Cystic Neutrophilic Granulomatous Mastitis Research Articles

Idiopathic granulomatous mastitis: a 5-year retrospective review of cases in a tertiary centre in Dublin, Ireland

AimsIdiopathic granulomatous mastitis (IGM) is a rare, benign, inflammatory breast disorder of unknown aetiology usually affecting women of reproductive age. It classically presents as a unilateral painful breast mass. It...

Inflammatory Lesions of the Breast.

Inflammatory lesions of the breast are rare but not infrequently pose problems both clinically and morphologically, particularly on needle core biopsies. These lesions range from acute inflammatory conditions to chronic lymphoplasmacytic and lymphohistiocytic to granulomatous inflammatory diseases. To provide a comprehensive overview of inflammatory lesions of the breast, with etiopathogenesis and clinical, radiologic, and pathologic features as well as differential diagnostic considerations, clinical management, and prognosis. The existing literature in the English language, including original research articles and review articles describing inflammatory lesions of the breast. Inflammatory lesions of the breast are characterized by a wide variety of clinical, radiologic, and morphologic features. The histopathologic differential diagnosis often includes a neoplastic process requiring ancillary studies and correlation with clinical and radiologic findings. Although most specimens display nonspecific findings precluding a definitive pathologic diagnosis, pathologists have a unique opportunity to play a crucial role in identifying key histologic features suggestive of certain entities, such as cystic neutrophilic granulomatous mastitis, immunoglobulin (Ig) G4 mastitis, or squamous metaplasia of lactiferous ducts, in the right clinical and radiologic context, and thereby guiding optimal and timely clinical management. The information presented herein will be helpful to practicing anatomic pathologists and pathology trainees in becoming more familiar with specific morphologic features and overcoming differential diagnostic challenges related to pathology reporting of inflammatory lesions of the breast.

Cystic neutrophilic granulomatous mastitis: sensitivity and specificity of 16s rRNA and Sanger sequencing for Corynebacterium spp

AimsCystic neutrophilic granulomatous mastitis (CNGM) is a subtype of granulomatous mastitis (GM) associated with Corynebacterium spp infection. We aimed to analyse the prevalence of Corynebacteria in CNGM and non-CNGM cases.MethodsBreast...

Cystic neutrophilic granulomatous mastitis: A study from tertiary care center in Kashmir

Cystic neutrophilic granulomatous mastitis: A study from tertiary care center in Kashmir

Role of conservative therapy prior to surgery in xanthogranulomatous mastitis: a case report

Xanthogranulomatous mastitis is an extremely rare condition that is characterised by the infiltration of the breast parenchyma by foamy histiocytes. There have been only 26 reported cases amongst 10 publications. The clinical and radiological presentation of xanthogranulomatous mastitis often causes diagnostic confusion due to its similarity to breast cancer and other forms of chronic inflammatory mastitis. A histological diagnosis is often required either by core needle biopsy or excisional biopsy. Upon review of the literature, surgical excision was the most predominant mode of management. We present a case of xanthogranulomatous mastitis in a 40-year-old female who presented with clinical and radiological features of breast malignancy. This was a significantly large mass with a dimension of 90.7 mm by 36.4 mm, which if surgically excised, would have led to permanent cosmetic changes. Multiple core needle biopsies were completed to consider other differentials of histiocytic lesions including cystic neutrophilic granulomatous mastitis, histiocytoid lobular breast carcinoma, Rosai-Dorfman disease and Erdheim-Chester disease. Clinical improvement was noted with reduction in size from prolonged antibiotic therapy suggesting an initial conservative approach in the management of xanthogranulomatous mastitis. By contributing our experience with xanthogranulomatous mastitis, we also present a review of literature on its aetiology, clinical features, and management of this pathology.

Idiopathic granulomatous mastitis and cystic neutrophilic granulomatous mastitis: two sides of the same coin or distinct entities?

