Lymphocytic Lobulitis Research Articles

Case Report: Sclerosing lymphocytic lobulitis of the breast: case report and literature review

Sclerosing lymphocytic lobulitis, also known as diabetic mastopathy, is a rare and benign pathology predominantly observed in young women with type I diabetes, typically with degenerative complications. Clinically, the lesion can mimic carcinoma. Biopsy remains the gold standard for a definitive diagnosis. Radical surgery is generally unnecessary when histological verification can be achievedusing core needle biopsy. This case report details the clinical and radiological findings, as well as the management of a 33-year-old patient with a 22-year history of type I diabetes who presented with sclerosing lymphocytic lobulitis.

Non-sclerosing (T-cell) and sclerosing (B-cell) lymphocytic lobulitis in diagnostic breast biopsies: Clinical, imaging, and pathologic features

Lymphocytic lobulitis (LL) is characterized by prominent lymphocytic infiltrates centered on lobules. Sclerosing lymphocytic lobulitis (SCLL) associated with diabetes mellitus (DM) or autoimmune disease (AI) was the first type to be described. Subsequently, non-sclerosing LL (NSCLL) was reported as an incidental finding in prophylactic mastectomies due to high risk germline mutations or a family history of breast cancer. The two types of LL were distinguished by stromal features and a predominant population of B-cells in the former and T-cells in the latter. In this study, 8 cases of NSCLL detected clinically or by screening were compared to 44 cases of SCLL. One case of NSCLL presented as a palpable mass, 2 as masses on screening, and 5 as MRI enhancement. In contrast, 80% of SCLL cases presented as palpable masses. Half the cases of NSCLL were associated with a BRCA1 or 2 mutation compared to 1 case of SCLL (2%). Three additional cases of NSCLL were associated with a strong family and/or personal history of breast cancer. Almost half (52%) of SCLL cases were associated with DM or AI, but only 25% of NSCLL. Immunoperoxidase studies confirmed a predominance of T-cells in NSCLL and B-cells in SCLL associated with DM or AI. It is important for pathologists to be aware of this new observation that NSCLL can be detected as a palpable mass or an imaging finding in diagnostic biopsies, as its presence can be indicative of a significant risk for breast cancer.

Mammography and Ultrasonography Manifestations of Sclerosing Lymphocytic Lobulitis of the Breast: A Series of Seven Case Reports.

The present study aimed to analyze mammography and ultrasonography (US) manifestations of sclerosing lymphocytic lobulitis (SLL) of the breast. A total of 8 pathologically confirmed SLL lesions from seven women (with one patient having bilateral breast lesions) were included in the study. All patients underwent preoperative mammography and US examinations. The findings from both modalities were classified and compared to their corresponding clinical data. Four patients were diagnosed with diabetes mellitus. Mammography results revealed that seven lesions presented as focal asymmetry or asymmetry. Seven lesions were observed as non-mass lesions on US examination. The most commonly observed US lesion features were as follows: seven lesions had focal non-ductal hypoechoic areas (87.5%), seven lesions exhibited posterior shadowing (87.5%), all lesions showed no vascularity or vessels in the rim (100%), no lesion had calcifications (0%), five lesions had an elasticity score of 3 (100%), one lesion showed retraction on the coronal plane (20%), and one lesion displayed a skipping sign on the coronal plane (20%). Based on these US findings, seven lesions (87.5%) were classified as BI-RADS 4. The mammography findings for SLL are often nonspecific. However, the US features of SLL typically present as non-mass lesions. The absence of calcification and vascularity and no retraction on the coronal plane inside the lesion may help to differentiate this disease from the conventional forms of breast carcinoma.

Diabetic Fibrous Mastopathy: Imaging Features With Histopathologic Correlation.

