Stromal Hyperplasia Research Articles

A rare case of breast intracanalicular fibroadenoma associated with pseudoangiomatous stromal hyperplasia in a 11-year-old female

A rare case of breast intracanalicular fibroadenoma associated with pseudoangiomatous stromal hyperplasia in a 11-year-old female

Rapidly-growing pseudoangiomatous stroma hyperplasia (PASH) causing bilateral gigantomastia in a 15-year-old patient

A 15-year-old female patient presented to our clinic with rapidly-growing breasts, causing her back and neck pain, mastalgia, and unwanted attention at school. Clinical evaluation showed bilateral enlarged breasts with multiple palpable tumors. Her height and body weight were 1.76 m and 54 kg, respectively. Both ultrasound and magnetic resonance imaging (MRI) were conducted. Histological biopsies showed pseudoangiomatous stroma hyperplasia (PASH). Bilateral diffuse multiple tumors leading to massive bilateral breast enlargement are rare, especially in pediatric patients. To the best of our knowledge, all previous reported cases were patients of 29 years old or older. We present the evaluation and treatment in a rare case of multiple PASH causing bilateral gigantomastia in an adolescent patient.Level of evidence: Level V, therapeutic study.

Our 20-Year Institutional Experience with Surgical Approach for Breast Hamartomas.

Hamartomas are rare, slowly-growing breast tumours. Clinical, radiological and histopathological examination together increase the diagnostic accuracy. To evaluate the clinicopathologic features of hamartomas and outline our clinical approach to hamartomas in our 20-year experience at our Breast Clinic. Between 1995 and 2015, 24 cases were retrospectively analyzed with a diagnosis of breast hamartoma at our Breast Clinic followed by excisional biopsy. Data was obtained on patient demographics, clinical examination, radiological findings and histopathological subtypes. Of 1338 benign breast tumours excised from January 1995 to January 2015, 24 (1.8%) were identified as breast hamartoma. Median age of patients was 42 (range, 13-70), whereas the median tumour size was 5 cm (1-10 cm). On preoperative imaging, hamartoma was most commonly misdiagnosed as fibroadenoma. Pathological examination of the 24 biopsy specimens revealed 3 cases with pseudoangiomatous stromal hyperplasia, and another hamartoma associated with a radial scar within the centre of the lesion. Of those, one patient was diagnosed with malignant phylloides tumour in the same breast. At a median follow-up 58.4 months, none of the patients recurred or developed malignancy. Hamartomas can often be missed by clinicians, due to its benign nature which is poorly understood. Despite their slow growth, hamartomas can reach large sizes and can cause breast asymmetry. Although it is rare, hamartoma can be seen along with malignancy, as it is formed from similar components of breast tissue. Therefore, careful diagnosis and appropriate management including surgery are required.

Ultrastructure study of the transgenic REN2 rat aorta – part 2: media, external elastic lamina, and adventitia

Background The renin-angiotensin-aldosterone system (RAAS) plays an important role in the development and progression of vascular stiffness, hypertension and accelerated atherosclerosis, which are associated with the metabolic syndrome (MetS) and type 2 diabetes mellitus. In addition to the intima, RAAS plays an important role in vascular media and adventitial remodeling. Methods Descending thoracic aortas of young male transgenic heterozygous (mRen2) 27 (Ren2) rats were utilized for ultrastructural study. This lean model of hypertension, insulin resistance, and oxidative stress harbors the mouse renin gene and is known to have increased aortic tissue levels of angiotensin II, angiotensin type 1 receptors, and elevated plasma aldosterone levels. Results Ultrastructural observations substantiate known and novel findings in the tunica media, internal and external elastic lamina, and tunica adventitia, which includes: increased media collagen - proteoglycan matrix expansion, increased secretory and proliferative activity and migration of vascular smooth muscle cells (VSMCs) into a newly developing subendothelial neointima, increased VSMC caveolae, mitochondria degeneration, apoptosis; and lipid retention at the elastin lamellar interface. Openings in the external elastic lamina allow pericyte-to-VSMC contacts. The tunica adventitia exhibits stromal pericyte hyperplasia with actively synthetic phenotype and pericyte-pericyte connections. Conclusion While these studies only represent a single snapshot in time, they provide an evaluation of early abnormal ultrastructural vascular remodeling in Ren-2 models of the conduit-elastic thoracic aorta.

