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Morphological analysis of yolk sac tumor.

Morphological analysis of imprint histology and cytology was performed in 7 patients with yolk sac tumor (YST). As a result, histological figures of YST were classified into 4 patterns. Endodermal sinus pattern was most frequently identified, followed by polyvesicular vitelline pattern. Imprint cytology findings of YST were also classified into 4 patterns. Cuboidal cells were most frequently observed; cells and nuclei were both cuboidal in shape and 25-40 mu and 20-25 mu in diameters, respectively. The chromatic showed fine to coarse granular patterns. The nuclear cytoplasmic (N/C) ratio was 50-70%, and each nucleus contained one to four nucleoli. Next to cuboidal cells, spindle-shaped cells were frequently noticed; 20-40 mu in size with spindle-shaped nuclei 10-20 mu in diameter and fine to coarse granular chromatic pattern. Naked cells and bizarre cells were also noticed. It was postulated that cuboidal cells and spindle-shaped cells were originated from the endodermal sinus pattern and the loose reticular pattern of YST, respectively. When utilized with rapid-frozen specimens, imprint cytology of YST is sufficient for rapid diagnosis during operations.

Adolescent↗

Immunoelectrophoretic differentiation of alpha-fetoprotein in disorders with elevated serum alpha-fetoprotein levels or during pregnancy.

Our study aims to make differential diagnosis by immunoelectrophoresis for some common conditions with elevated levels of serum alpha-fetoprotein (AFP). One hundred and nine cases with elevated AFP levels were included in this study: yolk sac tumor (n = 8), hepatocellular carcinoma (n = 26), gastric cancer (n = 12), chronic hepatitis (n = 27) and normal pregnancy (n = 36). Lectin agarose gel electrophoresis, antibody-affinity blotting, and immunoreaction were used to identify the specific patterns of AFP in the respective conditions. The results showed that there were three possible bands: L1, L2 and L3. Yolk sac tumor produced a prominent L2 band and a light L3 band. Hepatocellular carcinoma produced a prominent L1 band and a light L3 band. Gastric cancer produced only an L1 band. Chronic hepatitis had a light L1 band and a pronounced L3 band. In pregnancy, the AFP pattern is similar to that of hepatocellular carcinoma. Immunoelectrophoresis is a useful method facilitating the differentiation of AFP origins.

Biomarkers, Tumor↗

Primary yolk sac tumor of the urachus.

Pure yolk sac tumor is the most common malignant gonadal tumor of infants and toddlers. However, the majority of extragonadal germ cell tumors in the midline are either seminomas (germinomas) or teratomas, and pure yolk sac tumors account for only a small fraction of these lesions. To date, only 1 primary urachal pure yolk sac tumor has been reported in the literature. We describe another case, occurring in a 7-month-old male infant who presented with a rapidly enlarging intra-abdominal tumor with marked engorgement of the superficial venous plexus around the umbilicus. With periodic follow-up for 3 years following surgical extirpation of the tumor and adjuvant chemotherapy, this patient is still alive without evidence of disease. Notably, the glandular elements predominating in the frozen sections resulted in the initial misdiagnosis of the tumor as a urachal adenocarcinoma, although the entirely resected specimen revealed typical histologic patterns and Schiller-Duval bodies. Immunohistochemistry showed that the tumor cells were diffusely reactive to alpha-fetoprotein, alpha(1)-antitrypsin, and cytokeratin. Tumor cells were negative for p53 protein, but revealed overexpression for MDM2 protein. Flow cytometry demonstrated a diploid DNA content with S-phase being as high as 55.36%. This case emphasizes that pure yolk sac tumor can occur primarily in the remnant of the urachus in young children.

Antineoplastic Combined Chemotherapy Protocols↗

Yolk sac tumor of the liver combined with hepatocellular carcinoma.

Hepatic yolk sac tumor is extremely rare, and only nine cases have been reported previously to our knowledge. We report the occurrence of a tumor combining hepatocellular carcinoma and yolk sac tumor. The clinical, pathologic, and immunohistochemical findings are presented. The patient was a 62-year-old Japanese man who died of hepatic failure and uncontrolled ascites. On autopsy, a large hepatic tumor was observed, which microscopically was composed of hepatocellular carcinoma and yolk sac tumor. The two components were intermingled, and transition zones were evident. Immunohistochemically, both components were positive for alpha-fetoprotein, but only the yolk sac tumor component was positive for carcinoembryonic antigen, epithelial membrane antigen, stage specific embryonic antigen-1, placental alkaline phosphatase, and keratin. To our knowledge, this is the first reported case of hepatic yolk sac tumor associated with hepatocellular carcinoma. The present tumor is best considered a variant of hepatocellular carcinoma showing yolk sac differentiation, and it provides another explanation for the histogenesis of extragonadal yolk sac tumor.

