Primary pulmonary squamous cell carcinoma with colonic metastasis

Abstract

Lung cancer continues to have the highest mortality rate among cancers worldwide. At the time of diagnosis, 50% of lung cancer patients present with locally advanced or distant metastasis, commonly to the brain, bone, liver, and adrenal glands. Lung metastasis to the small bowel and colon is rare. Few cases of symptomatic colon metastasis have been reported, and it is rarely recognised clinically before severe complications occur. Our patient was a 64-year-old previously healthy male, an ex-smoker with a 20 pack-year history of smoking, who quit 4 years prior to his diagnosis of primary bronchogenic squamous cell carcinoma with local lymphatic invasion in January 2021. After two months, the patient started his scheduled treatment with multiple lines of immunochemotherapy. Follow-up in November 2022 showed disease progression, for which mediastinoscopy was performed for diagnostic evaluation, followed by palliative radiotherapy for local disease control. The patient was doing well, but after seven months, he presented to the hospital seeking medical advice due to abdominal pain and constipation for a duration of 2 weeks. A workup including a CT scan, colonoscopy, and biopsy was performed. The patient was diagnosed with poorly differentiated squamous cell carcinoma metastasis to the colon, and a right hemicolectomy was performed for palliation. In general, colonic metastasis of lung cancer is associated with a poor prognosis, with a survival range of 5 weeks to 1 year.

Introduction

Lung cancer is one of the most common cancers worldwide and the leading cause of cancer-related deaths. About half of those diagnosed have metastatic lesions to the brain, liver, bones, or adrenal glands [1]. However, it is very rare for lung cancer to metastasize to the gastrointestinal (GI) tract, especially the colon, with 0.5% of cases showing colon metastasis [2]. While surgery can help relieve symptoms such as obstruction and bleeding, improve quality of life, and reduce hospital stays, it has a limited effect on long-term survival.

Lung cancer patients with colonic metastasis typically have a poor prognosis, with reported survival ranging from only a few weeks to approximately 12 months [3]. These patients may remain asymptomatic, and colonic lesions are often identified incidentally during staging evaluations or routine surveillance imaging. This highlights the importance of comprehensive staging and regular follow-up, particularly given that colonic metastasis from lung cancer is rare and may present subtly. Herein, we report a case of symptomatic colonic metastasis originating from squamous cell carcinoma of the lung.

Case report

A 64-year-old male, a known case of low-grade bladder transitional cell carcinoma and an ex-smoker who quit 4 years ago with a 20 pack-year history, presented in January 2021 with a one-year history of productive cough that eventually progressed to haemoptysis. A chest CT performed as part of the workup showed complete left lower lobe collapse with features suggestive of an endobronchial lesion, along with a small peripheral right lower lobe nodule. Bronchoscopy confirmed the presence of a left endobronchial lung lesion. A biopsy of the lesion revealed invasive, moderately differentiated squamous cell carcinoma with negative molecular testing for ROS1, ALK, and EGFR mutations, and a PD-L1 expression level of 65%.

Based on the radiological findings at the time of presentation, including bilateral pulmonary lesions suspicious for metastatic involvement, the patient was staged as stage IV non-small cell lung cancer. Given the advanced stage of disease at diagnosis, curative surgical resection was not considered appropriate, and systemic therapy was selected as the first-line treatment in accordance with current management strategies for metastatic lung cancer.

The patient received multiple lines of immunochemotherapy starting in March 2021 with carboplatin, gemcitabine, and pembrolizumab, completing 13 cycles by October 2021. Due to disease progression, treatment was modified to paclitaxel with pembrolizumab. In March 2022, carboplatin was added to paclitaxel and pembrolizumab because of progressive mediastinal lymphadenopathy.

A follow-up oncology CT scan performed in May 2022 demonstrated a partial response (PR). The last cycles of paclitaxel and carboplatin were administered in July 2022; Paclitaxel was subsequently discontinued due to significant peripheral neuropathy with foot drop, therefore treatment was changed to navelbine combined with carboplatin and pembrolizumab starting in August 2022. However, after two cycles, chemotherapy was held because of worsening neuropathy and functional decline, and pembrolizumab monotherapy was continued.

Another follow-up CT scan in November 2022 showed an interval increase in the left lower lobe lung mass and right hilar lymph nodes, consistent with disease progression (PD). Given the progression and the need to further assess mediastinal involvement, mediastinoscopy was performed, and pathologically confirmed metastatic involvement of the mediastinal lymph nodes.

