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Basal cell carcinoma with ossification
Basal cell carcinoma with ossification Alan S. Boyd, MD,a,b and Lloyd E. King, Jr., MD, PhDa Nashville, Tennessee Background: Osteoma cutis, the presence of lamellar bone in the skin, is relatively common. This process is divided into two categories: primary osteoma cutis and secondary osteoma cutis. Objective: The purpose of this study was to describe the clinical and histopathologic features of patients in whom lamellar bone developed in cutaneous basal cell carcinoma. Methods: We evaluated the features of five cases of osteoma cutis associated with basal cell carcinoma and obtained detailed clinical information from those patients. Results: All five patients had significant underlying medical conditions, including two patients who were receiving interferon alfa-2b therapy. Three patients had been previously treated with electrodesiccation and curettage. The amount of sun exposure experienced by these patients varied. Histologically, the basal cell carcinomas were of the nodular or micronodular variety. Bone was found both in the stroma and intratumorally. Conclusion: The presence of bone within basal cell carcinomas is not uncommon and may be more prevalent in patients with an underlying medical disorder. (J Am Acad Dermatol 1998;38:906-10.)
The presence of bone in the skin is not uncommon. Cutaneous ossification is generally divided into two categories. Primary osteoma cutis includes multiple osteomas,1 congenital plate-like osteoma cutis,2 multiple miliary facial osteomas,3 Albright's hereditary osteodystrophy,4 and fibrodysplasia ossificans progressiva.5 Secondary osteoma cutis arises in cutaneous lesions or inflammatory conditions (Table I). Basal cell carcinomas with bone formation have been previously described,9,11,13 including several patients with the basal cell nevus syndrome.20 We describe an additional five cases. MATERIAL AND METHODS Five cases of basal cell carcinoma with bone formation were observed in a 6-month period (Table II). All patients were contacted by telephone and interviewed. Clinical information was obtained by direct interview with the patients (Table III). Biopsy specimens were processed routinely and stained with hematoxylin and eosin; stains for calcium were not performed.
From the Departments of Medicine (Dermatology)a and Pathology,b Vanderbilt University. Accepted for publication Feb. 23, 1998. Reprint requests: Alan S. Boyd, MD, 3900 The Vanderbilt Clinic, Nashville, TN 37232. Copyright © 1998 by the American Academy of Dermatology, Inc. 0190-9622/98/$5.00 + 0 16/1/89795
906
Fig. 1. A fragment of well-developed lamellar bone is present within a tumor nodule of basal cell carcinoma. Note the presence of melanin within the marrow. (Hematoxylin-eosin stain; original magnification ×200.)
RESULTS
Clinical findings The patients, three men and two women, ranged in age from 43 to 77 years. The lesions were 4 to 18 mm in diameter (average, 10.0 mm) and had been present an average of 4.6 years. Three lesions were on the trunk and two were on the face. Three of the lesions had previously been treated with electrodesiccation and curettage. All patients had significant underlying medical conditions that
Journal of the American Academy of Dermatology Volume 38, Number 6, Part 1
Boyd and King 907
Table I. Lesions associated with secondary osteoma cutis Acne vulgaris6-8 Actinic keratosis9 Atypical fibroxanthoma10 Basal cell carcinoma9,11 Bronchogenic carcinoma, metastatic12 Chondroid syringoma9 Chondroma9 Chronic venous insufficiency8 Dermatofibroma13 Dermatomyositis14 Desmoid tumor9 Desmoplastic melanoma15 Epidermal nevus16 Folliculitis8 Gardner’s syndrome17 Hemangioma9 Infundibular cyst9 Lipoma18 Lupus erythematosus8 Morphea14 Myositis ossificans14 Neurilemmoma9 Pilar cyst14 Pilomatricoma9 Pyogenic granuloma19 Scleroderma14 Syphilis8 Trauma8 Trichoepithelioma9
Fig. 2. A focus of osteoma cutis is seen in the stroma between aggregates of nodular basal cell carcinoma. (Hematoxylin-eosin stain; original magnification ×50.)
Fig. 3. Bone marrow elements present in a focus of osteoma cutis. (Hematoxylin-eosin stain; original magnification ×250.)
Table II. Histopathologic features of patients with bone deposition in basal cell carcinoma (BCC) Patient No.
