Primary epithelioid trophoblastic tumor of the lung: A case report.

ABSTRACT: Primary epithelioid trophoblastic tumor (ETT) of the lung is exceedingly rare. Only about three cases have been reported in Pubmed and worldwide literature. We presented a case of multiple primary ETT of the lung occurring in a 33-year-old Chinese female patient. Comprehensive physical examinations revealed no evidence of a primary lesion on the uterus or cervix uteri. Microscopic examination of the tumor demonstrated ETT of the lung, which was confirmed by immunohistochemical staining and declining level of beta-human choriogonadotropin ( ß -HCG) after the operation. Our case revealed that the ETT can occur in the lung and should be considered when a female had a tumor of lung with increasing ß -HCG.

Placental site trophoblastic tumor (PSTT): a case report and review of the literature.

Placental site trophoblastic tumor (PSTT), also known as atypical choriocarcinoma, syncytioma, chorioepitheliosis or trophoblastic pseudotumor, is a rare gestational trophoblastic disease (0.25-5% of all trophoblastic tumors) and it is composed by neoplastic proliferation of intermediate trophoblasts at placental implantation site. It consists of aggregates or sheets of large, polyhedral to round, predominantly mononucleated cells with a characteristic vascular and myometrial invasion. Main differential diagnoses are gestational choriocarcinoma (GC) and epitelioid trophoblastic tumor (ETT). We present a case of PSTT in a 25-year-old woman. Neoplastic cells showed moderate/high nuclear pleomorphism, abundant amphophilic, eosinophilic and clear cytoplasm, numerous mitotic figures (10 mitoses/10 HPF), and myometrial invasion. Other features are necrosis, vascular invasion with replacement of myometrial vessels by tumor cells and hemorrhage. The patient showed typical low serum ß-hCG levels and high serum humane placental lactogen (hPL) levels.

Epithelioid trophoblastic tumor: A case series.

An epithelioid trophoblastic tumor (ETT) is an extremely rare gestational trophoblastic tumor. Cases of ETT present with abnormal vaginal bleeding in women of reproductive age group with marginally elevated beta human chorionic gonadotrophin (B-hCG) levels. Here, we describe a series of four patients (all were females) including histomorphology, immunoprofiles, and diagnostic difficulty of this rare entity. All cases were in their reproductive age group. The mean pre-treatment hCG level was 665.24 (mIU/mL). Microscopically, all cases had a tumor showing an epithelioid appearance arranged in large nests and sheets. Individual tumor cells were round to polygonal with abundant eosinophilic cytoplasm, with central vesicular nuclei and prominent nucleoli. Areas of hemorrhage, necrosis, and intercellular hyaline-like material deposition were identified in all cases (100%). Immunohistochemically, tumor cells in all cases showed diffuse positivity for AE1/AE3 and p63 (100%). GATA3 was available in one case (25%), which was positive in the tumor cells. In one case (25%), hPL was focally positive, and in one case (25%), it was negative. SALL4 was performed in two cases (50%) and was negative in tumor cells. The mean Ki67 labeling index was 19.2 (range 10-30%). All four patients underwent surgical intervention and were treated with hysterectomy. The mean follow-up in this series was 39.4 months (range 6-70), and all patients are alive to date with a mean survival of 32.8 months (range, 4-67).

Epithelioid Trophoblastic Tumor Presenting as an Adnexal Mass: Report of a Diagnostically Challenging Case.

Epithelioid trophoblastic tumor (ETT) is a rare neoplasm derived from chorionic intermediate trophoblast cells, representing less than 2% of all gestational trophoblastic neoplasms. Classically, ETT presents as a uterine mass in women of reproductive age following a term pregnancy. The time from pregnancy to tumor development varies from months to several years. ETT most often arises in the endometrium, followed by the cervix. Extrauterine ETT are extremely infrequent, with few cases reported in the literature. We report a case of a 41-year-old woman, with history of three term pregnancies who presented with abdominal pain and elevated beta human chorionic gonadotropin (ß-hCG) level, ten years after her last pregnancy. Imaging reported a 3.5 cm adnexal mass, suspicious for ectopic pregnancy. Hysterectomy and mass resection revealed a 4.7 cm, tan-yellow, necrotic mass adjacent to the broad ligament. Histologic evaluation in conjunction with immunohistochemical stains revealed a tumor consistent with ETT. No connection to the endometrium was found grossly or microscopically. DNA fingerprinting analysis revealed the tumor to have two copies of paternal alleles, as seen in molar gestations. One of the primary differential diagnoses for ETT is squamous cell carcinoma due to similar morphologic features. In challenging cases, genetic analysis demonstrating paternally derived genes can establish the diagnosis. In this report, we discuss the challenges in the diagnosis of extrauterine ETT, due to its rarity and highly variable presentation, given that appropriate diagnosis is critical for correct patient management.

