Sclerosing Lesions Research Articles

Nonneoplastic and neoplastic sclerosing lesions of the breast.

Sclerosing lesions of the breast encompass a spectrum of benign and malignant entities and often pose a diagnostic challenge. Awareness of key morphologic features and pitfalls in the assessment of morphology and immunophenotype is essential to avoid over- or underdiagnosis and ensure optimal clinical management. This review summarizes nonneoplastic sclerosing lesions such as radial scar/complex sclerosing lesion, sclerosing adenosis, sclerosing intraductal papilloma, sclerosing variants of ductal adenoma and nipple adenoma, and fibroadenoma with extensive sclerosis, including their clinical presentation, characteristic morphology, differential diagnostic considerations, appropriate immunohistochemical work-up, when needed, and the clinical significance. In addition, atypical or neoplasticentities (such as atypical ductal hyperplasia, ductal carcinoma in situ, low-grade adenosquamous carcinoma, and fibromatosis-like metaplastic carcinoma) that can involve these sclerosing lesions are also briefly discussed.

Radial sclerosing lesions found on core needle biopsy: excision can be safely avoided.

Radial sclerosing lesions (RSLs) are benign breast lesions composed of glandular and epithelial proliferations with stellate architecture and fibro-elastotic stroma, which can mimic invasive carcinoma on imaging. Surgical management following a core biopsy diagnosis of RSLs remains controversial. We retrospectively identified core biopsies with RSLs without atypia who underwent subsequent surgical excision between 2015 and 2021. All core biopsy slides were reviewed to confirm the diagnosis. Imaging was reviewed to determine radiological-pathological concordance. An upgrade was defined as invasive carcinoma or ductal carcinoma in situ (DCIS) in the excision. The final cohort consisted of 130 core biopsies from 124 women (median age = 52 years, range = 27-76). The imaging modality was mammogram in 52 (40%) cases, MRI in 52 (40%) and ultrasound in 26 (20%). One hundred and seven (82%) core biopsies were vacuum-assisted and 23 (18%) were ultrasound-guided without vacuum assistance. The median lesion size on imaging was 9 mm (range = 2-41). Overall, two (1%) cases were upgraded at excision, including one microinvasive lobular carcinoma and one 2 mm focus of invasive mammary carcinoma with associated DCIS. In both cases, the upgraded foci of carcinoma were not closely associated with the biopsy site and were considered incidental upgrades. This study adds to the body of literature supporting observation, rather than routine excision of radial sclerosing lesions without atypia.

Imaging and Management of Radial Scars and Complex Sclerosing Lesions.

Radial scars and complex sclerosing lesions, often collectively referred to as radial sclerosing lesions (RSLs), are breast lesions characterized by sclerotic stroma with entrapped epithelial elements. RSLs have imaging features that overlap with those of breast malignancy and often become the target of imaging-guided biopsy given their suspicious imaging appearance. These can be identified in isolation or can also be associated with atypia or other high-risk lesions that have intrinsic malignant potential, increasing the risk of carcinoma and affecting prognosis and management of RSLs. Because of this, management of these lesions remains controversial. Traditional management has been surgical excisional biopsy. However, as more RSLs are identified (because digital breast tomosynthesis allows identification of more architectural distortions), optimal management is evolving. Physicians in some practices are using a multidisciplinary approach to the management of RSLs when deciding on surgical excision of these lesions versus imaging follow-up. These discussions also incorporate individual patient risk factors and greater patient informed medical decision making. Reported upgrade rates of RSLs at core needle biopsy vary and can depend on the sampling method, number of samples, gauge of the needle, target being sampled, and radiologic-pathologic concordance or discordance. A precise sampling technique also allows greater accuracy of diagnosis and lower upgrade rates for these lesions, with radiologic-pathologic correlation as an integral component for further management decisions. The authors review the overall histopathologic, clinical, and imaging features of RSLs and discuss appropriate management based on currently available data regarding upgrade rates. ©RSNA, 2023 Quiz questions for this article are available through the Online Learning Center.

