—  AMERICAN SOCIETY FOR CLINICAL PATHOLOGY   —

Assessment Exercise #1: The Differential Diagnosis of Artifacts in Gastrointestinal Biopsies


Henry D. Appelman
University of Michigan
Ann Arbor, MI


The Differential Diagnosis of Artifacts in Biopsies of the Gastrointestinal Tract

What is an artifact?

Houghton-Mifflin Dictionary on the Web, 2004:

Artifact: a structure or feature not normally present but visible as a result of an external agent or action, such as one seen in a microscopic specimen after fixation, or in an image produced by radiology or electrocardiography.
An inaccurate observation, effect, or result, especially one resulting from the technology used in scientific investigation or from experimental error: The apparent pattern in the data was an artifact of the collection method.
A feature not normally present but visible as a result of an external agent or action, such as one seen in a microscopic specimen after fixation

This discussion deals with artifacts, i.e., features not normally
present but visible as a result of external agents or actions
in endoscopic biopsies of the gut.

There is a sequence of events involved in obtaining and processing a gut biopsy, and these events may act as the external agents or actions mentioned above and alter the microscopic appearance of the tissue…

These events occur:

Before endoscopy
During endoscopy
During processing

Some of these artifacts mimic real histologic changes in disease, so they have a differential diagnosis. We have to determine if the biopsy changes are those of true disease, or if they are artifacts.

Differential Diagnosis #1

1. Disease
2. Artifact

Thought to be infectious for years, until…

They were observed to be peculiarly common in intraoperative, rather than percutaneous biopsies.

Figure 1 - Neutrophil clusters in liver lobules, in bunches, that is, micro-abscesses


Some of these artifacts so distort the histologic features that they lead to issues of adequacy of biopsy: Do the artifacts prevent me from making a diagnosis; i.e., is the biopsy useless for diagnosis?

Differential Diagnosis #2

1. Sufficient for DX
2. Insufficient for DX

Before Endoscopy: The Preparation

Artifacts due to endoscopy preparations

Hypertonic enemas (flex sigs, colons in kids)
Oral phosphosoda (colons in adults)

Hypertonic enemas (flex sigmoids, colonoscopies in kids)

flattened surface epithelium
focal surface tufting
edema
clumpy superficial hemorrhage
flattened surface epithelium focal surface tufting, confused with type 1 lesion of PMC edema
clumpy superficial hemorrhage, confused with ischemic hemorrhage

  Figure 2 - Enema effect
Oral phosphosoda (colonsoscopies in adults):

pseudo and true aphthous lesions
apoptosis
focal acute cryptitis

  Figure 3 - Endoscopic aphthous ulcer-like changes due to oral phosphosoda
Focal acute inflammation may be an artifact that does not require diagnosis. Oral phosphosoda is the main culprit.   Figure 4 - Oral phosphosoda artifacts


Very Focal Acute Cryptitis/Pititis/Glanditis

Common in gastrointestinal biopsies that are otherwise completely normal.
More common in teaching hospitals: require pathology residents

During endoscopy: the endoscope itself

air insufflation
obtaining the biopsy
retrieving the biopsy

Air insufflation produces holes that mimic

  1. adipocytes

  2. lymphatics

Obtaining the biopsy


Forceps—congestion, hemorrhage, crushing, squeezing, denudation of surface epithelium
Cautery—frying

The forceps induced changes may mimic disease:

Squeezing may leave a lamina propria devoid of crypt epithelium, mimicking ischemic injury.
Squeezing of Brunner's glands leads to the appearance of extravasated mucin and occasional confusion with signet ring carcinoma or lipid storage or Whipples disease
Crushing of the base of gastric can produce cells that resemble signet ring carcinoma cells.

Cautery artifact:

Sometimes helpful, as when it marks the margin of resection of an adenoma with invasive carcinoma.
Sometimes not helpful, as when

  1. An adenoma with carcinoma is removed piecemeal using cautery. Many pieces are cauterized, preventing identification of the margin of the entire lesion.

  2. An entire polyp is cauterized, thus preventing diagnosis

During processing: our fault

Artifacts that are our fault:

Everything that we see on a microscopic slide is the result of a series of artifacts.
We depend on the reproducibility of these artifacts in order to make diagnostic decisions.
Fixation clots the proteins
Dehydration takes out the water
Organic solvents like xylene dissolve the lipids so we can't see them
Paraffin: since when is that a part of normal anatomy?
Then the paraffin-filled tissue is cut really thin so it will transmit light.
Hematoxylin? Eosin? Totally unnatural

Tisssue preparation artifacts infrequently lead to changes that mimic diseases. A few examples:

Different fixatives lead to different nuclear details: we all get used to our own fixatives
Peculiar bias cuts of small intestine can produce areas that look avillous (flat)
Tissue cut too thickly, leading to a false impression of dysplasia

Many of these agents damage the tissue so severely that diagnosis is impossible.

Forceps: Squeezing, crushing, stripping of surface epithelium
Cautery
Inadequate fixation: dessicated
Shredding during cutting
Poor staining

Summary
Trying to diagnose diseases in GI biopsies is tough enough, but we also have to overcome artifacts, which make things even tougher.

References

  1. Driman DK, Preiksaitis HG: Colorectal inflammation and increased cell proliferation associated with oral sodium phosphate bowel preparation solution. Hum Pathol. 29:972-978, 1998

  2. Faigel DO, Furth EE, Bachwich DR. Aphthoid lesion of the rectum. Letter to the Editor. Gastrointestinal Endoscopy. 43:528-529, 1996. Documents the endoscopic aphthoid appearance of lymphoid follicles following oral phosphosoda.

  3. Jenkins D, Goodall A, Drew K, Scott BB. What is colitis? Statistical approach to distinguishing clinically important inflammatory change in rectal biopsy specimens. J Clin Pathol. 41:72-79, 1988

  4. Lee FD. Importance of apoptosis in the histopathology of drug related lesions in the large intestine. J Clin Pathol. 46:118-122, 1993

  5. Meisel JL, Bergman D, Graney D, Daunders DR, Rubin CE. Human rectal mucosa: proctoscopic and morphological changes caused by laxatives. Gastroenterol. 72:1274-1279, 1977

  6. Pockros PJ, Foroozan P. Golytely lavage versus a standard colonoscopy preparation. Effect on normal colonic mucosal histology. Gastroenterol. 88:545-548, 1985.

  7. Snover DC, Sandstad J, Hutton S. Mucosal pseudolipomatosis of the colon. Am J Clin Pathol. 84:575-580, 1985