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Updated: Oct 10, 2026

Multiplexed Fluorescent Immunohistochemical Staining of Four Endometrial Immune Cell Types in Recurrent Miscarriage
Published on: August 4, 2021
Chronic histiocytic intervillositis: a placental lesion associated with recurrent reproductive loss
1Department of Pathology, Baystate Medical Center, Springfield, MA, USA.
Insights
Chronic histiocytic intervillositis (CHIV) is an uncommon cause of recurrent spontaneous abortion and later pregnancy loss. This condition, characterized by histiocytic infiltration, has a high recurrence rate and poor perinatal outcomes.
Area of Science:
- Reproductive Medicine
- Pathology
- Immunology
Background:
- Chronic histiocytic intervillositis (CHIV) is an idiopathic placental lesion.
- It is identified in spontaneous abortion and placenta specimens.
- CHIV involves diffuse histiocytic infiltration of the intervillous space without villitis.
Purpose of the Study:
- To evaluate patients diagnosed with CHIV.
- To assess histopathology, leukocyte phenotype, perinatal outcomes, and clinical features.
- To determine the significance of CHIV in pregnancy complications.
Main Methods:
- Retrospective study of CHIV cases from 1977 to 2000.
- Review of clinical records and pathology specimens.
- Immunohistochemical staining for leukocyte phenotyping.
Main Results:
- CHIV identified in 31 of 45 specimens from 21 patients.
- Recurrence rate was 67%.
- Perinatal mortality was 77%; 18% of pregnancies reached 37 weeks.
- Severe intrauterine growth restriction observed in later trimesters.
- Infiltrate predominantly monocyte-macrophages (CD45Rb+, CD68+).
Conclusions:
- CHIV is an uncommon but significant cause of recurrent spontaneous abortion.
- It can also lead to pregnancy loss at later gestational ages.
- CHIV is characterized by a monocyte-macrophage infiltrate.
Abstract:
Chronic (histiocytic) intervillositis (CHIV), defined for the purposes of this study as diffuse histiocytic infiltration of the intervillous space without villitis, is an idiopathic lesion seen in the chorionic sacs of some spontaneous abortion specimens and placentas. In this retrospective study, we evaluated all patients diagnosed with CHIV from 2 hospitals between 1993 and 2000, plus 1 additional patient from 1977. Histopathology, phenotype of the leukocytic infiltrate, perinatal outcome, and other associated clinical features were assessed by review of clinical records and all available pathology specimens plus immunohistochemical staining. CHIV was found in 31 of 45 specimens examined from 21 patients (23 of 31 first trimester, 3 of 5 second trimester, and 5 of 9 third trimester). Recurrence rate was 67% for patients with more than one specimen reviewed. Overall perinatal mortality rate was 77%, and only 18% of pregnancies reached 37 weeks. Eight of 19 patients with 3 or more pregnancies had recurrent spontaneous abortion (RSA); 5 with primary RSA (> or = 3 consecutive spontaneous abortions (SAB) with no living children) and 3 with secondary RSA (> or = 3 consecutive SAB with 1 or more living children). Severe intrauterine growth restriction was seen in 5 of 8 second- and third-trimester placentas with CHIV. Patients were generally not of advanced maternal age (mean, 29.8 +/- 6.2 years), and there was no obvious racial predisposition. Autoimmune or allergic phenomena were identified in 11 patients. Immunohistochemical staining of the intervillous infiltrate showed a near uniform population of monocyte-macrophages at varying stages of maturity and activation: more than 90% CD45Rb and CD68 positive, 30% to 40% MAC387 positive, less than 5% CD3 positive, and CD1a, CD20, CD30, and CD56 negative. We conclude that CHIV is an uncommon but important cause of recurrent spontaneous abortion and, in some cases, loss at later gestational ages. HUM PATHOL 31:1389-1396.