S3033 HIV-AIDS: A Rare Cause of Cholestatic Cholangiopathy

Introduction: HIV/AIDS has been shown to affect hepatic parenchyma and biliary tree leading to inflammation and biliary strictures. With the advent of highly active antiretroviral therapy (HAART), it is rarely encountered, except in cases of resistance or medication non-compliance. Case Description/Methods: A 48-year-old man with history of HIV and poor compliance with HAART presented with abdominal pain, nausea and diarrhea. Physical exam showed scleral icterus and mild abdominal tenderness, with labs showing a T.bili. 16.9, AST 212, ALT 133, and ALP 3885. MRCP revealed intrahepatic biliary ductal dilatation of both lobes of liver and mild dilatation of the proximal extrahepatic CBD (9 mm) without cholelithiasis, biliary sludge or ductal stone suggesting nonspecific cholestasis. ERCP was performed which revealed papillary stenosis and moderately enlarged CBD (12 mm). Irregularities were noted in bilateral intrahepatic branches but not in ducts. A pancreatic and biliary sphincterotomy was performed. With minimal decrease in T.bili. and ALP, repeat MRCP was performed 3 months later showing persistent intrahepatic biliary ductal dilatation with normal CBD. Repeat ERCP showed patent prior sphincterotomy and the biliary tree was swept with nothing found. Further workup revealed a CD4 count of 17 and serology positive for cryptosporidium antigen. A diagnosis of HIV-cholangiopathy was made and the patient was restarted on HAART and nitazoxanide with gradual decline in T.bili and ALP. (Figure) Discussion: HIV/AIDS-cholangiopathy is a rarely encountered biliary syndrome, usually manifesting in severely immunosuppressed AIDS patients. Several opportunistic pathogens have been implicated in its pathogenesis with Cryptosporidium parvum being the most commonly associated pathogen. C. parvum predominantly affecting the biliary tract leading to apoptotic cell death of the cholangiocytes. Biliary involvement has been described in four cholangiographic patterns – papillary stenosis, extrahepatic strictures, intra and extrahepatic sclerosing lesions, and acalculous cholecystitis. Diagnosis can be established usually by MRCP or ERCP which shows papillary stenosis with intrahepatic ductal dilatation. Alternating multifocal intrahepatic strictures can also be seen giving a beaded appearance. The cornerstone of management involves the management of opportunistic infections with the initiation of HAART. The prognosis is usually poor due to advanced stages of immunosuppression and multiple opportunistic infections.Figure 1.: CT Abdomen pelvis showing intrahepatic biliary ductal dilation.

Rethinking Routine Surgical Excision for all Radial Sclerosing Lesions of the Breast

IntroductionThe need for routine surgical excision of a radial sclerosing lesions (RSL) of the breast identified on percutaneous biopsy remains controversial, as contemporary upgrade rates are lower than historically cited. Materials and methodsA prospectively-maintained database of high-risk breast biopsies undergoing multidisciplinary review at a single institution was queried to identify cases of RSL from 2/2015 to 11/2020. Demographic, radiologic, and pathologic variables were summarized using frequencies and analyzed in association with RSL excision status using mixed-effects logistic regression or Fisher's exact tests. Results217 RSL were identified, diagnosed at a mean age of 57 y. The median imaging size was 1.3 cm and the majority had estimated >50% of the target removed by core needle biopsy. 32.3% underwent surgical excision of the RSL biopsy site and 2/70 (2.9%) upgraded to ductal carcinoma in situ (DCIS) on final surgical pathology. Upgrade was significantly higher for atypical RSL (P = 0.02). None of the RSL (n = 60) without atypia who had undergone excision were upgraded. For those omitting surgical excision, there was no subsequent breast cancer diagnosis at the RSL site over a mean follow-up of 23 mo. ConclusionsSurgical excision may be omitted for RSL without atypia as this group has 0% risk of upgrade after multidisciplinary review.

