- Email: [email protected]
Fatal squamous cell carcinoma arising from transplant-associated porokeratosis
Case reports 931
J AM ACAD DERMATOL VOLUME 49, NUMBER 5
linked dominant chondrodysplasia punctata.7 Recently, Happle and Assim elaborated on the system of Blaschko’s lines on the head and neck.9 The mother and maternal grandmother of the first patient had whorled scarring alopecia and widely spaced conical teeth. In female patients, the clinical findings may be subtle, reflecting extreme lyonization. The scarring alopecia and dental abnormalities are permanent and can be used as markers to ascertain affected adult women. Severe neurologic manifestations in patients with incontinentia pigmenti have been reported and include seizures, mental retardation, spasticity, hemiparesis, and encephalopathy.3 Francis and Sybert noted that neurologic involvement usually occurred early in life and was associated with ocular involvement.10 Our experience, as illustrated by the first patient, is similar. However, we would like to emphasize that while neurologic disease is a real possibility, it actually occurs in only a minority of patients (approximately 20%). Whorled scarring alopecia is an interesting clinical observation that has not been described previously in incontinentia pigmenti. However, it seems logical that if lesions on the trunk and limbs follow Blaschko’s lines due to lyonization, then the scalp should be no different. Hence, this phenomenon
may not be rare, just not previously commented upon. REFERENCES 1. Smahi A, Courtois G, Vabres P, Yamaoka S, Heuertz S, Munnich A, et al. Genomic rearrangement in NEMO impairs NF-kappaB activation and is a cause of incontinentia pigmenti. The International Incontinentia Pigmenti (IP) Consortium. Nature 2000;405: 466 –72. 2. Zonana J, Elder ME, Schneider LC, Orlow SJ, Moss C, Golabi M, et al. A novel X-linked disorder of immune deficiency and hypohidrotic ectodermal dysplasia is allelic to incontinentia pigmenti and due to mutations in IKK-gamma (NEMO). Am J Hum Genet 2000;67:1555– 62. 3. Carney RG. Incontinentia pigmenti: a world statistical analysis. Arch Dermatol 1976;112:535– 42. 4. Traupe H. Functional X-chromosomal mosaicism of the skin: Rudolf Happle and the lines of Alfred Blaschko. Am J Med Genet 1999;85:324 –9. 5. Happle R. Lyonization and the lines of Blaschko. Hum Genet 1985;70:200 – 6. 6. Lyon M. Gene action in the X-chromosome of the mouse (Mus musculus L. ). Nature 1961;190:372–3. 7. Happle R. Genetic defects involving the hair. In: Orfanos CE, Happle R, editors. Hair and hair diseases. Berling: Springer-Verlag; 1990. p. 325– 62. 8. Happle R, Fuhrmann-Rieger A, Fuhrmann W. Wie verlaufen die Blaschko-Linien am behaarten Kopf? Hautarzt 1984;35:366 –9. 9. Happle R, Assim A. The lines of Blaschko on the head and neck. J Am Acad Dermatol 2001;44:612–5. 10. Francis J, Sybert V. Incontinentia pigmenti. Semin Cutan Med Surg 1997;16:54 – 60.
Fatal squamous cell carcinoma arising from transplant-associated porokeratosis Shane G. Silver, MD,a and Richard I. Crawford, MD, FRCPCa,b Vancouver, British Columbia, Canada Porokeratosis is a disorder of epidermal keratinization characterized by variably sized plaques with central depression and a well-demarcated keratotic border. Associations of porokeratosis with immunosuppression and of porokeratosis with malignancy have been observed. The authors report a case of fatal metastatic squamous cell carcinoma arising from porokeratosis in an immunosuppressed patient. (J Am Acad Dermatol 2003;49:931-3.)
From the Division of Dermatologya and Department of Pathology, University of British Columbia.b Funding source: None. Conflict of interest: None identified. Reprints not available from the authors. Correspondence: Richard I. Crawford, MD, Laboratory, St. Paul’s Hospital, 1081 Burrard St., Vancouver, British Columbia, Canada V6Z 1Y6. E-mail: [email protected]. Copyright © 2003 by the American Academy of Dermatology, Inc. 0190-9622/2003/$30.00 ⫹ 0 doi:10.1067/S0190-9622(03)00469-9
T
he premalignant potential of porokeratosis in immunocompetent patients has been well documented, with squamous cell carcinoma arising in approximately 7% of reported cases.1 Immunosuppression increases the incidence of porokeratosis. Anzai and colleagues described metastatic squamous cell carcinoma in a renal transplant patient with linear porokeratosis.2 Here we report the case of a woman who developed fatal metastatic squamous cell carcinoma from porokeratosis in the
932 Case reports
Fig 1. Large atrophic plaques with prominent threadlike borders on the left leg, typical of porokeratosis of Mibelli.