Diabetic fibrous mastopathy (DFM) is a rare benign fibrotic disease of the breast that develops in patients with longstanding and often uncontrolled diabetes mellitus. Clinically, patients may present with an irregular, firm, palpable mass, which may be solitary or multiple, occurring in one or both breasts. Diabetic fibrous mastopathy occurs most often in premenopausal women with heterogeneously or extremely dense breasts; mammography may show focal asymmetry or, less often, a noncalcified mass with indistinct or obscured margins, but there are usually no discrete findings. On US, DFM may have marked hypoechogenicity and posterior shadowing secondary to extensive fibrosis. Diabetic fibrous mastopathy features on contrast-enhanced MRI are also nonspecific, with gradual persistent nonmass enhancement reported. Because the clinical presentation and US features of DFM overlap with those of breast cancer, histopathologic correlation is needed to confirm diagnosis and exclude malignancy. These findings include collagenous stroma often with keloidal features and chronic perilobular and perivascular inflammation. Histopathologic findings of lymphocytic lobulitis and perivascular inflammation are common to other autoimmune conditions.

Case Report : Lymphocytic Lobulitis With Fibrocystic Disease Of The Breast

Lymphocytic lobulitis , is a fibroinflammatory benign condition of the breast which is associated with type 1 diabetes mellitus. This benign condition is uncommon and may be mistaken for inflammatory carcinoma of the breast. We report the case of a 61 year old female patient who presented with a lump in the right breast with a history of Type 2 diabetes mellitus. The lump was associated with discharge and recent onset pain. On examination a vague lump which was non mobile, involving the right breast was palpable. A single firm mobile right axillary lymph node was palpable. Peau d’orange or orange peel appearance which occurs due to blockage of sub dermal lymphatics by tumour infiltrates, was noted over the skin. Clinically the features were suggestive of inflammatory carcinoma. Mammogram suggested an inflammatory carcinoma. Ultrasound of the breast was suggestive of right duct ectasia and diffusely thickened breast with a Breast Imaging Radiology and Data System (BIRADS) score of 3. An incision biopsy was performed with histopathology confirming the lesion as lymphocytic lobulitis with fibrocystic breast disease. The patient was symptomatically managed with analgesics and reassured. She was observed on regular follow up and is currently healthy. Lymphocytic lobulitis is a rare benign lesion which mimics carcinoma. Clinically it presents with ill defined single or multiple breast lumps in young or middle aged women with thickening and hardening of skin. Magnetic Resonance Imaging better differentiates this otherwise indolent lesion from malignancies. A histopathological examination is usually confirmatory and required to alleviate concerns of patients regarding presence of a malignancy which has a much fearsome physical and psychological implication.

Case Report : Lymphocytic Lobulitis With Fibrocystic Disease Of The Breast

Lymphocytic lobulitis , is a fibroinflammatory benign condition of the breast which is associated with type 1 diabetes mellitus. This benign condition is uncommon and may be mistaken for inflammatory carcinoma of the breast. We report the case of a 61 year old female patient who presented with a lump in the right breast with a history of Type 2 diabetes mellitus. The lump was associated with discharge and recent onset pain. On examination a vague lump which was non mobile, involving the right breast was palpable. A single firm mobile right axillary lymph node was palpable. Peau d’orange or orange peel appearance which occurs due to blockage of sub dermal lymphatics by tumour infiltrates, was noted over the skin. Clinically the features were suggestive of inflammatory carcinoma. Mammogram suggested an inflammatory carcinoma. Ultrasound of the breast was suggestive of right duct ectasia and diffusely thickened breast with a Breast Imaging Radiology and Data System (BIRADS) score of 3. An incision biopsy was performed with histopathology confirming the lesion as lymphocytic lobulitis with fibrocystic breast disease. The patient was symptomatically managed with analgesics and reassured. She was observed on regular follow up and is currently healthy. Lymphocytic lobulitis is a rare benign lesion which mimics carcinoma. Clinically it presents with ill defined single or multiple breast lumps in young or middle aged women with thickening and hardening of skin. Magnetic Resonance Imaging better differentiates this otherwise indolent lesion from malignancies. A histopathological examination is usually confirmatory and required to alleviate concerns of patients regarding presence of a malignancy which has a much fearsome physical and psychological implication

Ultrasound as a Valuable Imaging Modality in Sclerosing Lymphocytic Lobulitis: Imaging Features Based on a Retrospective Cohort Analysis of 51 Cases.

