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Losada DM, Benetti-Pinto CL, Andrade LALA. Gonadoblastoma-Associated Mixed Gonadal Germ Cell Tumor with Dysgerminoma and Hepatoid Yolk Sac Tumor Components in 46XY Gonadal Dysgenesis. J Pediatr Adolesc Gynecol 2019; 32:558-560. [PMID: 31175959 DOI: 10.1016/j.jpag.2019.05.014] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2019] [Revised: 05/27/2019] [Accepted: 05/30/2019] [Indexed: 10/26/2022]
Abstract
BACKGROUND Disorders of sex development are congenital conditions with atypical chromosomal, gonadal, or anatomical sex development. Gonadal dysgenesis in patients containing a Y chromosome have a high risk of developing germ cell tumors with potential for malignant transformation. CASE We present the case of a 17-year-old phenotypic female with primary amenorrhea and 46,XY complete gonadal dysgenesis. Pelvic ultrasound showed a solid cystic lesion in the right gonad. Pathology showed a gonadoblastoma-associated mixed gonadal germ cell tumor with dysgerminoma and hepatoid yolk sac tumor. SUMMARY AND CONCLUSION To our knowledge, this mixed neoplasm association has not been previously reported and this case illustrates the challenges for the diagnosis of gonadal dysgenesis-associated tumors, emphasizing its recognition and prognostic implications.
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Affiliation(s)
- Daniele M Losada
- Department of Anatomic Pathology, University of Campinas, Campinas, São Paulo, Brazil.
| | | | - Liliana A L A Andrade
- Department of Anatomic Pathology, University of Campinas, Campinas, São Paulo, Brazil
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2
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Zeremski V, Mawrin C, Fischer T, Schalk E. Diagnostic and therapeutic challenges in extragonadal yolk sac tumor with hepatoid differentiation: A case report. Mol Clin Oncol 2016; 6:79-82. [PMID: 28123734 DOI: 10.3892/mco.2016.1080] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2016] [Accepted: 10/13/2016] [Indexed: 01/19/2023] Open
Abstract
Yolk sac tumors (YSTs) are rare aggressive tumors, arising most commonly in the gonads and occurring mainly in young adults. We herein report a case of an extragonadal YST with hepatoid differentiation localized in the brain and lung. A 41-year old man presented to our hospital with a generalized seizure. A head computed tomography and magnetic resonance imaging examination revealed a large mass in the left occipital lobe with associated edema. Following complete resection, the histopathological examination revealed that the mass was a highly malignant epithelial tumor with a hepatoid pattern. The serum lactate dehydrogenase and α-fetoprotein levels were elevated. Additional diagnostic imaging revealed a lesion in the upper lobe of the right lung, but no other tumor manifestations. Based on the clinical and immunohistochemical characteristics, hepatocellular carcinoma and hepatoid adenocarcinoma were excluded and the diagnosis of extragonadal hepatoid YST was established. A multimodal therapeutic approach (high-dose chemotherapy with autologous stem cell transplantation, radiation and surgery) was applied; however, the patient succumbed to refractory disease 10 months after the diagnosis. Therefore, the diagnosis and treatment of hepatoid YST is an interdisciplinary challenge.
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Affiliation(s)
- Vanja Zeremski
- Department of Hematology and Oncology, Medical Center, Otto-von-Guericke University Magdeburg, D-39120 Magdeburg, Germany
| | - Christian Mawrin
- Department of Neuropathology, Medical Center, Otto-von-Guericke University Magdeburg, D-39120 Magdeburg, Germany
| | - Thomas Fischer
- Department of Hematology and Oncology, Medical Center, Otto-von-Guericke University Magdeburg, D-39120 Magdeburg, Germany
| | - Enrico Schalk
- Department of Hematology and Oncology, Medical Center, Otto-von-Guericke University Magdeburg, D-39120 Magdeburg, Germany
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Stamatova D, Theilmann L, Spiegelberg C. A hepatoid carcinoma of the pancreatic head. Surg Case Rep 2016; 2:78. [PMID: 27488314 PMCID: PMC4972803 DOI: 10.1186/s40792-016-0197-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2016] [Accepted: 06/30/2016] [Indexed: 12/16/2022] Open
Abstract
Hepatoid carcinoma (HC) is an extremely rare form of neoplasm. Its cellular structure resembles that of a hepatocellular carcinoma (HCC). To date, only 26 cases of hepatoid carcinoma of the pancreas have been reported in the literature. We report the diagnosis of a hepatoid carcinoma of the pancreatic head in a 78-year-old male patient. The tumor was detected incidentally during routine abdominal ultrasound scanning. Laboratory tests did not show any abnormalities except for a monoclonal gammopathy of undetermined significance. After CT, MRI, and laparoscopic biopsy that failed to obtain the diagnosis, the patient underwent a Whipple procedure. The final pathology report described a hepatoid carcinoma of the pancreatic head (pathological T3, N0 (0/10), L0, V0, R0, M0). After the patient recovered, no further therapy was recommended by the tumor board and he was discharged. Regular follow-up was suggested; however, the patient suddenly died of acute coronary artery disease 2 months after surgery.
