Retiform Sertoli-Leydig cell tumours: clinical,morphological and immunohistochemical findings

AIMS: To determine the morphological and immunohistochemical profile of retiform Sertoli-Leydig cell tumours and to compare the observed profile with that of adult rete ovarii. METHODS AND RESULTS: Nineteen retiform Sertoli-Leydig cell tumours were studied, eight by immunohistochemistry, and five examples of rete ovarii from adult females were also evaluated immunohistochemically. The patients ranged in age from 3 to 74 years with a mean age of 31 years. Four patients were virilized and had an abdominal mass; two were virilized with amenorrhoea and two had amenorrhoea alone. Eight presented with an abdominal mass and one patient was pregnant. Two tumours were incidental findings. Information on stage was available in 16 patients: 14 tumours were stage 1, one was stage 2, and one was stage 3. Fifteen tumours were of intermediate differentiation and four were poorly differentiated. Papillary structures were evident grossly in four cases. Microscopically, all cases had a retiform pattern in addition to varying quantities of sex cord, gonadal stromal and heterologous elements. Heterologous elements were present in 13 cases and consisted of hepatocytes (n = 7), mucinous epithelium (n = 7) and skeletal muscle (n = 2). Immunohistochemical evaluation of eight tumours showed a more intense positivity for keratin in the retiform areas, whereas the gonadal stromal component had a more intense expression of inhibin. Inhibin stains Leydig cells strongly and hepatocytes moderately. Rete ovarii epithelium was positive for keratin and vimentin in the five cases studied, and for inhibin in one case. Follow-up was available on 13 patients. Three tumours behaved in a malignant fashion: one each was stage 1, 2, and 3 at diagnosis. CONCLUSIONS: Immunohistochemistry is useful in distinguishing retiform Sertoli-Leydig cell tumours from other tumours that they may resemble. Inclusion of inhibin is essential in a panel of antibodies to evaluate these tumours. The clinical behaviour of these neoplasms cannot always be predicted from their morphology or clinical stage.     

Yolk sac and allied tumours of the ovary

A review is presented of the histological appearances of 38 yolk sac tumours of the ovary and four so-called embryonal carcinomas together with the associated clinical features. It is suggested that these neoplasms belong to a single taxonomic group of embryonal ovarian tumours differing only in the concomitant types of differentiation. One yolk sac tumour occurred in an individual of 46 XY chromosome constitution and another in a patient with a gonadoblastoma in the contralateral ovary. The value of post-operative serial assays of serum AFP is stressed.     

Gastric cancer with choriocarcinoma and yolk sac tumor components: case report

Choriocarcinoma- and yolk sac tumor-like differentiation have rarely been reported in gastric cancers. We report a case of gastric adenocarcinoma, concurrently possessing choriocarcinoma and yolk sac tumor components, of a 74-year-old man. A hemorrhagic, 11 × 8 × 3 cm, tumor with ulceration was located in the body and pre-pylorus of the stomach. Histological examination of the resected specimens demonstrated intermingled proliferation of three different components, namely, adenocarcinoma, choriocarcinoma and yolk sac tumor, which were immunoreactive for carcinoembryonic antigen (CEA), beta-subunit of human chorionic gonadotropin (HCG) and alpha-fetoprotein (AFP), respectively. Gastric cancers with germ cell tumor components are uncommon and this is the second reported case of gastric cancer with choriocarcinoma and yolk sac tumor components.     

Yolk sac tumour of the ear

We report the second known case of yolk sac tumour of the external auditory canal, occurring in an eight-month-old girl. The excised tumour demonstrated histopathological and immunohistochemical features identical to those of yolk sac tumours of gonadal origin. The tumour was aneuploid by flow cytometry. The patient received chemotherapy post-operatively and has had no evidence of disease 13 months after surgery.     

Ovarian yolk sac tumor with virilization during pregnancy: immunohistochemical demonstration of Leydig cells as functioning stroma

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.     

Hepatoid variant of yolk sac tumor of the testis

A case of testicular yolk sac tumor (endodermal sinus tumor) consisting predominantly of hepatoid cells is documented. A mass measuring approximately 4 x 3 cm was noted in the left testis of a 64-year-old man. Preoperative examination revealed an elevated serum level of alpha-fetoprotein (5479 ng/mL). Histologically, the lesion was composed predominantly of sheet-like or trabecular proliferation of hepatocyte-like cells with eosinophilic or clear cytoplasm. The tumor cells were immunoreactive for alpha-fetoprotein, antimitochondrial antibody, cytokeratin (AE1/AE3), alpha-1-antichymotrypsin, alpha-1-antitrypsin, albumin, carcinoembryonic antigen and epithelial membrane antigen. It was necessary to distinguish this variant lesion from metastatic hepatocellular carcinoma, embryonal carcinoma and hepatoid carcinoma.     