Histologic type of BCC
Site
Presence of marrow
Previous bone deposition
Previous tumoral calcification
1 2 3 4 5
Nodular Pigmented nodular Nodular Nodular and infiltrative Micronodular
Adjacent to vellus hair follicle Intratumoral Adjacent to vellus hair follicle Reticular dermis Within a pilosebaceous unit
No Yes* Yes No Yes
Yes No No No No
No No No Yes No
*Pigment deposition was noted within the marrow.
ranged from hypothyroidism to receiving an allogeneic bone marrow transplantation. Patients 1 and 4 had been receiving interferon alfa-2b (Intron-A) therapy for chronic active hepatitis and chronic lymphocytic leukemia. The two female
patients were receiving estrogen replacement. All patients had had previous basal cell carcinomas, but none was hypercalcemic or hyperphosphatemic. Previous sun exposure was variable among these five patients.
Journal of the American Academy of Dermatology June 1998
908 Boyd and King
Table III. Clinical features of patients with basal cell carcinoma (BCC) with bone deposition
Symptoms
Previous treatment
Patient No.
Age (yr)/Sex
Site
Duration (yr)
Size (mm)
1 2 3
43/M 73/F 67/F
Right cheek Left back Left face
0.5 4.5 3
12 6 4
None Bleeding None
None EDC None
4
67/M
Left sternum
4
10
Bleeding, ulceration, itching
EDC
5
77/M
Right back
11
18
None
EDC
BMT, Bone marrow transplantation; CAD, coronary artery disease; CLL, chronic lymphocytic leukemia; EDC, electrodesiccation and curettage; HTN, hypertension; TA, rheumatoid arthritis; TNTC, too numerous to count.
Histopathologic findings Four tumors were of the nodular subtype and one was of the micronodular variety. Bone was deposited within the tumor itself (Fig. 1), in surrounding stroma (Fig. 2,) and adjacent to or within pilosebaceous units. The fragments showed calcified and well-developed lamellar bone. Osteocytes and osteoblasts were present in all five cases; in three cases the bone contained marrow elements (Fig. 3). Melanin deposits within the bone marrow elements were seen in one specimen (Fig. 1). One patient had previously developed bone in a basal cell carcinoma at another site. A second patient had developed calcification in a different basal cell carcinoma. DISCUSSION
Secondary osteoma cutis is relatively frequent and is responsible for about 85% of bone found in the skin.21 Pilomatricomas most commonly undergo ossification. Osteoma cutis arising in acne scars is another frequent occurrence6 and is typically found in young women with scarring acne. The finding of bone in basal cell carcinomas has been noted previously. Roth et al.9 found 10 cases in their evaluation of cutaneous ossification. All of these cases were on the face. Delacretaz and Christeler11 described another five cases more than 30 years ago. Since then, few reports of this phenomenon have appeared. We were able to observe five of these cases in 6 months, leading us to believe that it is not an uncommon occurrence. The pathophysiologic mechanisms for this phenomenon are unclear. The finding of heterotopic bone formation in acne scars7 and folliculitis8 sug-
gests that inflammation of the pilosebaceous unit may play a role. Bone developed adjacent to or within hair follicles in three of our patients. One basal cell carcinoma with osteoma formation showed some mild fibrosis, indicating that inflammation and disruption of the pilosebaceous unit may have taken place. Other authors11 believe that the inflammation of degenerating keratin pearls results in calcification and subsequent ossification. There is evidence that the osteoblasts responsible for heterotopic bone formation arise from connective tissue cells with fibroblast-like features.22 These have been termed determined osteogenic precursor cells and are likely derived from undifferentiated mesenchymal cells. Recently, a series of metalloproteinases termed bone morphogenetic proteins (BMPs) have been described.23 They are members of the transforming growth factor-β (TGF-β) superfamily. One of these proteins, BMP2, is believed to assist in the differentiation of osteoblasts from progenitor cells in the marrow.24 BMP-2 may also contribute to the ossification that is present in fibrodysplasia ossificans progressiva. These proteins cleave the triple helix of type I collagen in some animal models. Three of the lesions in our series had previously been treated with electrodesiccation and curettage. Because BMPs interact with extracellular matrix, it is plausible that infiltrating fibroblasts or primitive mesenchymal cells are transformed by these proteins into osteoblasts that produce heterotopic bone. A similar pattern may occur in other inflammatory conditions with secondary ossification but does not hold as well for solitary tumors. Two of our patients were receiving interferon
