Placental Site Reaction Research Articles

Histomorphological Analysis of Gestational Trophoblastic Disease Spectrum with Clinicopathological Correlation at a Teaching Hospital

Introduction: Clinically, all trophoblastic lesions are frequently combined under a broad spectrum of gestational trophoblastic diseases (GTDs) without the use of specific pathological terms. However, studies now demonstrate that various forms of GTDs demonstrate differences in etiology, histogenesis, morphology, and clinical behavior. Thus, the need for diagnostic histopathology of these lesions to distinguish gestational trophoblastic neoplasms from nonneoplastic lesions and molar pregnancies and also for early anticipation for early anticipation, risk category stratification, prognostication, management, and prediction of persistent GTD. Our study aimed to study the histomorphological patterns of various types of GTD with light microscopy and the pattern of occurrence of GTDs in relation to age, parity, and gestation. Materials and Methods: The present study was conducted in the department of pathology, from January 2020 to April 2022. All GTDs confirmed by histopathological examination by hematoxylin- and eosin-stained slides were included. Results: The spectrum of GTDs found in this study was seventy cases of hydatidiform mole (92.10%), three cases of exaggerated placental site (EPS) reaction (3.94%), and two cases of choriocarcinoma (2.63%) and one case (1.31%) of placental site trophoblastic tumor (PSTT). The most common presenting symptom was vaginal bleeding (93.42%). Conclusion: Hydatidiform mole forms the most common type of GTD with an incidence of complete moles more than partial moles. Histomorphological examination and analysis are helpful for confirmatory diagnosis. The most common clinical presentation of GTD was vaginal bleeding followed by amenorrhea. Emphasis on detailed descriptive morphological assessment can help in the histological distinction of benign lesions such as EPS reaction and placental site nodule and avert such cases from being erroneously diagnosed as neoplastic. The Ki-67 proliferation index helped in distinguishing the EPS reaction from neoplastic lesions such as PSTT which requires surgical intervention and chemotherapy.

Pathology of gestational trophoblastic disease (GTD)

Gestational trophoblastic disease (GTD) is subclassified into hydatidiform mole (HM), gestational trophoblastic tumours (GTT) and non-neoplastic trophoblastic lesions. HM, partial and complete, originate from villous trophoblast and are considered as preneoplastic conditions. The risk for the development of persistent GTD, mostly as invasive HM, ranges from 0.5% to 20%, which depends on the type of molar pregnancy. The risk of development of trophoblastic tumour after PHM is <0.5% and 2%-3% after CHM. GTT represent a spectrum of neoplasms that originates from the intermediate, largely extravillous, trophoblast and these include choriocarcinoma (CC), placental site trophoblastic tumour (PSTT), epithelioid trophoblastic tumour (ETT) and mixed trophoblastic tumour. Among tumour like conditions, exaggerated placental site reaction (EPSR) and placental site nodule (PSN) (s)/plaque (s) are included. The morphological appearances of HM can be mimicked by abnormal (non-molar) villous lesions, and similarly, GTT can be mimicked both by non-malignant tumour-like conditions and non-gestational tumours with trophoblastic differentiation, which add to the diagnostic dilemma of these rare conditions. GTT have a favourable prognosis and better response to specific chemotherapeutic regimens when compared with non-gestational malignant genital tract neoplasms. The correct diagnosis and classification of these rare conditions are therefore important. This article focusses on the morphological appearances, immunocytochemistry as an aid in the diagnosis and the changes in current WHO classification of GTDs (WHO 2020).

Spectrum of Pathological Lesions in Uterine Specimens with Focus on Gestational Trophoblastic Disease in Karachi

Background: The most common benign pathological lesion in women of reproductive age is uterine leiomyoma. Gestational trophoblastic disease includes tumors and tumor like lesions originating from trophoblastic tissue. The aim of this study was to find the spectrum of molar pregnancy and uterine pathologies focusing on gestational trophoblastic disease as no study has been done in the past few years. Methods: Endometrial and uterine specimens of patients (n=436) between the ages of 15-65 years were collected from a private hospital in Karachi from December 2018 to December 2019. This cross-sectional study was carried out by pathological diagnosis of patients’ samples under light microscopy using hematoxylin and eosin staining. Stratification was done about age and nature of specimen to control the effect modifiers. The post stratification Chi square test was applied and p value &lt;0.05 was considered significant. Results: Mean age of the patients was 36.1 years ±7.8. Total 436 uterine biopsies included 260(59.6%) hysterectomies, 56(12.8%) endometrial curetting’s, 117(26.8%) evacuation specimens and 3(0.7%) polypectomies. Common pathologies included 124(28.4%) leiomyomas, 61(14%) proliferative endometrium, 52(11.9%) adenomyosis and 32(7.3%) endometrial polyps. Gestational trophoblastic disease was seen in 9(2.06%). Seven (87.5%) were partial hydatidiform moles, one (12.5%) exaggerated placental site reaction and one choriocarcinoma. Mole was common between 26-30 years with mean age of 27.2 years and prevalence was 6/100 abortions. Conclusion: Leiomyoma was the commonest (28.4%) uterine pathology followed by proliferative endometrium (14.5%). However, endometrial stromal sarcoma and endometriosis were found 0.2% each. High prevalence of mole was seen in this study. Partial mole was most common and choriocarcinoma was least common. Keywords: Hydatidiform Mole; Pathology; Prevalence.

