Red flags for the differential diagnosis of granulomatous mastitis: a case report

The case was conducted by the Medical Outreach Clinic (MOC) of McLaren Macomb Hospital. MOC is a custom-built 40-foot motorhome that is a doctor’s office on wheels. It visits low-income suburbs of Detroit (MI), providing comprehensive and ongoing medical care for uninsured patients. Physician faculty, family medicine resident physicians, nurses, pharmacists, medical assistants, and medical and pharmacist students deliver wide-ranging care to those in need. The MOC staff offers a full spectrum of health care, including screenings, immunizations, acute care management, and treatment of chronic diseases, while also providing preliminary care for devastating health issues such as cancer. All medical treatments and procedures are at no cost to the patient. Medication, laboratory testing, and imaging are funded by the McLaren Macomb Foundation, the charitable arm of McLaren Macomb Hospital. If the MOC cannot meet a patient’s needs, they are referred to one of McLaren Macomb’s resident clinics or another McLaren Macomb physician.

Since the clinical presentation of GM is consistent with infectious mastitis, most patients receive antibiotics at the beginning of their treatment. As the infection is presumed based on physical exam findings, antibiotic therapy is usually initiated without microbiological proof. GM is by definition a sterile inflammatory disease; therefore, antibiotic therapy usually fails [8, 9]. This would explain the lack of success with the initial pharmacotherapy.

Mastitis affects 3–20% of lactating women. Although mastitis can occur at any time during lactation, the majority of cases occur in the first 6 weeks [10]. The patient was not breastfeeding, so the inflammatory and infectious diseases resulting from lactation, usually observed in mastitis, were ruled out by our team at MOC. Also, it was remarkable that the patient reported a similar episode in her left breast roughly 5 years ago, prior to childbearing, which resolved spontaneously without medical attention. This fact lowered the suspicion of a tumor. However, the BI-RADS grade of 5 raised our concern for breast cancer. Because of the rarity of the disease and the lack of consensus guidelines for GM, the tumor board meeting was valuable for its discussion of further options for treatments and diagnostic modalities.

In more than 50% of reported cases, the initial differential diagnosis of GM is malignancy or suspicion of breast carcinoma, and 15% of patients may present with regional lymphadenopathy [11], which was not a clinical manifestation in our current case.

The literature points out that the presence of peau d’orange may progress to ulceration; its presence is pathognomonic of cancer. [12] As it mimics breast cancer, GM is diagnosed by breast biopsy [7]. At the patient’s first visit to MOC, the absence of breast peau d’orange was documented, indicating that her condition might not be cancerous. In addition, the absence of carcinoma was confirmed by needle biopsy; however, because of the intrinsic limitations of this procedure, the severity of the clinical presentation, and the imaging reports, we concluded that a more definitive surgical procedure was necessary. The incisional biopsy confirmed the inflammatory process, compatible with cellulitic mastitis. GM is often initially misdiagnosed as cellulitis or furunculosis, and patients with GM may develop cellulitis, abscesses, and open draining sinuses [13, 14].

At this point, GM is our confirmed diagnosis. This reasoning is in accord with a multidisciplinary investigation conducted in Indiana reporting 12 times higher prevalence of idiopathic GM among Hispanic women immigrants from Central America than among non-Hispanic white women [15]. However, breast tuberculosis was also considered as a differential diagnosis in our patient, since she came from an endemic area [15] and presented with clinically suspicious breast lumps. Indeed, TB of the breast is an uncommon disease that is often difficult to differentiate from cancer of the breast when it presents as a lump [16]. The negative tests ruled out breast TB.

The optimal management of GM remains controversial [17, 18]. The main concern is the risk of recurrence observed for the different therapeutic approaches [19]. Antibiotics present the lowest efficacy in the treatment of mastitis in the absence of bacterial infection, with improvement rates ranging from 6 to 21% [20]. By comparison, corticosteroid therapy has a success rate of between 66 and 72%. In a metanalysis by Lei et al. [21], a pooled recurrence rate of 20% was reported for oral steroid therapy. Surgery alone or in combination with corticosteroids seems to have the lowest recurrence, with rates of 6.8 and 4%, respectively.

There are limited data in the literature and a lack of consensus on the use of antibiotic therapy for the treatment of GM [14]. Although the results were negative for a sample from abscess drainage, we decided to keep her on the empirical conservative therapeutic approach with TMP/SMX, following this urgent event. The antibiotic combination with an NSAID (meloxicam) had previously proven efficacious in controlling her pain. However, the patient developed glossitis, which was attributed to sulfonamide drug hypersensitivity reaction, and led us to change TMP/SMX to moxifloxacin. The drug reaction was confirmed by the absence of anemia or oral candidiasis, which are other common causes for glossitis [22], and its prompt regression once TMP/SMX was stopped.

The literature supports empirical therapy with antibiotics, anti-inflammatory agents, and surgery [14, 20, 21]. Although our patient’s responses were not optimal, the combination of surgical procedures, corticosteroids (methylprednisolone or prednisone), and antibiotics (the fluoroquinolone moxifloxacin was used) resulted in overall clinical improvement.