Upgrading Rate and Associated Factors of High-Risk Breast Lesions from Imaging Guided Breast Biopsy in King Chulalongkorn Memorial Hospital

Objective: To determine the underestimate rate of high-risk lesions from imaging guided breast biopsy to be malignancy from subsequent surgical excision in King Chulalongkorn Memorial Hospital and to determine the factor associated to imaging characteristics and geographic data. Materials and Methods: A retrospective review of 79 high-risk breast lesions of 78 patients who underwent imaging guided breast biopsy studies between January 1, 2010, and August 31, 2020, on women, aged 30 years or older in King Chulalongkorn Memorial Hospital. The upgrading rate of the high-risk lesions were calculated. Radiologic findings were analyzed by SPSS version 26. Results: Seventy-nine lesions were divided into three groups with 24 lesions of atypical ductal hyperplasia (ADH), 50 lesions of the papillary lesion, and five lesions of the complex sclerosing lesion. The authors found that the upgrade rate was about 58% in the ADH group, 28% in the papillary lesion group, and 20% in the complex sclerosing lesion group. Moreover, the authors found an increased upgrade rate among patient 50 years or older (43%) as compared with fourteen patients age under 50 years (32%). However, there was no statistically significant difference in radiologic findings or factors associated with upgrading rate to malignancy under subsequent surgical excision. Conclusion: Upgrading rate of high-risk lesions including ADH, papillary lesions, and complex sclerosing lesion were high in each lesion and the upgrade rate increased slightly in patient 50 years or older. However, there was no demonstrable radiologic manifestation or factor associated with upgrading to malignancy at subsequent surgical excision. Hence, radiologic-pathologic correlation or multidisciplinary discussion will be important roles in management of high-risk lesions. Keywords: Breast; High risk lesion; Atypical ductal hyperplasia (ADH); Papillary lesions; Radial scar; Complex sclerosing lesion

Malignancy Upgrade Rates of Radial Sclerosing Lesions at Breast Cancer Screening

Purpose To determine the upgrade rate for biopsy-proven radial scars and radial sclerosing lesions (RS). Materials and Methods In this retrospective study, radiology and pathology databases from two tertiary breast centers were searched to identify patients with biopsy-confirmed RS between March 1, 2012, and December 31, 2017, during which all mammography was performed with digital breast tomosynthesis (DBT). Adjunct modalities such as MRI or US are performed at our centers to better characterize lesions identified at DBT. Patient demographics, imaging, needle and excisional biopsies, and follow-up data were collected at the patient level. Clopper-Pearson interval estimate for upgrade was calculated for 95% confidence using PropCIs package with R version 4.1.0 (R Foundation for Statistical Computing) (1). Results During the study period, a total of 155 885 DBT examinations were performed. From these examinations, 146 biopsy-proven RS were identified in 142 women (median age, 58 years; age range, 26-87 years). A total of 80.1% (117 of 146) of all RS did not have associated atypia or malignancy, and 19.9% (29 of 146) had associated atypia at initial biopsy. A total of 66.7% (78 of 117) of RS without atypia or malignancy were surgically excised, 25.6% (30 of 117) were followed (median, 3 years; range, 1-7 years) with benign findings on imaging, and 7.7% (nine of 117) were lost to follow-up. The rate of malignancy upgrade was 0.9% (one of 117 [95% CI: 0.02, 4.7]); one RS without concurrent atypia or malignancy demonstrated invasive carcinoma at surgical excision. Conclusion RS without atypia had a low upgrade rate. Keywords: Mammography, Breast © RSNA, 2021.

EP.TH.803VAE for Breast Lesions of Uncertain Potential (B3) -A Quality Improvement Project

Abstract Aims Breast lesions of uncertain malignant potential (B3) account for 7% breast lesions biopsied. Management has been controversial and challenging for the MDT. Aim of the study was to compare current NHS BSP guidelines with our trust’s practice and the secondary outcome was a shorter patient pathway and cost effectiveness. Methods As per NHS BSP guidelines VAE should be performed for all B3 lesions diagnosed on 14g or vacuum assisted biopsy. We were referring them to other NHS trusts as there were no in-house facilities or doing an excisional biopsy if no resources for VAE available. From September 2019 VAEs started to be done by in-house consultant breast radiologist after getting the appropriate training and instruments. Data was collected from September 2019 to August 2020 for all patients. Results 22 VAEs were performed in one year. Out of those 6 (27.2%) were upgraded to malignancy and needed further surgery, 2 (9%) with atypia had 5 years mammographic surveillance and 14 (63%) were discharged including sclerosing lesions, radial scars, fibrosis and chronic inflammation. The cost of VAE in our hospital is £1330 vs. £2439 for Wire Guided wide local excision. This makes it cost effective. Conclusion We were following the VAE protocol as per NHS BSP guidelines. Despite added workload to radiology VAE is minimally invasive, safe and cost effective alternative to surgery providing thorough MDT discussion has taken place. Greater benefit was provided to patient as all VAEs were performed in radiology department avoiding general Anaesthesia and surgical trauma.

