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Thirty-five testicular germ cell tumours comprising 16 yolk sac tumours, 15 embryonal carcinomas and 13 seminomas were examined for the presence and distribution of laminin using an indirect immunoperoxidase technique. In addition, nine normal yolk sacs and 23 carcinomas of the lung were studied. All the yolk sac tumours were positively stained for laminin. Both extra- and intracellular staining were found. Hyaline, eosinophilic material present within the tumours was positively stained, although with varying intensity. In 12 out of 15 embryonal carcinomas, laminin was found as a membrane staining but cytoplasmic staining also occurred. In 10 out of 13 classical seminomas, a membrane staining of many tumour cells was found, while cytoplasmic staining occurred in only a few seminomas. In all but one of the yolk sacs, laminin was present in the membrane beneath both the mesoblastic outer cell layer and the visceral endoderm. Intracellular staining was seen in some of the cells in both cell layers. In nine out of 23 carcinomas of the lung, laminin occurred extra- as well as intracellularly. Thus, this study showed that in normal yolk sacs the presence of laminin was not found to be particularly associated with any of the cell layers. Likewise, demonstration of laminin within yolk sac tumours did not define different patterns or subtypes of the yolk sac tumour. In addition, demonstration of laminin was not found to be useful in differentiating either between yolk sac tumours and embryonal carcinomas or between seminomas and non-seminomatous germ cell tumours. The findings add, however, interesting knowledge to histogenesis and embryogenesis.

Fine needle aspiration (FNA) biopsy was performed preoperatively on 13 patients with testicular germ cell tumors. The cytologic typing of the tumors was based on the presence or absence of seminoma, embryonal carcinoma, yolk-sac tumor, choriocarcinoma and teratoma in the aspirate. The cytologic findings showed good agreement with the histologic findings. Only four cases showed a single type of tumor; the other nine cases showed as many as four different tumor components. A few characteristic cytologic features proved to be sufficient for tumor typing; this suggests that FNA biopsy cytology can also be useful in identifying metastatic germ cell tumors in extra-gonadal sites.

156 patients with stage I non-seminomatous testicular germ cell tumour entered a countrywide randomized study comparing the effect of postoperative irradiation of retroperitoneal lymph nodes with surveillance only. A total of 150 patients were included in this investigation of factors associated with increased risk of relapse. Thirty-four patients (23 per cent) had a relapse, i.e. 11/67 (16 per cent) in the former and 23/83 (28 per cent) in the latter group. Histopathological studies of the orchidectomy specimens were performed in order to identify features associated with relapse. Pure embryonal carcinoma and vascular involvement were significantly associated with increased risk of relapse. Thus, the relapse rate in the observation group in patients with pure embryonal carcinomas was 50 per cent (5/10) and 36 per cent (19/53) in all patients with tumours with vascular involvement.

In Denmark, 2600 cases of breast cancer are diagnosed, and 1200 women die from the disease, each year. Thus, an early diagnosis and treatment of breast cancer is desirable in order to improve the prognosis. Mammography is the best diagnostic tool for detecting nonpalpable malignant lesions. Early malignant lesions are, however, difficult to differentiate mammographically from benign lesions. This retrospective study was undertaken to determine the accuracy in diagnosing suspicious mammographic findings in nonpalpable breast lesions. Therefore, mammographic findings were compared to histologic findings from the biopsied tissue.

4773 Background: Proteinases play a role for invasiveness of malignancy so we examined data from a previous DNA oligo microarray study of patients with testicular germ cell tumors (TGCT). Methods: ...

The effects of neonatal thymus grafts implanted in nude mice previously transplanted with three different human malignant tumors – an adenocarcinoma of the colon, a malignant melanoma and a Burkitt’s lymphoma – were studied. In all immunologically reconstituted animals tumors were rejected. Tumor rejection started 2–3 weeks after thymus implantation, and was completed after 3–6 weeks. Histological examination of lymphoid tissues showed a correlation between immunological reconstitution and tumor rejection. The rejection process showed a characteristic histologic picture with 3 phases – an early, an intermediate and a late phase – these were similar in the three tumor types examined. The possible mechanisms of reconstitution and tumor rejection are discussed.

