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Metastatic squamous cell carcinoma in linear porokeratosis of Mibelli
Metastatic squamous cell carcinoma in linear porokeratosis of Mibelli A. Z. Lozinski, M.D.,*'** B. K. Fisher, M.D.,* J. B. Walter, M . D . , * * * and P. J. Fitzpatrick, M.B.B.S.**** Toronto, Ontario, Canada We describe the clinical and pathologic observations of a 45-year-old woman with linear porokeratosis who developed squamous cell carcinoma in lesional sites. The squamous cell carcinoma metastasized to a regional lymph node. This is the second case of metastatic squamous cell carcinoma reported in porokeratosis and the first reported in the linear variety. (J AM ACAD DERMATOL 1987;16:448-5 t.)
Porokeratosis is a rare genodermatosis inherited as an autosomal dominant trait. Lever and Schaumburg-Lever 1 describe five distinct forms: (1) the plaque type originally described by Mibelli, (2) a superficial disseminated form, (3) disseminated superficial actinic porokeratosis, (4) the punctate form, which occurs either on the elbows, wrists, fingers, palms, and soles, and (5) the linear form. Linear porokeratosis is characterized clinically by lesions forming a linear pattern. It usually appears in childhood and primarily involves the extremities. The involvement is frequently unilateral and distal. It may be mistaken for linear verrucous nevus, lichen striatus, lichen planus, or linear mosaic warts. 2, 3 No relationship to actinic radiation has been described in the linear variety; however, lesions may exhibit koebnerization. The histologic features of linear porokeratosis are essentially the same as those of the classic type of Mibelli, namely, a keratin-filled parakeratotic column with underlying dysplastic epidermal Fromthe DivisionofDermatology,WellesleyHospitalandUniversity ofTorontoMedicalSchool,*theDepartmentofPathology,Toronto General Hospitaland Universityof TorontoMedicalSchool,*** and the Departmentof RadiationOncology,Princess Margaret Hospitaland Universityof TorontoMedicalSchool.**** No reprintsavailable. **Now with the Departmentof Dermatology,VancouverGeneral Hospital and Universityof BritishColumbia,855 W. 10thAve., Vancouver,BritishColumbiaV5Z IL7, Canada.
448
Fig. 1. Unilateral linear hyperkeratotic lesions in linear porokeratosis. cells. The parakeratotic column is referred to as the cornoid lamella. The histologic changes are usually less pronounced in types 2, 3, 4, and 5 than in type 1.
Volume 16 Number 2, Part 2 February 1987
Metastatic SCC in linear porokeratosis
449
Fig. 2. Lesions show central atrophy with a raised border.
To the best o f our knowledge, metastatic squamous cell carcinoma in linear porokeratosis has not been reported to date. We herein report such a case.
CASE REPORT A 45-year-old white woman was referred to the regional cancer hospital (Princess Margaret Hospital) for treatment of squamous cell carcinoma that had developed in a hyperkeratotic lesion on the posterior aspect of her fight calf. The patient's dermatologic history dated back to the age of 9 years, when she developed a hemorrhagic rash on her right buttock. The buttock rash became hyperkeratotic and subsequently spread down the posterior aspect of her right thigh and calf. It later spread to the right midanterior and posterior aspect of her chest wall and to her right upper extremity. The eruption was occasionally pruritic, with exacerbations mainly in the summer months. The lesions had not changed in size since the patient's teens. There was no known family history of similar lesions. Ultraviolet lamp therapy and "creams" produced no change. After five x-ray treatments to all lesions during the patient's teens, the hyperkeratotic plaques were noted to have softened, Further details of these treatments are not known. There is a subsequent history of mitral stenosis and chronic atrial fibrillation. At the age of 47 years, the patient suffered a myocardial infarction and deep venous thrombosis of the right upper extremity. Initial examination revealed multicentric hyperker-
Fig. 3. Right inguinal node with metastatic squamous cell carcinoma in linear porokeratosis. atotic lesions on the right buttock, the posterior aspect of the right thigh and calf (Fig. 1), the fight posterior thoracic area, and the right arm. Lesions were noted to be atrophic centrally, with a raised ridge border
450
Journal of the American Academy of Dermatology
Lozinski et al
Fig. 4. Cornoid lamella (right) and adjacent squamous cell carcinoma (left). (Hematoxylineosin stain; × 40.) Bilateral groin adenopathy noted at this time was thought to be benign. In 1980 the patient returned for evaluation of a further enlargement of a right inguinal node (Fig. 3). Pathologic study of this lymph node showed well-differentiated squamous cell carcinoma. At this time, the results of skin biopsy of a lesion on the posterior aspect of the fight thigh were consistent with porokeratosis with adjacent areas of squamous cell carcinoma (Figs. 4 and 5). Treatment at this time consisted of excision of the right inguinal lymph node, followed by 5,000 cGy of radiation. The porokeratotic lesions with malignant change on her right thigh were excised. The patient subsequently developed other areas of squamous cell carcinoma within lesional skin on the posterior aspect of her fight thigh. These lesions were also managed by excision. At the submission of this paper, 5 years post presentation, there is no evidence of malignant recurrence. DISCUSSION
Fig. 5. Cornoid lamella of porokeratosis--keratin-filled epidermal invagination with central parakeratotic column. Note the absence of a granular layer underlying the parakeratotic column. (Hematoxylin-eosin stain; x 100.) (Fig. 2). An initial skin biopsy specimen from a lesion on the posterior aspect of the right calf in 1970 (not available) showed squamous cell carcinoma. Subsequent therapy consisted of local radiation (3,500 cGy).
