Pediatric Dermatology Vol. 31 No. 5 588–590, 2014
Nodular Cystic Fat Necrosis with Calcification in a Patient with Juvenile Dermatomyositis Katalin Ferenczi, M.D., Adrienne Berke, M.D., and Hanspaul S. Makkar, M.D., F.R.C.P.C. Department of Dermatology, University of Connecticut School of Medicine, Farmington, Connecticut
Abstract: Nodular cystic fat necrosis is a rare, benign form of encapsulated fat necrosis with distinct histology, characterized by cystic fat necrosis with lipomembranous changes and, in later stages, calcification. We report the case of a 7-year-old child with juvenile dermatomyositis who presented with three asymptomatic, firm, mobile nodules on the arms and neck. Histology was consistent with nodular cystic fat necrosis with prominent calcification. This is an unusual presentation of this entity because it has never been previously reported in association with juvenile dermatomyositis.
Nodular cystic fat necrosis is a rare type of benign encapsulated fat necrosis characterized by distinct histology showing cystic lipomembranous changes in the subcutaneous fat and calcification in later stages (1). Pryjemski and Schuster originally described it in 1977 (2). The lesions are solitary or multiple and tend to occur in regions susceptible to trauma, such as the elbows, knees, and shins. It has been reported in association with diabetes mellitus (3), erythema nodosum (4), Heerfordt syndrome (5), splinter granuloma (6), systemic sclerosis (7), and lupus erythematosus (8). Nodular cystic fat necrosis has never been described in patients with juvenile dermatomyositis (JDM) or adult dermatomyositis. We report the case of a 7-year-old girl with JDM who presented with three mobile subcutaneous nodules on the arms and neck. Histology showed encapsulated fat necrosis, calcification, and lipomembranous changes consistent with nodular cystic fat necrosis.
CASE REPORT A 7-year-old girl with a 2-year history of JDM presented for routine follow-up with a 3-month history of nontender, asymptomatic nodules involving both forearms and the right side of her neck. Her initial diagnosis of JDM had been established 2 years earlier based on her clinical examination, skin biopsy results, high muscle enzyme levels, and magnetic resonance imaging (MRI) findings. Specifically, she had originally presented with a characteristic facial and upper extremity eruption consistent with JDM, and a biopsy of one of these papules demonstrated interface dermatitis. Aldolase and creatine phosphokinase levels were also high. Although there was no clinical evidence of weakness, MRI of the proximal thigh demonstrated signal abnormalities consistent with inflammatory myositis. She responded well to an initial course of methotrexate and prednisone, followed by maintenance therapy of methotrexate
Address correspondence to Katalin Ferenczi, M.D., Department of Dermatology, 21 South Road, Farmington CT 06030, or e-mail: [email protected]. DOI: 10.1111/pde.12363
588
© 2014 Wiley Periodicals, Inc.
Ferenczi et al: Nodular Cystic Fat Necrosis, Juvenile Dermatomyositis
589
and hydroxychloroquine. Her cutaneous involvement had resolved completely until new nodules were noted on a follow-up examination. There was no history of trauma to the affected sites on the arms and neck. On physical examination, three freely mobile, firm, 1.0-cm 9 1.0-cm nodules were symmetrically distributed on the right and left inner proximal arms and the right neck. No other cutaneous lesions were noted. Excisional biopsy was performed on the nodules on the arms. Histologic examination of the excisional specimen revealed the presence of an encapsulated deep nodule with somewhat compartmentalized necrotic fatty tissue composed of cystic cavities lined by crenulated, hyaline membranes and very prominent calcification (Fig. 1A–C). There was a sparse perivascular inflammatory infiltrate composed of lymphocytes noted at the periphery of the lobules. A thin fibrous capsule surrounded the lobules of necrotic fat cells and cystic structures with lipomembranous changes. The histologic findings were consistent with nodular cystic fat necrosis with dystrophic calcification. Identical histology was noted in both excised specimens. DISCUSSION Nodular cystic fat necrosis is a rare, perhaps underreported, entity characterized by very distinct histology demonstrating lipomembranous changes of the subcutaneous fat, with cystic fat necrosis and calcification in later stages of the process. The size at presentation can range from 1 to 15 cm (9). Lesions are single or multiple and present as mobile subcutaneous nodules in areas vulnerable to trauma, most frequently on the upper and lower extremities. The etiology is not entirely clear. A history of antecedent trauma can be elicited in a subset of cases. It has been hypothesized that the development of nodular cystic fat necrosis may be related to vascular compromise of the subcutaneous fat, given the occurrence of these lesions in areas prone to trauma and ischemia. Lipomembranous fat necrosis is a nonspecific pattern of fat necrosis that can occur in many processes secondary to local or systemic events that cause a compromise in the blood supply of the subcutaneous tissue. This is supported by reports describing the development of such changes in splinter granuloma (6) and erythema nodosum (4), as well as in systemic diseases with an underlying vasculopathy, such as systemic lupus (8) and systemic sclerosis (7), or in diseases with an underlying microangiopathy, such as diabetes (3). Recent studies have suggested that lipomembranous changes result from the interaction
Figure 1. (A) The histologic findings revealed cystic fat necrosis surrounded by fibrous tissue with lipomembranous changes. Note the presence of prominent calcification (open arrow, hematoxylin and eosin [H&E], magnification 49). (B) At higher magnification, membranous lipodystrophy with feathery projections can be appreciated (closed arrow, H&E, magnification 209). (C) Higher magnification 409, showing calcification (open arrow) and adjacent lipomembranous changes (closed arrow).