Exaggerated Placental Site Reaction Following a Term Pregnancy: A Case Report

Exaggerated Placental Site Reaction Following a Term Pregnancy: A Case Report

Exaggerated placental site reaction mimicking a trophoblastic tumor: a case report

Exaggerated placental site reaction mimicking a trophoblastic tumor: a case report

A case report of complete mole with co-existent exaggerated placental site reaction and review of the literature.

Exaggerated placental site (EPS) is defined as a non-neoplastic trophoblastic lesion, which intermediate trophoblasts infiltrate exaggeratedly into endometrium and myometrium. These lesions may occur following normal pregnancy, ectopic pregnancy, abortus or molar pregnancy. Herein we share a case of EPS detected after evacuation due to molar pregnancy. We also review the related literature, where only a few reports exist describing the clinical course, histopathology and differential diagnosis of EPS.

The Expression and Diagnostic Utility of p63 in the Female Genital Tract

p63 plays a key role in epithelial development in various organs, being expressed in myoepithelial cells and in basal cells of stratified epithelia. In the female genital tract, p63 is expressed in the basal and parabasal cells of mature cervical, vaginal and vulval squamous epithelium, and also in cervical reserve cells at the transformation zone and in immature metaplastic and atrophic cervical squamous epithelium. In this review, the diagnostic utility of p63 immunohistochemical staining in various pathologic scenarios within the female genital tract is discussed. Cervical microglandular hyperplasia is p63 positive with a characteristic subcolumnar location due to expression in reserve cells. There is increased expression in cervical intraepithelial neoplasia, in accordance with the degree of dysplasia. One of the most useful applications of p63 is in the evaluation of problematic cervical carcinomas; most squamous carcinomas exhibit diffuse nuclear immunoreactivity whereas most adenocarcinomas and neuroendocrine carcinomas are negative or focally positive. In conjunction with neuroendocrine markers, p63 is useful in distinguishing between a squamous carcinoma and a small cell or large cell neuroendocrine carcinoma. In the normal endometrium, a population of p63-positive cells is present which may act as a stem cell population and which is increased in various forms of metaplasia. Placental site nodule and epithelioid trophoblastic tumor (lesions derived from chorionic-type intermediate trophoblast) are usually p63 positive whereas placental site reaction and placental site trophoblastic tumor (lesions derived from implantation site intermediate trophoblast) are usually negative; thus, p63 may be useful in the diagnostic algorithm of trophoblastic lesions. p63 positivity in ovarian epithelial tumors is uncommon and largely restricted to squamous and transitional neoplasms, including benign and borderline Brenner tumor. p63 is also positive in cervical transitional metaplasia, Walthard rests, vulval Paget disease secondary to an underlying urothelial malignancy, tubulosquamous polyp of the vagina, and ectopic prostatic tissue in the cervix.

Histopathology of gestational trophoblastic disease

The differential diagnosis of villous forms of gestational trophoblastic disease (GTD) includes hydropic abortion, complete and partial hytatidiform mole and placental mesenchymal dysplasia. In addition to histologic criteria, p57(KIP2) immunohistochemistry might be helpful. Choriocarcinoma represents the most immature form of GTD. This and downregulation of HSP-27 might contribute to the high chemosensitivity, compared to placental site (PSTT) and epitheloid trophoblastic tumor (ETT). Within the differential diagnosis of the non-villous forms of GTD an algorithmic approach of immunohistochemistry is very helpful. With an incidence of 1.6% of all abortions within the first trimester the exaggerated placental site reaction (EPS) is rare. There is no molecular indication that the EPS represents a precursor lesion of PSTT. The morphologic prediction of the behaviour of PSTT is not well established. Factors which might be associated with adverse outcome are age >35 years, interval since last pregnancy >2 years, growth outside the uterus, deep myometrial invasion, destructive growth, extensive coagulative necrosis, presence of cells with clear cytoplasm, high mitotic rate and a Ki-67 labeling index >50%. Recent molecular data suggest a neoplastic transformation of (cyto-) trophoblastic stem cells, within the pathogenesis of (non-villous) GTD. The detection of target molecules for a targeted therapy is currently irrelevant.

