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.     

α-Fetoprotein-producing gastric carcinoma presenting focal hepatoid differentiation in metastatic lymph nodes

 Hepatoid adenocarcinoma (HA) is a rare variant of adenocarcinoma of the stomach, which is clinically characterized by increased level of serum α-fetoprotein(AFP) and poor prognosis. Microscopic findings include both adenocarcinomatous and hepatoid elements. A case of gastric adenocarcinoma with focal hepatoid differentiation confined within the metastatic lymph nodes occurred in a 55-year-old woman, who developed an advanced gastric carcinoma composed entirely of a typical papillo-tubular adenocarcinoma. Metastatic tumors were present in 8 of 13 perigastric lymph nodes, and 3 of these showed medullary and trabecular tumour growth reminiscent of hepatocellular carcinoma with immunohistochemical positivity for AFP. Preoperative serum AFP was 630 ng/ml and dropped to 76 ng/ml 2 weeks after the operation. Microscopic and immunohistochemical studies on the entire primary tumour tissue failed to demonstrate a focus of hepatoid or an AFP-positive area. This suggests that elevation of serum AFP may be reflected by focal hepatoid differentiation only in the metastatic lymph nodes, requiring extensive evaluation of the metastatic tumour in regional lymph nodes in the case of AFP-producing gastric carcinoma. Received: 7 November 1996 / Accepted: 20 May 1997     

Histological Patterns in Germ-cell Tumours associated with Raised Serum Alpha-fetoprotein (AFP)

Serum alpha-fetoprotein (AFP) was studied in 237 patients with germ cell neoplasms of the gonads and extra-gonadal sites. Whenever possible serial determinations were performed. All patients in remission had normal serum AFP. Raised serum AFP was seen in patients with active disease whose tumours contained endodermal sinus tumour (EST). This included 29 patients with testicular tumours, 11 with ovarian, 3 with mediastinal, and one with a retroperitoneal tumour. In all these patients serum AFP levels were high and correlated well with the amount of EST within the tumour. Serum AFP became normal when the disease was eradicated. There was a gradual rise with recurrence of the disease. Slightly raised serum AFP (below 60 ng/ml) was present in two patients with embryonal carcinoma examined preoperatively. In four similar cases serum AFP was normal. All patients with pure teratoma had normal serum AFP. Seventeen patients with pure seminoma whose serum was examined preoperatively had normal serum AFP at all times. These findings indicate that raised serum AFP is associated with the presence of EST within the tumour, and AFP is a good and reliable tumour marker in patients with germ cell neoplasms containing EST.     

Mixed tumour of the vagina

A 33-year-old Japanese woman presented with a polypoid 2.5 × 2.5 × 1.9 cm mass located in the posterior wall of the lower vagina. Microscopically, the tumour was composed of benign epithelial and stromal-type elements. Predominant epithelial elements were mucinous glands with squamous metaplasia and islands of mature squamous epithelium. The stromal-type cells showed reticular or short fascicular patterns with a transition to the epithelial elements. There was no dual epithelial-myoepithelial combination in the glands as seen in so-called mixed tumours (pleomorphic adenomas) of the salivary gland. Immunohistochemically, the epithelial elements were strongly positive for cytokeratin, PKK1 and epithelial membrane antigen, while the stromal-type cells co-expressed PKK1 and vimentin. Staining for S-100 protein, muscle actin, alpha-smooth muscle actin, desmin, and CD34 was uniformly negative in the tumour cells. The DNA pattern was diploid. The patient is alive and well without recurrence for 50 months after excision. These results indicate that an epithelial cell proliferation, probably of the remnant vestibular gland, plays a major role in the development of mixed tumours of the vagina.     

