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

AIMS: 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. METHODS AND RESULTS: 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. CONCLUSIONS: 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.

Breast hamartoma: reassessment of an under-recognised breast lesion.

AIMS: Breast hamartomas are an under-recognised lesion because they lack a distinctive microscopic appearance. Microscopic diagnosis can often conclude 'no significant lesion' or 'normal breast tissue', leading to repeated biopsies and diagnostic delay. We describe the histological, immunohistochemical and radiological features of breast hamartomas with the aim of identifying specific signs to facilitate their diagnosis and to differentiate them from normal breast and fibroepithelial lesions. METHODS AND RESULTS: Forty-seven breast hamartomas were reassessed (histological diagnosis and imaging features). An immunohistochemical study [oestrogen receptor (ER), progesterone receptor (PR), CD34, high-mobility group A2 (HMGA2)] was performed. On breast imaging, hamartomas most often presented as probably benign solid masses with circumscribed margins and variable densities. Histologically, breast hamartomas resembled normal breast, although their stromal component was predominant, separating randomly scattered epithelial elements with areas of pure collagenous stroma. Pseudoangiomatous stromal hyperplasia (PASH) was present in 93.6% of cases and CD34 antibody highlighted intralobular, perilobular and interlobular distribution of CD34-positive fibroblasts. By comparison, CD34 was mainly expressed in the intralobular normal breast tissue stroma. Hamartoma stromal cells expressed HMGA2, ER and PR in 79%, 66% and 76.3% of our cases, respectively, compared to 7.7%, 23% and 19% in normal breast tissue, respectively (P < 0.0001; P = 0.0005; P < 0.0001). CONCLUSIONS: After ascertaining that core needle biopsy is effectively intralesional, breast hamartomas can be diagnosed with confidence by taking into account the presence of stromal changes, PASH, interlobular distribution of CD34-positive fibroblasts, HMGA2 and hormonal receptor stromal expression.

Bilateral axillary pseudoangiomatous stromal hyperplasia in a premenopausal woman: A case report with imaging findings.

Pseudoangiomatous stromal hyperplasia is a benign proliferative mesenchymal lesion of the breast. To date, only a few cases of axillary pseudoangiomatous stromal hyperplasia with imaging findings have been reported in the literature. Herein, we report a rare case of pseudoangiomatous stromal hyperplasia in both axillae in a previously healthy 46-year-old woman and describe the imaging findings, including ultrasonography and computed tomography findings.

MRI features of pseudoangiomatous stromal hyperplasia with histopathological correlation.

Pseudoangiomatous stromal hyperplasia (PASH), a rare, noncancerous lesion, is often an incidental finding on magnetic resonance imaging (MRI)-guided biopsy analysis of other breast lesions. We sought to describe the characteristics of PASH on MRI and identify the extent to which these characteristics are correlated with the amount of PASH in the pathology specimens. We identified 69 patients who underwent MRI-guided biopsies yielding a final pathological diagnosis of PASH between 2008 and 2015. We analyzed pre-biopsy MRI scans to document the appearance of the lesions of interest. All biopsy samples were classified as having ≤50% PASH or ≥51% PASH present on the pathological specimen. On MRI, 9 lesions (13%) appeared as foci, 19 (28%) appeared as masses with either washout or persistent kinetics, and 41 (59%) appeared as regions of nonmass enhancement. Of this latter group, 33 lesions (80%) showed persistent kinetic features. Masses, foci, and regions of nonmass enhancement did not significantly correlate with the percentage of PASH present in the biopsy specimens (P ≥ .05). Our findings suggest that PASH has a wide-ranging appearance on MRI but most commonly appears as a region of nonmass enhancement with persistent kinetic features. Our finding that most specimens had ≤50% PASH supports the notion that PASH is usually an incidental finding. We did not identify a definitive imaging characteristic that reliably identifies PASH.

Management of recurrent bilateral multifocal pseudoangiomatous stromal hyperplasia (PASH).