Sclerosing lymphocytic lobulitis (SLL) is a rare benign breast condition usually associated with diabetes mellitus and whose imaging features have been assessed in few studies, limiting the adoption of diagnostic guidelines. We aimed to identify the main morphological features associated with SLL on imaging examinations (mainly ultrasound and mammography) and to retrospectively evaluate the role that each method played in the diagnostic workup (detection and indication for biopsy). A retrospective study was conducted in a high-volume single center, encompassing 51 consecutive patients (100% female; 26-78 y; 43.7 ± 15.5 y) with histopathologically proven SLL (59 lesions; 0.5-6.1 cm). Most lesions (31/59; 53%) were found in asymptomatic individuals. Ultrasound detected 91.1% (51 out of 56 lesions assessed by this modality), of which 94.1% were non-circumscribed masses (BI-RADS® 4). Mammography detected 41.6% (15 out of 36 lesions assessed by this modality), with a predominance (80%) of non-calcified ones (masses, asymmetries and distortion). Two-year follow-up was achieved in 29 lesions (49%), showing complete remission (45%) or stability (41%) in most cases. Most lesions in this retrospective sample have been detected by means of ultrasound and had their need for biopsy indicated by this modality. Female diabetic patients younger than 40 years presenting with a palpable lesion and a non-circumscribed mass on ultrasound could be submitted to core biopsy; histopathologic findings suggestive of SLL should be considered concordant in this scenario, with subsequent conservative treatment.

MON-136 Rare Cause of a Suspicious Breast Lump in a Diabetic Woman: Broaden Your Differentials!

Introduction: Diabetic mastopathy is a rare fibro-inflammatory breast lesion that characteristically presents in premenopausal women with long-standing type 1 diabetes mellitus with multiple microvascular complications. Here we describe a case of diabetic mastopathy to emphasize the close communication between physician, radiologist and pathologist needed to avoid unnecessary repeated interventions in this vulnerable population. Case Report: A 50 year old woman with long standing type 1 diabetes mellitus and end stage renal disease on hemodialysis was referred for screening mammography. Mammography revealed heterogenous breast with architectural distortion in right breast at the 12:00 position. USG also showed a large irregular hypoechoic mass with posterior acoustic shadowing, 5.3 x 1.9 x 2.0 cm at the 12:00 position. BI-RADS Category was 5, interpreted as highly suggestive of malignancy. Ultrasound-guided core needle biopsy was done which revealed lymphocytic ductitis, sclerosing lobulitis with non-proliferative fibrocystic changes. A diagnosis of diabetic mastopathy was made. Subsequent annual mammograms continued to demonstrate the above findings and awareness of this diagnosis has prevented her from undergoing repeated biopsies. Discussion: The pathogenesis is linked to an autoimmune response to abnormal extracellular matrix accumulation secondary to effects of hyperglycemia. It can result in palpable breast masses which are often described as firm, mobile and painless. The US features are generally suspicious for malignancy while mammography may show focal asymmetry. The posterior acoustical shadowing which is secondary to fibrosis is the hallmark as seen in our patient. Core biopsy is generally needed for initial pathological diagnosis but may yield non-diagnostic findings in many cases. The characteristic histopathological features include lymphocytic lobulitis, ductitis, B cell vasculitis and dense keloid-like fibrosis. The differential diagnosis includes inflammatory myofibroblastic tumor, granulomatous mastitis, sclerosing lipogranulomatous response or sclerosing lipogranuloma. Although the above mentioned histopathologic features can be encountered in nondiabetic breast biopsies, epithelioid fibroblasts appear to be unique to the diabetic condition. The correlations between imaging and pathology play an important role in the diagnostic process. While in some cases the pathologist may not be provided with a history of diabetes mellitus, the characteristic fibrosis, sclerosing lobulitis with perilobular and perivascular lymphocytic infiltrates provide clues for an accurate diagnosis. Timely and accurate diagnosis of this rare cause of a breast mass can hopefully help women avoid unnecessary repeat biopsies as well as surgical procedures.