Fig 2. Scanning magnification histology of invasive squamous cell carcinoma arising within a lesion of porokeratosis, with a cornoid lamella on the left side of the field, and invasive carcinoma on the right.
Fig 3. Invasive squamous cell carcinoma demonstrating infiltrative architecture and marked cytologic atypia.
setting of prior renal transplantation and immunosuppressive therapy.
CASE REPORT A 49-year-old woman was referred for evaluation of intermittent swelling of her left lower extremity of 3 months duration. Repeated Doppler ultrasound examinations and computed tomography showed no evidence of deep venous thrombosis or intraabdominal malignancy. She had undergone empiri-
J AM ACAD DERMATOL NOVEMBER 2003
cal treatment with antibiotics with minimal improvement. The patient’s history was remarkable for renal transplantation performed 13 years previously and complicated by chronic rejection. During the preceding 2 weeks, her renal function had deteriorated to the point that arrangements were being made for reinstitution of dialysis. Her dermatologic history was significant. She recalled developing “psoriasis” on her lower extremities after a sunburn 7 years before her renal transplantation. She described gradual but relentless enlargement of individual lesions with the development of central erythema and a “scarred” appearance. Antipsoriatic treatments did not help. During the 9 months before her renal transplantation, she underwent surgery for 2 cutaneous malignancies, including basal cell carcinoma on her left postauricular skin and a superficially invasive acral lentiginous melanoma on her left heel. No further cutaneous malignancies were diagnosed until an invasive squamous cell carcinoma was excised from her left shin 9 months before our consultation. The original pathologic assessment was that the invasive squamous cell carcinoma had been completely excised, and no further treatment was initiated. This lesion was diagnosed and treated elsewhere, and we cannot comment on the clinical morphologic evaluation. The patient’s immunosuppressive medications included prednisone, cyclosporine, and azathioprine and had been continued without interruption from the time of her transplantation through the time of our consultation. Initial examination revealed a moderately cushingoid middle-aged woman with extensive actinic damage, particularly solar lentigines, over her face and upper and lower extremities. There was a strikingly asymmetric eruption of centrally atrophic and erythematous plaques with threadlike borders, numbering approximately 50 over the dorsal portion of her left foot, leg, and anterior portion of the thigh, with only four lesions on her right leg and thigh (Fig 1). The entire left lower extremity had pitting edema. Within the left inguinal fold was a palpable nontender lymph node measuring 0.5 cm ⫻ 1.5 cm. Punch biopsies of the atrophic erythematous plaques were performed, helping to confirm porokeratosis. A prominent cornoid lamella and adjacent reactive epidermal hyperplasia were characteristic of the Mibelli type of porokeratosis, in spite of the patient’s history of sunburn. Results of her previous biopsy of the left shin were reviewed and showed squamous cell carcinoma arising within the central portion of a lesion of porokeratosis (Figs 2, 3). She underwent biopsy of a left inguinal node, which helped confirm metastatic squamous cell carcinoma.
J AM ACAD DERMATOL VOLUME 49, NUMBER 5
The patient’s immunosuppressive therapies, aside from low-dose prednisone, were discontinued. A regular schedule of hemodialysis was instituted. The treatments of chemotherapy, radiation, and palliation were discussed with her. Unfortunately, before a decision could be made, she developed a bowel obstruction, with extensive intrapelvic metastases identified at repeated computed tomography. As nodal metastasis of the squamous cell carcinoma had already been confirmed pathologically, further biopsies of the intrapelvic metastases were not performed. Because of her extensive metastatic disease, development of sepsis, and ongoing difficulty with dialysis, the patient underwent palliative measures. She died 4 weeks after consultation. Permission for autopsy was denied.
