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Trichilemmomal carcinoma in a patient with Cowden's disease (multiple hamartoma syndrome)
Journal of the American Academy of Dermatology Volume 36, Number 6, Part 1
Belluno district (Veneto region, northeast Italy): age distribution and morbidity. A m J Med Genet 1990;suppl 7: 84-6. 5. Hanifin JM, Rajka G. Diagnostic features of atopic dermatiffs. Acta Derm Venereol Suppl (Stockh) 1980;92: 44-7. 6. Schmied C, Saurat J-H. Epidfmiologie de la dermatite atopique. Ann Dermatol Venereol 1989;116:729-34.
Brief communications
1021
7. Schachner L. A statistical analysis of a pediatric dermatology clinic. Pediatr Dermatol 1983;1:157-64. 8. Palazzo R, Schepis C, Dispinzeri A, et al. Study of cutaneous hydration in subjects with Down's syndrome. In: Cerimele D, Fabrizi G, Serri F, editors. Atti del 3 ° Simposio Intemazionale di Dermatologia Pediatrica 14-17 Settembre, 1988 Mazara del Vallo (TP). Napoli: L'Antologia, 1988:23944.
Trichilemmomal carcinoma in a patient with Cowden's disease (multiple hamartoma syndrome) Ann M. O'Hare, MD,* Philip H. Cooper, MD, and Harry L. Parlette HI, M D
Charlottesville, Virginia Cowden's disease (multiple hamartoma syndrome) is an autosomal dominant genodermatosis in which characteristic mucocutaneous lesions are associated with multiple-system disease. The index case, described in 1963 by Lloyd and Dennis, 1 was a 20-year-old woman with fibrocystic breast disease, breast cancer, and thyroid adenomas associated with prominent cutaneous findings. Subsequently, the disease has been more fully characterized 2 and additional cutaneous and extracutaneous manifestations noted. The gene for Cowden' s disease has been localized to a region on chromosome 10, and studies are under way to identify candidate genes in this region. 3 Virtually pathognomonic of Cowden' s disease are multiple facial trichilemmomas that are clustered around the eyes, mouth, ears, and nose. 4 Patients may also have mucosal papillomatosis that imparts a distinctive "cobblestone" appearance to the oral cavity. Acral and palmoplantar keratoses are another highly characteristic finding. More recently, multiple sclerotic dermal fibromas have been noted to be specific to Cowden's disease. 5 Salem and Steck 6 have designated cutaneous facial papules and oral From the Department of Dermatology, University of Virginia. Reprint requests: Harry L. Parlette IlI, MD, Department of Dermatology, University of Virginia, Charlottesville, VA 22908. *Dr. O'Hare is currently an intern in intemal medicine at Stanford University Medical Center, Stanford, Calif. J Am Acad Dermatol 1997;36:1021-3. Copyright © 1997 by the American Academy of Dermatology, Inc. 0190-9622/97/$5.00 + 0 16/54/79675
Fig. 1. Erythematous keratotic exophytic nodule (10 x 10 ram) on right cheek of patient with Cowden's disease. mucosal papillomatosis as major criteria for the diagnosis of Cowden' s disease and acral keratoses and palmoplantar keratoses as minor criteria. They suggested that the diagnosis can be made in the presence of either two major criteria or one major and one minor criterion. 6 When there is a family history of Cowden's disease, either one major or two minor criteria will suffice. Accurate diagnosis of Cowden's disease is critical because patients are at increased risk for several benign and malignant tumors. 7 Among female patients, fibrocystic breast disease and fibroadenomas
1022
Brief communications
Journal of the American Academy of Dermatology June 1997
Fig. 2. A, Lobulate keratinocytic neoplasm infiltrates the dermis. Note cyst containing homogeneous calcified keratin and lacking a granular layer. B, Cytologic evidence of mafignancy is accompanied by mitotic figures. (A and B, Hematoxylin-eosin stain. Original magnifications: A, x50; B, x250.)
