Diagnostic Pathology Molecular Oncology Pdf

[Thomas Merino]

Covering all aspects of molecular pathology as it relates to the transformation and pathogenesis of cancer, this award-winning volume in the Diagnostic Pathology series is an expert resource for pathologists at all levels of experience and training, both as a quick reference and as an efficient review to improve knowledge and skills. This easily accessible, point-of-care reference features templated, bulleted content that is generously illustrated with charts, graphs, tables, and color photomicrographs of histology with special stains.

The Division of Anatomic Pathology & Molecular Oncology provides a full range of consultative and diagnostic services. For our patient-care services, we place high value on diagnostic expertise, accuracy, state-of-the-art technology and service. Our expertise spans the full spectrum of Anatomic Pathology and includes surgical pathology, cytopathology, molecular oncology, and autopsy pathology. Subspecialties include pathology of the breast,bone and soft tissue, cardiac, FISH, gastrointestinal, genitourinary, gynecological, head & neck, hematopathology, hepatic, histochemistry, immunohistochemistry, neuropathology, pulmonary, and renal subspecialties, including a total of over twenty faculty.

The Molecular Oncology Laboratory at ARUP offers state-of-the-art facilities and expertise. It is one of the leading laboratories of its kind in the world, and includes eight expert faculty and the most important technologies, from next generation sequencing to Nanostring to Sequenom to digital droplet PCR to automated FISH imaging.

Patient care for diagnostic, prognostic and therapeutic purposes, involving morphologic diagnoses, histochemistry, immunohistochemistry, FISH, electron microscopy, immunofluorescence and a full spectrum of molecular analyses for mutations, insertions, deletions, methylation, copy number variations and translocations.

Research is a critical mission of the Division. Vibrant programs exist for diagnosis, prognosis, therapy and mechanisms of human disease, as indicated in our faculty biographies. Anatomic Pathology runs the Biorepository and Molecular Pathology (BMP) shared resource at the Huntsman Cancer Institute (HCI), to provide research histology, biorepository and molecular diagnostic research services to the Department, HCI and the University of Utah as a whole.

A pathology report (sometimes called a surgical pathology report) is a medical report that describes the characteristics of a tissue specimen that is taken from a patient. The pathology report is written by a pathologist, a doctor who has special training in identifying diseases by studying cells and tissues under a microscope.

The pathology report provides the definitive cancer diagnosis. It is also used for staging (describing the extent of cancer within the body, especially whether it has spread) and to help plan treatment.

For some cancer types, especially breast cancer and melanoma, the surgeon may also remove nearby lymph nodes, called the sentinel lymph nodes, so the pathologist can see if these contain cancer cells. The Sentinel Lymph Node Biopsy fact sheet describes this procedure and its use in determining the extent, or stage, of cancer in the body.

A pathologist may also examine cells that are present in bodily fluids, such as urine, cerebrospinal fluid (the fluid around the brain and spinal cord), sputum (mucus from the lungs), peritoneal (abdominal cavity) fluid, pleural (chest cavity) fluid, cervical/vaginal smears, and bone marrow.

Tissue or cell specimens must be cut into very thin slices, called sections, so the pathologist can look at them under a microscope. The specimen must be processed to make it solid before it can be cut into sections.

Once processed, the tissue is embedded into a permanent paraffin wax block to be cut. The paraffin-embedded tissue is then sliced into very thin sections that are placed onto microscopic slides. The slides are stained with dyes to help visualize parts of the cell and structures in the tissue. This is known as histologic (tissue) examination.

Fixed sections provide the maximum detail of the structures in a tissue sample, and they can be saved and analyzed in the future if needed. Preparing fixed sections normally takes several days. The pathologist typically sends a pathology report to the doctor within 10 days after the biopsy or surgery is performed.

Frozen sectioning is another approach used by a pathologist for tissue examination. Frozen sections are prepared when an immediate answer about a tissue sample is needed. For example, this type of examination would be used during surgery to provide the surgeon with a rapid diagnosis for an area of abnormal tissue and the extent of the abnormal area while the patient is in the operating room. To make frozen sections, the tissue sample is rapidly frozen, cut into sections using an instrument called a cryostat, stained, and examined by a pathologist. This can be done in about 15 to 20 minutes.

