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Case Study: Comprehensive pathology, histopathology and molecular typing in customising cancer treatment.
Clinical Features
A 40-year-old female presented to the ED with intermittent abdominal pain of two to three months duration, as well as PR and PV bleeding. Her past medical history included an appendectomy two years prior, and primary hyperparathyroidism. She had no family history of malignancy. On examination, the patient had a tender abdomen with absent bowel sounds.
MBBS (Hons), MPH, FRACP
Assoc/Prof Feeney is the head of cancer services at SJOGH Murdoch. His clinical interests are in breast, gastrointestinal cancer and melanoma. He is principal investigator of clinical trials investigating new treatments spanning breast, melanoma, colon, gastric, esophageal, lung, bladder, pancreas and renal cancer.
The patient’s initial laboratory test findings including full blood count, renal function tests and liver function tests were within normal limits, However, her CA125 was raised at 141KU/L.
Chest x-ray showed a right-sided basal pleural effusion with right basal pulmonary opacification. CT imaging of the abdomen and pelvis revealed a large, predominantly cystic, mass lesion in the central pelvis measuring 13.5cm x 9.3cm x 16.4cm, appearing to originate from the left ovary, with features highly concerning for ovarian carcinoma.
There were significant ascites and infiltration of the omentum with features concerning for metastatic disease. The sigmoid colon featured an abnormal thick-walled segment, approximately 5cm in length. There were at least two ill-circumscribed lesions in the liver (10mm and 7.5mm) which were non-specific but concerning for the presence of liver metastases.
Pathological Findings
The patient underwent an ultrasound-guided aspiration of ascitic fluid, which was found to be negative for malignancy on cytological examination.
She subsequently underwent surgery, which included a total abdominal hysterectomy/bilateral salpingo-oophorectomy, anterior resection, omentectomy and right hemicolectomy. At the time of surgery, the patient was noted to be free of any macroscopic peritoneal disease.
The anterior resection revealed presence of a 35mm circumferential and partly stenosing tumour in the sigmoid colon.
The histopathological findings revealed a low-grade (moderately differentiated) adenocarcinoma of the sigmoid colon, penetrating the visceral peritoneum (pT4a), exhibiting lymphovascular and perineural invasion, intermediate tumour budding, and metastatic involvement of lymph nodes. The resection margins were clear of tumour.
Metastatic disease was evident on the serosal surface of the uterus and left ovary, while both the omentum and right hemicolectomy showed no malignancy. Immunohistochemistry for mismatch repair proteins showed no loss of staining for MLH1, MSH2, MSH6 and PMS2, indicating a normal pattern of staining.
Molecular analysis did not detect any mutations in the KRAS, BRAF, NRAS, PIK3CA, PTEN or AKT1 genes.
A peritoneal fluid sample was sent for cytological evaluation and while no overtly malignant cells were seen in the smears, the cell block contained occasional, better-preserved cells with hyperchromatic nuclei and irregular nuclear contours. These cells showed positive immunohistochemical expression for CK20 and CDX2, in keeping with involvement by metastatic adenocarcinoma of primary gastrointestinal origin.
Post-surgical management
Post-surgical PET/CT imaging for staging purposes showed at least two FDG-avid hepatic metastases involving segment IV, with other low-density lesions seen on prior CT imaging not appearing FDG-avid. The right-sided pleural effusion was noted to have reduced following drainage.
Tiny nodules were seen in the right lung but no definite pulmonary metastatic disease was demonstrated. Subsequent MRI imaging of the liver showed five metastatic deposits in segments 3, 4 and 7, ranging from 2mm to 23mm, and a prominent inferior right internal mammary chain node.
The patient recovered well from her surgeries and underwent a six-month course of a combination of FOLFOX chemotherapy and Cetuximab monoclonal antibody treatment with plans for repeat staging scans at three and six months.
Post treatment PET/CT imaging showed complete metabolic response to therapy with the two previous FDG-avid hepatic metastases no longer avid, and resolution of the right pleural effusion, internal mammary lymph node and tiny pulmonary nodules.
Overall, the patient has had an excellent response with a prognosis likely measured in years of excellent quality of life and disease control.
This demonstrates the importance of knowing the primary histology of a cancer which can then guide subsequent appropriate molecular testing. In this case, the patient’s extended RAS genotype was wild-type and predicted an excellent response to chemotherapy and EGFR-inhibitor monoclonal antibody therapy.
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