of the breast are common, and breast cancer develops in 25% to 36% of patients. 8 Patients with Cowden's disease are also particularly at risk for thyroid carcinoma, colonic polyposis, and colon adenocarcinoma, as well as for tumors of the genitourinary tract. Tumors of the nervous system including meningiomas, neurofibrornas, and neuromas have been reported, 8 and evidence is growing for a significant association with Lhermitte-Duclos disease 9 a condition in which there is abnormal proliferation of neuronal cells in the cerebellum. Several mucocutaneous malignancies have been reported in patients with Cowden's disease including melanoma, basal cell carcinoma, squamous cell carcinoma, and Merkel cell carcinoma, s W e report a case of irichilemmonal carcinoma in a patient with Cowden's disease. Whereas multiple tricholemmomas are highly characteristic, trichilemmomal carcinoma has not been previously reported.
vealed a multilobate epithelial neoplasm with overt architectural and cytologic evidence of malignancy that extended from multiple epidermal connections into the dermis (Fig. 2). Although there were isolated loci of peripheral palisading and focal stromal retraction, the essential differentiation of the neoplasm was keratinocytic, on the basis of the polyhedral squamoid cells with modest to abundant cytoplasm. Multiple foci of clear cells were present (Fig. 2, B) that contained abundant glycogen. Better differentiated fields of squamous cells were associated with microcysts that contained focally calcified, homogeneous keratin that formed in the absence of an interposed keratohyaline granular layer (Fig. 2, A). Mitotic figures were numerous and some were abnormal (Fig. 2, B). Thickened, glassy basement membrane could not be identified. A diagnosis of trichilemmomal carcinoma was made. The lesion was removed by Moils micrographic surgery.
CASE REPORT
Trichilemmomal carcinoma is a cutaneous adnexal neoplasm of the external root sheath. It was first described in 1976 by Headington 1° and then more fully characterized by Ten Seldam. H Trichilemmomal carcinoma appears to be rare 12' 13 and most commonly occurs on the sun-exposed, hair-beating skin of elderly persons where it is often misdiagnosed as basal cell or squamous cell carcinoma. Characteristic histologic features include lobules of glycogen-laden clear cells, peripheral palisading, prominent basement membrane, and trichilemmo-
A 56-year-old man with Cowden's disease was first reported by Weary et al.2 in 1972. In December 1994 multiple biopsy-proven facial trichilemmomas, oral papillomatosis, and a high-arched palate were noted. His medical history was significant for goiter, colonic polyposis, multiple meningiomas, acoustic neuroma, hydrocele, and complex partial seizures. The patient was referred for evaluation of a raised, crusted, keratotic lesion on the fight side of his face (Fig: 1). Microscopic examination of a biopsy specimen re-
DISCUSSION
Journal of the American Academy of Dermatology Volume 36, Number 6, Part 1
mal keratinization--aU features reminiscent of the outer root sheath. 11-13 In addition, cytologic and architectural evidence o f malignancy should be present. It is not k n o w n whether trichilemmomal carcinoma can evolve from a preexisting t d c h o l e m m o m a or whether " d e n o v o " occurrence is more the rule. 14 Trichilemmomal carcinoma can be locally aggressive, but metastases appear to be rare. 15 W e suggest that, once the diagnosis o f C o w d e n ' s disease is established, routine biopsy o f facial Trichilemmomas is u n n ~ e s s a r y . However, biopsy should be performed on any changing or atypical facial lesion.
REFERENCES 1. Lloyd KM, Dennis M. Cowden's disease: a possible new symptom complex with multiple system involvement. Ann Intern Med 1963;58:136-42. 2. Weary PE, Gorlin RJ, Gentry WC, et al. Multiple hamartoma syndrome (Cowden's disease). Arch Dermatol 1972; 106:682-90. 3. Nelen MR, Padberg GW, Peeters E/El, et al. Localization of the gene for Cowden disease to chromosome 10q22-23. Nat Gene 1996;13:114-6. 4. Barax CN, Lebwohl M, Phelps RG. Multiple hamartoma syndrome. J Am Acad Dermatol 1987;17:342-6.
