Q. Should the bilirubin tablet test be used on all urine
submitted for urinalysis since it’s tenfold more sensitive than
the bilirubin dipstick test? Is this cost-effective or clinically
significant? Is it necessary to confirm all positive dipstick bilirubin
results with a tablet test?
A. Dipsticks are used to screen urine for a number
of potentially clinically significant substances. Dipsticks are
used because they have advantages over individual tablet tests:
These easy-to-use groups of tests provide complementary information
(for example, glucose and ketones in a diabetic), are performed
simultaneously, and the cost per individual screening test is low.
There is general agreement that a chemical urinalysis should include
screening tests for blood, protein, glucose, and white blood cells,
and that other tests should be included in the battery as clinically
appropriate. It is not considered essential to test routinely for
a substance just because that test is available or that the most
sensitive test available be used when performing a chemical urinalysis.
(For example, the standard protein dipstick test is less sensitive
than the microalbumin dipstick test yet it is far more commonly
On most strips where bilirubin dipstick testing is found, the
strip contains urobilinogen as a complementary test, and this combination
provides considerable additional utility that would not result from
tablet testing for bilirubin alone. The finding of bilirubin and
urobilinogen in the urine suggests hemolytic or primary hepatic
disease, whereas the finding of bilirubin alone suggests biliary
tree or upper intestinal obstruction. Most laboratory professionals
would endorse the use of a tablet test to confirm the bilirubin
dipstick test when the bilirubin alone is positive, as false positives
occur with some frequency (for example, they are associated with
some nonsteroidal antiinflammatory agents) and a good tablet test
exists. When bilirubin and urobilinogen are positive, the concern
over the presence of a substance (other than a grossly visible dye)
that causes a false-positive result in both tests is lower, and
some would advocate that recourse to serum tests (for example, a
liver panel) is a reasonable approach to further evaluating this
constellation of abnormal screening tests.
Always remember that the types of screening tests offered and
the approaches to further evaluations of positive screening tests
should fit the clinical context as defined by the laboratory medical
director in consultation with the participating medical staff.
Robert Novak, MD
Department of Pathology
Medical Center of Akron
Member, CAP Hematology/Clinical
Microscopy Resource Committee
Q. Besides its role
in diagnosing mesotheliomas, does the typing of mucins by histochemistry
(neutral versus acidic, sulfo- versus sialo-) have practical applications
in neoplastic surgical pathology?
A. The current role of mucin histochemistry in the
differential diagnosis of neoplasms is limited, as this function
has been assumed in large part by diagnostic immunohistochemistry.
Potential applications of mucin histochemistry include but are not
- Differentiating stromal and epithelial mucins. Stromal mucin
is positive with the colloidal iron (CI) and Alcian blue (AB)
stains and is removed by hyaluronidase digestion. Stromal mucin
is typically negative with the periodic acid-Schiff stain following
diastase digestion (PAS-D) and minimally mucicarmine positive.
In contrast, epithelial mucins are PAS-D and/or mucicarmine positive
and, when positive with the CI and AB stains, are hyaluronidase
resistant. This application is still used, albeit less frequently
today, when attempting to distinguish carcinoma from epithelial
mesothelioma. This technique can be applied also as an adjunct
to keratin immunohistochemistry in distinguishing carcinoma, particularly
sarcomatoid forms, and synovial sarcoma from other sarcomas with
epithelioid features; the latter exhibit only stromal mucin.
- Identifying glandular differentiation in adenocarcinoma. Documenting
of intracytoplasmic mucin is a rapid and cost-effective method
for establishing a diagnosis of adenocarcinoma. It is important
to remember, however, that epithelial neoplasms do not reproducibly
produce acid or neutral mucins. Therefore, identifying epithelial
mucin requires using two stains, singly or in combination, typically
PAS-D (neutral) and Alcian blue or mucicarmine (acid).
- Differentiating extraskeletal myxoid chondrosarcoma and chordoma
(Alcian blue and colloidal iron positive, hyaluronidase resistant)
from other myxoid neoplasms, particularly myxoid liposarcoma (AB/CI
positive, hyaluronidase sensitive).
- Differentiating chromophobe renal cell carcinoma from conventional
renal cell carcinoma and oncocytoma. This more recent, technically
difficult application requires use of the Hale’s technique with
careful attention to pH. Chromophobe renal cell carcinoma will
show a diffuse strong reaction with a characteristic reticular
pattern; the other neoplasms are characteristically negative or
focally positive with a granular or droplet-like pattern.
- Identifying high-risk gastric intestinal metaplasia (IM). Incomplete
intestinal metaplasia (types II and III) can be further subtyped
using the high iron diamine-Alcian blue (HID-AB) stain to identify
subsets of acid mucins. The HID-AB stains sialomucins blue and
sulfomucins brown-black. Using this stain, type III IM, in which
the columnar epithelial cells contain sulfomucins, can be differentiated
from type II IM, in which the columnar cells contain only blue-stained
sialomucins. Some, but not all, studies have shown that type III
is the form of IM seen most frequently in association with adenocarcinoma;
therefore, identifying this form may warrant close followup, additional
biopsies, or both. Recently, the presence of sulfomucins has been
associated with progression to adenocarcinoma in Barrett’s esophagus.
DeLellis RA, Faller GT. Cell and tissue staining methods. In: Silverberg
SS, ed. Principles and Practice of Surgical Pathology and Cytopathology.
3rd ed. New York, NY: Churchill Livingstone; 1997:43-62.
Shah KA, Deacon AJ, Dunscombe P, et al. Intestinal metaplasia
subtyping: evaluation of Gomori’s aldehyde fuchsin for routine diagnostic
use. Histopathology. 1997;31: 277-283.
Sheehan DC, Hrapchak BB. Theory and Practice of Histotechnology.
2nd ed. St. Louis, Mo.: C.V. Mosby; 1980.
Skinnider BF, Jones EC. Renal oncocytoma and chromophobe renal
cell carcinoma. A comparison of colloidal iron staining and electron
microscopy. Am J Clin Pathol. 1999;111:796-803.
Tickoo SK, Amin MB, Zarbo RJ. Colloidal iron staining in renal
epithelial neoplasms, including chromophobe renal cell carcinoma.
Emphasis on technique and patterns of staining. Am J Surg Pathol.
Torrado J, Ruiz B, Garay J, et al. Blood-group phenotypes, sulfomucins,
and Helicobacter pylori in Barrett’s esophagus. Am J Surg
Weiss SW, Goldblum JR. Enzinger and Weiss’s Soft Tissue Tumors.
4th ed. St. Louis, Mo.: C.V. Mosby; 2001.
W. Brown, MD
Core Histology Laboratory
Memorial Hermann Healthcare System
Member, CAP Surgical