Epidemiology, baseline characteristics and risk of progression in the first South-Asian prospective longitudinal observational IgA nephropathy cohort

IntroductionGlomerular Research And Clinical Experiments–IgA Nephropathy in Indians (GRACE-IgANI) is the first prospective South Asian IgAN cohort with protocolized follow-up and extensive biosample collection. Here we report the baseline clinical, biochemical, and histopathologic characteristics of GRACE IgANI and calculate baseline risk of progression for the cohort.Methods201 incident adults with kidney biopsy–proven primary IgAN were recruited into GRACE-IgANI between March 2015 and September 2017. As of April 30, 2020, the cohort had completed a median follow-up of 30 months (interquartile range [IQR] 16-39).ResultsThe commonest clinical presentation in GRACE IgANI was hypertension, with or without proteinuria, and nephrotic-range proteinuria was present in 34%, despite <10 months of lead time to kidney biopsy. The GRACE-IgANI kidney biopsy data demonstrated a disproportionate absence of active glomerular lesions and overrepresentation of segmental sclerosing lesions and tubulointerstitial fibrosis at presentation, often coexistent with relatively well-preserved estimated glomerular filtration rate (eGFR) and low levels of proteinuria, especially in males. Baseline risk of progression was calculated for each evaluable patient using 2 different risk prediction tools. The median 5-year absolute risk of end-stage kidney disease (ESKD) was 19.8% (IQR 2.7–57.4) and median 5-year risk of progression to the combined endpoint of 50% decline in eGFR or ESKD was 35.5% using the 2 tools.ConclusionsThe predicted risk of progression in this cohort was considerable. Over the next 5 years, we will dissect the pathogenic pathways that underlie this severe South Asian IgAN phenotype.

CHRONIC PERICARDITIS SECONDARY TO COXSACKIE VIRAL INFECTION PRESENTING AS FIBROSING MEDIASTINITIS

SESSION TITLE: Fellows Chest Infections Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: October 18-21, 2020 INTRODUCTION: Fibrosing mediastinitis (FM) is a rare fibroinflammatory disease classified as idiopathic or secondary. Most common infectious cause in the United states is histoplasma. Additional causes include malignancy, autoimmune, and sarcoidosis. CASE PRESENTATION: 45-year-old female presented with chest pain. A transthoracic echocardiogram (TTE) showed pericardial effusion with tamponade physiology and pericardial window with biopsy was done. Pathology showed fibrovascular tissue, adipose tissue with perivascular chronic inflammation. Cytology; negative for malignancy. Weakly positive Coxsackie titers were 1:16 and 1:8 for B1 & B2 respectively, negative bacterial, fungal, mycobacterial, and viral cultures. Negative Lyme antibody titers, mycoplasma IgG, cryptococcal and histoplasma antigens. Normal IgG levels. Negative rheumatological work up apart from weakly positive anti-nuclear antibody. Progressive symptoms of dyspnea despite treatment with anti-inflammatory medications. Subsequent CT showed mediastinal mass encasing the right pulmonary artery (PA) trunk (figure 1). Moderate to severe narrowing of the right PA seen on cardiac MRI. Bronchoscopy with EBUS guided TBNA revealed lymphocytes but no definite diagnosis. Endovascular biopsy of the mediastinal mass showed fibrillar sclerosing lesion with plasma cells and necrotizing granuloma. IgG staining positive for IgG4+ plasma cells but not enough to meet criteria for IgG4-related disease. Abundance of CD20+ve cells on histology. DISCUSSION: Patient did not meet criteria for IgG4-RD diagnosis. She tested negative for all secondary etiologies. Coxsackie virus infection causing chronic pericarditis leading to FM is our hypothesis. CONCLUSIONS: This represents the first report of FM caused by chronic pericarditis probably due to coxsackie viral infection. Reference #1: RadioGraphics 2019; 39:651-667 Reference #2: Ann Thorac Med. 12(3):209-212 DISCLOSURES: No relevant relationships by Sammar Alsunaid, source=Web Response no disclosure on file for Allen Burke; no disclosure on file for Joseph Friedberg; No relevant relationships by Van Holden, source=Web Response Consultant relationship with Medtronic Please note: $1001 - $5000 Added 06/11/2020 by Edward Pickering, source=Web Response, value=Consulting fee Consultant relationship with Merit Endotek Please note: $1-$1000 Added 04/06/2020 by Ashutosh Sachdeva, source=Web Response, value=Consulting fee Consultant relationship with Medtronic Please note: $1001 - $5000 Added 04/06/2020 by Ashutosh Sachdeva, source=Web Response, value=Consulting fee Speaker/Speaker's Bureau relationship with COOK Please note: $1001 - $5000 Added 04/06/2020 by Ashutosh Sachdeva, source=Web Response, value=Honoraria Consultant relationship with Medtronic Please note: $1001 - $5000 by Ashutosh Sachdeva, source=Web Response, value=Consulting fee Unrestricted education grant relationship with Olympus Please note: $1001 - $5000 by Ashutosh Sachdeva, source=Web Response, value=Grant/Research Support Consultant relationship with COOK Please note: $1001 - $5000 Added 04/27/2020 by Ashutosh Sachdeva, source=Web Response, value=Honoraria