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Affiliation(s)
- D Stamatova
- HELIOS Hospital Pforzheim, Kanzlerstrasse 2 - 7, Pforzheim, 75175, Germany. .,Department of Surgery, HELIOS Hospital Pforzheim, Kanzlerstrasse 2 - 7, Pforzheim, 75175, Germany.
| | - L Theilmann
- HELIOS Hospital Pforzheim, Kanzlerstrasse 2 - 7, Pforzheim, 75175, Germany.,Department of Gastroenterology, HELIOS Hospital Pforzheim, Kanzlerstrasse 2 - 7, Pforzheim, 75175, Germany
| | - C Spiegelberg
- HELIOS Hospital Pforzheim, Kanzlerstrasse 2 - 7, Pforzheim, 75175, Germany.,Institute of Pathology, HELIOS Hospital Pforzheim, Kanzlerstrasse 2 - 7, Pforzheim, 75175, Germany
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Human Hepatocyte-Derived Induced Pluripotent Stem Cells: MYC Expression, Similarities to Human Germ Cell Tumors, and Safety Issues. Stem Cells Int 2016; 2016:4370142. [PMID: 26880963 PMCID: PMC4736817 DOI: 10.1155/2016/4370142] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2015] [Accepted: 11/26/2015] [Indexed: 01/30/2023] Open
Abstract
Induced pluripotent stem cells (iPSC) are a most promising approach to the development of a hepatocyte transplantable mass sufficient to induce long-term correction of inherited liver metabolic diseases, thus avoiding liver transplantation. Their intrinsic self-renewal ability and potential to differentiate into any of the three germ layers identify iPSC as the most promising cell-based therapeutics, but also as drivers of tumor development. Teratoma development currently represents the gold standard to assess iPSC pluripotency. We analyzed the tumorigenic potential of iPSC generated from human hepatocytes (HEP-iPSC) and compared their immunohistochemical profiles to that of tumors developed from fibroblast and hematopoietic stem cell-derived iPSC. HEP-iPSC generated tumors significantly presented more malignant morphological features than reprogrammed fibroblasts or CD34+ iPSC. Moreover, the protooncogene myc showed the strongest expression in HEP-iPSC, compared to only faint expression in the other cell subsets. Random integration of transgenes and the use of potent protooncogenes such as myc might be a risk factor for malignant tumor development if hepatocytes are used for reprogramming. Nonviral vector delivery systems or reprogramming of cells obtained from less invasive harvesting methods would represent interesting options for future developments in stem cell-based approaches for liver metabolic diseases.
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Rittiluechai K, Wilcox R, Lisle J, Everett E, Wallace HJ, Verschraegen CF. Prognosis of hepatoid yolk sac tumor in women: what's up, Doc? Eur J Obstet Gynecol Reprod Biol 2014; 175:25-9. [DOI: 10.1016/j.ejogrb.2013.12.029] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2013] [Revised: 12/15/2013] [Accepted: 12/20/2013] [Indexed: 11/29/2022]
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Hepatoid adenocarcinoma: computed tomographic imaging findings with histopathologic correlation in 6 cases. J Comput Assist Tomogr 2008; 31:846-52. [PMID: 18043368 DOI: 10.1097/rct.0b013e318038f6dd] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE Hepatoid adenocarcinoma (HAC) is a special type of primary tumor with aberrant hepatocellular differentiation occurring in extrahepatic organs. Our objective was to review the computed tomographic findings of HAC and to correlate the imaging features with histopathologic findings. Institutional review board approval was obtained for this study. METHODS The computed tomographic findings images in 6 consecutive patients with pathologically proven HAC were reviewed retrospectively. Five patients were men and 1 was a woman (mean age, 56 years; age range, 36-68 years). All patients underwent contrast-enhanced computed tomography (CT) performed on a 4-slice multidetector row CT scanner. The mean time interval between CT and surgery was 5 days. Two radiologists who were unaware of the final histological diagnosis reviewed all computed tomographic images retrospectively. Lesion characteristic (ie, number, location, size, density, enhancement, heterogeneity, margin, distribution, presence of necrosis, lymphadenopathy, and distant metastasis) were evaluated. The correlation between the imaging and the pathological findings was analyzed. RESULTS Most patients had elevated serum alpha-fetoprotein levels (n = 4). The HAC appeared as large tumors (mean size, 4.2 x 3.4 x 3.9 cm), isodense at unenhanced CT (n = 4), moderately enhanced (n= 5), with necrotic areas (n = 6), regional lymphadenopathy (n = 5), and distant metastases (n = 4). The heterogeneity on computed tomographic images correlated well with the presence of hemorrhage and necrosis. CONCLUSIONS In an old patient with a large necrotic and moderately vascular tumor, the presence of distant metastases, regional lymphadenopathy, and characteristic increased serum alpha-fetoprotein level may suggest a diagnosis of HAC.
