Pseudoangiomatous Stromal Hyperplasia Research Articles

Diagnostic Approach to Mesenchymal and Spindle Cell Tumors of the Breast

Mesenchymal and spindle cell tumors of the breast represent a broad and heterogeneous group of lesions that may be sampled on core needle biopsy or surgical excision. Mesenchymal lesions unique to the breast are those that derive from the specialized breast myofibroblast, such as mammary myofibroblastoma and pseudoangiomatous stromal hyperplasia. However, any mesenchymal lesion arising in extramammary soft tissue may also arise in the breast, including fibroblastic, peripheral nerve sheath, adipocytic, and vascular lesions. The spindle cell lesions pose the greatest diagnostic challenge, due to the significant radiographic, morphologic, and immunophenotypic overlap within the category of mesenchymal lesions and more broadly with other nonmesenchymal breast lesions. The distinction is particularly challenging on the limited material of breast core needle biopsies, and caution should be taken before definitively classifying a breast spindle cell lesion on core needle biopsy to avoid unnecessary treatment if misdiagnosed. Consideration of a wide differential diagnosis, adequate sampling of a resection specimen, use of a targeted immunopanel, and selective use of molecular assays are essential steps for accurate classification of mesenchymal lesions in the breast. This review covers the clinical, histologic, and immunophenotypic features of mesenchymal tumors of the breast, with a special emphasis on the differential diagnoses unique to the breast and challenges encountered on breast core needle biopsy.

Pseudoangiomatous stromal hyperplasia (PASH) of the breast: A case series.

Pseudoangiomatous stromal hyperplasia (PASH) is a benign mesenchymal proliferative lesion of the breast. In 2005, only 109 cases have been reported since its initial description in 1986 by Vuitch et al. when it presented in one patient as a palpable breast mass. We retrospectively reviewed data from 2020 to 2023 of patients diagnosed with PASH by surgical excision. Our 13 cases represent one of the most numerous reported from a single institution. All histologic specimens were examined by a single pathologist. All patients had breast masses on imaging or were clinically evident. Eleven of the patients (84.6%) were diagnosed by surgical excision, whilst only two (15.4%) were diagnosed by core needle biopsy. Imaging revealed no strongly distinctive features for PASH. The age of the patients ranged from 25 to 68years. All but one of the women were premenopausal at the time of diagnosis. This study suggests that PASH is a lesion whose diagnosis is often incidental and the recommended treatment is more commonly surgical.

Nodular pseudoangiomatous stromal hyperplasia in a 22-year-old woman: a case report

Nodular pseudoangiomatous stromal hyperplasia in a 22-year-old woman: a case report

A rarely seen fast-growing tumor of the breast: Pseudoangiomatous stromal hyperplasia

Pseudoangiomatous stromal hyperplasia (PASH) is a benign lesion consisting of proliferated stromal cells of the breast with anastomotic slits reminding vascular spaces. It is very rare in childhood. In our study, we presented a 13-year-old female patient with a rapidly growing breast tumor diagnosed as PASH.

Molecular Breast Imaging Biopsy with a Dual-Detector System.