Hyperglycemia and T Cell infiltration are associated with stromal and epithelial prostatic hyperplasia in the nonobese diabetic mouse.

Prostatic inflammation and various proinflammatory systemic comorbidities, such as diabetes and obesity are associated with human benign prostatic hyperplasia (BPH). There is a paucity of in vivo models reflecting specific aspects of BPH pathogenesis. Our aim was to investigate the nonobese diabetic (NOD) mouse as a potential model for subsequent intervention studies. We used the NOD mouse, a model of autoimmune inflammation leading to type 1 diabetes to examine the effects of systemic inflammation and diabetes on the prostate. We assessed changes in prostatic histology, infiltrating leukocytes, and gene expression associated with aging and diabetic status. Both stromal expansion and epithelial hyperplasia were observed in the prostates. Regardless of diabetic status, the degree of prostatic hyperplasia varied. Local inflammation was associated with a more severe prostatic phenotype in both diabetic and nondiabetic mice. Testicular atrophy was noted in diabetic mice, but prostate glands showed persistent focal cell proliferation. In addition, a prostatic intraepithelial neoplasia (PIN)-like phenotype was seen in several diabetic animals with an associated increase in c-Myc and MMP-2 expression. To examine changes in gene and cytokine expression we performed microarray and cytokine array analysis comparing the prostates of diabetic and nondiabetic animals. Microarray analysis revealed several differentially expressed genes including CCL3, CCL12, and TNFS10. Cytokine array analysis revealed increased expression of cytokines and proteases such as LDLR, IL28 A/B, and MMP-2 in diabetic mice. Overall, NOD mice provide a model to examine the effects of hyperglycemia and chronic inflammation on the prostate, demonstrating relevance to some of the mechanisms present underlying BPH and potentially the initiation of prostate cancer.

MP06-09 SENESCENT PROSTATIC EPITHELIAL CELLS INDUCE PROLIFERATION OF FIBROBLAST DURING THE PROGRESSION OF BENIGN PROSTATIC HYPERPLASIA

INTRODUCTION AND OBJECTIVES:Benign prostatic hyperplasia (BPH) is a disease characterized by stroma hyperplasia. Our previous studies, stroma–epithelium ratios and collagen deposition were prevalen...

Histopathologic findings in breast surgical specimens from patients undergoing female-to-male gender reassignment surgery

Breast reduction surgery or mastectomy following administration of androgen therapy is part of the female-to-male gender reassignment process. Details regarding the histopathologic findings in breast tissue from patients undergoing female-to-male gender reassignment surgery are limited. We reviewed hematoxylin and eosin-stained sections of breast tissue from 148 patients who underwent breast reduction surgery or mastectomy as part of the female-to-male gender reassignment process at our institution between January 2014 and May 2017. The spectrum of histologic features in each case was catalogued. The median patient age was 27 years (range 18–60 years). Lobular atrophy was seen to some degree in 73% of cases and was prominent in 42%. A predominantly fibrotic stroma was seen in 45% of cases and areas resembling the fibrous stage of gynecomastia were seen in 41%. Other features included variably ectatic ducts in 96% of cases, cysts in 42%, apocrine metaplasia in 32%, fibroadenomatous change in 27%, usual ductal hyperplasia in 26%, and pseudoangiomatous stromal hyperplasia in 19%. Five cases (3%) demonstrated atypical hyperplasia (atypical ductal hyperplasia in 2; atypical lobular hyperplasia in 2; both atypical ductal hyperplasia and atypical lobular hyperplasia in 1). One case demonstrated high grade ductal carcinoma in situ. No invasive carcinomas were identified. In conclusion, the majority of breast specimens from patients undergoing female-to-male gender reassignment demonstrate at least some degree of lobular atrophy as well as ectatic ducts, fibrous stroma, and areas resembling the fibrous stage of gynecomastia. Only rare cases showed atypical lesions; the clinical significance of these lesions in this setting is uncertain.

