Running title: NOT EVERYTHING IS ALWAYS AS IT SEEMS
Authors Ana Munhoz 1,2; [email protected] Pedro Brandão 1,2,3,5; [email protected] Nuno Gonçalves 1, 4; [email protected] Paula Lago 1,4,5; [email protected] Marisa Santos 1,2,3,5; [email protected] Affiliation: 1 - Unidade Local de Saúde de Santo António - ULSSA, Porto, Portugal 2 - Serviço de Cirurgia Digestiva e Extra-Digestiva - ULSSA 3 - Unidade de Cirurgia Colorretal 4 - Serviço de Gastrenterologia 5 - Instituto de Ciências Biomédicas Abel Salazar - Universidade do Porto
Corresponding author: Ana Munhoz, e-mail – [email protected] Summary
Inflammatory bowel disease (IBD) is an idiopathic inflammatory disorder and the incidence has been increasing due to greater awareness of the disease and more sophisticated complementary diagnostic exams.
We report a case of a 66 -year-old patient with a history of left radical mastectomy followed by adjuvant chemoradiotherapy, and hormonal therapy until 2020 for an infiltrating lobular breast tumour 12 years ago. She was evaluated at the gastroenterology department with abdominal pain, bloating, vomiting, refractory constipation, and weight loss, with insidious onset of symptoms with clinical worsening in 2022. All the complementary tests were suggestive of Crohn's disease. In the following months, the patient had two hospitalizations due to partial intestinal occlusion of the small bowel, and was transferred to a surgical centre with experience in IBD. Intraoperatively, a frozen pelvis with thickening of the descending and sigmoid colon with suspicious adenopathy’s and segmental thickening of the small bowel was detected, although not suggestive of IBD. The histopathological result was compatible with invasive lobular carcinoma.
Currently, due to easy access to complementary diagnostic tests, IBD ends up being overdiagnosis, sometimes leading to diagnostic errors. In patients with atypical presentations, it is important to consider other diagnoses without neglecting the patient's personal history.
Background
Inflammatory bowel disease (IBD) is an idiopathic inflammatory disorder of the intestinal tract characterized by a chronic relapsing course. Most people diagnosed with IBD are age 35 or younger, and there is a second peak of diagnosis in the 60s. Typically, Crohn’s lesions attain segmental and asynchronous distribution with varying levels of seriousness, although the sites most frequently involved are the terminal ileum and the proximal colon. (1) Currently, the incidence of IBD has been increasing due to greater awareness of the disease and more sophisticated complementary diagnostic exams. However, in patients with atypical symptoms, other diagnosis must be considered, without neglecting the patient's personal history. This report describes a patient with late colon and small bowel metastases from lobular breast cancer mimicking IBD.
Case presentation
A 66-year-old woman with a history of left radical mastectomy followed by adjuvant chemoradiotherapy, and hormonal therapy with tamoxifen until 2015 and anastrozole until 2020 for an infiltrating lobular breast tumour 12 years ago.
Since 2021, she has presented with abdominal pain, bloating, vomiting, refractory constipation, and weight loss (11 kg in 4 months), with insidious onset of symptoms with clinical worsening in 2022.
Investigation
At that time, she was evaluated at the gastroenterology department and underwent a CT scan that was suggestive of Crohn's disease/ sclerosing mesenteritis, with mesenteric inflammatory infiltration associated with the retraction of some loops of the small bowel. An ileocolonoscopy (Figure 1 A and B) showed a stricture of the sigmoid colon with an infiltrative appearance but with no obvious inflammatory signs, which only allowed the passage of the gastroscope. The terminal ileum was normal and the biopsy was inconclusive.
In June 2023, a CT enterography was performed and also suggestive of Crohn's disease, with small bowel strictures, enteroenteric fistulae, engorgement of vasa recta and mesenteric involvement. In August, she started corticosteroids and therapy with ustekinumab.
In the following months, the patient had two hospitalizations due to partial intestinal occlusion of the small bowel, managed conservatively. The CT scans (Figure 2A and B) showed dilated loops of small bowel, but without complications.
In December, she was transferred with an intestinal occlusion to a surgical centre with experience in IBD. Nutritional optimization was performed with parenteral nutrition.
Treatment
The patient underwent surgery and intraoperatively, a frozen pelvis with thickening of the descending and sigmoid colon with suspicious adenopathy’s and segmental thickening of the small bowel was detected, although not suggestive of IBD. (Figure 3A and B) She underwent a left colectomy with colostomy and 2 segmental enterectomies. (Figure 4 A and B)
Outcome and follow-up
The postoperative course was uneventful. Feeding was started on the second postoperative day and the patient was discharged on day 15 without any complications. The histopathological result was compatible with invasive lobular carcinoma (CK 19 +; ER +: RP +; E-cadherin -; Beta-catenin -), PIK3CA +. At the time the patient is asymptomatic. The case was presented at the oncology department and was decided palliative treatment. She started the first line of treatment with aromatase inhibitors (AI) and cyclin-dependent kinase inhibitors (CKIs).
