The Biopsy Report: A Patient's Guide
Ed Uthman, MD (uthman@neosoft.com)

Diplomate, American Board of Pathology
12 Nov 1997

INTRODUCTION

Many medical conditions, including all cases of cancer, must be diagnosed by removing a sample of tissue from the patient and sending it to a pathologist for examination. This procedure is called a biopsy, a Greek-derived word that may be loosely translated as "view of the living". Any organ in the body can be biopsied using a variety of techniques, some of which require major surgery (e.g., staging splenectomy for Hodgkin's disease), while others do not even require local anesthesia (e.g., fine needle aspiration biopsy of thyroid, breast, lung, liver, etc). After the biopsy specimen is obtained by the doctor, it is sent for examination to another doctor, the anatomical pathologist, who prepares a written report with information designed to help the primary doctor manage the patient's condition properly.

The pathologist is a physician specializing in rendering medical diagnoses by examination of tissues and fluids removed from the body. To be a pathologist, a medical graduate (M.D. or D.O.) undertakes a five-year residency training program, after which he or she is eligible to take the examination given by the American Board of Pathology. On successful completion of this exam, the pathologist is"Board-certified." Almost all American pathologists practicing in JCAHO-accredited hospitals and in reputable commercial labs are either Board-certified or Board-eligible (a term that designates those who have recently completed residency but have not yet passed the exam). There is no qualitative difference between M.D.-pathologists and D.O.-pathologists, as both study in the same residency programs and take the same Board examinations. This part of procedure, the aspiration, is usually followed by the core biopsy, in which a slightly larger needle is used to extract core of bone. The calcium is removed from the bone to make it soft, the tissue is processed (see "Specimen Processing," below) and tissue sections are made. Even though the core biopsy procedure involves a bigger needle, it is usually less painful than the aspiration.

SPECIMEN PROCESSING

After the specimen is removed from the patient, it is processed in one or both of two major ways:

  1. Histologic sections. This involves preparation of stained, thin (less than 5 micrometers, or 0.005 millimeters) slices mounted on a glass slide, under a very thin pane of glass called a coverslip. There are two major techniques for preparation of histologic sections:

    • a. Permanent sections. This technique gives the best quality of specimen for examination, at the expense of time. The fresh specimen is immersed in a fluid called a fixative for several hours (the necessary time dependent on the size of the specimen). The fixative, typically formalin (a 10%solution of formaldehyde gas in buffered water), causes the proteins in the cells to denature and become hard and "fixed". Adequate fixation is probably the most important technical aspect of biopsy processing.

      The fixed specimen is then placed in a machine that automatically goes through an elaborate overnight cycle that removes all the water from the specimen and replaces it with paraffin wax. The next morning, a technical professional, called a histologic technician, or "histotech," removes the paraffin-impregnated specimen and "embeds" it in a larger bloc of molten paraffin. This is allowed to solidify by chilling and is set in a cutting machine, called a microtome. The histotech uses the microtome to cut thin sections of the paraffin block containing the biopsy specimen. These delicate sections are floated out on a waterbath and picked up on a glass slide.

      The the paraffin is dissolved from the tissue on the slide. With a series of solvents, water is restored to the sections, and they are stained in a mixture of dyes. The most common dyes used are hematoxylin, a natural product of the heartwood of the logwood tree, Haematoxyloncampechianum, which is native to Central America, and eosin, an artifcial aniline dye. The stain combination, casually referred to by pathologists as "H and E" yields pink, orange, and blue sections that make it easier for us to distinguish different parts of cells. Typically, the nucleus of cells stains dark blue, while the cytoplasm stains pink or orange.

    • b. Frozen sections. This technique allows one to examine histologic sections within a few minutes of removing the specimen from the patient, but the price paid is that the quality of the sections is not nearly as good as those of the permanent section. Still, a skilled pathologist and a knowledgeable surgeon can work together to use the frozen section's rapid availability to the patient's great benefit.


  2. Smears. The specimen is a liquid, or small solid chunks suspended in liquid. This material is smeared on a microscope slide and is either allowed to dry in air or is"fixed" by spraying or immersion in a liquid. The fixed smears are then stained, coverslipped, and examined under the microscope.

    Like the frozen section, smear preparations can be examined within a few minutes of the time the biopsy was obtained. This is especially useful in FNA procedures (see above), in which a radiologist is using ultrasound or CT scan to find the area to be biopsied. He or she can make one "pass" with the needle and immediately give the specimen to the pathologist, who can within a few minutes determine if a diagnostic specimen was obtained. The procedure can be terminated at that point, sparing the patient the discomfort and inconvenience of repeated sticks.

PATHOLOGIC EXAMINATION

A. THE GROSS DESCRIPTION

The pathologist begins the examination of the specimen by dictating a description of the specimen as it looks to the naked eye. This is the "gross exam" or the "gross." Some pathologists may refer to the gross exam as the"macroscopic." Most biopsies are small, nondescript bits of tissue, so the gross description is brief and serves mostly as a way to code which biopsy came from what area and to use for troubleshooting if there is a question of specimen mislabeling. A typical gross description of an endoscopic colon biopsy follows:
"Polyp of sigmoid colon." An ovoid, smooth- surfaced, firm, pale tan nodule, measuring 0.6 x 0.4 x 0.3 cm. Cassette 'A', all, bisected.