Purpose To develop a molecular breast imaging (MBI)-guided biopsy system using dual-detector MBI and to perform initial testing in participants. Materials and Methods The Stereo Navigator MBI Accessory biopsy system comprises a lower detector, upper fenestrated compression paddle, and upper detector. The upper detector retracts, allowing craniocaudal, oblique, or medial or lateral biopsy approaches. The compression paddle allows insertion of a needle guide and needle. Lesion depth is calculated by triangulation of lesion location on the upper detector at 0° and 15° and relative lesion activity on upper and lower detectors. In a prospective study (July 2022-June 2023), participants with Breast Imaging Reporting and Data System category 2, 3, 4, or 5 breast lesions underwent MBI-guided biopsy. After injection of 740 MBq technetium 99m sestamibi, craniocaudal and mediolateral oblique MBI (2-minute acquisition per view) confirmed lesion visualization. A region of interest over the lesion permitted depth calculation in the system software. Upper detector retraction allowed biopsy device placement. Specimen images were obtained on the retracted upper detector, confirming sampling of the target. Results Of 21 participants enrolled (mean age, 50.6 years ± 10.1 [SD]; 21 [100%] women), 17 underwent MBI-guided biopsy with concordant pathology. No lesion was observed at the time of biopsy in four participants. Average lesion size was 17 mm (range, 6-38 mm). Average procedure time, including preprocedure imaging, was 55 minutes ± 13 (range, 38-90 minutes). Pathology results included invasive ductal carcinoma (n = 1), fibroadenoma (n = 4), pseudoangiomatous stromal hyperplasia (n = 6), and fibrocystic changes (n = 6). Conclusion MBI-guided biopsy using a dual-head system with retractable upper detector head was feasible, well tolerated, and efficient. Keywords: Breast Biopsy, Molecular Breast Imaging, Image-guided Biopsy, Molecular Breast Imaging-guided Biopsy, Breast Cancer Clinical trial registration no. NCT06058650 © RSNA, 2024.

Infra-areolar subcutaneous mastectomy in the surgical treatment of adolescent gynecomastia.

Despite being a common condition in puberty, only 5-10% of pubertal gynecomastia need surgical treatment. Here the authors present their experiences with infra-areolar subcutaneous mastectomy in the surgical treatment of adolescent gynecomastia. The records of patients who underwent infra-areolar subcutaneous mastectomy for adolescent gynecomastia between January 2004 and December 2021 were reviewed retrospectively. The patients' demographic data, complaints and clinical presentation, physical examination, laboratory and radiological findings, surgical management, and postoperative follow-ups were evaluated. The patients were evaluated according to the localization of the gynecomastia (unilateral/bilateral) and according to the patients' body mass index (BMI) (normal/overweight). A total of 21 boys with a mean age of 15 ± 1.4years were operated by the senior author and infra-areolar subcutaneous mastectomy by a semilunar incision was performed for adolescent gynecomastia. The mean duration of the complaint was 24.2 ± 10.9months. Gynecomastia was bilateral in 15 (71.5%) and unilateral in 6 (28.5%) of the patients. Sixteen patients (76.2%) were normal weight, 5 (23.8%) were overweight. Chromosomal anomaly and hypogonadism were detected in two patients. Pseudoangiomatous stromal hyperplasia was detected in the pathology of one patient. The mean follow-up time was 2.7 ± 1years, seroma developed in 2 patients at the early postoperative period. Their long-term follow-up was uneventful without complication. The results of infra-areolar subcutaneous mastectomy are very promising in pubertal gynecomastia due to good skin elasticity and without obesity in the adolescent age group. We believe that this method provides an almost invisible incision and a natural pectoral appearance for adolescent patients who have experienced serious emotional problems related to their body images.

Abstract 283: Fibroblast diversity and immune microenvironment in pseudoangiomatous stromal hyperplasia (PASH): Associations with breast cancer risk

