- Email: [email protected]
Adult acral cutaneous myofibromas in a patient with generalized morphea
Adult acral cutaneous myofibromas in a patient with generalized morphea Joseph C. English III, MD, Amalie S. Derdeyn, BS, Paula D. Smith, MD, and James W. Patterson, MD Charlottesville, Virginia Myofibroma is the term for a group of solitary or generalized soft tissue tumors that may be located in the skin or within skeletal muscle, bone, and viscera. These tumors occur most commonly in children. However, examples of myofibroma have been reported in adults, in whom they usually present as solitary lesions of the head and neck, trunk, and extremities. “Cutaneous nodules” have been reported in both localized and systemic scleroderma, but to our knowledge, there are no specific reports of myofibromas developing in this patient population. We report a case of acral myofibromas in a patient with generalized cutaneous morphea. This occurrence is of interest in view of the possible role of myofibroblasts in the pathogenesis of scleroderma. (J Am Acad Dermatol 2002;46:953-6.)
M
yofibromas are solitary or generalized soft tissue tumors that may be located in the skin and subcutis, skeletal muscle, bone, or viscera.1 Cases that were formerly termed congenital (generalized) fibromatosis probably represent examples of myofibromatosis.2 The disease is present at birth in 50% of cases3 and develops before the age of 2 years in about 90%.4 A favorable outcome is generally reported for solitary, superficial lesions, and even spontaneous involution has been reported.1,2,5,6 However, recurrences are not unusual,1,6 and deaths can occur in cases with multiple visceral involvement.1,2 Though uncommon, cutaneous or subcutaneous myofibromas with identical histopathologic features have been reported in adults of widely ranging ages.3,4,7-9 These tumors are typically solitary and painless and tend to predominate on the extremities.7,9 They respond well to surgical excision, although recurrences have been reported.4,10 Localized and systemic scleroderma is a connective tissue disorder in which the myofibroblast may play an important role.11 Cutaneous nodules are known to occur, but to our knowledge, the development of myofibroma in these conditions has not been reported to date. We recently had the opportunity to
From the Departments of Dermatology and Pathology, University of Virginia Medical Center. Funding sources: None. Conflict of interest: None. Reprints not available from authors. Copyright © 2002 by the American Academy of Dermatology, Inc. 0190-9622/2002/$35.00 ⫹ 0 16/91/123151 doi:10.1067/mjd.2002.123151
evaluate a patient with generalized morphea who had several papulonodular lesions on the dorsa of the hands and digits. A biopsy specimen of one of these lesions showed the features of myofibroma.
CASE REPORT A 76-year-old woman with a long-term history of generalized morphea presented with the recent onset of asymptomatic skin lesions on her hands. Physical examination confirmed the presence of diffuse cutaneous sclerosis, consistent with the diagnosis of generalized morphea. Linear sclerotic lesions, suggestive of linear scleroderma, were also present on the right upper and lower extremities. She had approximately 6 firm, plum-colored lesions, ranging in size from papules to small nodules, on the dorsa of both hands, located over the sides of the metacarpophalangeal joints and the proximal portions of several phalanges (Figs 1 and 2). A biopsy of the lesion on the left middle finger was performed. Microscopic findings included a well-circumscribed zone of dense fibrosis, extending from the superficial papillary dermis to the mid-reticular dermis. There was a sharp demarcation at the base of the lesion. The fibrosis was hyaline in appearance, with numerous widely dispersed, small, rounded to spindled cells (Fig 3). In some cases, these cells formed short fascicles. Scattered small vessels were present throughout the lesion. The underlying deep reticular dermis had normally fenestrated collagen, prominent solar elastosis (which had been either obscured or replaced by the overlying tumor), intact eccrine sweat coils without atrophy and with a normal complement of perieccrine fat, and essentially no inflammation. Immunohistochemical staining showed that the rounded to spindled cells were positive for vimentin and smooth muscle actin (Fig 953
954 English et al
Fig 1. A 76-year-old woman with lesions of recent onset on the hands.
J AM ACAD DERMATOL JUNE 2002
Fig 4. The rounded to spindled cells were positive for smooth muscle actin.
DISCUSSION
Fig 2. A plum-colored tumor on the left middle finger.
Fig 3. Photomicrograph showing scattered rounded to spindled cells and vessels within a dense fibrotic stroma. (Hematoxylin-eosin stain; original magnification ⫻400.)