Pseudoangiomatous stromal hyperplasia (PASH) is a benign hyperplastic condition of the breast that can lead to macromastia. The standard treatment for PASH is focal excision or rarely reduction mammoplasty. We present a rare case of postpartum bilateral rapid breast enlargement and axillary growth that was refractory to reduction mammoplasty. Ultimately, the patient required bilateral mastectomy and two-stage implant-based breast reconstruction. This more extensive form along with its management represents one of the few reported cases in the literature. The decision to pursue bilateral mastectomy was undertaken after exhausting more conservative options. Excellent aesthetic outcome and pain relief was obtained following definitive extirpative and reconstructive surgery.

Pseudoangiomatous stromal hyperplasia causing severe breast enlargement in a 15-year-old girl: A case report.

Pseudoangiomatous stromal hyperplasia (PASH), composed of proliferated stromal mesenchymal cells of myofibroblastic origin, is a benign lesion of the breast. A few cases associated with pseudoangiomatous stromal hyperplasia of the breast have been reported. We report this case of a 15-year-old girl with PASH accompanied by severe enlargement and painful mass in the right breast. There were no other palpable masses or lymph nodes. Biopsy of the mass showed histopathologic features characteristic of fibroadenoma. The palpable mass was around 6x5cm in diameter, while clinical manifestations aroused suspicion of malignancy mimicking sarcoma of the breast. Although, biopsy of the mass showed benign histopathologic features; surgical excision was performed because of the damage caused by enlarging breast tissue and clinical suspicion of malignancy.

Atypical pseudoangiomatous stromal hyperplasia showing rapid growth of the breast: Report of a case.

Pseudoangiomatous stromal hyperplasia (PASH) of the breast is a benign lesion manifesting as myofibroblastic proliferation and anastomosing slit-like spaces. Atypical PASH is an extremely rare lesion characterized by cytological alteration of myofibroblast, presenting as myofibroblastic sarcoma arising from PASH. To our knowledge, only one other case has been reported since the first report of Rosen. We present a case of atypical PASH. A 39-year-old female presented with a round, elastic hard, painless mass in the left breast. Mammography and ultrasonography revealed no definitive sign of malignancy. Core needle biopsy report was suggestive of atypical PASH. Five months later, the mass had grown rapidly with pain. Considering the clinicopathological features, excision was performed. Pathological examination revealed the spindle cells proliferation in collagenous stroma. The spindle cell involved the adipose tissue and lobules and lined peudoangiomatous spaces. These cells exhibited marked cytological atypia and mitotic activity. Immunohistochemically, these spindle cells were positive for SMA, CD10, and bcl-2, and negative for podoplanin, p63, CD31, ERG and cytokeratins. The final diagnosis was atypical PASH. She is tumor-free on 12 months follow-up. The nature of atypical PASH remains unknown. Further studies are required for a clear definition, a new histological entity and diagnostic criteria.

How to manage pseudoangiomatous stromal hyperplasia: our clinical experience

Background/aim: Pseudoangiomatous stromal hyperplasia (PASH) is a rare and benign mesenchymal proliferative breast lesion. Our aim is to review the clinical and radiological features of PASH and define a standard approach for its diagnosis and management. Materials and methods: Clinical records of 35 consecutive patients with PASH were retrospectively reviewed between 2009 and 2015. Patients with clinically or radiologically detected mass and patients who underwent biopsy for other indications and were diagnosed incidentally were included in the study. Results: There were 34 female patients and one male patient with gynecomastia. Twenty-three patients had palpable masses, and 16 of them were diagnosed as PASH with a median size of 3.1 cm. PASH did not show any specific features in radiological imaging. Core needle biopsy was performed for 3 patients before surgical excision; however, the lesions had not been diagnosed as PASH. In pathological examination, lesions associated with PASH showed nonproliferative changes in 14 patients, proliferative changes without atypia in 17, one phyllodes tumor, one in situ tumor, and one invasive cancer. Conclusion: Imaging findings of PASH are nonspecific. It is difficult to give a true prognostic diagnosis through pathological evaluation of big masses with core needle biopsy. We recommend surgical excision, especially for big lesions with suspicious features.

