Bilateral invasive lobular breast carcinoma with synchronous gastric metastasis and orbital pseudotumor mimicking metastasis: a case report

In October 2021, a 54-year-old postmenopausal Egyptian woman presented to the center with bilateral breast masses. She has a history of hypertension and has reported a positive family history of her mother diagnosed with breast cancer at the age of 60 years. No relevant psychosocial history was reported. Clinical examination and initial radiographic assessment (Fig.  1 ) revealed bilateral upper outer quadrant breast masses. The left mass was approximately 6*5 cm with involvement of the ipsilateral axillary lymph nodes, and the right mass was 2*2 cm. Fig. 1 Initial radiographic assessment of bilateral invasive lobular carcinoma. A Mediolateral oblique (MLO) mammography for the left breast view demonstrating a high-density spiculated mass in the upper outer quadrant classified as BIRADS 5. B Targeted ultrasound of the left breast demonstrating a heterogeneous hypoechoic mass with ill-defined margins, measuring approximately 7.3 cm in maximal dimension. C Mammographic view of the right breast showing a smaller irregular mass in the upper outer quadrant Initial radiographic assessment of bilateral invasive lobular carcinoma. A Mediolateral oblique (MLO) mammography for the left breast view demonstrating a high-density spiculated mass in the upper outer quadrant classified as BIRADS 5. B Targeted ultrasound of the left breast demonstrating a heterogeneous hypoechoic mass with ill-defined margins, measuring approximately 7.3 cm in maximal dimension. C Mammographic view of the right breast showing a smaller irregular mass in the upper outer quadrant Tru-cut biopsies of both masses revealed grade II bilateral invasive lobular carcinoma (ILC). Immunohistochemistry (IHC) results demonstrated strong positivity for both ER (100% of tumor cells, 8/8) and progesterone receptor (PR) (100% of tumor cells, 8/8); however, human epidermal growth factor receptor-2 (HER-2) was negative. A contrast-enhancing CT scan of the chest, abdomen, and pelvis (CT CAP) showed bilateral breast masses with enlarged bilateral axillary lymph nodes. Moreover, there was gastric and colonic thickening, dilatation of both renal pelvicalyceal systems with abrupt caliber changes in the pelvi-ureteric junctions suggestive of pelvi-ureteric junction obstruction, moderate ascites, and ill-defined lucent areas in the manubrium sterni. No evidence of hepatic or pulmonary metastasis (Fig.  2 ). Creatinine levels was 1.39. Fig. 2 Post contrast multi-slice CT scan for the chest, abdomen and pelvis. A axial CT of the chest demonstrates bilateral irregular heterogeneously enhancing breast masses. B Axial CT of the abdomen shows a diffuse uniform gastric wall thickening suspicious for metastatic involvement Post contrast multi-slice CT scan for the chest, abdomen and pelvis. A axial CT of the chest demonstrates bilateral irregular heterogeneously enhancing breast masses. B Axial CT of the abdomen shows a diffuse uniform gastric wall thickening suspicious for metastatic involvement In November 2021, upper gastrointestinal endoscopy was performed regarding the gastric thickening, and biopsies were taken. The results confirmed metastatic invasive lobular carcinoma (Fig.  3 ). Fig. 3 Histopathological findings. A Gastric biopsy showing metastatic invasive lobular carcinoma with infiltrative growth pattern. B Breast tru-cut biopsy showing invasive lobular carcinoma with desmoplastic stroma Histopathological findings. A Gastric biopsy showing metastatic invasive lobular carcinoma with infiltrative growth pattern. B Breast tru-cut biopsy showing invasive lobular carcinoma with desmoplastic stroma Due to the heavy tumor burden, the patient was started on Taxol (80 mg/m²) as a palliative chemotherapy, completing 12 cycles from December 2021 to March 2022. Then followed by Tamoxifen and Zoladex as maintenance in March 2022. In October 2022, the patient complained of repeated vomiting and weight loss. She also presented with mouth deviation and right-sided ptosis. A repeated CT scan of the brain, chest, abdomen, and pelvis showed mild regression of the previously seen right axillary lymphadenopathy and bilateral dilatation of the renal pelvicalyceal system. However, it showed persistence of the right orbital intra-conal soft tissue and needed further assessment with MRI. Magnetic resonance imaging (MRI) of the brain (Fig.  4 ) revealed the right intrac-conal creeping orbital soft tissue involving the right medial rectus and inferior rectus muscles, abutting the posteromedial aspect of the right eye globe, and encasing the ill-defined optic nerve. The lesion also extends to the inferomedial aspect of the exta-conal space. This pattern was more likely to be an orbital pseudotumor rather than a metastatic deposit. MRI also illustrated multiple