A reappraisal of sclerosing nodular and/or polypoid lesions of the gastrointestinal tract rich in IgG4-positive plasma cells.

To describe additional cases of nodular and polypoid sclerosing lesions of the gastrointestinal tract (GIT) that are associated with numerous IgG4-positive plasma cells, review the pertinent literature to ascertain the relationship with systemic IgG4-related disease, and provide a reporting framework for such lesions. Five new cases of sclerosing polyps or nodules were collected over a 10-year period, occurring in four females and one male ranging in age from 32years to 56years (mean, 41.6years). Patients were asymptomatic or had epigastric pain, and one had rectal bleeding. None had autoimmune or other obvious IgG4-related disease, and serum IgG4 levels were normal. All were solitary nodules in the stomach (two cases), ileum, caecum, and rectum. Four lesions were submucosal and one was subserosal; all were well circumscribed, composed of hyalinised, keloidal fibrous tissue with lymphoplasmacytic inflammation. Obliterative phlebitis was not seen. Lineage-specific immunomarkers were negative. In excess of 10 IgG4-positive plasma cells per high-power field were seen, and the IgG4/IgG ratios were >0.4. Very few IgG4-related lesions in the tubular GIT are associated with disease at other sites and/or elevated serum IgG4 levels. The majority may represent a lesion in the spectrum of IgG4-related disease. The use of the term 'IgG4-positive nodule or polyp with probable histological features of IgG4-related disease' is advocated for nodular and/or polypoid lesions in the GIT with ≥10 IgG4-positive plasma cells in a high-power field and an IgG/IgG4 ratio of >0.4.

Digital Mammography Stereotactic Biopsy versus Digital Breast Tomosynthesis-guided Biopsy: Differences in Biopsy Targets, Pathologic Results, and Discordance Rates.