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Emerson RE, Ulbright TM. The use of immunohistochemistry in the differential diagnosis of tumors of the testis and paratestis. Semin Diagn Pathol 2006; 22:33-50. [PMID: 16512598 DOI: 10.1053/j.semdp.2005.11.003] [Citation(s) in RCA: 58] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
Although most testicular and paratesticular tumors can be recognized by their light microscopic features, some raise significant differential diagnostic questions. Immunohistochemical staining has proved of significant value in this situation. There is still a role for the traditional markers, including placental-like alkaline phosphatase and alpha-fetoprotein, but newer markers provide additional support and often have greater sensitivity and specificity for many diagnoses. OCT4 is virtually 100% sensitive and specific for seminoma, embryonal carcinoma, and intratubular germ cell neoplasia, unclassified type. Inhibin-alpha, among testicular tumors, is limited to those in the sex cord-stromal category or those having adrenocortical-type differentiation (testicular tumor of the adrenogenital syndrome) or of trophoblastic lineage. Calretinin is another positive marker for the sex cord-stromal tumors but has less specificity. Additional markers, including differential cytokeratins, c-kit, CD30, epithelial membrane antigen, S-100, melan-A, and others, are useful in specific situations. This article reviews the application of immunohistochemical markers for a number of differential diagnostic considerations in the testis and paratestis categorized according to their light microscopic patterns.
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Affiliation(s)
- Robert E Emerson
- Department of Pathology, Indiana University School of Medicine, Indianapolis, USA
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Ersoy O. Very high alpha-fetoprotein in a young man due to concomitant presentation of hepatocellular carcinoma and Sertoli cell testis tumor. World J Gastroenterol 2005; 11:7051-3. [PMID: 16437617 PMCID: PMC4717055 DOI: 10.3748/wjg.v11.i44.7051] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Studies reported that there is a close relationship between hepatocellular carcinoma (HCC) and testis carcinoma. Both tumors can be presented as synchronal tumors, or as testicular metastases of HCC or as hepatic metastases of testicular tumor( [7] ). HCC is one of the most common malignancies worldwide and the incidence of HCC increases with age( [8] ). The relationship between hepatitis B incidence and HCC rates is also well recognized. Alpha fetoprotein (AFP) is produced by 70% of HCC. Though a level of AFP >400 ng/mL is diagnostic for HCC, in the presence of active hepatitis B infection, the cut-off level should be considered to be at least 1 000-4 000 ng/mL. Like HCC, germ cell tumors of the testis also release AFP; but it is shown that some of Sertoli cell tumors of testis can also release AFP( [10] ). Herein we have reported about the first case of HCC in the literature which is presented concomitantly with Sertoli-Leydig tumor of testis, leading to extremely high level of AFP in a 21-year-old man.
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Affiliation(s)
- Ozdal Ersoy
- Sisili Etfal Education and Research Hospital, Kocamancur sok 16/6 80240, Sisili.
