Q&A column

Editor: Frederick L. Kiechle, MD, PhD

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Q. A semen analysis for viability was collected at 9:30 AM and not received in the laboratory until 1:40 PM. Our standard operating procedure says this test must be analyzed one hour after collection, with no disclaimers stated for late receivables. Therefore, it is my understanding that a specimen received five hours after collection would be considered unacceptable because the viability of the semen is compromised and the collection delivery does not follow our SOP. My supervisor advised accepting the specimen and putting a disclaimer on it: “The receipt time in lab was 1:40 PM. Test may be compromised.” This is not in the SOP. I feel this specimen should have been rejected and re-collected. This is not the first time this has occurred. Laboratory technicians put their name on the test with the disclaimer, not the supervisor.

A. The first issue is the laboratory has an SOP that states semen specimens “must be analyzed one hour after collection.” The specimen was collected at 9:30 AM and received at the lab at 1:40 PM. To test and report the specimen would be a deviation from the SOP. In short, the lab did not follow its standard operating procedure.

Second, it appears the lab is not following the current recommendations for semen analysis regarding sample collection. Per the WHO Laboratory Manual for the Examination and Processing of Human Semen, 5th ed., sections 2.2.5 and 2.2.6 recommend the semen sample be delivered to the laboratory within one hour of collection.

Third, the SOP should be updated to specifically address what to do in the event the specimen arrives in the laboratory outside of the allowable testing period.

Last, to help reduce the number of samples received out of stability, the lab should consider preparing an informational sheet or pamphlet to give to the patient that describes the allowable collection methods and time frame for return of the specimen to the laboratory. All aspects of semen analysis, including collection, should be standardized if the results are to provide valid, useful information.

World Health Organization. WHO Laboratory Manual for the Examination and Processing of Human Semen, 5th ed. Geneva: WHO Press; 2010.

Robert Saunders McGee Jr., MD, PhD
Medical Director, Global Anatomic Pathology/Histology
Covance Central Laboratory Services
Indianapolis
Member, CAP Reproductive Medicine Committee

Q. What is the PD-L1 immunohistochemistry combined positive score and how does it compare with the tumor proportion score?

A. On Sept. 22, 2017 the Food and Drug Administration granted accelerated approval to pembrolizumab (Keytruda) for patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma whose tumors express PD-L1 as determined by an FDA-approved test.¹

The approval was based on results of a phase two study (Keynote-059) that enrolled 259 patients with gastric or GEJ adenocarcinoma and showed an improved objective response rate in patients with tumors expressing PD-L1.^2,3 The FDA-approved PD-L1 test used in this study was the PD-L1 22C3 pharmDx (Dako) using the following combined positive score (CPS) formula, with PD-L1 expression defined as a CPS ≥ 1.

CPS is distinct from TPS. Both the combined positive score and the tumor proportion score (TPS) are FDA-approved IHC scoring systems for PD-L1 expression. However, the two scores apply to two different tumor types: CPS is used for gastric or GEJ adenocarcinoma, whereas TPS is used for non-small cell lung cancer. Additionally, TPS is defined as the percentage of viable tumor cells showing partial or complete membrane staining at any intensity; it does not consider staining in non-tumor cells.