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[Expression and diagnostic significance of OCT4, CD117 and CD30 in germ cell tumors].

OBJECTIVE: To study the immunohistochemical expression of OCT4, CD117 and CD30 in germ cell tumors and to assess their diagnostic value. METHODS: Immunohistochemical study for OCT4 was performed on formalin-fixed, paraffin-embedded tissues of 63 cases of germ cell tumors, including seminoma (21), dysgerminoma (7), germinoma (8), embryonal carcinoma (8), yolk sac tumor (6), mature teratoma (10) and immature teratoma (3), as well as 25 cases of non-germ cell tumors, including granulosa cell tumor (8), clear cell adenocarcinoma (4), Leydig's cell tumor (5), diffuse large B-cell lymphoma (4) and malignant melanoma (4). Besides, the expression of CD117 and CD30 in all germ cell tumors was studied. RESULTS: All cases of seminoma and germinoma, 6/7 cases of dysgerminoma and 7/8 cases of embryonal carcinoma were positive for OCT4, with strong nuclear staining. All other germ cell tumors and non-germ cell tumors were negative for OCT4, except for 1 case of yolk sac tumor and 1 case of clear cell adenocarcinoma which showed weak staining. Positive membranous expression of CD117 was demonstrated in 19/21(90.5%) seminoma, 5/7 dysgerminoma and 7/8 germinoma. Focal weak membranous staining was also noted in 1 case of yolk sac tumor. The melanocytes in teratoma were also positive for CD117. All cases of embryonal carcinoma were negative. On the other hand, positive membranous expression of CD30 were demonstrated in 6/8 embryonal carcinoma. One case of germinoma and 1 case of yolk sac tumor showed weak cytoplasmic positivity. All cases of seminoma and dysgerminoma, 7/8 germinoma and all cases of teratoma were negative for CD30. CONCLUSIONS: OCT4 is a sensitive and relatively specific marker for diagnosing seminoma, dysgerminoma, germinoma and embryonal carcinoma. CD117 and CD30 immunostains, when used in combination, represent valuable tools for distinguishing embryonal carcinoma and seminoma, dysgerminoma, germinoma.

Carcinoma, Embryonal↗

[Prepubertal testicular tumors].

Prepubertal testis tumours (T.T) are rare, with different characteristics and clinical course to adults and with a better prognosis. The authors report the experience of Maria Pia Hospital's over a 15 year period. There were 8 cases of T.T.: 3 Yolk sac tumours, 3 teratomas, 1 Leydig cell tumour and 1 epidermoide cyst. All patients are submitted to an inguinal orchiectomy. Follow-up ranged between six months and 14 years. There was no recurrence of the disease in seven patients are without disease recurrence. Mortality was nil.

Adolescent↗

Significance of cyclin E and p27 expression in malignant ovarian germ cell tumors: correlation with the cell proliferation activity and clinicopathologic features.

Although elevated cell proliferation activity is one of the most remarkable features known to characterize malignant ovarian germ cell tumors (MOGCTs), abnormalities in cell cycle regulation have yet to be thoroughly investigated in MOGCTs. Forty-two MOGCTs were immunohistochemically examined to determine their cyclin E and p27Kip1 (p27) expression in correlation with their cell proliferation activity and clinicopathological features. Cytosine methylation of p27 gene promoter CpG islands was estimated by methylation-specific PCR. The labeling index (LI) was calculated as a percentage of the positively stained tumor cells per total tumor cells counted. p27 LIs showed a significant inverse correlation with Ki-67 LIs in MOGCTs examined (p<0.05). The cyclin E LIs of yolk sac tumors were significantly higher than those of dysgerminomas (p<0.01). Two MOGCTs were methylation-positive (5%). Both p27 and cyclin E are thought to be involved in the cell cycle regulation of MOGCTs. p27 gene promoter methylation is rare in MOGCTs. An immunohistochemical evaluation of cyclin E may be a useful diagnostic modality for differentiating MOGCTs.

Adolescent↗

A collaborative study for the evaluation of lectin-reactive alpha-fetoproteins in early detection of hepatocellular carcinoma.

