Atraumatic Breast Fat Necrosis Mimicking Malignancy in End-Stage Renal Disease: A Case Report

Introduction

Fat necrosis in the breast is a benign process in which fat undergoes aseptic saponification by blood and tissue lipase [1]. Common etiological factors include trauma, surgery, radiotherapy, duct ectasia, and infection. Rarer causes include inflammatory conditions, such as polyarteritis nodosa, Weber-Christian disease, and granulomatous angiopanniculitis [1]. Clinical signs and radiological appearance of fat necrosis can simulate malignancy, and a combination of clinical, radiological, and pathological correlation is required for accurate diagnosis and appropriate management. We report an unusual case of atraumatic fat necrosis caused by extensive chronic calcific vasculopathy in a woman with underlying diabetes mellitus and end-stage renal disease (ESRD).

Case Report

A 61-year-old Southeast Asian woman presented with a history of a painful palpable left breast lump for 3 days. There was no fever or inciting trauma to the breasts. She had a past medical history of hemodialysis-dependent ESRD from diabetic nephropathy for the last 8 years and tertiary hyperparathyroidism with documented hypercalcemic episodes.

On physical examination, there was a palpable 2-cm firm and tender lump in the 12 o’clock position of the left breast, with no overlying skin changes, nipple retraction, or nipple discharge. There was no palpable axillary or supraclavicular lymphadenopathy.

An initial mammogram showed striking widespread vascular calcification affecting multiple larger vessels in both breasts, with some appearing notably thickened and continuous in a “tram track” pattern, reflecting the circumferential distribution of calcification in the vessels (Figure 1). No definite breast mass was seen.

Ultrasound evaluation revealed a poorly defined 3-cm, heterogeneous, predominantly hyperechoic mass-like area in the superficial 12 o’clock position of the left breast, which corresponded to the palpable symptomatic site (Figure 2). Vague hypoechoic components were associated with mild acoustic shadowing, and the lesion was otherwise barely distinguishable from the adjacent hyperechoic breast parenchyma. Doppler interrogation revealed minimally increased vascular flow internally. No suspicious lymph nodes were seen.

Histology from an initial ultrasound-guided percutaneous core needle biopsy of the left breast lesion showed mature adipose tissue as well as focal areas of infarction, with some aggregates of foamy macrophages suggestive of fat necrosis. No malignancy was found.

A repeat breast ultrasound performed 5 months later, when the patient reported a size increase of the palpable lump, showed a heterogeneous mass-like lesion that was similar in echogenicity from the previous scan but larger, measuring up to 5 cm (Figure 3). In view of its increasing size, the lesion was surgically excised to obtain a definitive histological diagnosis and to exclude underlying malignancy.

On histological examination, the most striking findings throughout the entire breast specimen were extensive areas of fat necrosis and parenchymal infarction, and extremely widespread circumferential vascular calcification and ossification affecting blood vessels of varying sizes, including those of larger caliber (Figure 4). Elastin stains also demonstrated involvement of the internal elastic laminae. This was of sufficient severity to result in focal vessel occlusion, with resultant infarction of adjacent fatty tissue. A “honeycomb” pattern of calcification of the adipocyte membranes was likely related to underlying hypercalcemia. The final histopathological diagnosis was extensive Mönckeberg sclerosis-like vascular calcification in the breast, associated with focal vascular occlusion, with secondary infarction and fat necrosis.

Discussion

This case presents an unusual instance in which extensive atraumatic fat necrosis developed due to severe calcific vasculopathy. The patient, who had multiple comorbidities, including type 2 diabetes mellitus, ESRD requiring dialysis, and calcium-phosphate disorder, presented with concerning breast changes. The case highlights that extensive arterial calcification in the breast can lead to significant breast tissue infarction. While initially raising concerns for malignancy due to the presentation as a firm, enlarging lesion, careful radiological evaluation and histopathological examination revealed the underlying vascular etiology. This case emphasizes the importance of considering vascular causes in the differential diagnosis of breast lesions, particularly in patients with significant cardiovascular risk factors and metabolic disorders.

Another entity that shares overlapping clinical features and the appearance of vascular calcifications in the breast is calciphylaxis. Calciphylaxis in the breast is a rare disease entity that manifests as cutaneous and subcutaneous ischemic infarcts caused by thrombo-occlusion of dermal blood vessels [2]. Patients develop severe pain from necrotic wounds, which are susceptible to infection, making it a highly morbid and life-threatening condition. Calciphylaxis is also associated with ESRD and derangements in calcium and phosphate homeostasis. The pathophysiological mechanism is postulated to involve hydroxyapatite crystal deposition in the tunica media of vessels, accompanied by subintimal fibroplasia, in response to elevated phosphate, calcium, and glucose levels. This leads to vascular steno-occlusion, which causes ischemic injury and tissue necrosis [2]. Cutaneous manifestations range from livedo reticularis to frank skin necrosis with ulceration [3]. Characteristic distinguishing features of calciphylaxis that were absent in our case were cutaneous involvement and predominant small vessel vasculopathy. The role of radiology in the diagnosis of calciphylaxis is not well established. While nuclear medicine studies were not performed in our case for diagnostic evaluation, recent literature suggests that whole-body bone scintigraphy with Tc-99m methylene diphosphonate can be useful to assess sites of active calciphylaxis, to guide biopsy and determine extent of the disease on the whole-body image. Typical features of a triple-phase bone scan include increased flow and pooling of tracer activity in the initial phase with increased uptake in the delayed phase in the regions involved with calciphylaxis [4].

