Introduction
•Granulomatous mastitis is a rare inflammatory breast disease that often presents as a breast mass and/or breast pain, and has a wide differential diagnosis including fungal or mycobacterial infection, autoimmune conditions such sarcoidosis , vasculitis, and rheumatoid arthritis, and secondary to infarction or fat necrosis, or in association with occult carcinoma
•Despite the wide differential, a large portion of cases remain unexplained, and thus the terminology “idiopathic granulomatous mastitis” is often used
•Idiopathic granulomatous mastitis remains a dilemma for clinical management, with response to empiric antibiotics alone generally poor, and surgical or immunomodulatory/steroid treatment with varying success
•Studies have documented a striking association of granulomatous lobular mastitis with Corynebacterium species, but an association of granulomatous mastitis with bacterial infection has not gained widespread recognition
•This study presents a retrospective single-institution experience of 35 patients with granulomatous mastitis, correlating cases with and without the cystic neutrophilic histologic pattern to gram stain/culture, clinical presentation, and outcome
Findings
•A pathology database was searched for breast biopsies showing granulomatous inflammation. Thencorresponding slides were evaluated for the presence or absence ofthe cystic neutrophilic granulomatous (CNGM), defined as a clear space surrounded by a rim of neutrophils, surrounded by granulomatous inflammation
•55 breast specimens with granulomatous inflammation from 35 patients were identified, and then divided into CNGM (31 specimens from 19 patients) vs those with granulomatous inflammation but non-CNGM (24 specimens from 16 patients)
•Patients with CNGM were more likely to be of Hispanic ethnicity, born outside the US/Canada, of younger age, with shorter interval since last childbirth, and never smokers as compared to non-CNGM
•16/19 (84%) of CNGM patients had gram-positive rods seen on histochemical stains, while non of the non-CNGM group had gram-positive rods identified (0/16).
•Of the available culture and molecular microbiology results from the CNGM group, one patient had culture positive for Corynebacterium species, one had growth of C minutissimum, one had growth of 1+Proprionobacterium, while another was reported as growth of “2+skin flora.” Molecular study identified C kroppenstedtii in an additional patient
•Two CNGM cases were found with >30 IgG4 + plasma cells/hpf, suggesting that the presence of IgG4+ plasma cells is unlikely to be specific for IgG4-related sclerosing disease in the breast
•In patients with available followup from both groups, granulomatous breast disease was treated with surgical, (empiric) antimicrobial, and/or immunomodulatory (steroids) modalities, and was often refractory to initial treatment, with over 30% having multiple surgical pathology specimens, and many with additional incision and drainage procedures. Clinical followup data were limited, but where available, patients often experienced a protracted course with eventual resolution (over 6-50 months)
Conclusions
•This single-center retrospective series demonstrates a significant association of the CNGM histologic pattern and the presence of Gram-positive rods in granulomatous mastitis, representing the largest study to date.
