Invasive lobular carcinoma of the breast with multifocal gastrointestinal, ovarian, and peritoneal metastases: a case report.

Introduction
Invasive lobular carcinoma (ILC) accounts for approximately 10–15% of all invasive breast cancers and differs markedly from invasive ductal carcinoma (IDC) in both histological pattern and metastatic behavior [1, 2]. Unlike IDC, which typically metastasizes bones, lungs, liver, brain, and brain, ILC demonstrates a predilection for less common sites such as the gastrointestinal (GI) tract, peritoneum, ovaries, and retroperitoneum [3–5].
Although metastases to the GI tract from breast cancer are rare in clinical practice, with an estimated incidence of 0.3–2%, autopsy studies have reported rates as high as 15–18%, suggesting that gastrointestinal involvement is underdiagnosed during life [4, 6]. ILC is more frequently associated with GI metastases than IDC, potentially owing to the tumor’s loss of E-cadherin expression and characteristic single-file infiltration pattern, which facilitates dissemination to serosal and mucosal surfaces [4, 7]
Clinically apparent gastrointestinal metastases from breast cancer are uncommon; however, autopsy studies suggest that gastrointestinal involvement occurs more frequently than is diagnosed during life [8, 9]. Metastatic ILC may infiltrate the submucosa or serosa without forming discrete masses, resulting in subtle or nonspecific symptoms and inconclusive imaging findings. As a result, diagnosis is often delayed or mistaken for primary gastrointestinal or gynecologic malignancy [10].
We describe a rare and instructive case of estrogen receptor-positive ILC with multifocal metastatic involvement of the stomach, ovaries, peritoneum, rectum, and jejunum occurring several years after definitive treatment of the primary tumor. This case underscores the diagnostic challenges associated with metastatic ILC and emphasizes the importance of maintaining clinical vigilance when new gastrointestinal symptoms or unexplained tumor marker elevations arise in long-term breast cancer survivors.

Case presentation
A 43-year-old Iranian woman with a remote history of Hodgkin’s lymphoma treated with chemotherapy during adolescence presented in 2015 with a palpable mass in the right breast and ipsilateral axillary lymphadenopathy (Table 1; Fig. 1). Core needle biopsy confirmed invasive lobular carcinoma of the breast, histologic grade 2, with strong estrogen receptor (ER) and progesterone receptor (PR) expression, negative human epidermal growth factor receptor 2 (HER2), and a Ki-67 proliferation index of approximately 15–16%. Baseline staging investigations revealed no evidence of distant metastatic disease.

The patient received neoadjuvant chemotherapy with doxorubicin and cyclophosphamide followed by paclitaxel, after which she underwent a right modified radical mastectomy. Histopathological examination demonstrated multifocal invasive lobular carcinoma with focal ductal features, the largest invasive focus measuring 19 mm. Lymphovascular and perineural invasion were present. Two axillary lymph nodes were involved by metastatic carcinoma, and additional tumor deposits were identified in axillary adipose tissue. Given the extent of regional nodal involvement beyond the sampled nodes, the final pathological stage was reported as pT1c with advanced nodal disease. Adjuvant radiotherapy was administered to the chest wall and regional lymphatic basins (50 Gy in 25 fractions), followed by adjuvant endocrine therapy with tamoxifen and ovarian suppression using triptorelin.
From 2015 to 2021, the patient remained clinically stable. Follow-up consisted of regular physical examinations, periodic serum CA 15-3 measurements, and routine imaging as per institutional protocol. During this period, no radiologic evidence of recurrence was identified. In early 2021, a gradual but persistent rise in serum CA 15-3 was noted, increasing from baseline values of approximately 20 U/mL to 204 U/mL. Whole-body 18F-fluorodeoxyglucose positron emission tomography–computed tomography (FDG PET–CT) demonstrated a mildly hypermetabolic right cervical lymph node (SUVmax 3.5). Both core needle biopsy and subsequent excisional biopsy revealed reactive changes without malignancy. Considering biochemical progression without a clear anatomic correlation, endocrine therapy was modified to letrozole in combination with continued ovarian suppression.
Approximately 3 months later, the patient developed new-onset dyspepsia and vague epigastric discomfort. Repeat FDG PET–CT demonstrated diffuse, mild hypermetabolic activity within the gastric wall (SUVmax 4.8), without discrete mass formation. Upper gastrointestinal endoscopy revealed patchy nodular erythema involving the gastric body and antrum. Histological examination of mucosal biopsies showed infiltration by small, discohesive malignant cells arranged in single files within the lamina propria (Fig. 2A,B). Immunohistochemical staining demonstrated positivity for pancytokeratin, GATA3, estrogen receptors (ER), and progesterone receptors (PR), with negative staining for HER2 and β-catenin, confirming gastric metastasis from the known breast primary (Fig. 3). Systemic chemotherapy was initiated with paclitaxel and gemcitabine and later transitioned to docetaxel and gemcitabine. Following disease stabilization, maintenance therapy with palbociclib in combination with fulvestrant was administered, subsequently followed by exemestane and palbociclib.
In 2023, despite the absence of suspicious findings on transvaginal ultrasonography and pelvic magnetic resonance imaging, a bilateral salpingo-oophorectomy was performed. This intervention was undertaken both for definitive ovarian suppression in the setting of hormone receptor-positive metastatic disease and because of the recognized predilection of invasive lobular carcinoma for occult ovarian involvement. Histopathological evaluation unexpectedly revealed metastatic lobular carcinoma in both ovaries (Figs. 4, 5), and cytological examination of peritoneal washings demonstrated malignant cells, confirming peritoneal dissemination (Fig. 6). Chemotherapy was resumed with carboplatin and gemcitabine.
In early 2024, the patient developed constipation and intermittent rectal bleeding. Cross-sectional imaging did not demonstrate new metastatic lesions. Colonoscopy revealed patchy erythema of the rectal mucosa, and biopsies confirmed metastatic invasive lobular carcinoma with immunohistochemical features consistent with breast origin (Fig. 1C,D). Systemic therapy was adjusted to weekly docetaxel.
During 2025, while receiving palliative chemotherapy, the patient developed symptoms of partial small-bowel obstruction. Magnetic resonance enterography demonstrated focal mural thickening and enhancement of jejunal loops, suggestive of metastatic involvement. Supportive care was provided alongside continued systemic therapy. Throughout the disease course, no radiologic evidence of extra-abdominal organ metastases has been identified. The patient remains under active oncologic management with ongoing clinical monitoring (Table 1).

