Intense prostate-specific membrane antigen receptor expression in coronary artery pypass graft scar tissue: A potential molecular imaging pitfall

Abstract

⁶⁸Gallium-PSMA positron emission tomography/computer tomography has been utilized recently for the diagnosis and staging of prostate cancer. PSMA is a transmembrane protein that is expressed not only in the prostate gland but also in other tissues. While some pitfalls have been addressed, there are still uncertainties. Herein, we report a 79-year-old male with prostate cancer who underwent a PSMA scan after coronary artery bypass graft surgery, revealing disease progression and PSMA-avid foci at the surgical stitch sites. This report discusses the immunohistochemical and molecular imaging mechanisms underlying PSMA expression in surgical scar tissues, providing critical insights for optimizing radiologic reporting in such situations.

Introduction

Prostate cancer is the second most prevalent malignant neoplasm in men worldwide. ¹ Currently, this challenging disease is experiencing a rise in its occurrence, emphasizing the growing necessity for personalized management.^2,3 To date, many developed and developing countries rely on ⁶⁸Gallium prostate-specific membrane antigen (⁶⁸Ga-PSMA) positron emission tomography/computed tomography (PET/CT) imaging to stage and monitor patients with prostate cancer.^4,5 This novel modality provides a comprehensive assessment of the entire body, offering valuable insights into the disease extent. ⁶ It has revolutionized the evaluation of the disease by enabling the detection of primary and recurrent lesions, as well as subtle metastatic sites. ⁷ It also showed superiority in evaluation of hybrid synchronous histopathologies as well as patients with multiple primary neoplasms.^8–10 The mechanism behind the uptake and localization of PSMA by cancer cells involves the overexpression of PSMA antigen on their surface, allowing for targeted binding and internalization of PSMA-targeted agents. ¹¹ However, the specificity of PSMA is not absolute. PSMA expression has been observed in various non-prostatic malignancies, affecting its diagnostic accuracy. ¹⁰ It can also be expressed in benign conditions and can occur in postsurgical and reactive scenarios, potentially compromising the reliability of PSMA-based imaging. ¹⁰ These factors highlight the importance of cautious interpretation when relying solely on PSMA-based imaging in clinical decision making. In this case report, we present a patient with prostate cancer who exhibited PSMA localization at the sites of coronary artery bypass graft (CABG) stitches, which is an unexpected location for PSMA expression. To our knowledge, this is the first reported instance of multifocal PSMA expression at the site of CABG surgery. This case also provides insights into the molecular and histopathological perspectives of this distinctive pattern of PSMA expression.

Case report

Clinical history

A 79-year-old male patient with a history of prostate cancer underwent multiple lines of therapy. These included bilateral surgical castration orchiectomy performed about 8 years ago, followed by salvage radiotherapy and 1 year of androgen deprivation therapy, resulting in complete remission up until a year ago. Recently, the patient experienced a myocardial infarction and subsequently underwent CABG surgery. Six months following the surgery, a ⁶⁸Ga-PSMA PET/CT scan was requested to assess disease status after a marginal rise in PSA (from 1 ng/mL to 3.2 ng/mL).

Imaging findings

The ⁶⁸Ga-PSMA PET/CT study revealed evidence of a few enlarged abdominopelvic lymphadenopathy (LAP) indicating disease recurrence. These PSMA-avid metastatic LAP were found involving right external iliac, para-aortic, and aortocaval regions (Figure 1). In addition, sagittal PET and sagittal PET/CT images of the chest revealed recent ancillary evidence of multifocal PSMA lesions localized within CABG surgical stitches (Figure 1). The maximum standardized uptake value (SUVmax) was high (up to 11.2). The patient’s clinical scenario was discussed in a multidisciplinary clinic in order to establish a course of action. Due to the patient’s clinical condition and low level of prostate-specific antigen (PSA), obtaining histopathologic confirmation from the CABG site was deemed burdensome and invasive. Instead, it was preferred to rely on biochemical correlation by measuring alkaline phosphatase levels and regularly monitoring PSA. With the exception of a minor elevation in PSA, all other laboratory tests yielded normal results. When correlated with the patient’s past surgical history, it was confirmed that this expression is attributable to non-neoplastic surgical scar PSMA tissue uptake. The patient is currently scheduled to receive hormonal therapy and maintain regular follow-up until adequate disease control is achieved.

Figure 1.

A gallium-68 prostate-specific membrane antigen (⁶⁸Ga-PSMA PET/CT) scan was performed for a 79-year-old man 6 months after coronary artery bypass graft (CABG) surgery. (a) Maximum intensity projection; (b) sagittal PET/CT; and (c), sagittal PET images showed multiple PSMA avid foci at the site of CABG surgical stitches with the maximum standardized uptake value (SUVmax: 11.2) (arrows). Increased PSMA expression in abdominal lymph nodes was also observed (dotted arrow). (d)-(f) Axial PET/CT images of abdominopelvic regions revealed evidence of a few PSMA-avid enlarged abdominopelvic lymphadenopathy (LAP), indicating nodal disease recurrence. These PSMA-avid metastatic LAP were found involving the right external iliac, para-aortic, and aortocaval regions, with SUVmax values of 3.6, 10.1, and 7.3, respectively (dotted arrows).

