Polyarteritis Nodosa of the Breast: Presentation and Management

International Journal of Surgery 7 (2009) 446–450

Contents lists available at ScienceDirect

International Journal of Surgery

journal homepage: www.theijs.com

Polyarteritis nodosa of the breast: Presentation and management

Haitham Hassan Khalil a,e,*, Jo Marsden a, Nuzhat Akbar c, Patrick Gordon d, Jonathan Roberts a, Klaus-Martin Schulte b a Breast Care Unit, Department of General Surgery, Kings College Hospital, London SE59RS, United Kingdom b Endocrine Surgery Unit, Department of General Surgery, Kings College Hospital, London SE59RS, United Kingdom c Department of Pathology, Kings College Hospital, London SE59RS, United Kingdom d Department of Rheumatology, Kings College Hospital, London SE59RS, United Kingdom e Breast Care Unit, Department of General Surgery, Good Hope Hospital, Heart of England NHS Foundation Trust, Rectory Road, Sutton Coldﬁeld, Birmingham B75 7RR, United Kingdom article info abstract

Article history: Polyarteritis nodosa (PAN) of the breast is a rare condition where literature review identiﬁed eleven Received 26 September 2008 patients so far. The clinical presentation ranged from localized disease involving the breast parenchyma Received in revised form and skin only to breast manifestations as part of systemic PAN. The diagnosis of PAN could be challenging 18 May 2009 as it can mimic breast cancer, inﬂammatory carcinomatosis or breast infection including mastitis and Accepted 5 June 2009 necrotizing fasciitis. The key importance is accurate diagnosis to avoid unnecessary other treatment Available online 21 June 2009 modalities and the timely recognition of PAN in cases of localized forms. The authors present three new cases which represent the full range of the clinical spectrum and their management. Keywords: Polyarteritis nodosa Ó 2009 Published by Elsevier Ltd on behalf of Surgical Associates Ltd. Breast Cancer

1. Introduction We here present further 3 cases of breast PAN with different presentation including literature review and differential diagnosis. Polyarteritis Nodosa (PAN) belongs to a group of inflammatory disorders characterized by necrotizing vasculitis of small and 2. Patients and methods medium sized blood vessels.1 Whether systemic or focal in appearance all manifestations share histopathological findings of Case 1. A 21-year-old Afro-Caribbean multi-paraous woman 2 arteritis. The term PAN presently includes classic PAN, cutaneous presented to the breast care unit in 2004 with a sudden onset 2 PAN and microscopic PAN (microscopic polyangiitis [MPA]). Multi- necrotizing skin lesion involving the central, upper and lower organ involvement is more common than isolated organ involve- lateral quadrants of left breast leading to inflammatory, hyperpig- 3 ment. PAN affecting the breast alone has been reported in very few mented, tender skin changes (Fig. 1a). She concomitantly suffered patients. To date, eleven patients with PAN involving the breast from a gangrene of the dorsum and the distal small finger of the left 1,3–11 have been reported in the medical literature. In those it pre- hand. Medical history revealed sickle cell disease with recurrent sented as an isolated vasculitis of the parenchymatous mammary deep venous thrombosis, retinopathy and pulmonary hypertension. tissue, as cutaneous PAN lesions of the breast skin envelope with The clinical differential diagnosis at that time contained a non- involvement of breast fibro-glandular tissue, or finally as involve- lactational breast abscess, inflammatory carcinomatosis, necro- ment of the glandular mammary tissue as part of the systemic tizing fasciitis and sickle cell crisis. Generalised sepsis urged classic PAN. a thorough surgical debridement of necrotic tissues with use empirical antibiotics. Surgical debridement revealed full thickness infarction of the skin and underlying breast parenchyma. Delayed Abbreviations: ACR, American College of Rheumatology; CHCC, Chapel Hill second stage coverage of the defect was performed using a meshed Consensus Conference; MPA, Microscopic Polyangiitis; PAN, Polyareteritis Nodosa; split thickness graft (5 days). Light microscopy and culture of the ANCA, Antineutrophil Cytoplasmic Antibody; AAV, ANCA Associated Vasculitis; AIP, removed breast tissue failed to detect an organism. Histopathology Acute Intermittent Porphyria. revealed extensive vasculitis of small and medium sized vessels * Corresponding author. Tel.: þ44 7711740386. E-mail addresses: [email protected], [email protected] with fibrinoid necrosis of vessel walls in absence of malignancy (H.H. Khalil). (Fig. 1b). Blood cultures to exclude septic emboli proved to be

