ABSTRACT

Neuroendocrine tumors (NETs) of the breast represent 1% of breast carcinomas. Histopathological misinterpretation of breast NET is common. We present the case of a female patient who had a breast mass diagnosed as invasive ductal carcinoma initially by histopathological examination. Fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) revealed 2 ametabolic hypodense liver lesions. Subsequently, the patient underwent fibroblast activation protein inhibitor (FAPI)-PET/CT, which did not reveal any FAP expression in the liver lesions, but increased FAP expression was observed in the soft tissue mass of the mesenteric root. Consequently, the pathology of the biopsy taken from the nodule in the right breast was revised, and a diagnosis of grade 2 NET was established. The benefit of FAPI-PET/CT on NETs has been previously investigated. Further prospective studies are required to establish the role of FAPI-PET/CT in NET management

Introduction

Metastatic neuroendocrine tumors (NETs) are exceedingly rare in breast cancer, representing less than 1% of all breast carcinomas (1,2). A study examining 18 cases of NETs metastasizing to the breast revealed that 62% of these tumors originated from the gastrointestinal tract and 28% from the lungs. Notably, 44% of these tumors were initially misdiagnosed as primary breast carcinoma (1). We present a rare case of metastatic NET initially reported as invasive ductal carcinoma (IDC), which was demonstrated through [⁶⁸Ga]gallium-fibroblast activation protein inhibitor (⁶⁸Ga-FAPI) positron emission tomography/computed tomography (PET/CT) and [⁶⁸Ga]Ga-DOTATATE PET/CT imaging.

Case Report

A 59-year-old female patient presented with a 1-year history of nausea, vomiting, and flushing. During a physical examination, a breast mass was detected, which led to a tru-cut biopsy. Histopathological analysis initially indicated IDC (Figure 1). She was subsequently referred to our clinic for staging. Fluorodeoxyglucose (FDG) PET/CT revealed a slightly hypermetabolic 7-mm nodule in the right breast and two hypodense, ametabolic liver lesions (Figure 2A). Considering the ametabolic nature of these liver lesions, lobular carcinoma was suspected, prompting [⁶⁸Ga]Ga-DOTA-FAPI-04 PET/CT. This imaging did not demonstrate any FAP expression in the liver lesions, but increased FAP expression was observed in the mesenteric root soft tissue mass and right breast nodular lesion (Figure 2B). Maximum standardized uptake value of uptake in the mesenteric root was 16. Upon retrospective re-evaluation of the patient’s clinical findings, the mesenteric root soft tissue mass, as demonstrated by [⁶⁸Ga]Ga-DOTA-FAPI-04 PET/CT, along with symptoms such as nausea, vomiting, and flushing, were consistent with a diagnosis of NET. Based on these findings, the histopathological examination was repeated, and the diagnosis was revised to NET (Figure 3). In addition to revising the primary pathological sample, histopathological examination of biopsies obtained from the mesentery and liver confirmed the diagnosis of grade 2 NET. Consequently, [⁶⁸Ga]Ga-DOTATATE PET/CT was performed. Imaging revealed a soft tissue mass in the mesenteric root with increased somatostatin receptor (SSTR) expression, multiple SSTR-positive bone, liver, and lymph node metastases, and metastatic SSTR-positive nodules in both breasts (Figure 2C).

Informed consent was obtained from the patient for all modalities.

Literature Review and Discussion

Although the FAPI uptake pattern of NETs is not exactly established, heterogeneous uptake has been reported (3). In addition to that, [⁶⁸Ga]Ga-FAPI PET/CT’s utility in primary and metastatic NETs was previously demonstrated in case reports (4,5,6,7). Despite the high FAP expression of the primary tumor (mass in mesenteric root) in our case, the absence of FAPI uptake by liver and bone metastases was remarkable. In this case, ¹⁸F-FDG PET/CT was requested for the preoperative staging of breast cancer. However, the ¹⁸F-FDG PET/CT scan revealed a mildly FDG-avid nodule in the right upper outer quadrant of the breast. In addition, soft tissue mass in the mesenteric root and hypodense nodules in the right hepatic lobe were FDG-negative. Concurrently, magnetic resonance imaging of the liver interpreted these liver nodules as suggestive of metastases. In the literature, there is a substantial amount of data suggesting that [⁶⁸Ga]Ga-FAPI PET/CT, because of the absence of background liver activity, can better detect metastatic lesions (8). Therefore, we performed [⁶⁸Ga]Ga-FAPI PET/CT to evaluate the possibility of lobular breast carcinoma and its metastasis in the liver. However, [⁶⁸Ga]Ga-[⁶⁸Ga]Ga-FAPI PET/CT images did not show uptake in the liver lesions. Instead, an additional FAPI-avid mass within the mesenteric root that was inseparable from the bowel loops was detected in the abdominal region, along with multiple metastatic nodules in both breast lobes, raising the suspicion that the primary tumor might not be in the breast but rather in the abdominal mass, possibly a NET. As a result, a biopsy was recommended to the lesion in the mesenteric root and revealed a diagnosis of G2 NET. Afterwards [⁶⁸Ga]Ga-DOTATATE PET was performed for staging of NET. [⁶⁸Ga]Ga-DOTATATE imaging revealed SSTR positivity in the breast, abdominal, and liver lesions. Additional multiple bone metastases were detected.

In this case, following these three imaging modalities, the patient’s clinical diagnosis and stage changed significantly. Initially referred to our clinic for preoperative staging of breast cancer, the patient was ultimately diagnosed with metastatic NET, leading to the initiation of systemic treatment. NET metastases in the breast are quite rare, and biopsy alone may not be sufficient. In such cases, molecular imaging techniques such as [⁶⁸Ga]Ga-FAPI and [⁶⁸Ga]Ga-DOTATATE can be beneficial.

The images of PET/CTs using 3 different tracers all showed multiple foci of increased uptake of radiopharmaceutical in the abdomen and breast, in which [⁶⁸Ga]Ga-FAPI PET/CT displayed the highest tumor-to-background ratio. However, [⁶⁸Ga]Ga-DOTATATE PET/CT detected more metastatic lesions and liver and bone metastases, which were missed by both ¹⁸F-FDG and [⁶⁸Ga]Ga-FAPI PET/CT.

In this study, both modalities led to a complete change in the patient’s histopathological diagnosis and, concurrently, a shift in the treatment algorithm.

Ethics

Informed Consent: Informed consent was obtained from the patient for all modalities.

Authorship Contributions

Surgical and Medical Practices: N.A.S., S.Ç., B.B.Ö., Concept: N.A.S., S.Ç., B.B.Ö., L.K., Design: N.A.S., L.K., Data Collection or Processing: K.A., G.B., Ö.S., Analysis or Interpretation: N.A.S., L.K., Literature Search: K.A., G.B., Ö.S., Writing: N.A.S., K.A., G.B., Ö.S., S.Ç., B.B.Ö., L.K.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study received no financial support.