Brief communications 1023 5. Requena L, Gufierrez J, Sanchez Yus E. Multiple sclerotic fibromas of the skin: a cutaneous marker of Cowden's disease. J Cutan Pathol 1991;19:346-51. 6. Salem OS, Steck WD. Cowden's disease (multiple hamartoma and neoplasia syndrome). J Am Acad Dermatol 1983;8:686-95. 7. Shapiro SD, Lambert WC, Schwartz RA. Cowden's disease: a marker for malignancy. Int J Dermatol 1988;27: 232-7. 8. Mallory SB. Cowden syndrome (multiple hamartoma syndrome). Dermatol Clin 1995;13:27-31. 9. Albrecht S, Haber RM, Goodman JC, et al. Cowden syndrome and Lhermitte-Duclosdisease. Cancer 1992;70:86976. 10. Headington yr. Tumors of the hair follicle: a review. Am J Pathol 1976;85:480-514. 1l. Ten Seldam REJ. Tricholemmocarcinoma. Australas J Dermatol 1977;18:62-72. 12. Swanson PE, Marrogi AJ, Williams DJ, Tricholemmal carcinoma: clinicopathologic study of 10 cases. J Cutan Pathol 1992;19:100-9. 13. Wong T-Y, Suster S. Tricholemmal carcinoma: a clinicopathologic study of 13 cases. Am J Dermatopathol 1994; 16:463-73. 14. Reis JP, Tellechea O, Cunha MF, et al. Trichilemmal carcinoma: a review of 8 cases. J Cutan Pathol 1993;20:44-9. 15. Gaughan RN, Rennet GJ, Templer JW. Metastatic tricholemrnal carcinoma [abstract]. Otolaryngol Head Neck Surg 1986;95(suppl):74.
Oral erosive lichen planus with epidermolytic hyperkeratosis during interferon alfa-2b therapy for chronic hepatitis C virus infection Todd E. Schlesinger, MD, a Charles Camisa, MD, a J. Douglas Gay, MD, b and W i l m a F. Bergfeld, M D a, b Cleveland, Ohio A n association between chronic active hepatitis and lichen planus (LP) was established in several studies) Interferon alfa-2a therapy for hepatitis caused b y the hepatitis C virus (HCV) has been reported to initiate, 2 clear, 3 exacerbate, 4, 5 or have no effect6 on L P lesions. W e describe oral L P initiated in a patient treated with interferon alfa-2b for chronic active hepatitis caused b y HCV. From the Departments of Derrrlatologya and Pathology?Cleveland Clinic Foundation. Reprint requests: Charles Camisa, MD, 9500EuclidAve.,Desk A61, Cleveland, OH 44195. J Am Acad Dermatol 1997;36:1023-5. Copyright © 1997 by the AmericanAcademyof Dermatology,Inc. 0190-9622/97/$5.00+ 0 16/54/80023
CASE REPORT A 39-year-old anti-HCV and HCV-RNA-positive man with histologically proven chronic active hepatitis with cirrhosis received his first course of recombinant human interferon alfa-2b (Intron A, Schering, Kenilworth, N.J.) from May 1994 through September 1994 at a dosage of 3 million units (MU) 3 times per week, not associated with cutaneous or oral abnormalities. A second course of interferon alfa-2b therapy, at a dosage of 5 MU 3 times per week was initiated in January 1995. One month later, erythematous, scaly plaques developed on the scalp, chest, back, buttocks, legs, and genitalia, as well as painful areas inside his mouth. Examination revealed scattered, psoriasiform plaques of various sizes, some covered with a Fine silvery scale on the scalp, back, arms, and legs. Plaques on the arms corresponded to sites of
Belluno district (Veneto region, northeast Italy): age distribution and morbidity. A m J Med Genet 1990;suppl 7: 84-6. 5. Hanifin JM, Rajka G. Diagnostic features of atopic dermatiffs. Acta Derm Venereol Suppl (Stockh) 1980;92: 44-7. 6. Schmied C, Saurat J-H. Epidfmiologie de la dermatite atopique. Ann Dermatol Venereol 1989;116:729-34.