Lack of Genetic Association Between Exaggerated Placental Site Reaction and Placental Site Trophoblastic Tumor

Exaggerated placental site (EPS) reaction is a reactive or an exuberant physiologic process involving intermediate trophoblasts infiltrating the underlying endomyometrium at the implantation site. Sharing similar cytological and immunohistochemical features with the tumor cells of placental site trophoblastic tumor, a biological link between the 2 lesions can be speculated. Because placental site trophoblastic tumor has a unique sex chromosomal requirement in its genome that requires a paternal X chromosome (i.e. a female antecedent gestation), we investigated whether EPS carries the similar genetic profile by DNA genotypic analysis. Twenty cases of EPS were reviewed and analyzed by AmpFlSTR Identifiler polymerase chain reaction amplification system (Applied Biosystems, Inc., Foster City, CA). The genetic profile of all cases demonstrated unique paternal alleles to that of the paired maternal tissue, confirming the trophoblastic origin of EPS. The presence of an XY genome (male) was identified in 11 cases (55%), and an XX genome (female) was seen in the rest of 9 cases (45%). Therefore, EPS is a trophoblastic lesion that can arise from either male or female gestations. The assignment of sex chromosomes in our study (XY, 55% and XX, 45%) does not support a neoplastic association between placental site trophoblastic tumor and EPS.

Exaggerated placental site reaction following an elective abortion

We encountered a case of exaggerated placental site (EPS) reaction following an elective abortion. EPS is a miscellaneous trophoblastic lesion. There have been few reports describing its clinical course, and the ultrasonogram and magnetic resonance imaging characteristics have not been reported previously. We present the ultrasonogram and magnetic resonance imaging findings of EPS together with histopathological observations.

Exaggerated placental site reaction mimicking choriocarcinoma

Exaggerated placental site reaction mimicking choriocarcinoma

Nodular Histiocytic Hyperplasia of the Endometrium

We describe the clinical and pathologic features of four cases of nodular histiocytic proliferation in the endometrium. We have been able to find only one brief reference to this lesion in the literature. The lesion in each case was a detached nodule composed of aggregates of histiocytes within a biopsy or curettage specimen. The constituent cells differed from foamy histiocytes of the endometrium in that they had either lobulated or ovoid, vesicular nuclei, distinctive cytoplasmic margins, and a moderate amount of amphophilic cytoplasm. Mitoses were frequent (up to 11 per 10 high-power fields) in one case but were absent in the remaining cases. On immunohistochemical staining, CD68 and lysozyme were strongly expressed in the cytoplasm. Neither estrogen receptor nor progesterone receptor was expressed in contrast to the background endometrium. The cells were also negative for S-100 and cytokeratin. Each patient's postcurettage course was uneventful. The cause of nodular histiocytic proliferation of the endometrium is currently unknown, although response to intracavitary debris has been suggested. The lesion should not be confused with a variety of reactive, inflammatory, or neoplastic conditions, such as xanthogranulomatous endometritis, malakoplakia, histiocytic granuloma, hormonal changes of the endometrial stroma, Langerhans' cell histiocytosis, morular metaplasia, extravillous trophoblast, or exaggerated placental site reaction.

Placental Site Trophoblastic Tumor: A 17-Year Experience at the New England Trophoblastic Disease Center

Sixteen patients with recurrent placental site trophoblastic tumor were identified in the cancer registry of the New England Trophoblastic Disease Center for the years 1982 to 1999. Three patients were excluded when theirdiagnosis was changed to exaggerated placental site reaction in a review of the pathology report. This article presents the results of an investigation of the records of the 13 remaining patients. The mean age of study subjects at the time of diagnosis was 31 years, and mean gravidity was 2.2. Antecedent gestational events included seven full-term pregnancies (53.8%), two spontaneous abortions, three therapeutic abortions, and one molar pregnancy. Only one patient was diagnosed because of persistent β-human chorionic gonadotropin (β-hCG) elevation. The remaining 12 presented with irregular bleeding or amenorrhea. The time from the antecedent gestational event to diagnosis ranged from 2 weeks to 5 years (mean, 16.5 months). One woman had a serum β-hCG level of 2000 mIU/ml at the time of diagnosis, but the remaining 12 patients had β-hCG levels below 500 mIU/ml. Diagnosis was made by endometrial curettage in 12 of the 13 patients and by hysterectomy in 1 patient. Four patients had pelvic metastases at the time of diagnosis. Average follow-up was 56 months. All of the women underwent hysterectomy (one after failed treatment with uterine resection and chemotherapy). In the week after surgery, one patient, who presented with metastases and was receiving chemotherapy, developed septic shock (unrelated to myelosuppression) and died. She was excluded from the final analysis. The remaining three patients who presented with metastases and five of the nine other patients were treated with adjuvant chemotherapy. The chemotherapy regimens included various combinations of methotrexate, actinomycin D, cyclophosphamide, etoposide, vincristine, and cisplatin. Two of the three patients with presenting metastases and three patients with no initial metastases had a recurrence (5 of 12, 43%). All five patients with a recurrence had been treated with chemotherapy (5 of 8, 63%). Recurrences were treated with additional chemotherapy, local excision, or both. Mitotic count was the only variable to reach significance in a statistical analysis of possible predictors of tumor recurrence. Patients with a recurrence had median mitotic counts of 10 mitoses per 10 high-power fields (HPF) compared with median counts of 2 mitoses per 10 HPF for patients who did not have a recurrence (P =.04). No patient with a mitotic count of 5 or fewer mitoses per 10 HPF had a recurrence, and all of those with counts above 5 had a recurrence.

