Teaching Case

It is extremely difficult to distinguish tuberculosis from other breast diseases and especially cancer. The improvement of MRI techniques especially by using contrast media, is expected to improve the diagnostic accuracy.

We present a 69 year old woman with a painful fixed lump growing rapidly at the upper outer quadrant of her left breast. The lump appeared one month prior to examination after a car accident and was gradually expanded in diameter. Our patient had no other complaints or clinical symptoms. She reported that when she was 22 years old she developed pulmonary tuberculosis manifested primarily as pleural effusion. Aspiration was treatment of choice. She was asymptomatic ever-since. Physical examination revealed a palpable painful cystic mass, adherent to surrounding tissues and slightly tender with lobulated surface, approximately 10cm in diameter. An ultrasonographic scan was then requested. The ultrasonographic characteristics of the mass were hypoechogenicity, limited compressibility and distal sound enhancement. Purulent (ehogenic) contents were visible inside the cyst, which was bordered by thick hyperechoic capsule. Skin was thickened (Fig.1a). Color Doppler flow imaging analysis was negative to show internal vascular signals. With Power Doppler blood, flow was indicated in the lesion’s capsule (Fig.1b). Behind major pectoralis muscle another hypoechoic cystic lesion was discovered (Fig.2a). Due to inflammation symptoms Doppler waveform parameters were considered as unreliable. Carcinoma, pyogenic abscess, or inflammation entered our differential diagnosis. Mammography was the next step towards correct diagnosis. Mammography revealed a large, dense, well defined lump measuring 10x8cm just behind involuted mammary gland, accompanied by thickening of the overlying skin. No calcification was found (Fig.3a-3b). In posterior-anterior chest x-ray the left lower border of the heart shadow was obliterated by a hazy opacity. Pleural effusion was present in the left costophrenic angle (Fig.4a). Lateral chest view showed a well defined mass lying in front of the heart. Anterior border of the heart shadow was obliterated. Lower zone pulmonary fibrosis possible due to old pulmonary infection was also present (Fig.4b). Computed tomography revealed a large mass extending from the upper to the lower part of the left breast. The mass was presented with thickened walls and internal septa. There was also a cystic pleural based lesion with calcified walls in contact with a calcified pleural plaque (Fig.5a-5b). Magnetic resonance scan of the thorax showed a large regularly bordered mass in the left breast, in close contact with anterior thoracic wall posteriorly, and subcutaneous fat anteriorly. A second smaller pleural mass was close to it. In the unenhanced T1 weighted image both masses were characterized by low signal intensity and smooth borders (Fig.6a). In the T2 weighted image both masses were characterized by extremely high and homogeneous signal intensity (Fig.6b). Those findings were suggestive of cysts but no contrast medium was injected to exclude other lesions with high water content such as mucinous carcinoma or phyllodes tumor. Serum protein electrophoresis results were normal. Fine needle aspiration cytology was considered with granulomatous suppurative lesion. Direct staining was negative mycobacterium of tuberculosis. The culture grew Mycobacterium tuberculosis sensitive to antituberculous drugs ( Isoniazid 0.2, Isoniazid 1.0, Streptomycin 5.0, Streptomycin 10.0, Rifampicin 20.0, Rifampicin 40.0, Ethambutol 2.0 and Ethambutol 4.0). Under general anesthesia a cystic mass extending to the thoracic wall was found. The cavity was drained and the wall was excised for histological and molecular biology examination. Histological examination (Fig.7a) showed granulomatous inflammatory lesion (double arrows) with Langehans-type giant cells (arrow) and focal caseous necrosis. Fibrosis was prominent. Surface of the segment was covered with granular tissue. Molecular biology with Multiplex Polymerase Chain Reaction (PCR) showed that the specimen was PCR negative for Mycobacterium Spp. The patient has commenced a three month course of quadruple anti-tuberculous chemotherapy with ethambutol, isoniazid, rifampicin, pyrazinamide and B6 vitamin therapy. For another three months she continued with pyrazinamide and B6 vitamin. Pleural cavity remains after surgical drainage of breast lesion three months after therapy (Fig. 8a).

Hippocrates named tuberculous lesions “pthisis” from the Greek word meaning “to decay”. Sir Astley Cooper was the first one who described a case of breast tuberculosis in 1829 and called it “scrofulous swelling of the bosom”. Later on, in 1952, McKeown an Wilkinson described two forms of breast tuberculosis, the primary in which breast infection is the only manifestation of the disease and the secondary one in which the patient had already tuberculosis diagnosed elsewhere. Primary form is an infection of the breast through abrasions or through the openings of ducts in the nipple. Secondary form is the result of reverse lymph flow in the axillary lymph nodes or it may be due to direct spread of the infection from intra-thoracic foci. Routes of infection include: 1. Hematogenous spread. 2. Lymphatic spread from intra-thoracic foci or from an intra-abdominal foci. 3. Direct extension from adjacent tissues or via abrasions of the skin. According to clinical, radiological and pathological appearance of the disease there are three types of breast tuberculosis: 1. Nodular tuberculosis which is characterized by a well-circumscribed, slowly growing, painless mass. Often the mass, getting larger, infiltrates the skin. At this point the tumor becomes painful, causing ulceration, and discharge from one or more sinus tracts. This course makes differentiation from carcinoma very difficult. 2. Diffuse type or disseminated tuberculous mastitis is characterized by multiple foci, which may lead to sinus formation. The overlying skin is thickened and painful ulcers may develop. Axillary lymph nodes are frequently infiltrated. 3. Sclerosing type, were excessive fibrosis is the dominant feature. It is slow-growing, and suppuration is rare. Clinically there is a hard, painless lump with nipple retraction. Clinical examination usually fails to differentiate carcinoma from tuberculosis. In mammography nodular tuberculosis reveals a dense, well-defined round or oval shadow, without the classic halo sign seen in fibroadenoma. Rarely infiltrating strands or skin thickening are present. Mammography is unreliable and differential diagnosis must be done from inflammatory or scirrous carcinoma. In the diffuse type breast is very dense, skin is thickened, painful and tense. Mammography shows a picture similar to that of an inflammatory carcinoma. In sclerosing type mammography reveals an homogeneous dense mass with fibrous septa and nipple retraction. Ultrasonography is useful in characterizing the ill defined densities shown on mammography in order to confirm the presence of fluid and exclude the presence of a solid mass . Magnetic Resonance Imaging (MRI) could be used in differentiation between scar granuloma and recurrence. Even with MRI, differentiation of a granuloma from an adenocarcinoma is difficult. Fine needle aspiration cytology may reveal suppuration or characteristics of a granulomatous lesion. Open biopsy is the most reliable examination. According to the literature an initial clinical diagnosis of breast tuberculosis is usually not made pre-operatively. This is because breast pain and mass are non-specific symptoms and imaging signs are unreliable. The most important inflammatory conditions encountered in the breast are: 1. Puerperal mastitis. 2. Non-pueperal mastitis which includes infected cyst, purulent mastitis with abscess formation and plasma cell mastitis. 3. Granulomatous mastitis which includes foreign body mastitis, specific diseases (as tuberculosis, sarcoidosis, syphylis, actinomycosis and typhus), parasitic diseases (as hydatid disease, cysticercosis, filariasis, schistosomiasis) and finally rare autoimmune diseases (as Wegener granulomatosis, giant cell arteritis, polyarteritis).