4) and negative for S-100, C-kit, factor XIII, and CD68. On the basis of the histopathologic features and staining characteristics of the lesion, a diagnosis of myofibroma was made. The patient refused any additional surgical procedures.
Adult myofibromas are typically superficial tumors that are confined to the dermis and subcutis.4 Although most studies have described solitary lesions, multifocal lesions confined to one anatomic region have been reported.10 Myofibromas in adults follow a benign course and respond well to excision, although local recurrence is possible.4,10 Microscopically, these tumors closely resemble their pediatric counterparts. They are well circumscribed and usually include 2 components: plump spindled cells, resembling myofibroblasts, that are arranged in short fascicles1,5 and vascular foci composed of polygonal to small spindled cells with hyperchromatic nuclei. Areas with the latter changes bear a resemblance to hemangiopericytoma,12-15 and in fact, some authors have concluded that infantile myofibromatosis and hemangiopericytoma are histogenetically related.12,14 However, “monophasic” variants of myofibroma that feature only one of these components also occur.13 In our case, plump spindled cells and small mature-appearing vessels predominated, and hemangiopericytoma-like areas were not observed. The spindled cells of myofibroma express vimentin and smooth muscle actin and are usually negative for desmin.8 Nodular lesions have been reported in both localized and systemic scleroderma. In the case of diffuse systemic scleroderma, nodules have developed both in sclerotic16-18 and nonsclerotic skin.19 These lesions have been described as keloidal,16,17 though in several reports, biopsy specimens of nodular lesions showed typical changes of scleroderma.18,19 Mizutani et al20 found high levels of tenascin expression in nodular lesions, comparable to levels in morphea and hypertrophic scar, whereas the skin of diffuse systemic scleroderma expressed intermediate levels of this extracellular matrix protein. This result, combined with histopathologic findings and
English et al 955
J AM ACAD DERMATOL VOLUME 46, NUMBER 6
other data, suggested that the nodules of nodular scleroderma most closely resembled a hypertrophic scar.20 Nodular morphea in a linear configuration has been reported,21 and there has also been a report of malignant fibrous histiocytoma and an extra-abdominal desmoid tumor arising in a woman with L-tryptophan-induced eosinophilia-myalgia syndrome.22 Myofibroblasts represent a significant component of both of these tumors.23,24 There is evidence that the myofibroblast may play an important role in the pathogenesis of scleroderma. In an ultrastructural study of peripheral nerves of patients with morphea, Kobayasi and Serup25 found changes in the mesenchymal portions of these nerves that included infiltration by inflammatory cells and myofibroblasts; they suggested that perineural cells could be a possible source of these myofibroblasts. Using immunohistochemical methods, Kirk et al11 found a predominance of myofibroblasts among cultured fibroblasts from skin biopsy specimens of patients with scleroderma. In a subsequent study, Kirk and Mayes26 suggested that interleukin 1 may promote myofibroblast longevity (and therefore fibrosis) in sclerodermatous skin. In an investigation of scleroderma lung disease, Ludwicka et al27 performed bronchoalveolar lavage studies. They found cells with the characteristics of myofibroblasts in over half of their patients with scleroderma but not in healthy control subjects. These cells may be involved in the interstitial pulmonary fibrosis that occurs in scleroderma, in part through stimulation by elevated levels of platelet-derived growth factor and transforming growth factor 1.28 In view of these findings, it appears likely that myofibroblasts are involved in the pathogenesis of nodules of localized and systemic scleroderma, although the reasons that nodules form in only a minority of these individuals remain to be determined. It is possible that some of the nodules that develop in patients with scleroderma may represent true myofibromas. REFERENCES 1. Chung EB, Enzinger FM. Infantile myofibromatosis. Cancer 1981; 48:1807-18. 2. Spraker MK, Stack C, Esterly NB. Congenital generalized fibromatosis: a review of the literature and report of a case associated with porencephaly, hemiatrophy, and cutis marmorata telangiectatica congenita. J Am Acad Dermatol 1984;10: 365-71. 3. Wolfe JT III, Cooper PH. Solitary cutaneous “infantile” myofibroma in a 49-year-old woman. Hum Pathol 1990;21:562-4. 4. Hogan SF, Salassa JR. Recurrent adult myofibromatosis. A case report. Am J Clin Pathol 1992;97:810-4. 5. Sonoda T, Itami S, Seguchi S, Kurata S, Takayasu S. Infantile
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16. 17.
18. 19.
20.
21. 22.
23.
