bromochloroacetic-acid and Endodermal-Sinus-Tumor

Extraovarian yolk sac tumors (YSTs) arising in the omentum represent an exceedingly rare malignancy.. A 37-year-old Korean woman was admitted with a history of lower abdominal pain of 3 weeks duration. Pelvic computerized tomography (CT) scanning reported a bilateral ovarian malignancy with peritoneal seeding. Exploration findings revealed a greater omental mass and the result of frozen biopsy was adenocarcinoma or mesothelioma. She was treated with supracolic omentectomy, bilateral salpingo-oophorectomy, pelvic and paraaortic lymph node dissection, multiple peritoneal biopsies and appendectomy. Histological evaluation of the specimen after operation exhibited typical patterns of YST and stained for alpha-fetoprotein (AFP) and cytokeratin. Four courses of bleomycin, etoposide, and cisplatin (BEP) combination chemotherapy repeated every 3 weeks were added to therapy and she has remained free of disease for 1 year after completion of the therapy.. To our knowledge this is the fourth case of primary omental YST. A review of the literature indicates that the diagnosis of YST requires proper evaluations of tumor makers and a skilled pathologist for analysis of frozen sections.

Topics: Adult; alpha-Fetoproteins; Antineoplastic Combined Chemotherapy Protocols; Appendectomy; Bleomycin; Cisplatin; Endodermal Sinus Tumor; Etoposide; Fallopian Tubes; Female; Histocytochemistry; Humans; Keratins; Lymph Node Excision; Omentum; Ovariectomy; Peritoneal Neoplasms; Peritoneum; Tomography, X-Ray Computed

Primary mediastinal germ cell tumors are uncommon tumors that can pose diagnostic difficulties due to their morphologic spectrum and unusual site. Immunohistochemistry plays an increasing role in the diagnosis of these tumors. Whereas the immunophenotype of testicular yolk sac tumors (YST) is rather well known, the opposite is true for primary mediastinal YST leading us to investigate the immunohistochemical features of 14 such neoplasms. Fourteen cases of primary mediastinal YST were reviewed and representative whole tissue sections were selected for immunohistochemical analysis using antibodies directed against CAM5.2, SALL4, OCT3/4, glypican-3, CD30, α-fetoprotein (AFP), CD117, placental alkaline phosphatase (PLAP), GATA-3, and CDX2. The percentage of positive tumor cells and the intensity of staining were evaluated and scored. All cases (100%) showed strong and diffuse expression of CAM5.2 and SALL4, 10 cases (71%) reacted with glypican-3 and AFP in a patchy manner, 5 cases (36%) showed focal positivity with PLAP and GATA-3, 4 cases (29%) showed staining for CDX2, 3 (21%) showed expression of CD117, and a single case was positive for CD30 (7%). None of the cases showed any staining for OCT3/4. Primary mediastinal YST appear to have a similar immunohistochemical phenotype as their testicular counterparts. Coexpression of CAM5.2, SALL4, glypican-3, and AFP provides the best support for YST differentiation; however, it has to be noted that none of these markers is specific for these tumors and immunohistochemical results will always have to be interpreted in the context of morphologic, clinical, and radiologic information.

Topics: Adolescent; Adult; Biomarkers; Cell Differentiation; Child; Diagnosis, Differential; Endodermal Sinus Tumor; Humans; Immunohistochemistry; Immunophenotyping; Keratins; Male; Mediastinal Neoplasms; Middle Aged; Octamer Transcription Factor-3; Testicular Neoplasms; Transcription Factors; Young Adult