Frozen sections are suitable for preparing tissue for some tests, such as immunofluorescence and immunohistochemistry. However, the fixed (permanent) section preserves more detail and is more commonly used to make a diagnosis than frozen sections.

The gross description includes the color, weight, and size of a tissue sample as seen by the naked eye. It may also include the shape of the tissue sample and any visible abnormalities. And it will indicate the body site from where the tissue was taken from, how many samples were taken, and whether and how many lymph nodes were removed.

The microscopic description in a pathology report includes information about the appearance of the cells after they have been stained with routine stains such as hematoxylin and eosin (also known as H&E) and viewed under the microscope. H&E staining helps identify different types of cells and tissues and provides important information about the pattern and shape of cells and the structure of the tissue. With H&E staining, hematoxylin shows the ribosomes, chromatin (genetic material) within the nucleus, and some other structures in the nucleus as a deep blue-purple color. Eosin shows the cytoplasm, collagen, connective tissue, and other structures that surround and support the cell as an orange-pink-red color.

This description may also include the type and number of cells seen in the tissue sample, how abnormal the cells look (also called the tumor grade), and whether there are notable cell features (such as their arrangement and behavior).

Certain molecular tests, sometimes called biomarker tests, are done as part of the initial pathology analysis for all cases of a given cancer type. For example, a pathology report for a patient with suspected breast cancer will include the results of testing for estrogen and progesterone receptors and the protein HER2/neu. The results of these tests can help identify what treatments are best for an individual patient.

Pathology examination is increasingly incorporating analyses of the structure and sequence of DNA extracted from fresh and fixed tissue samples to refine the cancer diagnosis through improved subtyping and stratification of tumor types and to better inform treatment.

In the comments section of the pathology report, the pathologist may note unusual features of the sample, such as information about the cytogenetic and/or molecular characteristics of a tumor, or provide additional information. The comments section is often used by the pathologist to provide more details about the disease and its diagnosis and to recommend additional tests that might be needed. It may include relevant clinical history or test results, abnormal findings that could change a typical diagnosis, previous samples or diagnoses for the patient, and other possible diagnoses. It will also mention tests that are still in process (i.e., pending).

Patients should be aware that pathology report results will often appear in the patient portal at the same time the doctor receives them. This means that patients may see their report before their doctor has had a chance to review it and discuss it with them.

Although the diagnosis of most cancers is straightforward, patients or their doctors may want to get a second opinion from another pathologist. Patients interested in getting a second opinion should talk with their doctor. They will need to obtain the slides and/or paraffin block from the pathologist who examined the sample or from the hospital where the biopsy or surgery was done.

Many institutions provide second opinions on pathology specimens. NCI-designated cancer centers or academic institutions sometimes provide second opinions. Patients should contact the facility in advance to determine if this service is available, the cost, and shipping instructions.

For each patient, the results of all pathology examinations and any other tests ordered by the pathologists are reviewed together by the tumor review board, a group of doctors who are experts in different specialties who plan the treatment approach for a patient.

The Laboratory of Diagnostic Molecular Oncology provides a wide range of molecular testing. Our testing involves both the diagnosis and monitoring of hematolymphoid malignancies and solid tumors. This testing is performed on a variety of specimen types including blood, bone marrow, fresh or frozen tissue, paraffin embedded tissue and body fluids.

The laboratory occupies a unique niche when it comes to the war on cancer. As a clinical laboratory we get feedback from physicians and patients by helping with early cancer diagnosis and by guiding the most effective patient therapy. As a research laboratory we continue to discover and develop new cancer diagnostics that will support patient care. For example we have developed a novel assay integrating cell morphology with fluorescent in situ hybridization to improve the accuracy of bladder cancer diagnosis (see figure above).

Due to continuing efforts to integrate these novel assays into routine laboratory testing the number of assays performed in-house continues to expand. In addition, this laboratory also coordinates the send-outs of esoteric molecular oncology testing to reference laboratories.

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