Abstract Benign breast disease (BBD) affects over one million women annually in the United States and is diagnosed in nearly half of all women during their lifetime. Pseudoangiomatous stromal hyperplasia (PASH), a common BBD subtype, is characterized by an overaccumulation of tissue fibroblasts. Current research suggests a pivotal role of the immune microenvironment in progression of BBD to breast cancer, suggesting its composition as a determinant of breast cancer risk. Our study evaluates whether fibroblast variations and immune microenvironment differences in BBD biopsies containing PASH lesions are associated with subsequent breast cancer development. We evaluated BBD biopsies from women who subsequently developed breast cancer (cases, N=5) or remained cancer-free (controls, N=5). Using Opal-based multiplex immunofluorescence (mIF) assays, we mapped expression of fibroblast markers linked to breast cancer associated fibroblasts (CAFs), including vimentin (VIM), smooth muscle actin (ACTA2), fibroblast specific protein-1 (S100A4/FSP1), fibroblast associated protein (FAP), integrin beta-1 (CD29/ITGB1), and platelet derived growth factor receptor beta (PDGFRβ) and markers of key immune cells (T cells: CD4, CD8; dendritic cells: CD11c; B cells: CD20; and macrophages: CD68) along with MKI67 as a proliferation marker. Our results revealed marked differences in fibroblast marker expression and immune cell populations between these groups in the normal lobules in the BBD biopsies. PASH cases showed elevated PDGFRβ and CD29/ITGB1 expression in VIM-positive fibroblasts, markers characteristic of CAF subtypes known to accumulate in more aggressive tumor microenvironments. Conversely, a higher percentage of FSP1+/VIM+ cells, similar to that of a different CAF subtype, was noted in the lobules of PASH controls. This difference in biomarker expression, along with corresponding variations in immune cell counts, suggests a complex interplay between fibroblast composition and immune response that ultimately modulate cancer risk in PASH-containing BBD tissues. Additionally, increased MKI67 expression in PASH cases potentially signals the higher likelihood of cancer development. This work advances our understanding of fibroblast heterogeneity in BBD and its implications for breast cancer risk and progression, and paves the way for innovative strategies to improve clinical outcomes for BBD patients to reduce their incidence of breast cancer. Citation Format: Nicole Cruz-Reyes, Matilde Rossi, Melody Stallings Mann, Bryan McCauley, Tanya Hoskin, Robert Vierkant, Stacey Winham, Amy Degnim, Mark E. Sherman, Derek C. Radisky. Fibroblast diversity and immune microenvironment in pseudoangiomatous stromal hyperplasia (PASH): Associations with breast cancer risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 283.

Bilateral gigantomastia due to benign breast tumors: a case series and brief review focusing on bilateral diffuse pseudoangiomatous stromal hyperplasia

Gigantomastia is a rare condition characterized by excessive hypertrophy of the connective tissue of the breast, which can cause physical and emotional distress. Surgical intervention is crucial for improving patients’ quality of life; however, it is challenging to balance minimizing the risk of recurrence and maximizing favorable aesthetic outcomes. This study documents the successful management of three rare cases of bilateral gigantomastia resulting from benign tumors. These cases included rapidly growing bilateral diffuse tumorous pseudoangiomatous stromal hyperplasia (PASH) and bilateral juvenile giant fibroadenoma, with no long-term recurrence observed. We discuss the diagnostic challenges and management considerations for gigantomastia, with a focus on reviewing PASH and its differential diagnosis. The findings offer valuable insights into the successful management of diverse gigantomastia cases caused by benign tumors, potentially aiding clinicians in making more informed decisions regarding optimal patient care.

A Case of Breast Pseudoangiomatous Stromal Hyperplasia with Local Recurrence

A Case of Breast Pseudoangiomatous Stromal Hyperplasia with Local Recurrence

First Case Report of Synchronous Presentation of Tumoriform Psudoangumatous Stromal Hyperplasia (PASH) and Malignant Phyllodes Tumor in One Breast Lesion

Pseudoangiomatous stromal hyperplasia (PASH) of the breast is a benign proliferative mesenchymal lesion with possible hormonal etiology. PASH is mostly identified as an incidental finding in the final histopathology of excised breast specimens. However, another less common presentation of PASH is the tumoriform palpable lesion. Herein, we report an unusual case of tumorous PASH of the breast with a deceiving clinical presentation mimicking invasive mammary carcinoma, and a surprising final histopathological diagnosis. Our report indicates that widening the differential diagnosis of a breast mass, to include rare and uncommon diseases, as well as careful decision making are essential measures to avoid overlooking a serious diagnosis or over treating a simple disease.

