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Abstract
Sarcomatoid carcinoma is a rare type of tumour consisting of neoplastic cells expressing both epithelial and mesenchymal cell markers. The small intestine is a rare site for sarcomatoid carcinoma and to date, a few cases have been reported. In this manuscript, a case of jejunal sarcomatoid carcinoma in a man in his 50s is reported. A review of the literature on sarcomatoid carcinomas of small bowel is presented.
- Small intestine
- Small intestine cancer
- Pathology
- Cancer intervention
- Immunohistochemistry
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Background
Sarcomatoid carcinoma is a rare type of cancer with cells having both mesenchymal (sarcoma) and epithelial (carcinoma) phenotypes.1 They may arise in different organs such as the lungs and bladder, but the intestinal presentation is rare. The molecular basis of sarcomatoid carcinoma of the small intestine is mainly unknown. The therapeutic regimen is mainly surgery and chemotherapy and may not increase the survival of the patients.1 2 In this manuscript, we present a rare case of large jejunal sarcomatoid carcinoma presented with abdominal pain and partial bowel obstruction with nausea and vomiting.
Case presentation
A man in his 50s with a medical history of quadriplegia due to a motor vehicle accident and chronic constipation presented with diarrhoea, lower abdominal pain, nausea and vomiting. A CT scan revealed sigmoid colitis and an 8 cm (greatest dimension) left lower quadrant small bowel mass. Laparotomy showed a mid-jejunum mass compressing the bowel wall that was completely resected.
Gross examination of the specimen shows a soft large and creamy tumour within the bowel wall (figure 1A–C). Microscopically, the specimen reveals an invasive neoplasm composed of solid sheets of spindle cells (figure 1D). The spindle cells have a moderate amount of eosinophilic cytoplasm, hyperchromatic, ovoid to elongated nuclei, some with prominent nucleoli. Mitotic activity is brisk and with atypical mitotic figures. Focal necrosis and haemorrhage are present. Immunostaining shows the tumour cells are positive for cytokeratin AE1/AE3, vimentin, EMA (focal) and CAM5.2 (focal) (figure 2), and negative for CD117, DOG1, CD34, S100, SMA, desmin, CK7 and CK20 (stains not shown). Ki-67 proliferative index was up to 50–60%. The overall findings supported a malignant spindle cell neoplasm, consistent with sarcomatoid carcinoma of the small intestine.
Gross and microscopic features of the intestinal sarcomatoid carcinoma. CT scan of the abdomen shows the tumour in the left lower quadrant (A). Gross image (B) and a section of the tumour (C) show a tan creamy texture. H&E staining of the tumour cells is shown (D).
Immunohistochemical staining of the tumour shows positivity for pan-cytokeratin AE1/AE3, Cam5.2, EMA and vimentin. EMA, epithelial membrane antigen.
Investigations
No specific blood or serum markers have been identified for this malignancy. In certain cases, imaging studies, cytology or biopsy may be conducted prior to surgery. In our patient’s case, CT imaging revealed a substantial 8 cm mass in the small bowel compressing the intestine, leading to the decision to proceed with surgical treatment. Pathologic evaluation of the specimen confirmed the diagnosis of sarcomatoid carcinoma.
Differential diagnosis
In the differential diagnosis of sarcomatoid carcinoma, carcinosarcoma should be considered. However, the malignant cells of sarcomatoid carcinomas co-express both mesenchymal and epithelial markers while carcinosarcomas are composed of two different cell types that either express mesenchymal or epithelial markers. The malignant cells of our patient co-expressed cytokeratin (epithelial marker) and vimentin (mesenchymal marker), thus this is truly a sarcomatoid carcinoma.
Treatment
Early-stage disease can be managed with staging and surgical resection, as in this case. Other treatment options and targeted therapy attempts for later-stage disease of sarcomatoid carcinoma are highlighted in table 1.
Summary of demographics, surgical and pathologic features of sarcomatoid carcinoma of the small intestine published in English in PubMed since 2000
Outcome and follow-up
4 days following surgery, the patient became hypotensive and short of breath. He was admitted to the intensive care unit for closer management. However, his condition worsened, requiring increased respiratory support. Despite efforts, he passed away after 1 day.