Discussion
Breast cancer is the most common malignancy in women and the second leading cause of cancer death. (2) Diagnosis at an early stage increases survival rates but despite treatment more than half of the patients experience tumour recurrence or metastasis, some of which present many years after the initial diagnosis. (3) Breast cancer can metastasize to many sites; however, a different pattern of recurrence has been reported for different breast cancer subtypes. Common sites of metastasis are bones, lungs, the central nervous system, and the liver. (4) Gastrointestinal (GI) involvement is rare, occurring only in 3.4% to 4.5% of patients, with few cases reported. (2,3)
GI metastasis can present with nonspecific GI symptoms, such as abdominal pain, diarrhea, weight loss, bowel obstruction, anemia, and bleeding. (3)
The presentation can be similar to GI malignancies or IBD, and it is challenging to differentiate them, with mucosal nodularity, stenosis, decreased distensibility, angulation, and tethering. (5) Often, the radiographic imaging is not particularly helpful, and can be easily mistaken for Crohn’s disease delaying diagnosis and treatment.
Invasive lobular carcinoma (ILC) is typically a hormone receptor positive disease and has a low probability of response to primary chemotherapy. Patients with ILC has usually poorer outcomes than patients with invasive ductal carcinoma and a greater frequency of metastatic disease in unusual sites, such as the GI tract. (5)
In patients with a history of breast cancer, the GI tract should be thoroughly investigated even in presence of nonspecific GI symptoms with endoscopy with biopsy. However, in cases where metastases only involve the submucosa, it might result in false negative results. Complete histopathologic and immunohistochemical evaluations and comparison with the original breast carcinoma pathologic findings are crucial to support the diagnosis and improve patient care.
Establishing the exact diagnosis as early as possible is crucial. The treatment of choice for metastatic breast cancer is usually systemic chemotherapy and/or hormonal therapy, but there is a lack of consensus regarding the standard approach for GI metastases. (3) Primary resection has not been shown to improve survival but may be used as a palliative tool to symptomatic control. (3) In our case, the patient presented in our centre with bowel obstruction, refractory to conservative treatment. She was initially misdiagnosed with IBD and did not respond to the treatment with corticosteroids and ustekinumab. In this setting, the initial plan was surgical treatment and she underwent a left colectomy with colostomy and 2 segmental enterectomies. When the diagnosis of GI metastasis of invasive lobular breast carcinoma was established, the patient started the first line of palliative treatment with aromatase inhibitors (AI) and cyclin-dependent kinase inhibitors (CKIs).
Conclusion
Currently, due to easy access to complementary diagnostic tests, IBD ends up being overdiagnosis, sometimes leading to diagnostic errors.
In patients with atypical presentations, it is important to consider other diagnoses without neglecting the patient's personal history.
In patients with a history of breast cancer, although the GI tract is an uncommon site of breast cancer metastases, recognizing the range of possible presentations is important for an early and accurate diagnosis and treatment.
Funding statement This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.
Declaration of interest There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported
Patient consent Written informed consent has been obtained.
Author contributions and acknowledgements AM wrote the draft which was reviewed by MS, who edited and finalized the version. The remaining authors were involved in patient management.
References 1 – Gatta G, Di Grezia G., Di Mizio V., Landolfi C., Mansi L., De Sio I., Rotondo A., Grassi R. Crohn’s Disease Imaging: A Review. Gastroenterology Research and Practice, Volume 2012 2 – Alves de Lima D. C. Breast cancer metastasis to the colon. Endoscopy 2011; 43: E143–E144 3 – Noor A., Lopetegui-Lia N., Desai A., Mesologites T., Rathmann J. Breast Cancer Metastasis Masquerading as Primary Colon and Gastric Cancer: A Case Report. Am J Case Rep, 2020 4 – Inoue H., Arita T., Kuriu Y., Shimizu H., Kiuchi J., Yamamoto Y., Konishi H., Morimura R., Shiozaki A., Ikoma H., Kubota T., Fujiwara H., Okamoto K., Otsuji E. Colonic Metastasis from Breast Cancer: A Case Report and Review of the Literature. In Vivo. 2022 Jan-Feb;36(1):522-527 5 – Montagna E., Pirola S., Maisonneuve P., Roberto G., Cancello G., Palazzo A., Viale G., Colleoni M. Lobular Metastatic Breast Cancer Patients With Gastrointestinal Involvement: Features and Outcome. Clinical Breast Cancer, Vol. 18, No. 3, e401-5
Legends to tables/figures/videos
Figure 1 A and B – An ileocolonoscopy showed a stricture of the sigmoid colon Figure 2 A and B – CT scan showed dilated loops of small bowel suggestive of small bowel obstruction Figure 3 A and B – Intraoperative findings: thickening of the descending and sigmoid colon with suspicious adenopathy’s and segmental thickening of the small bowel Figure 4 A and B– Surgical piece: left colectomy and 2 segmental enterectomies