Journal of the American Academy of Dermatology Volume 38, Number 6, Part 1
Underlying diseases
6 yr after BMT, hepatitis RA, after gastrectomy anemia Hypothyroidism CLL Neurodegenerative disease, HTN, CAD
Boyd and King 909
Medications
Interferon alfa-2b Ibuprofen, iron, estrogen Thyroid replacement, estrogen, calcium++ supplement Interferon alfa-2b, prednisone, chlorambucil Fosinopril, furosemide, amlodipine digoxin
alfa-2b therapy, one for chronic hepatitis C and the other for chronic lymphocytic leukemia. The use of this cytokine for cutaneous conditions has been well documented,25,26 including for the successful treatment of basal cell carcinoma.27 However, the administration of interferon alfa-2b and production of heterotopic ossification has not been described. Bedossa et al.28 described seven patients with chronic hepatitis C who were given interferon alfa-2b for 6 to 18 months. Later hepatic biopsy specimens disclosed decreased TGF-β1. If this interferon affects other members of the TGF superfamily (BMPs), similarly bone deposition would presumably be inhibited. No patients had an increased serum calcium or phosphorus that may have led to tissue calcium deposition. However, all patients had a significant underlying medical problem, so it is possible that they may be more predisposed to the development of osteoma cutis within their basal cell carcinomas. REFERENCES 1. Gardner RJM, Yun K, Craw SM. Familial ectopic ossification. J Med Genet 1988;25:113-7. 2. Sanmartin O, Alegere V, Martinez-Aparicio A, BotellaEstrada R, Aliaga A. Congenital plate-like osteoma cutis: case report and review of the literature. Pediatr Dermatol 1993;10:182-6. 3. Helm F, De La Pava S, Klein E. Multiple miliary osteomas of the skin. Arch Dermatol 1967;96:681-2. 4. Eyre WG, Reed WB. Albright's hereditary osteodystrophy with cutaneous bone formation. Arch Dermatol 1971;104:634-42. 5. Rogers JG, Geho WB. Fibrodysplasia ossificans progressiva: a survey of forty-two cases. J Bone Joint Surg 1979;61A:909-14. 6. Jewell EW. Osteoma cutis. Arch Dermatol 1971;103: 553-5.
Previous BCCs
Sun exposure
Increased serum calcium or phosphorus
2 1 7
+++ + +
– – –
TNTC
++
–
TNTC
+++
–
7. Basler RS, Taylor WB, Peacor DR. Postacne osteoma cutis. Arch Dermatol 1974;110:113-4. 8. Tomsick RS, Menn H. Ossifying basal cell carcinoma. Int J Dermatol 1989;21:218-9. 9. Roth SI, Stowell RE, Helwig EB. Cutaneous ossification. Arch Pathol 1963;76:44-54. 10. Chen KTK. Atypical fibroxanthoma of the skin with osteoid production. Arch Dermatol 1980;116:113-4. 11. Delacretaz J, Christeler A. Les phenomenes d'ossification dans les epitheliomas cutanes. Dermatologica 1967; 134:305-11. 12. Bettendorf U. Bone formation by cancer metastases. Virchows Arch (Berlin) 1976;369:359-65. 13. Buselmeier TJ, Uecker JH. Invasive basal cell carcinoma with metaplastic bone formation associated with a longstanding dermatofibroma. J Cutan Pathol 1979;6:496500. 14. Orlow SJ, Watsky KL, Bolognia JL. Skin and bones: part II. J Am Acad Dermatol 1991;25:447-62. 15. Moreno A, Lamarca J, Martinez R, Guiz M. Osteoid and bone formation in desmoplastic malignant melanoma. J Cutan Pathol 1986;13:128-34. 16. Coskey RJ, Mehregan AH. Metaplastic bone formation in an organoid nevus. Arch Dermatol 1970;102:233. 17. Oikarinen A, Tuomi ML, Kallinonen M, Sandberg M, Vaananen K. A study of bone formation in osteoma cutis employing biochemical, histochemical and in situ hybridization techniques. Acta Derm Venereol (Stockh) 1992;72:172-4. 18. Weedon D, editor. The skin. New York: Churchill Livingstone; 1992. 19. Fulton RA. Bone formation in a cutaneous pyogenic granuloma. Br J Dermatol 1980;102:351-2. 20. Mason JK, Helwig EB, Graham JH. Pathology of the nevoid basal cell carcinoma syndrome. Arch Pathol 1965;79:401-8. 21. Cottoni F, Dell'Orbo C, Quacci D, Tedde G. Primary osteoma cutis. Am J Dermatopathol 1993;15:77-81. 22. Puzas JE, Miller MD, Rosier RN. Pathologic bone formation. Clin Orthop 1989;245:269-81. 23. Sarras MP. BMP-1 and the astacin family of metalloproteinases: a potential link between the extracellular matrix, growth factors and pattern formation. Bioessays 1996;18:439-42.