1743-9191/$ – see front matter Ó 2009 Published by Elsevier Ltd on behalf of Surgical Associates Ltd. doi:10.1016/j.ijsu.2009.06.005 H.H. Khalil et al. / International Journal of Surgery 7 (2009) 446–450 447

Fig. 1. (a) Intraoperative picture showing areas of necrosis with surrounding zone of erythema and cellulites of the left breast skin envelope mimking inflammatory mastitis, abscess or inflammatory carcinomatosis. (b) Microscopic picture of adipo-fibro-glandular tissue showing small to medium sized vessels with fibrinoid necrosis, acute inflammation and thrombotic occlusion of lumen, Elastic Van Gieson (EVG)100 HPF stain confirmed vessels to be arteries rather than veins (arrow a), mammary ducts in the vicinity (arrow b). No granulomas were seen excluding granulomatous vasculiltis, e.g. Wegener’s granulomatosis.

negative. In view of these results the patient was referred to the needle biopsy revealed necrosis and inflammatory granulation rheumatology team for further evaluation with immunological and tissue insufficient for complete histological analysis. Histopa- inflammatory workup which are shown in Table 1. The patient was thology of the excisional biopsy of the nodule then revealed subsequently diagnosed with microscopic PAN (MPA) where anti- a localized form of healed arteritis (Fig. 2b). Immunohistochemical proteinase 3 (PR3) Antineutrophilic Cytoplasmic Antibody (ANCA) staining for cytokeratin MNF 116 was negative and special stains for was positive; she was started on corticosteriod therapy and organisms were all negative. No further management was provided azathioprine which achieved complete remission. Hospital stay for the patient who was referred for follow-up and more evaluation was prolonged due to delayed wound healing. One year later she by the rheumatology team where immunological and inflamma- developed leg ulcers, which healed on steroid therapy. No further tory workup was performed (Table 1). vasculitic episodes have been encountered since. Case 3. This 50 years old Afro-Caribbean woman had a remark- Case 2. A 45-year-old Asian woman noticed the spontaneous able medical background. She was known to suffer from acute appearance of a painless lump in the upper outer quadrant of the intermittent porphyria AIP with renal failure and secondary left breast with a progressive course over a week’s time. Clinical hyperparathyroidism cured by total parathyroidectomy in 2006. examination revealed a well defined 2.5 cm non-tender lump She presented with bilateral extensive necrotic leg ulcers initially which felt equivocal. Mammogram found a non-suspicious fibro- thought to represent cutaneous calciphylaxis despite a low or glandular parenchyma pattern, while ultrasound revealed a 2.0 cm normal calcium phosphate product (Fig. 3a). Multiple skin biopsies complex cyst with internal echoes of low signal intensity and failed to prove PAN. The disease rapidly