Introduction
The lectures, associated reading, and formative slide practicals represent an integrating arc of learning that culminate in the (virtual) Slide Practical 4 where you are introduced to an example of the histopathology work-up of a cancer case. It has been necessarily abbreviated to focus on the role of histopathology and immunohistochemistry in the reporting of the case. However, you should be aware of the pre-analytical events that precede the analytical and post-analytical summaries presented.
The case presented here illustrates the use of diagnostic, prognostic and predictive tests to inform the future management of the patient by the oncology team.
There will be a formal review of vSP4 later in the module. Here we will look at the clinical and histopathological background to the case. As you should expect, and welcome, there will be some underpinning reading and research for you to do.
Clinical History
The patient was a 65 year-old female who was referred to the breast clinic after finding a non-mobile lump in her left breast. Her clinical history was that of a non-smoker, occasional/social drinker without a family history of breast cancer. She was a mother of three and was post-menopausal.
Mammography and ultrasound investigations of her left breast revealed a 3 cm mass along with a number of smaller, satellite lesions. Further MRI investigations of the patient’s thorax revealed a suspicious mass in her liver. Therefore, a modified radical mastectomy was performed on her left breast and the lesion in her liver was sampled using CT-guided needle core biopsies.
All of the tissue removed, along with the resected lymph nodes, was sent to the histopathology department for processing and reporting.
The patient was diagnosed with a primary invasive ductal carcinoma which had metastasised to her axillary lymph nodes and to her liver.
Materials
You are provided with a digital case work-up in Westminster Slide Box: vSP4. This consists of a number of whole slide images (WSIs) of sections from the patient’s tissue samples. These include a Haematoxylin and eosin (HE) stained section of the primary tumour (ID 188). An example of one of the lymph nodes is included (ID186). There are core samples from the liver nodule stained for both routine HE (ID 189) and a short immunohistochemistry panel as shown in the table below. Note that these last images include control sections.
Study the WSIs of the HE-stained sections. Using accurately labelled images to support your work, describe the histopathology of the primary tumour and the liver core biopsy. You should support your description with no more than 4 images. The figure legends will count towards the word limit. (25%, 375 words*)
Using your case as an example, discuss the histopathological investigation of the sentinel lymph node. (25%, 375 words*)
With reference to all of the evidence available to you, provide an illustrated description of the patterns of immunohistochemical staining visible with the different antibodies and discuss how these results will inform the pathologist’s report. You should support your description with no more than 8 images. The figure legends will count towards the word limit. (50%, 750 words*)
Total word limit for Part 1 = 1350 words
Supporting reading for Part 1 (and this is not an exhaustive list):
Pathology Outlines – Stains & molecular markers [WWW Document], n.d. URL https://www.pathologyoutlines.com/stains.html (accessed 02/07/21).
Rakha, et al. (2014). Updated UK recommendations for HER2 assessment in breast cancer. J Clin Pathol. 68(2), 93-99.
Royal College of Pathologists (2016). Pathology reporting of breast disease in surgical excision specimens incorporating the dataset for histological reporting of breast cancer. [A lengthy but important document. Focus on Sections 1.7, 5, 6, 7 and 8. The remainder for extended reading. Available from https://www.rcpath.org/uploads/assets/7763be1c-d330-40e8-95d08f955752792a/G148_BreastDataset-hires-Jun16.pdf]
Shah, et al. (2014). Pathogenesis, prevention, diagnosis and treatment of breast cancer. World J Clin Oncol. 5(3): 283–298.
Zaha (2014). Significance of immunohistochemistry in breast cancer. World J Clin Oncol. 5(3): 382-392.
Moll et al. (2008). The human keratins: biology and pathology. Histochemistry and Cell Biology, 129(6), 705–733. [***A core reference on keratins in pathology]
The lymph node microenvironment and its role in the progression of metastatic cancer. Seminars in Cell & Developmental Biology, 38, 98-105. [Some extended background that you may find interesting]
vSP4 Part 2 (50% of the Coursework Marks)
The case study below contains a scenario, laboratory findings and questions you are required to answer.
Scenario
The patient is a 10-year-old girl of African origin, with swelling of the jaw and tonsils causing discomfort whilst swallowing. Six months previously, the patient had been diagnosed with Epstein-Barr Virus infection. However, the patient did not seem to recover and her condition began to worsen over time. Signs include fever, lethargy, severe night sweats and weight loss over the past six weeks. There is no history of major disease within the family and the patient eats a normal healthy diet.
After physical examination for lymphadenopathy, biopsy samples of the tonsil and lymph node were taken. A blood test was also requested with the results shown in Table 1 and Figure 1.
Due to concern over the blood test and biopsy results, immunocytochemical tests were performed on the biopsy tissue. Measurements were as follows:
Table 2. Immunocytochemistry results for the patient.
Further cytogenetic testing was carried out on peripheral blood and lymph node samples from which an abnormal translocation was identified (Figure 2).
Figure 2. Cytogenetic results revealing a chromosomal rearrangement.
Questions to address in your report. The percentage values refer to the suggested distribution of effort for Part 2, not marks.
Using examples, evaluate how genetic alterations contribute to the development of the haematological malignancy presented in your case. (20%, 300 words*)
Explain why morphological examination was necessary to investigate the patient and compare the value of this technique with ONE other diagnostic method performed in your case study. (40%, 600 words*)
Discuss how targeted drugs provide new opportunities for the treatment of haematological malignancies. You should provide one example relevant to your case and briefly describe how response to treatment may be monitored. (40%, 600 words*)
Total word limit for Part 2 = 1500 words