Coexisting Epithelioid Trophoblastic Tumor and Placental Site Trophoblastic Tumor During Asymptomatic Relapse: A Case Report and Literature Review.

Gestational trophoblastic neoplasms are a group of trophoblastic tumors that include choriocarcinoma (CC), epithelioid trophoblastic tumors (ETTs), and placental site trophoblastic tumors (PSTTs). Mixed gestational trophoblastic neoplasms include combinations of CCs with ETTs and/or PSTTs; combinations of ETTs and PSTTs have also been described. This report describes the case of a 49-yr-old female with mixed ETT and PSTT discovered due to menstrual delay and a positive beta-human chorionic gonadotropin in serum 11 yr after normal pregnancy; it is an asymptomatic recurrence of the neoplasm after 2 yr. Moreover, only the ETT recurred without evidence of PSTT by biopsy and without any increase in human chorionic gonadotropin levels, even though human chorionic gonadotropin was positive in the first onset of the disease. We also reviewed published English literature, which revealed that there are only 36 cases of mixed trophoblastic tumors to date, of which pure mixed ETT and PSTT were reported only in four cases including our case. The most common combination is CC admixed with an ETT (52%), followed by CC with PSTT in 30.5%. CC admixed with an ETT and/or PSTT account for 83% of the cases, of which pure mixed ETT and PSTT were reported only in 4 cases (11%). The rarity of this condition entails reporting of all cases to facilitate future research and clinical management.

Cystic Trophoblastic Tumor in a Primary Central Nervous System Post-Chemotherapy Germ Cell Tumor: The First Case Report.

Cystic trophoblastic tumor (CTT) is an uncommon trophoblastic proliferation of germ cell tumor origin, mostly reported in post-chemotherapy metastases of testicular germ cell tumors and rarely primary untreated testicular tumors. To date, we are not aware of occurrence in a non-testicular tumor. A 12-year-old boy presented with limb swelling, increased appetite, weight gain, and precocious puberty. Evaluation revealed right frontal lobe mass and elevated α-fetoprotein and ß-human chorionic gonadotrophin. After response to neoadjuvant chemotherapy, the tumor was resected. Microscopically, the resection contained predominantly smooth muscle tissue with scattered small foci of glandular teratoma and CTT. Immunohistochemistry (SALL4, glypican 3) revealed no residual yolk sac tumor. Fluorescence in situ hybridization revealed gain of chromosome 12p. The patient has been disease-free for 13 years. This report expands the spectrum of primary central nervous system germ cell tumors with the occurrence of CTT in this site.

Epithelioid Trophoblastic Tumor: Expanding the Clinicopathologic Spectrum of a Rare Malignancy.

Epithelioid trophoblastic tumor is a malignancy derived from the chorionic laeve-type intermediate trophoblast with sufficient rarity that the vast majority of literature on the topic exists in the form of case reports and small series. Classically, it is regarded as a well-circumscribed tumor with an expansile growth pattern that occurs in reproductive-aged women, usually after a normal pregnancy. However, we recently encountered a case of epithelioid trophoblastic tumor with aggressive spread throughout the abdomen and pelvis in a 68-yr-old female presenting 30 yr after her last delivery. Although to our knowledge this is the first report in a postmenopausal patient to be confirmed by molecular analysis of short tandem repeats, there are multiple similar case reports spanning a variety of clinical settings that deviate from the original description. We therefore sought to synthesize the clinicopathologic data among the available reports in the English literature, with emphasis on pathologic findings. While the overarching themes are largely unchanged, this series of 77 patients reveals a broader spectrum of disease and highlights frequent misdiagnosis. Here we present a clinicopathologic update on this rare entity, with emphasis on a practical approach to diagnosis.

Precision genotyping diagnosis of lung tumors with trophoblastic morphology in young women.