progressed in bouts which a rather irregular thickened capsule. These features were initially were mirrored by extreme elevations of CRP and ESR. Table 1 shows interpreted as a complex cyst or necrotic tumour (Fig. 2a). Core the immunological and inflammatory markers. The diagnosis was finally made by elevated ANCA titres. Major visceral haemorrhage led to angiography demonstrating typical aneurysmata of the Table 1 middle sized visceral arterial branches with active bleeding of one CASE 1 CASE 2 CASE 3 of these lesions. During her prolonged admission over 7 months A. Clinical presentation (ACR) Absent Absent Present repeated surgical debridement became necessary for management B. Immunological and inflammatory markers: of these extensive gangrenous areas in both lower limbs. Partially 1. Rheumatoid Factor (<20.0 lu/ml) 42a 9.7 10.1 these were covered by mesh grafts. Whilst the initial presentation 2. Immunoglobulins IgG (7.00–18.60 g/l) 20.8bb 24.20a involved the lower body half only, she then presented with acute IgA (0.78–4.80 g/l) bb 9.37a onset bilateral breast tenderness in the late course of her disease. IgM (0.49–2.00 g/l) bb b On clinical examination, both breasts were tender, though without 3. Antineutrophil Cytoplasmic Positive Negative Positive significant abnormality apart from symmetrical thickening of the Antibody (ANCA) 4. Other Auto-Antibodies fibro-glandular tissue and dilated superficial veins. Mammogram AntiMitochondrial antibody Negative Negative Negative revealed marked vascular calcifications seen throughout both Anti Gastric Parietal Cell Antibody Negative Negative Negative breasts with focal areas of benign, dense clusters of calcification, Liver Kidney Microsome Negative Negative Negative but no focal masses (Fig. 3b). Bilateral breast ultrasound was non- Anti-smooth Muscle Antibodies Negative Negative Positive specific revealing inflamed fibro-glandular tissue in the retro- Double stranded Autoantibodies Negative Negative Negative 5. C Reactive Protein (CRP) < 5 mg/L 267.1ab 277a areolar region, but no evidence of focal collections to suggest an 6. Erythrocyte sedimentation rate (ESR) Raised Not raised Raised abscess or any other focal abnormality. Computed tomography scan 7. Complement showed areas of calcification in the glandular parenchyma. Core ab b C3 (0.70–1.65 g/l) 1.74 needle biopsy of both breasts revealed fibrinoid necrosis and whole C4 (0.16–0.54 g/l) 0.13cb b C. Histopathology results Confirms Confirms Confirms thickness inflammation of small and blood vessels giving the PAN PAN PAN appearances of small vessel vasculitis (Fig. 3c). The patient had at that time been under the protocol high-dose management for PAN a High. b Normal. according to ACR recommendations including cyclophosphamide, c Low. azathioprine and corticosteroids. Unfortunately, the patient died 448 H.H. Khalil et al. / International Journal of Surgery 7 (2009) 446–450

