GM 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.
With the increasing use of FNAC as the initial investigation for breast lesions, more cases will probably be encountered by the cytopathologist, necessitating an increased awareness of this disease entity.
Among the only three large series describing the FNAC features of GM in the literature, the usefulness of FNAC in GM has been debated, with some authors confirming the useful role of FNAC,10,11
whereas others have concluded that the various causes of granulomatous inflammation cannot be confidently differentiated by FNAC.9
The diagnostic cytological criteria for GM remain poorly defined, and the common features that have been evaluated include necrosis, giant cells, epithelioid histiocytes, granulomas, and neutrophils present in the background.
In our study, most cases showed single epithelioid histiocytes present within the smears and this should alert the cytopathologist to the possibility of a granulomatous inflammation. The appearance of these histiocytes was distinct, with reniform to plump nuclei and a moderate to abundant pale pink cytoplasm. This appears to be a common feature, having been reported in all cases of GM in the literature.9–12,15–18
Most studies reported aggregates of epithelioid histiocytes or granulation tissue fragments, probably representing granulomas which are characteristic of GM. In our series, granulomas were present in only half of the cases, and their presence is therefore suggestive but not pathognomonic for GM.
Take home messages
- The cytological diagnosis of granulomatous mastitis (GM) is difficult because the features overlap with other aetiologies, including tuberculosis, and there are no specific features
- The absence of necrosis and a predominantly neutrophilic infiltrate in the background favour a diagnosis of GM
- A diagnosis of GM should also be considered when high numbers of epithelioid histiocytes are seen in smears, even in the absence of granulomas
- The definitive diagnosis of GM relies on histology of fine needle biopsies and negative microbiological investigations
The presence of other inflammatory cells was more variable. In our series, there was an overwhelming predominance of neutrophils over lymphocytes. This finding was similar to that of another study of nine cases, which demonstrated moderate to abundant numbers of neutrophils in the FNAC preparations.10
Most other reports have described a mixed inflammatory cell infiltrate.
Another characteristic FNAC feature was the absence of caseous necrosis in the background. This is particularly important in the differentiation from an infective cause of granulomatous inflammation.
“In our series, granulomas were present in only half of the cases, and their presence is therefore suggestive but not pathognomonic for granulomatous mastitis”
The single most important differential diagnosis of GM is tuberculosis, which remains endemic in many regions. Treating tuberculosis with steroids would aggravate the infection, whereas giving unnecessary antituberculosis drugs may cause numerous side effects. In tuberculosis mastitis, the common features include epithelioid histiocytes, Langhan’s giant cells, granulomas, and caseous necrosis. The presence of neutrophils is not a common feature unless there is concomitant suppuration. Thus, there is considerable overlap because epithelioid histiocytes, giant cells, and granulomas are common to both entities. The presence of predominantly neutrophils in the background, and the lack of caseous necrosis may favour a diagnosis of GM rather than tuberculosis. Other differential diagnoses are rare specific causes of granulomatous inflammation, including fungal infection or non-infectious causes, such as sarcoidosis or Wegener’s granulomatosis. Because GM is essentially a diagnosis of exclusion, all causes of granulomatous inflammation must be actively excluded. An FNAC diagnosis of GM cannot be made easily, and a confident diagnosis may require histological samples, negative microbiological investigations, and clinical correlation.
In our study, we found that the most common cytological feature of GM was the presence of epithelioid histiocytes, followed by the presence of predominantly neutrophils in the background, multinucleated giant cells, and granulomas. The absence of caseation was also important. Although there is considerable overlap with tuberculosis, the absence of caseation and the presence of mostly neutrophils may favour a non-infective aetiology. It is also of interest to note that the presence of granulomas and giant cells tends to correlate with the cellularity of the epithelioid histiocytes in the FNAC preparation. Thus, in a suboptimal or low cellularity aspirate, granulomas or giant cells may be absent, and the cytopathologist should be alerted to the possibility of GM if epithelioid histiocytes are seen.