Throughout the course of treatment, the patient underwent periodic radiological reassessment to evaluate treatment response and disease progression. Despite systemic therapy, imaging demonstrated persistent mediastinal nodal disease with ongoing evidence of metastatic involvement, in the context of already advanced (stage IV) disease, and therefore, surgery was not considered a treatment option at any stage of management. Accordingly, the patient continued on palliative-intent management. He received palliative radiotherapy to the mediastinal lymph nodes and chest mass in January 2023 for local disease control. Post-radiotherapy, systemic treatment was resumed with navelbine and pembrolizumab, after which the patient remained on palliative systemic therapy with supportive care.

In July 2023, nearly 2 years after his initial lung cancer diagnosis, the patient presented to the hospital with a 2-week history of constipation and gradually increasing abdominal pain. On admission, physical examination revealed abdominal distention with hyperactive bowel sounds and diffuse tenderness, otherwise unremarkable systemic examination. Laboratory workup showed microcytic anemia.

Enhanced CT scan of the abdomen revealed marked wall thickening and multiple colonic masses in the transverse, ascending and descending colon (Figs. 1 and 2). These findings were highly suspicious for malignancy. Subsequently, colonoscopy with biopsy was performed, which showed lesions in the cecum, ascending colon and hepatic flexure, and biopsy confirmed poorly differentiated squamous cell carcinoma with a morphological pattern similar to that of the previously diagnosed lung cancer.

Fig. 1.

Enhanced CT scan of the abdomen. Axial view revealed marker wall thickening and multiple colonic masses in segmental distribution in the ascending colon and hepatic flexure.

Fig. 2.

Enhanced CT scan of the abdomen. The coronal view shows luminal narrowing in the same segments

Given the extent of disease and symptomatic bowel involvement, a palliative surgical intervention was considered with the aim of relieving symptoms and improving quality of life. Accordingly, a comprehensive preoperative assessment was undertaken. This revealed an Eastern Cooperative Oncology Group (ECOG) performance status of 2–3, indicating significantly limited ambulation and symptomatic burden. The American Society of Anaesthesiologists (ASA) classification was assessed as class III, reflecting the presence of severe systemic disease alongside the existing comorbidities, including diabetes mellitus.

The informed consent process included a detailed discussion of the anticipated benefits, palliative intent, and potential risks of the proposed surgical intervention. After ensuring a clear understanding of the surgical goals and expected outcomes, the patient expressed an informed preference to proceed with surgery. Consequently, the decision was made to undertake palliative surgical intervention.

In September 2023, an extended right hemicolectomy with resection of Meckel’s diverticulum was done.

Intraoperatively, seven lesions were identified in the appendix, ascending colon, hepatic flexure, transverse colon (including the distal third), and splenic flexure, in addition to bulky lesions found in Meckel’s diverticulum; all causing severe luminal narrowing (Figs. 3 and 4). The histopathological examination revealed transmural poorly differentiated squamous cell carcinoma. Immunohistochemical staining showed positivity for PanCK, P63, and CK5/6 and negative results for LCA, CD3, CD20, CD30, and SOX10.

Fig. 3.

Multiple colonic metastasis shown in transverse colon causing severe luminal narrowing

Fig. 4.

Multiple colonic metastasis shown in transverse colon causing severe luminal narrowing

Postoperatively, the patient was started on a liquid diet on postoperative day 2 following the return of bowel function, as evidenced by active bowel sounds and passage of flatus, which was well tolerated. A soft diet was introduced on postoperative day 3 and was also tolerated without complications. An overall improvement in gastrointestinal symptoms was observed, accompanied by regular bowel movements and a noticeable improvement in the patient’s quality of life.

Following surgical management of colonic metastasis, the patient was discharged in stable general condition in February 2024. The patient subsequently died outside the hospital in March 2024, with the cause of death documented as cardiopulmonary arrest. Overall survival following surgery was approximately three weeks, and the patient was deceased at the time of the last follow-up.

Thus, the case was labelled as colonic metastasis of squamous cell carcinoma of the lung.

Discussion

Colon metastases from lung squamous cell carcinoma have been seldom reported in the literature and are rarely recognised clinically until significant complications have developed [4]. This case reports a metastasis of lung squamous cell carcinoma to the ascending colon, hepatic flexure and cecum. The diagnosis was confirmed following the evaluation of the patient’s clinical presentation, which included abdominal pain and constipation. Abdominal pain is the most common complaint for patients with lower GI involvement, in addition to lower gastrointestinal bleeding and perforation, resembling those of primary colon cancer [5]. Symptomatic colonic metastasis warrants emergent workup. CT scan and colonoscopy are crucial for diagnosis and directing subsequent management. In this case, the diagnosis was confirmed by colonic biopsy showing poorly differentiated squamous cell carcinoma morphologically identical to the known primary lung tumour. He was managed with multiple lines of immunochemotherapy (Carboplatin, Gemcitabine, Paclitaxel, Navelbine, and Pembrolizumab), palliative radiotherapy to the mediastinal lymph nodes, and later an extended right hemicolectomy with resection of Meckel’s diverticulum for the subsequent colonic obstruction caused by metastatic lesions.

