Primary breast arteriovenous malformation in a patient with Cowden syndrome and bilateral ductal carcinoma in situ: a case report

Introduction

We present a case report of 39-year-old female with Cowden syndrome, bilateral ductal carcinoma in situ (DCIS), and a large arteriovenous malformation (AVM) abutting the skin of the left breast. While treatment of breast AVM has been described in a limited number of prior case reports, this combination presents unique clinical considerations that have not been previously described. This case illustrates the importance of early recognition, thorough workup, and multidisciplinary management in the treatment of a breast AVM. In addition, we highlight the utility of a two-stage approach with pre-operative embolization for ensuring optimal safety and cosmesis. These factors should be considered in the evaluation and treatment of a new breast mass, particularly when clinical evaluation suggests hyperdynamic flow. We present this article in accordance with the CARE reporting checklist (available at https://abs.amegroups.com/article/view/10.21037/abs-23-81/rc).

Case presentation

The patient first palpated a mass in her upper inner left breast in her early 20s. Her history was notable for paternal Ashkenazi Jewish ancestry and maternal breast cancer diagnosed at age 57 years. She underwent excision of a presumed hemangioma with pathology re-classifying the growth as an AVM (Figure 1). She first noted recurrence of the mass five years later while breastfeeding her first child, but did not seek further treatment at this time as she remained relatively asymptomatic and had been reassured that her lesion was nonmalignant.

Figure 1 Timeline of key diagnostic events and interventions. AVM, arteriovenous malformation; DCIS, ductal carcinoma in situ.

A screening mammogram at age 38 demonstrated a 1.6 cm of grouped microcalcifications in the upper right breast, contralateral to the side of her AVM. Stereotactic biopsy revealed focal atypical ductal hyperplasia (ADH). Following these findings, she underwent a right breast excisional biopsy demonstrating 1.9 cm of low-grade DCIS [estrogen receptor (ER)/progesterone receptor (PR)+] and ADH with anterior margin <1 mm. Given her age and history, she was referred for genetic screening, which identified a PTEN (phosphatase and tensin homologue) mutation and a diagnosis of Cowden syndrome.

Given this high-risk mutation, she underwent a screening magnetic resonance imaging (MRI), which demonstrated the known AVM, extensive non-mass enhancement of the lower outer left breast extending from chest wall to base of nipple, and an abnormal left axillary node. Core biopsies of these findings revealed grade 2 DCIS (ER/PR−) and benign nodal tissue.

She subsequently presented to our group for evaluation. She denied symptoms beyond the presence of a visible, palpable left breast mass. Her clinical exam demonstrated grade II ptosis, a right breast lumpectomy incision, and a visible, soft mass in the upper inner left breast (Figure 2) with associated bruit (Appendix 1).

Figure 2 Clinical photographs depicting breast appearance at preoperative, post-mastectomy, and post-reconstruction timepoints. (A) Preoperative photograph demonstrating visible AVM over left upper breast. (B) Two weeks after bilateral skin-sparing mastectomy with tissue expander placement. (C) Three months after gel-based implant reconstruction. AVM, arteriovenous malformation.

We conducted an extensive mutual discussion regarding treatment options. Her elevated risk of uterine cancer precluded use of adjuvant tamoxifen for her right-sided disease. Segmental resection of her extensive left-sided disease would have likely required nipple-areolar complex excision and resulted in a large cosmetic deformity. Furthermore, her high-risk mutation placed her at elevated risk of recurrent disease. Given these considerations, the patient elected to undergo bilateral skin-sparing mastectomies with reconstruction.

Preoperative contrast-enhanced MRI (Figure 3) and chest computed tomography angiography demonstrated a 2.4 cm × 4.7 cm × 7.7 cm left breast AVM supplied by small branches of the left internal mammary (IMA) and thoracodorsal arteries (3 and 2 mm, respectively) with a 9 mm torturous draining vein. We determined that staged, preoperative embolization would be beneficial to minimize intraoperative bleeding, facilitate flap dissection, and evaluate risk of future reconstruction by assessing postoperative perfusion of the overlying skin.

Figure 3 Preoperative contrast-enhanced breast MRI. Left: 3D MRI showing left breast AVM with numerous feeding arteries (arrows) and a large (9 mm) tortuous draining vein (arrowheads). Right: axial MRI views demonstrating superficial location of AVM. MRI, magnetic resonance imaging; AVM, arteriovenous malformation.

Four days prior to her planned mastectomies, the patient underwent preoperative n-butyl cyanoacrylate glue embolization of the AVM with interventional radiology. The lesion was first approached trans-arterially through the left subclavian artery (Figure 4) to the IMA and thoracodorsal artery branches using a 4-Fr. Steerable catheter and coaxial 2.7-Fr. Microcatheter for glue delivery. Despite use of intra-arterial vasodilators, small vessel size and vasospasm significantly reduced antegrade flow and prevented the glue from fully penetrating the nidus. This was overcome by ultrasound and fluoroscopy-guided direct puncture of the nidus using a 25-G needle (Figure 5) with further injection of glue. No complications were noted, and post-procedural evaluation of the overlying skin revealed no evidence of ischemia.