Porokeratosis is a relatively rare disease. Its precise incidence is unclear, but a review of the literature in 1974 revealed only 250 reported cases. In the review of Mehregan et al,4 the linear variant constituted seven of a total of 197 cases of porokeratosis. Epidermal malignancies m a y occur in all types of porokeratosis. To date, there have been reports of seventeen cases of squamous cell carcinoma, three of basal cell carcinoma, and five with concurrent or solitary Bowen's disease in porokera-
Volume 16 Number 2, Part 2 February 1987
tosis. 48 The incidence of malignant change was 7% in 250 cases of porokeratosis reviewed in 1974. 5 It was previously thought that squamous cell carcinoma in this context had a low propensity to metastasize. Evidence to the contrary was reported by Machino et al, 9 whose case of metastatic squamous cell carcinoma in disseminated porokeratosis had a fatal outcome. To our knowledge, ours is the second case of metastatic squamous cell carcinoma in porokeratosis and the first in linear porokeratosis. It is thought that porokeratosis evolves from a clone of abnormal epidermal cells at the base of the cornoid lamella. These ceils are thought to be more sensitive to ultraviolet light than normal epidermal cells and often show degenerative and dysplastic changes. Malignancy is thought to develop from these areas of epidermal dysplasia. ~o One may speculate that earlier x-irradiation played a role in producing the multifocal malignant change in our patient. All carcinomas occurred within the field of previous irradiation. The interval between x-ray exposure and malignant transformation was more than 25 years. Goerttler and Jung 5 noted previous x-ray treatment in four of seventeen cases of malignant change within porokeratosis. In three cases, with intervals of 13 to 17 years between x-ray and carcinoma, a causal relationship was suspected. X-irradiation was not thought to be a contributing factor in the fourth case, in which malignant change occurred within 2 years of exposure.
Metastatic SCC in linear porokeratosis
451
Widespread lesions of porokeratosis present a p r o b l e m in management. Solitary lesions freq u e n t l y can be excised or destroyed. Other modalities include liquid nitrogen, topical steroids, 5fluorouracil, topical vitamin A, oral retinoids, and various topical keratolytic agents. 2 For widespread lesions, most of these methods are unsatisfactory or unrealistic. Monitoring is therefore most important, if lesions persist, for the detection of early malignant transformation and possible metastases. REFERENCES
1. Lever WF, Schaumburg-Lever G. Histopathology of the skin. 6th ed. Philadelphia: J B Lippincott Co, 1983. 2. Rahbari H, Cordero A, Mehregan All. Linear porokeratosis. Arch Dermatol 1974;109:526-8. 3. Witkowski J, Parish L. Linear porokeratosis presenting as mosaic plantar warts. Int J Dermatol 1982;1:401-4, 4. Mehregan AH, Khalili H. Fazel Z. Mibelli's porokeratosis of the face: a report of seven cases. J AM ACAD DERMATOt.1980;3:394-6. 5. Goerttler EA, Jung EG. Parakeratosis, Mibelli and skin carcinoma: a critical review. Humangcnetik 1975;26: 291-6. 6. Coskey RJ, Mehregan AH. Bowen disease associated with porokeratosis of Mibelli. Arch Dermatol 1975; 111:1480-1.
