Biopsy

The term biopsy reflects the Greek words βίος bios, "life," and ὄψις opsis, "a sight."[2]

The French dermatologist Ernest Besnier introduced the word biopsie to the medical community in 1879.[3]

Lung biopsy in a case of suspected lung cancer under control of computed tomography.

When cancer is suspected, a variety of biopsy techniques can be applied. An excisional biopsy is an attempt to remove an entire lesion. When the specimen is evaluated, in addition to diagnosis, the amount of uninvolved tissue around the lesion, the surgical margin of the specimen is examined to see if the disease has spread beyond the area biopsied. "Clear margins" or "negative margins" means that no disease was found at the edges of the biopsy specimen. "Positive margins" means that disease was found, and a wider excision may be needed, depending on the diagnosis.

When intact removal is not indicated for a variety of reasons, a wedge of tissue may be taken in an incisional biopsy. In some cases, a sample can be collected by devices that "bite" a sample. A variety of sizes of needle can collect tissue in the lumen (core biopsy). Smaller diameter needles collect cells and cell clusters, fine needle aspiration biopsy.[4]

Pathologic examination of a biopsy can determine whether a lesion is benign or malignant, and can help differentiate between different types of cancer. In contrast to a biopsy that merely samples a lesion, a larger excisional specimen called a resection may come to a pathologist, typically from a surgeon attempting to eradicate a known lesion from a patient. For example, a pathologist would examine a mastectomy specimen, even if a previous nonexcisional breast biopsy had already established the diagnosis of breast cancer. Examination of the full mastectomy specimen would confirm the exact nature of the cancer (subclassification of tumor and histologic "grading") and reveal the extent of its spread (pathologic "staging").

There are two types of liquid biopsy (which is not really a biopsy as they are blood tests that do not require a biopsy of tissue): circulating tumor cell assays or cell-free circulating tumor DNA tests.[5] These methods provide a non-invasive alternative to repeat invasive biopsies to monitor cancer treatment,[6] test available drugs against the circulating tumor cells,[7] evaluate the mutations in cancer and plan individualized treatments. In addition, because cancer is a heterogeneous genetic disease, and excisional biopsies provide only a snapshot in time of some of the rapid, dynamic genetic changes occurring in tumors, liquid biopsies provide some advantages over tissue biopsy-based genomic testing.[8] In addition, excisional biopsies are invasive, can’t be used repeatedly, and are ineffective in understanding the dynamics of tumor progression and metastasis.[9][10] By detecting, quantifying and characterisation of vital circulating tumor cells or genomic alterations in CTCs and cell-free DNA in blood, liquid biopsy can provide real-time information on the stage of tumor progression, treatment effectiveness, and cancer metastasis risk.[11] This technological development could make it possible to diagnose and manage cancer from repeated blood tests rather than from a traditional biopsy.[11][12][13][14]

Circulating tumor cell tests are already available but not covered by insurance yet at maintrac and under development by many pharmaceutical companies. Those tests analyze circulating tumor cells (CTCs)[12][15] Analysis of individual CTCs demonstrated a high level of heterogeneity seen at the single cell level[16] for both protein expression and protein localization and the CTCs reflected both the primary biopsy and the changes seen in the metastatic sites.

Analysis of cell-free circulating tumor DNA (cfDNA) has an advantage over circulating tumor cells assays in that there is approximately 100 times more cell-free DNA than there is DNA in circulating tumor cells.[5] These tests analyze fragments of tumor-cell DNA that are continuously shed by tumors into the bloodstream. Companies offering cfDNA next generation sequencing testing include Personal Genome Diagnostics and Guardant Health.[8] These tests are moving into widespread use when a tissue biopsy has insufficient material for DNA testing or when it is not safe to do an invasive biopsy procedure, according to a recent report of results on over 15,000 advanced cancer patients sequenced with the Guardant Health test.[17]

A 2014 study of the blood of 846 patients with 15 different types of cancer in 24 institutions was able to detect the presence of cancer DNA in the body. They found tumor DNA in the blood of more than 80 percent of patients with metastatic cancers and about 47 percent of those with localized tumors. The test does not indicate the tumor site(s) or other information about the tumor. The test did not produce false positives.[18]

Such tests may also be useful to assess whether malignant cells remain in patients whose tumors have been surgically removed.[19] Up to 30 percent are expected to relapse because some tumor cells remain.[20] Initial studies identified about half the patients who later relapsed, again without false positives.[18]

Another potential use is to track the specific DNA mutations driving a tumor. Many new cancer medications block specific molecular processes. Such tests could allow easier targeting of therapy to tumor.[18]

For easily detected and accessed sites, any suspicious lesions may be assessed. Originally, this was skin or superficial masses. X-ray, then later CT, MRI, and ultrasound along with endoscopy extended the range.

A biopsy of the temporal arteries is often performed for suspected vasculitis. In inflammatory bowel disease (Crohn's disease and ulcerative colitis), frequent biopsies are taken to assess the activity of disease and to assess changes that precede malignancy.[21]

Biopsy specimens are often taken from part of a lesion when the cause of a disease is uncertain or its extent or exact character is in doubt. Vasculitis, for instance, is usually diagnosed on biopsy.

• Kidney disease: Biopsy and fluorescence microscopy are key in the diagnosis of alterations of renal function. The immunofluorescence plays vital role in the diagnosis of Crescentic glomerulonephritis.
• Infectious disease: Lymph node enlargement may be due to a variety of infectious or autoimmune diseases.
• Metabolic disease: Some conditions affect the whole body, but certain sites are selectively biopsied because they are easily accessed. Amyloidosis is a condition where degraded proteins accumulate in body tissues. In order to make the diagnosis, the gingival.
• Transplantation: Biopsies of transplanted organs are performed in order to determine that they are not being rejected or that the disease that necessitated transplant has not recurred.
• Fertility: A testicular biopsy is used for evaluating the fertility of men and find out the cause of a possible infertility, e.g. when sperm quality is low, but hormone levels still are within normal ranges.[22]