Conflicting pathology reports: a diagnostic dilemma

Abstract

Short tandem repeat (STR) analysis is a polymerase chain reaction (PCR)-based technology that is based on typing highly polymorphic repeats of 2-6 base pairs of DNA. Typically these repeats are inherited in codominant mode, so that the number of repeats in each allele is independently determined. Such analysis enables the identification of loss of heterozygosity (LOH) or a shift in a genetic region, and reveals whether two cell populations are genetically "similar" or different.2 Emerging first as a DNA identity tool in the forensic setting, several clinical diagnostic uses for STR typing have already been established: for example, follow-up of engraftment after bone marrow transplantation; identification of uniparental disomy pattern of inheritance; and assessment of maternal cell contamination in prenatal specimens. 13 The authors report a case in which STR typing was used to resolve a diagnostic dilemma involving two discrepant specimens from a patient with a brain tumor. case report History and ExaminationA 47-year-old, right-handed man presented to the emergency center with a 2-day history of progressive right leg weakness. His medical history was significant for heavy smoking of 40 pack-years. His physical examination findings were remarkable for right lower-extremity weakness and mild upper-limb dysmetria. However, findings on chest radiographs were unremarkable, and brain MRI studies obtained with contrast revealed two separate ring-enhancing lesions localized to the left frontal lobe (Fig. 1). The radiological differential diagnosis included multiple brain metastases, multicentric glioblastoma, lymphoma, or, less likely, brain abscesses. A stereotactic biopsy sample taken from the left frontal anterior lesion was most compatible with metastatic small cell carcinoma with neuroendocrine features ( Fig. 2A and B). At that time the working diagnosis, based on the history of heavy smoking, multiple brain lesions on MRI studies, and the pathology report was that of metastatic small cell lung carcinoma. Ten days after his initial presentation, the patient presented to the emergency center complaining of worsening right leg weakness, headaches, and blurred vision, and was admitted for urgent radiation treatment. Radiation Treatment and Subsequent OperationA chest CT scan performed at the time of admission abbreviatioNs LOH = loss of heterozygosity; PCR = polymerase chain reaction; STR = short tandem repeat. The differential diagnosis of a brain lesion with two discordant pathology reports includes the presence of collision tumor, metaplastic changes, and labeling errors that occurred during the processing of the specimen. The authors present a case in which the first brain biopsy from a 47-year-old patient with a history of heavy smoking was compatible with metastatic small cell carcinoma, and the second biopsy taken during decompression craniotomy 3 weeks later was compatible with WHO Grade IV glioblastoma. Using short tandem repeat (STR) analysis of the two specimens and nontumorderived patient DNA, the autho...

Patient Safety Issues in Pathology: From Mislabeled Specimens to Interpretation Errors

“…Implementation of safety measures such as open communication with the patient and formalized checklists incorporated in transfer of information/specimens from the operating room to the laboratory and vice versa have shown significant efficacy in reducing labeling errors (as in aviation) [23]. Root cause analysis performed in CV1 ultimately determined that the error occurred during the initial specimen processing stage due to a clerical mistake [16].…”

“…Shahar et al [16] described a 47-year-old man who presented to the emergency room after reports of progressive right lower extremity weakness. Relevant history included 40-packyear of tobacco abuse as well as upper-limb dysmetria.…”

Editorial: Errors in the pathology laboratory

“…The latter is most useful when contaminant tissue is present in the paraffin block, so residual tissues may be available for molecular probing. Molecular DNA fingerprinting for tissue and sample identity, as used in the case reported by Dr. Shahar and colleagues, 11 has been critical for this type of analysis. 4,12 A final step in preventing errors is safety measures at the postanalytical phase involving the interpretation of a pathology report in view of the clinical presentation and other laboratory data by the pathologist and the clinical team.…”