Carcinoma, Hepatocellular↗

Fine-needle aspiration of testicular lesions: report of 17 cases.

In this article we report on our diagnostic experience of fine-needle aspiration biopsies (FNAB) performed on 17 patients with testicular lesions in the period from 1994-1998. The cytological diagnosis was consistent with seminoma in 7 cases, sex cord-stromal tumors in 3 cases (2 Sertoli cell tumors, 1 Leydig cell tumor), embryonal carcinoma in 3 cases, and yolk-sac tumor in 1 case; the other 3 patients were suffering from flogistic pathology. The cytological diagnosis was confirmed in all cases after surgery. According to our experience, ultrasound FNAB of testicular lesions proved to be a very reliable technique in predicting malignancy with high sensitivity and specificity. None of the patients developed local recurrences or inguinal lymph-node metastasis due to FNAB. Therefore, tumor stage classification (TNM) was not modified in any patient.

Adolescent↗

Ovarian yolk sac tumor associated with endometrioid carcinoma and mucinous cystadenoma of the ovary.

The clinicopathologic and immunohistochemical findings of an unusual case of ovarian yolk sac tumor associated with endometrioid carcinoma and mucinous cystadenoma of the ovary are reported. The tumor was detected in a 51-year-old postmenopausal woman who presented with abdominal swelling and a pelvic mass. The patient underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy and omentectomy. The tumor was confined to the right ovary and measured 16.0 cm in greatest dimension. Microscopic examination revealed that the tumor had a yolk sac component associated with an endometrioid carcinoma, grade I, and a mucinous cystadenoma. A background of atypical endometriosis was noted. Immunoperoxidase studies showed that the yolk sac component stained diffusely with a cytokeratin cocktail and was focally positive for alpha-fetoprotein. It was negative for keratin 7. In contrast, the endometrioid carcinoma stained positive for keratin 7 in addition to the cytokeratin cocktail, but was negative for alpha-fetoprotein. After surgery, the patient received three cycles of chemotherapy. However, the disease progressed and the patient died 10 months after the diagnosis of the ovarian tumor.

Antineoplastic Combined Chemotherapy Protocols↗

Testicular yolk sac carcinoma in a calf.

A testicular yolk sac carcinoma (YSCA) was diagnosed in a 28-day-old male Japanese black calf. Macroscopically, the abdominal cavity was filled with reddish gelatinous masses of various sizes. There were no testes in the scrotum or pelvic cavity. Histologically, the masses consisted of the tissues showing a variety of patterns; loose reticular network, pseudopapillary arrangement, festoon, solid nest, and labyrinthine pattern. Tumor cells were round to oval, with single central or polar nuclei with sharply defined nuclear borders and deeply basophilic chromatin. Tumor cells sometimes had glycogen granules, periodic acid-Schiff (PAS)-positive inclusions, or sudanophilic droplets in their cytoplasm. Hyaline matrices were found in extracellular areas and were intensely PAS positive. Immunohistochemically, most of the tumor cells and hyaline matrices had positive reactivity to anti-alpha-fetoprotein and anti-placental-alkaline-phosphatase antibodies. Positive reaction to anti-laminin antibody appeared only in hyaline matrices. This is the first case of a tumor in a domestic animal with histologic and immunohistochemical features analogous to those of human YSCA, endodermal sinus type.

Alkaline Phosphatase↗

Transcription factor GATA-6 is expressed in malignant endoderm of pediatric yolk sac tumors and in teratomas.

Transcription factors GATA-4 and GATA-6 play critical roles in mammalian yolk sac differentiation and function. Previously, we showed that GATA-4 is a potential marker for malignant yolk sac endoderm in pediatric germ cell tumors. This highly malignant tissue can cause diagnostic problems because yolk sac components may be difficult to differentiate from other, especially immature, tissue types in teratomas. In the search for new molecular markers for germ cell tumors, we have surveyed GATA-6 expression in benign and malignant pediatric germ cell tumors using mRNA in situ hybridization and immunohistochemistry. GATA-6 was expressed in most yolk sac tumors examined and also in nonmalignant tissues including gut/respiratory epithelium, sebocytes, and neuroepithelium in mature and immature teratomas. Given that GATA-6 has not been discovered in sebocytes before, this finding was confirmed by immunohistochemistry of normal mouse samples, indicating a function for this transcription factor in the mammalian skin. Taken together, GATA-6 can be used to identify yolk sac components in pediatric germ cell tumors. Furthermore, it is also expressed in specific tissues in teratomas. GATA-6, together with GATA-4, can thus be used as a novel molecular marker in characterizing of pediatric germ cell tumors.