of damaged fat cells with macrophages, probably as a consequence of inflammatory and ischemic disturbance of fatty tissue (4). Similarly, the development of dystrophic calcification, a frequent finding in this entity, has been
590 Pediatric Dermatology Vol. 31 No. 5 September/October 2014
associated with tissue alteration secondary to an underlying chronic inflammatory process or local trauma or tissue injury. Calcinosis is a recognized manifestation of many connective tissue diseases, especially JDM and systemic sclerosis. In our patient, the presence of calcification in these lesions was prominent, and one could speculate that the patient’s underlying disease played a role in the development of such prominent calcification since pathologic calcifications develop in 20% to 40% of children with juvenile dermatomyositis. Histologically, nodular cystic fat necrosis should be differentiated from lipoma, angiolipoma, alpha-1 antitrypsin deficiency panniculitis and pancreatic fat necrosis (3), but cystic fat necrosis with lipomembranous changes is not seen in lipoma or angiolipoma. Panniculitis secondary to alpha-1 antitrypsin deficiency and pancreatic fat necrosis were excluded because of the lack of an inflammatory component with neutrophils and the absence of gastrointestinal symptoms, respectively. In conclusion, we report a case of nodular cystic fat necrosis with prominent dystrophic calcification in a patient with JDM, an association that, to the best of our knowledge, has not been previously reported. Whereas dystrophic calcification is well known to occur in later stages of this entity, we hypothesize that the underlying disease could have played a role, at
least in part, in the development of massive calcium deposits in our patient. REFERENCES 1. Pujol RM, Wang CY, Gibson LE et al. Lipomembranous changes in nodular-cystic fat necrosis. J Cutan Pathol 1995;22:551–555. 2. Przyjemski CJ, Schuster SR. Nodular-cystic fat necrosis. J Pediatr 1977;91:605–607. 3. Kubota Y, Nakai K, Moriue T et al. Nodular cystic fat necrosis in a patient with diabetes mellitus. J Dermatol 2009;36:353–354. 4. Ahn SK, Lee BJ, Lee SH et al. Nodular cystic fat necrosis in a patient with erythema nodosum. Clin Exp Dermatol 1995;20:263–265. 5. Ueda N, Satoh T, Yamamoto T et al. Nodular cystic fat necrosis in Heerfordt’s syndrome. J Eur Acad Dermatol Venereol 2007;21:708–709. 6. Lee HJ, Ahn SK, Hong SP et al. Nodular cystic fat necrosis with lipomembranous change observed in splinter granuloma. Int J Dermatol 2014;53:e135–e137. 7. Toritsugi M, Yamamoto T, Nishioka K. Nodular cystic fat necrosis with systemic sclerosis. Eur J Dermatol 2004;14:353–355. 8. Demitsu T, Yoneda K, Iida E et al. A case of nodular cystic fat necrosis with systemic lupus erythematosus presenting the multiple subcutaneous nodules on the extremities. J Eur Acad Dermatol Venereol 2008;22:885–886. 9. Sonmez E, Safak T, Kecik A. Giant nodular cystic fat necrosis: a report of a rare case. J Plast Reconstr Aesthet Surg 2009;62:152–154.
