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.

Sixteen cases of anaplastic carcinoma (ACA) and 4 cases of malignant haemangioendothelioma (HAE) of the thyroid were studied by light microscopy and immunohistochemistry.

97 cases of acute necrotizing granulomatous lymphadenitis (so called “reticulozytärabszedierende Lymphadenitis” were examined retrospectively with the Warthin-Starry stain, in order to detect bacteria in patients with cat-scratch disease (CSD). 27 patients with CSD were found and among those, bacteria were demonstrated in 4. The organisms were pleomorphic rods of about 3 micron length and occurred in clumps within foci of fresh necrosis.

Twelve duodenal carcinoid tumours are presented, 4 of them located in the ampulla. Symptoms included the Zollinger-Ellison syndrome (4 patients), the carcinoid syndrome (1 patient), mechanical obstruction (3 patients), bleeding (1 patient) and abdominal pain (1 patient). Two further tumours were detected by chance.

In order to study the nature and significance of various giant cells encountered in seminomatous tumors of the testis, we reviewed the morphology of 243 consecutive pure seminomas and 107 combined (mixed) tumors, as well as the long term clinical follow-up in 26 patients. Giant cells were grouped into histocytic or neoplastic ones and the latter subtyped according to morphologic and immunocytochemical characteristics. Neoplastic giant cells were found in 34.6% of all pure seminomas and in 11.2% of all combined tumors, i.e. twice as often as histocytic giant cells in either tumor group. The various types of neoplastic giant cells were found alone or in combinations with other types. Giant cells capable of elaborating B-HCG were seen in 19.3 % of all pure seminomas and in 9.3% of seminomatous components of combined tumors. These incidences argue strongly against a trophoblastic element infiltrating a seminoma from a concomitant occult choriocarcinomatous focus. Large mononuclear giant cells, seen in spermatocytic seminomas, were observed in 15.6% of all pure seminomas, particularly in combination with B-HCG producing giant cells. Another type, characterized by marginated nuclei and eosinophilic cytoplasm were invariably part of a mononuclear cell population of similar features and encountered focally in 9.1% of all pure seminomas.

A histological review of 72 undifferentiated thyroid tumors was performed in order to discover small cell anaplastic carcinomas and Non-Hodgkin lymphomas. Cases suspected to be lymphoma were examined for the presence of Ig and keratin and lectins with a PAP-procedure.

Although they cannot be regarded as pathognomonic, there are numerous definite changes in the fine structure of the testis in Klinefelter’s syndrome. Several alterations in Leydig cells and Sertoli cells suggest an impaired biological function. In addition, in both cell types ultrastructural alterations interpreted as signs of immaturity or regression can be observed. The multiplication of the basement membrane, the amount of collagen fibers in and between the Ley-dig cells, and the occurrence of non-myelinated nerve fibers in the tubular wall are not completely understood and merit closer attention.

It is uncertain whether the so called intratubular atypical germ cells (carcinoma in situ cells) demonstrable in the testicular tissue around different germ cell tumors and in testicular biopsies of patients with impaired fertility are identical with regard to their morphology and further development. Thus atypical germ cells of 18 patients with testicular germ cell tumors and of 3 patients with atypical germ cells in testicular biopsies without tumor were studied by electron microscopy and/or by immunohistochemistry. The atypical germ cells show characteristic alterations distinguishing them from normal germ cells, especially spermatogonia. However, there are no differences between atypical germ cells in the above mentioned groups. Immunohistochemical reactions are negative with anti-alpha-fetoprotein and anti-beta-human-chorionic-gonadotropin, but 6 of the 15 cases are positive with antiferritin. However, this positive reaction occurs in cases in different diagnostic groups. Atypical germ cells of the different groups cannot be distinguished by electron microscopy or immunohistochemical methods, but further investigations vestigations, including cell cultures, may provide more information.