A series of 170 consecutive patients with testicular germ cell tumors (88 seminomas and 82 non-seminomas) had preoperative serum samples and primary tumor tissue examined for the presence of the tumor markers, alphafetoprotein (AFP) and human chorionic gonadotropin (HCG) by immunologic techniques. Staging was performed, using a clinico- radiological system, i.e., stage I, tumor confined to testis; stage II, metastases to abdominal lymph nodes only: stage III, metastases to supradiaphragmatic lymph nodes and/or extranodal disease. Seminoma:all 36% had stage II+III disease. 55% of the patients with AFP had localized disease, and 45% had stage II+III. The frequency of patients with stage I non-seminoma with raised serum HCG was 63% compared to 37% in stage II+III. Within the group of HCG-positive non-seminomas, 60% were in stage I and 40% in stage II. Since a high frequency of patients with metastatic disease did not occur among the patients with AFP or HCG in preoperative serum samples or in primary tumor tissue, we conclude that neither AFP nor HCG are especially associated with metastatic properties. The higher frequency of patients with raised serum values among all patients with metastatic disease compared to localized disease may only reflect a greater tumor burden.

The effects of neonatal murine thymus grafts implanted in nude mice previously transplanted with three different human malignant tumours were studied. Reconstitution resulted in tumour rejection, which started 2-3 weeks after thymus implantation and was complete after 3-6 weeks. The rejection process showed a characteristic histologic picture with 3 phases, an early, an intermediate, and a late phase, which were similar in the 3 tumour types examined. Histological examination of lymphoid tissues of successfully thymus grafted mice showed reconstitution of varying degrees. Numbers of plaque forming cells (PFC) of the spleen of tumour transplanted, thymus grafted mice were equal to or higher than the numbers of PFC in normal BALB/c controls. Mice, thymus grafted only always showed intermediate PFC-values. Responses to the T-cell mitogen, phytohaemagglutinin-P (PHA) were only partially reconstituted, whether the nude mice were tumour transplanted or not. In addition tumour rejection in tumour-bearing nude mice treated with T-cells only, was studied. The rejection process was similar to that observed when a whole thymus gland was implanted. Finally, implantation of embryonic bovine thymus grafts was performed in tumour transplanted nude mice. When these grafts were accepted, tumours were also rejected. Possible mechanisms of reconstitution and the reasons for the varying results are discussed.

A carcinoid tumor of the larynx is reported. The tumor was initially interpreted as a poorly differentiated squamous carcinoma and treated with irradiation. One year later a laryngectomy was performed and a carcinoid tumor was found in the resection specimen. The patient died after 2 years with disseminated disease. Carcinoid tumors in the larynx are rare. In the literature 45 cases of laryngeal carcinoid tumors have been reported. The diagnosis of this laryngeal tumor is difficult but important because irradiation is ineffective. Surgical treatment should be performed.

Among 665 patients referred for breast complaints, 100 women (15%) had mammographically detected nonpalpable lesions suspected of malignancy. Using a mammography directed hook wire marking, 115 excisional biopsies were carried out. A correct biopsy containing the lesion was obtained in 113 instances. There were 2 failures, due to displacements of the wire in one case and surgical inexperience in another case. Two patients had minor wound complications. Invasive carcinoma was found in 12 and carcinoma in situ in 4 biopsies, i.e., a cancer rate of 16% of patients and 14% of biopsies. The biopsy procedure was simple, time saving, and acceptable of patients. The excisions were small and the cosmetic results excellent. During mammography for control of wire position, and during dressing and surgical manipulations the flexible hooked wire remained as originally placed in all cases but one.