Histological scoring of immune and stromal features in breast and axillary lymph nodes is prognostic for distant metastasis in lymph node-positive breast cancers.

The prognostic importance of lymph node (LN) status and tumour‐infiltrating lymphocytes (TILs), is well established, particularly TILs in triple negative breast cancers (TNBCs). So far, few studies have interrogated changes in involved and uninvolved LNs and evaluated if their morphological patterns add valuable information for the prediction of disease progression in breast cancer. In a cohort of 309 patients enriched for TNBCs (170/309), we histologically characterised immune and stromal features in primary tumours and associated involved and uninvolved axillary LNs on routine haematoxylin and eosin stained sections. Of the 309 patients, 143 had LN‐positive disease. Twenty‐five histopathological features were assessed, including the degree of TIL presence, quantitative and qualitative assessment of germinal centres (GCs) and sinus histiocytosis. Multivariate and cross‐validated proportional hazard regression analyses were used to identify optimal covariate sets for prediction of distant metastasis‐free survival (DMFS). The degree of intratumoural and peritumoural immune infiltrate was associated with architectural changes in both uninvolved and involved LNs. By including clinicopathological characteristics as well as tumour and LN histopathological features in L2‐regularised proportional hazard models, the prediction of 5‐year DMFS was improved by 3–15% over the baseline in all cancers and in TNBCs. In LN‐positive cancers, the combination of Salgado's classification, lymphocytic lobulitis, size and number of GCs in the uninvolved LNs and location of GCs in the involved LNs carried significant prognostic information. From these features, a multivariate cross‐validation‐stable risk signature was constructed, which identified low‐risk groups within both LN‐positive breast cancers and the LN‐positive TNBCs group with a 10‐year DMFS probability of 78 and 87%, respectively. This study illustrates that, by incorporating histopathological patterns of involved and uninvolved LNs combined with primary tumour immune and stromal features, the prediction of developing distant metastasis in LN‐positive breast cancers can be estimated more accurately.

Image analysis of immune cell patterns in the human mammary gland during the menstrual cycle refines lymphocytic lobulitis

To improve microscopic evaluation of immune cells relevant in breast cancer oncoimmunology, we aim at distinguishing normal infiltration patterns from lymphocytic lobulitis by advanced image analysis. We consider potential immune cell variations due to the menstrual cycle and oral contraceptives in non-neoplastic mammary gland tissue. Lymphocyte and macrophage distributions were analyzed in the anatomical context of the resting mammary gland in immunohistochemically stained digital whole slide images obtained from 53 reduction mammoplasty specimens. Our image analysis workflow included automated regions of interest detection, immune cell recognition, and co-registration of regions of interest. In normal lobular epithelium, seven CD8[Formula: see text] lymphocytes per 100 epithelial cells were present on average and about 70% of this T-lymphocyte population was lined up along the basal cell layer in close proximity to the epithelium. The density of CD8[Formula: see text] T-cell was 1.6 fold higher in the luteal than in the follicular phase in spontaneous menstrual cycles and 1.4 fold increased under the influence of oral contraceptives, and not co-localized with epithelial proliferation. CD4[Formula: see text] T-cells were infrequent. Abundant CD163[Formula: see text] macrophages were widely spread, including the interstitial compartment, with minor variation during the menstrual cycle. Spatial patterns of different immune cell subtypes determine the range of normal, as opposed to inflammatory conditions of the breast tissue microenvironment. Advanced image analysis enables quantification of hormonal effects, refines lymphocytic lobulitis, and shows potential for comprehensive biopsy evaluation in oncoimmunology.

In-silico insights on the prognostic potential of immune cell infiltration patterns in the breast lobular epithelium.