Adolescent↗

Anterior mediastinal nonseminomatous germ cell tumor with malignant transformation: a case report.

OBJECTIVE: We report a case of a 21-year-old man who presented with the unusual symptoms of heart failure and was found to have an anterior mediastinal yolk sac tumor. METHODS: A review of the literature using the Ovid search engine was performed. RESULTS: The patient was treated with the current standard of neoadjuvant chemotherapy: bleomycin, etoposide, and cisplatin (BEP) with marked reduction in tumor size, followed by en bloc surgical resection. The final pathology revealed teratoma with malignant change: chondrosarcoma, adenocarcinoma, and poorly differentiated sarcoma. CONCLUSIONS: This is a rare initial presentation of an anterior mediastinal germ-cell tumor with treatment consisting of neoadjuvant therapy and surgical resection. In addition, we present the adverse and extremely rare malignant degeneration of this tumor.

Adult↗

[Case of yolk sac tumor decreasing in size and the normalizing of alph-fetoprotein level by anticancer chemotherapy].

A 19-year old man was hospitalized suspected of a mediastinal tumor with superior vena caval syndrome. As the chest X-ray film and thoracic CT scan on admission revealed a huge anterior mediastinal tumor, and the value of serum alpha-fetoprotein (AFP) was high, we made a diagnosis of malignant mediastinal tumor from the germ cell. Radiation therapy was not effective, but a combination chemotherapy consisted of cis-platinum, adriamycin, and vincristine was clearly effective, decreasing the size of the tumor and normalizing the value of serum AFP. As the tumor acquired tolerance to the anticancer drugs before long, the chemotherapy became ineffective and the patient died 9 months after the initiation of the treatment. This tumor had endodermal sinus structure, Schiller-Duval body, and eosinophilic hyaline globulus which were histological characteristics of yolk sac tumor, and was confirmed to be originated from anterior mediastinum.

Adult↗

Cytomorphology of yolk sac tumor of the liver in fine-needle aspiration: a pediatric case.

Yolk sac tumors (YST) in extragonadal locations are rare. Cytologic diagnosis of YST on fine-needle aspiration (FNA) smears may be a challenge to the cytopathologist. Further neo-adjuvant therapy may be based on cytologic diagnosis making accuracy important. We studied FNA material from a hepatic mass in a pediatric patient to further define the cytomorphologic features of hepatic YST. Features include large pleomorphic balls of tumor cells with high nuclear to cytoplasmic ratios, papillary or microglandular pattern of growth, cytoplasmic and intranuclear vacuoles, and prominent nucleoli. Positive immunohistochemical studies included alpha-fetoprotein, cytokeratin AE1/AE3, and CAM 5.2, which are useful in supporting the diagnosis. We report a pediatric patient in whom the diagnosis of hepatic YST was made by cytologic, histologic, and immunohistochemical studies. The subsequent liver biopsy was consistent with the FNA diagnosis. Our findings may further help to characterize the cytomorphologic features of this rare lesion.

Biomarkers, Tumor↗

DNA content and expression of tumour markers in germ cells adjacent to germ cell tumours in childhood: probably a different origin for infantile and adolescent germ cell tumours.

The origin of testicular germ cell tumours occurring during childhood is poorly understood. In adults, the classical seminomas and non-seminomas originate from carcinoma in situ of the testis, which can usually also be detected in seminiferous tubules adjacent to the tumours. In order to contribute with information regarding a possible association between carcinoma in situ and the childhood group of germ cell tumours, we investigated seminiferous tubules adjacent to 13 infantile yolk sac tumours, five infantile teratomas, and six adolescent germ cell tumours of various types, using morphological evaluation, immunohistochemical staining with markers for carcinoma in situ cells, and densitometric DNA measurement of the germ cells. We detected clear differences between the germ cell populations adjacent to adolescent and infantile germ cell tumours. The former were associated with both normal germ cells and carcinoma in situ cells, like germ cell tumours occurring in adult men. Although we were in doubt in two cases, the infantile cell germ cell tumours were in general not associated with carcinoma in situ cells. The aetiology of infantile yolk sac tumours and teratomas may therefore be fundamentally different from that of adolescent and adult germ cell tumours. The origin of yolk sac tumours and teratomas remains to be elucidated.

Adolescent↗

Erythrina cristagalli lectin-reactive alpha-fetoprotein-E2: a marker of hepatocellular carcinoma and other malignancies.