Lectin-affinity electrophoretic separation of serum alpha-fetoprotein (AFP) was carried out using AFP Differentiation Kits, which used Lens culinaris agglutinin-A (Kit L) and erythroagglutinating phytohemagglutinin (Kit P). Separated AFP bands were detected with a sensitive antibody-affinity blotting technique and determined quantitatively by densitometry, and the results were expressed as percentages of the intensity of total AFP bands. Sera from 424 patients with acute hepatitis, chronic hepatitis, liver cirrhosis, hepatocellular carcinoma, and extrahepatic tumors were assayed for proportion of AFP present as Lens culinaris agglutinin-A-reactive AFP (AFP-L3) and erythroagglutinating phytohemagglutinin-reactive AFPs (AFP-P4+P5). From the maximum Youden indices determined, cutoff levels were set at 15% for both AFP-L3 and AFP-P4+P5 to discriminate between patients with chronic hepatitis and liver cirrhosis and patients with hepatocellular carcinoma. AFP-L3 and AFP-P4+P5 showed sensitivities of 55.3 and 61.0% at specificities of 93.9% and 82.3%, respectively. Thirty-eight % of tumors that measured less than 20 mm in diameter were positive for AFP-L3 and AFP-P4+P5. AFP-L3 exceeded the cutoff level of 15% 4.0 +/- 4.9 months before detection of hepatocellular carcinomas by imaging techniques with a sensitivity of 48% and a specificity of 81%. Thus, these tests are useful for the early detection of hepatocellular carcinomas in patients with hepatitis or liver cirrhosis.

Carcinoma, Hepatocellular↗

Yolk sac tumor in a case of testicular feminization syndrome.

A 17 month old who had been diagnosed as having testicular feminization syndrome (noted during inguinal herniorrhaphy) was operated on because of an abdominal mass that had a high serum level of alpha-fetoprotein. Histologically, the lesion was a yolk sac tumor. The alpha-fetoprotein level normalized within 2 months of the surgery, through the administration of adjunctive chemotherapy containing cisplatinum. The patient is disease-free 4 years postoperatively. When performing inguinal herniorrhaphy in a girl, the surgeon should be prepared to deal with testicular feminization syndrome. If gonadal neoplasm is deniable at the time of diagnosis, careful follow-up examinations are needed until completion of the development of secondary sex characteristics.

Androgen-Insensitivity Syndrome↗

Clinical stage I nonseminomatous germ cell tumors of the testis in childhood and adolescence: an analysis of 31 cases.

A 20-year single-institution experience of clinical stage I nonseminomatous germ cell tumors of the testis (NSGCTT) in childhood and adolescents was reviewed in relation to clinical characteristics, treatment modalities, and survival. Thirty-one patients with clinical stage I NSGCTT were seen between 1980 and 2000: 14 children and 17 adolescents. Yolk sac tumors and/or teratomas occurred in the children, whereas mixed histologies, including embryonal carcinoma, were predominant in the adolescents. After orchiectomy, the children were assigned to surveillance and the adolescents to active treatment: 16 underwent retroperitoneal lymph node dissection (RPLND) and 1 had adjuvant cisplatin-based chemotherapy because of a high-risk histology. Three of the 14 children (21.4%) relapsed 3, 7, and 8 months after orchiectomy: all 3 had yolk sac tumors and presented with increased alpha-fetoprotein levels. No patients had retroperitoneal relapse; two recurred locally and one in the lung. All three children were treated with cisplatin-based chemotherapy with or without surgery. Among the 16 adolescents undergoing RPLND, 4 (25%) had nodal metastases. Three of the 12 patients (25%) who had negative nodes at RPLND relapsed in the lung 3, 7, and 8 months after RPLND. All were treated with cisplatin-based chemotherapy with or without surgery. Five-year relapse-free and overall survival rates for the whole series were 80.6% and 100%, respectively. This series enabled the authors to pinpoint several important aspects of stage I NSGCTT in children and adolescents. In particular, almost all the childhood cases had the same yolk sac tumor histology, the children tended to have localized disease, and an increased alpha-fetoprotein level had a very high predictive value, suggesting that follow-up should include AFP measurements. A conservative approach is the best option in children, while adolescent NSGCTT behaves like the adult disease and management must include similar treatment strategies.

