Subcutaneous panniculitis refers to a broad spectrum of nonsuppurative inflammatory processes involving the subcutaneous fat layer of the skin (Ho and Lam 2002; Walsh et al. 2008; Pinho et al. 2007). Normal subcutaneous fat is incorporated as fat cells arranged into lobules surrounded by fibrous septa containing small blood vessels, lymphatic channels, and nerves (Fernando et al. 2003).
Clinically, subcutaneous panniculitis usually presents as tender or painless nodules within an extremity, trunk, neck, face, or breast (Ho and Lam 2002; Walsh et al. 2008; Fernando et al. 2003). Subcutaneous panniculitis typically is associated with the fat of the lower extremities (Pinho et al. 2007). However, subcutaneous panniculitis in the breast is rare and a palpable breast abnormality can be misjudged as cancer at clinical examination (Cho and Park 2013).
Subcutaneous panniculitis is divided into five histopathologic patterns (Ho and Lam 2002; Walsh et al. 2008; Fernando et al. 2003; Ter Poorten and Thiers 2002; Ferrara et al. 2013): 1) lobular panniculitis without vasculitis, 2) lobular panniculitis with vasculitis, 3) septal panniculitis without vasculitis, 4) septal panniculitis with vasculitis, and 5) mixed panniculitis involving septa and lobules. Lobular panniculitis may be related to idiopathic Weber-Christian disease, trauma, intragenic injections, cold exposure, sickle cell disease, alpha-1 antitrypsin deficiency, pancreatic disease, systemic lupus erythema, scleroderma, erythema induratum, and paraneoplastic disease. Septal panniculitis may be associated with erythema nodosum, eosinophilic fasciitis, and polyarteritis nodosa. Mixed panniculitis may occur in lupus profundus, and subcutaneous sarcoidosis. Once a vasculitis has been detected within the subcutaneous tissue by histopathology, polyarthritis nodosa, erythema nodosum, and nodular vasculitis should be considered (Ferrara et al. 2013; Gilchrist and Patterson 2010).
The histologic findings in our case were compatible with panniculitis with vasculitis involving medium-sized arteries and small vessels. As neither giant cells nor granuloma formation were demonstrated in our patient, erythema nodosum and nodular vasculitis were considered less likely. However, polyarteritis nodosa, microscopic polyangiitis, or other forms of vasculitis were considered.
Sonographic findings of subcutaneous panniculitis, with or without vasculitis, vary with pathologic stage and reflect the degree of fibrosis (Baillie and Mok 2004; Taboada et al. 2009; Tan et al. 2006). During the initial stage, subcutaneous fat cells are destroyed with subsequent hemorrhage and inflammatory infiltrate. During the subsequent reparative phase, fibroblasts proliferate within the surrounding tissues; during the final stage, fibrosis gradually replaces fat necrosis with little or no calcification. On sonography, subcutaneous breast panniculitis usually appears as a hyperechoic focus within the hypoechoic subcutaneous fat, leading to non-uniformity of the subcutaneous tissue during the initial stage of pathology (Ho and Lam 2002; Taboada et al. 2009). During the subsequent reparative and final stages, the margins of the lesions range from well defined, to indistinct or spiculated, depending on the degree of fibrosis. Subcutaneous fat necrosis in panniculitis may present as a complex mass with mural nodules, an isoechoic mass, a hypoechoic solid mass, or an anechoic cystic mass with posterior acoustic enhancement or shadowing (Fernando et al. 2003; Cho and Park 2013). Posterior acoustic enhancement may be associated with serous fluid within fat necrosis, and posterior acoustic shadowing may related to oil cysts with calcifications (Fernando et al. 2003; Taboada et al. 2009).
Subcutaneous masses with increased echogenicity are almost always benign (Baillie and Mok 2004). Benign male breast lesions resembling a malignancy on gray-scale and Color Doppler sonography show at least one of six criteria: an irregular shape, non-circumscribed margins, a heterogeneous internal echotexture, an echogenic interface, posterior acoustic shadowing, and increased internal vascularity (Yitta et al. 2010; Cho and Park 2013; Tan et al. 2013). Mimickers of breast malignacy include gynecomastia, fat necrosis, ruptured epidermal cyst, pseudoangiomatous stromal hyperplasia, subareolar abscess, intraductal papilloma, hematoma, and atypical fibroadenoma (Yitta et al. 2010; Ng et al. 2014; Cho and Park 2013). The breast lesion in our patient presented with four of six malignant features on sonography.