Background Digital breast tomosynthesis (DBT)-guided biopsy is increasingly used in practice. It is important to know expected changes in biopsy targets, pathologic results, and discordance rates. Purpose To compare biopsy target types, pathologic results, and discordance rates for 2 years preceding and 2 years following implementation of DBT-guided biopsy. Materials and Methods All 9-gauge vacuum-assisted core biopsies from a single tertiary breast center that used digital mammography (DM) stereotactic guidance from 2013 to 2015 and DBT-guided biopsy from 2015 to 2017 were retrospectively reviewed. All mammographic examinations were performed with DBT. Patient demographics, biopsy target type, pathologic reports, surgical excision specimens when available, breast density, and imaging follow-up results were recorded. Biopsy targets and discordance rates between radiologic and pathologic examinations were compared between the two biopsy groups. Generalized mixed modeling was used to examine results before and after DBT-guided biopsy. Results A total of 1313 women underwent 1405 breast biopsies: 643 by using DM (August 2013 to July 2015) (median age, 56 years; interquartile range, 49-66 years) and 762 by using DBT (August 2015 to July 2017) (median age, 58 years; interquartile range, 50-67 years), (P = .58). Calcifications were the most common biopsy target for both groups, constituting 89.9% (578 of 643) of DM-guided biopsies and 71.1% (542 of 762) of DBT-guided biopsies (P = .03). The rate of architectural distortion biopsies was 2.0% (13 of 643) with DM-guided biopsy and 17.7% (135 of 762) with DBT-guided biopsy (P = .01). Although overall malignancy rate was similar for DM-guided biopsy (27.8% [179 of 643]) and DBT-guided biopsy (24.8% [191 of 762], P = .54), DBT-guided biopsy helped identify a similar percentage of invasive malignancies (37.4% [72 of 191] vs 29.0% [52 of 179] at DM P = .35), but more radial sclerosing lesions (8.3% [95% confidence interval {CI}: 6.0, 10.0] vs 1.7% [95% CI: 1.0, 3.1]) (P = .01). The discordance rate was 1.4% (95% CI: 1.0, 2.7) with DM-guided biopsy and 4.5% (95% CI: 3.2, 6.3) with DBT-guided biopsy (P = .01). Of the 34 discordant DBT-guided biopsies, 30 were architectural distortions. Conclusion With the transition to digital breast tomosynthesis-guided biopsy, more architectural distortions were biopsied, more radial sclerosing lesions were identified, and more discordance existed in radiologic and pathologic examinations, with a similar percentage of carcinomas diagnosed. © RSNA, 2020 Online supplemental material is available for this article.

Complex sclerosing lesion of the breast displaying progression to invasive cancer: A case report

A 70 year old lady presented with two lumps in the right breast since around fifteen years which were increasing in size since the past one year. Mammography showed a solid-cystic and a lobulated lesion in the right breast which were categorized as BIRADS (Breast Imaging- Reporting and Data System) category 4/5. On FNAC, a diagnosis of Atypical Ductal Hyperplasia, NHSBSP (National Health Service Breast Screening Programme) Category C4 was made and histopathologic examination advised. Subsequently right sided simple mastectomy was received the larger mass in which showed extensive areas of sclerosing adenosis with superimposed ductal carcinoma in situ. The subareolar mass showed a papillary lesion displaying epithelial overgrowth with features compatible with ductal carcinoma in situ. A thorough search revealed invasive nests in the vicinity of the papillary lesion. A diagnosis of Infiltrating Ductal Carcinoma arising in a multifocal complex sclerosing lesion with extensive intraductal carcinoma and intracystic papillary carcinoma was made. This case offers to display a pathologic continuum of sclerosing breast lesions evolving into atypical hyperplasias, intraductal carcinoma and invasive carcinoma. This falls in line with the current thoughts on premalignant nature of sclerosing lesions of the breast.

IgG4-related disease: review of the histopathologic features, differential diagnosis, and therapeutic approach.

Immunoglobulin G4-related disease (IgG4-RD) is an uncommon disorder that demonstrates characteristic clinicopathologic features including sclerosing lesions with storiform fibrosis, increased IgG4+ plasma cells with an increased IgG4+/IgG+ plasma cell ratio, obliterative phlebitis, and often an increased serum IgG4 level. This review summarizes the characteristic histopathologic and clinical features of IgG4-RD with detailed discussion of the histopathologic characteristics of the most commonly involved anatomic sites. We also present recent advances in our understanding of the pathophysiologic mechanisms of IgG4-RD and discuss updates on the treatment, prognosis, and outcomes of this rare disease, including discussion of the possible association between IgG4-RD and malignancy.