Idiopathic granulomatous mastitis (IGM) is a benign mimic of breast carcinomas. It is defined histologically by the presence of granulomas and inflammation. The closely related cystic neutrophilic granulomatous mastitis (CNGM) shows lipogranulomas, with a reported association with corynebacteria. A large cohort of IGM was reviewed to compare clinical, microbiological and histological features between non-CNGM IGM and CNGM. Cases of IGM were reviewed for histological parameters including the presence of lipogranulomas and composition of inflammatory cells. Clinical data were obtained through hospital records. The cohort included 79 cases, including 51 non-CNGM IGM and 28 CNGM. Comparing non-CNGM IGM and CNGM, there were no differences in clinical or demographical data, other than a younger age of presentation (36.2 vs 41.5 years, p=0.012) for CNGM. Most IGM resolved within the follow-up period (n=57/64, 89.1%), with similar outcomes regardless of treatment (p>0.05). In CNGM, there were more infiltrates of neutrophils (p=0.001), histiocytes (p=0.047), and multinucleated giant cells (p=0.006), but less lymphocytes (p=0.008). Corynebacteria was cultured in two (25%) cases of CNGM, and one non-CNGM IGM (14.3%). Gram-positive bacilli were identified in two cases of CNGM. 'Early' lipogranulomas were observed closely associated to inflamed ducts in three cases of CNGM. Apart from age, there was no distinct clinical or microbiological feature for CNGM. These findings do not support CNGM as a distinct entity. Rather, CNGM-pattern may represent a continuum of IGM, possibly age-related and attributable to ductal inflammation and cystic changes in the breast parenchyma.

Cystic Neutrophilic Granulomatous Mastitis

Granulomatous lobular mastitis (GLM) is an infrequent inflammatory breast disease, which can simulate malignancy on the basis of clinical and imaging features. It is typically found in parous or lactating women. The differential diagnosis of granulomatous mastitis includes infections caused by bacterial, fungal or mycobacterial agents, and autoimmune disorders like rheumatoid arthritis, sarcoidosis, giant cell vasculitis, and granulomatosis with polyangiitis. Cystic neutrophilic granulomatous mastitis (CNGM) is a sporadic sub-type of GLM that can be linked with infection with Gram-positive bacilli, specifically, Corynebacterium. It is characterised by lipogranulomas that comprise of "cystic" spaces lined by neutrophils which may contain Gram-positive rod-shaped bacteria. The majority of cases of GLM are still "idiopathic" as this pattern of inflammation still remains a mystery. We herein report three cases of CNGM and review the relevant literature. Key Words: Granulomatous mastitis, Corynebacterium, Gram-positive rods, Inflammatory breast disease, Cystic neutrophilic granulomatous mastitis.

Further Characterization of Clinicopathologic Features of Cystic Neutrophilic Granulomatous Mastitis

Clinical and demographic features of cystic neutrophilic granulomatous mastitis (CNGM) have not been fully explored due to the rarity of the disease. Herein we studied clinicopathologic characteristics of CNGM in a sizable hospital-based cohort. A case-control study was performed to compare clinicopathologic characteristics between patients with CNGM and granulomatous mastitis other than CNGM and between CNGM with and without Corynebacterium identification. Cases of CNGM (n = 31) and non-CNGM (n = 30) were included. Compared with the non-CNGM group, patients with CNGM were statistically significantly younger (median age: 38 vs 43 years), were less likely to be smokers (9% vs 40%), were more likely to have a painful lesion (97% vs 77%) or a larger mass-like lesion (median size: 4.6 vs 1.9 cm), and tended to have a higher Breast Imaging Reporting and Data System score in radiologic studies (score ≥4: 81% vs 53%), positive Corynebacterium identification results (36% vs 0%), and a longer resolving time (12 vs 6 months; all P values for above comparisons <.05). Among CNGM cases, patients with and without Corynebacterium identification shared a similar clinicopathologic profile. Our study further demonstrated that CNGM is a unique infectious disease with distinct clinicopathologic features.