Malignant phyllodes tumour with a noninvasive ductal carcinoma component

 A malignant phyllodes tumour with a noninvasive ductal carcinoma component is reported. The patient was an 80-year-old Japanese woman with a breast tumour detected by routine physical examination. A simple mastectomy was performed. The excised tumour was 10.5×9.4×5.4 cm in size and bulged into the skin with ulceration. The macroscopic appearance was that of a phyllodes tumour. Histologically the tumour consisted mainly of stromal components with a leaf-like structure lined by atypical ductal epithelium. The epithelial component showed gradual evolution to intraductal papillary carcinoma in a few areas. The stromal component was composed mainly of fibrosarcoma with areas of osteosarcoma and rhabdomyosarcoma. Neither stromal invasion of intraductal carcinoma nor transition between the stromal and epithelial elements was seen. Three months after the operation, death occurred, with multiple pulmonary and subcutaneous metastases. This case probably represents malignant change in both the stromal and the epithelial components of a phyllodes tumour. Since the two elements were independent, the possibility that a phyllodes tumour may be one of the origins of true carcinosarcoma is raised. Received: 11 March 1997 / Accepted: 5 May 1997     

Infantile vaginal tumour with alpha-fetoprotein synghesis.

A 17-month-old girl with a vaginal embryonal carcinoma (germ cell tumour) is reported. Alpha-fetoprtoein (AFP) was elevated before treatment in blood and vaginal fluid. Normal levels of AFP in blood and vaginal fluid were found after radiation and comination chemotherapy. By an indirect immunoperoxidase staining AFP was demonstrated in tumour tissue. 24-month-old local recurrence was preceded by a slight increase in serum AFP, and AFP could also be demonstrated in vaginal fluid and vaginal smears.     

Pancreatic cancer and fibrinogen storage disease

BACKGROUND: Ductal adenocarcinoma is the most common type of pancreatic carcinoma while squamous, carcinosarcoma, sarcoma, giant cell carcinoma, and clear cell types are all rare. Hepatocellular fibrinogen storage disease is also an uncommon disorder which may be associated with hepatocellular carcinoma. Two cases of pancreatic carcinoma were encountered in a family with fibrinogen storage disease, further raising the possibility of a predilection to malignancy in this unusual disorder. The tumour in one case was of the rare clear cell type. These two cases are the basis for this report. METHODS: Sections were cut from retrieved paraffin embedded tissue and stained for routine histology. Immunohistochemistry using the avidin-biotin technique was applied for the expression of the markers p53 (D07), carcinoembryonic antigen (CEA), c-erbB-2, epithelial membrane antigen (EMA), and alpha-fetoprotein (AFP). RESULTS: Both cases were adenocarcinoma of pancreatic ductal origin. The tumour in one case showed features of a clear cell carcinoma. The tumour cells expressed p53, CEA, and EMA immunoreactivity and were negative for c-erbB-2 and AFP. CONCLUSIONS: Hepatocellular fibrinogen storage disease is rare and has been described in association with chronic hepatitis, cirrhosis, and rarely with hepatocellular carcinoma. This represents the first report of its association with carcinoma outside of the liver.     

Alpha-fetoprotein production by a hepatoid adenocarcinoma of the uterus.

A case of a 62 year old Japanese woman with an endometrial adenocarcinoma producing alpha-fetoprotein (AFP) is described. Microscopically, the tumour was composed of a major medullary portion and a minor tubular adenocarcinoma which had invaded the myometrium, the myometrial lymphatics and blood vessels. Neoplastic cells in the medullary portion were polygonal with glycogen-rich cytoplasm. Vascular permeation by neoplastic cells was prominent. Extensive hepatoma-like features were observed. The tumour cells lacked features suggestive of a diagnosis of embryonal carcinoma or endodermal sinus tumour. The production of AFP by the tumour cells was demonstrated immunohistochemically using the PAP technique. Only two cases of AFP producing endometrial adenocarcinomas have been reported previously.     

Serum alpha-foetoprotein as a marker for endodermal sinus tumour (yolk sac tumour) or a vitelline component of "teratocarcinoma".