DISCUSSION Porokeratosis is found with increased incidence in immunosuppressed patients.3-9 Disseminated superficial actinic porokeratosis is the most common clinical variant of porokeratosis developing in immunosuppressed states; however, porokeratosis of Mibelli and linear porokeratosis have also been reported.3-9 The clinical and histologic findings in our patient were characteristic of the Mibelli type. Immunosuppression due to a variety of causes, including therapy for leukemia or lymphoma and organ transplantation, has been associated with the development of porokeratosis. Malignant transformation is described in all variants of porokeratosis but is most common in linear porokeratosis and rare in disseminated superficial actinic porokeratosis.1,10-12 Despite its association with malignancy, porokeratosis is still considered by many to be a benign disease and is either monitored or controlled with medical therapies or destructive measures.13 Therapy may be impractical, depending on the number of lesions of porokeratosis and general medical status of the patient. To our knowledge, there have been 4 case reports of metastatic squamous cell carcinoma developing from porokeratosis in immunocompetent patients.2,14-16 This case report describes the development, in an immunosuppressed patient, of fatal metastatic squamous cell carcinoma from porokeratosis. Our review of the literature failed to reveal specific recommendations for the treatment of porokeratosis in immunosuppressed patients. We believe patients with a few scattered lesions of po-
Case reports 933
rokeratosis should undergo definitive destructive therapy such as cryotherapy, laser therapy, or surgical excision. However, many patients present with multiple lesions, which are not amenable to widespread treatment. Treatment in these patients requires close surveillance and a low threshold for biopsy of any lesion suspicious for early squamous cell carcinoma. REFERENCES 1. Otsuka F, Someya T, Ishibashi Y. Porokeratosis and malignant skin tumors. J Cancer Res Clin Oncol 1991;117:55– 60. 2. Anzai S, Takeo N, Yamaguchi T, Sato T, Takasaki S, Terashi H, et al. Squamous cell carcinoma in a renal transplant recipient with linear porokeratosis. J Dermatol 1999;26:244 –7. 3. Herranz P, Pizarro A, De Lucas R, Robayna MG, Rubio FA, Sanz A, et al. High incidence of porokeratosis in renal transplant recipients. Br J Dermatol 1997;136:176 –9. 4. Lederman JS, Sober AJ, Lederman GS. Immunosuppression: a cause of porokeratosis? J Am Acad Dermatol 1985;13:75–9. 5. Bencini PL, Tarantino A, Grimalt R, Ponticelli C, Caputo R. Porokeratosis and immunosuppression. Br J Dermatol 1995;132:74 – 8. 6. Knoell KA, Patterson JW, Wilson BB. Sudden onset of disseminated porokeratosis of Mibelli in a renal transplant patient. J Am Acad Dermatol 1999;41:830 –2. 7. Wilkinson SM, Cartwright PH, English JSC. Porokeratosis of Mibelli and immunosuppression. Clin Exp Dermatol 1991;16:61–2. 8. Tsambaos D, Spiliopoulos T. Disseminated superficial porokeratosis: complete remission subsequent to discontinuation of immunosuppression. J Am Acad Dermatol 1993;28:651–2. 9. Raychaudhuri SP, Smoller BR. Porokeratosis in immunosuppressed and nonimmunosuppressed patients. Int J Dermatol 1992;31:781–2. 10. Brodkin RH, Rickert RR, Fuller W, Saporito C. Malignant disseminated porokeratosis. Arch Dermatol 1987;123:1521– 6. 11. Chernosky ME, Rapini RP. Squamous cell carcinoma in lesions of disseminated superficial actinic porokeratosis: a report of two cases. Arch Dermatol 1986;122:853– 4. 12. Abadir R, Zurowski S. Case report: squamous cell carcinoma of the skin in both palms, axillary node, donor skin graft site and both soles—associated hyperkeratosis and porokeratosis. Br J Radiol 1994;67:507–10. 13. Schamroth JM, Zlotogorski A, Gilead L. Porokeratosis of Mibelli: overview and review of the literature. Acta Derm Venereol 1997; 77:207–13. 14. Lozinski AZ, Fisher BK, Walter JB, Fitzpatrick PJ. Metastatic squamous cell carcinoma in linear porokeratosis of Mibelli. J Am Acad Dermatol 1987;16:448 –51. 15. Machino H, Miki Y, Teramoto T, Shiraishi S, Sasaki MS. Cytogenetic studies in a patient with porokeratosis of Mibelli, multiple cancers and a forme fruste of Werner’s syndrome. Br J Dermatol 1984;111:579 – 86. 16. Sawai T, Hayakawa H, Danno K, Miyauchi H, Uehara M. Squamous cell carcinoma arising from giant porokeratosis: a case with extensive metastasis and hypercalcemia. J Am Acad Dermatol 1996;34:507–9.