Pseudoangiomatous stromal hyperplasia of the breast: multimodality imaging findings

Background/Aim: Pseudoangiomatous stromal hyperplasia (PASH) is a rare benign mesenchymal proliferative breast lesion. The literature contains little information on the radiological results of this uncommon tumor. In this study, we aim to define the radiologic findings of PASH through our institutional experience.
 Materials and Methods: Patients with PASH of the breast reported in the surgical database of our institution from 2020 to 2023 were retrospectively reviewed. PASH was detected in 11 female patients among the patients who underwent a total of 2172 breast tru-cut biopsies. Nine patients whose imaging studies could be recalled from the picture archiving systems (PACS) were included in the study. BI-RADS, 5th edition, was used to analyze and classify radiologic findings.
 Results: The median age of cases was 41 (range 22–53). Our single-center incidence was found to be 0.5%. Considering the sonographic findings, all of the lesions had an oval shape. On mammography, they were defined as focal asymmetry or circumscribed masses. An MRI was available in three cases. All three cases were hypointense on T1-weighted sequences and hyperintense on T2-weighted sequences. They displayed type 1 or type 2 enhancement curves in the dynamic contrast-enhanced images. No diffusion restriction was detected.
 Conclusion: In this study, tumor-forming PASH were generally circumscribed oval hypoechoic solid masses with minimal vascularity and no posterior acoustic features on ultrasound. On mammography, calcification, architectural distortion, or spiculation were not present in any of the cases. MRI findings were t2 hyperintensity, type 1–2 enhancement kinetics, and no diffusion restriction. In all imaging modalities, the imaging characteristics point to a benign lesion.

A rare case of gigantomastia caused by pseudoangiomatous stromal hyperplasia

Gigantomastia is a rare pathologic condition characterized by an excessive and abnormal breast hypertrophy. To date, there is no exact definition or classification of this disease. Pathogenesis still unclear. The purpose of this article is to present a case of extreme and disabling gigantomastia caused by pseudoangiomatous stromal hyperplasia, one of the rarest etiology of gigantomastia.

Low-grade fibromyxoid sarcoma of the breast: genetic characterization and immunohistochemical comparison to morphologic mimics

Spindle cell lesions of the breast elicit a specific, relatively limited differential diagnosis, and accurate classification often requires careful morphologic evaluation and immunohistochemical workup. Low-grade fibromyxoid sarcoma (LGFMS) is a rare malignant fibroblastic tumor with deceptively bland spindle cell morphology. Involvement of the breast is exceedingly rare. We examined the clinicopathologic and molecular characteristics of three cases of breast/axillary LGFMS. In addition, we interrogated the immunohistochemical expression of MUC4, a commonly used marker of LGFMS, in other breast spindle cell lesions. LGFMS presented in women at 23, 33, and 59 years of age. Tumor size ranged from 0.9 to 4.7 cm. Microscopically, they were circumscribed nodular masses composed of bland spindle cells with fibromyxoid stroma. Immunohistochemically, tumors were diffusely positive for MUC4 and negative for keratin, CD34, S100 protein, and nuclear beta-catenin. Fluorescence in-situ hybridization demonstrated FUS (n=2) or EWSR1 (n=1) rearrangements. Next-generation sequencing identified FUS::CREB3L2 and EWSR1::CREB3L1 fusions. MUC4 immunohistochemistry performed on 162 additional breast lesions demonstrated only weak and limited expression in a subset of cases of fibromatosis (10/20, ≤30% staining), scar (5/9, ≤10%), metaplastic carcinoma (4/23, ≤5%), and phyllodes tumor (3/74, ≤10%). MUC4 was entirely negative in cases of pseudoangiomatous stromal hyperplasia (n=9), myofibroblastoma (n=6), periductal stromal tumor (n=3), and cellular/juvenile fibroadenoma (n=21). LGFMS can rarely occur in the breast and should be considered in the differential diagnosis of breast spindle cell lesions. Strong and diffuse MUC4 expression is highly specific in this histologic context. Detection of an FUS or EWSR1 rearrangement can confirm the diagnosis.

Pseudoangiomatous stromal hyperplasia of the breast, imaging and clinical perspective: Areview.