Trophoblast lesions and trophoblast tumors

The clinico-pathologic characteristics and the histological/immunohistological differential diagnosis of villous trophoblastic lesions (complete, partial, and invasive hydatiform moles), gestational choriocarcinoma and trophoblastic tumors and pseudotumors of the placental site (placental-site trophoblastic tumor, exaggerated placental site reaction, placental site nodule) are reviewed in context with aspects of cytogenetics, epidemiology and molecular pathogenesis.

Ectopic placental site reaction in the Fallopian tube

Although decidual change in the Fallopian tube following either intra-uterine or ectopic pregnancy is not uncommon, ectopic placental site reactions from prior unrecognized ectopic pregnancy are extremely rare. We describe the occurrence of an ectopic placental site reaction in a Fallopian lube, previously occluded by a Falope ring, which was subsequently re-anastomosed at salpingoplasty. The patient, a 37 year old women, subsequently had a partial salpingectomy performed a year after an intra-uterine pregnancy. Bela-HCG levels had consistently remained in the normal range. However, histological examination of the excised segments of Fallopian tube revealed an ectopic placental site reaction in the right Fallopian tube. Large mononuclear cells with bizarre atypical nuclei were present in the plicae, arranged in a nodular fashion, resembling placental site reactions as seen in the uterus. Immunohistochemical staining revealed negative staining for beta-HCG but focal positive staining for placental alkaline phosphatase and generalized positive staining for low molecular weight cytokeratin, (CAM 5.2) in keeping with intermediate trophoblast. Some suture material was present on the serosal surface of the Fallopian tube, surrounded by concentric layers of fibrosis and a focal foreign body type giant cell reaction; a marker of the previous surgery. It is possible that the previous surgery on the Fallopian tube may have played a role in the occurrence of the placental site reaction. The differential diagnosis of these histological appearances includes degenerate decidua and metastatic carcinoma. The possibility of a placental site trophoblastic tumour should also be considered but this lesion was too small to produce a tumour like mass and no mitoses were identified. The bizarre appearance of the cells may give rise to an erroneous diagnosis of malignancy, especially on small laparoscopic biopsies of the Fallopian tubes.

Placental Site Trophoblastic Tumor: With Features Between an Exaggerated Placental Site Reaction and a Placental Site Trophoblastic Tumor

Chorionic villi, whose presence in cases of trophoblastic disease is normally used to exclude both a choriocarcinoma and placental site trophoblastic tumor (PSTT), were present in the initial uterine curettage specimen of a trophoblastic tumor. The lesion shared morphologic features of both an exaggerated placental site reaction and a PSTT. There was infiltration of the posterior wall of the uterus by small clusters and isolated cells which had a prominent affinity for vessels and resembled a usual placental bed reaction. There was, however, deep involvement of myometrium with extension to the cervix, and the condition persisted for 5 months after uterine evacuation. Because different treatment is entailed, identification of this lesion as a tumor of nonvillous trophoblast is also of great importance in a region where the more usual forms of trophoblastic disease represent a declining but not infrequent event. When products of gestation are examined, the possibility of a PSTT should be considered and the clinician alerted if there is a suggestion of excessive intermediate trophoblastic activity, regardless of the presence of chorionic villi. While this may result in the unnecessary followup of some cases, it would permit, with the aid of serial beta-hCG and HPL levels, the earlier detection of PSTTs.

Exaggerated placental site reaction presenting 18 months after pregnancy and puerperal sterilisation

(1986). Exaggerated placental site reaction presenting 18 months after pregnancy and puerperal sterilisation. Journal of Obstetrics and Gynaecology: Vol. 6, No. 4, pp. 266-267.