Carcinosarcoma of the colon: report of a case with morphological, ultrastructural and molecular analysis

Abstract

Background: Carcinosarcoma of the colon is a rare histopathological entity with uncertain histogenesis, that shows both epithelial and mesenchymal malignant differentiation. Carcinosarcoma rarely affects the gastrointestinal tract and only few cases are reported in the colon. Herein we describe a carcinosarcoma of the ascending colon, with morphological, ultrastructural and molecular analysis.

Case presentation: An 81-year-old man was hospitalised for asthenia, weight loss and iron-deficiency anaemia. The patient underwent colonoscopy and adenocarcinoma was diagnosed by endoscopic biopsy. A right hemicolectomy was performed and, during surgical operation, liver metastases were detected. Histological examination of the surgical specimen revealed areas of both carcinomatous and sarcomatous differentiation, completely separated by fibrous septae. The sarcomatous component exhibited areas of smooth muscle and osteoblastic differentiation, with focal osteoid material deposition. Molecular analysis conducted separately on the epithelial and mesenchymal components revealed the same p53 gene mutation (R282W in exon 8) and identical polymorphisms in p53 exon 4, in EGFR exons 20 and 21, and in c-kit exon 17. Microsatellite markers analysis revealed a common loss of heterozygosis on 18q. Overall, the data are consistent with a common origin of the two tumor components. The patient was treated with 8 cycles of oral capecitabine (1250 mg/m2 twice a day for 14 days repeated every 28 days) and two years after surgery is alive with liver metastases.

Conclusion: Carcinosarcoma of the colon is a rare tumour with both epithelial and sarcomatous components. Molecular analysis of the current case suggests the histogenesis from a common cell progenitor.

Figure 1

Tumour appearance on H&E. Carcinomatous component (left) and sarcomatous component (right) are completely separated by fibrous septae.

Figure 2

Immunohistochemical analysis on the sarcomatous component (smooth muscle actin). Fascicular spindle cells of the sarcomatous component are immunoreactive for smooth muscle actin in their cytoplasm. Internal control is positive, as shown by blood vessels staining.

Figure 3

Immunohistochemical analysis on the sarcomatous component (osteonectin). Bizarre large cells of the sarcomatous component are immunoreactive for osteonectin in their cytoplasm.

Figure 4

Ultrastructural examination: (a) Carcinomatous component: glandular epithelial structure with surface microvilla (arrow); in the inset: enlargement of the basement membrane (arrow) and hemidesmosomes (red arrows). (b) Sarcomatous component: spindle cells with actin cytoplasmic thin filaments and focal densities (enlargement in the inset). Scale bar: 2µm.

Figure 5

DHPLC diagram and p53 sequencing analysis. (a) DHPLC diagram. The carcinomatous component is represented in black while the sarcomatous component in red and the wild-type control sample in blue. The same genetic alteration in both tumour components is illustrated by the presence of an extra peak in the neoplastic specimens in comparison with the normal control. (b) Sequencing analysis showing p53 exon 8 mutation R282W (arrow).

Figure 6

STR analysis evidenced a loss of heterozygosity on 18q21. Analysis of a representative marker of 18q21 (microsatellite D18S858) is shown. The carcinomatous (A) and sarcomatous (B) components shared an almost complete loss of the second allele (arrow) in comparison to the normal (C) counterpart.