The benign signs of breast incidentalomas on standard chest CT scans include small size (mean ± standard deviation, 13.4 ± 8.7 mm), oval shape, calcifications, no axillary lymphadenopathy, and inhomogeneous contrast enhancement (Bach et al. 2013). However, there is no significant difference between benign and malignant breast lesions with regards to margin characteristics on chest CT (Bach et al. 2013). Therefore, non-contrast chest CT is insufficient to differentiate between a benign vs. malignant breast lesion in our patient. Although neither mammography nor breast MRI were performed in our case, mammography and MRI findings of subcutaneous panniculitis, with or without vasculitis, can also vary with different pathologic stage and reflect the degree of fibrosis (Pinho et al. 2007; Baillie and Mok 2004; Taboada et al. 2009; Tan et al. 2006).
Mammography is superior to sonography regarding the evaluation of microcalcifications (Pinho et al. 2007). Breast panniculitis (with or without vasculitis) on mammography has been described as a focal asymmetry, mass, or radiolucent lesion with suspicious microcalcifications (curvilinear, branching, punctate, or amorphous) paralleling the course of fat necrosis (Pinho et al. 2007). Coarse calcifications, radiolucent appearance, and local skin thickening on mammography are benign features of breast panniculitis. Benign features on breast MRI include local cutaneous involvement, high signal intensity on precontrast T1-weighted images and low signal intensity on precontrast fat-suppressed T1-weighted images suggesting fat, and continuous rim enhancement on MRI kinetic analysis instead of a wash-out curve (Pinho et al. 2007; Taboada et al. 2009; Sabate et al. 2006). During the reparative and final stage of the disease, BPWV could present with indistinct or spiculated margins and architectural distortion on sonography, mammography and MRI, which may be indistinguishable from breast malignancy (Pinho et al. 2007; Taboada et al. 2009; Sabate et al. 2006).
Histopathologic features of BPWV, including granulomatous and nongranulomatous manifestations and size of inflamed vessels, are not useful in predicting extent of disease (Hernandez-Rodriguez et al. 2008). Diagnosis of isolated or systemic subcutaneous panniculitis with vasculitis is established by a combination of clinical and histologic features, laboratory abnormalities, immunologic markers, exclusion of specific infectious agents, and even visceral angiography (Pinho et al. 2007; Hernandez-Rodriguez et al. 2014).
The pathogenesis of cutaneous vasculitis is mediated by serum immune complexes or antineutrophil cytoplasmic antibodies (Hernandez-Rodriguez et al. 2014). Half of the cases of BPWV have presented as an isolated breast lesion whereas the other half of cases presented as a component of a systemic disease (Hernandez-Rodriguez et al. 2008). Isolated cutaneous panniculitis with vasculitis can regress spontaneously or develop into late systemic disease, with the patient eventually developing malignant hypertension and subsequent end-stage renal disease (Pinho et al. 2007; Hernandez-Rodriguez et al. 2014; Chen and Carlson 2008; Selga et al. 2006). In our review of the literature, renal involvement was seen in 70% of cases of polyarteritis nodosa at diagnosis. Polyarteritis nodosa or microscopic polyangiitis can be considered a self-limiting disease with a relapse rate of between <10% and 57% (Hernandez-Rodriguez et al. 2014).
In our case, BPWV did not coincide with chronic hypertension and chronic renal disease. Furthermore, negative ANCA, negative serum autoimmune markers, lack of malignancy, and lack of either arthralgia or myalgia ruled out the likelihood of systemic vasculitis (Hernandez-Rodriguez et al. 2008). Because panniculitis and/or vasculitis were not present at other sites or organs at the time of diagnosis or during follow-up, idiopathic isolated BPWV was considered the most likely diagnosis. Bacterial pneumonia might be another possible etiology. Three cases of skin leukocytoclastic vasculitis complicating Klebsiella pneumonia bacteremia have been reported in the English literature (Huang et al. 2013; Lloret et al. 2002; Lum et al. 2000). However, all three cases presented with cutaneous rash or pustulosis instead of a single breast nodule.
To date, seventeen cases of isolated BPWV have been reported without evidence of systemic vasculitis (Hernandez-Rodriguez et al. 2008; Kafantari et al. 2008). Only one of the 17 cases was male. Our case is, thus, the second case of isolated panniculitis with vasculitis of the male breast. Fourteen of 18 cases (77.8%, including our case) were proven by excisional biopsy, mastectomy, or incisional biopsy. The other four cases were proven by core-needle biopsy. Sono-guided core-needle biopsy with an 18-gauge needle could not provide the diagnosis of breast vasculitis in our case. This suggests that excisional biopsy or a larger gauge needle during core-needle biopsy should be used to detect the component of breast vasculitis.
Patients with isolated BPWV have an excellent prognosis with resection alone without systemic corticosteroid or immunosuppressive therapy. They have been reported to have a lower relapse rate (as in our case) compared with breast vasculitis with systemic involvement (Hernandez-Rodriguez et al. 2008).