| Abstract|| |
Placental site nodule is an uncommon, benign, generally asymptomatic lesion of trophoblastic origin, which may often be detected several months to years after the pregnancy from which it resulted. This entity may have bizarre histologic findings and should be distinguished from other aggressive lesions like placental site trophoblastic tumor, epithelioid trophoblastic tumor and squamous cell carcinoma.
Keywords: Gestational trophoblastic diseases, trophoblast, intermediate trophoblast
|How to cite this article:|
Jacob S, Mohapatra D. Placental site nodule: A tumor-like trophoblastic lesion. Indian J Pathol Microbiol 2009;52:240-1
| Introduction|| |
Placental site nodule (PSN) is a rare, benign lesion which represents remnants of intermediate trophoblast from a previous gestation that has failed to completely involute , Although PSN occurs in the reproductive age group, a temporal association with recent pregnancy is usually lacking and often the time interval between pregnancy and diagnosis of PSN can be several years. These lesions are discovered as incidental findings in curettage or hysterectomy specimens performed for evaluation of irregular uterine bleeding, abnormal cervical smears, post coital bleeding etc. ,, Infertility is a rare mode of presentation in PSN. PSN needs to be differentiated from aggressive lesions of intermediate trophoblast like placental site trophoblastic tumor and epithelioid trophoblastic tumor and from nontrophoblastic diseases like squamous cell carcinoma. ,
| Case Report|| |
A 32 year old female presented with complaints of secondary infertility. She had a full term normal vaginal delivery three years ago. Her menstrual history was unremarkable. There was no history of abortions or irregular bleeding per vaginum since then. General physical examination and routine gynecologic check up were normal. Serum prolactin and progesterone levels were within normal limits. A premenstrual endometrial biopsy was done in order to rule out anovulatory cycles or any other pathology.
Adequate endometrial tissue was received. Microscopic examination revealed multiple variable sized, well circumscribed round to ovoid paucicellular eosinophilic nodules of tissue haphazardly distributed amidst fragments of endometrium [Figure 1]. The nodules showed extensive hyalinization, within which were seen cells with indistinct outlines placed in small groups, singly or in cords [Figure 2a]. Some of the cells were small with scant amount of clear cytoplasm and uniform nuclei, while others were larger with pleomorphic, hyperchromatic bizarre nuclei and abundant eosinophilic cytoplasm [Figure 2b]; few multinucleated forms were also present. No mitotic figures were noted. Occasional cells revealed the presence of rounded eosinophilic hyaline bodies in the cytoplasm [[Figure 2] inset]. Periodic acid Schiff (PAS) staining exhibited abundant cytoplasmic glycogen within the small cells. The endometrial glands showed proliferation of the lining epithelium; occasional glands revealed subnuclear vacuoles. No decidua or chorionic villi were present.
| Discussion|| |
Gestational trophoblastic disease constitutes a diverse group of lesions, which also includes neoplastic and non-neoplastic proliferations of trophoblast unaccompanied by chorionic villi.  A spectrum of lesions derived from the intermediate trophoblast have been described, viz placental site nodule or plaque, exaggerated placental site reaction, placental site trophoblastic tumor and epithelioid trophoblastic tumor. , Placental site nodule (PSN) represents remnants of placental site tissue that has failed to involute and may remain in the uterus for several years after the pregnancy from which it resulted. The interval from the most recent known pregnancy till the time of detection ranges widely from one month to 8 years with an average of 3 years.  The mean age at diagnosis is in the early thirties with the age range as broad as 20 to 49 years. , The clinical indications for surgical evaluation included metro-menorrhagia, hypermenorrhoea, dysmenorrhoea, recurrent abortions, post-coital bleeding, abnormal cervical smear, infertility etc. ,
Although the overwhelming majority involve the endometrium, PSN can occasionally be seen in the cervix and rarely in the Fallopian tube More Details and ovary. ,,,, PSN is generally of microscopic size but when evident grossly, it appears as yellowish or tan surface nodules in the endometrium. The size of the lesion varies from 1mm to 14mm with average of 2.1mm. , Microscopically, PSN is characterized by single or multiple, small round or ovoid, well defined extensively hyalinized eosinophilic nodules composed of cords, clusters and single cells of intermediate trophoblast. The cells are small with glycogen rich clear cytoplasm or large with abundant eosinophilic to amphophilic cytoplasm. Nuclear hyperchromatism, multinucleation and degenerative atypia are common, but mitotic figures are rarely seen. , Small, round eosinophilic cytoplasmic inclusions and Mallory's hyaline have been described within the trophoblastic cells. , PSN is a benign lesion with no evidence of recurrence requiring no specific treatment or follow up. ,
The differential diagnosis of PSN includes other lesions of intermediate trophoblast like placental site trophoblastic tumor, epithelioid trophoblastic tumor and exaggerated placental site reaction. The small size, presence of well defined, poorly cellular hyaline nodules with paucity of mitotic figures and lack of association with current or recent pregnancy differentiate PSN from these trophoblastic lesions. PSNs are positive for placental alkaline phosphatase and negative/focally positive for Mel-CAM and hpL in contrast to placental site trophoblastic tumors. , Exaggerated placental site reaction is distinguished by an admixture of intermediate trophoblast and syncytiotrophoblastic cells laid out in cords and nests and by the absence of hyaline nodules. Placental site trophoblastic tumour differs from PSN by features of trophoblastic infiltration of muscle fibers and vasculotropism.  Nontrophoblastic lesions that may be confused with PSN include squamous cell carcinoma. Larger size, greater cytological atypia with mitosis and presence of keratinized cells are pointers towards squamous carcinoma. Additionally, immunoreactivity for inhibin alpha and cytokeratin 18 and a low Ki-67 labeling index favor PSN.  PSN has also often been misinterpreted as hyalinized decidua. Decidual cells have more distinct cell membranes, basophilic cytoplasm and pale, uniform nuclei in contrast to the amphophilic or deeply eosinophilic cytoplasm and hyperchromatic, often pleomorphic nuclei of PSN. Intermediate trophoblastic cells are positive for both cytokeratin and hpL, while decidual cells are negative. 
To conclude, PSN may have bizarre histologic features necessitating differentiation from aggressive lesions of intermediate trophoblast and from squamous carcinoma. The lack of association with recent pregnancy compounds the problem. Herein lies the importance of this, infrequently encountered, less known benign trophoblastic lesion.
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Department of Pathology, Christian Medical College and Hospital, Ludhiana
[Figure 1], [Figure 2a], [Figure 2b], [Figure 2]