Analysis of PI-RADS 4 cases: Management recommendations for negatively biopsied patients

PurposeTo evaluate if subgroups of patients assigned to MRI category PI-RADS 4 regarding clinical and MRI imaging aspects have distinct risks of prostate cancer (PCa) to facilitate adequate clinical management of this population, especially after negative targeted biopsy. MethodsThis prospective, IRB approved single center cross-sectional study includes 931 consecutive patients after mp-MRI at 3 T for PCa detection. 193 patients with PI-RADS assessment category 4 received subsequent combined targeted MRI/US fusion-guided and systematic 12-core TRUS-guided biopsy as reference standard and were finally analyzed. The primary endpoint was PCa detection of PI-RADS 4 with MRI subgroup analyses. Secondary endpoints were analyses of clinical data, location of PCa, and detection of targeted biopsy cores. ResultsPCa was detected in 119 of 193 patients (62%) including clinically significant PCa (csPCa; Gleason score ≥3 + 4 = 7) in 92 patients (48%). MRI subgroup analysis revealed 95% PCa (73% csPCa) in unambiguous PI-RADS 4 index lesions without additional, interfering signs of prostatitis in the peripheral zone or overlaying signs of severe stromal hyperplasia in the transition zone according to PI-RADS v2. Transition zone confined PI-RADS-4-lesions with overlaying signs of stromal hyperplasia showed PCa only in 11% (4% csPCa). Targeted biopsy cores missed the csPCa index lesion in 7% of the patients. PSA density (PSAD) was significantly higher in PCa patients. ConclusionsSmall csPCa can reliably be detected with mp-MRI by experienced readers, but can be missed by targeted MR/US fusion biopsy alone. Targeted re-biopsy of unambiguous (peripheral) PI-RADS-4-lesions is recommended; whereas transition zone confined PI-RADS-4-lesions with overlaying signs of stromal hyperplasia might be followed-up by re-MRI primarily.

Androgen excess in breast cancer development: implications for prevention and treatment.

The aim of this review is to highlight the pivotal role of androgen excess in the development of breast cancer. Available evidence suggests that testosterone controls breast epithelial growth through a balanced interaction between its two active metabolites: cell proliferation is promoted by estradiol while it is inhibited by dihydrotestosterone. A chronic overproduction of testosterone (e.g. ovarian stromal hyperplasia) results in an increased estrogen production and cell proliferation that are no longer counterbalanced by dihydrotestosterone. This shift in the androgen/estrogen balance partakes in the genesis of ER-positive tumors. The mammary gland is a modified apocrine gland, a fact rarely considered in breast carcinogenesis. When stimulated by androgens, apocrine cells synthesize epidermal growth factor (EGF) that triggers the ErbB family receptors. These include the EGF receptor and the human epithelial growth factor 2, both well known for stimulating cellular proliferation. As a result, an excessive production of androgens is capable of directly stimulating growth in apocrine and apocrine-like tumors, a subset of ER-negative/AR-positive tumors. The key role of androgen excess in the genesis of different subtypes of breast cancer has significant clinical implications for both treatment and prevention. Our belief stems from a thorough analysis of the literature, where an abundance of evidence is present to justify a clinical trial that would investigate the effectiveness of treating the underlying excessive androgen production.