Fig. 2. (a) Ultrasound image showing a 20 mm poor echogenic mass in left breast contains some fluid with internal echoes thicked capsule with a provisional diagnosis of a complex cyst and a necrotic tumour, it was graded as U4 (suspicious mass). (b) Microscopic picture showing vasculitic changes in breast PAN. One of the main microscopic features includes focal destruction of elastic lamina which could be demonstrated using special elastic tissue staining elastic Van Gieson (EVG)200 HPF. Intimal thickening and recanalized thrombosis are characteristics of healed arteritis. due to recurrent septicaemia and upper gastrointestinal bleeding visceral involvement.1,3–11 All three cases share the involvement of one month later. the glandular breast tissue in the inflammatory process. They demonstrate the three clinical manifestations of PAN in the breast: 3. Discussion - a breast nodule, with or without other cutaneous or systemic Breast involvement is a rare site of apparently localized vascu- findings; litis; it can either be granulomatus or necrotizing in nature.4 Our - full thickness skin necrosis and necrosis of underlying soft cases demonstrate that it may be more common than expected tissues in the setting of multi-focal cutaneous vasculitis; when a high index of suspicion is used in the diagnostic approach. - Predominantly systemic PAN with involvement of the breast. Diagnosis relies on histopathological examination of representative tissue specimen and the use of highly specific immunological tests The glandular tissue of the breast is an exocrine organ. PAN has in patients with suspicious features. These diagnostic modalities been previously reported to involve isolated organs including other should be performed in all patients with an otherwise unexplained exocrine organs such as appendix,13 gallbladder,14 cervix,15 epi- inflammatory change of the breast – even if systemic manifesta- pdidymis,16 alimentary canal,17,18 pancreas,19 salivary glands,20 tions are lacking at that point. The key importance of such an prostate.21 approach is the avoidance of unnecessary other treatment modal- Arteritis could either affect the mammary tissue or the over ities and the timely recognition of PAN. As seen here, breast lying skin and subcutaneous tissue (cutaneous PAN). These distinct manifestations can be amongst the first clinical manifestations and entities of the disease should not be confused as cutaneous PAN is an accurate diagnosis is the key to initial and long-term manage- associated with good prognosis.7,22,23 Review of the literature ment of this rare yet devastating disease. Multiple studies prove revealed only one case that presented with a tender breast mass, that such early diagnosis of PAN can reduce both mortality and ulceration and central necrosis and erythematosus tender necrotic morbidity due to the disease.12 nodules in the legs and the arms. Clinically this was interpreted as It is clinically of prime importance to differentiate between a multi-focal cutaneous PAN with isolated mammary tissue PAN at isolated and systemic PAN which mainly depends on the exclusion the age of 34 postpartum with the presumptive diagnosis as of visceral involvement as isolated form has a much more favour- puerperal mastitis.4 The first case in this series presented with the able prognosis.4 similar clinical manifestations but not related to pregnancy or Review of the literature shows that PAN of the breast presents as lactation and at a younger age (21 years). We have failed to find a localized isolated lesion or part of systemic disease that include evidence that PAN of the breast is induced by or related to lactation.