Brief communications
1021
7. Schachner L. A statistical analysis of a pediatric dermatology clinic. Pediatr Dermatol 1983;1:157-64. 8. Palazzo R, Schepis C, Dispinzeri A, et al. Study of cutaneous hydration in subjects with Down's syndrome. In: Cerimele D, Fabrizi G, Serri F, editors. Atti del 3 ° Simposio Intemazionale di Dermatologia Pediatrica 14-17 Settembre, 1988 Mazara del Vallo (TP). Napoli: L'Antologia, 1988:23944.
Trichilemmomal carcinoma in a patient with Cowden's disease (multiple hamartoma syndrome) Ann M. O'Hare, MD,* Philip H. Cooper, MD, and Harry L. Parlette HI, M D
Charlottesville, Virginia Cowden's disease (multiple hamartoma syndrome) is an autosomal dominant genodermatosis in which characteristic mucocutaneous lesions are associated with multiple-system disease. The index case, described in 1963 by Lloyd and Dennis, 1 was a 20-year-old woman with fibrocystic breast disease, breast cancer, and thyroid adenomas associated with prominent cutaneous findings. Subsequently, the disease has been more fully characterized 2 and additional cutaneous and extracutaneous manifestations noted. The gene for Cowden' s disease has been localized to a region on chromosome 10, and studies are under way to identify candidate genes in this region. 3 Virtually pathognomonic of Cowden' s disease are multiple facial trichilemmomas that are clustered around the eyes, mouth, ears, and nose. 4 Patients may also have mucosal papillomatosis that imparts a distinctive "cobblestone" appearance to the oral cavity. Acral and palmoplantar keratoses are another highly characteristic finding. More recently, multiple sclerotic dermal fibromas have been noted to be specific to Cowden's disease. 5 Salem and Steck 6 have designated cutaneous facial papules and oral From the Department of Dermatology, University of Virginia. Reprint requests: Harry L. Parlette IlI, MD, Department of Dermatology, University of Virginia, Charlottesville, VA 22908. *Dr. O'Hare is currently an intern in intemal medicine at Stanford University Medical Center, Stanford, Calif. J Am Acad Dermatol 1997;36:1021-3. Copyright © 1997 by the American Academy of Dermatology, Inc. 0190-9622/97/$5.00 + 0 16/54/79675
Fig. 1. Erythematous keratotic exophytic nodule (10 x 10 ram) on right cheek of patient with Cowden's disease. mucosal papillomatosis as major criteria for the diagnosis of Cowden' s disease and acral keratoses and palmoplantar keratoses as minor criteria. They suggested that the diagnosis can be made in the presence of either two major criteria or one major and one minor criterion. 6 When there is a family history of Cowden's disease, either one major or two minor criteria will suffice. Accurate diagnosis of Cowden's disease is critical because patients are at increased risk for several benign and malignant tumors. 7 Among female patients, fibrocystic breast disease and fibroadenomas
1022
Brief communications
Journal of the American Academy of Dermatology June 1997
Fig. 2. A, Lobulate keratinocytic neoplasm infiltrates the dermis. Note cyst containing homogeneous calcified keratin and lacking a granular layer. B, Cytologic evidence of mafignancy is accompanied by mitotic figures. (A and B, Hematoxylin-eosin stain. Original magnifications: A, x50; B, x250.)
