[Problems in the classification of thyroid tumors. Their significance for prognosis and therapy]. / Probleme der Klassifizierung von Schilddrüsentumoren. Ihre Bedeutung für Prognose und Therapie.

Standardized nomenclatures of tumors are mandatory for epidemiological investigations as well as for the correct interpretation of pathological diagnoses by the clinician. Not least thanks to the activity of the World Health Organization (WHO), uniform tumor nomenclatures in worldwide use have been adopted for most organs. This applies also for the thyroid, even in Switzerland, where many pathologists had formerly been convinced that only the special and rather complicated nomenclature of Langhans, adapted by Wegelin, was consistent with the special tumor situation in Switzerland, a former endemic goiter area. The simplified classification of WHO is demonstrated for the group of malignant tumors of the thyroid and the problems concerning their classification are discussed. Difficulties of classifications arise in well differentiated tumors rather than in undifferentiated, anaplastic forms. For example, it is not possible to assess unequivocally the malignancy of strongly encapsulated forms of highly differentiated follicular tumors. They are then called, rather evasively, "atypical adenomas". The difficulties do not lie in the system of classification but in the tumor's specific manner of growth, and the clinician should be aware of this. Otherwise he may overstrain the diagnostic potentialities of his pathologist.

Hyperplasia and hypertrophy of Leydig cells associated with testicular germ cell tumours containing syncytiotrophoblastic giant cells.

In patients with seminomas and non-seminomatous germ cell tumours of the testis syncytiotrophoblastic giant cells (STGC) are largely responsible for elevated levels of chorionic gonadotropin. In searching for these cells, the question arises whether hyperplasia and/or hypertrophy of Leydig cells in the adjacent testicular tissue is a relevant finding. To elucidate this problem we analysed the tumour-free testicular tissue of 20 seminomas and 20 combined seminomatous and non-seminomatous germ cell tumours with or without immunohistochemically demonstrable STGC morphometrically. Extension of Leydig cell areas and the surface areas of Leydig cells per tubule are increased significantly in seminomas and combined tumours when STGC are present. There is also an apparent increase in the number of Leydig cells per tubule in seminomas and combined germ cell tumours with STGC. The difference, however, is not significant statistically in the group of seminomas. Hypertrophy and/or hyperplasia of Leydig cells must be considered as a relevant finding in germ cell tumours with STGC. It is most easily recorded by evaluating the surface area of Leydig cells per test area or per tubule.

Malignant haemangioendothelioma of the thyroid, immunohistochemical evidence of heterogeneity.

26 cases of malignant haemangioendothelioma (MHE) of the thyroid gland were investigated immunohistochemically with the endothelial marker UEA-1 lectin and the panepithelial marker Lu-5. The results were compared with the results of staining for factor VIII-related antigen in the same cases observed in a previous study of Pfaltz et al. The 26 cases were classified on light microscopic grounds without reference to the immunohistochemical results as classical MHE (15 cases) and borderline cases intermediate between MHE and undifferentiated carcinoma (11 cases). 7 of the 15 classical MHE revealed one or both of the vascular markers, but did not express the epithelial marker. One case showed no staining and another reacted only with Lu-5. Vascular and epithelial markers were found in 6 cases of the 15 classical MHE and in 2 of the 11 borderline cases. These findings indicate that MHE of the thyroid may represent a heterogeneous group of lesions. Tumours positive only for endothelial markers strongly support the hypothesis that MHE is of endothelial origin, whereas tumours which reacted only to the epithelial marker may be undifferentiated carcinomas. Cases with both epithelial and endothelial features on immunohistochemical investigation may represent either tumours in which the malignant cells are in transition from epithelial to mesenchymal differentiation as suggested by Eckert et al. or are tumours of malignant endothelial cells with epithelial differentiation particularly of their cytoskeleton.

The WHO histological classification of thyroid tumors: a commentary on the second edition.

This article introduces the revised WHO classification of thyroid tumors, giving an account of the major changes made and the reasons behind the changes, as well as listing the actual classification now recommended. It is intended to draw general attention to the revision, the full version of which will be published separately.

Differences between subcutaneous and intraperitoneal forms of three human testicular teratocarcinomas in nude mice.

Three human testicular teratocarcinomas were serially passaged following subcutaneous transplantation into nude mice. Tumor cell suspensions from selected passages were injected intraperitoneally. The subcutaneous transplants of each tumor conserved the morphological characteristics of one component of the primary tumor, namely an embryonal carcinoma in one case and a yolk sac tumor in two. The latter maintained the capacity to synthesize alpha-fetoprotein (AFP). After intraperitoneal injection of cell suspensions, tumors, either attached to or even invading abdominal organs or in the form of free-floating tumor spheroids, were observed. AFP could be localized within the attached growths but not in the spheroids. A critical tumor volume and/or vascularization seemed to be necessary for AFP production in tumor cells. In spheroids from one tumor, cytogenetic analysis revealed both human and murine cells. Thus, these spheroids, apparently composed of tumor cells in the center and murine cells at the periphery, can not be considered to be embryoid bodies.

