Clinical Pathology

James Dent chats to Dr Robert Rawson about clinical pathology.

Summary Writer:  Divya Iver

Script Writer:  Elizabeth Campbell

Editor:  Robert Rawson

Interviewee:  Robert Rawson

About clinical pathology

Clinical pathologists are specialists in the anatomical, biochemical and physiological processes that maintain a healthy body and the pathological mechanisms that disturb this balance. Through the examination of the changes in tissue architecture caused by disease, pathologists are able to provide critical information regarding diagnosis, prognosis and appropriate treatment modalities.

In this podcast, we explore the field of clinical pathology. Particularly, anatomical pathology. Further, you will gain an insight into some of the techniques pathologists use. Most importantly, you will hear critical information that junior doctors should know about this fascinating specialty.

About Dr Robert Rawson

Robert Rawson completed his Fellowship with the Royal College of Pathologists of Australasia in 2016. Further, he was appointed the Cameron Pathology Fellow at the Melanoma Institute of Australia and Royal Prince Alfred Hospital for 2016. In addition, he held a position as a staff specialist at Royal Darwin Hospital. After that, in 2018, Robert returned to Royal Prince Alfred.

Robert’s primary interests include dermatopathology, particularly melanocytic pathology, and gynaecological pathology.

Secondly, he is involved in numerous research collaborations within the Melanoma Institute Australia Translational Research Group at Sydney University. Moreover, he won the Premier’s Award for Outstanding Cancer Research in 2016. And he received the Sydney Research Clinical Researcher Scholarship in 2019. In addition, Robert is committed to the medical education of pathology registrars and medical students.

In his spare time, Robert is a volunteer lifesaver and a keen triathlete. Recently, he was selected to represent Australia at the 2019 Triathlon World Championships in Switzerland.

Clinical Pathology

With Dr Robert Rawson, Pathologist at Royal Prince Alfred Hospital, Sydney, NSW, Australia

Introduction

Clinical pathologists are specialists in the anatomical, biochemical and physiological processes that maintain a healthy body and the pathological mechanisms that disturb this balance. Through examination of the changes in tissue architecture caused by disease, pathologists are able to provide critical information regarding diagnosis, prognosis and appropriate treatment modalities. Numerous diagnostics techniques are now used by clinical pathologists to provide such information. In this podcast, we explore the field of clinical pathology, particularly anatomical pathology, and gain an insight into some of the techniques used, as well as critical information that junior doctors should know about this fascinating specialty.

  • Pathology provides insight into the basic science of disease and impacts the decision-making process in medicine
  • Pathologists undergo a rigorous training pathway and are central to patient care in hospitals and in primary health care
  • Pathology provides diagnostic and prognostic information and can be used to direct treatment
  • The specialty of pathology may be further subdivided into haematologists, microbiologists, chemical pathologists, genetic pathologists, forensic pathologists and anatomical pathologists
  • Anatomical pathologists look at biopsies and excisional specimens to provide information regarding the disease process and its management

Case

A 52-year-old female presents to the emergency department with left lower quadrant abdominal pain. She has associated nausea and has vomited today. She is unsure when she last used her bowels. Her abdominal examination reveals bloating, tenderness of the left iliac fossa and bowel sounds are not audible. CT of her abdomen shows a large left-sided ovarian mass causing extra-mural small bowel obstruction.