A newly isolated lectin Erythrina cristagalli (ECL) was tested for separation of human alpha-fetoprotein (AFP) glycoforms by affinity electrophoresis at 0.5 mg/ml and separated AFP bands were detected by antibody-affinity blotting. Three AFP bands, AFP-E1, AFP-E2 and AFP-E3 in order of increasing affinity, were obtained. Sera from control patients with chronic hepatitis and cirrhosis gave a major band of AFP-E1 and a minor or trace band of AFP-E2 (3.4 +/- 2.3%), while those from patients with mostly advanced hepatocellular carcinomas had increased proportions of AFP-E2 band (16.6 +/- 10.2%). With a cutoff level of 8% (mean + 2SD of AFP-E2 for controls), the sensitivity for hepatocellular carcinoma was 72% at a specificity of 100%. Gastrointestinal tumors had much higher percentages of AFP-E2 and occasionally positive AFP-E3. Most of the yolk sac tumors examined showed AFP-E3 in addition to AFP-E2, although AFP-E3 was a minor band. Thus, AFP-E2 is potentially a clinically useful marker for differentiation of increased AFP in hepatocellular carcinoma and other malignancies from that in precancerous chronic hepatitis or cirrhosis.

Biomarkers, Tumor↗

Telomerase activity as a biological marker in some gynecological tumors: comparison with tissue and serum CA 125.

BACKGROUND: Since telomerase activity is detectable in cancer cells but not in some normal somatic cells, it has been considered as a potential diagnostic marker as well as a target for possible anticancer strategies. The purpose of this study was to assess the value of telomerase activity determination in some gynecological tumors and to compare it with the CA 125 tissue and serum profile. PATIENTS AND METHODS: The telomerase activity was determined in 11 gynecological tumors: 7 ovarian carcinomas, 2 carcinomas of the fallopian tube and 2 cervical carcinomas, and compared to the activity in the normal peritoneal tissue of the same patients. Additionally, the levels of CA 125 were measured in the tumor and normal peritoneum tissue samples as well as in the patients' sera. RESULTS: In ovarian tumors, the telomerase activity was detected in 71.4% (5 out of 7), while in the carcinomas of the fallopian tube and cervical carcinomas such activity was not observed. Negative for telomerase activity were also all samples of peritoneum. The range of CA 125 in the tumor tissue was 99 U/g-803667 U/g of tissue and in the normal peritoneum 71 U/g-4925 U/g of tissue. CONCLUSION: In conclusion, telomerase activity could be detected in some of the gynecological tumors, but for clinical use as a diagnostic marker it is inferior to CA 125.

Adenocarcinoma↗

Establishment of a leukemia cell line with i(12p) from a patient with a mediastinal germ cell tumor and acute lymphoblastic leukemia.

We report the establishment of a leukemia cell line (UoC-B10) from a patient who developed leukemia several months after the diagnosis of a mediastinal yolk sac tumor. The patient's yolk sac tumor responded to combination chemotherapy, and a mature teratoma with focal areas of hematopoiesis was subsequently resected. However, 5 months after the initial diagnosis, the patient developed an acute lymphoblastic leukemia with a precursor B-cell phenotype. Cytogenetic analysis showed an i(12p) abnormality in the patient's leukemia cells and in the UoC-B10 cell line. The i(12p) was also identified retrospectively in the mediastinal tumor cells by fluorescent in situ hybridization analysis. The UoC-B10 cell line, which has been growing continuously for > 24 months in culture, was Epstein-Barr virus negative and was generally concordant with the patient's leukemia cells by analysis of immunophenotype, karyotype, and genotype. The UoC-B10 cell line possesses receptors for granulocyte-colony-stimulating factor, a cytokine which the patient received as part of his treatment protocol. This cell line may be useful in studying the relationship between i(12p) and hematological differentiation of human mediastinal germ cell tumors.

Adult↗

Cerebral composite atypical teratoid/rhabdoid tumor and yolk sac tumor in the frontal lobe of an infant. Case report.

A 1-year-old male infant presented with a rare cerebral composite tumor consisting of atypical teratoid/rhabdoid tumor (AT/RT) with epithelial and mesenchymal components and yolk sac tumor (YST) with Schiller-Duval bodies. He was admitted to our medical center with a 2-month history of right hemiparesis. Computed tomography and magnetic resonance imaging revealed a large, intra-axial solid tumor with a cyst in the left frontal lobe. Total resection of the tumor was performed. Histological examination showed two different main growth patterns: solid sheets of undifferentiated polygonal cells and a few rhabdoid cells with rosette structures and rhabdomyoblastic cells; and reticular or papillary structures with occasional Schiller-Duval bodies in a myxoid matrix. The immunohistochemical and electron microscopy findings indicated composite AT/RT and YST. Initial total resection of the tumor was subsequently followed by local recurrence, hydrocephalus, and spinal metastasis. Despite adjuvant chemotherapy, the patient died 9 months after admission. AT/RT is a recently established entity of the central nervous system. The present case of composite AT/RT and YST in the frontal lobe indicates the poor prognosis of such tumors.

Brain Neoplasms↗