Journal of the American Academy of Dermatology June 1998
910 Boyd and King 24. Riley EH, Lane JM, Urist MR, et al. Bone morphogenetic protein-2. Clin Orthop 1996;324:39-46. 25. Ringenberg QS, Anderson PC. Interferons in the treatment of skin disease. Int J Dermatol 1986;25:273-9. 26. Stadler R, Mayer-da-Silva A, Bratzke B, Garbe C, Orfanos C. Interferons in dermatology. J Am Acad Dermatol 1989;20:650-6. 27. Ikic D, Padovan I, Pipic N, Cajkovac V, Kusic Z,
Dakovic N. Interferon reduces recurrences of basal cell and squamous cell cancers. Int J Dermatol 1995;34:5860. 28. Bedossa P, Poynard T, Mathurin P, Lemaigre G, Chaput JC. Transforming growth factor β1; in situ expression in the liver of patients with chronic hepatitis C treated with alpha interferon. Gut 1993;34:S146-7.
DONATE YOUR OLD BOOKS AND JOURNALS The American Academy of Dermatology’s Task Force to Provide Educational Materials to Developing Countries has a list of Dermatology Teaching Centers throughout the world that have no library or operational budget and would be grateful for textbooks published in 1985 or later, journals published in 1980 or later, clinical and histopathologic slides (must be correctly labeled and categorized), and old instuments and equipment. The donor must send the material at his or her own expense. Materials plus shipping costs are considered a donation to the Academy. Donated materials are matched with the “needs list” from a center in need. Precise instructions concerning packaging, shipping, and tax implications will be sent to the donor. If interested, please send inventory, listing author, title, and date of publication for books. List journals by name, volume number, date, whether bound or unbound, and whether complete or incomplete (if incomplete, indicate what is missing). If you are reading this announcement in a country or area in need of such teaching materials, please write with full particulars detailing your needs and facilities. Your donation will be a valuable and cherished contribution to the welfare of millions of patients in developing and newly democratized countries. For further information, please contact: American Academy of Dermatology Department of Member Services P.O. Box 4014 Schaumburg, IL 60168-4014 Please do not send materials to this address. You will receive instructions and the recipient’s address when an appropriate match is made.
The presence of bone in the skin is not uncommon. Cutaneous ossification is generally divided into two categories. Primary osteoma cutis includes multiple osteomas,1 congenital plate-like osteoma cutis,2 multiple miliary facial osteomas,3 Albright's hereditary osteodystrophy,4 and fibrodysplasia ossificans progressiva.5 Secondary osteoma cutis arises in cutaneous lesions or inflammatory conditions (Table I). Basal cell carcinomas with bone formation have been previously described,9,11,13 including several patients with the basal cell nevus syndrome.20 We describe an additional five cases. MATERIAL AND METHODS Five cases of basal cell carcinoma with bone formation were observed in a 6-month period (Table II). All patients were contacted by telephone and interviewed. Clinical information was obtained by direct interview with the patients (Table III). Biopsy specimens were processed routinely and stained with hematoxylin and eosin; stains for calcium were not performed.
From the Departments of Medicine (Dermatology)a and Pathology,b Vanderbilt University. Accepted for publication Feb. 23, 1998. Reprint requests: Alan S. Boyd, MD, 3900 The Vanderbilt Clinic, Nashville, TN 37232. Copyright © 1998 by the American Academy of Dermatology, Inc. 0190-9622/98/$5.00 + 0 16/1/89795
906
Fig. 1. A fragment of well-developed lamellar bone is present within a tumor nodule of basal cell carcinoma. Note the presence of melanin within the marrow. (Hematoxylin-eosin stain; original magnification ×200.)
