Lecture 11 - Role of Pathology in Diagnosis and Management of Neoplastic Disease Flashcards
What does a pathologist do?
- a person who examines and provides reports on specimens from living people
- a medically qualified prison who specialises in pathology as a postgraduate subject
- a person who does post mortems
A knowledge of pathology helps to explain…
the clinical features and natural history of most common diseases
- in order to understand changes in disease tissues, one needs to know about normal tissues biology
- also important for prognosis and treatment
What 4 things are involved in the role of pathology in the diagnosis and management of neoplastic disease?
- understanding tumour pathology and pathological assessments
- types of specimens received
- techniques used: gross/microscopic, immunohistochemistyr, molecular biology
- pathology as a clinical discipline (including MDT meetings)
Why is an understanding of tumour pathology important? x3
- clinical presentation and natural history
- terms used to classify neoplasms and their clinic relevance
- treatment options
Describe briefly 3 differences between benign and malignant lumps
Benign = smooth, well circumscribed and mobile Malignant = irregluar, poorly-defined, may be fixed to adjacent tissues
Clinical assessment of breast lumps:
- describe a fibroadenoma
- describe a breast carcinoma
Fibroadenoma - commonest benign breast neoplasm - mostly occur in younger women - smooth, well circumscribed, highly mobile of palpation Breast carcinoma - commonest malignant breast neoplasm - mostly occur in older women - irregular, poorly circumscribed, rarely mobile on palpation (due to local invasion)
How can neoplasms be classified in terms of their origin/differentiation?
- most malignant neoplasms are epithelial
- most benign neoplasms are mesenchymal
In which layer do majority of colonic neoplasms arise and why?
glandular epithelium of mucosa
- in contract with a high conc of carcinogens
- high turnover of cells, susceptible to mutations affecting dividing cells
How does clinical presentation differ in colon carcinomas arising the cecum/ascending colon and in the signmoid colon?
Cecum/ascending colon
- often polypoid
- rarely cause bowel obstruction
- incidiuous presentation e.g. anaemia, weight loss
Sigmoid colon
- often stenosing
- frequently cause bowel obstruction or paradoxical diarrhoea
What are the 3 types of specimens that can be obtained for pathological assessment?
- Biopsies
- endoscopic biopsies e.g. GI tract, bronchus
- needle biopsies (radiologically guided)
- punch biopsies e.g. skin - Cytology specimens (cells)
- smears e.g. cervical
- endoscopic brushings
- body fluids
- fine needle aspiration specimens - Surgical resection specimens
What is the main role of biopsies and cytology specimens?
- mainly taken to confirm a diagnosis of malignant and identify histological type
- information used to plan further treatment
What are the limitations of biopsying tumours?
- tumour heterogeneity
- targeting the lesion accurately: small lesions, inaccessible, surrounding stromal reaction e.g. pancreatic cancer
What is the advantage and disadvantage of cytology specimens?
Advantage
- less invasive
- fine needles are much thinner
- may provide access to sites not suitable for biopsy e.g. pancreas
Disadvantage
- smaller tissue samples provided, interpretation may be more difficult than larger specimens obtained using biopsy
What are the surgical resection specimens used for?
- surgery is intended to be a definitive treatment for cancer, or palliative in some cancers
Pathological Assessments are used to: - confirm diagnosis of malignancy
- determine the aggressiveness of a tumour (grading)
- assess the extent of spread (staging)
- examine completeness of excision
This info can be used to determine further treatment e.g. adjuvant chemotherapy
Describe the TMN staging method
T = tumour - size and or extent of spread of primary lesion N = nodes - extend of spread to lymph nodes M = metastases - presence/absence of distant metastases
Describe the Duke’s system for staging colorectal cancer
A = confined to submucos/muscle B = through muscle to serosa C = lymph node involvement D = distant metastases
What are the 5 year survival statistics for each stage of Duke’s classification
multiples of 30! Stage A = 90% survival Stage B = 60% survival Stage C = 30% survival Stage D = >1% survival
What can be established on macroscopic assessment of tumour resection specimens?
size, shape extent of local spread proximity to surgical resection margins identification of lymph nodes other e.g. colour, haemorrhage, necrosis
What can be established on microscopic assessment of tumour resection specimens?
Confirms of establishes a diagnosis or cancer Features that are assessed include: - histological type (glandular, squamous) - degree of differentiation (grading) - frequency of mitosis - local invasion (staging - vascular invasion - examination of lymph nodes
What is included in the Royal College of Pathologist’s minimum datasets for reporting cancers?
- prognostic information
- accurate date for caner registration
- feedback on the quality of resection
- selecting patients for adjuvant therapy (including clinical trials)
- auditing effectiveness of pre-operative staging procedures
What are the two features required of a substance used in immunohistochemistry?
can binding to a specific marker on cell
has a mechanism of secondary visualisation e.g. fluorescense
What are the 3 things that can be derived from immunohistochemistry?
- establishing a diagnosis of malignancy
e. g. clonality in lymphoid neoplasms, B and T cells inflitrates - Prognostic markers
e. g. Ki-67 labelling index for metastatic potential - identifying therapeutic options
e. g. HER 2 present? perceptive use
What is Ki-67 labelling index?
- a stain that may be used to determine low or high metastatic potential
- most cases well-differentiated by conventional histological criteria and behaviour difficult to predict
- Ki67 labelling index <2% - low metastatic potential
- Ki67 labelling index >20% - high metastatic potential
What are the 2 molecular techniques?
- in situ hybridisation
- probes recognising RNA and DNA can be applied to tissue sections
- e.g for kappa and lambda chains
- e.g. EBV virus present - RNA or DNA extracted from fresh or paraffin embeddd samples of tumour tissue
What is post-transplant lymphoproliferative disease?
- spectrum of lymphoproliferative disease occurring in the setting of immmunosupression
- range from polyclonal lymphoid hyperplasia to monoclonal malignant lymphoma
- majority related to infected with EBV
- virus infects B lymphocytes, remains in latent phase, controlled by EBV- specific T cell response
- immunosuppressive drugs interfere with T cell function and enable uncontrolled division of EBV infected B cells
- most cases present during first 12 moths post traplant - focal mass or diffuse infiltrates
What is the role of the MDT?
- many important decisions relating to the diagnosis and treatment of malignant neoplasms now take place in the setting of MDT meetings
- core members include: histopathologists, radiologists, surgeons, oncologists, other HCPs
- the presence of recognised MDT meetings and regular attendance by core members is now a requirement in order for a hospital to be recognised as a Cancer Treatment Centre
- regularly monitored by Cancer peer Review Teams