Pseudoangiomatous stromal hyperplasia (PASH) is a benign breast pathology, which most commonly presents incidentally along with other breast pathologies. The etiology and pathogenesis of PASH are still unknown; however, there is some evidence suggesting PASH is hormone dependent. The clinical history, presentation, and imaging appearance of PASH are variable. Clinically, PASH has a wide spectrum of presentations, from being silent to gigantomastia. On imaging, PASH demonstrates various benign to suspicious features. Here we summarize PASH's clinical presentation, histopathology, imaging features, and management.

Giant juvenile fibroadenomas with and without prominentpseudoangiomatous stromal hyperplasia (PASH)-like change: clinicopathological and molecular characteristics.

Juvenile fibroadenomas (JFA) are biphasic fibroepithelial lesions (FEL) usually occurring in adolescent female patients. Giant (G) JFA, like other FEL, may exhibit prominent pseudoangiomatous stromal hyperplasia (PASH)-like change. We sought to determine clinicopathological and molecular characteristics of GJFA with and without PASH. Archives were searched for cases of GJFA (1985-2020). All were stained for androgen receptor (AR), beta-catenin, CD34 and progesterone receptor (PR). Cases were sequenced using a custom 16-gene panel - MED12 (exons 1 and 2), TERT promoter (-124C>T and -146Ctable>T), SETD2, KMT2D, RARA (exons 5-9), FLNA, NF1, PIK3CA (exons 10, 11 and 21), EGFR, RB1, BCOR, TP53, PTEN, ERBB4, IGF1R and MAP3K1. Twenty-seven GJFA from 21 female patients aged 10.1-25.2 years were identified. Size ranged from 5.2 to 21 cm. Two patients had multiple, bilateral and later recurrent GJFA. Thirteen (48%) cases showed prominent PASH-like stroma. All were positive for stromal CD34, negative for AR and beta-catenin and one case showed focal PR expression. Sequencing showed MAP3K1 and SETD2 mutations in 17 samples, with KMT2D, TP53 and BCOR aberrations in 10 (45%), 10 (45%) and seven (32%) cases, respectively. Tumours with a PASH-like pattern had higher prevalence of SETD2 (P = 0.004) and TP53 (P = 0.029) mutations, while those without PASH had more RB1 mutations (P = 0.043). MED12 mutation was identified in one case. TERT promoter mutation was observed in four (18%), including two recurrences. Gene mutations along more advanced phases of the proposed FEL pathogenetic pathway in GJFA are unusual, and suggest a mechanism for more aggressive growth in these tumours.

Pseudoangiomatous stromal hyperplasia of the breast

Pseudoangiomatous stromal hyperplasia of the breast is a rare benign mesenchymal lesion of the breast. We present a case of a 49-year-old female patient who consulted for having a rapidly and progressively growing tumor in her left breast. Breast ultrasound showed a heterogeneous and hypoechoic lesion with several nodules. Mammography showed an oval tumor with diffuse margins without microcalcifications. Ultrasound-guided core needle biopsy revealed cellular findings compatible with breast fibroma. The anatomopathological diagnosis was pseudoangiomatous stromal hyperplasia of the breast. This is a rare benign mesenchymal tumor secondary to exacerbated proliferation of mature fibroblasts and myofibroblasts, whose triggering factor is still unknown. Most present as diffuse lesions, and the diagnosis is often incidental or in the context of other breast pathologies.

Pseudoangiomatous stromal hyperplasia of the breast: Clinical evaluation.