7. Glickman FS. Porokeratosis associated with basal cell carcinoma. Cutis 1982;29:446-9. 8. Shrum JR, CooperPH, GreerKE, Landes HB. Squamous cell carcinoma in disseminated superficial actinic porokeratosis. J AM ACADDERNAa'OL1982;6:58-62. 9. Machino H, Miki Y, Teramoio T, et al, Cytogeneticstudies in a patient with porokeratosis of Mibelli, multiple cancers and a formc fruste of Werner's syndrome. Br J Dermatol 1984;3:579-86. 10. Reed RJ, Leone P. Porokeratosis: a mutant clonal keratosis of the epidermis. Arch Dermatol 1970;101:340-7.
Porokeratosis is a rare genodermatosis inherited as an autosomal dominant trait. Lever and Schaumburg-Lever 1 describe five distinct forms: (1) the plaque type originally described by Mibelli, (2) a superficial disseminated form, (3) disseminated superficial actinic porokeratosis, (4) the punctate form, which occurs either on the elbows, wrists, fingers, palms, and soles, and (5) the linear form. Linear porokeratosis is characterized clinically by lesions forming a linear pattern. It usually appears in childhood and primarily involves the extremities. The involvement is frequently unilateral and distal. It may be mistaken for linear verrucous nevus, lichen striatus, lichen planus, or linear mosaic warts. 2, 3 No relationship to actinic radiation has been described in the linear variety; however, lesions may exhibit koebnerization. The histologic features of linear porokeratosis are essentially the same as those of the classic type of Mibelli, namely, a keratin-filled parakeratotic column with underlying dysplastic epidermal Fromthe DivisionofDermatology,WellesleyHospitalandUniversity ofTorontoMedicalSchool,*theDepartmentofPathology,Toronto General Hospitaland Universityof TorontoMedicalSchool,*** and the Departmentof RadiationOncology,Princess Margaret Hospitaland Universityof TorontoMedicalSchool.**** No reprintsavailable. **Now with the Departmentof Dermatology,VancouverGeneral Hospital and Universityof BritishColumbia,855 W. 10thAve., Vancouver,BritishColumbiaV5Z IL7, Canada.
448
Fig. 1. Unilateral linear hyperkeratotic lesions in linear porokeratosis. cells. The parakeratotic column is referred to as the cornoid lamella. The histologic changes are usually less pronounced in types 2, 3, 4, and 5 than in type 1.
Volume 16 Number 2, Part 2 February 1987
Metastatic SCC in linear porokeratosis
449
Fig. 2. Lesions show central atrophy with a raised border.
To the best o f our knowledge, metastatic squamous cell carcinoma in linear porokeratosis has not been reported to date. We herein report such a case.
CASE REPORT A 45-year-old white woman was referred to the regional cancer hospital (Princess Margaret Hospital) for treatment of squamous cell carcinoma that had developed in a hyperkeratotic lesion on the posterior aspect of her fight calf. The patient's dermatologic history dated back to the age of 9 years, when she developed a hemorrhagic rash on her right buttock. The buttock rash became hyperkeratotic and subsequently spread down the posterior aspect of her right thigh and calf. It later spread to the right midanterior and posterior aspect of her chest wall and to her right upper extremity. The eruption was occasionally pruritic, with exacerbations mainly in the summer months. The lesions had not changed in size since the patient's teens. There was no known family history of similar lesions. Ultraviolet lamp therapy and "creams" produced no change. After five x-ray treatments to all lesions during the patient's teens, the hyperkeratotic plaques were noted to have softened, Further details of these treatments are not known. There is a subsequent history of mitral stenosis and chronic atrial fibrillation. At the age of 47 years, the patient suffered a myocardial infarction and deep venous thrombosis of the right upper extremity. Initial examination revealed multicentric hyperker-
Fig. 3. Right inguinal node with metastatic squamous cell carcinoma in linear porokeratosis. atotic lesions on the right buttock, the posterior aspect of the right thigh and calf (Fig. 1), the fight posterior thoracic area, and the right arm. Lesions were noted to be atrophic centrally, with a raised ridge border
450
Journal of the American Academy of Dermatology
Lozinski et al
Fig. 4. Cornoid lamella (right) and adjacent squamous cell carcinoma (left). (Hematoxylineosin stain; × 40.) Bilateral groin adenopathy noted at this time was thought to be benign. In 1980 the patient returned for evaluation of a further enlargement of a right inguinal node (Fig. 3). Pathologic study of this lymph node showed well-differentiated squamous cell carcinoma. At this time, the results of skin biopsy of a lesion on the posterior aspect of the fight thigh were consistent with porokeratosis with adjacent areas of squamous cell carcinoma (Figs. 4 and 5). Treatment at this time consisted of excision of the right inguinal lymph node, followed by 5,000 cGy of radiation. The porokeratotic lesions with malignant change on her right thigh were excised. The patient subsequently developed other areas of squamous cell carcinoma within lesional skin on the posterior aspect of her fight thigh. These lesions were also managed by excision. At the submission of this paper, 5 years post presentation, there is no evidence of malignant recurrence. DISCUSSION
Fig. 5. Cornoid lamella of porokeratosis--keratin-filled epidermal invagination with central parakeratotic column. Note the absence of a granular layer underlying the parakeratotic column. (Hematoxylin-eosin stain; x 100.) (Fig. 2). An initial skin biopsy specimen from a lesion on the posterior aspect of the right calf in 1970 (not available) showed squamous cell carcinoma. Subsequent therapy consisted of local radiation (3,500 cGy).