[Fibroepithelial tumors of the anogenital mammary-like glands]. / Fibroépitelial'nye opukholi anogenital'nykh mammaropodobnykh zhelez.

Mammary-like glands are a normal anatomical component of the anogenital region. The tumors occurring in them morphologically mimic the similar diseases of the breast. The paper presents a case of vulvar fibroadenoma with leaf-like outgrowths and apocrine metaplasia in a 38-year-old female patient. It describes the clinical and morphological characteristics of fibroadenomas and benign phyllodes tumors in the anogenital region.

Nonmass enhancement on breast MRI: review of patterns with radiologic-pathologic correlation and discussion of management.

OBJECTIVE: The purpose of this article is to review the varied appearances and associated diagnoses of nonmass enhancement on breast MRI with radiologic-pathologic correlation. CONCLUSION: Knowledge of the distribution and internal characteristics of these findings is helpful to determine when core needle biopsy is indicated. Correlating imaging with pathologic findings is critical in making appropriate recommendations regarding clinical management.

A case report and a literature review of double mammary pseudoangiomatous stromal hyperplasia associated with galactoma during pregnancy.

Pseudoangiomatous stromal hyperplasia (PASH) is a benign interstitial hyperplasia of the breast that usually occurs in premenopausal or perimenopausal women. It is usually characterized by localized lesions or clear boundary masses, and diffuse double breast enlargement is rare. PASH is considered a hormone-dependent disease that is commonly progesterone related. There are no imaging characteristics, and both benign and suspicious malignant signs can be seen. The definitive diagnosis of PASH depends on a pathological diagnosis, and it is necessary to be vigilant in distinguishing between benign and malignant tumors with similar breast histopathology. Here, we report the case of a 23-year-old multipara patient with bilateral diffuse pseudoangiomatous stromal hyperplasia of the breast during pregnancy who presented with macromastia and reviewed the literature to further understand the clinical features, pathological diagnosis, differential diagnosis, treatment and prognosis of pseudoangiomatous stromal hyperplasia of the breast.

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 68 years. 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.

Innovative technique for managing extreme relapsing bilateral pseudoangiomatous stromal hyperplasia (PASH) in a young woman: A case report highlighting a novel intervention in reconstruction.

INTRODUCTION: Pseudoangiomatous stromal hyperplasia (PASH) is a rare breast stromal lesion that typically manifests clinically as a palpable unilateral, painless lump that is freely movable and has a rubbery or firm consistency. The diagnosis can be confirmed by a core needle biopsy (CNB) or surgical excision. Treatment options include medical treatment with hormonal management for asymptomatic patients or local excision and breast reduction in rare cases. CASE PRESENTATION: We reported the case of a 24-year-old woman with a history of taking contraceptive pills for about a year. Examination revealed extremely enlarged, sore, and swollen breasts, particularly the right side, marking her third PASH relapse. The patient underwent a surgical skin-reducing mastectomy (SRM) using a novel technique with an immediate prepectoral implant covered by a dermal flap to reconstruct the breast shape due to the large PASH lesions and aiming for optimal cosmetic outcomes. The procedure was complication-free with no recurrence after 18 months of follow-up. DISCUSSION: Mastectomy followed by immediate implantation offers benefits such as prompt restoration of breast shape with fewer surgeries. CONCLUSION: This case report highlights the successful use of immediate implantation in reconstructing large recurrent benign breast diseases. The outcomes indicate that immediate implantation shows promise as a suitable choice for carefully selected patients managing large, relapsing bilateral benign breast diseases. However, due to common complications such as infection and implant loss, it is not generally recommended for benign lesions. The decision should be made on a case-by-case basis, considering the size, recurrence, and individual suitability.

Pseudoangiomatous stromal hyperplasia of the breast: Clinical evaluation.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Pseudoangiomatous Stromal Hyperplasia of the Breast in a Female Adolescent Presenting as Bilateral Gigantomastia.