Fig. 3. (a) Bilateral lower limb extensive vasculitic necrotic ulcers involving cutaneous and subcutaneous tissue as part of systemic PAN. (b) Bilateral mammogram showing focal & radial calcification as part of systemic PAN. Differential diagnosis of radial calcification includes atherosclerosis, comedo mastitis and calciphylaxis. (c) Microscopic picture of breast PAN (H & E)100 HPF showing vasculitis associated with fibrinoid necrosis. One of the characters is the presence of acute and chronic inflammatory cells (neutrophils, lymphocytes) infiltrates within the breast parenchyma. H.H. Khalil et al. / International Journal of Surgery 7 (2009) 446–450 449

The search of the medical literature revealed 5 cases of isolated been controversy in the classification of the ANCA associated mammary tissue PAN with no systemic signs or constitutional vasculitis (AAV) including the MPA which was not included in ACR manifestations.1,9–11 The reported age in this group ranged from 45 classification as patients classified as PAN by ACR may have been to 78 years. All the lesions were tender firm breast mass with MPA by CHCC.31 In this study ANCA titres were elevated in the two reported size between 2 and 5 cm. except one case which presented patients with multi-focal cutaneous involvement and the systemic with a non-tender lump1 that was clinically suspicious for cancer; form as show in Table 1. Although there is no clear data concerning four cases were unilateral, whilst one was bilateral. The second case the ethnic background of PAN in general there have been some in this series presented with a 25 mm non-tender firm mass which epidemiological studies in the United States and Europe which was clinically suspicious mimicking cancer. This underscores that demonstrated prediction and genetic susceptibility in white and localized breast PAN may simulate malignancy, as in any other Caucasians.32,33 In this study, two patients were of afro-Caribbean organ. It should be part of the differential diagnosis of breast cancer origin and one of Asian origin, where this reflect geographical/ and to be subjected to triple assessment. The relationship of breast ethnic difference or due to environmental factors it is unclear and arteritis in general and breast cancer is unknown. There is only one more data is needed to verify the epidemiological basis of PAN. The case diagnosed with arteritis and focal fibrinoid necrosis as an differential diagnosis of vasculitis of the breast can be summarized incidental finding during histopathological examination of the with respect to clinical, pathological and radiological terms as breast tissue post-mastectomy for breast cancer in a patient with outlined in the following algorithm: known polymyalgia rheumatica.24 There are existing schemes for the classification of vasculitis which are widely used including American College of Rheuma- tology (ACR)25 and Chapel Hill Consensus Conference (CHCC).26 Six cases reported between 1968 and 1998 presented with mammary PAN in association with typical constitutional symptoms of PAN such as fatigue, headache, arthralgia, myalgia, and mild pyrexia.5,6,7,8 Two of them fulfilled the American College of Rheu- matology (ACR) criteria for classification as systemic PAN.5,7 Their age range was between 58 and 72 years, and they presented with either unilateral (2 cases) or bilateral (4 cases) indurated tender masses. It was not mentioned at which stage the breast became involved leaving us with insufficient data about the time course of breast manifestations in the systemic course of the disease. The third case in this series had suffered from severe systemic PAN for a year where she died within weeks after the breasts were bilat- erally clinically involved for the first time throughout long progression of the disease. Imaging modalities made a relatively poor contribution to establishing the diagnosis. Mammographic evaluation has not been reported in all of the previously reported case. Those reported revealed no evidence of malignancy, but in one case reported by Orbo,11 calcification of the arteries was a prominent feature of both breast X-rays, which was also observed in our third case showing extensive radial calcifications. Thin slice CT scan evaluation of the breast revealed areas of radial calcification but couldn’t prove to be superior over the mammogram in this particular case. In this rare presentation it is also worth noting the differential diagnosis of radial calcification which includes atherosclerosis of the older population, comedo mastitis and calciphylaxis.27,28 Calciphylaxis could be a cause of extensive calcification of vessels involving all organs.28 In the third case, this has been excluded by normal PTH and serum calcium. The radial calcifications of breast tissue would hence rather be a specific finding of severe PAN. The laboratory abnormalities in PAN reflect the degree of the inflammation and in systemic PAN according to the vascular impairment of specific organs.4 The lack of specific serological tests *Take home message and immunological abnormalities are characteristic of PAN.29 The ACR criteria for classification of PAN are of proven value to diagnose Recently, two systems have been proposed for the nomenclature the systemic form of the disease.25 They are unlikely to be reliable of primary vasculitides: the 1990 American College of Rheuma- in localized forms.30 Table 1 shows the serological and immuno- tology (ACR) classification criteria39 and the 1994 Chapel Hill logical abnormalities in all 3 patients. ANCA is a marker of systemic Consensus Conference (CHCC)40 definitions. The Chapel Hill defi- vasculitis, which might be positive in a few patients (10–20%) of nitions are biopsy dependent and surrogate features for the systemic PAN.2 In 1994 the CHCC recognized that histological data defining histology are required to allow their practical application. would not be available in some patients due to clinical conditions In concordance clinical examination and imaging investigation are that would preclude obtaining appropriate biopsy or due to non- fairly non-specific for the diagnosis of breast PAN which leads to representative histopathological features. This allowed the intro- a clinical dilemma. A high index of suspicious is required to reach duction of the concept of surrogate markers and ANCA but was not this difficult diagnosis which could be summarized in the used in the definitions in either the ACR or CHCC.25,26,31 There has following: 450 H.H. Khalil et al. / International Journal of Surgery 7 (2009) 446–450