Idiopathic Granulomatous Mastitis: Diagnosis and Histopathologic Features, A Review

Background: Idiopathic granulomatous mastitis (IGM) is a rare benign inflammatory breast condition, mostly affecting women of reproductive age within a few years of pregnancy. Due to diverse clinical and radiologic features, IGM can mimic a vast spectrum of breast conditions. Therefore, histological findings are one of the most essential bases of diagnosis. Methods: A literature search was performed to review the characteristics of IGM with an emphasis on histopathological features in English sources from 2010 to 2022. The key words used for PubMed database search were “breast”, “granulomatous mastitis”, “histopathology”, and “pathology.” Results: In total, 192 articles were retrieved, from which 38 most relevant manuscripts were selected for this review article. Conclusion: The diagnosis of IGM depends on clinical, radiologic, and pathologic findings. Palpable mass is the most frequent complaint. An irregular hypoechoic mass with varying degrees of posterior phenomena is the most common sonographic finding. Histologically, IGM is characterized by a non-caseating lobulocentric granulomatous inflammation; composed of tight aggregates of epithelioid histiocytes with or without multinucleated giant cells. At times, the presence of cystic empty vacuoles lined by neutrophils is noted that is commonly associated with cystic neutrophilic granulomatous mastitis (CNGM), a variant of IGM. Atypical findings for IGM includes: The presence of atypia and/or malignancy, caseous necrosis, marked eosinophilic infiltration, absence of granulomatous inflammation, etc.

Detection of Corynebacterium kroppenstedtii in Granulomatous Lobular Mastitis Using Real-Time Polymerase Chain Reaction and Sanger Sequencing on Formalin-Fixed, Paraffin-Embedded Tissues.

Associations between granulomatous lobular mastitis (GLM) and Corynebacterium kroppenstedtii have been reported since 2002, but large-scale studies to assess the actual prevalence of this bacterium in GLM have not been performed. To assess the prevalence of C kroppenstedtii in GLM using real-time polymerase chain reaction and Sanger sequencing. We analyzed formalin-fixed, paraffin-embedded tissues from 67 cases of GLM by sequential DNA amplification and sequencing to assess the rate of C kroppenstedtii detection in GLM. A retrospective analysis including patient demographics, history of pregnancy and lactation, clinical signs and symptoms, radiographic findings, histologic pattern, Gram stain results, and microbial cultures was performed on 67 cases of GLM. In addition, 10 cases of nongranulomatous breast abscess were included as controls. C kroppenstedtii 16S rRNA SYBR real-time polymerase chain reaction was positive on formalin-fixed, paraffin-embedded tissues from 46 of 67 (68.7%) GLM cases, while all control cases were negative. Among the positive cases, the majority showed features of cystic neutrophilic granulomatous mastitis. C kroppenstedtii was highly prevalent in GLM cases and was not found to be associated with nongranulomatous breast abscess in our study (P < .001).

Cystic neutrophilic granulomatous mastitis: A case report

Cystic neutrophilic granulomatous mastitis [CNGM] is a recently characterized entity, with specific histopathological details that differentiate it from other types of chronic idiopathic mastitis. The presence of gram-positive bacilli within cystic-like spaces surrounded by neutrophils, in a context of suppurative granulomatous inflammation, define this entity. The importance of its recognition in the diagnostic report lies in its association with infection by corynebacterial species, so that treatment with antibiotics can be targeted. Here we present a case of CNGM of left breast in a 34-year-old female.

Idiopathic Granulomatous Lobular Mastitis: An Imitation of Breast Carcinoma

Since idiopathic granulomatous lobular mastitis, also known as idiopathic granulomatous mastitis or granulomatous lobulitis, was first described by Kessler and Wolloch in 1972, no consensus on the ideal and definitive treatment for this phenomenon has been reached thus far. Idiopathic granulomatous lobular mastitis mostly frequently observed in women of childbearing age within a few years of pregnancy with a higher incidence in patients of Hispanic, Native American, Middle Eastern, and African descent. This entity, per se, is a rare, benign, chronic inflammatory breast condition of unknown aetiology mimicking two common breast disorders. The first is breast inflammations or infection, such as cystic neutrophilic granulomatous mastitis; granulomatous mastitis due to Corynebacterium;other infections with granulomas, mycobacteria, fungi, cat scratch disease, and Brucella; granulomatosis with polyangiitis (Wegener's granulomatosis); sarcoidosis; and squamous metaplasia of lactiferous ducts. The second is breast carcinoma in some challenging cases. Of note, no consensus, per se, has been declared on its therapeutic management. The following vignette case described in this report involves idiopathic granulomatous lobular mastitis imitating breast carcinoma. It is important to note that, the aetiology of idiopathic granulomatous lobular mastitis is unknown, its diagnosis is difficult, and physicians should be vigilant and aware of this condition in order of abstaining from an overtreatment for malignancy or overlooking a true malignancy.

