Citrate platelet counts remain acceptable within CAP and CLIA frameworks when used for the correct indication (that is, suspicion of EDTA pseudothrombocytopenia) and fully validated as an LDT. They should not be routinely ordered or provided in parallel with EDTA counts when the EDTA measurement is clearly valid.
Daniel Dees, DCLS, MLS(ASCP)CM
Medical Director, Clinical Hematology
Brigham and Women’s Hospital
Instructor of Pathology
Harvard Medical School
Boston, Mass.
Member, CAP Hematology/Clinical Microscopy Committee
For more information about using sodium citrate tubes, see the answer provided by Dr. Dees in the September 2025 Q&A column.
We periodically republish answers to questions that remain relevant. The following question and answer was first published in November 2022. At that time, Dr. Parkash was a member of the CAP Surgical Pathology Committee.
Q. Is secretory change in endometrial hyperplasia acceptable in the absence of progestin therapy? What is the appropriate way to address an endometrial biopsy with secretory glandular changes and an increase in the gland-to-stroma ratio?
A. Secretory change superimposed on endometrial hyperplasia is well recognized, as are the challenges of making this diagnosis. Although secretory change is most commonly seen in the setting of progestin therapy for previously diagnosed endometrial hyperplasia, it may also be seen de novo due to the effect of progesterone, resulting from ovulation or pregnancy, on preexisting hyperplasia.
Glandular crowding in secretory endometrium is normal and is due to the glands coiling. The pattern of crowding is more or less uniform. Hyperplasia presents as a spatially distinct lesion with abnormal glandular crowding that is distinct from the background normal secretory endometrium.1,2 The glands show architectural abnormalities, such as dilation, crowding, and branching. Severe glandular abnormalities, such as confluent or cribriform growth and complex papillary patterns, indicate carcinoma. The secretory changes in hyperplasia are nonuniform, weak, and patchy. Pseudostratification is frequently present, if only focally. Mitotic activity may also be focal as progestins suppress proliferative activity.3
Two small studies suggest that the Ki-67 proliferative index may be useful for distinguishing normal secretory endometrium from hyperplastic endometrium with secretory changes.1,4 However, there is debate about how to best measure the Ki-67 index, and there is significant overlap in the Ki-67 proliferative index between secretory endometrium and non-atypical hyperplasia with secretory change.
I take a conservative approach to borderline cases by communicating the uncertainty of the diagnosis to the clinician and recommending resampling in six months. A small study involving patients who were diagnosed with simple hyperplasia with secretory change showed that virtually all patients demonstrated normal endometrium at six months or one year.5
- Truskinovsky AM, Lifschitz-Mercer B, Czernobilsky B. Hyperplasia and carcinoma in secretory endometrium: a diagnostic challenge. Int J Gynecol Pathol. 2014;33(2):107–113.
- Bell CD, Ostrezega E. The significance of secretory features and coincident hyperplastic changes in endometrial biopsy specimens. Hum Pathol. 1987;18(8):830–838.
- Deligdisch L. Hormonal pathology of the endometrium. Mod Pathol. 2000;13(3):285–294.
- Gurda GT, Baras AS, Kurman RJ. Ki-67 index as an ancillary tool in the differential diagnosis of proliferative endometrial lesions with secretory change. Int J Gynecol Pathol. 2014;33(2):114–119.
- Tresserra F, Lopez-Yarto M, Grases PJ, Ubeda A, Pascual MA, Labastida R. Endometrial hyperplasia with secretory changes. Gynecol Oncol. 2003;88(3):386–393.
Vinita Parkash, MBBS, MPH
Associate Clinical Professor of Pathology
Yale School of Medicine
Senior Research Scientist in Health Policy
Yale School of Public Health
New Haven, Conn.