of the breast are common, and breast cancer develops in 25% to 36% of patients. 8 Patients with Cowden's disease are also particularly at risk for thyroid carcinoma, colonic polyposis, and colon adenocarcinoma, as well as for tumors of the genitourinary tract. Tumors of the nervous system including meningiomas, neurofibrornas, and neuromas have been reported, 8 and evidence is growing for a significant association with Lhermitte-Duclos disease 9 a condition in which there is abnormal proliferation of neuronal cells in the cerebellum. Several mucocutaneous malignancies have been reported in patients with Cowden's disease including melanoma, basal cell carcinoma, squamous cell carcinoma, and Merkel cell carcinoma, s W e report a case of irichilemmonal carcinoma in a patient with Cowden's disease. Whereas multiple tricholemmomas are highly characteristic, trichilemmomal carcinoma has not been previously reported.
vealed a multilobate epithelial neoplasm with overt architectural and cytologic evidence of malignancy that extended from multiple epidermal connections into the dermis (Fig. 2). Although there were isolated loci of peripheral palisading and focal stromal retraction, the essential differentiation of the neoplasm was keratinocytic, on the basis of the polyhedral squamoid cells with modest to abundant cytoplasm. Multiple foci of clear cells were present (Fig. 2, B) that contained abundant glycogen. Better differentiated fields of squamous cells were associated with microcysts that contained focally calcified, homogeneous keratin that formed in the absence of an interposed keratohyaline granular layer (Fig. 2, A). Mitotic figures were numerous and some were abnormal (Fig. 2, B). Thickened, glassy basement membrane could not be identified. A diagnosis of trichilemmomal carcinoma was made. The lesion was removed by Moils micrographic surgery.
CASE REPORT
Trichilemmomal carcinoma is a cutaneous adnexal neoplasm of the external root sheath. It was first described in 1976 by Headington 1° and then more fully characterized by Ten Seldam. H Trichilemmomal carcinoma appears to be rare 12' 13 and most commonly occurs on the sun-exposed, hair-beating skin of elderly persons where it is often misdiagnosed as basal cell or squamous cell carcinoma. Characteristic histologic features include lobules of glycogen-laden clear cells, peripheral palisading, prominent basement membrane, and trichilemmo-
A 56-year-old man with Cowden's disease was first reported by Weary et al.2 in 1972. In December 1994 multiple biopsy-proven facial trichilemmomas, oral papillomatosis, and a high-arched palate were noted. His medical history was significant for goiter, colonic polyposis, multiple meningiomas, acoustic neuroma, hydrocele, and complex partial seizures. The patient was referred for evaluation of a raised, crusted, keratotic lesion on the fight side of his face (Fig: 1). Microscopic examination of a biopsy specimen re-
DISCUSSION
Journal of the American Academy of Dermatology Volume 36, Number 6, Part 1
mal keratinization--aU features reminiscent of the outer root sheath. 11-13 In addition, cytologic and architectural evidence o f malignancy should be present. It is not k n o w n whether trichilemmomal carcinoma can evolve from a preexisting t d c h o l e m m o m a or whether " d e n o v o " occurrence is more the rule. 14 Trichilemmomal carcinoma can be locally aggressive, but metastases appear to be rare. 15 W e suggest that, once the diagnosis o f C o w d e n ' s disease is established, routine biopsy o f facial Trichilemmomas is u n n ~ e s s a r y . However, biopsy should be performed on any changing or atypical facial lesion.
REFERENCES 1. Lloyd KM, Dennis M. Cowden's disease: a possible new symptom complex with multiple system involvement. Ann Intern Med 1963;58:136-42. 2. Weary PE, Gorlin RJ, Gentry WC, et al. Multiple hamartoma syndrome (Cowden's disease). Arch Dermatol 1972; 106:682-90. 3. Nelen MR, Padberg GW, Peeters E/El, et al. Localization of the gene for Cowden disease to chromosome 10q22-23. Nat Gene 1996;13:114-6. 4. Barax CN, Lebwohl M, Phelps RG. Multiple hamartoma syndrome. J Am Acad Dermatol 1987;17:342-6.
