COLORECTAL CANCER (The role of the histopathologist)
Mention the word pathologist to a member of the general public and, depending upon their age/generation, they picture Quincy, Grayling Russell (Morse), McCallum or Sam Ryan (Silent Witness). The public and media’s obsession with unnatural death does little to quash this misconception that all pathologists are forensic pathologists. In fact forensic pathologists only account for around 3% of histopathologists and 2% of pathologists as a whole. Many histopathologists (myself included) do perform the occasional non-forensic autopsy, but the average histopathologist spends most of his day examining pieces of tissue removed from the living. These tissue samples range from small biopsies and needle cores to whole organs.
Professor Marco Novelli – Professor of Gastrointestinal Pathology, UCL and Consultant Histopathologist, Independent Histopathology Services.
Why do we get sent these pieces of tissue?
As histopathologists our main clinical roles involve diagnosing disease, assessing disease activity, screening for early changes of cancer, assessing surgical resection specimens and accessing the effects of therapy. The clinical management of colorectal cancer has changed dramatically over the last 10 years. Patient survival has improved and, although surgery remains the primary treatment modality, there are now a variety of additional treatment options for patients with colorectal carcinoma (including chemotherapy, radiotherapy and radiofrequency ablation). These days patients are managed by a multidisciplinary team including surgeons, oncologists (clinical and medical), radiologists, pathologists, palliative care physicians, nurses and administrators each of whom have an important role in the patient care pathway.
The histopathologist’s main roles in colorectal cancer management are in confirmation of the initial diagnosis of cancer and in the grading and staging of resected tumours. Patients clinically suspected of having a colorectal tumour are investigated typically with imaging and endoscopy. If a tumour is visualised at sigmoidoscopy/colonoscopy the endoscopist usually takes small biopsies from the tumour. These are put into specimen pots containing a formalin-based fixative and sent to the histopathology laboratory for processing, sectioning and staining. From receipt in the pathology laboratory it typically takes 18–24 hours to turn tissue biopsies into histological sections, although more rapid processing can sometimes be performed in urgent cases. The sections are then examined under a microscope by a histopathologist and a tissue diagnosis made.
The vast majority of colorectal cancers are adenocarcinomas. These account for over 95% of colorectal malignancies, but there are a number of other types of malignant tumour that can occur in the large intestine including lymphomas, sarcomas and melanomas. Benign inflammatory diseases such as diverticulitis may also present as a ‘tumour’ mass. Clinically and radiologically many of these conditions can mimic adenocarcinomas. As their respective treatments differ markedly, surgeons usually require a tissue diagnosis before they will consider surgical intervention. In most circumstances oncologists also require a firm tissue diagnosis before they will consider neoadjuvent, curative or palliative therapies.
Once a firm diagnosis of colorectal cancer has been made the tumour is staged primarily using radiological techniques (typically one of, or a combination of, CT, MRI, PET and ultrasound scanning). This staging attempts to determine how large the primary tumour is, whether it has spread locally, surgical resectability, and whether there is any evidence of metastatic spread to the lymph nodes, liver or other parts of the body.
If metastatic spread is suspected further biopsies of liver lesions, lymph nodes or other organs may be performed to confirm or refute the presence of metastases. Surgical resection remains the treatment of choice for most patients who are medically fit and have a respectable tumour with no evidence of metastases.
Surgery offers the best chance of a cure and can be augmented with postoperative chemotherapy and radiotherapy. The requirement for further therapies following surgical resection is dependent upon a number of factors, but foremost amongst these are whether the primary tumour has been completely removed and the stage of the tumour. It is at this point that the histopathologist becomes involved again. The assessment of surgically resected colorectal tumours is one of the most time consuming jobs of a gastrointestinal histopathologist. Upon receipt in the pathology laboratory the resected specimen is briefly inspected, incised to allow drainage of intestinal contents, and immersed in a large volume of a formalin-based fixative. The specimen is then allowed to fix for 48–72 hours. Upon complete fixation the specimen is re-examined by the pathologist, the gross appearances described and dimensions of the specimen recorded. The size and extent of the tumour is assessed and samples of the tumour, lymph nodes and background bowel taken for histology. This process typically takes 30 minutes to an hour for each specimen. It is crucial because the final staging of the tumour is based on samples removed from the main specimen at this stage. The tissue samples are then processed to make slides, which takes a further 24 hours. All in all, it takes a minimum of three, and more usually four, working days to turn a surgical bowel specimen into histological slides. Reporting the histology slides is relatively quick process in comparison to cutting up the specimen, typically taking 15 to 20 minutes. The histopathologists examines the tumour cells to see how aggressive they look (Tumour Grade) and to determine how far the tumour has spread – both direct local spread into surrounding tissues and metastatic spread into the lymph nodes (Tumour Stage). This information is all included in the final histopathology report, which is sent to members of the multidisciplinary team looking after the patient. Based on these findings the surgeons are able to tell if they have managed to completely remove the primary tumour and to access the quality of their surgery. The oncologist is able to provide the patient with a long-term prognosis and to discuss further treatment options (if any further treatment is required). The data also allows the radiologists to audit their reporting practice. Histopathology is central to the clinical management of cancers. The histopathologist should no longer be considered a dark shady character who lives in the mortuary, but should be seen as an integral member of the multidisciplinary teams looking after cancer patients.
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What is the Oncotype DX® Breast Cancer Assay?
Oncotype DX® is a test that examines a breast cancer patient’s tumour tissue at a molecular level, and gives information about the patient's individual disease. By providing an individualised assessment of the magnitude of chemotherapy benefit and the likelihood of distant recurrence at 10 years, Oncotype DX® can inform adjuvant treatment decisions.
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What is required for the Oncotype DX® assay to be performed and how long does it take?
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