Case 7 -

Granulomatous Mastitis Salam Al-Sam MBBS, PhD, FRCPath The Princess Alexandra Hospital NHS Trust Hamstel Road, Harlow, Essex, CM20 1QX, UK

Clinical Presentation 52 year-old woman presented with a unilateral breast mass. Mammography demonstrated an ill-defined opacity. Physical examination revealed a firm/hard mass, 3 cm in size (P5 R3). Fine Needle Aspiration was performed and reported as C5 malignant. Mastectomy and axillary sampling was performed based on high clinical and cytological suspicion. Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Diagnosis: Granulomatous Mastitis Discussion: Granulomatous lobular mastitis is a rare disease primarily affecting young women during reproductive life. This entity was first described by Kessler and Wolloch in 1972 and further elaborated by Cohen in 1977. About 60 cases have been described in the English literature. Clinically, the condition may closely mimic carcinoma, and cytological and histopathological appearance, if not recognized as granulomatous disease may be misinterpreted as a carcinoma, often with disastrous consequences. The present case demonstrates a false positive diagnosis of an entirely benign condition which resulted in mastectomy and axillary clearance. Clinical Features: The age range was 30-50, the present case fell outside this range, 52 years of age. In few patients, involvement of the contralateral breast was noted. In a significant number of cases, the clinical impression prior to surgery was that of a malignant neoplasm. All of the patients reported by Kfoury & Al bhalal presented with a painful mass in the affected breast. Few patients also had draining sinuses in the skin. There was a history of fever in a minority group of patients. Pathological Finding: Classical histological features of granulomatous lobular mastitis are represented by non-caseating granulomas. The granulomas were formed by epithelioid cells and giant cells, more commonly of Langhans type. Microabscess formation was not seen.. All special stains for microoganisms were negative. Culture results were negative in all cases submitted for culture. A predominance of T cells was noted in the infiltrate in the half the cases. Cytological features: Aspirated material is usually moderately cellular and consisted of epithelioid histiocytes, lymphocytes, plasma cells, neutrophils and multinucleated Langhans-type giant cells. However, no cheesy, necrotic material in the background was noted. The findings were incorrectly interpreted as carcinoma cells in this case. Due to high clinical suspicion of malignancy, the surgeon proceeded to mastectomy and axillary clearance. Smears stained with Giemsa showed numerous degenerating and viable neutrophils, epithelioid granulomas, clusters of foamy histiocytes and scattered multinucleated giant cells. Fragments of small blood vessels surrounded by leucocytes were often present and in a few cases, multinucleated giant cells were seen in juxtaposition to the vessels. No acid fast bacilli or fungi were identified in smears stained with Ziehl Neelsen and Grocott Methenamine Silver stains. FNA cytology remains one of the important and first line measures to investigate breast disease. The case demonstrate the importance of considering all findings followed by open discussion at MDT meeting before major surgery is contemplated. The cytological diagnosis of GM is difficult because the features overlap with other aetiologies, including tuberculosis. Specific features are absent. The absence of necrosis and a predominantly neutrophilic infiltrate in the background favour a diagnosis of Granulomatous Mastitis (GM). This diagnosis should also be considered when abundant epithelioid histiocytes are seen in smears, even in the absence of granulomas. However, the definitive diagnosis of GM depends on histology from fine needle biopsies and negative microbiological investigations. Granulomatous mastitis is an uncommon breast lesion that is well known for its worrisome clinical presentation as a hard breast lump, particularly in younger women. The aetiology of most cases is idiopathic, to be distinguished from the rare specific granulomatous conditions including tuberculosis, sarcoidosis, and Wegener's granulomatosis. Clinically and radiologically, GM is difficult to distinguish from carcinoma. The disease usually occurs in women of reproductive age, and may be associated with lactation or may occur in the postpartum period. The course of the disease is characterised by slow resolution, which is often punctuated by abscess or discharging sinus formation, particularly after large core needle biopsies. A variety of lesions may be characterized by a granulomatous inflammation in the breast. Granulomas may be due to an infectious process or may be part of a systemic disease such as Wegener's granulomatosis, sarcoidosis, etc. Occasionally, granulomas may be seen in association with breast carcinoma including lymph nodes draining breast carcinoma. The diagnosis of granulomatous lobular mastitis remains a diagnosis of exclusion and should be entertained when all other known causes of granulomatous inflammation have been excluded. Tuberculous mastitis usually shows caseating granulomas, which are not necessarily