RESULTS
Clinical findings The patients, three men and two women, ranged in age from 43 to 77 years. The lesions were 4 to 18 mm in diameter (average, 10.0 mm) and had been present an average of 4.6 years. Three lesions were on the trunk and two were on the face. Three of the lesions had previously been treated with electrodesiccation and curettage. All patients had significant underlying medical conditions that
Journal of the American Academy of Dermatology Volume 38, Number 6, Part 1
Boyd and King 907
Table I. Lesions associated with secondary osteoma cutis Acne vulgaris6-8 Actinic keratosis9 Atypical fibroxanthoma10 Basal cell carcinoma9,11 Bronchogenic carcinoma, metastatic12 Chondroid syringoma9 Chondroma9 Chronic venous insufficiency8 Dermatofibroma13 Dermatomyositis14 Desmoid tumor9 Desmoplastic melanoma15 Epidermal nevus16 Folliculitis8 Gardner’s syndrome17 Hemangioma9 Infundibular cyst9 Lipoma18 Lupus erythematosus8 Morphea14 Myositis ossificans14 Neurilemmoma9 Pilar cyst14 Pilomatricoma9 Pyogenic granuloma19 Scleroderma14 Syphilis8 Trauma8 Trichoepithelioma9
Fig. 2. A focus of osteoma cutis is seen in the stroma between aggregates of nodular basal cell carcinoma. (Hematoxylin-eosin stain; original magnification ×50.)
Fig. 3. Bone marrow elements present in a focus of osteoma cutis. (Hematoxylin-eosin stain; original magnification ×250.)
Table II. Histopathologic features of patients with bone deposition in basal cell carcinoma (BCC) Patient No.
Histologic type of BCC
Site
Presence of marrow
Previous bone deposition
Previous tumoral calcification
1 2 3 4 5
Nodular Pigmented nodular Nodular Nodular and infiltrative Micronodular
Adjacent to vellus hair follicle Intratumoral Adjacent to vellus hair follicle Reticular dermis Within a pilosebaceous unit
No Yes* Yes No Yes
Yes No No No No
No No No Yes No
*Pigment deposition was noted within the marrow.
ranged from hypothyroidism to receiving an allogeneic bone marrow transplantation. Patients 1 and 4 had been receiving interferon alfa-2b (Intron-A) therapy for chronic active hepatitis and chronic lymphocytic leukemia. The two female
patients were receiving estrogen replacement. All patients had had previous basal cell carcinomas, but none was hypercalcemic or hyperphosphatemic. Previous sun exposure was variable among these five patients.
Journal of the American Academy of Dermatology June 1998
908 Boyd and King
Table III. Clinical features of patients with basal cell carcinoma (BCC) with bone deposition
Symptoms
Previous treatment
Patient No.
Age (yr)/Sex
Site
Duration (yr)
Size (mm)
1 2 3
43/M 73/F 67/F
Right cheek Left back Left face
0.5 4.5 3
12 6 4
None Bleeding None
None EDC None
4
67/M
Left sternum
4
10
Bleeding, ulceration, itching
EDC
5
77/M
Right back
11
18
None
EDC
BMT, Bone marrow transplantation; CAD, coronary artery disease; CLL, chronic lymphocytic leukemia; EDC, electrodesiccation and curettage; HTN, hypertension; TA, rheumatoid arthritis; TNTC, too numerous to count.