Trophoblastic differentiation has been previously described in somatic carcinomas at different primary sites, including the lung. Lung carcinomas with trophoblastic morphology presenting in women during the reproductive years pose a unique diagnostic challenge due to their overlapping microscopical and immunophenotypical features with metastatic choriocarcinoma of gestational origin. Distinction between the two entities is paramount as they require different chemotherapeutic regimens and have a markedly different prognostic outlook. Here we report a series of three female patients (ages 37-48 years) presenting with lung masses. Two of the three patients were noted to have elevated serum beta-hCG levels at the time of their presentation, while serum beta-hCG was not evaluated preoperatively in the third patient. None of them had a clinical history of molar pregnancy or gestational trophoblastic neoplasia. Core biopsies of the lung masses were performed in two patients and one patient underwent a wedge resection, showing poorly differentiated carcinoma in all cases with scattered multinucleated giant cells, hemorrhage, and necrosis. Beta-hCG immunostain was performed in two cases and showed diffuse immunoreactivity. Clinical history and imaging studies were not conclusive in any of the cases to rule out a gestational origin. Short tandem repeat genotyping analysis was performed to compare the allelic patterns between tumor and normal tissues and revealed identical profiles in one case, consistent with somatic origin, and unique paternal alleles in two cases, confirming metastatic gestational choriocarcinoma. The patient with primary somatic lung carcinoma died of disease within 15 months despite chemotherapy, while both patients with gestational choriocarcinoma responded well to chemotherapy and are alive without evidence of disease. Our cases illustrate the diagnostic pitfalls of lung tumors with trophoblastic differentiation in young women. Genotyping analysis offers precise diagnostic distinction between primary lung carcinoma and gestational choriocarcinoma with major therapeutic and prognostic implications for the patients.

Intermediate trophoblastic tumor: the clinical analysis of 62 cases and prognostic factors.

PURPOSE: The aim is to analyze the clinical characteristics of intermediate trophoblastic tumor (ITT). METHODS: 12 cases diagnosed at Qilu Hospital of Shandong University from January 2005 to December 2016 were investigated. Additionally, 50 cases were selected from MEDLINE and CBM databases between January 2010 and December 2016. The clinical data extracted from those aforementioned 62 cases were analyzed. RESULTS: There were 42 cases with placental site trophoblastic tumor (PSTT), 19 cases with epithelioid trophoblastic tumor (ETT), and 1 case with mixed type (PSTT and ETT). No significant differences were found between PSTT and ETT in terms of age, type of antecedent pregnancy, main complaints, serum ß-hCG peak, FIGO stage or prognosis. However, the interval between antecedent pregnancy and the onset was longer in ETT than in PSTT (P = 0.01). FIGO stage was irrelevant to serum ß-hCG (P = 0.263). All 62 cases underwent surgeries and seven cases preserved fertility. Fifteen cases with high risk factors were not treated with adjuvant chemotherapy. Univariate analysis results showed that age ≧ 40 years, serum ß-hCG peak ≧ 1000 IU/L and nonstandard treatment were associated with poor survival, but only age remained significant on multivariate analysis for ITT (P = 0.018). CONCLUSION: PSTT and ETT have similar clinical characteristics generally. Serum ß-hCG can not reflect the progress of ITT. Age ≧ 40 years is the independent high risk factor for ITT.

Atypical Placental Site Nodule Arising in a Postcesarean Section Scar: Case Report and Review of the Literature.

The distinction between benign and malignant trophoblastic lesions often presents a diagnostic challenge, even in entities with defined morphologic and immunohistochemical criteria. Lesions arising from chorionic-type intermediate trophoblast, namely placental site nodule (PSN) and epithelioid trophoblastic tumor (ETT), can be distinguished by existing criteria. However, a putative intermediate lesion termed "atypical placental site nodule" (APSN) has been described in the literature but is not well-classified. We present a case of APSN, along with a brief literature review, and we propose more definitive morphologic and immunohistochemical criteria for this entity, in order to facilitate easier diagnosis and gather more information regarding outcomes.

Management and prognostic factors of epithelioid trophoblastic tumors: Results from the International Society for the Study of Trophoblastic Diseases database.