centrilobular. Tuberculous mastitis may be part of a systemic disease or may be the only manifestation of tuberculosis. Positive cultures for acid-fast bacilli or demonstration of acid-fast bacilli in sections would confirm the diagnosis. This was not the case in this patients. Other bacterial infections, such as brucellosis, have also been reported as a cause of granulomatous mastitis. [9] Bacterial cultures of the lesions and positive serology may help to establish the diagnosis. Fungal infections would give necrotizing granulomatous mastitis The diagnosis of granulomatous lobular mastitis should be seriously questioned in immunocompromised patients, since these patients are prone to fungal infections, either as part of systemic disease or localized to the breast. Immunocompetent patients might have fungal infection of the breast (i.e., histoplasma, cryptococcus). Parasitic infections (i.e., Wuchereria, taenia, solium and filaria) have also been reported as rare causes of granulomatous lobular mastitis. The etiology of granulomatous lobular mastitis is not known. Its association to lactation and pregnancy, its occurrence in young parous women, and its similarity to autoimmune thyroiditis favor an autoimmune process. However, this hypothesis has been challenged by some. FNA of granulomatous mastitis must be differentiated from breast carcinoma to avoid unnecessary surgery. This can be achieved by; considering the possibility Comparing the findings with known breast carcinoma. The features of GM do not fit with those of breast carcinoma. Presence of giant cells should alert the pathologist for the possibility. Presence of spindle cells does not exclude rare types of breast carcinoma such as metaplastic carcinoma. The cytoplasm of epithelioid histeocytes is fainter and not as uniform as that of a malignant epithelial cell. References Cohen C. Granulomatous mastitis. Am Med J 1977;52:14-6. Kent L, Band Tang PH. Postlactational tumoral granulomatous mastitis; a localized immune phenomenon. Am J Surg 1979;138:326-9. Carmatt HL, Ramsey-Stewart G. Granulomatous mastitis. Med J of Australia 1981;1:356-9. Davies JD, Burton PA. Postpartum lobular granulomatous mastitis. J Clin Path 1983;36:363. Fletcher MA, Grath-Riddel RH, Talbot IC. Granulomatous mastitis: a report of seven cases. J Clin Path 1982;35:941-5. Bassler R, Birke F. Histopathology of tumour-associated sarcoid-like stromal reaction in breast cancer. Virchows Arch (A) 1988;412:231-9. Jayaram G. Cytomorphology of tuberculous mastitis. Acta Cytologica 1985;29:974-8. Banerjee A, Green B, Burke M. Tuberculous and granulomatous mastitis. Practitioner 1989;233:754-6. Gilbert P, Holst F, Rossbach J, Pauli HK. Durch Brucellose verursachte granulomatose non-puerperale Mastitis - eine Kasuistik. Geburtshilfe Frauenheilkd 1991;51:747-9. Osborne BM. Granulomatous mastitis caused by histoplasma and mimicking inflammatory breast carcinoma. Hum Path 1989;20:47-52. Houn HD, Granger JK. Granulomatous mastitis secondary to histoplasmosis. Diag Cyto 1991;17:282-5. Rowe PH. Granulomatous mastitis associated with a prolactinoma. British J Clin Practice 1984;38:32-4. Axelsen RA, Reasbeck P. Granulomatous lobular mastitis: report of a case with previously undescribed histopathological abnormalities. Path 1988;20:383-9. Adams DH, Hubscher SG, Scott DGI. Granulomatous mastitis - a rare cause of erythema nodosum. Postgraduate Medical J 1987;63:581-2. Going JJ, Anderson TJ, Wilkinson S, Chetty U. Granulomatous mastitis. J Clin Path 40(5):535-40, 1987. Mcansh S, Greenberg M, Barraclough B, Pacey F. Fine-needle aspiration cytology of granulomatous mastitis. Acta Cytologica 34(1):38-42, 1990. Kumarasinghe MP, Amarasekera LR. Granulomatous mastitis - a well-defined entity. Ceylon Med J 1990;35:143-5. Jorgensen MB, Nielsen DM. Diagnosis and treatment of granulomatous mastitis. Am J Med 1992;93:97-117. Donn MD, Rebbeck P, Wilson C, Andgilks CB. Idiopathic granulomatous mastitis. Arch Path Lab Med 1994;118:822-5. Galea MH, Robertson JFR, Ellis IO, Elston CWW, Blaney RW. Granulomatous lobular mastitis. Austr NZ J Surg 1989;59:547-50. Hala Kfoury, MD; Lulu Al Bhlal, MD granulomatous lobular mastitis:a clinicopathological study of 12 cases Ann Saudi Med 1997;17(1):43-46. Fine needle aspiration cytology of granulomatous mastitis G M K Tse1, C S P Poon4, B K B Law2, L M Pang3, W C W Chu3 and T K F Ma5Journal of Clinical Pathology 2003;56:519-521 Idiopathic Granulomatous Mastitis: Case Report and Review of the Literature Shigeru Imoto1, Tomoki Kitaya2, Tetsuro Kodama3, Takahiro Hasebe4 and Kiyoshi Mukai4 Japanese Journal of Clinical Oncology 1997, Vol.27, no.4, Pages 274-277 A 36-Year-Old Woman With a Unilateral Breast MassShakira Payne, MD; Steve Kim, MD; Kasturi Das, MD; Neena Mirani, MDArchives of Pathology and Laboratory Medicine: Vol. 130, No. 1, pp. e1-e2. Granulomatous mastitis: Evaluation of 83 cases from University of Malaya Medical Centre Azna WH, Jayaram G, Yip CH Biomed Imaging Interv J 2005; 1(1):e6-2 doi: 10.2349/biij.1.1.e6-2 Cytologic features of granulomatous mastitis. Report of a case with fine needle aspiration cytology and immunocytochemical findings. Kobayashi TK, Sugihara H, Kato M, Watanabe S. Acta Cytologica1998 May-Jun;42(3):716-20