24.
myofibromatosis: report of two cases. J Dermatol 1994;21: 508-13. Stanford D, Rogers M. Dermatological presentations of infantile myofibromatosis: a review of 27 cases. Australas J Dermatol 2000;41:156-61. Daimaru Y, Hashimoto H, Enjoji M. Myofibromatosis in adults (adult counterpart of infantile myofibromatosis). Am J Surg Pathol 1989;13:859-65. Guitart J, Ritter JH, Wick MR. Solitary cutaneous myofibromas in adults: report of six cases and discussion of differential diagnosis. J Cutan Pathol 1996;23:437-44. Requena L, Kutzner H, Hugel H, Rutten A, Furio V. Cutaneous adult myofibroma: a vascular neoplasm. J Cutan Pathol 1996;23: 445-57. Granter SR, Badizadegan K, Fletcher CD. Myofibromatosis in adults, glomangiopericytoma, and myopericytoma: a spectrum of tumors showing perivascular myoid differentiation. Am J Surg Pathol 1998;22:513-25. Kirk TZ, Mark ME, Chua CC, Chua BH, Mayes MD. Myofibroblasts from scleroderma skin synthesize elevated levels of collagen and tissue inhibitor of metalloproteinase (TIMP-1) with two forms of TIMP-1. J Biol Chem 1995;270:3423-8. Mentzel T, Calonje E, Nascimento AG, Fletcher CD. Infantile hemangiopericytoma versus infantile myofibromatosis. Study of a series suggesting a continuous spectrum of infantile myofibroblastic lesions. Am J Surg Pathol 1994;18:922-30. Zelger BW, Calonje E, Sepp N, Fink FM, Zelger BG, Schmid KW. Monophasic cellular variant of infantile myofibromatosis. An unusual histopathologic pattern in two siblings. Am J Dermatopathol 1995;17:131-8. Variend S, Bax NM, van Gorp J. Are infantile myofibromatosis, congenital fibrosarcoma and congenital haemangiopericytoma histogenetically related? Histopathology 1995;26:5762. Magid MS, Campbell WG Jr, Ngadiman S, Godwin TA, Ward R. Infantile myofibromatosis with hemangiopericytoma-like features of the tongue: a case study including ultrastructure. Pediatr Pathol Lab Med 1997;17:303-13. James WD, Berger TG, Butler DF, Tuffanelli DL. Nodular (keloidal) scleroderma. J Am Acad Dermatol 1984;11:1111-4. Sasaki T, Denpo K, Ono H, Nakajima H. Nodular scleroderma in systemic sclerosis under D-penicillamine therapy. J Dermatol 1992;19:968-71. Krell JM, Solomon AR, Glavey CM, Lawley TJ. Nodular scleroderma. J Am Acad Dermatol 1995;32:343-5. Yamamoto T, Furuse Y, Katayama I, Nishioka K. Nodular scleroderma in a worker using a silica-containing abrasive. J Dermatol 1994;21:751-4. Mizutani H, Taniguchi H, Sakakura T, Shimizu M. Nodular scleroderma: focally increased tenascin expression differing from that in the surrounding scleroderma skin. J Dermatol 1995;22:26771. Hsu S, Lee MW, Carlton S, Kramer EM. Nodular morphea in a linear pattern. Int J Dermatol 1999;38:529-30. Mainetti C, Masouye I, Salomon D, Chavaz P, Saurat JH. L-tryptophan-induced eosinophilia-myalgia syndrome associated with primary cutaneous malignant fibrous histiocytoma and extraabdominal desmoid tumor. Cancer 1993;72:2712-5. Salloum H, Kanitakis J, Chouvet B, Grimand P, Claudy A. [Extraabdominal desmoid tumor. Microscopic aspects and histogenesis]. Ann Dermatol Venereol 1993;120:685-8. French. Antonescu CR, Erlandson RA, Huvos AG. Primary fibrosarcoma and malignant fibrous histiocytoma of bone—a comparative ultrastructural study: evidence of a spectrum of fibroblastic differentiation. Ultrastruct Pathol 2000;24:83-91.
