Q & A Feature
NGC Q & A
The former diagnostic categories of benign cellular changes
including reactive and reparative changes were eliminated from the
2001 Bethesda System. Please clarify what exactly is required for
inspection purposes regarding pathologist review of cytotechnologist-screened
slides in light of the Bethesda 2001 changes. Pap smears formerly
diagnosed as “benign cellular changes” are now placed
in the “negative for intraepithelial lesion or malignancy”
category of Bethesda 2001.
A. With Bethesda 2001 the category of “benign
cellular changes” was eliminated as a separate interpretation
and instead was incorporated into the interpretation of "negative
for intraepithelial lesion or malignancy" (Negative) as a
qualifier. This is similar to the specification of cases that are
negative and, for example, also have fungus or trichomonas. The
interpretation of reactive/reparative changes should continue to
be designated and therefore reviewed by the pathologist, when appropriate.
CLIA mandates pathologist review of all cases interpreted as showing
reactive or reparative changes, atypical squamous or glandular cells
of undetermined significance, dysplasia, cervical intraepithelial
neoplasia, squamous intraepithelial lesions, or malignancy, and
this requirement is reflected in the CAP cytopathology checklist.
The need for pathologist review of these cases is supported by the
literature and reflected in the Pap program statistics, which show
that cases of malignancy are not uncommonly misinterpreted as reactive/reparative.
This is compounded by the distracting inflammation, blood, and degeneration
often associated with malignant cases. For these reasons, a pathologist
must carefully examine these cases.
As an aside, the pathologist’s review of cases interpreted
by the cytotechnologist as reactive/repair is a billable event,
even if the final interpretation is negative for intraepithelial
lesion or malignancy.
Margaret H. Neal, MD
KWB Pathology Associates
Member, CAP Cytopathology Committee
Checklist question CYP.0440 asks the following: “Is there
a documented policy for ensuring that nongynecologic specimens with
a high potential for cross-contamination are processed and stained
separately from other specimens?” This question applies to
non-gyn specimens. Should it also apply to Paps? Would you recommend
staining Paps separately from non-gyn specimens?
A. CLIA ’88 requires that “effective measures are taken
to prevent cross-contamination between gynecologic and nongynecologic
specimens during the staining process” and that “nongynecologic
specimens that have a high potential for cross-contamination are
stained separately from other nongynecologic specimens, and the
stains are filtered or changed following staining.”1
The greatest potential for cross-contamination occurs when staining
very cellular nongynecologic specimens. Cross-contamination of gyn
specimens has not been a problem. Although Pap tests may be stained
together in batches, they should be stained separately from non-gyn
specimens to prevent their contamination by cellular, positive non-gyn
Laboratories can develop their own methods to prevent cross-contamination
of non-gyn specimens. Here are several possible methods:
- Use a rapid
stain, such as toluidine blue, to detect cellular cases. Filter
all stains after each cellular specimen is stained.
- Prepare cellular
body fluids by liquid-based methods, cytocentrifuge techniques,
or filter methods to obtain a thin, uniform layer of cells.
- Use a staining
sequence, staining paucicellular specimens before highly cellular
ones, filtering or changing solutions after staining a cellular
specimen. For example, stain clear CSF specimens first, followed
by more cellular specimens such as direct smears from sediment
of highly cellular specimens last (that is, highly cellular, positive
body fluids). Filter or change stains after each cellular sample
- Use at least
two staining setups and, while using one, filter the other so
that a clean set is always available.
each time the stains are filtered or changed. This will keep track
of these steps to prevent cross-contamination and provide documentation
or combination of methods chosen is at the discretion of the individual
laboratory. It should be described in a procedure manual and its
use should be documented.
1. Department of Health
and Human Services, Health Care Financing Administration. Clinical
Laboratory Improvement Amendments of 1988; final rule. Federal
Register. 1992(Feb. 28):7169 [42CFR493.1257(a)(1)].
Theresa M. Voytek, MD
Member, CAP Cytopathology Committee