Behind the Scenes: The Critical Importance of Cancer Cell Pathology and the Pathologist Sherry T. Emery, M.D., Chief of Pathology Northeast Health System
Barriers to Understanding
Questions for 2010 What is modern pathology? What is a modern pathologist? What is their role in modern cancer care?
Pathology Defined Greek root pathos -suffering An ancient field of medicine, root of most disciplines A study of all that which befalls the human body by means of the examination or organs, tissues, individual cells, body fluids and whole bodies One of the Diagnostic Branches of Medicine- also includes most of radiology IMPORTANT Autopsy pathology fading as an important component of modern pathology
Divisions of Pathology Anatomic Pathology Surgical Pathology Dermatopathology Hematopathology Cytology Autopsy Pathology Forensic Pathology Clinical Pathology the machines Molecular Pathology involves development of molecular and genetic approaches to the diagnosis of tumors Research
Clinical Pathology
Clinical Pathology Diagnosis of disease based upon laboratory analysis of body fluids such as blood and urine and using the tools of chemistry, microbiology, hematology, blood bank and molecular pathology Examples of importance in cancer care include serum tumor markers and special genetic and molecular tests performed on tissues(her2/neu in breast cancer, EGFR in lung cancer)
What is a Pathologist? M.D. 5 or more years of training after medical school Most pathologists are NOT forensic pathologists!
The Pathologist and Cancer Essential to DIAGNOSIS: The diagnosis should be as meaningful, accurate and as useful as possible Elements of importance include: Organ of tumor origin Tumor type Tumor size Differentiation Status of margins Lymphatic/Vascular invasion Lymph node status
Tumor Features Cancer is characterized by unregulated growth, invasion and metastasis Tumor types include: carcinoma, lymphoma, sarcoma, leukemia, melanoma, neural tumors Also consider pre-cancers and risk factor conditions For example in breast: Ductal carcinoma in situ Lobular carcinoma in situ Atypical ductal hyperplasia Atypical lobular hyperplasia Flat epithelial atypia
A Carcinoma of the Uterus
In the WAR on CANCER know the ENEMY Consult the Intelligence Report The Pathology Report
Synoptic Reporting and Staging
Example Clinical History 61 year old woman with no family history of breast cancer found to have new density on screening mammogram. Core biopsy proved to be positive for invasive breast carcinoma. Patient scheduled for wide excision of mass with sentinel lymph node biopsy.
The Frozen Section Results within 20 minutes
The Main Specimen
Specimen Radiograph
Orienting with Ink
Slicing the Specimen
Processing in Histology: Overnight
Cutting the Blocks
Making the Slides
Specimen = Blocks and Slides
Now It s My Turn!
Examining the Tumor
Estrogen and Progesterone R
The Brown Stains Immunoperoxidase/immunohistochemistry(IHC) Sandwich technique using monoclonal antibodies Antibodies to a variety of cellular components hormone receptors(er/pr) epithelial markers/keratins(ck7/ck20) lymphoid markers(cd3/cd20/cd30) soft tissue components(cd34/sma/desmin) invasion markers(calponin, p63, HMW keratin) site of origin markers(ttf-1, mammoglobin)
Her2/neu by FISH FISH (fluorescence in situ hybridization) DNA probes labeled with detection moiety applied to tissue sections or cell suspensions Good for measuring number of copies of DNA Good for studying relations of probes to one another Downside is scope requirement, scoring problems SISH is coming! EXAMPLE: Her2/D17Z1 ratio=1.2; No amplification
The Final Report I. Right Breast Infiltrating Carcinoma Procedure: Wide Excision Tumor Type: Ductal Tumor Size: 0.8 cm Differentiation: Moderate (Nottingham combined histologic score) In-situ component: Scant to absent Lymphatic invasion: Not identified Surgical margins: Close; tumor 2 mm from deep margin ER/PR Status: ER 95% positive; PR 95% positive Her2/neu status: Block submitted for FISH analysis AJCC Pathologic Tumor Stage: pt1b,n0,mx
Final Report Cont. II. Lymph nodes, right sentinel: Two lymph nodes negative for tumor F.S. Diagnosis #2: Two lymph nodes without tumor Questions raised by the report: Does the patient need a re-excision? Does moderate grade change treatment? Would an extra i.e. Oncotype DX be helpful?
Presentation at Tumor Board A multidisciplinary approach to determining care Present at the meeting: Oncologist Consultant oncologist Surgeon Radiation therapist Radiology Pathology Oncology Nursing Sometimes run in clinic format
The Extras in Pathology Growing list of additional tests used to augment the histologic interpretation of a tumor. Serve as guides to determining treatment. c-kit testing in Gastrointestinal Stromal Tumors Her2/neu testing in breast cancer MSI testing in colon tumors CD20 testing in lymphomas KRAS and EGFR testing in lung tumors HPV genotype testing in cervical dysplasia Multigene testing Oncotype DX, RedPath
It Takes a Village
Thank you! An expert is a person who tells you a simple thing in a confused way, in such a fashion as to make you think the confusion is your own fault. WB Castle, Harvard Medical Bulletin, 1955