J AM ACAD DERMATOL VOLUME 49, NUMBER 5
linked dominant chondrodysplasia punctata.7 Recently, Happle and Assim elaborated on the system of Blaschko’s lines on the head and neck.9 The mother and maternal grandmother of the first patient had whorled scarring alopecia and widely spaced conical teeth. In female patients, the clinical findings may be subtle, reflecting extreme lyonization. The scarring alopecia and dental abnormalities are permanent and can be used as markers to ascertain affected adult women. Severe neurologic manifestations in patients with incontinentia pigmenti have been reported and include seizures, mental retardation, spasticity, hemiparesis, and encephalopathy.3 Francis and Sybert noted that neurologic involvement usually occurred early in life and was associated with ocular involvement.10 Our experience, as illustrated by the first patient, is similar. However, we would like to emphasize that while neurologic disease is a real possibility, it actually occurs in only a minority of patients (approximately 20%). Whorled scarring alopecia is an interesting clinical observation that has not been described previously in incontinentia pigmenti. However, it seems logical that if lesions on the trunk and limbs follow Blaschko’s lines due to lyonization, then the scalp should be no different. Hence, this phenomenon
may not be rare, just not previously commented upon. REFERENCES 1. Smahi A, Courtois G, Vabres P, Yamaoka S, Heuertz S, Munnich A, et al. Genomic rearrangement in NEMO impairs NF-kappaB activation and is a cause of incontinentia pigmenti. The International Incontinentia Pigmenti (IP) Consortium. Nature 2000;405: 466 –72. 2. Zonana J, Elder ME, Schneider LC, Orlow SJ, Moss C, Golabi M, et al. A novel X-linked disorder of immune deficiency and hypohidrotic ectodermal dysplasia is allelic to incontinentia pigmenti and due to mutations in IKK-gamma (NEMO). Am J Hum Genet 2000;67:1555– 62. 3. Carney RG. Incontinentia pigmenti: a world statistical analysis. Arch Dermatol 1976;112:535– 42. 4. Traupe H. Functional X-chromosomal mosaicism of the skin: Rudolf Happle and the lines of Alfred Blaschko. Am J Med Genet 1999;85:324 –9. 5. Happle R. Lyonization and the lines of Blaschko. Hum Genet 1985;70:200 – 6. 6. Lyon M. Gene action in the X-chromosome of the mouse (Mus musculus L. ). Nature 1961;190:372–3. 7. Happle R. Genetic defects involving the hair. In: Orfanos CE, Happle R, editors. Hair and hair diseases. Berling: Springer-Verlag; 1990. p. 325– 62. 8. Happle R, Fuhrmann-Rieger A, Fuhrmann W. Wie verlaufen die Blaschko-Linien am behaarten Kopf? Hautarzt 1984;35:366 –9. 9. Happle R, Assim A. The lines of Blaschko on the head and neck. J Am Acad Dermatol 2001;44:612–5. 10. Francis J, Sybert V. Incontinentia pigmenti. Semin Cutan Med Surg 1997;16:54 – 60.
Fatal squamous cell carcinoma arising from transplant-associated porokeratosis Shane G. Silver, MD,a and Richard I. Crawford, MD, FRCPCa,b Vancouver, British Columbia, Canada Porokeratosis is a disorder of epidermal keratinization characterized by variably sized plaques with central depression and a well-demarcated keratotic border. Associations of porokeratosis with immunosuppression and of porokeratosis with malignancy have been observed. The authors report a case of fatal metastatic squamous cell carcinoma arising from porokeratosis in an immunosuppressed patient. (J Am Acad Dermatol 2003;49:931-3.)
From the Division of Dermatologya and Department of Pathology, University of British Columbia.b Funding source: None. Conflict of interest: None identified. Reprints not available from the authors. Correspondence: Richard I. Crawford, MD, Laboratory, St. Paul’s Hospital, 1081 Burrard St., Vancouver, British Columbia, Canada V6Z 1Y6. E-mail: [email protected]. Copyright © 2003 by the American Academy of Dermatology, Inc. 0190-9622/2003/$30.00 ⫹ 0 doi:10.1067/S0190-9622(03)00469-9
T
he premalignant potential of porokeratosis in immunocompetent patients has been well documented, with squamous cell carcinoma arising in approximately 7% of reported cases.1 Immunosuppression increases the incidence of porokeratosis. Anzai and colleagues described metastatic squamous cell carcinoma in a renal transplant patient with linear porokeratosis.2 Here we report the case of a woman who developed fatal metastatic squamous cell carcinoma from porokeratosis in the
932 Case reports
Fig 1. Large atrophic plaques with prominent threadlike borders on the left leg, typical of porokeratosis of Mibelli.