1. Unexplained inflammatory necrotic pathological process 9. Levy A, Weinberger A, Mor C, Pinkhas J. Localized polyarteritis nodosa: involving the breast including the skin envelope. cases involving the lower extremities and the breast. Rheumatol Int 1986; 6:43–4. 2. Any patient presenting with breast lump and/or mastalgia with 10. Ng WF, Chow LTC, Lam PWY. Localized polyarteritis nodosa of breast – report of one of the following: two cases and a review of the literature. Histopathology 1993;23:535–9. a. Previous or concomitant presentation of inflammatory 11. Yamashina M, Wilson TK. A mammographic finding in focal polyarteritis nodosa. Br J Radiol 1985;58:91–2. cutaneous nodules including digital distal gangrene and or 12. Bonsib SM. Polyarteritis nodosa. Semin Diagn Pathol 2001;18(1):14–23. livedo reticularis. 13. Plaut A. Asymptomatic focal arteritis of the appendix, eighty-eight cases. Am J b. History of systemic PAN as classified by the ACR criteria. Pathol 1951;27:247. 14. Bohrod MG, Bodon GR. Isolated polyarteritis nodosa of the gallbladder. Am Surg c. Mammogram showing radial calcifications. 1970;36:681–5. 15. Crow J, McWhinney N. Isolated arteritis of the cervix uteri. Br J Obstet Gyneocol Finally the high index of suspicious could be confirmed by 1979;86:393–8. histopathological examination with or without positive immuno- 16. McLean NR, Burnett RA. Polyarteritis nodosa of epididymis. Urology 1983;21:70–1. logical and inflammatory laboratory test. 17. Rosai J. Arteritis in Ackerman’s Surgical pathology. 7th ed. St Louis: Mosby; 1989. In conclusion, PAN of the breast is rare; however involvement of pp. 1696–1699. the breast seems to be more frequent than that of other exocrine 18. Vavricka SR, Dirnhofer S, Degen L. Polyarteritis nodosa mimicking inflammatory bowel disease. Clin Gastroenterol Hepatol 2007;5(11). A22. glands. The main difficulty is to differentiate PAN of the breast from 19. Ito M, Sano K, Inaba H, Hotchi M. Localized necrotizing arteritis. A report of two mammary vasculitis in more general terms and from breast cancer. cases involving the gallbladder and pancreas. Arch Pathol Lab Med The differentiation from necrotizing fascitis and acutely infective 1991;115(8):780–3. 20. Schiess AV, Modglin FR. Polyarteritis nodosa involving the parotid gland. Report condition is of the essence to correctly treat this disorders which of a case. Oral Surg Oral Med Oral Pathol 1967;24(5):617–20. may rapidly lead to an extensive necrotic inflammatory process, 21. Ganza´lez-La Riviere O, de la Torre-Rendo´ n F, Hernańdez-Va´squez R, Arce- which may become life-threatening due to sepsis. Imaging and Salinas Ca. Polyarteritis nodosa mimicking prostatic cancer. J Rheumatol 2000;27(10):2504–6. laboratory examinations are of limited value and wherever the 22. Lindberg K. Ein Beitrag zur Kenntnis der Periarteritis nodosa. Acta Med Scan suspicion of PAN is raised mainly a sufficient tissue sample will lead 1931;76:183–225. to a histopathological diagnosis. Treatment is guided by the 23. Ruiter M. The so-called cutaneous type of periarteritis nodosa. Br J Dermatol 1958;70:102–6. presentation. Localized necrotic skin manifestation and necrosis of 24. Horne D, Crabtree T, Lewkonia R. Breast arteritis in polymyalgia rheumatica. mammary tissue are managed by surgical debridement and J Rheumatol 1987;14:613–5. management of the defect and immunosuppressive treatment 25. Lightfoot Jr RW, Michel BA, Block DA, et al. The American College of Rheuma- should only be commenced once a tissue diagnosis has confirmed tology 1990 criteria for the classification of polyarteritis nodosa. Arthritis Rhem 1990;33:1088–93. PAN. Non-tender firm masses of the breast should undergo triple 26. Jennette JC, Falk RJ, Andrany K, Bacon PA, Churg J, Gross WL, et al. Nomen- assessment by core needle biopsy. Confirmation of PAN should then clature of systemic vasculitis proposal of an international consensus confer- lead to an early referral to the rheumatology team for further ence. Arthritis Rheum 1994;37(2):187–92. 