Two distinctly different kinds of motile components were recently found in stage III-VI (1) rat spermatids (2). One of them, the early flagellum, a naked 9+2 axoneme produces wave-like motions and torsions (Figs. la and lb). Later stages where a spindle-shaped body is recognizable are restricted to bending (Fig. 2). Testicular spermatozoa are equipped with a hooked head and immotile (Fig. 3). Modification of flagellar motion seems to be due to thickening of the flagellum by formation of accessory structures such as a mitochondrial sleeve, dense fibers and fibrous sheath (Figs. 4 and lb)(3). Earlier investigations demonstrated elastic skeletal function of the accessory elements in mammalian spermatozoa, where the axoneme is the only component of active motility (4). Dense fibers and the fibrous sheath differentiate in absence of the axoneme but their arrangement is not sym-metric (5). Ultrastructural analysis of dynein-lacking human spermatozoa revealed asymmetric arrangement of the longitudinal columns of the fibrous sheath, possibly a result of disturbed flagellar motility already at the level of spermatids (6). In fact, early human spermatid flagella display motions similar to those found in the rat (7).

Thirty-six malignant hemangioendotheliomas of the thyroid were examined immunohistochemically using antibody probes to factor VIII-related antigen in order to reevaluate the histogenesis of this neoplasia. The 36 cases were reclassified according to their light microscopic features without prior knowledge of the immunohistochemical results. Three different tumor types were discerned: Group I: classical hemangioendotheliomas (20 cases); Group II: borderline cases between malignant hemangioendotheliomas and anaplastic carcinomas (14 cases) and Group III: anaplastic carcinomas with hemangio-endotheliomatous features (2 cases). Factor VIII-related antigen could be demonstrated in 12 (60%) tumors of group I, 3 (21%) tumors of group II and in neither tumor of group III. Five control cases with the typical histological picture of anaplastic carcinoma of the thyroid were negative for factor VIII-related antigen. The results of our study suggest that at least part of the tumors termed as malignant hemangioendotheliomas are in fact derived from endothelial cells.

Giant spermatogonia (GS) characteristically appear singly between their normal counterparts. Their cytoplasm is clear by light microscopy and their ovoid nuclei, measuring at least 13 micron in diameter, contain homogeneously distributed chromatin. These cells were described originally in the last century and were interpreted as isolated physiological giant cells of the sexual epithelium (Stieve 1930). In our own study we found GS in the normal testis at an average frequency of 0.65/50 tubules. GS occur at the same frequency in testicular tissue surrounding germ cell tumors and in biopsy specimens from men with impaired fertility, except in the so-called mixed atrophy of the testis where increased numbers of GS per tubule are found. Ultrastructurally, GS are distinguishable from normal spermatogonia, from atypical germ cells and from seminoma cells. In addition, we found several distinct ultrastructural differences between GS and cells of pre-spermatogenesis as reviewed in the literature.

It is generally believed that the histological pattern of papillary thyroid carcinomas has no influence on the course of the disease. However, we were puzzled by the evident differences in the clinical course of these tumours and decided to re-examine all microscopic specimens available at the Institute of Pathology of the University of Zürich. These had been obtained from 169 surgical cases operated on between 1962 and 1977. We classified the material according to precise morphological criteria and matched it with a number of clinical and catamnestic data in order to determine which parameters correspond best with the development of the disease. Although the fate of patients below 50 years of age is slightly more favourable than that of older subjects, age is by no means the most important factor. In fact, the prognosis correlates significantly better with the initial local extension of the primary tumour (occult, intrathyroid or extrathyroid). Furthermore, this parameter is closely related to the histological pattern of our various papillary carcinoma subtypes which we graded according to differentiation. All factors considered, the morphological pattern appears to offer a rewarding approach to the provision of an accurate prognosis.