Scattered inflammatory cells are commonly observed in mammary gland tissue, most likely in response to normal cell turnover by proliferation and apoptosis, or as part of immunosurveillance. In contrast, lymphocytic lobulitis (LLO) is a recurrent inflammation pattern, characterized by lymphoid cells infiltrating lobular structures, that has been associated with increased familial breast cancer risk and immune responses to clinically manifest cancer. The mechanisms and pathogenic implications related to the inflammatory microenvironment in breast tissue are still poorly understood. Currently, the definition of inflammation is mainly descriptive, not allowing a clear distinction of LLO from physiological immunological responses and its role in oncogenesis remains unclear. To gain insights into the prognostic potential of inflammation, we developed an agent-based model of immune and epithelial cell interactions in breast lobular epithelium. Physiological parameters were calibrated from breast tissue samples of women who underwent reduction mammoplasty due to orthopedic or cosmetic reasons. The model allowed to investigate the impact of menstrual cycle length and hormone status on inflammatory responses to cell turnover in the breast tissue. Our findings suggested that the immunological context, defined by the immune cell density, functional orientation and spatial distribution, contains prognostic information previously not captured by conventional diagnostic approaches.

Lymphocyte subsets contribute to the degree of lobulitis and ductitis in sclerosing lymphocytic lobulitis of the breast

AimsSclerosing lymphocytic lobulitis (SLL) of the breast is characterised by lymphocytic lobulitis, ductitis, vasculitis and dense keloidal fibrosis with epithelioid fibroblasts. However, the subsets of the infiltrating lymphocytes and their...

Sclerosing Lymphocytic Lobulitis Mimicking a Tumor Relapse in a Young Woman with a History of Breast Cancer

Sclerosing lymphocytic lobulitis or diabetic mastopathy is a benign entity with non-specific imaging features which can mimic breast carcinoma. It is a condition commonly associated with long standing diabetes and has also been linked with various auto-immune diseases. We present the case of a 27-year-old woman with a history of carcinoma of the left breast and otherwise unremarkable medical history, who developed sclerosing lymphocytic lobulitis in the right breast during follow-up.

Evaluating breast lymphoplasmacytic infiltrates: a multiparameter immunohistochemical study, including assessment of IgG4

Lymphoplasmacytic infiltrates in the breast, a modified skin appendage, include lymphocytic lobulitis, other nonspecific benign proliferations, and mucosa-associated lymphoid tissue (MALT)-type lymphoma. Distinguishing these entities, all of which may be B-cell rich and may have associated sclerosis, can be difficult. In addition, the proportion that represents IgG4-related disease is unknown, and the similarity of MALT lymphomas to primary cutaneous marginal zone lymphoma is uncertain. To address these questions, the clinical, histologic, and immunohistochemical features of 50 benign and malignant breast lymphoplasmacytic infiltrates (10 lymphocytic lobulitis, 1 granulomatous, 19 not otherwise specified, 20 MALT lymphomas) were evaluated. Compared with the MALT lymphomas, benign cases had a less dense infiltrate (P < .001), fewer but more histologically apparent germinal centers (P < .001), and more marked fibrosis (P < .0001). Greater than 60% B cells were present in 23% (7/30) benign cases versus 75% (15/20) MALT lymphomas (P = .0003). Plasma cells were predominantly IgG+ in 83% (24/29) benign cases and predominantly IgM+ in 73% (14/19) MALT lymphomas (P < .0001). None of the benign cases had greater than 50 IgG4+ plasma cells/high-power field, and only 1 lymphocytic lobulitis case had an IgG4/IgG ratio exceeding 40% and no clinical evidence for extramammary IgG4-related disease. Although there may be some overlapping features, routine histopathology together with limited immunohistochemical stains can distinguish benign from neoplastic lymphoplasmacytic infiltrates in the breast. Despite frequent sclerosis, the breast is not a common site of unrecognized IgG4-related sclerosing disease. Although there are similarities, breast MALT lymphomas can be separated from cutaneous marginal zone lymphoma.