Transition zone prostate cancer: Logistic regression and machine‐learning models of quantitative ADC, shape and texture features are highly accurate for diagnosis

The limitation of diagnosis of transition zone (TZ) prostate cancer (PCa) using subjective assessment of multiparametric (mp) MRI with PI-RADS v2 is related to overlapping features between cancers and stromal benign prostatic hyperplasia (BPH) nodules, particularly in small lesions. To evaluate modeling of quantitative apparent diffusion coefficient (ADC), texture, and shape features using logistic regression (LR) and support vector machine (SVM) models for the diagnosis of transition zone PCa. Retrospective. Ninety patients; 44 consecutive TZ PCa were compared with 61 consecutive BPH nodules (26 glandular/35 stromal). 3 T/T2 -weighted (T2 W) fast spin-echo, diffusion weighted imaging. A radiologist manually segmented lesions on axial images for quantitative ADC (mean, 10th , 25th -centile-ADC), T2 W-shape (circularity, convexity) and T2 W-texture (kurtosis, skewness, entropy, run-length nonuniformity [RLNU], gray-level nonuniformity [GLNU]) analysis. A second radiologist segmented one-fifth of randomly selected lesions to determine the reproducibility of measurements. The reference standard was histopathology for all lesions. Quantitative features were selected a priori and were compared using univariate and multivariate analysis. LR and SVM models of statistically significant features were constructed and evaluated using receiver operator characteristic (ROC) analysis. Subgroup analysis of TZ PCa vs. only stromal BPH and in lesions measuring <15 mm was performed. Agreement in measurements was assessed using the Dice similarity coefficient (DSC). Mean, 25th and 10th -centile ADC, circularity, and texture (entropy, RLNU, GLNU) features differed between groups (P < 0.0001-0.0058); however, at multivariate analysis only circularity and ADC metrics (P < 0.001) remained significant. LR and SVM models were highly accurate for the diagnosis of TZ PCa (sensitivity/specificity/AUC): 93.2%/98.4%/0.989 and 93.2%/96.7%/0.949, respectively, with no significance difference between the LR and SVM models (P = 0.2271). Reproducibility of segmentation was excellent (DSC 0.84 tumors and 0.87 BPH). Subgroup analyses of TZ PCa vs. stromal BPH (AUC = 0.976) and in <15 mm lesions (AUC = 0.990) remained highly accurate. LR and SVM models incorporating previously described quantitative ADC, shape and texture analysis features are highly accurate for the diagnosis of TZ PCa and remained accurate when comparing TZ PCa with stromal BPH and in smaller lesions. 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:940-950.

Establishment and Validation of Extra-transitional Zone Prostate Specific Antigen Density (ETzD), a Novel Structure-based Parameter for Quantifying the Oncological Hazard of Prostates with Enlarged Stroma

Extra-transitional zone density (ETzD), a novel parameter is proposed to stratify the deviation of prostate specific antigen (PSA) due to structural change according to stromal hyperplasia of prostate. ETzD was conducted on a concept to estimate the PSA density (PSAD) after hypothetical enucleation of the transitional zone of an enlarged prostate by a non-linear regression prediction model with intrinsic linearity, from the retrospective analysis of PSA change observed actual enucleation by laser. The performance to predict the presence and severity of malignancy was validated by two cohorts of 3,440 prostate biopsies and 2,783 radical prostatectomy specimens. The performance of ETzD was compared with conventional parameters. The receiver operative curve of area under curve (AUC) of ETzD to predict the presence of malignacy was 0.862 (95% CI; 0.843~0.881), better than PSA, PSAD or transitional zone PSAD (TzPSAD). The AUC of ETzD to predict an unfavorable cancer among prostate cancer patients was 0.736 (95% CI; 0.705~0.768), which performs better than PSA and comparable to PSAD or TzPSAD. In summary, the performance of ETzD as a universal parameter to quantify the oncological hazard of a prostate was validated and the superiority to conventional parameters was verified.

Pseudoangiomatous stromal hyperplasia presenting as a tumor.

Pseudoangiomatous stromal hyperplasia presenting as a tumor.

Pseudoangiomatous stromal hyperplasia presenting as an enlarging breast mass: A case report

Pseudoangiomatous stromal hyperplasia (PASH) is an occasional histological finding in the breast tissue, which rarely presents as a clinical mass. We here report a case of progressively increasing breast lump that had radiological ambiguous findings but on excision proved to be PASH on histology and immunohistochemistry (IHC). On microscopy, PASH has to be distinguished from low-grade vascular tumors as stromal spaces in it mimic the endothelium-lined vascular spaces. In view of nonspecific radiological picture, histopathological confirmation by core needle or excision is mandatory. It may coexist with in situ or invasive breast malignancies also. IHC with stromal and vascular markers is the key to diagnosis of PASH; also these tumors show positivity with progesterone markers pointing to endocrine stimulation as a possible etiology. In asymptomatic PASH, expectant management is indicated; however, in symptomatic and enlarging masses, surgical treatment should be preferred.