Figure 4 Preoperative angiogram depicting catheter tip in left subclavian artery, a large branch of the IMA (black arrows), and branches of the thoracoacromial, lateral thoracic, and subscapular arteries (white arrows) feeding the feeding the AVM (white arrowheads). IMA, internal mammary artery; AVM, arteriovenous malformation.

Figure 5 Direct injection of a liquid embolic (nBCA glue and lipiodol mixture) into the AVM nidus via a 21-G needle (back arrow) with filling of the terminal branches of the IMA feeder (black arrowhead) and thoracodorsal artery (white arrows). nBCA, n-butyl cyanoacrylate; AVM, arteriovenous malformation; IMA, internal mammary artery.

Surgery followed with bilateral skin sparing mastectomies, left axillary sentinel node biopsy with radiotracer identification, and immediate reconstruction with sub-pectoral tissue expanders (Figure 2B). Intraoperative findings demonstrated close approximation of the AVM to the overlying dermis, large vessels in a serpentine pattern associated with the AVM, and thrombus in some of these vessels secondary to embolization. We felt the preoperative embolization facilitated flap dissection with bleeding comparable to that of a routine skin-sparing mastectomy. Pathology demonstrated DCIS of the left breast, two negative axillary sentinel lymph nodes, and no remaining disease of the right breast. These results indicated an excellent overall prognosis with low risk of recurrence or metastatic disease. She experienced no postoperative complications and subsequently underwent bilateral breast reconstruction with permanent silicone gel implants at 5 months after her index operation (Figure 2C). She is without evidence of recurrence after 24 months and has expressed satisfaction with clinical and cosmetic outcomes.

All procedures performed in this study were in accordance with the ethical standards of the institutional review committee of Stanford Hospital & Clinics (FWA00000934) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

AVMs are vascular proliferations consisting of direct connections between arteries and veins without intervening capillaries. Acquired AVMs are the result of new fistula formation due to causes including trauma (iatrogenic or injury), aneurysm erosion, neoplasia, or infection (1). Congenital AVMs are less-common and can be associated with a number of genetic conditions including Cowden syndrome (2,3). They often present early in life as a palpable mass or thrill, cosmetic deformity, bleeding, pain, or, in rare cases, high-output cardiac failure from AV shunting. Misdiagnosis and attempted excision of an AVM could result in potentially dangerous hemorrhage, highlighting the importance of clinical examination and preoperative imaging in the workup of a breast mass.

Seven prior case reports have described congenital, primary breast AVMs (Table 1). One male patient with AVM of the chest involving the breast (also fed by the IMA) underwent preoperative embolization followed by surgical excision, similar to our staged approach (6).

We elected for preoperative embolization based on the superficial location and large size of the AVM and involved vessels, which increased the risk of primary surgical excision. Staged embolization also allowed evaluation of remaining perfusion to the overlying skin prior to implant-based reconstruction. If ischemia were to occur, this staged approach could allow for development of collateral circulation or demarcation and excision of nonviable tissue at the time of subsequent surgery. Furthermore, staged treatment of soft tissue AVM with embolization followed by surgical resection has been shown to reduce risk of recurrence (11). These benefits were felt to outweigh the potential risks of catheter site bleeding, infection, radiation exposure, tissue ischemia, and embolization failure. However, given the rarity of breast AVM and novelty of a two-staged approach, the true benefit of perioperative embolization has yet to be definitively established.

Our case was unique due to the additional findings of bilateral DCIS in the setting of Cowden syndrome, one of a family of diseases caused by a mutation in the PTEN tumor suppressor gene PTEN. This rare condition (estimated prevalence of 1:250,000) (12) is characterized by hamartomatous growths including AVM (2) and increased risk of malignancy, namely breast, thyroid, renal, uterine, colorectal, and skin cancers (13). Lifetime breast cancer risk in females with Cowden syndrome is estimated at 66–90% (14,15). Similar to patients with BRCA1/2 mutations, guidelines recommend that females with Cowden syndrome undergo annual high-risk breast MRI screening starting at age 30 and should be considered for prophylactic bilateral mastectomy (13). It is worth noting that while the AVM in this case was the first noted manifestation of the patient’s underlying condition, her eventual diagnosis resulted from a contralateral breast lesion detected on mammographic screening over 10 years later.

Conclusions

Although rare, AVM of the breast should be considered in the differential diagnosis of breast mass, particularly in those with clinical signs of hyperdynamic flow. This case highlights the benefits of staged treatment of congenital AVM of the breast in a high-risk patient with Cowden syndrome and DCIS. Preoperative embolization was performed to minimize the risk of intraoperative hemorrhage and postoperative ischemia. Early recognition, thorough preoperative imaging, and a multidisciplinary approach contributed to a successful outcome in this case.

Acknowledgments

Funding: None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://abs.amegroups.com/article/view/10.21037/abs-23-81/rc

Peer Review File: Available at https://abs.amegroups.com/article/view/10.21037/abs-23-81/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://abs.amegroups.com/article/view/10.21037/abs-23-81/coif). D.M.H. has provided input on medical device company product development for Folde and medical device testing for UserWise; participated in a phase 1 first-in-man trial of Adient Co. as the Medical Monitor; and has taken a retainer to prepare an evaluation on behalf of the defendant in a medical malpractice case. None of the above represent conflicts of interest to the current manuscript. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional review committee of Stanford Hospital & Clinics (FWA00000934) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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