956 English et al
25. Kobayasi T, Serup J. Nerve changes in morphea. Acta Derm Venereol 1983;63:321-7. 26. Kirk TZ, Mayes MD. IL-1 rescues scleroderma myofibroblasts from serum-starvation-induced cell death. Biochem Biophys Res Commun 1999;255:129-32. 27. Ludwicka A, Trojanowska M, Smith EA, Baumann M, Strange C, Korn JH, et al. Growth and characterization of fibroblasts ob-
J AM ACAD DERMATOL JUNE 2002
tained from bronchoalveolar lavage of patients with scleroderma. J Rheumatol 1992;19:1716-23. 28. Ludwicka A, Ohba T, Trojanowska M, Yamakage A, Strange C, Smith EA, et al. Elevated levels of platelet derived growth factor and transforming growth factor-beta 1 in bronchoalveolar lavage fluid from patients with scleroderma. J Rheumatol 1995; 22:1876-83.
M
yofibromas are solitary or generalized soft tissue tumors that may be located in the skin and subcutis, skeletal muscle, bone, or viscera.1 Cases that were formerly termed congenital (generalized) fibromatosis probably represent examples of myofibromatosis.2 The disease is present at birth in 50% of cases3 and develops before the age of 2 years in about 90%.4 A favorable outcome is generally reported for solitary, superficial lesions, and even spontaneous involution has been reported.1,2,5,6 However, recurrences are not unusual,1,6 and deaths can occur in cases with multiple visceral involvement.1,2 Though uncommon, cutaneous or subcutaneous myofibromas with identical histopathologic features have been reported in adults of widely ranging ages.3,4,7-9 These tumors are typically solitary and painless and tend to predominate on the extremities.7,9 They respond well to surgical excision, although recurrences have been reported.4,10 Localized and systemic scleroderma is a connective tissue disorder in which the myofibroblast may play an important role.11 Cutaneous nodules are known to occur, but to our knowledge, the development of myofibroma in these conditions has not been reported to date. We recently had the opportunity to
From the Departments of Dermatology and Pathology, University of Virginia Medical Center. Funding sources: None. Conflict of interest: None. Reprints not available from authors. Copyright © 2002 by the American Academy of Dermatology, Inc. 0190-9622/2002/$35.00 ⫹ 0 16/91/123151 doi:10.1067/mjd.2002.123151
evaluate a patient with generalized morphea who had several papulonodular lesions on the dorsa of the hands and digits. A biopsy specimen of one of these lesions showed the features of myofibroma.
CASE REPORT A 76-year-old woman with a long-term history of generalized morphea presented with the recent onset of asymptomatic skin lesions on her hands. Physical examination confirmed the presence of diffuse cutaneous sclerosis, consistent with the diagnosis of generalized morphea. Linear sclerotic lesions, suggestive of linear scleroderma, were also present on the right upper and lower extremities. She had approximately 6 firm, plum-colored lesions, ranging in size from papules to small nodules, on the dorsa of both hands, located over the sides of the metacarpophalangeal joints and the proximal portions of several phalanges (Figs 1 and 2). A biopsy of the lesion on the left middle finger was performed. Microscopic findings included a well-circumscribed zone of dense fibrosis, extending from the superficial papillary dermis to the mid-reticular dermis. There was a sharp demarcation at the base of the lesion. The fibrosis was hyaline in appearance, with numerous widely dispersed, small, rounded to spindled cells (Fig 3). In some cases, these cells formed short fascicles. Scattered small vessels were present throughout the lesion. The underlying deep reticular dermis had normally fenestrated collagen, prominent solar elastosis (which had been either obscured or replaced by the overlying tumor), intact eccrine sweat coils without atrophy and with a normal complement of perieccrine fat, and essentially no inflammation. Immunohistochemical staining showed that the rounded to spindled cells were positive for vimentin and smooth muscle actin (Fig 953
954 English et al
Fig 1. A 76-year-old woman with lesions of recent onset on the hands.
J AM ACAD DERMATOL JUNE 2002
Fig 4. The rounded to spindled cells were positive for smooth muscle actin.
DISCUSSION
Fig 2. A plum-colored tumor on the left middle finger.
Fig 3. Photomicrograph showing scattered rounded to spindled cells and vessels within a dense fibrotic stroma. (Hematoxylin-eosin stain; original magnification ⫻400.)
4) and negative for S-100, C-kit, factor XIII, and CD68. On the basis of the histopathologic features and staining characteristics of the lesion, a diagnosis of myofibroma was made. The patient refused any additional surgical procedures.