原发性性腺外卵黄囊瘤40例临床病理分析

目的：探讨原发性性腺外卵黄囊瘤( extragonadal yolk sac tumor, eYST)的临床病理特征、组织来源、形态学特点、免疫表型及鉴别诊断。方法回顾性分析40例原发性eYST的临床病理资料、形态学和免疫表型特征,结合文献对其临床病理特点进行分析。结果40例eYST中男性24例、女性16例,年龄6个月~42岁,平均12岁,≥12岁者17例,占42.5%。肿瘤分别位于纵隔16例(40.0%)、骶尾12例(30.0%)、腹膜后5例(12.5%)、松果体4例(10.0%)、阴道3例(7.5%)。40例患者中32例为纯YST(80.0%),8例(20.0%)含有1~2种其他类型的生殖细胞肿瘤(germ cell tumor, GCT)成分。结论原发性eYST少见,纵隔和骶尾是eYST最常见的解剖部位;发生在纵隔的肿瘤患者大部分限于成年男性,患者平均年龄明显大于骶尾、腹膜后、松果体和阴道肿瘤的患者(P<0.05),发生在其他部位的eYST多限于青春期前的儿童;一些成人eYST的病例包含其他类型的GCT成分,儿童eYST总是为纯YST;eYST表现出多形性的组织学特征,结合免疫表型对明确诊断、鉴别诊断有一定价值。     

Glypican 3 has a higher sensitivity than alpha‐fetoprotein for testicular and ovarian yolk sac tumour: immunohistochemical investigation with analysis of histological growth patterns

Zynger D L, McCallum J C, Luan C, Chou P M & Yang X J
(2010) Histopathology 56, 750–757
Glypican 3 has a higher sensitivity than alpha‐fetoprotein for testicular and ovarian yolk sac tumour: immunohistochemical investigation with analysis of histological growth patterns Aims: Glypican 3 (GPC3) has been reported to be overexpressed in yolk sac tumour (YST), but the sensitivity has not been compared with α‐fetoprotein (AFP). YST can form numerous growth patterns and the expression of GPC3 in these patterns has not been studied. The aim was to address these aspects. Methods and results: Sections from testicular or ovarian YST were subjected to immunohistochemistry using GPC3 (n = 39) and AFP (n = 24). Overall immunoreactivity for each case and specific histological patterns were semiquantitatively evaluated (0–3+) and intensity of reactivity was scored (0–3). All cases expressed GPC3 (1+, 5%; 2+, 8%; 3+, 87%) with strong intensity (2.9). The majority expressed AFP (58%) but immunoreactivity was often focal (0, 42%; 1+, 33%; 2+, 25%) and intensity was low (1.0). Using GPC3, >75% of the microcystic (n = 38), macrocystic (n = 26), solid (n = 21), glandular‐alveolar (n = 8), endodermal sinus (n = 7), polyvesicular vitelline (n = 5), enteric (n = 4) and micropapillary (n = 2) growth patterns displayed 2+ or 3+ positivity. Conclusions: YST can display a variety of growth patterns that can be confused with other germ cell tumour components. GPC3 detects all growth patterns tested and has a higher sensitivity for detecting YST than AFP.     

Metastatic neoplasms involving the ovary: a review with an emphasis on morphological and immunohistochemical features

The ovary is a common site of metastatic tumour. In many cases of ovarian metastasis there is a known history of malignancy but in other cases the ovarian tumour is the first manifestation of disease. In this review metastatic colorectal, appendiceal, gastric, breast, pancreatic and biliary tract, hepatocellular, renal, transitional and cervical carcinomas and metastatic malignant melanoma involving the ovary are discussed, as is the issue of synchronous ovarian and endometrial carcinomas. Peritoneal tumours, including primary peritoneal carcinoma, mesothelioma and intra-abdominal desmoplastic small round cell tumour, involving the ovary are also discussed, together with a variety of other rare, metastatic ovarian neoplasms. Many metastatic adenocarcinomas involving the ovary, especially those exhibiting mucinous differentiation, closely mimic primary ovarian adenocarcinomas with morphologically bland areas simulating benign and borderline cystadenoma. This is referred to as a maturation phenomenon. In recent years immunohistochemistry, especially but not exclusively differential cytokeratin (CK7 and CK20) staining, has been widely used as an aid to distinguish between a primary and secondary ovarian adenocarcinoma. While immunohistochemistry undoubtedly has a valuable role to play and is paramount in diagnosis in some cases, the results must be interepreted with caution, especially in mucinous tumours, and within the relevant clinical context. We feel the significance of differential cytokeratin staining is not always understood by histopathologists and this can result in erroneous interpretation. We critically discuss the value of immunohistochemistry and associated pitfalls with each tumour type described.     