OBJECTIVE: Epithelioid Trophoblastic Tumor (ETT) is an extremely rare form of Gestational Trophoblastic Neoplasia (GTN). Knowledge on prognostic factors and optimal management is limited. We identified prognostic factors, optimal treatment, and outcome from the world's largest case series of patients with ETT. METHODS: Patients were selected from the international Placental Site Trophoblastic Tumor (PSTT) and ETT database. Fifty-four patients diagnosed with ETT or mixed PSTT/ETT between 2001 and 2016 were included. Cox regression analysis was used to identify prognostic factors for overall survival (OS). RESULTS: Forty-five patients with ETT and 9 patients with PSTT/ETT were included. Thirty-six patients had FIGO stage I and 18 had stages II-IV disease. Patients were treated with surgery (n = 23), chemotherapy (n = 6), or a combination of surgery and chemotherapy (n = 25). In total, 39 patients survived, including 22 patients with complete sustained hCG remission for at least 1 year. Patients treated with surgery as first line treatment had early-stage disease and all survived. Most patients treated with chemotherapy with or without surgery had FIGO stages II-IV disease (55%). They underwent multiple lines of chemotherapy. Eleven of them did not survive. Interval since antecedent pregnancy and FIGO stage were prognostic factors of OS (p = 0.012; p = 0.023 respectively). CONCLUSIONS: Advanced-stage disease and an interval of ≥48 months since the antecedent pregnancy are poor prognostic factors of ETT. Surgery seems adequate for early-stage disease with a shorter interval. Advanced-stage disease requires a combination of treatment modalities. Because of its rarity, ETT should be treated in a centre with experience in GTN.

Two cases of epithelioid trophoblastic tumors in postmenopausal women.

OBJECTIVE: Epithelioid trophoblastic tumor is a rare gestational trophoblastic neoplasm usually presenting in women of reproductive age, with a history of a prior gestational event. Its presentation in postmenopausal women is extremely rare. Immunohistochemical staining is a helpful aid to distinguish epithelioid trophoblastic tumor from other gestational trophoblastic neoplasms. Correct diagnosis is crucial for clinical management that can vary according to the type of gestational trophoblastic neoplasm. METHODS: We report the case of a 63-year-old postmenopausal woman 33 years after her last full-term pregnancy and another case of a 57-year-old postmenopausal woman who had had a first-trimester abortion 30 years previously as her last gestational event, both presenting cervical epithelioid trophoblastic tumors. In both cases, immunohistochemistry played an important role in differentiating this entity from other gestational trophoblastic neoplasms. Surgery was the primary treatment in both cases. The first patient remained disease-free and died 5 years later due to a rectal adenocarcinoma, and the second patient remains disease-free at publication. RESULTS: In both cases, the hysterectomy specimen confirmed the presence of two large epithelioid trophoblastic tumors arising in the endocervix and lower uterine segment with no extrauterine disease. Nuclear positivity for p63 allowed differentiation from a placental site trophoblastic tumor. The Ki67 proliferative index was 20% and 35%, respectively. CONCLUSIONS: Epithelioid trophoblastic tumors may occur a long time after a prior gestational event and should even be excluded in postmenopausal women with uterine masses. Immunohistochemical staining is helpful to make the differential diagnosis with other gestational trophoblastic neoplasms.

Case report of pulmonary epithelial trophoblastic tumor in a young female patient.

INTRODUCTION: An epithelial trophoblastic tumor (ETT) is a kind of rare trophoblastic tumor that may have the correlation with a prior gestational event. Especially, the one that appears in the lung is extremely rare. CASE SUMMARY: Here, we present a 24-year-old female patient with the chief complain of vaginal bleeding for more than 1 month, who was found to have a large mass (7.5 × 4.5 cm) in the right lower lobe, and it was finally confirmed as lung ETT by postoperative pathology after a successful radical resection of the pulmonary lobe. CONCLUSIONS: As the reason of an extreme rare occurrence of the ETT, doctors can easily misdiagnose the disease. When the patient was found to have a mass with irregular vaginal bleeding and a high level of beta-human chorionic gonadotropin, we need to consider ETT. Currently, surgery is still the most effective method.

Primary Cystic Trophoblastic Tumor of the Testis: A Study of 14 Cases.

Cystic trophoblastic tumor (CTT) has been described in postchemotherapy retroperitoneal lymph node dissections of patients with testicular germ cell tumors. Prognostically, this lesion is similar to teratoma and no further treatment is required after surgery in the absence of other components. CTT has not, however, been reported in the testis. We identified 14 CTTs in the treated (4) and untreated (9; no information for 1 patient) testes of patients 15 to 43 years old (median, 25) with mixed germ cell tumors. The CTT was a minor component (<1% to 10%) and associated with teratoma (14), embryonal carcinoma (7), yolk sac tumor (7), seminoma (1), and choriocarcinoma (1). At follow-up, CTT and teratoma were also found in 2 subsequent resections (spermatic cord and pelvis mass) in 2 patients. The CTTs were not grossly distinct but on microscopic examination were cystic to partly solid, with cysts often containing fibrinoid material and lined by mononucleated squamoid cells with eosinophilic to pale, frequently vacuolated cytoplasm and having pleomorphic nuclei with dense, often smudged chromatin. Mitotic activity was inconspicuous. Immunostains for hCG (6/6), inhibin (6/6), and p63 (2/6) were focally positive. The pathogenesis of CTT is not completely understood. As untreated patients without choriocarcinoma may have CTT in the testis, it is suggested that testicular CTT represents a form of regressed choriocarcinoma or a late morphologic phase in the transformation of choriocarcinoma to teratoma.