The case represents an unusual metastatic pattern of primary lung squamous cell carcinoma manifesting by seven metastatic lesions involving the right colon after a two-year interval following the initial diagnosis of the primary lung cancer.in addition to the favourable clinical response to palliative colonic resection, this case further distinguishes itself from prior cases in the literature.

The pathophysiology of lung metastasis is not fully understood till now. This multifactorial process is controlled by several factors, including lung cancer stem cells, the microenvironment of the tumour, and the expression of different molecules such as vascular growth factors VEGF-A, VEGF-C, VEGF-D, which play a key role in angiogenesis and lymphangiogenesis [6]. Many studies highlighted the role of epithelial-mesenchymal transition (EMT) in tumour progression and metastasis. EMT demonstrated the phenotypic conversion of the epithelial cell into an invasive, migratory mesenchymal cell, marked by the downregulation of epithelial cell markers such as E-cadherin and the upregulation of mesenchymal cell surface markers, by which squamous cell carcinoma acquires the ability to invade and disseminate to distal sites like the colon in our case [7].

Metastatic patterns, including the route of transmission and the site of metastasis, vary depending on the histological cell type of the primary tumour, sex and age of patients at time of diagnosis. It is found that squamous cell carcinoma was more common in elderly male patients, whereas adenocarcinoma tends to occur more in young female patients.

Studies showed that the most common metastatic sites for small cell lung cancer were the liver and nervous system, whereas bone, the respiratory system and glandular tissues were common sites for adenocarcinoma. However, squamous cell carcinoma was more prone to local invasion and had the lowest incidence of distant metastasis. Several factors contribute to the pathophysiology of variation of anatomical metastasis sites of each histological cell type; different cell types have different molecular genetic expressions involved in metastasis, including growth factor receptors, adhesion molecules, and chemokines. Moreover, some cell types show a better ability to thrive in specific organs than others, which is called the seed and soil hypothesis [8].

Different histological cell types cause GI metastasis in different sites, although squamous cell carcinoma was the most common histological cell type that causes colon metastasis in many reviews [5, 8].

Colonic metastasis tends to manifest years after initial diagnosis and treatment of the primary lung tumour; the probability of colonic metastasis should be considered in any patient with a history of primary lung tumour who presents with new gastrointestinal manifestations [9].

Treatment of lung squamous cell carcinoma with GI metastasis should be individualised according to the patient’s clinical condition. Colonic lesions presenting with obstruction or massive haemorrhage require prompt and emergent surgical treatment [10]. Chemotherapy remains the mainstay of management; however, it has been associated with an increased risk of GI bleeding and perforation [11]. Due to the poor prognosis of colonic metastasis with a survival range of 5 weeks to 1 year [3], early intervention with aggressive surgical or local ablative therapy could be considered in stable patients. The results of palliative management vary according to the histological type. Surgery of colonic metastasis from squamous cell lung cancer provides excellent palliation without adverse effect on survival [12].

Conclusion

This report describes a case of symptomatic colonic metastasis from primary lung cancer. Symptoms ranged from abdominal pain to severe gastrointestinal bleeding. Lung cancer patients, especially with advanced disease, may develop gastric metastases synchronously or years after diagnosis, warranting suspicion when new abdominal symptoms arise. Timely diagnosis and appropriate management of colonic metastases from squamous cell lung cancer can improve survival and prevent complications. In our case, palliative surgical colonic resection provides resolution of obstruction symptoms, improvement of life quality without affecting overall life expectancy, as the patient was discharged after operation in a good general condition. Limitations of palliative therapy may be seen in non-surgical candidates as it carries a relatively high perioperative risk. This case highlights a rare clinical scenario with valuable implications for practice.

Author contributions

[Author 1] performed the surgical procedure; [Author 1, 2, 3, 4, 5] contributed to data collection and literature review; all authors read and approved the final manuscript.

Funding

This research received no external funding.

Data availability

The data sets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.

Declarations

Ethics approval

This case report was approved by the Ethical Committee in accordance with Istishari Arab Hospital Guidelines and Regulations.

Consent to participate

Consent to participate was obtained from the son of the deceased patient, who is the legal next of kin, in accordance with ethical guidelines and institutional regulations.

Consent for publication

Consent to publish was obtained from the son of the deceased patient, who is the legal next of kin. All necessary permissions for the publication of this case report were granted by him, thereby respecting patient autonomy and confidentiality.

Competing interests

The authors declare no competing interests.