Adenomatoid tumours: an immunohistochemical and ultrastructural appraisal of their histogenesis

The histogenesis of adenomatoid tumour has continued to provoke debate since Golden and Ash suggested the term in 1945 for a characteristic benign neoplasm typically found in the uterus, fallopian tube or epididymis. Endothelial, epithelial, mesonephric, müllerian and mesothelial histogenesis have been suggested. The balance of evidence suggests mesothelial derivation, but two recent studies point to endothelial origin for at least some of these tumours. Twenty-two histologically typical adenomatoid tumours were studied by electron microscopy, mucin histochemistry and immunohistochemistry. Ultrastructurally, all cases showed vacuolated cells bearing long bushy microvilli and the features were not those of endothelial cells. Glandular spaces contained acid mucopolysaccharide consistent with hyaluronic acid. Immunohistochemical double labelling techniques showed the cells lining such spaces to contain cytokeratin in the absence of factor VIII related antigen and receptors for Ulex europaeus I lectin which were expressed in the endothelium of tumour blood vessels. The evidence points to mesothelial histogenesis in all cases examined.     

A practical approach to immunohistochemical diagnosis of ovarian germ cell tumours and sex cord–stromal tumours

Immunohistochemistry can be useful in the diagnosis of ovarian germ cell tumours and sex cord–stromal tumours. A wide variety of markers are available, including many that are novel. The aim of this review is to provide a practical approach to the selection and interpretation of these markers, emphasizing an understanding of their sensitivity and specificity in the particular differential diagnosis in question. The main markers discussed include those for malignant germ cell differentiation (SALL4 and placental alkaline phosphatase), dysgerminoma (OCT4, CD117, and D2‐40), yolk sac tumour (α‐fetoprotein and glypican‐3), embryonal carcinoma (OCT4, CD30, and SOX2), sex cord–stromal differentiation (calretinin, inhibin, SF‐1, FOXL2) and steroid cell tumours (melan‐A). In addition, the limited role of immunohistochemistry in determining the primary site of origin of an ovarian carcinoid tumour is discussed.     

Development of the secondary human yolk sac: correlation of sonographic and anatomical features.

Transvaginal ultrasound examination of the secondary yolk sac was performed in 145 first trimester pregnancies with a normal outcome (Group A), in 10 normal pregnancies undergoing artificial termination (Group B) and in 25 pregnancies that subsequently failed (Group C) due to embryonic death (n = 17) or to spontaneous abortion of a live embryo (n = 8). The yolk sac structure of all cases from Group B and from 12 cases of Group C were examined morphologically, in order to investigate the changes secondary to normal yolk sac senescence or to pregnancy complication and to evaluate the relationship existing between these changes and ultrasound features. The yolk sac diameter measured in vivo increased significantly between 6 and 10 weeks of gestation and then decreased significantly. Morphologically, the yolk sac showed degenerative changes after 9 weeks of gestation suggesting that the disappearance of the yolk sac in normal pregnancies was a spontaneous event of embryonic development rather than the result of mechanical compression by the expanding amniotic cavity. Yolk sac measurements in complicated pregnancies were not predictive of pregnancy outcome. Irrespective of gestational age, important degenerative changes were found in pregnancies complicated by embryonic death or disappearance, suggesting that variation of yolk sac size and appearance in these cases is the consequence of abnormal embryonic development of death rather than being the primary cause of early pregnancy failure.     

Possible liver cell differentiation in testicular germ cell tumours

Germ cell tumours may imitate various structures of the developing embryo and foetus. Certain structures have, however, very rarely or never been observed in these tumours. Thus the presence of hepatic tissue in testicular germ cell tumours has not been reported. In a series of 37 non-seminomatous testicular tumours seven tumours contained epithelial structures showing morphological and functional resemblance to liver cell trabeculae. These structures were present in tumours with yolk sac tumour (YST) components and most of the tumours also contained teratoid elements. With the immunoperoxidase technique the epithelial structures were heavily stained for alpha-foetoprotein (AFP) and ferritin in all cases, while positive staining for albumin, prealbumin and transferrin was occasionally found. Alpha-I-antitrypsin and haemoglobin F were demonstrated in few scattered cells. Whether or not these epithelial structures should be included among the various patterns of YST or considered to be teratoid components is uncertain. It is suggested that examinations of the heterogeneity of the concomitant serologic AFP may support one or other assumption.