Histopathologic findings Four tumors were of the nodular subtype and one was of the micronodular variety. Bone was deposited within the tumor itself (Fig. 1), in surrounding stroma (Fig. 2,) and adjacent to or within pilosebaceous units. The fragments showed calcified and well-developed lamellar bone. Osteocytes and osteoblasts were present in all five cases; in three cases the bone contained marrow elements (Fig. 3). Melanin deposits within the bone marrow elements were seen in one specimen (Fig. 1). One patient had previously developed bone in a basal cell carcinoma at another site. A second patient had developed calcification in a different basal cell carcinoma. DISCUSSION
Secondary osteoma cutis is relatively frequent and is responsible for about 85% of bone found in the skin.21 Pilomatricomas most commonly undergo ossification. Osteoma cutis arising in acne scars is another frequent occurrence6 and is typically found in young women with scarring acne. The finding of bone in basal cell carcinomas has been noted previously. Roth et al.9 found 10 cases in their evaluation of cutaneous ossification. All of these cases were on the face. Delacretaz and Christeler11 described another five cases more than 30 years ago. Since then, few reports of this phenomenon have appeared. We were able to observe five of these cases in 6 months, leading us to believe that it is not an uncommon occurrence. The pathophysiologic mechanisms for this phenomenon are unclear. The finding of heterotopic bone formation in acne scars7 and folliculitis8 sug-
gests that inflammation of the pilosebaceous unit may play a role. Bone developed adjacent to or within hair follicles in three of our patients. One basal cell carcinoma with osteoma formation showed some mild fibrosis, indicating that inflammation and disruption of the pilosebaceous unit may have taken place. Other authors11 believe that the inflammation of degenerating keratin pearls results in calcification and subsequent ossification. There is evidence that the osteoblasts responsible for heterotopic bone formation arise from connective tissue cells with fibroblast-like features.22 These have been termed determined osteogenic precursor cells and are likely derived from undifferentiated mesenchymal cells. Recently, a series of metalloproteinases termed bone morphogenetic proteins (BMPs) have been described.23 They are members of the transforming growth factor-β (TGF-β) superfamily. One of these proteins, BMP2, is believed to assist in the differentiation of osteoblasts from progenitor cells in the marrow.24 BMP-2 may also contribute to the ossification that is present in fibrodysplasia ossificans progressiva. These proteins cleave the triple helix of type I collagen in some animal models. Three of the lesions in our series had previously been treated with electrodesiccation and curettage. Because BMPs interact with extracellular matrix, it is plausible that infiltrating fibroblasts or primitive mesenchymal cells are transformed by these proteins into osteoblasts that produce heterotopic bone. A similar pattern may occur in other inflammatory conditions with secondary ossification but does not hold as well for solitary tumors. Two of our patients were receiving interferon
Journal of the American Academy of Dermatology Volume 38, Number 6, Part 1
Underlying diseases
6 yr after BMT, hepatitis RA, after gastrectomy anemia Hypothyroidism CLL Neurodegenerative disease, HTN, CAD
Boyd and King 909
Medications
Interferon alfa-2b Ibuprofen, iron, estrogen Thyroid replacement, estrogen, calcium++ supplement Interferon alfa-2b, prednisone, chlorambucil Fosinopril, furosemide, amlodipine digoxin
alfa-2b therapy, one for chronic hepatitis C and the other for chronic lymphocytic leukemia. The use of this cytokine for cutaneous conditions has been well documented,25,26 including for the successful treatment of basal cell carcinoma.27 However, the administration of interferon alfa-2b and production of heterotopic ossification has not been described. Bedossa et al.28 described seven patients with chronic hepatitis C who were given interferon alfa-2b for 6 to 18 months. Later hepatic biopsy specimens disclosed decreased TGF-β1. If this interferon affects other members of the TGF superfamily (BMPs), similarly bone deposition would presumably be inhibited. No patients had an increased serum calcium or phosphorus that may have led to tissue calcium deposition. However, all patients had a significant underlying medical problem, so it is possible that they may be more predisposed to the development of osteoma cutis within their basal cell carcinomas. REFERENCES 1. Gardner RJM, Yun K, Craw SM. Familial ectopic ossification. J Med Genet 1988;25:113-7. 2. Sanmartin O, Alegere V, Martinez-Aparicio A, BotellaEstrada R, Aliaga A. Congenital plate-like osteoma cutis: case report and review of the literature. Pediatr Dermatol 1993;10:182-6. 3. Helm F, De La Pava S, Klein E. Multiple miliary osteomas of the skin. Arch Dermatol 1967;96:681-2. 4. Eyre WG, Reed WB. Albright's hereditary osteodystrophy with cutaneous bone formation. Arch Dermatol 1971;104:634-42. 5. Rogers JG, Geho WB. Fibrodysplasia ossificans progressiva: a survey of forty-two cases. J Bone Joint Surg 1979;61A:909-14. 6. Jewell EW. Osteoma cutis. Arch Dermatol 1971;103: 553-5.