Complex sclerosing lesions and radial sclerosing lesions on core needle biopsy: Low risk of carcinoma on excision in cases with clinical and imaging concordance

Complex or radial sclerosing lesions (CSL/RSL) are uncommon diagnoses on core needle biopsy with a reported upgrade rate ranging between 0% and 23%. As a result, their management remains controversial. In this study, we sought to determine the rate of malignancy on excision for patients with pure CSL/RSL on core biopsy, and to evaluate future breast cancer risk when CSL/RSL is managed without excision. We retrospectively reviewed 118 cases of CSL/RSL diagnosed on image-guided breast biopsies between 2005 and 2014 at our institution. Of 98 analyzed patients, 34 (35%) underwent excision and 64 (65%) were observed. Demographic and clinical variables between excision and observation groups were compared. In excised specimens, factors associated with upgrade to malignancy were evaluated. The median age at diagnosis was 49 years (range, 27-88 years). In the excision group, 3/34 cases were associated with malignancy, an overall upgrade rate of 9%. All malignant cases had core needle biopsies interpreted as discordant and were BIRADS 4B or more on imaging. In the observation group, at a median follow-up of 2.2 years, 3/64 (5%) patients developed ipsilateral cancers, all of which were distant from the index CSL/RSL. In our series, we report a 9% malignancy rate on excision of BIRADS >4C lesions characterized as CSL/RSL on core biopsy. In patients with concordant biopsies and BIRADS 4A or lower lesions who underwent observation, we found a low rate of subsequent ipsilateral cancers. Further studies are needed to confirm that for CSL/RSL in concordant core biopsies and BIRADS 4A or lower, nonpalpable lesions, observation may be a reasonable alternative to excision.

Next generation sequencing of the nidus of early (adenosquamous proliferation rich) radial sclerosing lesions of the breast reveals evidence for a neoplastic precursor lesion.

We sought to determine if adenosquamous proliferation of early cellular radial sclerosing lesions of the breast harbours hot spot mutations and to help clarify its relationship to low‐grade adenosquamous carcinoma as a potential form of early neoplasia. Four low‐grade adenosquamous carcinomas, early radial sclerosing lesions from 13 individuals, and 4 benign proliferative breast lesions were microdissected and assessed with a 50‐gene Hot‐spot cancer panel. Early radial sclerosing lesions were selectively microdissected concentrating on their adenosquamous proliferation (nidus). Hot spot mutations in PIK3CA were detected in ten (77% of) radial sclerosing lesions, in one low‐grade adenosquamous carcinoma, and in usual ductal hyperplasia and apocrine adenosis. Over three quarters of individuals with cellular (adenosquamous proliferation rich) early radial sclerosing lesions tested harboured somatic mutations in PIK3CA suggesting that adenosquamous proliferation is a clonal lesion. Its relationship to low‐grade adenosquamous carcinoma remains unclear in view of the small sample size and unmatched radial sclerosing lesions and low‐grade adenosquamous carcinomas.

Pathology of Podocytopathies Causing Nephrotic Syndrome in Children.

Nephrotic syndrome (NS) in children includes a diverse group of diseases that range from genetic diseases without any immunological defects to causes that are primarily due to immunological effects. Recent advances in molecular and genomic studies have resulted in a plethora of genetic defects that have been localized to the podocyte, the basic structure that is instrumental in normal filtration process. Although the disease can manifest from birth and into adulthood, the primary focus of this review would be to describe the novel genes and pathology of primary podocyte defects that cause NS in children. This review will restrict itself to the pathology of congenital NS, minimal change disease (MCD), and its variants and focal segmental glomerulosclerosis (FSGS). The two major types of congenital NS are Finnish type characterized by dilated sausage shaped tubules morphologically and diffuse mesangial sclerosis characterized by glomerulosclerosis. MCD has usually normal appearing biopsy features on light microscopy and needs electron microscopy for diagnosis, whereas FSGS in contrast has classic segmental sclerosing lesions identified in different portions of the glomeruli and tubular atrophy. This review summarizes the pathological characteristics of these conditions and also delves into the various genetic defects that have been described as the cause of these primary podocytopathies. Other secondary causes of NS in children, such as membranoproliferative and membranous glomerulonephritis, will not be covered in this review.