[Bilateral germ cell tumors of the testis]. / Bilaterale Keimzelltumoren des Hodens.

Before the introduction of effective chemotherapy for testicular germ cell tumours, the relative frequency of bilateral germ cell tumours was about 1.6%. Now, as more patients with unilateral tumours survive, an increase in this percentage is to be expected. We therefore compared a series of 397 patients with testicular germ cell tumours observed between 1950-1975 with a series of 333 patients with such tumours observed between 1976-1985, after the introduction of chemotherapy with cis-platinum. In both series 7 patients had bilateral germ cell tumours, i.e. 1.8% of cases in the first series and 2.1% of cases in the second series. Since the second series of cases with a much shorter follow-up has an unbalanced ratio of seminomatous to non-seminomatous tumours, an increase in bilaterality can be expected. The prophylactic and therapeutic implications of an increase in bilateral germ cell tumours of the testis are discussed.

Intracranial mixed germ cell tumor with syncytiotrophoblastic giant cells and precocious puberty.

A 9-year-old male patient developed a germ cell tumor in the right basal ganglia which secreted beta-human chorionic gonadotropin (beta-HCG) and caused precocious puberty. Histology and immunohistochemical staining for placental alkaline phosphatase (PLAP), alpha-fetoprotein (alpha-FP), and beta-HCG showed a mixed population of neoplastic germinocytes, embryonal carcinoma, and syncytiotrophoblastic giant cells (STGC). Immunohistochemical double-staining for alpha-FP and beta-HCG revealed that these two markers were produced by different subsets of cells. Expression of the proliferation marker Ki-67 showed a growth fraction of 53% for the neoplastic germinocytes and embryonal carcinoma cells, but only 21% for the STGC.

Solid cell nests (SCN) in Hashimoto's thyroiditis.

In Hashimoto's thyroiditis squamous metaplasia has been described by several authors. Such foci resemble the so-called solid cell nests (SCN) of the thyroid, epidermoid structures thought to be remnants of the fourth endodermal pouch. These cell nests can be identified by their particular histological appearances and by their positive reaction with polyclonal anti-CEA. In order to study this phenomenon more closely we examined the H & E-stained histological sections of 79 cases of Hashimoto's thyroiditis systematically. In 39 cases cell nests of three different types could be demonstrated: Small groups of elongated cells organized into solid epidermoid clusters, larger epithelial cells forming solid nests or similar epithelial but cystic structures. 29 of these 39 cases were further investigated immunohistochemically for the presence of thyroglobulin, CEA (polyclonal antiserum) and calcitonin. The first type of cell nest did not show any CEA-positivity, whereas the second and third type contained CEA-positive cells in 73% of the cases. In no cases were thyroglobulin- or calcitonin-positive cells identified in these epidermoid foci. Slide series of 25 of the 39 cases have further been investigated immunohistochemically for the presence of CEA (monoclonal antiserum), chromogranin, keratin and the epitope for Lu-5. In these additional series foci of epidermoid cells could be demonstrated in up to 15 of the 25 cases. They showed a positive reaction for the monoclonal CEA antiserum in only 3 of 15 cases, for anti-keratin in 5 of 14 cases and for Lu-5 in 13 of 15 cases. Immunoreactions for chromogranin were negative in all cases. Our findings suggest that epidermoid cell nests in Hashimoto's thyroiditis more closely resemble SCN than foci of follicular cell squamous metaplasia.

Haemangioblastoma. An immunohistochemical study of ten cases.

Ten cases of cerebellar haemangioblastoma were studied using the immunoperoxidase technique for glial fibrillary acidic protein (GFAP), Factor VIII-related antigen (F8RA), Ulex europeus agglutinin 1 (UEA-1), S-100 protein, neurone-specific enolase (NSE), leucocyte common antigen, synaptophysin, chromogranin and eight polypeptide hormones (bombesin, pancreatic polypeptide, somatostatin, thyroglobulin, calcitonin, glucagon, insulin and gastrin). GFAP and S-100 were demonstrated at the periphery of all tumours and in small groups of cells in the centre of four cases. Most of these cells had the morphology of reactive astrocytes but some had the appearance of stromal cells. In general stromal cells gave negative results. F8RA and UEA-1 stained the endothelial cells in each case but there was no stromal cell reactivity. NSE was present in the stromal cell component of all tumours. There was no staining for synaptophysin, for chromogranin, or any of the polypeptide hormones. It therefore appears that some haemangioblastomas contain an admixed non-neoplastic astrocytic element. NSE, F8RA and UEA-1 staining demonstrates that the endothelial and stromal cell parts of the tumour are antigenically distinct. Recent reports of polypeptide hormone expression cannot be confirmed and it is therefore unlikely that stromal cells originate from primitive peptidergic neurones.

Structure and motility of primary cilia in the follicular epithelium of the human thyroid.

In order to clarify contradictory reports concerning ciliary structure and function, follicular epithelium from macroscopically normal portions of 37 surgical specimens of human thyroid were processed for video-microscopy and/or transmission electron microscopy. The cilia of living cells were immotile. In transverse sections the cilia revealed a 9 + 0 pattern at the base of the shaft, whereas towards the distal end the number of microtubular doublets diminished. Dynein arms, radial spokes and central microtubules were absent. The immotility and structure of these primary cilia implies that their function is not related to motility. The phylogenetic and ontogenetic development of the thyroid suggests that tumor cells of follicular origin displaying abnormal secondary cilia may represent a pathological variant of differentiation.