The correlation between serum alpha-foetoprotein (AFP) and the clinical pathological finding of 24 germ cell tumours arising from the testes (14 cases), the ovaries (3 cases), the mediastinum (3 cases), the retroperitoneal region (2 cases), and the sacrococcygeal region (2 cases) are presented. Irrespective of marked differences in age and sex of the patients, primary site of the tumours and clinical outcome, the 24 cases constituted a homogeneous group in fundamental histological patterns and in AFP synthesis. In all cases of endodermal sinus tumour or teratocarcinomas with a distinct vitelline component an increased serum AFP concentrations was found in the pre-operative serum samples. AFP was also demonstrated in the tumour tissue by quantitative determination of AFP in tumour homogenate (5 cases) and, by immunofluorescence technique, positive staining of the cells lining the endodermal sinuses and of the hyaline globules was found (3 cases). In 12 germ cell tumours without vitelline components in the tumour tissue sections, a normal AFP concentration below 20 mug/1 was found in preoperative serum samples.     

Hormonal activity of epithelial ovarian tumours in post-menopausal women

Concentrations of progesterone and oestradiol in peripheral serum and tumour cyst fluid were measured in 42 post-menopausal women with epithelial ovarian tumours (17 cancer, 6 borderline malignant, 19 benign tumours) and in 19 post-menopausal women without ovarian neoplasms. The hormonal response of the endometrium was assessed, progestogen and oestrogen receptor content in the tumour tissue case recorded, and tumour deoxyribonucleic acid (DNA) ploidy was measured by flow cytometry.

No significant differences were found between the mean serum steroid levels in patients with malignant, borderline or benign tumours, but the mean serum levels of oestradiol in patients with malignant or benign ovarian tumours were higher than those in the controls. Endometrial hormonal activity was seen in 19% of the samples studied. Malignant and benign mucinous epithelial tumours were the types most frequently associated with hormonal activity. Increased levels of sex steroids were seen in the cyst fluid of serous malignant and borderline malignant tumours, while benign tumours were inactive.

The steroid receptor content of the various tumour types did not vary significantly. Ten (59%) out of 17 ovarian carcinomas were found to be aneuploid and 41% diploid as measured by flow cytometry. No significant differences in serum levels of progesterone and oestradiol were found between aneuploid and diploid ovarian carcinomas.

These results contribute to our knowledge of the hormonal activity of epithelial ovarian tumours in post-menopausal women.     

肾脏混合性上皮间质肿瘤

目的探讨肾脏混合性上皮间质肿瘤的临床病理特征。方法观察4例肾脏混合性上皮间质肿瘤的临床资料、镜下及免疫组织化学特点。结果患者3例女性,1例男性。临床表现主要为腰部不适和血尿,影像学检查示肾脏囊实性占位性病变。病理检查：肉眼肿瘤呈囊实性结构,镜下肿瘤由上皮和间质成分共同构成。上皮细胞可呈立方状、柱状、鞋钉样;其中1例上皮成分呈苗勒管上皮分化和肠上皮分化。间质成分为梭形细胞,并可见特征性呈束状分布的平滑肌组织和厚壁血管。免疫组织化学：上皮细胞AE1／AE3阳性,间质细胞雌激素受体（ER）、孕激素受体（PR）、平滑肌肌动蛋白（SMA）阳性。患者行肾切除术,术后随访未见复发。结论肾脏混合性上皮间质肿瘤为具有独特组织病理学特点的良性肿瘤,需要和肾脏其他良恶性肿瘤鉴别。     

Microheterogeneity of Alpha-fetoprotein in Patient Serum as Demonstrated by Lectin Affino-electrophoresis