bilateral cerebral white matter foci, which are likely to be ischemic changes, and mild ventriculomegaly. Fig. 4 Brain and Orbit MRI. A On October 4th 2022, Axial MRI demonstrating an ill-defined intra-Conal soft tissue lesion in the right orbit. B On October 31st 2022, Follow-up axial MRI showing persistence of the orbital lesion. C Sagittal MRI illustrating the infiltrative soft tissue lesion abutting the globe and extending within the orbit Brain and Orbit MRI. A On October 4th 2022, Axial MRI demonstrating an ill-defined intra-Conal soft tissue lesion in the right orbit. B On October 31st 2022, Follow-up axial MRI showing persistence of the orbital lesion. C Sagittal MRI illustrating the infiltrative soft tissue lesion abutting the globe and extending within the orbit An ophthalmologic examination revealed mild limitations of the right eye abduction. Fundus examination showed normal findings, no signs of metastasis or optic nerve compression. As a result, the patient was treated with corticosteroids that showed improvement in the symptoms, and urgent palliative radiotherapy was postponed. In January 2023, a bone scan was performed and didn’t reveal metastatic osseous deposits (Fig.  5 ). Furthermore, on Sep 2023, the patient complained of headache, visual disturbances in the right eye, dysarthria, and weakness in buccal muscles and lower limbs. A nerve conduction study showed axonal motor polyneuropathy affecting the lower limbs, which made the patient undergo 6 sessions of plasma exchange as advised by the neurologist. No further details regarding neurological examination was provided or present in the patient’s record. Fig. 5 Comparative 99mTc-MDP bone scan. A Baseline whole body bone scan (Feb 2022) showing no evidence for active metastatic osseous deposits. B Follow up whole body bone scan (Jan 2023) showing no interval development of metastatic bone disease Comparative 99mTc-MDP bone scan. A Baseline whole body bone scan (Feb 2022) showing no evidence for active metastatic osseous deposits. B Follow up whole body bone scan (Jan 2023) showing no interval development of metastatic bone disease The patient was under follow-up with the ophthalmologist, receiving topical corticosteroids for the eye, with stationary disease and a mild headache till January 2023, after which she was lost to follow-up. The clinical timeline was depicted in Fig.  6 . Fig. 6 A clinical timeline illustrates the progression of symptoms A clinical timeline illustrates the progression of symptoms

In contrast to most reported gastric ILC metastases, which appear years after initial diagnosis [ 13 ], this case demonstrated synchronous gastric involvement at primary diagnosis. This pattern likely reflects the biological hallmarks of aggressive ILC which is the loss of E‑cadherin permits diffuse, non‑cohesive infiltration of distant tissue planes, while submucosal growth allows GI seeding without early luminal symptoms. Therfore, diagnostic delay and patient debilitation may also contribute [ 14 ]. Our patient presented with vomiting, and contrast‑enhanced CT revealed gastric and colonic wall thickening that radiologically mimicked a primary gastrointestinal malignancy. This is consistent with the literature, which describes non‑specific upper‑ and lower‑GI symptoms in metastatic breast disease, including epigastric pain, distention, obstruction, early satiety and weight loss [ 15 ]. The diagnosis was established only after endoscopic biopsy of the gastric thickening, which demonstrated metastatic ILC, underscoring the importance of maintaining a high index of suspicion when breast cancer patients present with GI symptoms [ 16 ]. A stepwise diagnostic approach is therefore warranted, combining cross‑sectional imaging of the abdomen and pelvis [ 17 ], endoscopic evaluation with targeted biopsies [ 18 ], and immunohistochemical confirmation using ER, PR, GATA3, GCDFP‑15 and mammaglobin to confirm breast origin and avoid unnecessary surgical intervention [ 19 ]. It was found that the role of immunohistochemistry in differentiating metastatic from primary GI malignancy [ 20 , 21 ]. The concurrent orbital lesion raised an important differential between metastasis and idiopathic orbital inflammatory pseudotumor. Breast cancer is one of the leading causes of secondary orbital tumors [ 22 ], with ILC particularly over‑represented [ 23 ]. Clinically, both entities can present with proptosis, diplopia, ocular pain and reduced vision [ 24 ], and on imaging both may appear as ill‑defined infiltrative lesions involving orbital fat and extraocular muscles, sometimes with paradoxical enophthalmos in scirrhous breast carcinoma [ 25 ]. CT and MRI may also mimic thyroid ophthalmopathy, lymphoma or orbital inflammation, so imaging alone is rarely sufficient [ 26 ]. Steroid responsiveness is a useful but imperfect differentiator. Pseudotumor typically