Adolescent↗

[A case of stage IIIB2 infantile yolk sac tumor of testis achieved complete remission by "COMPE" chemotherapy].

A case of metastatic infantile yolk sac tumor of testis is reported herein. The patient was 23 months old with a painless swelling of the right scrotal contents. Histological examination revealed yolk sac tumor. Six months later, the serum alpha-fetoprotein (AFP) was re-elevated and solitary lung metastasis had developed. After 4 courses of chemotherapy with cisplatin (CDDP), vincristine (VCR), methotrexate (MTX), peplomycin (PEP) and Etoposide (COMPE), serum AFP was normalized and lung metastasis disappeared. He has shown no evidence of disease for 5 years with normal physical growth. Aggressive chemotherapy including CDDP might be used for Stage III infantile testicular cancer.

Antineoplastic Combined Chemotherapy Protocols↗

Sonographic appearance of a testicular yolk sac tumor in a 2-year-old boy.

Yolk sac tumor (YST) of testis is the most common of all childhood testicular malignancies. We report a case of testicular YST in a 2-year-old boy. The tumor appeared sonographically as an ovoid, homogeneous, well-circumscribed, isoechoic, solid testicular mass with good sound-through transmission and increased internal vascularity on color Doppler imaging. The serum alpha-fetoprotein level was 4,396 ng/ml. Pathological examination confirmed YST at at stage I. Although the sonographic appearance of YST of the testis is nonspecific, the diagnosis is achievable in clinical practice on the combination of elevated serum alpha-fetoprotein level and sonograms depicting a solid testicular hypervascular mass.

Child, Preschool↗

Clear cell carcinoma simulating the "endometrioid-like variant" of yolk sac tumor.

The authors report a case of clear cell carcinoma of the ovary simulating the "endometrioid-like variant" of YST only recently described by Clement. The tumor was characterized histologically by a villoglandular component intermingled with an endometrioid like glandular pattern, nuclear pleomorphism with abnormal mitotic figures, eosinophilic hyaline PAS-D resistant bodies and diffuse, typical sopranuclear and subnuclear vacuolization according to Clement's description. Clinical features as the old age of the patient and laboratory investigations, suggested the possibility of a surface epithelial origin of the neoplasia, that was substantiated by subsequent additional sections and by immunohistochemical staining for AFP, AAT and CEA.

Adenocarcinoma, Clear Cell↗

[P53 protein expression in malignant germ cell tumor of ovary and its relationship with clinical course and prognosis].

To study the relationship of P53 protein expression with clinical course and prognosis in malignant germ cell tumor of ovary P53 protein expression was examined by immunohistochemical ABC methods in 82 cases of the neoplasm and 20 cases of normal ovary tissue. The results showed that no expression of P53 protein was detected in normal ovarian tissue. The total expression rate of P53 protein was 24.39% in neoplasm, and the expression was not significantly correlated with the different histological types of neoplasm. The study however found that the protein expression of p53 gene was significantly correlated with the clinical stages and prognosis of the neoplasm.

Choriocarcinoma↗

[Clear cell carcinoma of the ovary simulating a yolk sac tumor].

Clear cell carcinoma (CCC) of the ovary is uncommon. In young patients, this tumor may simulate a yolk sac tumor. In this case, the morphologic distinction between these tumors is often difficult but the immunohistochemical staining for CA125 and alpha foeto protein (AFP) and the response to chemotherapy are particularly helpful to resolve this problem of differential diagnosis. We report a case of a 17 year old patient who was operated for a tumor of the right ovary. The diagnosis of a yolk sac tumor was first suggested. However, because of the non response to chemotherapy, a second laparotomy was performed; the definitive pathologic examination concluded to the diagnosis of a CCC of the ovary. The young age and the immunohistochemical staining for AFP are unusual and misleading features for a CCC. Our objective about this particular case is to discuss the anatomoclinical aspects of the CCC of the ovary and to prove the role of immunohistochemistry in the differential diagnosis.

Adenocarcinoma, Clear Cell↗

Ovarian yolk sac tumor with endometrioid carcinoma arising from endometriosis in a postmenopausal woman, with special reference to expression of alpha-fetoprotein, sex steroid receptors, and p53.