The morphology of resected residual retroperitoneal tumour tissue from 18 patients treated with a combined chemotherapy regime for advanced testicular non-seminomatous germ cell tumours was studied. In five cases (28%) the resected tissue comprised only fibrous tissue and in ten cases (56%) only mature teratoma (T) was present. Embryonal carcinoma (EC) with yolk sac tumour (YST) differentiation was found in addition to T in one case and in two cases the resected tissue comprised pure EC. In all patients with residual T, T had also been present in the primary tumour. Resected tissue containing T was investigated for the presence of various marker proteins, including alpha-1-antitrypsin (A1 AT), carcino-embryonic antigen (CEA), ferritin (FER), lactoferrin (LF), and pregnancy-specific beta-1-glycoprotein (SP1), in addition to the well-established markers for germ cell tumours, alphafetoprotein (AFP) and human chorionic gonadotropin (HCG). AFP and HCG were present in only two cases. A1 AT and CEA were demonstrated in various amounts in epithelial structures in 11 out of 11 cases with T, while FER was found in ten and LF and SP1 in seven cases. Since A1 AT, CEA and LF were also found in the secreted material within the lumen of the teratoid structures, aspiration of cystic fluid for demonstration of these proteins in addition to AFP and HCG is recommended for diagnostic assessment. CEA and SP1 are suggested for localization and treatment of tumour tissue with the recently-developed methods using specific antibodies which are either radiolabelled or conjugated to anti-neoplastic drugs.

The fifteenth case of malignant Sertoli cell tumour is reported and the literature is reviewed. The reported case was unilateral with lung metastases. Immunohistochemical examination showed positive staining reaction within the tumour cells for vimentin and cytokeratin, while AFP, HCG, PLAP, EMA and CEA were not found, which is in accordance with the staining pattern found in normal Sertoli cells.

Increased serum levels of fetal hemoglobin (HbF) in patients with testicular malignancy have been suggested to be due to reactivation of HbF synthesis in the bone marrow. Since HbF is known to be present in the normal yolk sac, a series of 12 testicular germ cell tumors containing yolk sac tumor (YST) components and/or embryonal carcinoma (EC) were examined by the indirect immunoperoxidase technique for the presence of HbF in the tumor tissue. In nine tumors, the YST components, i.e., cells of the microcystic and reticular patterns as well as of endodermal appearance, were positively stained. In addition, groups of positively stained cells were found in the mesenchymal stroma of the tumors. In seven tumors, varied numbers of EC tumor cells were also HbF-positive. In the vessels positively stained, blood cells occurred to a variable extent. The appearance and distribution of HbF-positive cells in the YST components are in accordance with the various types of blood-forming cells hitherto accepted to be present in the normal conceptus during development. In addition, the staining results indicate that YST imitates not only the yolk sac proper, but also other fetal structures. Furthermore, the results support the suggestion, that the HbF in the peripheral blood of patients with testicular tumors may originate in the tumor tissue, and not necessarily in the bone marrow. Evaluation of HbF as a serologic tumor marker in such patients is, therefore, recommended.

The effects of single agent therapy with 1-(-chloroethyl)-3-cyclohexyl-1-nitrosourea, 5-fluorouracil, and 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide on a human malignant melanoma transplanted and passed serially in thymusless nude mouse were studied. Tumor response varied. A single dose of 1-(-chloroethyl)-3-cyclohexyl-1-nitrosourea induced initial tumor regression, but thereafter growth resumed at a rate similar to that in the untreated control animals. Wehn 1-(-chloroethyl)-3-cyclohexyl-1-nitrosourea was given in divided dosage at an interval of 8 days, marked and persistent tumor regression was observed. 5-Fluorouracil had no effect. Treatment with 5-(3,3 dimethyl-1-triazeno)-imidazole-4-carboxamide was always reflected by almost total regression of tumors, an effect that was independent of dose within the range tested in this study. The results resemble those reported from clinical practice in patients with disseminated malignant melanomas treated with the same agents. This suggests that the pattern of drug susceptibility is preserved after transplantation of tumors in the nude mouse. The human tumor-nude mouse system is advocated as a new in vivo model for determination of individual tumor response to chemotherapeutic agents, and its potential as a model for the proving of new chemotherapeutic agents is suggested.

