Giant cell arteritis is an inflammatory lesion of the large- and medium-sized arteries, usually involving the temporal arteries of older women. Rarely, the breast has been reported as the primary site of involvement. Patients usually present with breast masses that are tender or painful in most reported cases. The disease may be associated with constitutional symptoms that resemble polymyalgia rheumatica, but most reported cases do not have an established diagnosis of autoimmune disease. Clinically, giant cell arteritis of the breast may mimic breast carcinoma. Establishing the diagnosis is important because most patients achieve remission of symptoms after treatment with prednisone.
Giant cell arteritis (GCA) is an inflammatory lesion of the large- and medium-sized arteries, which usually involves the cranial arteries of older women. Patients commonly present with temporal headaches, visual impairment, fever, scalp tenderness, jaw claudication, and polymyalgia rheumatica (PMR).1,2 The PMR symptoms include proximal morning stiffness and pain, tiredness, fever, weight loss, and occasional night sweats.3 Anemia and an elevated erythrocyte sedimentation rate are often present.1,2 The definitive diagnostic test is a temporal artery biopsy that shows granulomatous arteritis with giant cells and destruction of the elastic lamina.1 In addition to the more-frequent involvement of branches of the external carotid arteries, involvement of the aorta, coronary, renal, and mesenteric arteries may occur.3 Although GCA involving the breast is a rare occurrence, the clinical and imaging findings may generate concern for malignancy.
Usually, GCA involves the carotid arteries and their branches, especially the temporal arteries.4 Less commonly, locations such as the thyroid gland, tongue, lower limbs, uterus and adnexa, and breast can be involved.4 Giant cell arteritis of the breast (GCAB) was first described by Waugh in 1950.5 Since then, only 20 additional cases have been reported, to our knowledge, in the literature (Table). The disease occurs in older women, with an age range between 52 and 79 years.6 The typical presentation is a breast mass (19 of 21 cases; 90%) that is either unilateral (9 of 21 cases; 43%)4,7–14 or bilateral (10 of 21 cases; 48%).2,5,6,9,15–20 Multiple masses in the breast are present in most cases (10 of 19 cases; 53%).2,6,7,9,13,15,17–20 In most patients, the masses are painful or tender (16 of 19 cases; 84%).2,4–9,12–15,17–20 On occasion, the masses are accompanied by nipple retraction (2 of 19 cases; 11%)16,20 and axillary lymphadenopathy (4 of 19 cases; 21%).6,7,16,17 In 2 cases (2 of 21; 10%), breast masses were absent, and the patients presented with unilateral, burning pain and erythema21 or tenderness.22
Giant cell arteritis of the breast may be associated with constitutional symptoms similar to those of PMR, such as anorexia, weight loss, myalgia, arthralgia, and fever.4,7–11,14–19,22 Mild anemia, leukocytosis, and an elevated erythrocyte sedimentation rate have also been reported.2,4–12,14–19,21,22 Autoantibodies, such as antinuclear antibody and rheumatoid factor, have only been detected in 2 of 14 cases (1%) in which they were examined.4,8 In most patients who experienced PMR-like symptoms, the onset of symptoms was concurrent with the development of breast pathology.2
Breast imaging studies were described in 9 of 21 reported cases (43%). Where specified, imaging findings included calcifications in vessels in one case.6 Except for one case associated with carcinoma, imaging did not reveal any mass lesions, even when breast lumps had been detected on breast examination.6 Imaging findings were described as either normal or negative for malignancy2,15,20–22 or included findings such as enlarged, heterogeneous, mixed echogenicities19 ; mild fibrocystic dysplasia9 ; or dense breast tissue.6 Carcinoma has been reported in association with GCAB in 3 cases (1%). In 2 of those, imaging studies were not described.10,11 The third case showed a mass distorting the architecture of the surrounding breast on mammography.4 The diagnoses of carcinoma were made on simple mastectomy10 and excisional biopsies4 (2 cases).
The microscopic findings of GCAB include a transmural inflammatory infiltrate of the walls of small- and medium-sized arteries, composed of lymphocytes, plasma cells, histiocytes, and multinucleated giant cells.* Giant cells may be absent in a subset of cases.10,15 Some cases show a mixed inflammatory infiltrate, which includes neutrophils and eosinophils.5,7,8,11,17,21 Fragmentation of the internal elastic lamina is typical.† There is intimal proliferation and narrowing of the vascular lumina and possible thrombus formation.6,18,22 Fibrinoid necrosis has been described in some but not all cases7,8,10,15,16 (Figure).
