nephrogenic systemic fibrosis mimicking inflammatory breast cancer     

  

Nephrogenic Systemic Fibrosis Mimicking Inflammatory Breast Carcinoma
By Solomon, Garron J; Wu, Elizabeth; Rosen, Paul Peter 
* Nephrogenic systemic fibrosis, previously known as nephrogenic fibrosing dermopathy, is a newly recognized systemic fibrosing disorder primarily affecting patients with chronic renal failure. Patients with skin involvement often develop papules and plaques with peau d'orange surface changes. The lower extremities and trunk are most commonly affected. The most important histologic differential diagnosis is with scleromyxedema. To our knowledge, we report the first case of nephrogenic systemic fibrosis involving the breasts of a 61-year-old woman with end-stage renal disease, clinically mimicking inflammatory breast carcinoma. We propose that nephrogenic systemic fibrosis be considered in the differential diagnosis as a rare possibility when cutaneous changes in the breast suggest inflammatory breast carcinoma in a patient with renal failure. 
(Arch Pathol Lab Med. 2007;131:145-148) 
Nephrogenic systemic fibrosis (NSF) is a recently described systemic fibrosing disorder primarily affecting patients with chronic renal insufficiency. Although the exact cause is unknown, bone marrow-derived circulating fibrocytes are suspected to be involved in the pathogenesis of this rare condition. Skin involvement in NSF frequently presents on the extremities as erythematous papules or plaques, often with peau d'orange surface changes and woody induration. Truncal involvement is less common, and breast involvement has not previously been reported. 
We report here a case of a woman with advanced renal disease who presented with bilateral breast swelling leading to the clinical impression of inflammatory breast carcinoma. Biopsy of one of the breasts revealed NSF. 
REPORT OF A CASE 
The patient is a 61-year-old woman with end-stage renal disease on hemodialysis who presented with tense swelling and ''dimpling'' of both breasts. The patient's medical history also included diabetes mellitus, hypertension, asthma, and hypercoagulability, with a recent thrombectomy performed for a left arm thrombosis involving her arteriovenous shunt. The patient was taking many medications including epoetin alfa. The patient's only significant laboratory findings were an elevated creatinine (10.2 mg/dL), a mild normocytic normochromic anemia (hemoglobin, 11.0 g/dL), and mild thrombocytopenia (platelet count, 140 10^sup 3^/µL). She had no palpable breast mass on physical examination. The clinical impression was inflammatory breast carcinoma, for which a biopsy was performed. The referring pathologist noted ''an infiltrating pattern of fibroblastic cells'' and submitted the slides for consultation to rule out fibromatosis. 
MATERIALS AND METHODS 
Clinical information was obtained from patient records. The diagnosis was based on examination of histologic sections stained with hematoxylin-eosin. Stromal mucin was demonstrated with the Alcian blue histochemical procedure, and CD68-reactive and CD34- reactive cells were identified by immunohistochemistry using a standard avidin-biotin method. 
PATHOLOGIC FINDINGS 
The excisional biopsy specimen of the left breast measured 5.0 4.0 1.0 cm with an attached skin ellipse measuring 5.0 1.0 cm. The microscopic sections showed marked thickening of the dermis with accumulation of thick collagen bundles separated by clefts in the papillary and reticular dermis (Figures 1 and 2). There was focal extension into the subcutaneous tissue along thickened fibrous septae. Within the dermis there was a laminar proliferation of small blood vessels surrounded by a predominantly plasmacytic infiltrate (Figure 3). Higher magnification of the collagenous stroma revealed an increased number of spindled cells resembling fibroblasts and increased stromal mucin (Figures 4 and 5). The stromal spindle cells were largely CD68-positive and CD34-positive (Figure 6, a and b). 
COMMENT 
Nephrogenic systemic fibrosis is an emerging disease principally affecting individuals with advanced chronic renal disease.1 It has also been associated with chronic hepatic disease and the hepatorenal syndrome.2 The scleroderma-like cutaneous manifestations of this clinicopathologic entity were first recognized in 1997 in a cohort of renal dialysis patients and reported by Cowper and colleagues3 in 2000. The term nephrogenic fibrosing dermopathy (NFD) was introduced in 2001.4 Subsequently, an autopsy performed on an individual diagnosed with NFD revealed fibrosis of the diaphragm, psoas muscle, renal tubules, and rete testis, suggesting that the fibrosing disorder was not limited exclusively to the integument.5 Additional reports demonstrated that the lungs, heart, and skeletal muscle can also be affected,6,7 and as a consequence, the preferred terminology is now NSF/NFD.