•These results provide increasing evidence of a potential role of Corynebacterium species in a specific subset of patients with granulomatous mastitis (54% of granulomatous mastitis had the CNGM pattern in their study)
•Organisms localize to the clear microcystic space in the center of the neutrophilic granulomatous inflammation and are often present in a single focus on the slide, in very small numbers; Thus, pathologists should carefully analyze biopsies showing granulomatous mastitis for fungal, mycobacterial and bacterial organisms, with special attention to the microcystic spaces of CNGM on Gram stain
•Further studies are needed to refine treatment
Introduction
•Gynecomastia, defined as breast enlargement in men, represents the most common abnormality of the male breast
•Although particularly seen at puberty and aging, it can be seen during all stages of life
•It is believed to be the result of hormonal imbalance, although it can also occur in normal adult males as well as those with diseases that directly or indirectly lead to elevated estrogen exposure (eg liver disease, testicular tumors)
•Histologically, both glandular and stromal proliferation is seen
•It is a common clinical indication for surgical excision in males. While usually a routine specimen, on occasion an atypical ductal proliferation is seen. This situation is often disconcerting for pathologists, perhaps due to its infrequent occurrence, the difficulty distinguishing between florid usual ductal hyperplasia (of gynecomastia), and the lack of understanding of the clinical ramifications
•The purpose of this study was to study ADH arising in gynecomastia not only from a clinicopathological perspective, but also to determine the utility of immunostains in distinguishing ADH from the usual proliferative changes associated with gynecomastia
Findings
•Cases of gynecomastia from an academic hospital with a large breast consultation service were searched for
•17 in-house hospital cases of ADH arising in gynecomastia out of 317 total gynecomastia cases (5.4%) were found; a total of 25 cases of ADH arising in gynecomastia with sufficient material for this study were found
•9 cases of DCIS arising in gynecomastia and 36 cases of gynecomastia with UDH were included for comparison
•The following definitions were used:
•Atypical ductal hyperplasia: ductal proliferations with some, but not all, the morphological features (cytological and architectural atypia) characteristic of DCIS. Cytologically, small monotonous cells, and at least partially arranged architecturally with growth patterns including cribriform, micropapillary, and solid
•Usual ductal hyperplasia: ductal proliferation comprised of heterogeneous overlapping cells varying in size, shape, and orientation with poorly defined cell borders. Architecturally, patterns could include solid, cribriform-like/fenestrated, or micropapillary with irregular lumens or stretched bridge formation
•Active gynecomastia: presence of glandular proliferation with predominantly micropapillary UDH and adjacent stromal edema
•Inactive gynecomastia: little to no epithelial hyperplasia and the dominant feature was stromal fibrosis
•Clinicopathologic features are outlined in Table 1. Amongst the clinical findings:
•Average age 42 years, with a distinct peak 23-28 years. Those with DCIS were older, with average age 59 years (range 44-77)
•Most patients presented as ‘mass’ (11 cases) or ‘gynecomastia’ (12 cases); the rest presented with calcifications on mammography
•20% of ADH cases were bilateral versus 1/3 of UDH cases
•Histologically, findings included the following:
•Nearly one half of ADH cases showed micropapillary pattern alone or in combination with cribriform growth (see Table 1) and in contrast all cases of UDH showed a micropapillary appearance. DCIS were predominantly cribriform (5 of 9 cases) or and/or micropapillary (5 of 9)
•The degree of nuclear variation was discriminatory between ADH and UDH. ADH showed very little variation (monotonous) (22 of 25 cases), while the vast majority of UDH showed moderate/marked variation (polymorphous)
•There was a trend of decreasing nuclear size with increasing degree of cytologic atypia
•Mitoses were seen in all, but most commonly in DCIS (67%)
•Increasing proportions of lesional calcifications were seen with increasing cytologic atypia
•Most ADH cases showed a background of inactive gynecomastia while UDH showed mostly active gynecomastia
•Immunohistochemical findings are outlined in Table 2. Amongst the findings:
•Using an ‘H-score’ for ER determined by multiplying the percentage of lesional cells staining at various intensities (none=0, weak=1, moderate=2, strong=3), they found that ADH showed high ER expression compared to UDH (H score >270 in 88% and 14%, respectively)
•CK5/6 luminal epithelial staining was decreased in ADH (68%) versus UDH (11%)
Conclusions
•Finding ADH in the background of gynecomastia is quite infrequent (only in about 0.4-7%)
•ADH could be discerned from UDH with reasonable consistency due to differences of several features, including that ADH showed typically a cribriform pattern with similarly sized cells to those of normal ductal cells and little nuclear variation (cellular monotony) while in contrast UDH was composed typically of polymorphous, relatively larger cells with micropapillary growth
•More ADH cases (68%) showed CK5/6 staining in <10% of luminal cells as compared to UDH (11%), and more cases of ADH showed ER positivity versus UDH, and thus the authors found that these combination of staining patterns were consistent enough to help pathologists classify most epithelial proliferations in the male breast