shows clear and sustained clinical and radiological improvement, whereas orbital metastasis usually demonstrates only minimal or transient response [ 27 ]. Where doubt persists, biopsy with immunohistochemistry (ER, PR, GATA‑3, cytokeratin) confirms the diagnosis [ 28 ]. In our patient, the orbital lesion remained radiologically stable and showed sustained clinical improvement on systemic and topical corticosteroids over more than a year, supporting a diagnosis of idiopathic orbital pseudotumor rather than metastasis [ 29 , 30 ]. We acknowledge that absence of histological confirmation is a limitation, and that orbital ILC metastases can closely mimic inflammatory disease. Thereby, in any patient with current or remote ILC who develops new‑onset orbital inflammation, a low threshold for orbital biopsy alongside oncological review and dedicated cross‑sectional imaging is warranted [ 27 , 31 ]. The relationship between orbital inflammation and active malignancy in our case may be coincidental, paraneoplastic, or reactive to the systemic pro‑inflammatory state of metastatic disease, with hematogenous spread the leading proposed mechanism for true orbital seeding [ 32 ]. Once tumor cells are established in orbital fat or extraocular muscles, local inflammation and fibrosis can further blur the radiological distinction from pseudotumor [ 33 ]. Rare reports of atypical immunophenotypes in orbital deposits suggest that some tumors may carry molecular traits that favor orbital tropism [ 34 ]. Moreover, our patient developed an axonal motor polyneuropathy after taxane exposure, raising the question of chemotherapy‑induced peripheral neuropathy (CIPN) versus a paraneoplastic process. Taxane‑related CIPN affects 30‑60% of treated patients [ 35 , 36 ], but is typically sensory‑predominant, length‑dependent and symmetric [ 37 ]. The motor‑predominant pattern observed is atypical for CIPN and raises the possibility of a paraneoplastic motor neuropathy, which occurs in 1‑5% of cancer patients and has been described in association with breast cancer, particularly with anti‑amphiphilic or anti‑CV2/CRMP5 antibodies. The distinction matters clinically because paraneoplastic neuropathies may respond to immunomodulation, whereas CIPN is managed with dose modification and supportive care [ 38 ]. The absence of paraneoplastic antibody testing and dedicated electromyography is a recognized limitation. The patient was managed initially with weekly paclitaxel (80 mg/m²), reflecting the heavy tumor burden which is the gastric metastasis, ascites, bilateral pelvicalyceal dilatation and extensive nodal disease, which favored chemotherapy over endocrine therapy in line with guideline recommendations for rapidly progressive HR‑positive/HER2‑negative disease [ 39 ]. Once disease control was achieved, maintenance was transitioned to tamoxifen with goserelin. The combination of tamoxifen and goserelin does not represent the conventional endocrine maintenance strategy for postmenopausal HR‑positive/HER2‑negative metastatic breast cancer, in which an aromatase inhibitor combined with a CDK4/6 inhibitor remains the recommended first‑line standard. This treatment choice should therefore be interpreted in the context of local drug availability and clinical practice patterns rather than as a recommended standard of care, particularly given that recent reports have shown favorable responses to combinations of endocrine therapy and CDK4/6 inhibitors in HR‑positive/HER2‑negative metastatic ILC with orbital involvement [ 40 ]. Surgical resection of the gastric lesion was not pursued, consistent with evidence that primary tumor or metastatic site resection in de novo stage IV disease offers no overall survival benefit and is reserved for complications such as obstruction or bleeding [ 41 ], and aligned with the observation that orbital pseudotumor and metastatic ILC require careful radiological and clinical evaluation to be reliably distinguished [ 42 ]. This report has several limitations. The biopsy of the orbital lesion was not performed, and the diagnosis of pseudotumor was based on clinical and radiological features combined with the steroid empirical response. Although this approach is consistent with clinical practice, histological confirmation would have provided definitive exclusion of metastasis. Furthermore, paraneoplastic antibody testing was not performed for the polyneuropathy evaluation, limiting the ability to distinguish between taxane-induced and paraneoplastic etiologies. Also, CDK4/6 inhibitors were not used due to drug accessibility, which may have affected treatment outcomes. Additionally, the patient was lost to follow-up in early 2023, preventing long-term outcome assessment. Lastly, the single-case nature of this report limits generalizability, and the association between orbital pseudotumor and metastatic ILC remains observational.

