Diagnostic Complexity in Colonic Sarcomatoid Carcinoma: A Case Report and Literature Review

Introduction

Initially described by Virchow in 1864, sarcomatoid carcinoma (SC) is a very rare and highly aggressive malignant neoplasm with a very poor prognosis [1,2]. It can arise from various anatomic locations, including but not limited to, the upper aerodigestive tract, female reproductive organs, head and neck, and soft tissues [2,3]. Its extraordinary invasiveness can be explained by its unique biphasic histological profile, composed of both epithelial and mesenchymal cells. The epithelial phenotype provides proliferative capacity, while the mesenchymal component enhances plasticity and invasion, with both contributing to its poor prognosis [4]. Consequently, various terms such as pseudo-sarcomatous carcinoma, spindle cell carcinoma, carcinosarcoma, and carcinoma with mesenchymal stroma have also been used [2,3,5].

We report a case of colonic sarcomatoid carcinoma we encountered in our clinical practice to help to build a body of evidence concerning this rare neoplasm.

Case Report

A 56-year-old man who was a heavy smoker presented to our clinic after sudden onset of constipation a few days ago. His past medical history was relevant for hypertension, uncontrolled diabetes mellitus type 2, and benign prostate hyperplasia. On presentation, vital signs were within normal range, he was not in acute distress, and he appeared well-nourished but pale and fatigued. He denied significant weight loss, anorexia, or night sweats in recent months. The physical examination was unremarkable, except for a distended abdomen that was tender on deep palpation. Thereafter, a colonoscopy was performed and showed a necrotic, ulcerated mass in the sigmoid colon (Figure 1).

He said that approximately 5 months ago an abdominal MRI done without a specific clinical indication did not show any abnormal mass growth. Thereafter, to alleviate his symptoms and restore his bowel function, he underwent radical tumorectomy with stapled latero-lateral anastomosis, revealing a large tumor with a macroscopically distorted shape (Figure 2). Exploratory laparotomy was significant for peritoneal carcinomatosis and multiple liver metastatic lesions. This was further documented by an abdominal CT scan that showed dozens of hypodensities in the liver (Figure 3). On histologic evaluation, the tumor displayed a high degree of atypia, with spindle-shaped, epithelioid, and pleomorphic cells (Figures 4, 5). The final diagnosis was stage pT4 pN2b pM1c sarcomatoid carcinoma of the sigmoid colon penetrating the visceral peritoneum and adhering to the abdominal wall, with negative margins, and 7/7 lymph nodes positive for malignancy.

Immunohistochemical stains revealed strong immunoreactivity for vimentin in the pleomorphic and spindle-shaped component, while the cytokeratin was positive in the epithelioid cells (Figure 6). Anti-myogenin, anti-H-caldesmon, and anti-CDX2 were negative, ruling out the possibility of rhabdomyosarcoma (Figure 7). Based on morphology and immunohistochemistry, a diagnosis of a spindle cell and pleomorphic sarcomatoid carcinomatosis was made. The patient did not have a chance to receive adjuvant chemotherapy, and after a few days, he came back again with worsening abdominal distention associated with fever. He was transferred to the intensive care unit, where he died after about a week.

Discussion

In the limited cases reported in the literature, most of the sarcomatoid carcinomatous cases were in the female genital tract [2], followed by the respiratory system, where they represent less than 1% of all small cell lung carcinoma cases [3]. Such neoplasms are rarely found anywhere in the gastrointestinal tract, arising all the way from the oral cavity, with nearly one-third of them involving the gingiva [6], to the anus. Furthermore, SC originating primarily in the colon specifically were much less frequent [7,8], representing around 5% of the digestive tract cases [2]. The median age at diagnosis of sarcomatoid carcinoma was in the mid-to-late 60s [2,4,9,10]. The initial clinical presentation can be highly variable, including a palpable abdominal mass, melena or hematochezia, and intestinal obstruction, and can even be misdiagnosed as acute appendicitis or manifest with symptoms and signs related to distant metastases [8,11–16]. Our patient was aware of an obstructive intestinal condition that appeared abruptly, and at the time of diagnosis his cancer was already in an advanced stage.

Since it was first reported by Weider and Zekan, it has long been considered a highly aggressive and fatal disease associated with very poor prognosis and a high recurrence rate [2,17,18]. The survival time is influenced by the patient’s age, sex, and race, with a preponderance for white females, along with the tumor’s grade and stage, and most importantly, the primary tumor site. For instance, Patients with sarcomatoid renal cell carcinomas have a median survival time of 6 months [19]. The worst prognosis is for tumors arising in the endocrine and digestive tract, with an overall survival time of about 5 months [2]. These low overall survival times are associated with the tumor’s tendency for metastasis and chemoresistance, and diagnosis is usually made when the cancer is already at an advanced stage.

Histologically, the epithelial element of these tumors is a high-grade adenocarcinoma, and the sarcomatous tissue cells are spindle-shaped [14,20]. In fact, since this tumor consists of epithelial and mesenchymal cells, it can theoretically disseminate through hematogenous and/or lymphatic routes, with possible peritoneal and serosal spread. This can explain the metastasis in our patient’s liver parenchyma and adjacent serosal structures and lymph nodes. This biphasic property is an important feature, since superficial or inadequate biopsies can lack the tumoral tissue component and thus impede the correct diagnosis and subsequent treatment. When identified, spindled-shaped sarcomatoid cells can suggest a wide range of differential diagnoses, including SC, poorly-differentiated carcinoma, pleiomorphic rhabdomyosarcoma, leiomyosarcoma, and malignant melanoma with spindle cell variants, which highlights the importance of immunohistochemical studies, in which they should stain positive for cytokeratin 20 and vimentin [10], along with other markers in certain diseases, including desmin and SMA, which are indicative of a muscular component. Although there are no treatment guidelines, radical tumorectomy with chemotherapy and close follow-up have been proposed as a practical approach for treatment [14].

Although the histogenesis of sarcomatoid carcinomas remains unclear, hypotheses such as the “combination”, the “collision”, and “epithelial-to-mesenchymal transition” (EMT) have been proposed in an attempt to understand their biological behavior [21]. Although both a carcinomatous and sarcomatous component are present and may suggest a distinct origin, and as counterintuitive as it may seem, molecular analysis showed the presence of the same genetic mutations in both types of cells [22,23]. The combination theory proposes a monoclonal origin for these admixed components, which is supported by genetic studies showing molecular evidence [24,25]. A pluripotent cell, capable of both sarcomatous and epithelial differentiation could have acquired a malignant potential. On the other hand, when whetted specificities without any transition features have been identified between the 2 cell populations, the collision hypothesis advocated for their emergence from distinct malignant clones[7,26]. Therefore, the term “collision tumor” is sometimes used to designate this neoplasm. The conversion theory, also known as epithelial-to-mesenchymal transition (EMT), suggests that some cells within the tumor transform into mesenchymal cells, adopting a spindle-shaped morphology while progressively losing their epithelial characteristics [27]. This spindle shape is a result of the gradual loss of the E-cadherin and keratin network [28,29].

Conclusions

This case highlights the acute invasiveness of colonic sarcomatoid carcinomas. Due to the presence of 2 distinct admixed histological types, it progresses rapidly to large and life-threatening masses with a poor prognosis. Further research is needed to develop treatment strategies to achieve a better prognosis and improve patient outcomes.