[Cryptococcoma of the adrenal gland]. / Kryptokokkom der Nebenniere.

The case is described of a 49-year-old man who developed cryptococcal meningo-encephalitis ten months before his death. Six months later complicating hydrocephalus occurred which required the implantation of a ventriculo-peritoneal shunt. A further four months later the patient, who was receiving anticoagulation therapy due to deep vein thrombosis, died from intraventricular cerebral haemorrhage. In a blood culture taken shortly before his death, growth of Cryptococcus neoformans was detected. At autopsy, which confirmed cerebral haemorrhage as the cause of death, a large cryptococcoma of the left adrenal gland was discovered as an incidental finding. We presume that this cryptococcoma was the source of the new haematogenous dissemination of the disease. We review the literature and discuss the increasing importance of cryptococcosis.

[Combination of heart myxoma with primary nodular adrenal cortex dysplasia. Case report of a further kinship of this rare familial syndrome]. / Kombination von Herzmyxom mit primärer nodulärer Dysplasie der Nebennierenrinde.Beobachtung einer weiteren Sippe dieses eigenartigen familiären Syndroms.

Another case of the rare syndrome of combined papillary cardiac myxoma and primary adrenocortical nodular dysplasia is reported. The lesions were discovered incidentally at autopsy in a 64-year-old woman who had died of cerebrovascular stroke. Further investigation of the family by echocardiography revealed a small left atrial tumor in the 33-year-old son of the patient. Pathological examination after surgical resection of the tumor confirmed the diagnosis of atrial myxoma. The patient also exhibited cutaneous nodules with histologic features of myxofibroma. Some morphological aspects of this peculiar familial syndrome are discussed, with special emphasis on the finding of follicular tumors of the thyroid possibly associated with this syndrome.

[Hippel-Lindau syndrome: morphology and immunohistochemistry of tumors related to this syndrome]. / Hippel-Lindau-Syndrom: Morphologie und immunhistochemisches Verhalten einiger dem Syndrom zugeordneter Tumoren.

Hippel Lindau syndrome (HLS), inherited as a simple dominant trait, is characterized by angiomatosis in the brain and retina, and also by cysts and tumours in various abdominal organs. Microscopically there is a striking morphological similarity between some of these tumours and especially between those in the brain (hemangioblastomas) and in the kidneys (renal cell carcinomas). Biopsy and autopsy material from two patients with HLS was examined chiefly by immunohistochemical methods, to investigate further the origin of these tumours. The cerebral hemangioblastomas of both patients showed tumour cells with a positive immunohistochemical reaction for neuron-specific enolase (NSE), suggesting a neural or neuroendocrine origin, while corresponding investigation of the kidney tumours did not produce similar clear results. Systemic immunohistochemical investigation of all tumours related to this syndrome is recommended.

Abnormal basement membrane structures in autoimmune thyroid disease.

Thyroidectomy specimens of 8 patients with focal thyroiditis, 7 with diffuse thyroiditis, 13 with Graves' disease and 5 with nodular goiter were investigated by electron microscopy for changes in the follicular basement membrane. Five different types of abnormal basement membrane structures (ABMS), analogous to the ones described in the glomerular basement membrane, were found. Type 1 ABMS were present in all diagnostic groups and seemed to be nonspecific. Type 2 ABMS, thought to represent immune complex deposits, were frequently present in patients with focal or diffuse thyroiditis and in patients with Graves' disease, but could not be demonstrated in thyroidectomy specimens of patients with nodular goiter. The occurrence of type 2 ABMS in both focal and diffuse thyroiditis suggests a common etiology of these two morphologic entities. ABMS types 3, 4, and 5 could not be detected in nodular goiter but were seen in various amounts in all other diagnostic groups. The origin of these structures remains to be explained.

[Occurrence of fibrosis in subacute de Quervain thyroiditis]. / Die Fibrosierungstendenz bei subakuter Thyreoiditis de Quervain.

Subacute thyroiditis of de Quervain is histologically characterized by an inflammatory reaction with histiocytes and giant cells around residues of colloid, producing a tubercle-like granulomatous picture. A variable degree of fibrosis occurs, but recovery is generally almost complete. Investigation of a series of thyroid glands with de Quervain's thyroiditis gave the impression of rather extensive and increasing fibrosis in most of these glands. To substantiate this impression we reviewed the histological slides of all our cases of de Quervain's thyroiditis diagnosed at the Department of Pathology of the University of Zurich between 1940-1950 and 1974-1984. In the majority of the glands of both periods we found rather extensive fibrosis involving more than 50% of the surface. In young patients the fibrosis seemed to be more extensive than in older subjects. There was no sex difference. A certain degree of fibrosis appears to be characteristic of de Quervain's thyroiditis. Differences of frequency and degree of fibrosis between the two periods could not be demonstrated.