Necrotic testicular tumors are relatively frequent and can present a significant diagnostic challenge. Because of differing treatments for seminomas versus nonseminomas, accurate diagnosis is critical. Eleven totally (n=9) or almost totally (n=2) necrotic testicular tumors were retrieved from our consult files. The submitting pathologists favored benign processes in 4 cases, Leydig cell tumor in 1, and lymphoma in 1. The cases were evaluated for histologic features and, when material was available, by immunostaining with 7 antibodies: keratin (AE1/AE3), OCT4, placental alkaline phosphatase, alpha-fetoprotein (AFP), CD117, CD30, and S100. Only distinct reactivity in a cellular distribution in the necrotic zone was considered positive; nuclear reactivity alone was scored for OCT4 and membrane reactivity for CD117 and CD30. Mean patient age was 35 years (range 16-63). Mean tumor size was 19 mm (range 7-53). All patients presented with unilateral testicular masses (6 right, 5 left); 2 also had acute pain. The combination of histologic features, immunostains and, in 1 case, serum AFP permitted classification of 8 tumors (4 seminomas, 3 embryonal carcinomas, 1 yolk sac tumor). Three were not classifiable. The necrotic seminomas lacked associated coarse intratubular calcifications and were positive for OCT4 (4/4) and CD117 (3/3) but negative for keratin (0/4) and CD30 (0/4). The necrotic embryonal carcinomas had associated coarse intratubular calcifications and were positive for keratin (2/3), OCT4 (2/2), and CD30 (3/3). OCT4 stained 1 unclassifiable tumor, which lacked other specific markers. We did not find placental alkaline phosphatase, AFP, and S100 stains useful, although S100 did highlight tumor "ghost" cells in 1 case. Other features in most cases included intratubular germ cell neoplasia (6/11), tubular atrophy/hyalinization (10/11), tumor "ghost" cells (10/11), scar (9/11), and inflammation (10/11). Of the 5 patients with available follow-up, 3 were free of disease at 1, 5, and 8 years after orchiectomy (2 necrotic seminomas and 1 germ cell tumor, unclassified). One patient with yolk sac tumor (age 63 y) developed widespread metastases after 15 months and died of disease. The final case was initially misinterpreted as "testicular infarction, no malignancy" and 16 months later the patient developed a large retroperitoneal seminoma. Most totally necrotic testicular tumors can be placed into clinically important groups by assessment for coarse intratubula

Topics: Adolescent; Adult; alpha-Fetoproteins; Biomarkers, Tumor; Carcinoma, Embryonal; Disease-Free Survival; Endodermal Sinus Tumor; Humans; Immunohistochemistry; Keratins; Ki-1 Antigen; Male; Middle Aged; Necrosis; Octamer Transcription Factor-3; Orchiectomy; Proto-Oncogene Proteins c-kit; Seminoma; Testicular Neoplasms; Young Adult

Yolk sac tumors (YSTs) have a variety of morphologic patterns, some of which can resemble either endometrioid adenocarcinoma (EAC) or clear cell carcinoma (CCC). Immunohistochemical staining for alpha-fetoprotein (AFP) is usually only focal and thus is not always helpful in the diagnosis of YST, and pancytokeratin (CK) is expressed by all three tumors. We studied a battery of immunohistochemical markers with specific attention to the utility of cytokeratin 7 (CK7) in differentiating YST from EAC and CCC. A total of 46 ovarian tumors were retrieved for this study: 16 YST, 19 EAC, and 11 CCC. The three groups were analyzed for the expression of CK7, AFP, Leu-M1 (CD15), EMA, and WT1 by immunohistochemistry. In addition, CK and c-kit (CD117) were studied in the YSTs. All of the YSTs tested (100%) were positive for CK. CK7 was considered negative in all 16 YST cases (100%), although a few tumor cells (1%-2%) stained in 4 cases. In contrast, 17 of 19 EACs and all 11 CCCs had diffuse 3+ to 4+ positivity for CK7; the two other EACs showed 2+ positivity for CK7 (40% and 30% of the tumors). AFP was positive in 12 of 15 YSTs (80%), but was generally focal with 1+ staining in 10 cases (67%); only 2 cases were 3+. All of the EACs and CCCs were negative for AFP. Leu-M1 was 1+ in 9 of 15 YSTs (60%), while the remaining 6 were considered negative. Leu-M1 was positive in 10 of 15 EACs tested (67%), but the staining was variable with 1 case 3+, 3 cases 2+, and 6 cases 1+. In the CCCs, 10 cases (91%) were 3+ to 4+, and 1 case was 1+. EMA was essentially negative in 15 of 15 YSTs (100%), with 3 completely negative and 12 showing very focal (<5%) staining. Eight of 12 EACs showed 4+ staining, 3 showed 3+ staining, and 1 showed 2+ staining. All of the 11 CCCs (100%) showed 4+ staining. WT1 was negative in all cases of YST and CCC; 16 of 18 EAC tested (89%) were negative for WT1, but 2 (11%) were 4+ positive. C-kit was negative in all YSTs. In conclusion, it is important for pathologists to be aware that YSTs may mimic EACs and CCCs and that this distinction is important for the clinical management of patients with these tumors. AFP staining is focal in most YST, so an absence of staining does not exclude this diagnosis. CK7 and EMA are essentially negative in YST but are diffusely positive in CCC and EAC, making them useful markers for differentiating YSTs from both CCCs and EACs. Leu-M1 may also be helpful for distinguishing YSTs from CCCs.