Pseudoangiomatous stromal hyperplasia (PASH) is a rare idiopathic proliferative mesenchymal breast disease related to hormonal imbalance, and thus extremely rare in children and adolescents. In addition, PASH manifests as a bilateral gigantomastia in some cases with no established cause or treatment. Here, we report a case of a rapidly developed PASH presenting with bilateral gigantomastia in a 14-year-old premenarchial female patient. Considering the patient's age and emotions and the need for nipple-areolar complex repositioning, we performed reduction mammoplasty rather than total mastectomy despite the possibility of recurrence. Although some masses could not be completely removed, no complications, such as infection, wound dehiscence, or hematoma occurred postoperatively. The patient was stable during the 18-month follow-up period, although an evidence of recurrent and residual disease was noted upon ultrasonography.

A review of pediatric macromastia etiology and indications for reduction mammaplasty.

BACKGROUND: Macromastia in adolescents is both physically and psychologically debilitating during a period in life when individuals are particularly vulnerable to peer pressure and social norms. Early recognition and intervention by both pediatricians and surgeons are critical to avoid unnecessary suffering. While reduction mammaplasty is the gold standard for the management of symptomatic macromastia in adults, the management of macromastia in pediatric patients remains controversial. In particular, there is great discussion regarding the timing of reconstructive breast surgery in pediatric patients. METHODS: A comprehensive review of the literature was performed to identify all articles related to macromastia in patients ≤16 years of age, the age at which full development is typically achieved in the United States. The etiologies of pediatric macromastia, approaches to management, and outcomes are summarized herein. FINDINGS: Pathological breast hypertrophy in pediatric patients is a rare finding and may occur secondary to juvenile hypertrophy of the breast (JHB) and pseudoangiomatous stromal hyperplasia (PASH). While medical management of these pathologies has been attempted with varying success, reduction mammaplasty is safe and effective in pediatric patients. There are, however, a number of pediatric-specific considerations that must be taken into account prior to surgery. We provide an algorithm for approaching pediatric macromastia.

The Relationship of Pseudoangiomatous Stromal Hyperplasia (PASH)-Like Appearance in Invasive Breast Carcinomas with PASH Areas in Non-Tumoral Breast Parenchyma as Well as on Axillary Lymph Node Involvement.

Objectives: The aim of this study were to determine the relationship of pseudoangiomatous stromal hyperplasia (PASH)-like appearance in invasive breast carcinomas (IBCs) with PASH foci in the non-tumoral breast parenchyma as well as axillary lymph node involvement. Methods: In this study, 200 consecutive cases with IBC were re-examined. Cases with and without PASH-like appearance in IBC were determined. Each case was assessed regarding the presence of accompanying PASH foci (CD34+, CD31-) in the non-tumoral areas in addition to other clinicopathological parameters. Results: PASH-like appearance within the IBC was present in 22 of the 200 cases (11%) and absent in 178 (89%). The presence of PASH foci in the non-tumoral breast parenchyma was significantly more common in IBC with PASH-like appearance compared to the group without such areas. However, there was no significant difference between the groups regarding other clinicopathological parameters (age, tumor size, nuclear and histological grade, Estrogen receptor/Progesterone receptor status, HER2 status, and Ki-67 proliferation index), lymphovascular invasion (LVI), and axillary lymph node involvement. There was no significant difference between the two groups regarding the histopathological findings observed in the non-tumoral areas. Conclusion: PASH-like appearance within IBC was found to be associated with higher rate of PASH foci in the non-tumoral breast parenchyma. However, such cases do not show a difference as regards LVI and axillary lymph node metastasis.

Tumoral pseudoangiomatous stromal hyperplasia (PASH) of the male breast: A systematic analysis.