Previous BCCs
Sun exposure
Increased serum calcium or phosphorus
2 1 7
+++ + +
– – –
TNTC
++
–
TNTC
+++
–
7. Basler RS, Taylor WB, Peacor DR. Postacne osteoma cutis. Arch Dermatol 1974;110:113-4. 8. Tomsick RS, Menn H. Ossifying basal cell carcinoma. Int J Dermatol 1989;21:218-9. 9. Roth SI, Stowell RE, Helwig EB. Cutaneous ossification. Arch Pathol 1963;76:44-54. 10. Chen KTK. Atypical fibroxanthoma of the skin with osteoid production. Arch Dermatol 1980;116:113-4. 11. Delacretaz J, Christeler A. Les phenomenes d'ossification dans les epitheliomas cutanes. Dermatologica 1967; 134:305-11. 12. Bettendorf U. Bone formation by cancer metastases. Virchows Arch (Berlin) 1976;369:359-65. 13. Buselmeier TJ, Uecker JH. Invasive basal cell carcinoma with metaplastic bone formation associated with a longstanding dermatofibroma. J Cutan Pathol 1979;6:496500. 14. Orlow SJ, Watsky KL, Bolognia JL. Skin and bones: part II. J Am Acad Dermatol 1991;25:447-62. 15. Moreno A, Lamarca J, Martinez R, Guiz M. Osteoid and bone formation in desmoplastic malignant melanoma. J Cutan Pathol 1986;13:128-34. 16. Coskey RJ, Mehregan AH. Metaplastic bone formation in an organoid nevus. Arch Dermatol 1970;102:233. 17. Oikarinen A, Tuomi ML, Kallinonen M, Sandberg M, Vaananen K. A study of bone formation in osteoma cutis employing biochemical, histochemical and in situ hybridization techniques. Acta Derm Venereol (Stockh) 1992;72:172-4. 18. Weedon D, editor. The skin. New York: Churchill Livingstone; 1992. 19. Fulton RA. Bone formation in a cutaneous pyogenic granuloma. Br J Dermatol 1980;102:351-2. 20. Mason JK, Helwig EB, Graham JH. Pathology of the nevoid basal cell carcinoma syndrome. Arch Pathol 1965;79:401-8. 21. Cottoni F, Dell'Orbo C, Quacci D, Tedde G. Primary osteoma cutis. Am J Dermatopathol 1993;15:77-81. 22. Puzas JE, Miller MD, Rosier RN. Pathologic bone formation. Clin Orthop 1989;245:269-81. 23. Sarras MP. BMP-1 and the astacin family of metalloproteinases: a potential link between the extracellular matrix, growth factors and pattern formation. Bioessays 1996;18:439-42.
Journal of the American Academy of Dermatology June 1998
910 Boyd and King 24. Riley EH, Lane JM, Urist MR, et al. Bone morphogenetic protein-2. Clin Orthop 1996;324:39-46. 25. Ringenberg QS, Anderson PC. Interferons in the treatment of skin disease. Int J Dermatol 1986;25:273-9. 26. Stadler R, Mayer-da-Silva A, Bratzke B, Garbe C, Orfanos C. Interferons in dermatology. J Am Acad Dermatol 1989;20:650-6. 27. Ikic D, Padovan I, Pipic N, Cajkovac V, Kusic Z,
Dakovic N. Interferon reduces recurrences of basal cell and squamous cell cancers. Int J Dermatol 1995;34:5860. 28. Bedossa P, Poynard T, Mathurin P, Lemaigre G, Chaput JC. Transforming growth factor β1; in situ expression in the liver of patients with chronic hepatitis C treated with alpha interferon. Gut 1993;34:S146-7.
DONATE YOUR OLD BOOKS AND JOURNALS The American Academy of Dermatology’s Task Force to Provide Educational Materials to Developing Countries has a list of Dermatology Teaching Centers throughout the world that have no library or operational budget and would be grateful for textbooks published in 1985 or later, journals published in 1980 or later, clinical and histopathologic slides (must be correctly labeled and categorized), and old instuments and equipment. The donor must send the material at his or her own expense. Materials plus shipping costs are considered a donation to the Academy. Donated materials are matched with the “needs list” from a center in need. Precise instructions concerning packaging, shipping, and tax implications will be sent to the donor. If interested, please send inventory, listing author, title, and date of publication for books. List journals by name, volume number, date, whether bound or unbound, and whether complete or incomplete (if incomplete, indicate what is missing). If you are reading this announcement in a country or area in need of such teaching materials, please write with full particulars detailing your needs and facilities. Your donation will be a valuable and cherished contribution to the welfare of millions of patients in developing and newly democratized countries. For further information, please contact: American Academy of Dermatology Department of Member Services P.O. Box 4014 Schaumburg, IL 60168-4014 Please do not send materials to this address. You will receive instructions and the recipient’s address when an appropriate match is made.