Diagnosing and treating rare lesions in a low resource setting: lessons from ahybrid epithelioid trophoblastic tumor and choriocarcinoma.

OBJECTIVE: To raise awareness of the existence of a rare type of malignant trophoblastic tumor and discuss the diagnostic challenges and management of this lesion in a low resource setting. CASE REPORT AND INTERVENTION: A 35 -year -old G6P3 woman was referred to our facility on account of persistent vaginal bleeding due to a suspected incomplete miscarriage with a cervical mass. Her serum ß-HCG was elevated (36,900 mIU/ml) and examination showed a bleeding cervical mass. An initial histopathological diagnosis of moderately differentiated squamous cell carcinoma was reviewed to epithelioid trophoblastic tumor resulting in an extra-fascial hysterectomy. A final histopathological diagnosis of hybrid Epithelioid Trophoblastic Tumor and Choriocarcinoma (ETT/CC) was made after external review and immunohistochemistry. She received subsequent chemotherapy. CONCLUSION: Epithelioid trophoblastic tumor and its hybrids are difficult to diagnose. They may be diagnosed as moderately differentiated squamous cell carcinoma especially in low resource settings where cervical squamous cell carcinoma is relatively more common. A high index of suspicion, a serum ß HCG test and close collaboration between clinicians and pathologists can help make the diagnosis. FUNDING: None.

[Clinical and radiological features of gestational trophoblastic tumors]. / Tumeurs trophoblastiques gestationnelles: aspects cliniques et radiologiques.

Gestational trophoblastic disease incorporates a group of diseases which differ from each other by their regressive evolution, their evolution to metastasis and to recurrence. It is a severe disease that affects women of childbearing age. Gestational trophoblastic tumors (GTT) are the malignant forms of gestational trophoblastic diseases. They are always a result of pregnancy, more often molar pregnancy (hydatidiform mole). The most common type of gestational trophoblastic tumors (GTT) is the invasive mole because, in most cases, the diagnosis is made when cancer is still confined to the uterus. Choriocarcinoma is a more rare type of tumor, often developing distant metastases. When there is a progression to a trophoblastic tumor, the assessment of locoregional extension and distant metastases is essential to establish an appropriate treatment protocol. We here report three clinical cases of GTT by describing their clinical presentations and the use of imaging techniques in the diagnosis and management of these disorders.

Role of P57KIP2 Immunohistochemical Expression in Histological Diagnosis of Hydatidiform Moles.

PURPOSE: To determine the significance of P57KIP2 immunohistochemistry expression in the histopathological diagnosis of hydatidiform mole. MATERIALS AND METHODS: Hydatidiform mole patients at King Chulalongkorn Memorial Hospital between January 1999 and December 2011 were recruited. Two gynecologic pathologists reviewed histopathologic slides to confirm diagnosis. Formalin-fixed, paraffin-embedded tissue sections were stained using a bstandard immunostaining system with monoclonal antibodies against P57KIP2 protein. Correlations among pathological features, immunohistochemical expression and clinical data were analyzed. RESULTS: One hundred and twenty-seven hydatidiform mole patients were enrolled. After consensus review, 97 cases were diagnosed as complet (CHM) and 30 cases as partial (PHM). Discordance between the first and final H and E diagnoses was found in 19 cases (14.9%, k= 0.578). Significant pathological features to classify the type of hydatidiform mole are central cisterns, trophoblastic proliferation, trophoblastic atypia, two populations of villi, fetal vessels and scalloped borders. After performing immunohistochemistry for P57KIP2, 107 cases were P57KIP2 negative and 20 cases positive. Discordant diagnoses between final H and E diagnosis and P57KIP2 immunohistochemistry was identified in 12 cases (9.4%). Sensitivity of final H and E diagnosis for CHM was 89.7%; specificity was 95.0%. PHM sensitivity and specificity of final H and E diagnosis was 95.0% and 89.7%, respectively. CONCLUSIONS: Histopathological diagnosis alone has certain limitations in accurately defining types of hydatidiform mole; P57KIP2 immunohistochemistry is practical and can be a useful adjunct to histopathology to distinguish CHM from non-CHM.