Fig 2. Scanning magnification histology of invasive squamous cell carcinoma arising within a lesion of porokeratosis, with a cornoid lamella on the left side of the field, and invasive carcinoma on the right.
Fig 3. Invasive squamous cell carcinoma demonstrating infiltrative architecture and marked cytologic atypia.
setting of prior renal transplantation and immunosuppressive therapy.
CASE REPORT A 49-year-old woman was referred for evaluation of intermittent swelling of her left lower extremity of 3 months duration. Repeated Doppler ultrasound examinations and computed tomography showed no evidence of deep venous thrombosis or intraabdominal malignancy. She had undergone empiri-
J AM ACAD DERMATOL NOVEMBER 2003
cal treatment with antibiotics with minimal improvement. The patient’s history was remarkable for renal transplantation performed 13 years previously and complicated by chronic rejection. During the preceding 2 weeks, her renal function had deteriorated to the point that arrangements were being made for reinstitution of dialysis. Her dermatologic history was significant. She recalled developing “psoriasis” on her lower extremities after a sunburn 7 years before her renal transplantation. She described gradual but relentless enlargement of individual lesions with the development of central erythema and a “scarred” appearance. Antipsoriatic treatments did not help. During the 9 months before her renal transplantation, she underwent surgery for 2 cutaneous malignancies, including basal cell carcinoma on her left postauricular skin and a superficially invasive acral lentiginous melanoma on her left heel. No further cutaneous malignancies were diagnosed until an invasive squamous cell carcinoma was excised from her left shin 9 months before our consultation. The original pathologic assessment was that the invasive squamous cell carcinoma had been completely excised, and no further treatment was initiated. This lesion was diagnosed and treated elsewhere, and we cannot comment on the clinical morphologic evaluation. The patient’s immunosuppressive medications included prednisone, cyclosporine, and azathioprine and had been continued without interruption from the time of her transplantation through the time of our consultation. Initial examination revealed a moderately cushingoid middle-aged woman with extensive actinic damage, particularly solar lentigines, over her face and upper and lower extremities. There was a strikingly asymmetric eruption of centrally atrophic and erythematous plaques with threadlike borders, numbering approximately 50 over the dorsal portion of her left foot, leg, and anterior portion of the thigh, with only four lesions on her right leg and thigh (Fig 1). The entire left lower extremity had pitting edema. Within the left inguinal fold was a palpable nontender lymph node measuring 0.5 cm ⫻ 1.5 cm. Punch biopsies of the atrophic erythematous plaques were performed, helping to confirm porokeratosis. A prominent cornoid lamella and adjacent reactive epidermal hyperplasia were characteristic of the Mibelli type of porokeratosis, in spite of the patient’s history of sunburn. Results of her previous biopsy of the left shin were reviewed and showed squamous cell carcinoma arising within the central portion of a lesion of porokeratosis (Figs 2, 3). She underwent biopsy of a left inguinal node, which helped confirm metastatic squamous cell carcinoma.
J AM ACAD DERMATOL VOLUME 49, NUMBER 5
The patient’s immunosuppressive therapies, aside from low-dose prednisone, were discontinued. A regular schedule of hemodialysis was instituted. The treatments of chemotherapy, radiation, and palliation were discussed with her. Unfortunately, before a decision could be made, she developed a bowel obstruction, with extensive intrapelvic metastases identified at repeated computed tomography. As nodal metastasis of the squamous cell carcinoma had already been confirmed pathologically, further biopsies of the intrapelvic metastases were not performed. Because of her extensive metastatic disease, development of sepsis, and ongoing difficulty with dialysis, the patient underwent palliative measures. She died 4 weeks after consultation. Permission for autopsy was denied.