Microheterogeneity of alpha-fetoprotein (AFP) present in the sera of 76 patients was studied by lectin affino-immunoelectrophoresis. Seventeen patients had benign liver disorders and the remaining 59 patients were treated for primary or secondary liver cancer or yolk sac tumour. By means of Con A, AFP was divided into two variants, while lentil lectin (LCA) made it possible to separate AFP in three variants. In some patients the relative concentrations of Con A and LCA AFP variants were similar; these patients were believed to produce AFP of the same 'profile'. Fourteen AFP profiles were observed by estimation of the area enclosed by precipitates corresponding to respective AFP variants. It was also possible to estimate the AFP profile on the basis of a simple visual analysis of the electrophoretic plates. The obtained results indicate that the AFP profiles of patients with cancer were variable. In spite of variations of the AFP profile in cancer patients, in most cases it was possible to differentiate primary liver cancer from yolk sac tumour and from liver metastases of cancer. In addition, in two-thirds of hepatoma patients the AFP profile was different from the profile observed in patients with benign liver disorders.     

Tracheal carcinosarcoma (true malignant mixed tumour) in a Belgian Blue heifer

This report describes a case of a carcinosarcoma or true malignant mixed tumour (salivary gland type) of the trachea in a Belgian Blue heifer. At post-mortem examination a nodular, well-circumscribed, firmly attached mass was found in the tracheal wall, severely compressing the tracheal lumen. Histologically the tumour was biphasic, with varying proportions of epithelial elements dispersed throughout a matrix showing varying degrees of myxo-chondroid and cartilaginous differentiation. The histological features of the tumour were consistent with a combination of an adenoid cystic carcinoma and a chondrosarcoma. Immunolabelling demonstrated smooth muscle actin in the cytoplasm of both the epithelial and mesenchymal components, thus fulfilling the diagnostic criteria for a mixed tumour. To our knowledge this is the first report of a mixed tumour of the trachea in a domestic animal.     

Pulmonary blastoma

Summary A primary pulmonary tumour in a four year old boy arising from the subpleural zone of the lung is described. It contains both stromal and epithelial elements at the primary site and in the bony metastases. The combination of the age of the patient, the site of the tumour, the stromal and epithelial elements present in the tumour suggest that this is a true pulmonary blastoma. Electronmicroscopy showed the presence of intranuclear viral particles.     

A mixed cell tumour in a Seychelles kestrel (Falco araea)

A mixed cell tumour is described in a young, free-living Seychelles kestrel (Falco araea). The tumour consisted of lymphangiomatous, epithelial, fibrosarcomatous and chondromatous elements.     

两种不同抗体双弹头标记物导向治疗肝癌的比较

在动物实验的基础上，比较了抗ＡＦＰ单克隆抗体（ｍＡｂ）和抗ＡＦＰ多克隆抗体（ｐＡｂ）两种不同抗体双弹头标记物在肝癌患者体内的生物代谢情况。结果显示，两种抗体标记物的血浆清除半衰期均在２４ｈ左右，ｍＡｂ标记物的清除较ｐＡｂ标记物略慢。尿清除的半衰期，ｍＡｂ标记物约为１２０ｈ，而ｐＡｂ标记物则约为１８ｈ，表明二者的体内生物代谢不同，疗效可能不一。     

A Case of Ovarian Endodermal Sinus Tumour with Recurrence of a Large Benign Teratoma

A 14 year old girl was operated for a left side ovarian tumour (weight: 1900 g). Histological examination: endodermal sinus tumour, combined with embryonal carcinoma and dysgerminoma. Serum-alpha-fetoprotein (AFP) was highly elevated (2630 μg/l), and serum human chorionic gonadotropin (hCG) was slightly elevated (100 IU/l), but 2 1/2 months after operation the AFP concentration was less than 20 μg/l, and hCG less than 15 IU/l. After 2 years of intermittent treatment with combination chemotherapy (VAMBLE) the patient developed a left side abdominal tumour (weight: 4600 g). Histological examination: Benign teratoma. There was no sign of recurrence of the malignant disease, and serum AFP and hCG are still normal.     