Evaluation of p40 as a Myoepithelial Marker in Different Breast Lesions

Objective: The identification of myoepithelial cells (MEC) is a valuable clue in the differential diagnosis of breast lesions. A series of breast lesions with occasional absence of or decrease in the staining for some MEC markers was analyzed for the expression of a novel marker, p40, and results were compared to the p63 staining profile. Methods: Samples (n = 34) from patients with benign sclerosing lesions (n = 11), ductal carcinoma in situ (n = 13) and adenomyoepithelial lesions (n = 10) and associated normal breast tissues (n = 31) were selected to evaluate the differential expression of p40 and p63 using immunohistochemistry. Triple-negative, cytokeratin 5 (CK5)-expressing invasive breast carcinomas (n = 19) were also assessed for p40 expression. Results: Normal structures showed similar diffuse and strong MEC positivity using p40 and p63 in all 31 cases. The two antibodies performed similarly in all 34 breast lesions acknowledged to present altered expression of MEC markers; focal losses of expression occurred in a parallel fashion. CK5-positive carcinomas expressed p40 more frequently than p63 (18/19 vs. 8/19) and the staining was more marked. Conclusions: It seems that both antibodies can be used interchangeably for MEC identification, but show differences in the labeling at least in a subset of tumor cells in triple-negative carcinomas.

Keratin Expression Patterns in Stromal Cells of Benign Sclerosing Lesions of the Breast: A Potential Diagnostic Pitfall.

Metaplastic carcinomas arising in association with benign sclerosing lesions (BSLs) are rare malignancies in which a neoplastic spindle cell proliferation can be recognized extending beyond the boundaries of the complex sclerosing lesion or papilloma. However, in cases in which the metaplastic carcinoma is of the low-grade fibromatosis-like type or is a low-grade adenosquamous carcinoma, distinction from the background BSL can be a significant challenge. Cytokeratin (CK) and/or p63 immunostains are helpful in confirming the diagnosis of metaplastic carcinoma, but the expression patterns of these markers in the stromal cells of BSLs have not been well characterized. To characterize the expression patterns of CKs and p63 in BSLs. We evaluated the spindle cell component of 55 BSLs using CK 5/6, CK 903, CK MNF116, and p63. A total of 45 cases (81%) showed no staining for CKs or p63 in benign stromal cells. CK 5/6, CK 903, and p63 were positive in one case each. CK MNF116 stained spindle cells within 10 BSLs. No cases showed spindle cell reactivity for all 4 markers. Positive cases demonstrated very focal, weak staining of spindle cells; only 1 case showed focal, moderate CK staining. Spindle cell positivity was not associated with lesion type, growth pattern, spindle cell atypia, or mitoses. These findings suggest that although the presence or absence of expression of CK 5/6, CK 903, and p63 may be useful to distinguish BSL from metaplastic carcinomas arising in this setting, CK MNF116 positivity may be a diagnostic pitfall.

Adenosquamous proliferation of the breast and low grade adenosquamous carcinoma: a common precursor of an uncommon cancer?

Low grade adenosquamous carcinoma (LGASC) is rare but commonly reported to arise in association with benign proliferative and sclerosing breast lesions which themselves may show associated sclerosing or 'adenosquamous proliferation' (ASP) resembling LGASC, but are often derided as reactive mimics or attributed to earlier biopsy. Among other benign lesions, radial sclerosing lesion (RSL) may be associated with LGASC, yet attention is typically focused on its relationship to more common forms of mammary carcinoma. This study aimed to assess the presence and extent of ASP in the context of RSL in a small cohort of 20 cases and its similarity to LGASC.Twenty consecutive breast excisions that had a principal or incidental diagnosis of RSL were reviewed. RSLs that displayed foci of ASP were further examined with immunohistochemical markers for p63, calponin, cytokeratin 5/6, oestrogen and progesterone receptors.Sixty percent of excisions contained ASP either associated with a RSL or a concurrent papilloma, which morphologically and immunohistochemically were indistinguishable from the neoplastic ducts of LGASC. RSL with and without ASP broadly corresponded to accepted definitions for 'early' and 'late' lesions, respectively. ASP corresponded to the characteristic compact branching ducts of the core or nidus of a RSL.The morphological and immunophenotypic similarity of the ASP found in RSL and papillomata to LGASC warrants serious consideration that they are a potential precursor to LGASC, which may most commonly involute given the rarity of clinically apparent LGASC. Further study including micro-dissection of foci of ASP to compare its molecular genetic profile to that of LGASC is required.