Adult myofibromas are typically superficial tumors that are confined to the dermis and subcutis.4 Although most studies have described solitary lesions, multifocal lesions confined to one anatomic region have been reported.10 Myofibromas in adults follow a benign course and respond well to excision, although local recurrence is possible.4,10 Microscopically, these tumors closely resemble their pediatric counterparts. They are well circumscribed and usually include 2 components: plump spindled cells, resembling myofibroblasts, that are arranged in short fascicles1,5 and vascular foci composed of polygonal to small spindled cells with hyperchromatic nuclei. Areas with the latter changes bear a resemblance to hemangiopericytoma,12-15 and in fact, some authors have concluded that infantile myofibromatosis and hemangiopericytoma are histogenetically related.12,14 However, “monophasic” variants of myofibroma that feature only one of these components also occur.13 In our case, plump spindled cells and small mature-appearing vessels predominated, and hemangiopericytoma-like areas were not observed. The spindled cells of myofibroma express vimentin and smooth muscle actin and are usually negative for desmin.8 Nodular lesions have been reported in both localized and systemic scleroderma. In the case of diffuse systemic scleroderma, nodules have developed both in sclerotic16-18 and nonsclerotic skin.19 These lesions have been described as keloidal,16,17 though in several reports, biopsy specimens of nodular lesions showed typical changes of scleroderma.18,19 Mizutani et al20 found high levels of tenascin expression in nodular lesions, comparable to levels in morphea and hypertrophic scar, whereas the skin of diffuse systemic scleroderma expressed intermediate levels of this extracellular matrix protein. This result, combined with histopathologic findings and
English et al 955
J AM ACAD DERMATOL VOLUME 46, NUMBER 6
other data, suggested that the nodules of nodular scleroderma most closely resembled a hypertrophic scar.20 Nodular morphea in a linear configuration has been reported,21 and there has also been a report of malignant fibrous histiocytoma and an extra-abdominal desmoid tumor arising in a woman with L-tryptophan-induced eosinophilia-myalgia syndrome.22 Myofibroblasts represent a significant component of both of these tumors.23,24 There is evidence that the myofibroblast may play an important role in the pathogenesis of scleroderma. In an ultrastructural study of peripheral nerves of patients with morphea, Kobayasi and Serup25 found changes in the mesenchymal portions of these nerves that included infiltration by inflammatory cells and myofibroblasts; they suggested that perineural cells could be a possible source of these myofibroblasts. Using immunohistochemical methods, Kirk et al11 found a predominance of myofibroblasts among cultured fibroblasts from skin biopsy specimens of patients with scleroderma. In a subsequent study, Kirk and Mayes26 suggested that interleukin 1 may promote myofibroblast longevity (and therefore fibrosis) in sclerodermatous skin. In an investigation of scleroderma lung disease, Ludwicka et al27 performed bronchoalveolar lavage studies. They found cells with the characteristics of myofibroblasts in over half of their patients with scleroderma but not in healthy control subjects. These cells may be involved in the interstitial pulmonary fibrosis that occurs in scleroderma, in part through stimulation by elevated levels of platelet-derived growth factor and transforming growth factor 1.28 In view of these findings, it appears likely that myofibroblasts are involved in the pathogenesis of nodules of localized and systemic scleroderma, although the reasons that nodules form in only a minority of these individuals remain to be determined. It is possible that some of the nodules that develop in patients with scleroderma may represent true myofibromas. REFERENCES 1. Chung EB, Enzinger FM. Infantile myofibromatosis. Cancer 1981; 48:1807-18. 2. Spraker MK, Stack C, Esterly NB. Congenital generalized fibromatosis: a review of the literature and report of a case associated with porencephaly, hemiatrophy, and cutis marmorata telangiectatica congenita. J Am Acad Dermatol 1984;10: 365-71. 3. Wolfe JT III, Cooper PH. Solitary cutaneous “infantile” myofibroma in a 49-year-old woman. Hum Pathol 1990;21:562-4. 4. Hogan SF, Salassa JR. Recurrent adult myofibromatosis. A case report. Am J Clin Pathol 1992;97:810-4. 5. Sonoda T, Itami S, Seguchi S, Kurata S, Takayasu S. Infantile
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16. 17.
18. 19.
20.
21. 22.
23.