Nodule-forming pseudoangiomatous stromal hyperplasia of the breast: case report.

Pseudoangiomatous stromal hyperplasia (PASH) is an uncommon benign proliferation of fibrous stroma, containing slitlike pseudovascular spaces lined by myofibroblasts. Less than 200 cases of PASH have been described in the English literature with the largest series including 40 cases. A 48-year-old woman with no particular past medical history, presented with a complaint of a slow, progressive, painless left breast mass. The patient underwent mammography which revealed a well delineated left breast nodule with microcalcifications classified BI-RADS 4. An excisional biopsy was performed on the mass to confirm the histological diagnosis. The specimen was a well-circumscribed whitish tumor measuring 3 x 3 cm with several microcysts (A). Histological examination revealed proliferation of fibrous stroma, with spindle cells and a network of slit-like empty clefts within acellular hyalinized stroma (B). The spindle cells were positive for CD34 and smooth muscle actin but were negative for Factor VIII. The final pathological diagnosis was nodular PASH. Postoperative course was uneventful and the patient is still being followed-up.

Developmental disorders and malformations of the breast.

Developmental abnormalities and malformations of the breast are rare and encompass a variety of genetic, syndromic, acquired and sporadic conditions. Abnormalities in development may include irregularities in the nipple areolar complex and/or the underlying glandular tissue, resulting in under or overdevelopment of breasts. Age of presentation and clinical severity is dependent on the underlying biologic cause. Abnormalities may involve the entirety of unilateral or bilateral breasts, particularly in association with syndromic conditions or endocrine abnormalities. Disordered development may also be focal, resulting in tumor-like lesions such as hamartomas, pseudoangiomatous stromal hyperplasia and gynecomastia. In this review, we discuss the disorders of breast development including etiologies, clinical presentations and corresponding histopathologic features.

Quantification of Leydig cells and stromal hyperplasia in the postmenopausal ovary of women with endometrial carcinoma

Endometrioid endometrial carcinomas (EECs) are correlated with high serum levels of androgens and estrogen. We hypothesized that Leydig cells and ovarian stromal hyperplasia contribute to postmenopausal ovarian androgen production and are observed more frequently in EEC patients. Ovaries of postmenopausal women with EEC (n = 36) or non-endometrioid endometrial carcinoma (NEEC; n = 19) were examined for the presence of hilar Leydig cells and compared with ovaries resected for benign conditions (n = 22). Leydig cells were counted manually, and a Leydig cell density was calculated per millimeter squared hilar surface. Ovarian stromal hyperplasia was scored as atrophic, moderate hyperplastic, or marked hyperplastic. In all endometrial carcinomas, these findings were correlated with the serum levels of sex steroids and hormone receptor expression in their endometrial carcinomas. In EEC patients, mean number of Leydig cells was 282.8 cells compared with 76.3 cells in NEEC patients and 66.4 cells in controls. Leydig cells, marked stromal hyperplasia, and combined presence were observed more frequently in EEC patients compared with NEEC and controls. Combined presence was associated with higher serum sex steroid levels and increased tumor expression of estrogen and progesterone receptor. A cutoff value for Leydig cell hyperplasia could be proposed at a total of 300 Leydig cells bilaterally, examining a representative cross section of both hili. Concluding, we have quantified hilar Leydig cells and demonstrated that Leydig cells may contribute to the development of EEC by increased androgen production in postmenopausal women. The correlation between sex hormone levels and Leydig cell hyperplasia may support endometrial pathology screening in these women.

Pseudoangiomatous stromal hyperplasia: Presentation and management - a clinical perspective.

