Cancerous ‘floater’: a lesson learned about tissue identity testing, endometrial cancer and microsatellite instability

Abstract

A 46-year-old woman presented with endometrial cells on a pap smear and underwent endometrial curettage. The specimen revealed secretory endometrium and a possible endometrial polyp. In addition, a single 4 mm fragment of well-differentiated adenocarcinoma was found. Tissue identity DNA genotyping was performed and the adenocarcinoma tissue fragment showed a drastically different allelic pattern from that of the background endometrium. To confirm tissue contamination, genotyping of three other tumor specimens-probable sources for a contaminant-was performed but failed to identify a match. Without confirmation of contamination, a second endometrial curettage was obtained from the patient, in which similar adenocarcinoma tissue was once again found. Further workup demonstrated that the patient had a microsatellite unstable (MSI) endometrial adenocarcinoma by immunohistochemistry and molecular testing. The patient subsequently underwent staging surgery, which revealed an early-stage, well-differentiated endometrioid adenocarcinoma. This case study illustrates an uncommon, yet important caveat of tissue identity testing by DNA genotyping, where MSI instability can significantly alter the allelic pattern of DNA polymorphisms in the tumor genome, leading to erroneous conclusion regarding the tissue identity. Awareness of this phenomenon is crucial for a molecular pathologist to avoid interpretation errors of tissue identity testing in a cancer diagnostic workup.

The feasibility of detecting endometrial and ovarian cancer using DNA methylation biomarkers in cervical scrapings

“…Indeed, psammoma bodies of OC can be detected in cytology in 0%–27% of OC patients, depending on the series [ 31 ], indicating that OC tissue can migrate through the endometrial cavity and cervix where it can be collected by Pap smear [ 32 ]. A high incidence of abnormal cervical cytology was also observed in women with high-grade EC, a lesson learned about “cancerous floater” [ 33 34 ]. In addition to the mechanical aspect, frequent changes in DNA methylation showed evidence of an extensive field effect in breast cancer and methylation was also frequently found in histologically ‘normal’ cervical tissues adjacent to cancer lesions [ 35 36 ].…”

Cost-Effective Next Generation Sequencing-Based STR Typing with Improved Analysis of Minor, Degraded and Inhibitor-Containing DNA Samples

“…Other biomedical applications of NGS-based STR analysis might comprise the authentication of tissue specimens in clinical laboratory testing [ 41 , 42 ], in particular in conjunction with molecular diagnosis based on NGS [ 43 ]. Moreover, the maSTR assay might be used for cell line authentication in biomedical research [ 44 ].…”

Successful Identification of a Neoplastic Tissue Contaminant in Surgical Pathology

“…[3][4][5][6] Currently, molecular genetic fingerprinting techniques are commonly used to resolve issues of tissue specimen identity. [7][8][9][10][11][12] Benign mucosal biopsy contaminants (eg, 1 fragment of benign duodenum with multiple fragments of squamous mucosa in a specimen labeled "esophagus") can occur and are presumed to represent contamination during the biopsy procedure. If the contaminating tissue is benign or otherwise without pathologic abnormality, a diagnosis can be rendered; however, there still may be value in investigating the source of these contaminants.…”

“…Other methods of determining tissue identity include immunohistochemical testing of blood cell antigens, human leukocyte antigen genotyping, and recently a digital pathology solution using an image search tool database 3–6 . Currently, molecular genetic fingerprinting techniques are commonly used to resolve issues of tissue specimen identity 7–12 …”