Porokeratosis is a relatively rare disease. Its precise incidence is unclear, but a review of the literature in 1974 revealed only 250 reported cases. In the review of Mehregan et al,4 the linear variant constituted seven of a total of 197 cases of porokeratosis. Epidermal malignancies m a y occur in all types of porokeratosis. To date, there have been reports of seventeen cases of squamous cell carcinoma, three of basal cell carcinoma, and five with concurrent or solitary Bowen's disease in porokera-
Volume 16 Number 2, Part 2 February 1987
tosis. 48 The incidence of malignant change was 7% in 250 cases of porokeratosis reviewed in 1974. 5 It was previously thought that squamous cell carcinoma in this context had a low propensity to metastasize. Evidence to the contrary was reported by Machino et al, 9 whose case of metastatic squamous cell carcinoma in disseminated porokeratosis had a fatal outcome. To our knowledge, ours is the second case of metastatic squamous cell carcinoma in porokeratosis and the first in linear porokeratosis. It is thought that porokeratosis evolves from a clone of abnormal epidermal cells at the base of the cornoid lamella. These ceils are thought to be more sensitive to ultraviolet light than normal epidermal cells and often show degenerative and dysplastic changes. Malignancy is thought to develop from these areas of epidermal dysplasia. ~o One may speculate that earlier x-irradiation played a role in producing the multifocal malignant change in our patient. All carcinomas occurred within the field of previous irradiation. The interval between x-ray exposure and malignant transformation was more than 25 years. Goerttler and Jung 5 noted previous x-ray treatment in four of seventeen cases of malignant change within porokeratosis. In three cases, with intervals of 13 to 17 years between x-ray and carcinoma, a causal relationship was suspected. X-irradiation was not thought to be a contributing factor in the fourth case, in which malignant change occurred within 2 years of exposure.
Metastatic SCC in linear porokeratosis
451
Widespread lesions of porokeratosis present a p r o b l e m in management. Solitary lesions freq u e n t l y can be excised or destroyed. Other modalities include liquid nitrogen, topical steroids, 5fluorouracil, topical vitamin A, oral retinoids, and various topical keratolytic agents. 2 For widespread lesions, most of these methods are unsatisfactory or unrealistic. Monitoring is therefore most important, if lesions persist, for the detection of early malignant transformation and possible metastases. REFERENCES
1. Lever WF, Schaumburg-Lever G. Histopathology of the skin. 6th ed. Philadelphia: J B Lippincott Co, 1983. 2. Rahbari H, Cordero A, Mehregan All. Linear porokeratosis. Arch Dermatol 1974;109:526-8. 3. Witkowski J, Parish L. Linear porokeratosis presenting as mosaic plantar warts. Int J Dermatol 1982;1:401-4, 4. Mehregan AH, Khalili H. Fazel Z. Mibelli's porokeratosis of the face: a report of seven cases. J AM ACAD DERMATOt.1980;3:394-6. 5. Goerttler EA, Jung EG. Parakeratosis, Mibelli and skin carcinoma: a critical review. Humangcnetik 1975;26: 291-6. 6. Coskey RJ, Mehregan AH. Bowen disease associated with porokeratosis of Mibelli. Arch Dermatol 1975; 111:1480-1.
7. Glickman FS. Porokeratosis associated with basal cell carcinoma. Cutis 1982;29:446-9. 8. Shrum JR, CooperPH, GreerKE, Landes HB. Squamous cell carcinoma in disseminated superficial actinic porokeratosis. J AM ACADDERNAa'OL1982;6:58-62. 9. Machino H, Miki Y, Teramoio T, et al, Cytogeneticstudies in a patient with porokeratosis of Mibelli, multiple cancers and a formc fruste of Werner's syndrome. Br J Dermatol 1984;3:579-86. 10. Reed RJ, Leone P. Porokeratosis: a mutant clonal keratosis of the epidermis. Arch Dermatol 1970;101:340-7.