Pseudoangiomatous stromal hyperplasia (PASH) is a benign breast condition of collagen proliferation. In this article, four cases are presented in series to illustrate the varying clinical presentations of PASH at mammography and sonography, as well as the vastly differing age groups that can be affected. A literature review of the aetiology, pathology and management of PASH is included to provide a comprehensive but succinct overview of the condition, what it is and how to recognise and manage it.

Pseudoangiomatous stromal hyperplasia: Presentation and management – a clinical perspective

Pseudoangiomatous stromal hyperplasia (PASH) is a benign breast condition of collagen proliferation. In this article, four cases are presented in series to illustrate the varying clinical presentations of PASH at mammography and sonography, as well as the vastly differing age groups that can be affected. A literature review of the aetiology, pathology and management of PASH is included to provide a comprehensive but succinct overview of the condition, what it is and how to recognise and manage it.

Histologic findings associated with false-positive multiparametric magnetic resonance imaging performed for prostate cancer detection

Magnetic resonance imaging (MRI)/ultrasound fusion-targeted biopsy (TB) has been shown to more accurately identify higher-grade prostate cancers compared with standard-of-care systematic sextant prostate biopsy (SB). However, occasional false-positive imaging findings occur. We investigated the histologic findings associated with false-positive prostate MRI findings. A retrospective review was performed on our surgical pathology database from 2014 to 2017 selecting patients with no cancer detected on TB with concurrent SB after at least 1 prior benign SB session. Histologic features evaluated included percentage of core involvement by chronic inflammation, percentage of core composed of stroma, percentage of glands involved by atrophy, and presence of the following features: acute or granulomatous inflammation, stromal nodular hyperplasia, adenosis, squamous metaplasia, basal cell hyperplasia, and presence of skeletal muscle. Histologic findings were compared between TB and concurrent SB. We identified 544 patients who underwent TB. Of these, 41 patients, including 62 targeted lesions, met criteria. Compared with SB tissue, the mean percentage of stroma was increased in TB (P = .02). Basal cell hyperplasia was also found to be more common on TB (P = .02). Both high percentage of stroma (P = .046) and presence of basal cell hyperplasia (P = .038) were independent predictors on multivariate analysis. The combination of high chronic inflammation, high stroma, acute inflammation, and basal cell hyperplasia was associated with TB (P = .001). Atrophic glands and chronic inflammation showed a positive correlation (r = 0.67, P = .003), which was especially seen in high prostate imaging reporting and data system lesions. Specific benign histologic entities are associated with false-positive findings on prostate MRI.

Select Choices in Benign Breast Disease: An Initiative of the American Society of Breast Surgeons for the American Board of Internal Medicine Choosing Wisely® Campaign.

Up to 50% of all women encounter benign breast problems. In contrast to breast cancer, high-level evidence is not available to guide treatment. Management is therefore largely based on individual physician experience/training. The American board of internal medicine (ABIM) initiated its Choosing Wisely® campaign to promote conversations between patients and physicians about challenging the use of tests or procedures which may not be necessary. The American society of breast surgeons (ASBrS) Patient safety and quality committee (PSQC) chose to participate in this campaign in regard to the management of benign breast disease. The PSQC solicited initial candidate measures. PSQC surgeons represent a wide variety of practices. The resulting measures were ranked by modified Delphi appropriateness methodology in two rounds. The final list was approved by ASBrS and endorsed by the ABIM. The final five measures are as follows. (1) Don't routinely excise areas of pseuodoangiomatous stromal hyperplasia (PASH) of the breast in patients who are not having symptoms from it. (2) Don't routinely surgically excise biopsy-proven fibroadenomas that are < 2cm. (3) Don't routinely operate for a breast abscess without an initial attempt to percutaneously aspirate. (4) Don't perform screening mammography in asymptomatic patients with normal exams who have less than a 5-years life expectancy. (5) Don't routinely drain nonpainful, fluid-filled cysts. The ASBrS Choosing Wisely® measures that address benign breast disease management are easily accessible to patients via the internet. Consensus was reached by PSQC regarding these recommendations. These measures provide guidance for shared decision-making.