24.
myofibromatosis: report of two cases. J Dermatol 1994;21: 508-13. Stanford D, Rogers M. Dermatological presentations of infantile myofibromatosis: a review of 27 cases. Australas J Dermatol 2000;41:156-61. Daimaru Y, Hashimoto H, Enjoji M. Myofibromatosis in adults (adult counterpart of infantile myofibromatosis). Am J Surg Pathol 1989;13:859-65. Guitart J, Ritter JH, Wick MR. Solitary cutaneous myofibromas in adults: report of six cases and discussion of differential diagnosis. J Cutan Pathol 1996;23:437-44. Requena L, Kutzner H, Hugel H, Rutten A, Furio V. Cutaneous adult myofibroma: a vascular neoplasm. J Cutan Pathol 1996;23: 445-57. Granter SR, Badizadegan K, Fletcher CD. Myofibromatosis in adults, glomangiopericytoma, and myopericytoma: a spectrum of tumors showing perivascular myoid differentiation. Am J Surg Pathol 1998;22:513-25. Kirk TZ, Mark ME, Chua CC, Chua BH, Mayes MD. Myofibroblasts from scleroderma skin synthesize elevated levels of collagen and tissue inhibitor of metalloproteinase (TIMP-1) with two forms of TIMP-1. J Biol Chem 1995;270:3423-8. Mentzel T, Calonje E, Nascimento AG, Fletcher CD. Infantile hemangiopericytoma versus infantile myofibromatosis. Study of a series suggesting a continuous spectrum of infantile myofibroblastic lesions. Am J Surg Pathol 1994;18:922-30. Zelger BW, Calonje E, Sepp N, Fink FM, Zelger BG, Schmid KW. Monophasic cellular variant of infantile myofibromatosis. An unusual histopathologic pattern in two siblings. Am J Dermatopathol 1995;17:131-8. Variend S, Bax NM, van Gorp J. Are infantile myofibromatosis, congenital fibrosarcoma and congenital haemangiopericytoma histogenetically related? Histopathology 1995;26:5762. Magid MS, Campbell WG Jr, Ngadiman S, Godwin TA, Ward R. Infantile myofibromatosis with hemangiopericytoma-like features of the tongue: a case study including ultrastructure. Pediatr Pathol Lab Med 1997;17:303-13. James WD, Berger TG, Butler DF, Tuffanelli DL. Nodular (keloidal) scleroderma. J Am Acad Dermatol 1984;11:1111-4. Sasaki T, Denpo K, Ono H, Nakajima H. Nodular scleroderma in systemic sclerosis under D-penicillamine therapy. J Dermatol 1992;19:968-71. Krell JM, Solomon AR, Glavey CM, Lawley TJ. Nodular scleroderma. J Am Acad Dermatol 1995;32:343-5. Yamamoto T, Furuse Y, Katayama I, Nishioka K. Nodular scleroderma in a worker using a silica-containing abrasive. J Dermatol 1994;21:751-4. Mizutani H, Taniguchi H, Sakakura T, Shimizu M. Nodular scleroderma: focally increased tenascin expression differing from that in the surrounding scleroderma skin. J Dermatol 1995;22:26771. Hsu S, Lee MW, Carlton S, Kramer EM. Nodular morphea in a linear pattern. Int J Dermatol 1999;38:529-30. Mainetti C, Masouye I, Salomon D, Chavaz P, Saurat JH. L-tryptophan-induced eosinophilia-myalgia syndrome associated with primary cutaneous malignant fibrous histiocytoma and extraabdominal desmoid tumor. Cancer 1993;72:2712-5. Salloum H, Kanitakis J, Chouvet B, Grimand P, Claudy A. [Extraabdominal desmoid tumor. Microscopic aspects and histogenesis]. Ann Dermatol Venereol 1993;120:685-8. French. Antonescu CR, Erlandson RA, Huvos AG. Primary fibrosarcoma and malignant fibrous histiocytoma of bone—a comparative ultrastructural study: evidence of a spectrum of fibroblastic differentiation. Ultrastruct Pathol 2000;24:83-91.
956 English et al
25. Kobayasi T, Serup J. Nerve changes in morphea. Acta Derm Venereol 1983;63:321-7. 26. Kirk TZ, Mayes MD. IL-1 rescues scleroderma myofibroblasts from serum-starvation-induced cell death. Biochem Biophys Res Commun 1999;255:129-32. 27. Ludwicka A, Trojanowska M, Smith EA, Baumann M, Strange C, Korn JH, et al. Growth and characterization of fibroblasts ob-
J AM ACAD DERMATOL JUNE 2002
tained from bronchoalveolar lavage of patients with scleroderma. J Rheumatol 1992;19:1716-23. 28. Ludwicka A, Ohba T, Trojanowska M, Yamakage A, Strange C, Smith EA, et al. Elevated levels of platelet derived growth factor and transforming growth factor-beta 1 in bronchoalveolar lavage fluid from patients with scleroderma. J Rheumatol 1995; 22:1876-83.