Topics: Adenocarcinoma, Clear Cell; alpha-Fetoproteins; Biomarkers, Tumor; Carcinoma, Endometrioid; Diagnosis, Differential; Endodermal Sinus Tumor; Female; Humans; Immunohistochemistry; Keratin-7; Keratins; Lewis X Antigen; Mucin-1; Ovarian Neoplasms; Proto-Oncogene Proteins c-kit; WT1 Proteins

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.

Topics: alpha 1-Antitrypsin; alpha-Fetoproteins; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Bleomycin; Chemotherapy, Adjuvant; Cisplatin; DNA, Neoplasm; Endodermal Sinus Tumor; Etoposide; Flow Cytometry; Humans; Immunohistochemistry; Infant; Keratins; Male; Nuclear Proteins; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-mdm2; Tomography, X-Ray Computed; Treatment Outcome; Urachus; Urinary Bladder Neoplasms

A case is reported of yolk sac tumor occurring in the left ovary and complicated by pregnancy. The 22-year-old patient presented at 28 weeks gestation with virilization and elevated serum levels of testosterone and alpha-fetoprotein. The tumor showed the typical features of yolk sac tumor with a mixture of islands of Leydig cells. The accumulations of Leydig cells were well demarcated from the cellular components of the yolk sac tumor and were distributed throughout the tumor, although with predominant localization at the periphery. By immunohistochemistry the Leydig cells were intensely positive for vimentin and negative for cytokeratins, allowing clear distinction from the cell components of the yolk sac tumor, which were positive for cytokeratins and negative for vimentin. Testosterone was also identified in the cytoplasm of the Leydig cells. After tumor resection the testosterone and alpha-fetoprotein levels declined simultaneously; this, together with the immunohistochemical demonstration of testosterone, indicates that the Leydig cells were responsible for the endocrine manifestations. Furthermore, antibodies against inhibin alpha-subunit and calretinin could be used to detect the Leydig cells. The present case, a combination of yolk sac tumor and Leydig cells acting as a functioning stroma and causing virilization during pregnancy, is very rare.

Topics: Adult; alpha-Fetoproteins; Endodermal Sinus Tumor; Female; Humans; Immunohistochemistry; Keratins; Leydig Cells; Male; Ovarian Neoplasms; Pregnancy; Pregnancy Complications; Stromal Cells; Testosterone; Virilism

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Choriocarcinoma; Chorionic Gonadotropin, beta Subunit, Human; Endodermal Sinus Tumor; Fatal Outcome; Humans; Keratins; Lung Neoplasms; Male; Mediastinal Neoplasms; Radiography, Thoracic; Tomography, X-Ray Computed

Three cases of primary mediastinal yolk sac tumors with prominent spindle cell features are presented. The patients were three men 24-34 years of age (mean 29). Clinically, two patients presented with symptoms of chest pain and cough; no clinical information was provided for the third patient. Grossly, the tumors were described as large mediastinal masses, with a hemorrhagic and necrotic cut surface. Histologically, the tumors were characterized by a predominantly atypical spindle cell proliferation admixed with areas that showed focally the characteristic reticular growth pattern of yolk sac tumors, with the presence of Schiller-Duval bodies and intra- and extracellular hyaline globules. Immunohistochemical studies performed in one case showed positive staining for keratin and alpha-fetoprotein in both the spindle cell and reticular components of the tumor. Follow-up information was obtained in two patients; they both died of tumor with metastases to the lungs 1 year after initial diagnosis. The present cases expand the spectrum of histopathologic growth patterns that may be observed in yolk sac tumors of the mediastinum and stress the issue of careful sampling and evaluation of mediastinal neoplasms for arriving at the correct diagnosis.