Diabetes and the breast

Diabetes and the breast

Sclerosing Lymphocytic Lobulitis Manifesting as Suspicious Microcalcifications with Hashimoto's Thyroiditis in a Young Woman

Sclerosing lymphocytic lobulitis (SLL) is a rare inflammatory disorder, which is also known as fibrous mastopathy and lymphocytic mastitis. It is commonly associated with autoimmune disorders, particularly type 1 diabetes and thyroiditis. We report the case of a 28-year-old woman diagnosed as SLL with Hashimoto's thyroiditis, but without diabetes. She presented suspicious microcalcifications without palpable mass in routine mammograms in both breasts. She had been diagnosed as Hashimoto's thyroiditis several years before and had been followed up in endo-clinics.

Mastopatía diabética: lesión poco conocida que simula un cáncer de mama

Diabetic mastopathy is an uncommon complication that usually occurs in patients with longstanding diabetes mellitus. This entity often presents as a palpable hard and irregular mass that mimics breast carcinoma. Imaging features are nonspecific and a histological diagnosis is required to exclude malignancy. The pathological features of diabetic mastopathy show dense keloid-like fibrosis associated with lymphocytic ductulitis, lobulitis and vasculitis. We report the case of a woman with a longstanding history of insulin-dependent diabetes mellitus and a hard, painless and irregular mass in her breast. Mammography and ultrasound examination showed a suspicious lesion (BIRADS IV). Sonographically-guided core biopsy of the mass was performed and pathological features revealed fibrosis compatible with diabetic mastopathy.

Diabetic mastopathy, a clinicopathological correlation of 34 cases

Diabetic mastopathy (DM) is an unusual fibrous disease of the breast. We report 34 cases with clinicopathological correlation and follow-ups. Patients mean age was 57 years and 24 had histories of diabetes mellitus. The DM presented as a palpable breast mass in 85.3% of the cases clinically. Image findings were often as an irregular hypoechoic mass (44.4%) on ultrasound and negative or non-specific density (67.6%) on mammogram. Histologically, we found that the majority of DM occurred in the upper outer/central part of the breast (76%) and the size ranged from 0.5 to 3.7 cm. All cases showed lymphocytic lobulitis and vasculitis, keloidal fibrosis, lobular atrophy and varying degree of epithelioid fibroblasts. Examining the surrounding normal tissue of the excision specimens revealed that the margins of DM were often poorly circumscribed and irregularly demarcated from the sounding breast tissue. Vascular calcifications were identified in 10 of 24 excisional specimens, suggesting a hypothesis that vascular damage and scar/wounding healing process could contribute to the pathogenesis of DM. Twenty-one cases had repeated procedures for uncertain descriptive diagnosis. This is the largest study of diabetic mastopathy to date with clinical and imagining correlation. Recognition of this benign entity is important to better understanding the pathogenesis and to avoid unnecessary procedures.

Sclerosing lymphocytic lobulitis in a male patient with asthma

Sclerosing lymphocytic lobulitis is commonly but not exclusively associated with type I diabetes mellitus. Association with other autoimmune diseases is known and also disease is infrequently seen in males. We herein report a rare case of sclerosing lymphocytic lobulitis in a male patient with asthma. Recognition of this entity in the absence of diabetes and awareness of its existence in males is important to avoid unwarranted surgical procedures because it may mimic carcinoma both clinically and radiologically.

A Case of Diabetic Mastopathy

Diabetic mastopathy is an unusual fibroinflammatory breast lesion that is characteristically presented in premenopausal women with long-standing diabetes with multiple microvascular complications. This patient was a 49-year-old postmenopausal woman with diabetic nephropathy, neuropathy, and retinopathy. Although palpable mass was detected on the left breast, an ultrasonography could not distinguish it from breast cancer. Excisional biopsy was conducted. Histological findings indicated diabetic mastopathy with keloid-like fibrosis, perivascular lymphocytic infiltration, and lymphocytic lobulitis without evidence of malignancy. After excision, there has been no recurrence until now. (Endocrinol Metab 27:244-246, 2012)