Am Acad Dermatol. 2011;65(6):1073-1084.
Berlingeri-Ramos AC, Morales-Burgos A, Sánchez JL, Nogales EM. Spitz nevus in a Hispanic population: a clinicopathological study of 130 cases. Am J Dermatopathol. 2010;32(3):267-275.
Requena C, Requena L, Kutzner H, Sánchez Yus E. Spitz nevus: a clinicopathological study of 349 cases. Am J Dermatopathol. 2009;31(2):107-116.
3. Gardner’s syndrome
This patient has an inherited syndrome consisting of multiple large bowel adenomatous polyps with a high incidence of malignant transformation. Histologically, the cystic lesions most closely resemble:
e) Pilomatricomas
The multiple epidermoid cysts that are found in Gardner’s syndrome (familial adenomatous polyposis) are most common on the legs, face, scalp and arms; histologically, they demonstrate pilomatricoma-like changes. Besides the gastrointestinal polyps and tumors, other important manifestations include desmoid tumors, osteomas, dental abnormalities, pigmented lesions of the ocular fundus and other neoplasms. (The association of familial adenomatous polyposis with central nervous system tumors is called Turcot syndrome).
References
Shen Z, Hoffman JD, Hao F, Pier E. More than just skin deep: faciocutaneous clues to genetic syndromes with malignancies. Oncologist. 2012;17(7):930-936.
Thiers BH, Sahn RE, Callen JP. Cutaneous manifestations of internal malignancy. CA Cancer J Clin. 2009;59(2):73-98.
4. Stratum corneum
Cross-linkage of involucrin into the stratum corneum envelope results from the activity of which enzyme?
b) Epidermal transglutaminase
Enzymes can serve as markers for various stages of keratinization. Ornithine decarboxylase is a reliable marker for proliferative activity in epidermal cells, and is found primarily in the basal layer. Nucleases are most active in the immediate suprabasal region. Transpeptidases are found in the mid-epidermis. Transglutaminases in the stratum granulosum appear to cross-link precursor proteins (such as involucrin) in the process of forming the stratum corneum. Transglutaminase deficiency has been implicated in the pathogenesis of lamellar ichthyosis. Steroid sulfatase at the junction of the living epidermis and stratum corneum is responsible for the conversion of cholesterol sulfate to cholesterol. Steroid sulfatase deficiency appears to play a role in the pathogenesis of X-linked ichthyosis.
References
Aufenvenne K, Rice RH, Hausser I, et al. Long-term faithful recapitulation of transglutaminase 1-deficient lamellar ichthyosis in a skin-humanized mouse model, and insights from proteomic studies. J Invest Dermatol. 2012;132(7):1918-1921.
Hasegawa T, Shimada H, Uchiyama T, Ueda O, Nakashima M, Matsuoka Y. Dietary glucosylceramide enhances cornified envelope formation via transglutaminase expression and involucrin production. Lipids. 2011;46(6):529-535.
Bruce Thiers, MD, FAAD, is professor and chairman of the Department of Dermatology and Dermatologic Surgery at the Medical University of South Carolina in Charleston, SC.
The content of these questions and answers are taken from the Galderma Pre-Board Seminar. The online version of the Galderma Pre-Board Seminar will be available starting April 15, 2015. To register, visit www.galdermausa.com/Our-Commitment/Resident-Education.aspx
1. Which statement concerning this condition is true?
a) Unscheduled DNA synthesis is markedly reduced in the variant group
b) Palmer pits are a cutaneous marker for the disease
c) It is caused by a defect in the type A gene on chromosome 5
d) Genetic heterogeneity can be demonstrated by complementation group analysis
e) Jaw cysts are present in up to 50% of affected individuals
2. Kamino bodies are found in the epidermis near the dermoepidermal junction. The most likely diagnosis is:
a) Spitz nevus
b) Nevus spilus
c) Giant congenital nevus
d) Dysplastic nevus
e) Malignant melanoma
3. This patient has an inherited syndrome consisting of multiple large bowel adenomatous polyps with a high incidence of malignant transformation. Histologically, the cystic lesions most closely resemble:
a) Trichilemmomas
b) Trichoepitheliomas
c) Trichofolliculomas
d) Neurilemmomas
e) Pilomatricomas
4. Cross-linkage of involucrin into the stratum corneum envelope results from the activity of which enzyme?
a) Steroid sulfatase
b) Epidermal transglutaminase
c) Gamma-glutamyl transpeptidase
d) Nuclease
e) Ornithine decarboxylase
Answers
1. Xeroderma pigmentosum
1. Which statement concerning this condition is true?
d) Genetic heterogeneity can be demonstrated by complementation group analysis
Scheduled DNA synthesis = S phase DNA synthesis. Unscheduled DNA synthesis = non-S phase (repair) DNA synthesis. In cells from most patients with xeroderma pigmentosum (except those in the variant group), unscheduled DNA synthesis is markedly reduced. This is caused by a defect early in the nucleotide excision repair pathway. In the variant group, the defect may be present in the ligase step of excision repair, in post-replication repair or in some other pathway. Cockayne syndrome is caused by a defect in the type A gene on chromosome 5. Palmer pits and jaw cysts are associated with basal cell nevus syndrome. Patients with Rothmund-Thomson syndrome and Chediak-Higashi syndrome also may have ultraviolet sensitivity and reduced DNA repair capacity.
References
Hanawalt PC. The awakening of DNA repair at Yale. Yale J Biol Med. 2013;86(4):517-523.
Knoch J, Kamenisch Y, Kubisch C, Berneburg M. Rare hereditary diseases with defects in DNA-repair. Eur J Dermatol. 2012;22(4):443-455.
2. Spitz nevus
Kamino bodies are found in the epidermis near the dermoepidermal junction. The most likely diagnosis is:
a) Spitz nevus
Kamino bodies are eosinophilic globules found near the dermoepidermal junction in Spitz nevi; they are thought to result from increased proliferation of keratinocytes and melanocytes and sudden death byapoptosis of some of these cells. They have also been reported, but much less commonly, in malignant melanoma.
References
Ferrara G, Gianotti R, Cavicchini S, Salviato T, Zalaudek I, Argenziano G. Spitz nevus, Spitz tumor, and spitzoid melanoma: a comprehensive clinicopathologic overview. Dermatol Clin. 2013;31(4):589-598.
Metzger AT, Kane AA, Bayliss SJ. Differences in treatment of Spitz nevi and atypical Spitz tumors in pediatric patients among dermatologists and plastic surgeons. JAMA Dermatol. 2013;149(11):1348-1350.
Zayour M, Bolognia JL, Lazova R. Multiple Spitz nevi: a clinicopathologic study of 9 patients.
J Am Acad Dermatol. 2012;67(3):451-8, 458.e1-2.
Luo S, Sepehr A, Tsao H. Spitz nevi and other Spitzoid lesions part I. Background and diagnoses.
J Am Acad Dermatol. 2011;65(6):1073-1084.
Berlingeri-Ramos AC, Morales-Burgos A, Sánchez JL, Nogales EM. Spitz nevus in a Hispanic population: a clinicopathological study of 130 cases. Am J Dermatopathol. 2010;32(3):267-275.
Requena C, Requena L, Kutzner H, Sánchez Yus E. Spitz nevus: a clinicopathological study of 349 cases. Am J Dermatopathol. 2009;31(2):107-116.
3. Gardner’s syndrome
This patient has an inherited syndrome consisting of multiple large bowel adenomatous polyps with a high incidence of malignant transformation. Histologically, the cystic lesions most closely resemble:
e) Pilomatricomas
The multiple epidermoid cysts that are found in Gardner’s syndrome (familial adenomatous polyposis) are most common on the legs, face, scalp and arms; histologically, they demonstrate pilomatricoma-like changes. Besides the gastrointestinal polyps and tumors, other important manifestations include desmoid tumors, osteomas, dental abnormalities, pigmented lesions of the ocular fundus and other neoplasms. (The association of familial adenomatous polyposis with central nervous system tumors is called Turcot syndrome).