In 55 patients with ultrasonically demonstrated suspected hepatic malignancy, a fine needle aspiration biopsy and a coarse needle biopsy of the same focal lesion were performed under ultrasonic guidance. In 41 of 48 cases with proven malignancy, both biopsies were positive. In the remaining seven cases, only the fine needle aspiration biopsy yielded malignant cells. Tumor typing was possible in 2 primary and 33 metastatic tumors by examination of either the cytologic or the histologic specimen; an additional 6 metastatic tumors could be typed only by evaluation of the histologic specimen. Grading of six adenocarcinomas was performed with higher accuracy in the histologic than in the cytologic specimen. Exact determination of the primary site was not possible in metastatic tumors by use of either type of needle biopsy specimen. Since the less traumatic fine needle aspiration biopsy requires fewer prebiopsy precautions and has other advantages, the coarse needle biopsy should be restricted to the few cases in which the former does not yield sufficient information.

39 patients with testicular germ cell tumor metastases were treated with vinblastine intravenous bolus injection day 1 and day 36 and bleomycin intramuscularly twice weekly for 10 weeks. 8 patients had complete remission. 4 of these are alive with no evidence of disease for 91 + to 109 + months. Studied with Wilk's method for stepwise discriminant analysis tumor volume and performance status significantly predicted the patients who had complete remission. Studied with Cox's proportional hazard model for multivariate analysis hCG in the primary tumor, serum lactate dehydrogenase, performance status, and complete remission had a significant impact on survival. The information from the risk factors may be useful in a differentiated treatment of patients with testicular germ cell tumor metastases.

Skin biopsy specimens from a patient with disseminated connective tissue nevi and from her son and daughter who had no such clinical alterations were studied with the electron microscope. The nevi showed increased amounts of thick elastic fibres, which were composed of irregularly arranged, often finger-like, subunits surrounded by a thready material. Both structures probably represent malformed components of elastic fibres, the thready material representing malformed elastic fibrils. Many of the collagen fibrils showed increased diameters and twistings, which alterations are believed to represent malformation of collagen. The fibroblasts showed changes which might be related to a pathological protein synthesis. Examination of biopsy specimens from normal skin of the patient and from the skin of her son and daughter failed to demonstrate similar alterations. The present case is regarded as an entity, distinct from dermatofibrosis lenticularis disseminata and from shagreen patch.

A 20-day-old human conceptus was studied by the indirect immunoperoxidase technique for the presence of a series of plasma proteins: prealbumin (PA), albumin (ALB), alpha-fetoprotein (AFP), alpha 1-antitrypsin (A1AT), carcioembryonic antigen (CEA), immunoglobulin G (IgG), ferritin (FER), transferrin (TR), fetal haemoglobin (HbF), human chorionic gonadotropin (HCG), human placental lactogen (HPL) and pregnancy specific beta 1-glycoprotein (SP1). In the embryo only FER and TR were found. The yolk sac was positively stained for several proteins: PA, ALB, AFP, A1AT, IgG, FER, TR and HbF were demonstrated in the endodermal cells and PA, ALB, IgG and TR in the mesothelial cells. The syncytiotrophoblast of the chorionic villi were heavily stained for all the placental proteins. HCG and HPL were additionally demonstrated in the cytotrophoblast. The Hofbauer cells of the chorionic and villous stroma stained positively for A1AT and FER. TR appeared as a characteristic band on the apical surface of the syncytiotrophoblast. The findings indicate that the yolk sac is the principle source of some of the plasma proteins also in the very early conceptus and the assumption that the yolk sac is the functional antecedent of the liver is supported. The distribution of the various placental proteins is in accordance with the present knowledge that the syncytiotrophoblast is the major site of synthesis of these proteins. Finally correlation of functional aspects of embryonic structures and germ cell tumours is recommended.