New Insights of Corynebacterium kroppenstedtii in Granulomatous Lobular Mastitis based on Nanopore Sequencing

Background The etiology of granulomatous lobular mastitis (GLM) remains unknown. This study aimed to detect bacteria in GLM using Nanopore sequencing and identify the relationship between GLM and Corynebacterium kroppenstedtii. Methods and materials The bacterial detection on fresh samples (including breast pus and tissue) of 50 GLM patients using nanopore sequencing and culture methods. The bacterial detection rate of participants with different stages were compared and analyzed. Formalin-fixed and paraffin-embedded (FFPE) tissues from 39 patients were performed on Gram staining to identify Gram-positive bacilli (GPB) within lipid vacuoles. Moreover, the clinicopathological characteristics of GLM patients in different bacterial subgroups were also conducted. Results In 50 GLM patients, the detection rate of bacteria was 78% using nanopore sequencing method, especially in the early stage of GLM (over 80%), which was significantly higher than that using culture methods (24%, p < 0.001). The dominant bacteria were Corynebacterium species (64%), especially for the Corynebacterium kroppenstedtii. The detection rate of C. kroppenstedtii in nanopore sequencing method (56%) was higher than that in culture methods (16%, p < 0.001). Gram staining positive of bacteria in 7 patients, and 5 of them were C. kroppenstedtii. Thirty-one patients (31/39, 79.5%) exhibited typical histological structure of cystic neutrophilic granulomatous mastitis (CNGM), and eighteen patients detected with C. kroppenstedtii. Conclusion Nanopore sequencing showed rapid and accurate bacteria detection over culture method in GLM patients. GLM is not sterile inflammation and closely related to C. kroppenstedtii. CNGM was associated with Corynebacterium infection, especially for C. kroppenstedtii.

Mastitis Quística Granulomatosa Neutrofílica, Reporte De Caso

Cystic neutrophilic granulomatous mastitis (CNGM) is a recently characterized entity, with specific histopathological details that differentiate it from other types of chronic idiopathic mastitis. The presence of gram-positive bacilli within cystic-like spaces surrounded by neutrophils, in a context of suppurative granulomatous inflammation, define this entity. The importance of its recognition in the diagnostic report lies in its association with infection by corynebacterial species, so that treatment with antibiotics can be targeted, beyond the anti-inflammatory treatment that is usually administered to idiopathic mastitis.We describe the case of a 35-year-old female patient with no related history, with intermittent breast pain, associated with the presence of multiple hard, palpable nodules in both breasts, with results from multiple previous private biopsies that described chronic granulomatous mastitis with a tubercular reaction, for which she received treatment for tuberculosis. Despite this, the clinical response was partial. Histological slides were reviewed at the institution and the diagnosis of CNGM was then established.The presentation of this case was considered important due to its low recognition among pathologists, despite presenting characteristics already defined by previous studies.

Granulomatous Mastitis: A Clinical and Diagnostic Dilemma.