References
Shen Z, Hoffman JD, Hao F, Pier E. More than just skin deep: faciocutaneous clues to genetic syndromes with malignancies. Oncologist. 2012;17(7):930-936.
Thiers BH, Sahn RE, Callen JP. Cutaneous manifestations of internal malignancy. CA Cancer J Clin. 2009;59(2):73-98.
4. Stratum corneum
Cross-linkage of involucrin into the stratum corneum envelope results from the activity of which enzyme?
b) Epidermal transglutaminase
Enzymes can serve as markers for various stages of keratinization. Ornithine decarboxylase is a reliable marker for proliferative activity in epidermal cells, and is found primarily in the basal layer. Nucleases are most active in the immediate suprabasal region. Transpeptidases are found in the mid-epidermis. Transglutaminases in the stratum granulosum appear to cross-link precursor proteins (such as involucrin) in the process of forming the stratum corneum. Transglutaminase deficiency has been implicated in the pathogenesis of lamellar ichthyosis. Steroid sulfatase at the junction of the living epidermis and stratum corneum is responsible for the conversion of cholesterol sulfate to cholesterol. Steroid sulfatase deficiency appears to play a role in the pathogenesis of X-linked ichthyosis.
References
Aufenvenne K, Rice RH, Hausser I, et al. Long-term faithful recapitulation of transglutaminase 1-deficient lamellar ichthyosis in a skin-humanized mouse model, and insights from proteomic studies. J Invest Dermatol. 2012;132(7):1918-1921.
Hasegawa T, Shimada H, Uchiyama T, Ueda O, Nakashima M, Matsuoka Y. Dietary glucosylceramide enhances cornified envelope formation via transglutaminase expression and involucrin production. Lipids. 2011;46(6):529-535.
Bruce Thiers, MD, FAAD, is professor and chairman of the Department of Dermatology and Dermatologic Surgery at the Medical University of South Carolina in Charleston, SC.
Answers
1. Xeroderma pigmentosum
1. Which statement concerning this condition is true?
d) Genetic heterogeneity can be demonstrated by complementation group analysis
Scheduled DNA synthesis = S phase DNA synthesis. Unscheduled DNA synthesis = non-S phase (repair) DNA synthesis. In cells from most patients with xeroderma pigmentosum (except those in the variant group), unscheduled DNA synthesis is markedly reduced. This is caused by a defect early in the nucleotide excision repair pathway. In the variant group, the defect may be present in the ligase step of excision repair, in post-replication repair or in some other pathway. Cockayne syndrome is caused by a defect in the type A gene on chromosome 5. Palmer pits and jaw cysts are associated with basal cell nevus syndrome. Patients with Rothmund-Thomson syndrome and Chediak-Higashi syndrome also may have ultraviolet sensitivity and reduced DNA repair capacity.
References
Hanawalt PC. The awakening of DNA repair at Yale. Yale J Biol Med. 2013;86(4):517-523.
Knoch J, Kamenisch Y, Kubisch C, Berneburg M. Rare hereditary diseases with defects in DNA-repair. Eur J Dermatol. 2012;22(4):443-455.
2. Spitz nevus
Kamino bodies are found in the epidermis near the dermoepidermal junction. The most likely diagnosis is:
a) Spitz nevus
Kamino bodies are eosinophilic globules found near the dermoepidermal junction in Spitz nevi; they are thought to result from increased proliferation of keratinocytes and melanocytes and sudden death byapoptosis of some of these cells. They have also been reported, but much less commonly, in malignant melanoma.