A case of a yolk sac tumor (YST) with an ovarian endometrioid adenocarcinoma arising from endometriosis in a postmenopausal woman is described. Clinically, the case showed an aggressive course and did not respond to chemotherapy; the patient died of her disease 6 months after the operation. Histologically, the tumor consisted predominantly of an endometrioid adenocarcinoma, but it also showed microscopic features characteristic of YST. The tumor also contained benign endometriotic lesions with direct transition to the endometrioid adenocarcinoma. Immunohistochemical study revealed that not only the YST, but also the endometrioid adenocarcinoma was partly positive for alpha-fetoprotein. There was an inverse relationship between the endometriosis and the endometrioid adenocarcinoma in terms of the expression of sex steroid receptors and p53: adenocarcinoma cells were positive for p53 but negative for sex steroid receptors, whereas endometriotic epithelial cells were positive for sex steroid receptors but negative for p53.

Adenocarcinoma↗

Fine-needle aspiration cytology of Schiller-Duval bodies of yolk-sac tumor.

The objective of this study was to find the cytological equivalent of Schiller-Duval bodies seen in histology in order to employ the findings as a diagnostic clue for yolk-sac tumor (YST) in aspiration biopsy. A YST, aspirated from the retroperitoneal lymph node of a 29-yr-old Asian man with testicular complex mature teratoma, contained numerous Schiller-Duval bodies on cell block sections. In the corresponding smears, a network of tumor cell-coated, anastomosing, thin-walled, rigid hematopoietic channels with dramatic changes in diameter was observed, in agreement with the diagram based on the reconstruction of 48 serial plastic sections done by Kazancigil et al. (Am J Cancer 1940;40:199-212). In addition, some of the hematopoietic channels folded over several times like a long, narrow balloon pinched at its joints, i.e., "balloon animal"-like. Many segments of the allantoic viteline vascular network, fractured by smearing, exhibited three- or four-way branchings, bulbous protrusions, and cauliflower-like branchings of widely variable diameter.

Adult↗

[A case of adult pure yolk sac tumor of the testis achieving pathological complete response by chemotherapy].

We report a case of pure yolk sac tumor of the left testis in a 22-year-old male. He consulted a physician with left back pain and induration of his left scrotal content in December, 1992. Intravenous pyelography (IVP) revealed left hydronephrosis. Computerized tomography (CT) revealed para-aortic lymph node swelling and lung metastases. Left high inguinal orchiectomy was performed. Histopathological diagnosis was pure yolk sac tumor. After two courses of "COMPE" chemotherapy consisting of cisplatin, vincristine, methotrexate, peplomycin and etoposide, two courses of "high dose "COMPE" chemotherapy and three courses of "high dose COME" chemotherapy without peplomycin, he achieved a partial response (the regression rate of the pulmonary metastases and the retroperitoneal lymph node metastasis were 100% and 96.0% on CT, respectively) and the residual masses in the retroperitoneum were removed. Necrosis and xanthogranulomatous fibrosis were found in the resected material. The patient showed no evidence of disease two years after chemotherapy.

Adult↗

Intracardiac yolk sac tumor and dysrhythmia as an etiology of pediatric syncope.

This report describes a new etiology of pediatric syncope. Epilepsy, brain anomalies, infection, electrolyte abnormalities, and trauma are commonly identified etiologies of seizures in the pediatric population. We report here a child with third-degree heart block and right ventricular outflow tract obstruction related to an intracardiac tumor presenting with syncope and seizure-like activity. Echocardiography revealed a large (3 x 8-cm) intracardiac mass filling the right atrium, extending across the tricuspid valve into the right ventricle and crossing the atrial septum into the left atrium, extending into the left ventricular outflow tract. She underwent emergent cardiopulmonary bypass with removal of the majority of the tumor mass, clearing both the left and right ventricular outflow tracts of obstruction and repairing the tricuspid valve. Postoperative cardiac conduction remained blocked and required permanent pacing. The initial serum alpha-fetoprotein level was grossly elevated, and the tumor showed characteristic histopathologic features of a yolk sac tumor. Four years after the completion of her chemotherapy, she remains clinically well, with no evidence of recurrent tumor by echocardiography or radiographic studies, and her alpha-fetoprotein remains in the normal range. The clinical manifestations of tumor infiltration of the heart with complete heart block resulting in loss of consciousness with tonic-clonic movements are detailed. Although rare, cardiac syncope has multiple known causes and should be suspected in any patient with sudden loss of consciousness and pallor. In the pediatric population, cardiac rhythm disturbances are typically the result, rather than the cause, of acute cardiac emergencies. Pediatricians should be aware of depressed cardiac output and dysrhythmias as etiologies of new-onset syncope. Evaluation should include a cardiac assessment with electrocardiogram to exclude a life-threatening arrhythmia as a potential cause.