Granulomatous mastitis (GM) is a challenging inflammatory disorder of the breast. In this study we aimed to present the detailed clinical and morphological features of GM cases, diagnostic clues for specific and idiopathic etiologies, the difficulties in evaluating trucut biopsies, and the results of different therapeutic approaches. We retrospectively analysed the clinical, radiological and morphological features of 114 GM cases diagnosed with fine needle aspiration, and trucut, incisional, and excisional biopsy. The mean age was 35.8. Only eight cases were older than 45 years. Bilateral involvement was observed in 4 (3.5%) cases. The most common clinical symptoms were breast mass/abscesses, tenderness, and skin changes. Microbiological culture was positive in 4 cases for gram-positive bacteria. Only 3 cases showed a positive tuberculin/PCR test for tuberculosis. The major USG finding was a hypoechoic well-defined or ill-defined mass/abscess; MRI finding was heterogeneous non-mass contrast enhancement. Cases diagnosed with cytology (35 cases) did not have breast malignancy either in their history or clinical follow up period. Fine needle aspiration cytology materials revealed epitheloid granulomas mixed with neutrophils, lymphocytes accompanied by giant cells, and suppurative necrosis. Histopathological reevaluation of 65 trucut/incisional/ excisional biopsies revealed granuloma formation in 65 (100%), Langhans type giant cells in 59 (90.7%), microabscess formation in 41 (63%), caseous necrosis in 1 (1.5%), neutrophilic cysts in 30 (46.1%), eosinophilic infiltration in 48 (73.8%), interlobular inflammation in 14 (21.5%), fat necrosis in 5 (7.6%), ductal ectasia in 6 (9.2%), and lactational changes in 4 (6.1%) cases. Granulomas were lobulocentric in 58 cases, foreign body type/fat necrosis-related in 6 case, and periductular in 1 case. Cystic neutrophilic granulomatous mastitis was observed in one case. We also evaluated the histochemical stains of these 65 biopsies. Only one sample was positive for acido-resistant bacilli (ARB) by the EZN method and one sample was positive for gram-positive bacilli by gram stain. Small, superficial trucut biopsies may cause difficulties in determining the etiology and differential diagnosis of granulomatous mastitis. For optimal management and timing the appropriate therapy, the ideal biopsy procedure, special stains, and a multidisciplinary team consisting of the surgeon, pathologist, and radiologist are the most important issues.

Cystic neutrophilic granulomatous mastitis during chemotherapy treatment for invasive breast carcinoma \u2013 a rare lesion that simulates tumor progression

BackgroundCystic neutrophilic granulomatous mastitis (CNGM) is an uncommon and recently described pattern of granulomatous mastitis. To our knowledge, no cases have been described during chemotherapy for invasive breast cancer.Case presentationA 42-year-old female patient had a diagnosis of invasive breast carcinoma (3-cm nodule). During neoadjuvant chemotherapy, she presented with an enlargement of the breast nodule that measured 7.0-cm on palpation. The lesion did not show typical inflammatory clinical findings and simulated tumor progression. A core biopsy showed granulomas with pseudocystic spaces with gram-positive bacilli (Corynebacterium sp.), and numerous circumjacent neutrophils. She was treated with antibiotics and resumed chemotherapy. Surgical specimen showed a 1.0-cm residual carcinoma and extensive xanthogranulomatous inflammation with no evidence of residual CNGM.ConclusionCNGM is usually associated with typical clinical presentation of mastitis. It is an important pattern of granulomatous inflammation to be recognized in the breast since it directly impacts treatment. The present case highlights its potential occurrence during chemotherapy treatment of breast cancer mimicking progression of breast malignancy.

Cystic neutrophilic granulomatous mastitis – a review of 12 consecutive cases

Cystic neutrophilic granulomatous mastitis (CNGM) is an uncommon but increasingly recognised cause of mastitis, often associated with Corynebacterium ssp. infection. We studied the histopathological and clinical features of CNGM in a Canadian setting, and the work-up required to identify pathogenic microorganisms. A retrospective search for breast specimens with abscess, acute, chronic and/or granulomatous inflammation from 1998 to 2018 was performed. Haematoxylin and eosin slides were reviewed for typical histological features of CNGM. Histochemically stained slides for microorganisms were also reviewed. Repeat Gram stains were performed if initially negative. Electronic medical records were abstracted for microbiology results and relevant clinical data. Twelve cases were identified. All were female, aged 25-57years, mainly Caucasian, with one Venezuelan and two of Chinese ethnicity. Most were parous (10 of 12); five of 12 had an endocrinopathy. Bacteria were identified in one or more specimens from eight of 12 patients; additional Gram stains revealed organisms in four of 12 cases. Of four bacterial cultures, one grew Corynebacterium kroppenstedtii. 16S polymerase chain reaction for three samples was negative. Two patients had multiple breast biopsies, showing early palisaded granulomas followed by classic features of CNGM. The patients had various management approaches, including surgery and antimicrobials. CNGM may present as palisaded granulomatous inflammation, without the expected 'cystic' pattern, suggesting that there is an evolution of histomorphology with this infection. Most patients with CNGM are parous, and there may be an association with endocrinopathies. Application of multiple Gram stains increases the yield of microorganism identification. Recognition of CNGM in breast biopsies and collaborative communications are essential to direct appropriate therapy.