References
Ferrara G, Gianotti R, Cavicchini S, Salviato T, Zalaudek I, Argenziano G. Spitz nevus, Spitz tumor, and spitzoid melanoma: a comprehensive clinicopathologic overview. Dermatol Clin. 2013;31(4):589-598.
Metzger AT, Kane AA, Bayliss SJ. Differences in treatment of Spitz nevi and atypical Spitz tumors in pediatric patients among dermatologists and plastic surgeons. JAMA Dermatol. 2013;149(11):1348-1350.
Zayour M, Bolognia JL, Lazova R. Multiple Spitz nevi: a clinicopathologic study of 9 patients.
J Am Acad Dermatol. 2012;67(3):451-8, 458.e1-2.
Luo S, Sepehr A, Tsao H. Spitz nevi and other Spitzoid lesions part I. Background and diagnoses.
J Am Acad Dermatol. 2011;65(6):1073-1084.
Berlingeri-Ramos AC, Morales-Burgos A, Sánchez JL, Nogales EM. Spitz nevus in a Hispanic population: a clinicopathological study of 130 cases. Am J Dermatopathol. 2010;32(3):267-275.
Requena C, Requena L, Kutzner H, Sánchez Yus E. Spitz nevus: a clinicopathological study of 349 cases. Am J Dermatopathol. 2009;31(2):107-116.
3. Gardner’s syndrome
This patient has an inherited syndrome consisting of multiple large bowel adenomatous polyps with a high incidence of malignant transformation. Histologically, the cystic lesions most closely resemble:
e) Pilomatricomas
The multiple epidermoid cysts that are found in Gardner’s syndrome (familial adenomatous polyposis) are most common on the legs, face, scalp and arms; histologically, they demonstrate pilomatricoma-like changes. Besides the gastrointestinal polyps and tumors, other important manifestations include desmoid tumors, osteomas, dental abnormalities, pigmented lesions of the ocular fundus and other neoplasms. (The association of familial adenomatous polyposis with central nervous system tumors is called Turcot syndrome).
References
Shen Z, Hoffman JD, Hao F, Pier E. More than just skin deep: faciocutaneous clues to genetic syndromes with malignancies. Oncologist. 2012;17(7):930-936.
Thiers BH, Sahn RE, Callen JP. Cutaneous manifestations of internal malignancy. CA Cancer J Clin. 2009;59(2):73-98.
4. Stratum corneum
Cross-linkage of involucrin into the stratum corneum envelope results from the activity of which enzyme?
b) Epidermal transglutaminase
Enzymes can serve as markers for various stages of keratinization. Ornithine decarboxylase is a reliable marker for proliferative activity in epidermal cells, and is found primarily in the basal layer. Nucleases are most active in the immediate suprabasal region. Transpeptidases are found in the mid-epidermis. Transglutaminases in the stratum granulosum appear to cross-link precursor proteins (such as involucrin) in the process of forming the stratum corneum. Transglutaminase deficiency has been implicated in the pathogenesis of lamellar ichthyosis. Steroid sulfatase at the junction of the living epidermis and stratum corneum is responsible for the conversion of cholesterol sulfate to cholesterol. Steroid sulfatase deficiency appears to play a role in the pathogenesis of X-linked ichthyosis.
References
Aufenvenne K, Rice RH, Hausser I, et al. Long-term faithful recapitulation of transglutaminase 1-deficient lamellar ichthyosis in a skin-humanized mouse model, and insights from proteomic studies. J Invest Dermatol. 2012;132(7):1918-1921.
Hasegawa T, Shimada H, Uchiyama T, Ueda O, Nakashima M, Matsuoka Y. Dietary glucosylceramide enhances cornified envelope formation via transglutaminase expression and involucrin production. Lipids. 2011;46(6):529-535.
Bruce Thiers, MD, FAAD, is professor and chairman of the Department of Dermatology and Dermatologic Surgery at the Medical University of South Carolina in Charleston, SC.