Breast cancer remains the most frequently diagnosed cancer and a leading cause of death between women worldwide [ 1 , 2 ]. Invasive lobular carcinoma (ILC) is the second most common histological subtype, accounting for 10 to 15% of all breast cancers [ 3 ]. ILC is clinically and biologically distinct from IDC, particularly regarding its metastatic dissemination patterns. ILC exhibits characteristic loss of E-cadherin expression, ER positivity, HER2 negativity, and an infiltrative growth pattern that makes early mammographic detection challenging [ 3 ]. Furthermore, the evolving classification of HER2 status including the recently proposed HER2-low and HER2-ultra-low categories has added another layer of complexity to breast cancer subtyping and therapeutic decision-making, though most ILCs remain HER2-negative by conventional criteria [ 4 ]. Accurate nodal staging using imaging modalities such as MRI and ultrasound is also critical in ILC, as its diffuse growth pattern can lead to underestimation of disease extent on conventional imaging [ 5 ]. Additionally, ILC demonstrates unique metastatic tropism compared to IDC. While IDC typically metastasizes to the lungs, liver, and bones, ILC more frequently presents as bilateral multifocality and tends to metastasize and shows a propensity for serous surfaces and unusual sites such as the gastrointestinal tract, peritoneum, retroperitoneum, meninges, orbit, and gynecological organs [ 6 ]. Chikarmane et al. emphasized that radiologists and clinicians should be familiar with these subtype-specific metastatic patterns, as ILC tend to metastasize for unusual sites can lead to delayed or missed diagnoses if not actively considered during staging [ 7 ]. Recent reports have documented ILC metastases to the reproductive system, including the uterine corpus [ 8 , 9 ]. This underscores the vigilance and suspicion for any atypical metastatic presentations. Metastasis to the gastrointestinal tract is rare in breast cancer, occurring in only 1% of clinical cases, though autopsy series suggest rates of 8 to 18% [ 10 ]. This tropism is attributed to the loss of E-cadherin expression, which decreases the cell-to-cell adhesion, that facilitates submucosal infiltration of hollow visceral organs without forming discrete masses [ 11 ]. This growth pattern manifests as thickening of the gastric wall and the presentation with non-specific symptoms like vomiting and abdominal pain which mimics other diseases like inflammatory bowel disease or endometriosis [ 12 ]. The orbit represents another unusual but documented site of breast cancer metastasis, reported in 28% to 58.8% of secondary orbital tumors. ILC is considered the most common primary cancer to metastasize to the orbit. This is likely due to the same E-cadherin related discohesive biology that facilitates diffuse tissue infiltration. Differentiating orbital metastasis from orbital pseudotumor is a diagnostic challenge, as both present with proptosis, pain, diplopia, and ophthalmoplegia [ 6 ]. The management plan differs between both as pseudotumor typically responds to corticosteroids, while orbital metastasis requires systemic oncologic management plan. This case study aims to report a rare presentation of bilateral ILC with gastric and colonic metastases accompanied by a concurrent orbital inflammatory pseudotumor, highlighting the diagnostic challenges and discussing the differential of the orbital lesions whether orbital inflammation in the setting of metastatic malignancy may represent a paraneoplastic or para-inflammatory phenomenon.