Pseudoangiomatous stromal hyperplasia is a rare benign breast stromal proliferative lesion of the breast. Clinical presentation ranges from rapidly growing mass to incidental identification in routine screening. This difference in manifestation and its rarity makes it difficult to be a standard treatment protocol. Therefore, we aimed to share our clinical experience in Pseudoangiomatous stromal hyperplasia. The files of patients who underwent core biopsy or surgical excision due to a breast mass and resulted in pseudoangiomatous stromal hyperplasia between January 2013 and December 2021 were included in the study. 17 patients with a median age of 37 (22-68) were found Pseudoangiomatous stromal hyperplasia confirmed by surgical excision or core biopsy. Chosen treatment option was observation in 8 patients (47.1%), while surgical excision was used in 9 (52.9%) patients. The mean follow-up period was 55.24 ± 26.72 (13-102) months. None of the patients observed the Malignant transformation during the follow-up period. For Pseudoangiomatous Stromal Hyperplasia of the breast, surgical excision with clean margins or close follow-up after diagnosis confirmation by tissue biopsy is sufficient. Pseudoangiomatous Stromal Hyperplasia is not a risk factor for developing breast cancer.

Giant Juvenile Fibroadenoma: Case Report and Review of the Literature.

Fibroadenomas are common benign breast tumors. Fibroadenomas that exceed 5 cm in diameter, weigh more than 500 g, or replace more than four-fifths of the breast are characterized as giant. A fibroadenoma diagnosed in patients during childhood or adolescence is characterized as juvenile. An extensive PubMed search of the literature in English up until August 2022 was performed. In addition, a rare case of a gigantic fibroadenoma in an 11-year-old premenarchal girl who was referred to our adolescent gynecology center is presented here. Eighty-seven cases of giant juvenile fibroadenomas have been reported in the literature along with our case. Patients with giant juvenile fibroadenoma presented at a mean age of 13.92 years and usually after menarche. Juvenile fibroadenomas are usually unilateral, occurring either in the right or the left breast; the majority of them are diagnosed when they are already more than 10 cm in size, and they are most frequently treated with total lump excision. Differential diagnosis includes phyllodes tumors and pseudo-angiomatous stromal hyperplasia. Conservative management is feasible, but surgical excision is recommended to patients with suspicious imaging features or when the mass grows rapidly.

Pseudoangiomatous Stromal Hyperplasia of the Breast: A Case Report of a 32-year-old Woman

Pseudoangiomatous Stromal Hyperplasia (PASH) is a benign breast tumor with a histological pattern that mimics the appearance of angiomatous proliferation. The lesion appears as a complex tissue with slit-like spaces lined by spindle cells resembling endothelial cells with a background of stromal hyperplasia. PASH manifests as a palpable mass, multifocal nodules, or a large diffuse mass that makes the breast asymmetrical. We report a case of breast lump in a 32-year-old woman caused by PASH. Biopsy of the mass showed histopathologic features of PASH. This patient then received tumor excision to remove the mass. Treatment of PASH tumors depends on the size and growth rate of the tumor. Anti-hormonal therapy such as tamoxifen may be an option for non-invasive therapy, but after the diagnosis has been confirmed through a core biopsy and the tumor size is no more than 2 cm. Surgical excision of the tumor by minimizing damage to the surrounding breast tissue is the most recommended treatment.

Novel Pseudoangiomatous Stromal Hyperplasia Mass in a Breast Hamartoma: A Case Report

Breast fibroadenolipomas, otherwise known as hamartomas, are a relatively rare finding in regard to the occurrence of breast masses. Breast hamartomas make up approximately 4.8% of benign breast tumors in women. Breast hamartomas are uncommon, and our case presents with a 4.7 cm hamartoma with a focal, irregular mass inside of it which was histologically confirmed as pseudoangiomatous stromal hyperplasia (PASH). PASH is a benign mesenchymal lesion of the breast that is characterized by dense collagenous stroma forming “pseudoangiomatous” capillary-like spaces lined by spindle cells. [1] A rare condition overall, PASH is predominately discovered in premenopausal women, with fewer than 1,500 cases of PASH documented in literature [1]. Therefore, our case presentation describes a combination of two relatively rare phenomena within one palpable breast mass. Due to the absence of symptoms, the patient was scheduled for interval follow up to monitor the breast hamartoma for interval change in size, and definitive treatment by elective surgical excision was offered if accompanying symptoms developed.