Discussion
Clonal proliferations, both benign and malignant, are usually of one lineage of differentiation, and these are typically based on embryological lines. In general, tumours are of epithelial or mesenchymal differentiation, and pathologists conventionally use these broad lineage separations to diagnose and guide clinicians in the management of tumours. However, biphasic tumours are known to happen and have been extensively reviewed in the medical literature.3 4 Of the mixed lineage tumours that show both epithelial and mesenchymal features, there are broadly two different entities: carcinosarcomas and sarcomatoid carcinomas. Carcinosarcomas are tumours with two distinct epithelial and mesenchymal cell populations each with different immunophenotypic characteristics. Sarcomatoid carcinomas represent an epithelial neoplasm that may have derived from a single clonal cell that undergoes an epithelial–mesenchymal transition. Sarcomatoid carcinomas co-express both epithelial (eg, cytokeratin) and mesenchymal (eg, vimentin) markers.5 6 However, the nomenclature for sarcomatoid carcinoma is still ambiguous and sometimes it is used interchangeably with carcinosarcomas.7 A summary of the demographic, surgical and pathological attributes of sarcomatoid carcinoma in the small intestine, as presented in English-language publications accessible through PubMed since the year 2000 is mentioned in table 1.
Some of the suggested mechanisms for these biphasic tumours are depicted in figure 3.8 These biphasic tumours have been commonly reported in the respiratory system and gynaecological organs but they have been rarely reported in the gastrointestinal system and especially in the small intestine. In addition, in the arena of personalised medicine where cancer gene sequencing provides valuable therapeutic targets and prognostic clues, it is imperative to conduct genetic and molecular studies on these rare and biphasic types of neoplasms. The only in-depth molecular assessment of intestinal sarcomatoid carcinoma is from a male patient with multiple primary jejunal lesions. Whole exome sequencing revealed mutations in several critical driver genes, such as single nucleotide variations (SNV) in KRAS (allele frequency of 66.3% at position c.37G>T), TP53 (allele frequency of 47.7% at position c.871A>T) and EGFR (allele frequency of 4.2% at position c.1351C>T), as well as an insertion-deletion (Indel) mutation in CDKN2A (allele frequency of 11.1% involving a deletion from position c.104 to c.138).9 The tumour mutation burden (TMB) was 7.15 mutations/Mb, which categorises this tumour as a low TMB neoplasm (TMB<10 as the cut-off) with a possibly less favourable response to immunotherapeutic.10
Proposed mechanisms of carcinosarcomas and sarcomatoid carcinoma tumour development. The collision theory (A) suggests that cancer arises from two separate types of stem cells. In the combination theory (B), both carcinoma and sarcoma components are derived from a common stem cell. The conversion theory (C) suggests that the sarcomatoid component is derived from the carcinoma cells via the process of epithelial to mesenchymal transition. All three theories apply to carcinosarcomas but only the conversion theory fits the definition of sarcomatoid carcinoma. The figure was crafted by SSH using or modified from freely accessible templates provided by Servier Medical Art (https://smart.servier.com/).
Studies have shown that similar genes are mutated in small intestinal adenocarcinomas, including KRAS, TP53 and CDKN2A, along with other frequently mutated genes such as SMAD4, APC and PIK3CA.11 The TMB in small intestinal adenocarcinomas has been reported with a median range from 4.5 to 10.2.11 12 For small intestinal sarcomas, research predominantly focuses on gastrointestinal stromal tumours (GISTs), where mutations have been identified in KIT, PDGFRA, BRAF, RAS and NF1. GIST tumours in this region typically exhibit a low TMB, with a median of 5.1.12
Further studies on the genetics of intestinal sarcomatoid carcinomas are necessary to provide a better understanding of disease mechanisms and possible therapies. Important lessons could be learnt from the assessment of carcinosarcomas and sarcomatoid carcinomas of other organs.
Learning points
Sarcomatoid carcinoma is a rare type of tumour consisting of neoplastic cells expressing both epithelial (cytokeratin) and mesenchymal (vimentin) cell markers.
Epithelial-to-mesenchymal transition is a biological characteristic of epithelial cells, which may be key to understanding the biological behaviour of sarcomatoid carcinoma.
The involvement of the small intestine in sarcomatoid carcinoma is exceedingly rare, with patients generally experiencing an unfavourable prognosis.
Ethics statements
Patient consent for publication
Footnotes
Contributors The following authors were responsible for drafting the text, sourcing and editing of clinical images, investigation results, algorithms and critical revision for important intellectual content: RD, XT, SH. SH prepared the original diagrams. The following authors gave final approval of the manuscript: RD, XT, SH.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Case reports provide a valuable learning resource for the scientific community and can indicate areas of interest for future research. They should not be used in isolation to guide treatment choices or public health policy.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.