  • REMEMBER: when sending a specimen to pathology you are making a medical referral as you would to any other specialty
    • ALWAYS remember to include clinical information on this request form
  • Pathologists may use the following diagnostic tree
    • Is this a neoplastic process?
      • Does this presentation have features of a malignant neoplasm?
        • Primary malignancy
        • Metastatic Disease
      • Does this presentation have features of a benign neoplasm?
    • Is this an infective process?
    • Is this an inflammatory process?
  • History
    • Any features on history that could be relevant to the above diagnostic tree would be useful for a pathologist to have
    • Are there features which may indicate an inflammatory process?
      • Examples relevant to this case include pelvic inflammatory disease, endometriosis, inflammatory bowel disease
    • Is there a personal or family history of malignancy?
    • Does the patient have any systemic conditions?
    • Is the patient immunosuppressed?
    • Has the patient had any previous treatment?
    • What is the clinician’s suspicion and what clinical question do they want answered?
  • Serological tests such as serum tumour markers e.g. Serum CA 125
    • Serum CA 125 is elevated in approximately 50% of women with early stage ovarian cancer and in over 80% of females with advanced ovarian cancer
    • Specificity is limited and CA 125 can be raised in a variety of benign and malignant conditions such as endometriosis, uterine fibroids, pelvic inflammatory disease, cirrhosis, and pleural/ peritoneal fluid due to any cause
  • Radiological studies – e.g. pelvic ultrasound
  • Eventually pathological diagnosis is required
  • Cytology – study of cell type
    • Samples may be collected by fluid aspirate, fine needle aspirate, smear (e.g. pap smear)
    • Positives
      • Quick study
      • Cheap
      • May be able to be performed in rooms
    • Negatives
      • Only able to examine the cells and not how they interact with the tissue architecture around them
      • May not get enough material to do additional tests
  • Histology – study of tissue – cells within the tissue and the make of the matrix of the sample
    • Positives
      • Able to see the interaction of the cells of concern and the surrounding tissues
      • More material can be obtained to run extra tests
    • Negatives
      • Labour intensive process – sample needs to be fixed, sliced and stained prior to analysis
      • Time to final result may be prolonged
  • Which test is best in this case study?
    • If there is ascitic fluid – this may be aspirated and spun down to examine cytology
    • Fine needle and core biopsies are not to be performed on ovarian lesions
      • Risk of rupture if the lesion is cystic
      • Risk of seeding the tissue through pelvic/ peritoneal cavity
    • In this situation the best biopsy would be an excisional biopsy of ovarian mass and fallopian tube
      • Frozen section may be done during the operation – the sample can be quickly stained and examined to provide the surgeon with intraoperative advice plus a premlinary diagnosis
      • This cannot always be performed as freezing the sample degrades the tissue which makes microscopy challenging and destroys the sample for future testing
      • Is more suitable in situations where further excision may occur based on the findings in the frozen section
  • If this is a primary ovarian lesion, differentials include – epithelial tumour, stromal cell tumour, germ cell tumour
  • We must also consider whether this could be a metastasis
  • Different stains may be used to determine the above
    • Chemical stains – looking for a particular substance within the tissue
      • Mucin Stain – If mucin present indicates that this may be a glandular lesion such as adenoma/ adenocarcinoma
      • Iron Stain – hemochromatosis in the liver hepatocytes
      • Congo Red (amyloid) Stain – amyloid in cardiac myocytes
    • Immunohistochemical stains
      • Immunohistochemistry is particularly valuable in identifying tumour lineage
      • An immunohistochemical stain is an antibody that is attached to a dye
      • The antibody is washed across the tissue on the slide
      • If the relevant antigen is present on that slide, that antibody and dye will attach
      • Microscopy will show this to be a positive stain
      • There are different sensitivity and specificity profiles to these different stains
      • A panel of stains will be selected to tease apart the differentials above – Will aid in subclassification of the tumour to guide prognosis and treatment
  • Molecular tests
    • Fluorescent In-Situ Hybridization (FISH)
      • Looks for large changes in chromosomes of tumours e.g. amplifications, deletions, translocations
      • Sarcomas, haematological malignancies and neurological tumours often have specific molecular features that can be characterised with FISH studies
    • Sequencing techniques are also available to be able to prove particular mutations
      • Such as in dermatopathology – characterisation on BRAF mutations in melanomas
      • Molecular testing is also useful to determine if particular treatments would be effective in certain people e.g. commencement of drugs with molecular targets in lung cancer
  • Flow Cytometry – in conjunction with haematology colleagues
  • Microbiology
  • Serology
  • In recent years tumour syndromes and familial syndromes have been better understood
  • Pathologists are in a unique position to be able to identify when someone is at risk of having a tumour syndrome or familial syndrome
  • In this case
    •  If pathological diagnosis is carcinoma — it would be suggested that the patient have BRCA mutation screening and referral to genetic counselling if required
    • If pathological diagnosis is endometrioid or clear cell carcinoma – these patients are at high risk of Lynch Syndrome.
      • Lynch syndrome is an autosomal dominant disorder caused by several genetic mutations that impair the repair of DNA mismatch.
      • These patients have up to an 80% lifetime risk of developing colorectal cancer.
      • This condition is also associated with endometrial and ovarian tumours and other cancers of the gastrointestinal tract
      • If a related ovarian tumour is found it is recommended to also screen for colorectal cancer
  • In the case of conditions such as Lynch Syndrome where there are familial implications, clinical pathologists are always available to discuss the pathological diagnosis with patients and their families if required
  • Multidisciplinary team meetings to discuss such complex patients have been proven to improve patient outcomes and is a good environment to learn from other specialties
  • ALWAYS provide adequate clinical information to accompany your clinical pathology request. This contextualises why the sample was taken and may provide valuable clues as to the patient’s diagnosis, prognosis and treatment options
  • Samples may take a period of days to be completely analysed and reported. Always flag urgent cases with the pathologist as they may be able to expedite the process when clinically required
  • Pathology is a fascinating and varied career – There is exposure to many fields and always a role for critical thinking and problem solving. Consider approaching a pathologist and spending some time in their lab to fully appreciate the role and duties of the clinical pathologist if you are interested and want to know more about this field of medicine

Tags: #clinical pathology,#Flow Cytometry,#histology,#immunohistochemistry,#infections,#inflammation,#medical oncology,#microbiology,#molecular tests,#neoplasm,#oncology,#pathology,#serological tests,#serology

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