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Franke A, Ströbel P, Fackeldey V, Schäfer R, Göller T, Becker HP, Schöneich R, Müller-Hermelink HK, Marx A. Hepatoid Thymic Carcinoma. Am J Surg Pathol 2004; 28:250-6. [PMID: 15043316 DOI: 10.1097/00000478-200402000-00014] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
We describe the clinicopathologic findings in a so far unrecognized thymic tumor. The tumor occurred in a 70-year-old woman with respiratory distress but neither myasthenia gravis nor other symptoms. Metastases or another primary tumor were absent. The well-circumscribed neoplasm was located in the thymic region, measured 18 x 12 x 8 cm, and showed a homogeneous, tan-colored, soft cut surface. By histology, the tumor lacked a true capsule and a lobular growth pattern, was almost devoid of stroma, and infiltrated among remnant thymus lobules. The polygonal tumor cells formed solid sheets, trabeculae, or occurred as single cells that resembled hepatocytes. Proliferative activity was low. Portal structures, sinuses, and bile were absent as were areas of conventional thymoma, adenocarcinoma, or germ cell tumor. The tumor expressed cytokeratins 7 and 19, alpha1-antitrypsin, alpha1-antichymotrypsin, and hep-Par-1. Alpha-fetoprotein (AFP), human beta-chorionic gonadotropin (beta-HCG), placental alkaline phosphatase, CD5, CD30, CD31, CD34, CD45, CD68, CD99, S-100, HMB45, desmin, actin, or neuroendocrine markers were not expressed, and intratumorous CD1a+ or TdT+ immature T cells were absent. AFP was repeatedly undetectable in the blood. Mediastinal tumor recurrence was detected 6 months after surgery. Following radiochemotherapy, the patient has remained free of disease for 26 months. We conclude that this tumor is a thymic carcinoma (WHO type C thymoma). A diagnosis of hepatoid yolk sack tumor appears unlikely considering absence of a bona fide germ cell component, lack of AFP expression, and the patient's female gender. Because of its morphologic and immunohistochemical features, we propose the term "hepatoid thymic carcinoma" for this new type of thymic carcinoma.
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Affiliation(s)
- A Franke
- Department of Visceral and Thoracic Surgery, Central Army Hospital, Koblenz, Germany
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Tochigi N, Kishimoto T, Supriatna Y, Nagai Y, Nikaido T, Ishikura H. Hepatoid carcinoma of the ovary: a report of three cases admixed with a common surface epithelial carcinoma. Int J Gynecol Pathol 2003; 22:266-71. [PMID: 12819394 DOI: 10.1097/01.pgp.0000055173.04957.66] [Citation(s) in RCA: 53] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Hepatoid carcinoma of the ovary is an ovarian carcinoma that has phenotypic properties in common with hepatocellular carcinomas. However, the extent of the tumor cells' similarity to and their difference from hepatocytes is largely unknown. In addition, the precursor cell of origin for hepatoid carcinoma of the ovary has not been identified. Three cases of alpha-fetoprotein-producing hepatoid carcinoma of the ovary that were admixed with an adenocarcinoma of common surface epithelial type are reported. The hepatoid carcinomas had a trabecular architecture with canaliculi detected by polyclonal (but not monoclonal) anticarcinoembryonic antigen antibodies. A hepatic phenotype in the hepatoid tumor cells was further supported by the production of albumin mRNA by in situ hybridization. The adenocarcinomas in the three cases were mucinous (Case 1), serous (Case 2), and endometrioid (Case 3), respectively. The cytokeratin (CK) profile in both the hepatoid and adenocarcinomatous components was CK18+/CK19+/CK20+/-, whereas normal and neoplastic hepatocytes were CK18+/CK19-/CK20-. Although this study supports a hepatic phenotype in ovarian hepatoid carcinoma, the CK profile of hepatoid carcinoma differs from that of normal and neoplastic hepatocytes but resembles that of the associated common epithelial adenocarcinoma. These findings suggest that hepatoid carcinoma of the ovary is probably derived from carcinomas of surface epithelial origin by a process of neometaplasia or transdifferentiation.
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Affiliation(s)
- Naobumi Tochigi
- Department of Molecular Pathalogy, Chiba University Graduate School of Medicine, Chiba University Hospital, Chiba, Japan
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Theuerkauf I, Axmann C, Wolff M, Tschubel K, Fischer HP. Malignant mediastinal germ cell tumor with pure hepatoid differentiation. Pathol Res Pract 2003; 198:725-9. [PMID: 12530574 DOI: 10.1078/0344-0338-00327] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
We describe a germ cell tumor of anterior mediastinal origin, with pure hepatoid differentiation and elevated serum AFP in a 41-year-old man. This is the first report of such a neoplasm analyzed by conventional stains and immunohistochemistry. Hepatocellular differentiation was proved by immunoreactivity with HepPar-1 and alpha-fetoproein (AFP), membranous expression of carcinoembryonic antigen (CEA-poly) in a canalicuar pattern, and focal expression of cytokeratin 19 in abortive ductular structures. Our investigation shows that mediastinal germ cell tumors with hepatoid components typically arise in middle-aged men; they are of pure hepatoid differentiation, as demonstrated here, or exclusively associated with yolk sac structures.
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Affiliation(s)
- Ingo Theuerkauf
- Department of Pathology, University of Bonn, Sigmund-Freud-Str. 25, 533127 Bonn, Germany.
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