Nodular Cystic Fat Necrosis with Calcification in a Patient with Juvenile Dermatomyositis Katalin Ferenczi, M.D., Adrienne Berke, M.D., and Hanspaul S. Makkar, M.D., F.R.C.P.C. Department of Dermatology, University of Connecticut School of Medicine, Farmington, Connecticut
Abstract: Nodular cystic fat necrosis is a rare, benign form of encapsulated fat necrosis with distinct histology, characterized by cystic fat necrosis with lipomembranous changes and, in later stages, calcification. We report the case of a 7-year-old child with juvenile dermatomyositis who presented with three asymptomatic, firm, mobile nodules on the arms and neck. Histology was consistent with nodular cystic fat necrosis with prominent calcification. This is an unusual presentation of this entity because it has never been previously reported in association with juvenile dermatomyositis.
Nodular cystic fat necrosis is a rare type of benign encapsulated fat necrosis characterized by distinct histology showing cystic lipomembranous changes in the subcutaneous fat and calcification in later stages (1). Pryjemski and Schuster originally described it in 1977 (2). The lesions are solitary or multiple and tend to occur in regions susceptible to trauma, such as the elbows, knees, and shins. It has been reported in association with diabetes mellitus (3), erythema nodosum (4), Heerfordt syndrome (5), splinter granuloma (6), systemic sclerosis (7), and lupus erythematosus (8). Nodular cystic fat necrosis has never been described in patients with juvenile dermatomyositis (JDM) or adult dermatomyositis. We report the case of a 7-year-old girl with JDM who presented with three mobile subcutaneous nodules on the arms and neck. Histology showed encapsulated fat necrosis, calcification, and lipomembranous changes consistent with nodular cystic fat necrosis.
CASE REPORT A 7-year-old girl with a 2-year history of JDM presented for routine follow-up with a 3-month history of nontender, asymptomatic nodules involving both forearms and the right side of her neck. Her initial diagnosis of JDM had been established 2 years earlier based on her clinical examination, skin biopsy results, high muscle enzyme levels, and magnetic resonance imaging (MRI) findings. Specifically, she had originally presented with a characteristic facial and upper extremity eruption consistent with JDM, and a biopsy of one of these papules demonstrated interface dermatitis. Aldolase and creatine phosphokinase levels were also high. Although there was no clinical evidence of weakness, MRI of the proximal thigh demonstrated signal abnormalities consistent with inflammatory myositis. She responded well to an initial course of methotrexate and prednisone, followed by maintenance therapy of methotrexate
Address correspondence to Katalin Ferenczi, M.D., Department of Dermatology, 21 South Road, Farmington CT 06030, or e-mail: [email protected]. DOI: 10.1111/pde.12363
588
© 2014 Wiley Periodicals, Inc.
Ferenczi et al: Nodular Cystic Fat Necrosis, Juvenile Dermatomyositis
589
and hydroxychloroquine. Her cutaneous involvement had resolved completely until new nodules were noted on a follow-up examination. There was no history of trauma to the affected sites on the arms and neck. On physical examination, three freely mobile, firm, 1.0-cm 9 1.0-cm nodules were symmetrically distributed on the right and left inner proximal arms and the right neck. No other cutaneous lesions were noted. Excisional biopsy was performed on the nodules on the arms. Histologic examination of the excisional specimen revealed the presence of an encapsulated deep nodule with somewhat compartmentalized necrotic fatty tissue composed of cystic cavities lined by crenulated, hyaline membranes and very prominent calcification (Fig. 1A–C). There was a sparse perivascular inflammatory infiltrate composed of lymphocytes noted at the periphery of the lobules. A thin fibrous capsule surrounded the lobules of necrotic fat cells and cystic structures with lipomembranous changes. The histologic findings were consistent with nodular cystic fat necrosis with dystrophic calcification. Identical histology was noted in both excised specimens. DISCUSSION Nodular cystic fat necrosis is a rare, perhaps underreported, entity characterized by very distinct histology demonstrating lipomembranous changes of the subcutaneous fat, with cystic fat necrosis and calcification in later stages of the process. The size at presentation can range from 1 to 15 cm (9). Lesions are single or multiple and present as mobile subcutaneous nodules in areas vulnerable to trauma, most frequently on the upper and lower extremities. The etiology is not entirely clear. A history of antecedent trauma can be elicited in a subset of cases. It has been hypothesized that the development of nodular cystic fat necrosis may be related to vascular compromise of the subcutaneous fat, given the occurrence of these lesions in areas prone to trauma and ischemia. Lipomembranous fat necrosis is a nonspecific pattern of fat necrosis that can occur in many processes secondary to local or systemic events that cause a compromise in the blood supply of the subcutaneous tissue. This is supported by reports describing the development of such changes in splinter granuloma (6) and erythema nodosum (4), as well as in systemic diseases with an underlying vasculopathy, such as systemic lupus (8) and systemic sclerosis (7), or in diseases with an underlying microangiopathy, such as diabetes (3). Recent studies have suggested that lipomembranous changes result from the interaction
Figure 1. (A) The histologic findings revealed cystic fat necrosis surrounded by fibrous tissue with lipomembranous changes. Note the presence of prominent calcification (open arrow, hematoxylin and eosin [H&E], magnification 49). (B) At higher magnification, membranous lipodystrophy with feathery projections can be appreciated (closed arrow, H&E, magnification 209). (C) Higher magnification 409, showing calcification (open arrow) and adjacent lipomembranous changes (closed arrow).