27. Millis RR, Davis R, Stacey AJ. The defection and the significance of calcifications evaluation, and immunosuppressive therapy as timely evaluation of in the breast, a radiological and pathological study. Br J Radiol 1976;49(577): the systemic impact of the disease is a key factor in the prognosis. 12–26. The role of excisional therapy for localized forms of PAN is not 28. Sancho J, Sitges-Sierra A. Metabolic complications for patients with secondary hyperparathyroidism. In: Clark OH, Duh Q, editors. Textbook of endocrine sufficiently understood. PAN is primarily a systemic disease. In the surgery. San Francisco: WB Saunders; 1997. perspective of the Breast Clinician it remains a rare but important 29. Daoud MS, Hutton KP, Gibson LE. Cutaneous periarteritis nodosa a Clinico- differential diagnosis with serious impact on patient outcome. pathological study of 79 cases. Br J Dermatol 1997;136:706–13. 30. Callen JP. Cutaneous vasculitis and other neutrophilic dermatoses. Curr Opin Rheumatol 1993;5:33–40. Conflicts of interest 31. Watts RA, Lane SE, Hanslik T, Hauser T, Hellmich B, Koldingsnes Mahr A, et al. None declared. Development and validation of a consensus methodology for the classification of the ANCA-associated vasculitides and Polyarteritis Nodosa for epidemio- Funding logical studies. Ann Rheum Dis 2007;66:222–7. 32. Scott DG, Watts RA. Systemic vasculitis: epidemiology, classification and None declared. environmental factors. Ann Rheum Dis 2000;59:161–3. Ethical approval 33. Mahr A, Guillevin L, Poissonnet M, Ayme´ S. Prevalances of polyarteritis nodosa, microscopic polyangiitis, and Churg-Strauss syndrome in a French urban None declared. multiethnic population in 2000: a capture–recapture estimate. Arthritis Rheum 2004;51:92–9. 34. Nizami S, Mohiuddin K, Azem M, Zafar H, Memon M. Necrotizing fasciitis of the References breast. Breast 2006;12:168–9. 35. Waterworth AS, Horgan K. Pyoderma gangrenosum an usual differential 1. Pappo I, Beglaibter N, Amir G. Mammary arteritis mimicking cancer. Eur J Surg diagnosis for acute infection. Breast 2004;13:250–3. 1992;158:191–3. 36. Susmano A, Roseman D, Haber MH. Giant cell arteritis of the breast. A unique 2. Diaz-Perez JL, De Lagrań ZM, Diaz-Ramo´ n JL, Winklemann RK. Cutaneous Poly- syndrome. Arch Intern Med 1990;150:1900–4. arteritis Nodosa. Semin Med Surg 2007;26(2):77–86. 37. Treu¨ b RM, Pericin M, Kohler E, et al. Necrotizing granulomatosis of the breast. 3. Orbo A, Bostad L. Vasculitis of the breast. Case report and literature review. Br J Dermatol 1997;137:799–803. APMIS 1989;97:1003–6. 38. Wargotz ES, Lefkowitz CM. Granulomatous angiopanniculitis of the breast. Hum 4. Treu¨ b RM, Scheidegger EP, Pericin M, Singh A, Hoffmann U, Sauvant G, et al. Pathol 1989;20:1084–8. Periarteritis Nodosa presenting as a breast lesion: report of a case and review of 39. Elsner B, Harper FB. Disseminated Wegener granulomatosis with breast literature. Br J Dermatol 1999;141:1117–21. involvement. Arch Pathol 1969;87:544–7. 5. Nishizawa T, Enomoto H, Hino T, et al. Vasculitis of the breast with thrombo- 40. Hatteland K, Kluge T. Mondor’s disease: a subcutaneous form of periarteritis cytopenia. J Rheumatol 1979;6:595–7. nodosa? Acta Chir Scand 1965;129:67–71. 6. McCarty DJ, Imbrigia J, Hung JH. Vasculitis of the breasts. Arthritis Rheum 41. Du¨ ndar SV, Sivri B, Go¨ko¨z A. Vasculitis of breast in Behcet’s disease. A case 1968;11:796–801. report. Angiology 1988;39:921–4. 7. Dega FJ, Hunder GG. Vasculitis of the breast. An Unusual manifestation of 42. Holland NW, McKnight K, Challa VR, Agudela CA. Lupus panniculitis (pro- polyarteritis. Arthritis Rheum 1974;17:973–6. fundus) involving the breast: report of 2 cases and review of literature. 8. Nielsen BB, Lorentzen M. Arteritis I brystet. Ugeskr Laeger 1985;147:2230–2. J Rheumatol 1995;22:344–6.