Brief communications 1023 5. Requena L, Gufierrez J, Sanchez Yus E. Multiple sclerotic fibromas of the skin: a cutaneous marker of Cowden's disease. J Cutan Pathol 1991;19:346-51. 6. Salem OS, Steck WD. Cowden's disease (multiple hamartoma and neoplasia syndrome). J Am Acad Dermatol 1983;8:686-95. 7. Shapiro SD, Lambert WC, Schwartz RA. Cowden's disease: a marker for malignancy. Int J Dermatol 1988;27: 232-7. 8. Mallory SB. Cowden syndrome (multiple hamartoma syndrome). Dermatol Clin 1995;13:27-31. 9. Albrecht S, Haber RM, Goodman JC, et al. Cowden syndrome and Lhermitte-Duclosdisease. Cancer 1992;70:86976. 10. Headington yr. Tumors of the hair follicle: a review. Am J Pathol 1976;85:480-514. 1l. Ten Seldam REJ. Tricholemmocarcinoma. Australas J Dermatol 1977;18:62-72. 12. Swanson PE, Marrogi AJ, Williams DJ, Tricholemmal carcinoma: clinicopathologic study of 10 cases. J Cutan Pathol 1992;19:100-9. 13. Wong T-Y, Suster S. Tricholemmal carcinoma: a clinicopathologic study of 13 cases. Am J Dermatopathol 1994; 16:463-73. 14. Reis JP, Tellechea O, Cunha MF, et al. Trichilemmal carcinoma: a review of 8 cases. J Cutan Pathol 1993;20:44-9. 15. Gaughan RN, Rennet GJ, Templer JW. Metastatic tricholemrnal carcinoma [abstract]. Otolaryngol Head Neck Surg 1986;95(suppl):74.
Oral erosive lichen planus with epidermolytic hyperkeratosis during interferon alfa-2b therapy for chronic hepatitis C virus infection Todd E. Schlesinger, MD, a Charles Camisa, MD, a J. Douglas Gay, MD, b and W i l m a F. Bergfeld, M D a, b Cleveland, Ohio A n association between chronic active hepatitis and lichen planus (LP) was established in several studies) Interferon alfa-2a therapy for hepatitis caused b y the hepatitis C virus (HCV) has been reported to initiate, 2 clear, 3 exacerbate, 4, 5 or have no effect6 on L P lesions. W e describe oral L P initiated in a patient treated with interferon alfa-2b for chronic active hepatitis caused b y HCV. From the Departments of Derrrlatologya and Pathology?Cleveland Clinic Foundation. Reprint requests: Charles Camisa, MD, 9500EuclidAve.,Desk A61, Cleveland, OH 44195. J Am Acad Dermatol 1997;36:1023-5. Copyright © 1997 by the AmericanAcademyof Dermatology,Inc. 0190-9622/97/$5.00+ 0 16/54/80023
CASE REPORT A 39-year-old anti-HCV and HCV-RNA-positive man with histologically proven chronic active hepatitis with cirrhosis received his first course of recombinant human interferon alfa-2b (Intron A, Schering, Kenilworth, N.J.) from May 1994 through September 1994 at a dosage of 3 million units (MU) 3 times per week, not associated with cutaneous or oral abnormalities. A second course of interferon alfa-2b therapy, at a dosage of 5 MU 3 times per week was initiated in January 1995. One month later, erythematous, scaly plaques developed on the scalp, chest, back, buttocks, legs, and genitalia, as well as painful areas inside his mouth. Examination revealed scattered, psoriasiform plaques of various sizes, some covered with a Fine silvery scale on the scalp, back, arms, and legs. Plaques on the arms corresponded to sites of