<b><br>Aim:</b> The study was conducted to systematically analyze the recent peer-reviewed literature related to tumoral pseudoangiomatous stromal hyperplasia (PASH) in males.</br> <b><br>Materials and methods:</b> Articles published in peer-reviewed journals of repute from 2012 to 2023 were evaluated for eight variables: 1) the age of the patient, 2) clinical presentation, 3) laterality (unilateral or bilateral), 4) associated breast disorder, 5) the presence of systemic co-morbidity, 6) imaging modalities aiding diagnosis, 7) treatment, and 8) recurrence.</br> <b><br>Results:</b> There were 10 patients ranging in age from 1 year to 67 years (mean: 34.5 years). In 8 cases (80%), there were breast lumps; in 2 cases (20%), there were axillary lumps at presentation. Pain was not a prominent symptom. Six patients (60%) had another breast disorder at presentation and 3 (30%) had significant systemic co-morbidities, including diabetes and renal insufficiency. The greatest dimension of the lumps ranged from 2 cm to 12 cm, with 80% of the lumps being below 5 cm in size. Imaging modalities utilized in evaluation included breast ultrasound (USG), mammograms, computerized tomography (CT), and magnetic resonance imaging (MRI). All the cases were treated surgically, and the final diagnosis was made only after the analysis of the surgical specimen. Recurrence was recorded in 2 (20%) cases.</br> <b><br>Conclusions:</b> Tumoral PASH is a benign myofibroblastic proliferation disorder rarely reported in males. This condition should be considered a differential diagnosis of breast or axillary lumps, and an evaluation should be initiated accordingly. The recommended course of treatment is adequate surgical excision with regular clinical and radiological follow-up.</br>.

Pseudoangiomatous stromal hyperplasia in a healthy young adult male.

This case report describes the occurrence of a rapidly enlarging pseudoangiomatous stromal hyperplasia (PASH) tumor in a 20-year-old male patient. The diagnosis was made via tomosynthesis and ultrasound-guided biopsy with pathological correlation consistent with PASH. The patient's case was discussed, and he was recommended to undergo surgical resection of the mass to alleviate symptoms due to its large size. Surgical pathology confirmed the original diagnosis and the patient had an uncomplicated postoperative course. Here, we exhibit our imaging findings; review classic presentations of PASH on mammography, ultrasound, and MRI; and discuss histological characteristics of this benign entity.

Pseudoangiomatous stromal hyperplasia causing massive unilateral breast enlargement-a case report.

Background: Pseudoangiomatous stromal hyperplasia (PASH) is an uncommon mesenchymal benign breast neoplasm. PASH may present as a rapidly growing mass in pre-menopausal women. It is important to rule out other causes of a breast lump including fibroadenoma, hamartoma, phyllodes tumour and invasive adenocarcinoma. To our knowledge this is the largest case of PASH tumour in the English literature and the first to be managed with mastectomy and immediate breast implant reconstruction. Case Description: A 45-year-old woman with a history of bilateral breast augmentation for cosmesis and no other co-morbidities, presented with gross asymmetry between her right and left breasts on 13th December 2020. She complained about pain and the noticeable difference in clothing. She underwent triple assessment (history and examination, imaging, and biopsy). Bilateral mammograms showed the right breast had a possible mass. On ultrasound imaging there was evidence of extensive ill-defined hypoechoic changes. Core biopsies and a vacuum assisted core biopsy were taken from the mass and came back as PASH/fibrocystic change on 12th January 2021. Surgical options were discussed, and after some consideration she decided on mastectomy and immediate implant reconstruction on 15th March 2021. She underwent the operation on 9th September 2021 and the specimen weight was 1.911 kg and measured 27 cm × 22.6 cm × 7.4 cm which is the largest reported PASH tumour. She made an uncomplicated recovery and was seen in clinic 4 weeks later and was happy with the cosmetic outcome. PASH can present as incidental microscopic foci in biopsies to diffuse enlargement of the breast. PASH has no specific radiological or diagnostic features, therefore is diagnosed based on histology. PASH is not associated with an increased risk of malignancy and the management is dependent on the presentation. When PASH is discovered incidentally or is asymptomatic it can be followed up with serial mammography to assess growth. If there are any suspicious features or discordance following triple assessment or symptoms such as discomfort surgical excision is indicated. Conclusions: PASH should be considered as part of the differential diagnosis for rapid breast enlargement. Treatment options should be discussed early with the patient to prevent progression. For rapid breast enlargement mastectomy and immediate reconstruction should be considered and discussed with the patient.