Originally published in CAP TODAY
From the files of the CAP’s checklist-related
questions. Answers reviewed by Stephen J. Sarewitz, MD, chair of the
Checklists Committee and staff pathologist, Valley Medical Center, Renton,
Q. As of Sept. 30, 2004, the guidelines for
use of negative controls in the performance of immunohistochemistry
suggest a separate negative control for each block. Can our small tissue
lab, which is limited to skin specimens, perform automated batch runs of a
given antibody and use just one negative reagent control at the beginning
or end, or both, of each batch?
A. There are two types of negative
controls—negative tissue controls and negative reagent controls.
Negative tissue controls confirm the primary
antibody's specificity. For this, one would use one or more tissues known
to lack the target antigen—for example, a lab might use a leiomyoma and
neuroma as negative tissue controls for keratin. Absence of staining
confirms the specificity of the antibody. For negative tissue controls, it
is appropriate to use one slide per batch staining run. The same holds
true for positive tissue controls. The patient test slide, or the positive
control, can serve as the negative tissue control if either contains
cellular elements not expected to stain with the antibody. Best practice
is the use of multi-tissue blocks containing an appropriate variety of
control tissues as a combined positive and negative tissue control. Such
blocks can serve as a permanent record documenting the sensitivity and
specificity of every stain, particularly when mounted on the same slide as
the patient tissue.
The negative reagent control is a section of
patient tissue cut from the same paraffin block as the patient slide to be
immunostained. This section is subjected to the same steps in slide
preparation and staining, except application of the primary antibody. The
purpose of the negative re a gent control is to exclude the possibility
that some property of the patient tissue has caused nonspecific staining
with the detection system applied. Because each tissue block may be
different in this regard, there must be a negative reagent control slide
for each paraffin block that is stained in the run. For example, if you
are examining a large congenital nevus with HMB-45 and you stain blocks
1A, 1B, and 1C, you must run a corresponding negative reagent control
slide for each of those three blocks.
Q. For which immunohistochemical reagents
is the medical director allowed to extend the outdate?
A. The laboratory must follow the manufacturer's
recommendations for shelf life, storage, and use of materials.
The Federal Register prohibits the use of expired
materials. The laboratory can refer to the Jan. 24, 2003, Federal Register
(7164 [42CFR493.1252(d)] for more information. The federal regulations are
also available at www.phppo.cdc.gov/clia/regs/toc.aspx.
The only exception to this federal regulation is
in blood banking with rare antisera, where the anti sera may be used
beyond the expiration date, but only after stringent quality control
demonstrates that the material is still performing properly.
Q. We were recently inspected and asked
to implement a quality management program. Can you tell me specifically
what the CAP inspector is asking for? We check Pap results with biopsy
specimens and watch for more than one-step differences with Paps and
A. The CAP does not provide detailed requirements
and guidelines for a quality improvement plan in cytopathology because a
program can be designed a variety of ways, which are left to the
discretion of the individual laboratory. The suggestions presented in the
general chapters of the CAP Quality Improvement Manual in Anatomic
Pathology, including chapters two and three, apply to cytology.
Furthermore, a sample of a cytopathology quality improvement plan is
provided in the cytopathology chapter, page 95 of the second edition
In brief, the laboratory should monitor quality
indicators to look for trends or problems. Quality indicators include such
data as turnaround time, ASC/SIL (atypical squamous cells/squamous
intraepithelial lesions) ratio, 10 percent quality control rescreening
data, cytotechnologist-cyto pa thol ogist correlation, overall laboratory
abnormal rates, comparison of the percentage of each diagnostic category
reported by each screener with the overall laboratory percentage, and
several other parameters that are described in a variety of sources,
including the CAP checklist, CLIA regulations, and the aforementioned
quality improvement manual. It is useful to include comparisons with
national benchmark data, such as abnormal rates for gynecological cytology
published in the CAP checklist and CAP interlaboratory comparison program.
The laboratory should follow trends in data, establish appropriate
thresholds, and take corrective action when a problem is identified. Other
elements of quality improvement can include continuing education
activities and other activities performed in the laboratory that improve
Whatever plan you devise, it is important to
document monitors, take corrective action when appropriate, and review the
plan periodically to determine if it needs to be updated.
Q. I am trying to interpret cytopathology
checklist question CYP.05316 and explain to one of our pathologists what
is expected and when his name should appear on the report. The pathologist
has been skeptical of our cytology department since he lost his own
cytologist in an acquisition. Therefore, he has asked our cytology
department to send him all negative slides for his group of clients before
releasing results. He claims he does not thoroughly rescreen negative Pap
tests. I think he randomly reviews slides to check the quality of work
performed by our cytologists. If he randomly, and sometimes less than
thoroughly, reviews slides, should his name appear on the report?
A. Yes, the pathologist's name should be on the
report in this situation. Recent litigation has raised awareness of this
issue and led to publication of the aforementioned checklist question as
well as articles in the literature. Basic requirements for signatures on
reports are straightforward and sensible. The report should clearly
identify all individuals who have reviewed the slides and should not
include the name or signature of anyone who has not reviewed the slides.
The term "review" may reflect different practices
by technical supervisors in different laboratories—for example, rapid
rescreen, complete rescreen, or other. However, looking at a slide prior
to release of the report should clearly be considered review of the case
and would require the name of the physician reviewer on the report.
Retrospective review after the report has been sent would not require the
name of the reviewer on the report.
The CAP cytopathology checklist requires that a
pathologist review all cases with reactive or reparative changes, atypical
cells, cells indicative of a squamous intraepithelial lesion, and cells
suspicious for or diagnostic of malignancy, and that the name or signature
of the reviewing pathologist be clearly identified on the report. The
cytology records should also clearly indicate others who have reviewed the
slides. Cytotechnologists should be identifiable by name, initials, or
another identifier in laboratory records. Cytotechnologists' names are not
required but may be included in reports. It is important that a
pathologist's name or signature never appear with the diagnosis on
negative Pap reports unless he or she has personally reviewed the slides.
Legal issues remain for pathologists who have
their name on a report. If a Pap case comes to litigation, they will
likely be named in the suit. Although the medical director's name may
appear on the report, it should not be associated with the diagnosis
unless the director evaluated the case. The medical director's name must
be clearly differentiated from the name of those who reviewed the slides.
For more information on this subject, see the CAP
TODAY article "Whose name should go on this report anyway? Protecting
ourselves and our practices in the current legal environment" (Neal MH.
Q. I am working on a request from a
pathologist regarding benchmarking for histology technical staff. Is there
any data, resource, or other tidbit of information that may be helpful?
A. No information is available at this time;
however, a joint pilot study program is being developed by the National
Society for Histotechnology and the CAP to collect and study such data for
Dr. Sarewitz is LAP checklist commissioner and staff
pathology, Valley Medical Center, Renton, Washinton.