Electrocardiography↗

Multidrug resistance of testis cancers: the study of clinical relevance of P-glycoprotein expression.

Germ cell testicular tumors (GCTTs) are very sensitive to anticancer treatment. However some patients ultimately die of their disease due to tumor resistance. Multidrug resistance is mediated by the mdr1 gene product P-glycoprotein (P-gp) which is one important mechanism of drug resistance. This study attempted to examine the correlation between P-gp and tumor progression and to evaluate the clinical relevance of P-gp immunoreactivity in patients with GCTT. Expression of the P-glycoprotein was screened in 48 primary human GCTTs, that have not been treated with chemotherapy, using monoclonal antibody (C219) and immunoenzyme staining. Of the samples from 14 seminomatous germ cell testicular tumors (SGCT, 2 seminomas (14%), and of 34 non-seminomatous tumors (NSGCT) 18 (53%) showed high expression of P-glycoprotein. This difference proved to be significant (P = 0.006). The expression of P-gp showed a statistically significant positive correlation with cancers of advanced stages (P = 0.003) and cancers that showed resistance to chemotherapy (P = 0.0052). Detection of P-gp expression in patients with GCTTs before the application of anti-cancer treatment can be used as a useful prognostic marker to isolate patient subgroups with worse prognosis and less susceptibility to chemotherapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[A case report: simultaneous bilateral testicular tumors with different cell types--complete response after combination chemotherapy of cisplatin and irrinotecan hydrochloride--].

A 38-year-old man was admitted to our hospital complaining of bilateral scrotal swelling. On examination, the patient was found to have bilateral testicular tumors with jugular chain lymph node and para-aortic lymph node metastasis. He underwent bilateral inguinal orchiectomy. Histopathological examination of the excised tumors revealed seminoma, embryonal carcinoma, yolk sac tumor and immature teratoma in the right testis and seminoma in the left testis. The patient was treated postoperatively with two courses of BEP (bleomycin, etoposide, cisplatin) therapy and two courses of EP (etoposide, cisplatinum) therapy. The patient had lung metastasis during the follow-up period and we treated him with salvage combination chemotherapy of cisplatin and irinotecan hydrochloride (CPT-11). After the third course of cisplatin and CPT-11 chemotherapy the lung metastasis disappeared and we performed retroperitoneal lymph node dissection. The patient has remained free of disease 11 months after discharge.

Adult↗

[A giant testicular tumor detected with dyspnea due to lung metastases: a case report].

A 19-year-old male presented with dyspnea. Clinical examination revealed the left infant-head-sized testicular tumor, multiple lung metastases and retroperitoneal bulky lymph node metastasis with marked elevation of serum lactic dehydrogenase (LDH) and alpha-fetoprotein. Left radical orchiectomy followed by the chemotherapy with etoposide and cisplatin (EP) for 4 cycles was performed. The tumor weighed 1,700 g, and was pathologically diagnosed as mixed germ cell tumor consisting of embryonal carcinoma and yolk sac tumor. After the treatment, the tumor markers were normalized with partial response (PR) of lung metastases and complete response (CR) of retroperitoneal lymph node metastasis. Thereafter, biopsy of lung metastases through video-assisted thoracoscopic surgery (VATS) was performed, and pathologically no viable cells were detected. Five months after the treatment, he was seized with convulsion due to brain metastasis with hemorrhage. Therefore, a surgical resection of brain metastasis and 2nd line chemotherapy with etoposide, ifosfamide and cisplatin (VIP) chemotherapy for 3 cycles was performed. The patient has been free of recurrence for 21 months after the 2nd line chemotherapy.

Adult↗