Nodular Cystic Fat Necrosis With Calcification and Metaplastic Ossification

To the Editor:

Nodular cystic fat necrosis is a mobile firm nodule predominantly occurring on the lower extremities, histologically characterized by the presence of cystic cavities lined by crenulated, hyaline membranes (lipomembranous changes), and at later stages, calcification. In this report, we describe a case of nodular cystic fat necrosis that occurred in a patient with chronic venous insufficiency, which histologically showed features of fat necrosis, calcification, and metaplastic ossification.

A 52-year-old woman was admitted to our hospital complaining of relapse of leg ulcers. A few years ago, she had been hospitalized for the treatment of chronic leg ulcers. She had obesity [body mass index (BMI): 40]. Physical examination revealed well-circumscribed ulcers covered with necrotic tissues on the surface on the bilateral shins. Histological examination showed the features of chronic ulcer and denied vasculitis. Also, she had macular pigmentation around the ulcer due to stasis dermatitis. Venous ultrasonography revealed bilateral deep vein thrombosis. Further detailed physical examination revealed a solitary bony-hard, mobile subcutaneous nodule, sized 10 mm in diameter located on the left lower leg (Fig. 1). Histological examination revealed a well-circumscribed tumor composed of lobules of necrotic fat cells with lipomembranous lesions surrounded by a thin fibrous capsule in the adipose tissues (Figs. 2A, B), which was diagnosed as nodular cystic fat necrosis. Further, calcification and lamellar bony structures containing osteoblasts were found within the cystic structures (Fig. 3). Calcification was positive for Kossa stain.

FIGURE 1: Subcutaneous nodule on the lower leg (arrow).

FIGURE 2: A, A well-circumscribed tumor showing degeneration of fat tissues, septal fibrosis, calcification, and ossification. B, Prominent fat necrosis.

FIGURE 3: Higher magnification of extensive ossification and calcification.

Nodular cystic fat necrosis is a localized form of fat necrosis, characterized by discrete fat nodules. The lower extremity is the most commonly affected site, which suggests that venous insufficiency, antecedent trauma, and subsequent interruption of blood supply may be the main causing factors. Histologically, nodular cystic fat necrosis shows multiple, nonviable adipocytes surrounded by condensed fibrous tissues, along with lipomembranous changes and calcification. Previous studies have suggested that lipomembranous changes in localized lesions result from the interaction between residual elements of necrotic fat cells and macrophages, probably as a consequence of inflammatory and ischemic disorders in fatty tissues.¹ Lipomembranous changes are considered to be a nonspecific pattern of fat necrosis and sometimes associated with vascular diseases or connective tissue diseases due to the interruption of the blood supply in the subcutaneous tissues. Those conditions are termed by several names, and recently, the phrase of “mobile encapsulated adipose tissue” has been proposed.² The authors suggest that peritoneal mobile encapsulated adipose tissue of cows and subcutaneous fat necrosis in humans arise in the same way over time.

Calcification is occasionally associated with nodular cystic fat necrosis. The mechanisms of dystrophic calcification are thought to be due to the susceptibility of subcutaneous fat to trauma or ischemia. Once the fat cell is damaged, the liberated lipid then undergoes hydrolysis into glycerol and fatty acids. The fatty acids combine with calcium, resulting in calcification of the fat. Calcification is induced in its final stages,^3–5 via the long course of fat necrosis. By contrast, secondary ossification is rare in nodular cystic fat necrosis.

So far, secondary ossification is reported in association with various benign and malignant tumors, such as melanocytic nevi (nevus of Nanta), blue nevi, organoid nevi, acne, cutaneous mixed tumors, epidermal and dermoid cysts, trichoepithelioma, pilomatricoma, lipoma, dermatofibroma, pyogenic granuloma, basal cell carcinoma, squamous cell carcinoma, and melanoma.⁶ To the best of our knowledge, this is the first case of nodular cystic fat necrosis with metaplastic ossification. On the other hand, subcutaneous ossification is occasionally seen in association with trauma has been reported under the term of panniculitis ossificans traumatica in some cases.^7–9 Osteoblasts play a central role in the bone formation. Osteoblasts secret several inducing factors such as bone morphogenetic protein (BMP)-2, BMP-4, β-catenin, osteopontin, osteonectin, and osteocalcin,¹⁰ which exert effects on the precursor cells derived from mesenchymal or adipose-derived cells. BMPs are members of transforming growth factor-β (TGF-β) and transform the fibroblasts, primitive mesenchymal cells or progenitor cells in the bone marrow into osteoblasts.¹¹ TGF-β and connective tissue growth factor, which is regulated by TGF-β, may stimulate primitive mesenchymal cells or displaced embryonic cells in the stroma to differentiate into osteocytes.¹² In conclusion, we speculate that ischemic changes due to venous insufficiency in the lower legs induced local fat necrosis with lipomembranous changes, calcification, and secondary ossification in the present case.