The significance of VEGF-C/VEGFR-2 interaction in the neovascularization and prognosis of nephroblastoma (Wilms' tumour)

AIM: To investigate the immunohistochemical expression of vascular endothelial growth factor (VEGF)-C and VEGFR-2 in nephroblastoma tissue and correlate their presence with the survival rate of children diagnosed with stage III Wilms' tumour. METHODS AND RESULTS: The material included nephroblastoma tissue obtained from 25 children hospitalized in the Department of Paediatric Oncology, Haematology and Transplantology between 1997 and 2003. VEGF-C and VEGFR-2 expression was evaluated by immunohistochemical assay. VEGF-C was expressed in all cells of the blastemal component and in 30% of tumour cells in the stromal part. It was absent from epithelial elements. VEGFR-2 expression was spread over the surface of numerous stromal cells as well as all the epithelial cells forming dysplastic tubules. The blastemal component of Wilms' tumour was VEGFR-2-negative. VEGF-C-immunopositive stromal cells were situated in the closest proximity to VEGF-C-immunonegative but VEGFR-2-immunoreactive tubules. VEGF-C expression was of prognostic value for both clinical progression (P = 0.0005) and tumour-related death (P = 0.0365). CONCLUSIONS: VEGF-C expression in Wilms' tumour constitutes a potent unfavourable risk factor and may direct future antiangiogenic treatment strategies. The proximity of VEGF-C and VEGFR-2 in the stromal and epithelial components of nephroblastoma could be the neoplastic equivalent of the binary VEGF-C function observed in epithelial and endothelial morphogenesis.     

Adenomyolipoma of the uterus: a case report

Adenomyolipoma of the uterus is a rare, benign, polypoid lesion considered to be of hamartomatous origin or represent an unusual type of benign Müllerian mixed tumour with a heterologous element. The authors present a case of uterine adenomyolipoma and discuss its pathogenesis. A 62-year-old woman complained of lower abdominal pain and postmenopausal bleeding. Imaging techniques revealed a solid ovarian mass and a polypoid intrauterine lesion. The frozen section diagnosis of the ovarian mass was a thecoma. A total hysterectomy and bilateral salpingo-oophorectomy were performed. On gross examination a pedunculated, polypoid lesion of 7x4.5x3cm was found in the uterine cavity. Microscopically, the polypoid lesion contained both epithelial and mesenchymal elements. The epithelial elements were endometrial glands of various size, formed by proliferative endometrial cells. The mesenchymal elements were composed of endometrial stroma, smooth muscle and mature adipocytes. Both the epithelial and the mesenchymal elements showed a benign appearance, were intermingled with each other and periglandular stromal condensation was absent. The lesion had an irregular surface. Microscopic diagnosis was an adenomyolipoma. The peculiar shape and microscopic features of this lesion suggested that it was a variant of benign Müllerian mixed tumour.     

Alpha-fetoprotein: Cellular origin of a biological marker in rat liver under various experimental conditions

Summary Alpha₁-fetoprotein (AFP) was detected by serological, light and electron microscopic methods in various experimental models. These included (a) liver regeneration after partial hepatectomy or CCl₄ intoxication (mouse and rat); (b) liver intoxication by high doses of N-nitrosomorpholine (NNM) and chemical induction of hepatomas (rat). AFP levels varied greatly according to the animal species and strains used. Low and high AFP-producing species and strains were distinguished. In liver regeneration after hepatectomy or CCl₄ intoxication, cellular AFP was found in the cytoplasm of hepatocytes. In NNM-intoxicated livers, elevated AFP levels were associated with proliferation of canalicular epithelial cells in which AFP was localized. In early stages of hepatocarcinogenesis, significant AFP increase occurred after high-dose carcinogen feeding and AFP was also localized in proliferating canalicular epithelial cells. On low-dose NNM feeding, no cellular AFP was detected unless hepatomas had developed. At the stage of malignant conversion, distinct AFP staining and non-AFP staining hepatocellular carcinomas appeared in livers.