Discussion
ILC accounts for 10–15% of all breast malignancies and exhibits a metastatic pattern distinct from the more common ductal carcinoma [7, 11]. While ductal cancers typically spread to the lungs, liver, and brain, ILC demonstrates a predilection for the GI tract, peritoneum, and gynecologic organs [7, 12]. This specific tropism is mechanistically linked to the loss of E-cadherin expression, a cell-to-cell adhesion molecule; its absence allows ILC cells to disseminate in a discohesive, single-file pattern that infiltrates serosal surfaces and hollow viscera without forming distinct, mass-like lesions [4, 7].
​ This infiltrative behavior creates a significant discordance between clinical detection and actual disease burden. While clinical series estimate GI metastasis prevalence at only 0.3–2%, autopsy studies reveal rates as high as 15–18%, suggesting that a significant proportion of diagnoses are missed during the patient’s life [4, 6, 7]. The stomach is the most frequent site of GI involvement, followed by the colon and rectum [7, 12–14]. In our case, the patient exhibited sequential involvement of the stomach, ovaries, peritoneum, rectum, and jejunum, compatible with the diffused metastatic spread of ILC [8, 11].
A critical teaching point from this case is the failure of standard imaging to quantify the extent of ILC metastasis. Despite the patient having diffuse peritoneal and ovarian involvement, transvaginal ultrasound and pelvic MRI were unremarkable. This occult presentation is characteristic of ILC; the cells often coat the peritoneum or infiltrate the ovarian stroma without distorting the organ’s architecture or creating a mass effect visible on cross-sectional imaging [10]. Furthermore, while PET–CT identified the gastric lesion, it failed to capture the full extent of peritoneal disease. PET–CT often has lower sensitivity for ILC compared with ductal carcinoma owing to the tumor’s lower cellular density and lower metabolic activity. In clinical practice, this creates a dilemma: When tumor markers rise, clinicians often rely on PET–CT to localize disease. In this case, the decision to rely on PET–CT alone was driven by its utility in screening for distant metastasis, yet the negative findings on other modalities despite a CA 15–3 rising above 200 U/mL underscore the need for a lower threshold for endoscopic and laparoscopic evaluation in patients with ILC.
The time to onset of GI metastases can be variable. In our patient, gastric metastasis emerged approximately 6 years after initial treatment, aligning with the median interval of 6–7 years reported in literature, though latency can extend up to 30 years [12, 15]. Given the limitations of imaging, serum CA 15-3 served as the most reliable indicator of disease progression in this patient. The marker elevation preceded endoscopic findings, suggesting that in ILC survivors, a rising CA 15-3 should prompt a rigorous search for visceral metastasis even in the absence of radiological findings. Emerging literature supports this approach, identifying a potential role for CA 15-3 monitoring in detecting occult recurrences in lobular carcinoma [16].
Because symptoms such as dyspepsia, constipation, and rectal bleeding mimic primary GI disorders, histopathological confirmation is mandatory [8, 9]. The diagnostic distinction relies on an immunohistochemical panel: Metastatic ILC is typically CK7-, GATA3-, and ER/PR-positive, while being negative for E-cadherin and beta-catenin [11, 12]. In contrast, primary GI cancers are usually CK20- and CDX2-positive [14]. In this case, the biopsy confirmed the breast origin, preventing a misdiagnosis of a primary gastric or rectal cancer.
Management of GI metastases from ILC is primarily systemic, involving endocrine therapy, chemotherapy, and CDK4/6 inhibitors tailored to disease burden and receptor status [7]. Surgical intervention is typically reserved for complications such as obstruction, perforation, or hemorrhage [10, 15]. However, this case illustrates a specific role for oophorectomy. Although the ovaries appeared normal on imaging, a bilateral salpingo-oophorectomy was performed for hormonal suppression (ovarian ablation). The incidental discovery of bilateral ovarian metastases in the surgical specimen validates this aggressive approach and suggests that prophylactic oophorectomy in metastatic ILC may have diagnostic as well as therapeutic value, revealing occult disease reservoirs that escape radiological detection.

Conclusion
This case underscores the insidious nature of metastatic ILC. The rectum is a particularly rare site of metastasis and may present symptoms mimicking hemorrhoidal disease, further complicating diagnosis. Clinicians must maintain a high index of suspicion for GI and gynecologic metastases in patients with a history of lobular carcinoma who present with nonspecific abdominal symptoms or rising tumor markers. Early endoscopic evaluation and liberal use of biopsy with breast-specific immunohistochemistry are essential to avoid diagnostic delays.