NGC Q & A

May 2003
Q & A Feature

Q. 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
Tallahassee, Fla.
Member, CAP Cytopathology Committee

Q. 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 cases.

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 is stained.
• Use at least two staining setups and, while using one, filter the other so that a clean set is always available.
• Document each time the stains are filtered or changed. This will keep track of these steps to prevent cross-contamination and provide documentation during inspections.

The method 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.

Reference
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
Hartford Hospital
Hartford, Conn.
Member, CAP Cytopathology Committee