In the above example, the first item (in quotes) is an exact recitation of how the specimen was labeled by the doctor who took the biopsy. After that is a textual description of what the specimen looked like, followed by measurements indicating its size. The "Cassette 'A', all,bisected" phrase indicates that the specimen was cut in half ("bisected"), submitted for tissue processing in its entirety ("all") in a small container (cassette) labeled"A," which will eventually be placed in the tissue processor.

Larger organs removed as biopsies have correspondingly longer and more detailed gross descriptions. The following is the gross description of a spleen removed to assess whether Hodgkin's disease (a cancer of lymph tissues) has spread into it:

"Spleen". An entire spleen, weighing 127 grams, and measuring 13.0 x 4.1 x 9.2 cm. The external surface is smooth, leathery, homogeneous, and dark purplish-brown. There are no defects in the capsule. The blood vessels of the hilum of the spleen are patent, with no thrombi or other abnormalities. The hilar soft tissues contain a single, ovoid, 1.2-cm lymph node with a dark grey cut surface and no focal lesions
On section of the spleen at 2 to 3 mm intervals, there are three well-defined pale-grey nodules on the cut surface, ranging from 0.5 to 1.1 cm in greatest dimension. The remainder of the cut surface is homogeneous, dark purple, and firm.
Summary of cassettes: 1, hilar blood vessels; 2, hilar lymph node, entirely submitted; 3 - 6 spleen nodules, entirely submitted; 7 - 8, spleen, away from nodules.

In the spleen described above, the pathologist found a few lumps (nodules), representing the most important data in this gross examination. These possibly represent the tumors of Hodgkin's disease, subject to confirmation by the microscopic examination. Much of the remainder of the verbage relates to "pertinent negatives," or things that were routinely looked for but not found, such as a rupture of the spleen capsule (suggesting an intraoperative accident), blood clots ("thrombi") in the vessels supplying the spleen, and evidence of an infection (in which case the cut surface of the spleen would be soft instead of firm). In addition, a lymph node was serendipitously found adherent to the spleen, and this was briefly described as having anormal appearance.

The last paragraph of the gross description gives the identifying "codes" of the slices of the specimen submitted for microscopic examination in cassettes. The microscope slides prepared from the processed samples will be labeled with the same numbers as the cassettes, and the pathologist doing the microscopic examination can, by referring to the typed gross description, know from what part of the specimen the tissue on the slide came.

B. THE MICROSCOPIC EXAMINATION

The microscopic description, or the "micro" is a narrative description of the findings gained from examination of the glass slides under the microscope. The micro is considered somewhat "optional" in a written report.In such a case, the diagnosis (see below) is considered to speak for itself. Here is a the microscopic description on the report of the colon biopsy given above:
Specimen A: The sections show a polypoid structure consisting of a central fibrovascular core, surrounded by a mantle of mucosa showing an adenomatous architecture with a predominantly tubular pattern. The tubules are lined by tall columnar epithelium showing nuclear pseudostratification, hyperchromasia, increased mitotic activity, and loss of cytoplasmic mucin. There in no evidence of stromal invasion.
It can be readily seen that the language of microscopyis much more arcane than that used for gross descriptions. It is way beyond the scope of this monograph to cover the nuances of descriptive microscopic pathology. In general,microscopic descriptions are communications between pathologists for referral and quality assurances purposes.

C. THE DIAGNOSIS

This is analogous to the "bottom line" of a financial report. The purpose of the gross examination, the processing of the tissue, and the microscopic examination is to build alogical argument toward a terse assessment of what significance the biopsy has in regard to the patient'shealth. Here is the diagnosis for the colon biopsy, above:
Colon, sigmoid, endoscopic biopsy: tubular adenoma (adenomatous polyp)

This format is widely used, but variations occur. The first term is the organ or tissue involved ("colon"). The second term ("sigmoid") specifies the site in the colon from which the biopsy was obtained. The next term ("endoscopicbiopsy") denotes the type of surgical procedure used in obtaining the biopsy. Then follows the diagnosis proper, in this case "tubular adenoma," a common benign tumor of the large intestine and rectum, which increases the risk for developing colorectal cancer in the future. In this particular case, an older synonym for tubular adenoma,"adenomatous polyp," follows in parentheses.

Note: Please send all constructive comments regarding this FAQ to Ed Uthman, MD

This article is provided as is without any express or implied warranties. While every effort has been taken to ensure the accuracy of th einformation, the author assumes no responsibility for errors or omissions, or for damages resulting from use of the information herein.

Copyright (c) 1994-96, Edward O. Uthman. This material may be reformatted and/or freely distributed via online services or other media, as long as it is not substantively altered. Authors, educators, and others are welcome to use any ideas presented herein, but I would ask for acknowledgment in any published work derived therefrom.

version 1.2W, 11/12/97