Temporal artery biopsies were common in all cases tested,4,8,11,14 except in the case reported by Horne et al,10 in which the temporal artery biopsy done at the time of the mastectomy showed arteritis. Additional associated findings included thyroid follicular adenoma that also showed GCA18 and acute necrotizing panarteritis involving the small vessels in a muscle biopsy.14
The differential diagnosis of GCAB is quite diverse. The clinical presentation with firm breast lumps that may be fixed to the skin or causing nipple retraction is most alarming for breast carcinoma.16,20 The erythematous skin changes observed in several cases are especially concerning for inflammatory breast cancer.6,7,9,15,19,21 Some cases also featured axillary lymphadenopathy, raising a concern for metastatic disease.4,6,7,16,17 In fact, infiltrating carcinoma and carcinoma in situ were detected concurrently in 3 cases (1%).4,10,11 Interestingly, temporal arteritis and PMR have also been reported in association with squamous cell carcinoma of the tongue, myelodysplastic and myeloproliferative syndromes, prostate cancer, lung adenocarcinoma, and renal cell carcinoma.4 Vasculitis is considered by some a paraneoplastic syndrome associated with solid organ and hematologic malignancies.4 The vasculitis resolved with treatment for the malignancy and recurred with its progression or recurrence.4 In most cases, the malignancy was myelodysplastic syndrome. The most common solid malignancies included those of the urinary tract, lung, and gastrointestinal tract.4 In the case reported by Kafantari et al,4 all GCA-related symptoms resolved after resection of the tumor. Two other cases in the literature reported that PMR symptoms resolved with the medical treatment of prostate cancer23 and renal cell carcinoma after nephrectomy.24
The differential diagnosis of GCAB also includes other types of vasculitides involving the breast.19 Wegener granulomatosis is a disease characterized by necrotizing vasculitis affecting the upper and lower respiratory tract accompanied by glomerulonephritis. Rarely, other sites, such as the skin, joints, visceral organs, and the breast, can be involved.1 Breast involvement usually occurs during the course of the disease and only rarely as the initial manifestation.6 Clinically, this disease can also mimic breast carcinoma. In those cases, mammography may present lesions with irregular or stellate borders; however, calcifications are absent. Unlike GCA, the vasculitis affects arteries and veins. Histologic exam shows acute and chronic inflammatory cells within the breast parenchyma and fat. Vasculitis is seen in both arteries and veins within necrotic areas and the adjacent breast. Granulomas are present focally in the adjacent breast and at the periphery of the necrotic areas.1
Polyarteritis is a multisystemic panarteritis involving medium-sized and small arteries.6 Localized forms of the disease can affect the skin,25 gallbladder,26 and cervix.27 Polyarteritis involving the breast is a rare entity that usually does not involve other organs.28,29 Most cases have a unilateral breast lesion as the first manifestation.1 Polyarteritis involves arteries of various sizes, including arterioles, but spares veins.1 Microscopically, there is a transmural necrotizing vasculitis without a giant cell reaction.1 Eosinophils may be a prominent component of the mixed inflammatory cell infiltrate.1 There is occasional luminal occlusion due to narrowing or thrombosis.6
Other lesions in the differential diagnosis include other collagen vascular diseases, such as scleroderma and dermatomyositis.1 Superficial thrombophlebitis or Mondor disease, spontaneous infarction of the breast during pregnancy or lactation, and hemorrhagic infarction of the breast as a complication of anticoagulant therapy are also part of the differential diagnosis.19
Giant cell arteritis of the breast may go unrecognized clinically for several reasons. First, the breast is supplied by 2 branches of the subclavian artery, namely the internal mammary and the lateral thoracic arteries.2 Thus, the rich vascularization of the breast could result in an asymptomatic presentation.5 As evident from the reported cases, the patient population includes women of menopausal age. Hence, the constitutional symptoms may be attributed to menopause.22 In addition, the nontender nature of some masses and the fact that they often present in association with fibrocystic changes of the breast may cause GCA to go undetected.22
In none of the reported cases could a diagnosis of GCAB be achieved by needle core biopsy or fine-needle aspiration. A larger amount of tissue to ensure sampling of vessels was needed to establish the diagnosis.6 However, once the diagnosis was established and cancer had been excluded, treatment with prednisone was shown to be effective in most patients.8–11,14,15,17–19,21 Some patients improved with nonsteroidal anti-inflammatory drug treatment,6,9 and some patients had spontaneous remission after lumpectomy.4,5,12,13,16,20,22
Giant cell arteritis may present as a localized lesion of the breast in symptomatic or asymptomatic patients, which may be alarming, clinically and radiographically, for malignancy. It is most concerning when presenting as a unilateral breast lesion with skin changes mimicking inflammatory breast cancer. Establishing a diagnosis leads to appropriate therapy and symptom resolution in most cases. Approximately 2 of 21 reported cases (10%) were associated with breast carcinoma. Furthermore, GCAB may be seen as a paraneoplastic syndrome associated with a number of malignancies. Whether granulomas or vasculitis on core biopsy should lead to an excisional biopsy is a difficult question based on the few cases reported in the literature and is probably best handled on a case-by-case basis.
References 2, 4–6, 9, 11, 14, 16–19, 21, 22.
References 2, 4–8, 10, 11, 14, 17–19, 21, 22.
From the Department of Pathology, George Washington University, Washington, DC. Dr Tabbarah is now with the Neuropathology Division and Dr Voltaggio is now with the Gastrointestinal and Liver Division, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
The authors have no relevant financial interest in the products or companies described in this article.