DISCUSSION Porokeratosis is found with increased incidence in immunosuppressed patients.3-9 Disseminated superficial actinic porokeratosis is the most common clinical variant of porokeratosis developing in immunosuppressed states; however, porokeratosis of Mibelli and linear porokeratosis have also been reported.3-9 The clinical and histologic findings in our patient were characteristic of the Mibelli type. Immunosuppression due to a variety of causes, including therapy for leukemia or lymphoma and organ transplantation, has been associated with the development of porokeratosis. Malignant transformation is described in all variants of porokeratosis but is most common in linear porokeratosis and rare in disseminated superficial actinic porokeratosis.1,10-12 Despite its association with malignancy, porokeratosis is still considered by many to be a benign disease and is either monitored or controlled with medical therapies or destructive measures.13 Therapy may be impractical, depending on the number of lesions of porokeratosis and general medical status of the patient. To our knowledge, there have been 4 case reports of metastatic squamous cell carcinoma developing from porokeratosis in immunocompetent patients.2,14-16 This case report describes the development, in an immunosuppressed patient, of fatal metastatic squamous cell carcinoma from porokeratosis. Our review of the literature failed to reveal specific recommendations for the treatment of porokeratosis in immunosuppressed patients. We believe patients with a few scattered lesions of po-
Case reports 933
rokeratosis should undergo definitive destructive therapy such as cryotherapy, laser therapy, or surgical excision. However, many patients present with multiple lesions, which are not amenable to widespread treatment. Treatment in these patients requires close surveillance and a low threshold for biopsy of any lesion suspicious for early squamous cell carcinoma. REFERENCES 1. Otsuka F, Someya T, Ishibashi Y. Porokeratosis and malignant skin tumors. J Cancer Res Clin Oncol 1991;117:55– 60. 2. Anzai S, Takeo N, Yamaguchi T, Sato T, Takasaki S, Terashi H, et al. Squamous cell carcinoma in a renal transplant recipient with linear porokeratosis. J Dermatol 1999;26:244 –7. 3. Herranz P, Pizarro A, De Lucas R, Robayna MG, Rubio FA, Sanz A, et al. High incidence of porokeratosis in renal transplant recipients. Br J Dermatol 1997;136:176 –9. 4. Lederman JS, Sober AJ, Lederman GS. Immunosuppression: a cause of porokeratosis? J Am Acad Dermatol 1985;13:75–9. 5. Bencini PL, Tarantino A, Grimalt R, Ponticelli C, Caputo R. Porokeratosis and immunosuppression. Br J Dermatol 1995;132:74 – 8. 6. Knoell KA, Patterson JW, Wilson BB. Sudden onset of disseminated porokeratosis of Mibelli in a renal transplant patient. J Am Acad Dermatol 1999;41:830 –2. 7. Wilkinson SM, Cartwright PH, English JSC. Porokeratosis of Mibelli and immunosuppression. Clin Exp Dermatol 1991;16:61–2. 8. Tsambaos D, Spiliopoulos T. Disseminated superficial porokeratosis: complete remission subsequent to discontinuation of immunosuppression. J Am Acad Dermatol 1993;28:651–2. 9. Raychaudhuri SP, Smoller BR. Porokeratosis in immunosuppressed and nonimmunosuppressed patients. Int J Dermatol 1992;31:781–2. 10. Brodkin RH, Rickert RR, Fuller W, Saporito C. Malignant disseminated porokeratosis. Arch Dermatol 1987;123:1521– 6. 11. Chernosky ME, Rapini RP. Squamous cell carcinoma in lesions of disseminated superficial actinic porokeratosis: a report of two cases. Arch Dermatol 1986;122:853– 4. 12. Abadir R, Zurowski S. Case report: squamous cell carcinoma of the skin in both palms, axillary node, donor skin graft site and both soles—associated hyperkeratosis and porokeratosis. Br J Radiol 1994;67:507–10. 13. Schamroth JM, Zlotogorski A, Gilead L. Porokeratosis of Mibelli: overview and review of the literature. Acta Derm Venereol 1997; 77:207–13. 14. Lozinski AZ, Fisher BK, Walter JB, Fitzpatrick PJ. Metastatic squamous cell carcinoma in linear porokeratosis of Mibelli. J Am Acad Dermatol 1987;16:448 –51. 15. Machino H, Miki Y, Teramoto T, Shiraishi S, Sasaki MS. Cytogenetic studies in a patient with porokeratosis of Mibelli, multiple cancers and a forme fruste of Werner’s syndrome. Br J Dermatol 1984;111:579 – 86. 16. Sawai T, Hayakawa H, Danno K, Miyauchi H, Uehara M. Squamous cell carcinoma arising from giant porokeratosis: a case with extensive metastasis and hypercalcemia. J Am Acad Dermatol 1996;34:507–9.