In the present case, there was clinical concern for breast malignancy in view of the palpable, firm, and enlarging nature of the lesion over a period of 5 months. Malignant differentials for a rapidly growing mass in an elderly woman include malignant phyllodes tumor, medullary carcinoma, and a high-grade invasive carcinoma. However, distinguishing certain pseudotumors, such as fat necrosis, benign hyperplastic conditions, and inflammatory processes, from malignancies can be challenging on imaging, even with advanced modalities using contrast or radiotracers. This is because these conditions commonly contain metabolically active cells and demonstrate growth or infiltration into the surrounding breast tissue. They can present as ill-defined masses, exhibit contrast enhancement, and display increased 18F-fludeoxyglucose uptake on positron emission tomography scans, thereby mimicking the appearance of breast cancer [5–8]. However, the absence of a large hyperdense mass on mammography together with a lesion lacking in definitive margins on sonography were clues that the lesion was unlikely to be any of these mass-forming tumors. Ductal carcinoma in situ typically presents as suspicious calcifications on mammography in approximately 80% of cases, most often showing pleomorphic or fine linear branching morphology with a grouped distribution [9]. This contrasts with the thick “tram track” morphology of the breast calcifications in our case, or the coarse, dystrophic, and sometimes linear calcifications occasionally seen in breast amyloidosis [10] due to secondary hyperparathyroidism from ESRD [11].

In retrospect, the lack of a dense mass on mammography and relative hyperechoic appearance on sonography in this case were suggestive of pathology involving fat tissue. Radiological findings for fat necrosis vary according to the chronicity of presentation. In the early phase, fat necrosis is largely radiolucent on mammography and can have a thin fibrous capsule. On sonography, it can show an area of increased echogenicity, with surrounding soft tissue edema. As fat necrosis evolves with greater fibrosis and hardening, it appears denser on mammography and more hypoechoic on sonography. Fibrosis can appear spiculated in the chronic stage, mimicking breast malignancy [12]. Rim, arc-like, and thick dystrophic type calcifications can also appear in the fibrotic regions later. On magnetic resonance imaging (MRI), fat necrosis can manifest a wide spectrum of findings. Commonly, there will be rimmed and heterogeneous internal enhancement, due to the formation of granulation tissue, inflammatory changes, and angiogenesis, which can mimic malignancy [13]. The clue is to determine if there is fat signal within the enhancing mass, as fat necrosis is usually isointense to fat elsewhere in the breast [13]. However, gadolinium-based contrast administration would be contraindicated in patients with ESRD, and it would be difficult to differentiate fat necrosis from malignancy without contrast on MRI.

Diabetic mastopathy was also initially considered as a differential diagnosis, due to the patient’s comorbidities and the association of diabetes with accelerated breast arterial calcification. Diabetic mastopathy is a form of lymphocytic mastitis and stromal fibrosis that manifests as a painless palpable hard mass in men and women who have long-standing diabetes mellitus [14,15]. Multicentric or bilateral involvement is a relatively frequent phenomenon in the late stages of the disease. These breast masses would typically be homogenously dense on mammography and markedly hypoechoic, with extensive posterior acoustic shadowing, on sonography [14]. Often, sonographic features mimic more sinister pathology, such as breast malignancy. Characteristic histopathological features include a combination of connective tissue overgrowth and periductal lymphocytic infiltrate, which were not present in our case [15]. In addition, our patient presented with a painful, predominantly hyperechoic breast lump, which is contrary to the typical presentation of diabetic mastopathy.

Making the correct diagnosis of this benign condition is crucial to prevent unnecessary breast interventions, particularly in patients with existing medical comorbidities that increase the complications and risks associated with such procedures. Recognizing the predisposing clinical factors, etiology and radiological signs of fat necrosis will help enable a reasonable diagnosis to be established. As the underlying etiology may not be evident in a limited core biopsy, provision of relevant clinico-radiologic information to the pathologist is essential. No additional breast intervention is necessary, and management typically focuses on addressing symptoms, optimizing dialysis, treating calcium and phosphate imbalances, and managing diabetes.

Conclusions

This case highlights a rare and unusual presentation of atraumatic fat necrosis of the breast mimicking breast malignancy, both clinically and radiologically. Unlike the more common post-traumatic or post-surgical fat necrosis, this instance occurred in the absence of any known injury or intervention, making the diagnosis more challenging. It underscores the importance of considering fat necrosis in the differential diagnosis of breast masses in patients with ESRD, who often exhibit severe calcific vasculopathy, which can lead to tissue ischemia. Awareness of this potential mimic will be helpful in avoiding unnecessary interventions and guiding appropriate management.