Biopsy

• 1. Introduction

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  A biopsy puts living tissue under the scrutiny of a microscope, and what a pathologist reads there can change a patient's life. The word itself carries that weight: it joins the Greek bios, meaning life, and opsis, meaning a sight. To take a biopsy is, in the most literal sense, to look at life.

  The procedure is performed by surgeons, interventional radiologists, and interventional cardiologists. Its purpose is to extract cells or tissue and examine them closely enough to determine whether a disease is present and how far it has spread. Before a pathologist ever looks through a lens, the sample travels through a precise sequence: it is fixed, dehydrated, embedded, sectioned, stained, and mounted.

  Biopsies are most often sought when cancer or inflammation is suspected. But the questions this documentary will pursue go deeper. How did this technique begin? What are the different ways tissue can be collected, and why does the method matter? And what does the future look like when the biopsy no longer requires a needle at all?

• 2. A Needle and a Thyroid

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  Abulcasis, the Arab physician who lived from 1013 to 1107, performed one of the earliest diagnostic biopsies on record. He used a needle to puncture the thyroid and went on to characterize many types of goiter from what he found. That single act established the core logic of the biopsy: access the tissue, examine it, and draw a conclusion about the disease.

  Nearly eight centuries passed before the procedure acquired its modern name. The French dermatologist Ernest Besnier introduced the word biopsie to the medical community in 1879. Besnier worked in dermatology, a field where lesions are visible and accessible, and that surface accessibility was precisely where biopsy techniques first took hold.

  Skin and other superficial masses were the original targets. Over time, X-ray extended the reach of clinicians, and then CT, MRI, ultrasound, and endoscopy extended it further still, allowing suspicious areas deep within the body to be identified and sampled.

• 3. How the Sample Is Taken

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  When an entire suspicious area is removed in one procedure, that is called an excisional biopsy. The surgeon attempts to take out the whole lesion, and the pathologist then examines not just the tissue itself but the border around it. Clear margins, or negative margins, mean no disease was found at the edges. Positive margins mean disease was found there, and a wider removal may follow depending on the diagnosis.

  When removing the entire lesion is not appropriate, a wedge of tissue may be cut away in what is called an incisional biopsy. Some devices are designed to bite out a sample. Needles of varying sizes can collect tissue from within a channel, which is called a core biopsy. Smaller-diameter needles collect individual cells and cell clusters through fine needle aspiration.

  When the goal is to understand not just whether a cancer is present but exactly what kind, a larger excisional specimen called a resection comes to the pathologist. A mastectomy specimen, for example, allows the pathologist to confirm the subclassification of the tumor, its histologic grading, and the extent of its spread through pathologic staging, even when a prior biopsy had already established the diagnosis of breast cancer.

• 4. Reading the Tissue

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  After a sample arrives at the pathology laboratory, an extremely thin slice of tissue is cut from it and fixed to a glass slide. Any remaining tissue is saved in case further studies are needed. Dyes are then applied to the slide; the staining makes individual cells visible in ways that would otherwise be impossible under a microscope.

  The pathologist examines the stained slide and prepares a report listing any abnormal or important findings. That report travels back to the surgeon who performed the biopsy. Pathologic examination can determine whether a lesion is benign or malignant and can help distinguish between different types of cancer.

  For some conditions, the analysis goes further than the microscope alone. In Wilson's disease, clinicians use biopsy results to determine the quantitative copper level in the liver. In hepatitis, biopsies are taken less to establish the diagnosis and more to gauge how well treatment is working, measuring the reduction of inflammation and tracking the progression toward fibrosis or cirrhosis.

• 5. The Reach of the Biopsy

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  Flexible endoscopy brought the gastrointestinal tract within reach. Through the mouth, clinicians can now access the esophagus, stomach, and duodenum; through the rectum, the colon and terminal ileum. A variety of biopsy instruments, including the bioptome, can be introduced through the endoscope and used at the visualized site. Until recently, most of the small intestine could not be seen or sampled. The double-balloon push-pull technique changed that, allowing visualization and biopsy of the entire gastrointestinal tract.

  Needle core biopsies or aspirates of the pancreas can be made through the duodenum or stomach. For pancreatic cysts specifically, endoscopic ultrasound-guided fine-needle aspiration has become a diagnostic tool for distinguishing benign, potentially malignant, and malignant lesions; through-the-needle cytologic brushes have been developed to increase the cellular content of those aspirates.

  Bone marrow biopsy addresses blood diseases that cannot be diagnosed from a peripheral blood sample alone. In leukemia and lymphoma, it plays a role in staging the disease. The procedure uses a trephine to take a core of trabecular bone and then aspirates material. For transplanted organs, biopsies are used to confirm that rejection is not occurring and that the disease requiring the transplant has not returned.

• 6. Blood as the New Biopsy

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  Liquid biopsy is the name given to two blood-based tests that track cancer without cutting into tissue at all. One analyzes circulating tumor cells; the other targets cell-free circulating tumor DNA. The source is clear that liquid biopsy is not truly a biopsy in the traditional sense, because no tissue is removed.

  Cell-free DNA holds a practical advantage over circulating tumor cell assays: there is approximately one hundred times more cell-free DNA in the bloodstream than there is DNA inside circulating tumor cells. Companies including Personal Genome Diagnostics and Guardant Health offer next-generation sequencing tests based on cell-free DNA. Those tests moved into wider use particularly when a tissue biopsy provides insufficient material for DNA analysis or when an invasive procedure would not be safe.

  A 2014 study drew on blood from 846 patients with 15 different types of cancer across 24 institutions. Tumor DNA was detected in more than 80 percent of patients with metastatic cancers and in about 47 percent of those with localized tumors. The test produced no false positives. A related application looks at patients whose tumors have already been surgically removed; up to 30 percent of such patients are expected to relapse because some tumor cells remain, and initial studies using these tests identified about half the patients who later relapsed, again without false positives. The circulating tumor cell tests available through a company called maintrac are not yet covered by insurance.

• 7. Why Tissue Alone Is Not Enough

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  Cancer is a heterogeneous genetic disease. A single excisional biopsy captures only a snapshot of a tumor at one moment in time, and tumors change rapidly. Liquid biopsy offers something tissue biopsy cannot: the ability to detect, quantify, and characterize circulating tumor cells or genomic alterations continuously, giving real-time information on tumor progression, treatment effectiveness, and the risk of metastasis.

  Many newer cancer medications work by blocking specific molecular processes. Tracking the exact DNA mutations driving a particular tumor could allow therapy to be targeted with greater precision, and a blood test repeated over time makes that kind of ongoing surveillance possible.

  For inflammatory bowel disease, including Crohn's disease and ulcerative colitis, biopsies are taken frequently not just to measure current disease activity but to detect changes that precede malignancy. For vasculitis, biopsy of the temporal arteries is often the procedure that confirms the diagnosis. In the case of amyloidosis, where degraded proteins accumulate in body tissues, gingival tissue is one of the sites selectively biopsied because of how easily it can be accessed. The range of conditions that depend on biopsy for diagnosis or monitoring continues to expand, and the double-balloon technique that opened up the small intestine represents only one step in that ongoing extension of reach.