Evaluation of CD38 and CD138 as Diagnostic Markers in the Pathologic Diagnosis of Chronic Endometritis

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Background:Chronic endometritis (CE) is a prevalent gynecological disorder and a major cause of female infertility. However, clearly defined clinical or histopathological diagnostic criteria for CE are still lacking. Immunohistochemical (IHC) staining targeting plasma cell markers CD38 and CD138 has shown potential for diagnosing CE, but quantitative standards for these markers have not been established. This study aimed to determine quantitative thresholds of CD38- and CD138-positive plasma cells for the pathological diagnosis of CE, using hysteroscopic diagnosis as a reference, and to validate these thresholds by analyzing marker expression changes before and after anti-inflammatory therapy.Methods:A total of 165 endometrial biopsy samples were collected from infertile women and subjected to IHC staining for CD38 and CD138. The number of CD38- and CD138-positive cells was counted in hotspot areas under a high-power field (HPF, 40 × 10 magnification). To determine optimal diagnostic criteria, we tested a series of quantitative thresholds [ranging from ≥1 to ≥10 positive cells/HPF] and analyzed the consistency between pathological diagnoses based on each threshold and hysteroscopic diagnoses. Additionally, 90 patients with CE who received anti-inflammatory therapy were included to compare CD38 and CD138 expression levels before and after treatment, and the negative conversion rate was calculated to verify the superiority of the identified thresholds. Results:(1) CD38 and CD138 showed no significant difference in plasma cell detection in endometrial tissue (p = 0.630), but their combined use improved clinical diagnostic concordance compared with single-marker staining. (2) When the diagnostic criterion was defined as an average of ≥5 CD38- and CD138-positive cells/HPF in hotspot areas, no significant difference was observed between pathological and hysteroscopic diagnoses (McNemar test, p = 0.233), with moderate consistency (Kappa = 0.422, p < 0.05). This threshold was optimal among all criteria tested. (3) The number of CD38- and CD138-positive cells decreased significantly after anti-inflammatory therapy in 90 patients (p < 0.001). Using an average of ≥4 CD38- and CD138-positive cells/HPF as the diagnostic criterion yielded the highest CE negative conversion rate after treatment, with a statistically higher rate than criteria 1–3 (p < 0.05), while no significant difference was observed among criteria 4–7.Conclusions:We recommend combined hysteroscopic and pathological diagnosis for CE in infertile women. IHC staining for CD38 and CD138 provides reliable plasma cell identification and serves as an adjunctive tool for CE diagnosis. This study identifies an average of ≥5 CD38- and CD138-positive cells/HPF in hotspot areas as the primary reference cutoff for CE histopathologic evaluation, with moderate consistency with hysteroscopy (Kappa = 0.422), and ≥4 positive cells/HPF as the secondary cutoff for monitoring treatment response, which showed the highest negative-conversion rate (78.9%). Tailored to the diagnostic and treatment needs of infertile women, these clinically validated hierarchical thresholds, when integrated with hysteroscopy and histopathology, enhance the accuracy of adjunctive CE auxiliary diagnosis, and provide a targeted reference for clinical decision-making in infertility management and treatment response evaluation.