Topics: Adult; alpha-Fetoproteins; Biomarkers; Endodermal Sinus Tumor; Fatal Outcome; Humans; Immunohistochemistry; Keratins; Male; Mediastinal Neoplasms

Four cases of primary hepatoid yolk sac tumors of the anterior mediastinum are described. The patients were all men between the ages of 26 and 40 years (median 33). Clinically, they all presented with a history of shortness of breath and chest pain of several weeks' duration. None of the patients had a history of germ cell tumor elsewhere or evidence of any hepatic abnormality. Grossly, all the tumors were described as large mediastinal masses that impinged on adjacent structures. Histologically, they were characterized by sheets of medium-sized, round to polygonal neoplastic cells with moderate amounts of eosinophilic cytoplasm and round to oval nuclei with prominent nucleoli. The cellular proliferation was homogeneous and displayed moderate cellular atypia and scattered mitotic activity. All the tumors showed focally the presence of more conventional areas of yolk sac tumor, with islands of tumor cells showing a reticular pattern of growth admixed with scattered intra- and extracellular hyaline globules and occasional Schiller-Duval bodies. Immunohistochemical studies showed strong positivity of the tumor cells for alpha-fetoprotein in both components of the lesions. Follow-up information was available in three patients, all of whom developed lung metastases within a year after initial diagnosis. Two of these patients died of tumor within the same period, whereas a third patient has been lost to follow-up. The present cases illustrate an unusual histologic pattern of yolk sac tumor in the mediastinum and highlight the importance of considering this tumor in the differential diagnosis of lesions showing a hepatoid pattern of growth in the mediastinal area.

Topics: Adult; alpha-Fetoproteins; Biomarkers, Tumor; Diagnosis, Differential; Endodermal Sinus Tumor; Fatal Outcome; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Male; Mediastinal Neoplasms

Wilms tumors (WTs) are embryonic neoplasms of the kidney that are believed to arise from primitive metanephrogenic blastema. Our previous reports and those of others indicate that WTs show an increased expression of insulin-like growth factor II (IGF-II) mRNA. However, the precise role of IGF-II on Wilms tumorigenesis is not known. A central question is to determine whether the increased IGF-II expression in WTs simply reflects the fetal nature of WTs (effect), or is induced by specific changes in gene expression (cause).. This study included 31 sporadic WTs, 7 fetal and 3 adult kidneys and 1 yolk sac tumor. Clinical and histologic summaries of WT cases are shown in Table 1. In WTs, the relative area of blastemal, epithelial, poorly differentiated spindle cell and heterologous cell components were assessed. Dot and Northern blot hybridization, using cDNA probes, were done to assess the level of IGF-II mRNA expression. In situ RNA hybridization was employed to localize IGF-II transcripts. Immunohistochemistry was applied to frozen sections to demonstrate cytokeratin and type-IV collagen. These results were then correlated with the histology of WTs and their precursor lesions, i.e., nephrogenic rests (NRs).. Dot blot hybridization indicated that IGF-II transcripts were 32- to 64-fold more abundant in WTs than in the adjacent uninvolved kidneys. In situ hybridization showed that WTs, NRs, and fetal kidney shared a common feature in which IGF-II transcripts were predominantly associated with blastema. However, WTs and NRs differed from fetal kidney in that occasional epithelial structures and dense blastema showed aberrant, sustained IGF-II expression.. The data indicate two points. 1) There is an inverse correlation between nephroblastic differentiation and IGF-II expression in developing fetal kidney. 2) The IGF-II expression in WTs and NRs does not simply reflect the embryonal nature of the tumor but is rather significantly altered, suggesting a role as a transforming growth factor in Wilms tumorigenesis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Blotting, Northern; Cell Transformation, Neoplastic; Child; Collagen; Endodermal Sinus Tumor; Epithelium; Female; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; In Situ Hybridization; Insulin-Like Growth Factor II; Keratins; Kidney; Kidney Neoplasms; Male; Middle Aged; Precancerous Conditions; RNA, Messenger; Statistics as Topic; Transcription, Genetic; Transforming Growth Factors; Wilms Tumor