Cystic neutrophilic granulomatous mastitis: Corynebacterium species-associated infection with distinct histology

A 37-year-old gravida 2 para 2 woman presented with a painful, palpable breast mass and worsening open lesions for 5 months (Fig. 1a). Her lactation history showed uncomplicated breastfeeding for both children with no previous mastitis. Ultrasound revealed a heterogeneous echogenic area with indistinct borders suspicious for developing abscess (i.e. BI-RADS 2) (Fig. 1b). She was subsequently treated with multiple short courses of β-lactam antibiotics for presumed staphylococcal mastitis, but with minimal improvement.

Cystic Neutrophilic Granulomatous Mastitis: A Clinicopathological Study With 16s rRNA Sequencing for the Detection of Corynebacteria in Formalin-Fixed Paraffin-Embedded Tissue.

Cystic neutrophilic granulomatous mastitis (CNGM) is a histologically characterized variant of granulomatous lobular mastitis that is associated with lipophilic Corynebacterium species. It remains a largely underrecognized entity in India. Our aim was to study CNGM in the Asian Indian population and explore if 16s rRNA sequencing could be used on formalin-fixed paraffin-embedded (FFPE) tissue to identify the causative organism. We studied 24 cases with histological features of CNGM with hematoxylin and eosin, Gram, Ziehl-Neelsen, and Periodic acid-Schiff stains. Tuberculosis-polymerase chain reaction and 16s rRNA gene sequencing on DNA extracted from FFPE was attempted (N = 23). Gram-positive bacilli were seen in 20/24 cases. Routine culture with prolonged incubation yielded Corynebacterium species in 8 cases; 7 of these cases were evaluated by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) for species identification. C matruchotti was identified in one case by BD Phoenix. MALDI-TOF MS identified the remaining 7 cases as C kroppenstedtii (N = 4) and C tuberculostearicum (N = 2), with no identification in one. Corynebacteria were identified by 16s rRNA sequencing on DNA extracted from FFPE in 12/23 cases using a primer targeting the V5-V6 region that was found to be more conserved in Corynebacterium species. All cases were negative for the diagnosis of tuberculosis. CNGM can be identified by routine stains. Culture using routine media with prolonged incubation is often adequate to isolate the organism. 16s rRNA sequencing on DNA extracted from FFPE tissue can help make an etiological diagnosis in some cases where only paraffin blocks are available.

"Thick Section" Gram Stain Yields Improved Detection of Organisms in Tissue Sections of Cystic Neutrophilic Granulomatous Mastitis.

Cystic neutrophilic granulomatous mastitis (CNGM) is an uncommon subtype of granulomatous mastitis featuring epithelioid histiocytes/neutrophils rimming discrete cystic spaces. When present, gram-positive bacteria (typically Corynebacterium species) are identified within these cystic spaces, although they can be difficult to appreciate on tissue sections. Based on pilot gram-stained tissue sections of CNGM cases cut on 6 μm thickness (in which bacterial organisms were more readily identifiable) instead of the traditional 4 μm, a formal comparative analysis of 19 CNGM cases was performed on parallel 6-μm ("thick") vs 4-μm sections from one representative block per case. Biopsies (n = 17) and excisional specimens (n = 2) from 19 CNGM cases were included. Gram-positive palisaded rods were identified in seven cases using 4-μm sections and in 11 cases using 6-μm sections (sensitivity of 37% vs 58% in identifying organisms). Among all seven cases of organisms seen on the 4-μm section Gram stain, the paired 6-μm section Gram stain showed a higher number of and more readily identifiable bacteria. Thick section Gram stain of representative tissue blocks performed at 6 μm improves both detection rate and ease of identification of gram-positive organisms in CNGM.