of damaged fat cells with macrophages, probably as a consequence of inflammatory and ischemic disturbance of fatty tissue (4). Similarly, the development of dystrophic calcification, a frequent finding in this entity, has been
590 Pediatric Dermatology Vol. 31 No. 5 September/October 2014
associated with tissue alteration secondary to an underlying chronic inflammatory process or local trauma or tissue injury. Calcinosis is a recognized manifestation of many connective tissue diseases, especially JDM and systemic sclerosis. In our patient, the presence of calcification in these lesions was prominent, and one could speculate that the patient’s underlying disease played a role in the development of such prominent calcification since pathologic calcifications develop in 20% to 40% of children with juvenile dermatomyositis. Histologically, nodular cystic fat necrosis should be differentiated from lipoma, angiolipoma, alpha-1 antitrypsin deficiency panniculitis and pancreatic fat necrosis (3), but cystic fat necrosis with lipomembranous changes is not seen in lipoma or angiolipoma. Panniculitis secondary to alpha-1 antitrypsin deficiency and pancreatic fat necrosis were excluded because of the lack of an inflammatory component with neutrophils and the absence of gastrointestinal symptoms, respectively. In conclusion, we report a case of nodular cystic fat necrosis with prominent dystrophic calcification in a patient with JDM, an association that, to the best of our knowledge, has not been previously reported. Whereas dystrophic calcification is well known to occur in later stages of this entity, we hypothesize that the underlying disease could have played a role, at
least in part, in the development of massive calcium deposits in our patient. REFERENCES 1. Pujol RM, Wang CY, Gibson LE et al. Lipomembranous changes in nodular-cystic fat necrosis. J Cutan Pathol 1995;22:551–555. 2. Przyjemski CJ, Schuster SR. Nodular-cystic fat necrosis. J Pediatr 1977;91:605–607. 3. Kubota Y, Nakai K, Moriue T et al. Nodular cystic fat necrosis in a patient with diabetes mellitus. J Dermatol 2009;36:353–354. 4. Ahn SK, Lee BJ, Lee SH et al. Nodular cystic fat necrosis in a patient with erythema nodosum. Clin Exp Dermatol 1995;20:263–265. 5. Ueda N, Satoh T, Yamamoto T et al. Nodular cystic fat necrosis in Heerfordt’s syndrome. J Eur Acad Dermatol Venereol 2007;21:708–709. 6. Lee HJ, Ahn SK, Hong SP et al. Nodular cystic fat necrosis with lipomembranous change observed in splinter granuloma. Int J Dermatol 2014;53:e135–e137. 7. Toritsugi M, Yamamoto T, Nishioka K. Nodular cystic fat necrosis with systemic sclerosis. Eur J Dermatol 2004;14:353–355. 8. Demitsu T, Yoneda K, Iida E et al. A case of nodular cystic fat necrosis with systemic lupus erythematosus presenting the multiple subcutaneous nodules on the extremities. J Eur Acad Dermatol Venereol 2008;22:885–886. 9. Sonmez E, Safak T, Kecik A. Giant nodular cystic fat necrosis: a report of a rare case. J Plast Reconstr Aesthet Surg 2009;62:152–154.