Discussion

After a thorough analysis of the patient’s ⁶⁸Ga-PSMA PET/CT images, an initial suspicion of metastatic involvement might arise. While rare, cutaneous metastases typically present with a more superficial localization and irregular demarcations. ¹² When they occur, these cutaneous manifestations often appear as numerous dispersed lesions, distributed in a non-uniform manner. ¹² Common sites include the lower abdomen, thighs, and scrotum, with occasional extension to the chest, back, and face. ¹³ In most cases, cutaneous lesions present as multiple rubbery nodules or plaques, occasionally as solitary nodules, and rarely as edematous areas or non-specific rashes.^13,14 However, in this particular case, the observed pattern differs from these characteristic attributes as the PSMA-avid foci exhibit a consecutive and deeper distribution. Additionally, in this instance, the possibility of bone metastases can be dismissed from consideration. It is important to highlight that the patient did not encounter specific localized bone discomfort, and the CT scans did not reveal any radiologic signs to indicate bone metastasis. Equally important is the lack of a significant increase in PSA levels and the absence of an elevation beyond normal levels in alkaline phosphatase levels, effectively ruling out these two potential causes.

In certain clinical situations, the adoption of an alternative radiotracer in molecular imaging can prove advantageous in mitigating the occurrence of false-positive findings in instances of diagnostic uncertainty. For such contexts, the utilization of ¹¹C-choline PET/CT represents a viable approach. ¹¹C-choline PET/CT can detect recurrent prostate cancer sites based on phosphatidylcholine synthesis, a constituent of the cell membrane in prostate cancer. ¹⁵ Conversely, surgical scars, primarily comprising collagen, exhibit dissimilar cellular characteristics in comparison to neoplastic tissue. Therefore, it is improbable that ¹¹C-choline PET/CT would manifest substantial radiotracer uptake within surgical scar tissue.

⁶⁸Ga-PSMA PET/CT is an effective imaging modality that offers comprehensive evaluation of the prostate, lymph nodes, soft tissues, and bones. ⁴ Compared to traditional imaging methods, ⁶⁸Ga-PSMA PET/CT demonstrates higher levels of sensitivity and specificity, making it a valuable tool in the staging of high-risk prostate cancer and the detection of oligometastatic disease during biochemical recurrence. ¹⁶ This is not applicable in all scenarios; for example, the specificity of ⁶⁸Ga-PSMA PET/CT tends to be underwhelmed by various pitfalls that become increasingly unraveled with time. Inflammatory and infective conditions can mimic PSMA-avid lesions, but these can often be distinguished based on morphologic criteria seen on CT images. ¹⁶ For instance, subcutaneous multifocal PSMA-avid lesions have been reported in patients with prostate cancer, which were later identified as angiolipomas through histopathological examination. ¹⁷ Non-specific PSMA uptake at sites of recent surgical interventions, such as hernia repair with mesh grafting, has also been reported. ¹⁸ Clinical history correlation can be helpful in identifying and understanding these pitfalls. Immunohistochemistry (IHC) studies have shown that PSMA expression is associated with angiogenesis and vasculogenesis, which contributes to the discriminative power of PSMA PET/CT compared to contrast-enhanced magnetic imaging resonance (CEMRI). PSMA PET/CT has been successful in detecting local prostatic recurrence 5 years after prostatectomy that was initially misinterpreted as postsurgical scar on CEMRI. ¹⁹ Same evidence was also endorsed by patient with non-prostatic Juvenile Nasopharyngeal Angiofibroma. ²⁰ Postoperative PSMA PET/CT was helpful in accurately and sharply depicting tumor contour for LRT planning while MRI failed to do so due to post-inflammatory scarring. ²⁰

This advantage was not seen ultimately in all previous reports as evidence by IHC suggested that PSMA expression could be found in non-neoplastic reparative and regenerative scar tissues. ²¹ Focal PSMA expression was observed in non-neoplastic scar tissues, with varying degrees of intensity. ²¹ The pattern of expression denoted was focal and nearly half of the positive cases had weak expression, and the other half had strong expression. Recent observations have shown mild PSMA expression at the site of surgical scars using ⁶⁸Ga-PSMA PET/CT. ²² In our reported case, multifocal PSMA-avid foci were observed following CABG surgery, showing intense PSMA expression (SUVmax up to 11.2).

In conclusion, the presence of focal PSMA uptake at sites of surgical intervention should not be automatically attributed to prostate cancer. Careful clinical and biochemical correlation is necessary to make accurate interpretations. Such approach can help reach definitive diagnosis in uncertain cases and when biopsy seems impractical.