65 cases of focal lymphocytic thyroiditis and Hashimoto's disease and five cases of thyroiditis de Quervain were studied with immunohistological methods. In both focal lymphocytic thyroiditis and Hashimoto's disease, lymph follicles with active germinal centers were found which contained germinal center cells that stained positively for intracytoplasmic immunoglobulins (heavy and/or light chains). Positively staining germinal center cells made up only a minor portion of overall immunoglobulin-positive cells; most of the positive infiltrating cells were plasmacytes arranged in small groups or clusters among thyroid follicles. Thus the number of immunoglobulin-containing cells differed greatly between focal lymphocytic thyroiditis, where sites of infiltration were represented by lymph follicles, and Hashimoto's disease. In the former, only a few cells outside lymph follicles stained positively for intracytoplasmic immunoglobulins, whereas in the latter numerous cells within areas of coherent infiltration did. Furthermore, in most cases of Hashimoto's disease macrophages and giant cells with positive staining for lysozyme were present in variable numbers, while in focal thyroiditis they were less frequent or absent. Between these two immunohistologically separable groups, i.e. focal lymphocytic thyroiditis and Hashimoto's disease, there were many cases with features of both. Considering the occurrence of such intermediate forms and some immunohistological similarities between Hashimoto's disease and focal lymphocytic thyroiditis (nearly identical ratio of the different immunoglobulin classes and similar distribution of immunoglobulin-positive germinal center cells), it is likely that these lesions represent different activities of a same immunological process.

In 17 cases of male sterility with so-called "mixed atrophy" in testicular biopsies, the germinal epithelium was investigated by quantitative as well as by ultrastructural means. In 13 cases, the number of spermatids only was reduced, in 2 cases earlier stages of germinal cells were diminished also. Normal quantitative data were found in biopsies of 2 patients. Among ultrastructural alterations various disturbances of the acrosome were dominant. Additional ultrastructural findings in spermatids included binucleate forms and lack of mitochondrial sheaths in the middle-piece. The largely uniform changes in the tunica propria (fibrosis of the innermost layers, extensive changes of the basement membrane) were considered to be at least one of the cofactors responsible for the alterations of the germinal epithelium.

In order to obtain insight into the basic mechanism of cytoplasmic undulation in early spermatids, tubuli seminiferi of young adult rats were fixed in Stieve’s solution and examined immunohistochemically with anti-fast skeletal muscle myosin serum. A number of nuclei of spermatogonia, spermatocytes and spermatids stained intensely, but in addition the cytoplasm of early spermatids showed a positive reaction. It is suggested that myosin is involved in the cytoplasmic movements of earlier spermatids. The findings indicate a connection between contractile proteins and sterility in man.

Cushing's syndrome was found in 2 of 4 siblings all of which also had other malformations. After bilateral adrenalectomy no hyperpigmentation was noted. Morphologically the adrenals of both siblings with Cushing's syndrome showed the typical lesions of the so-called microadenomatosis or primary adrenocortical nodular dysplasia with foci of eosinophilic giant cells. This is a new form of Cushing's syndrome due to an inborn error of the adrenals and no hypothalamic-pituitary dysfunction.

Thyroid tissue of 300 routine autopsies was processed in a standardized manner. So-called solid cell nests (SCN) were found in 21 patients (7 %). These cases were investigated carefully by serial step sectioning. In order to explore the correlation of SCN to the C-cell system, the sections were stained by silver impregnation and the immunoperoxidase method. Morphometric analyses revealed a significant increase in the density of C cells in the proximity of the SCN. With progressive distance from the SCN, the C-cell density decreased and reached normal values. In 30 % of the cases argyrophilic and calcitonin-positive cells were found lying within the SCN. Occasionally, mixed follicles could be discerned: These were lined on the one side by a multilayered squamous epithelium, on the other side by normal monolayered cubic follicular epithelium, and contained a peculiar granular material. In one case, SCN were associated with intrathyroid portions of the parathyroids and adult adipose tissue, in a second case with adipose tissue only. Most probably SCN are vestiges of the ultimobranchial body and should be interpreted as such, despite the fact that other authors have expressed different views. The lack of disturbances in the calcium metabolism of the patients and the absence of medullary carcinoma in their family histories led us to interpret locally confined C-cell hyperplasia not as reactive nor premalignant, but rather as normal.

Das häufige Vorkommen arteriolärer Hyalinosen in Hoden verstorbener Patienten ist bekannt. Gleiche Gefäßveränderungen können auch in Hodenbiopsien und operativ entfernten Hoden gefunden werden. Um uns ein Bild über die Häufigkeit machen zu können, untersuchten wir eine Serie von 2400 Hodenbiopsien und einzelnen operativ entfernten Hoden systematisch lichtmikroskopisch, teils auch histochemisch und elektronenoptisch im Hinblick auf arterioläre Hyalinosen. Dabei konnten in 3,75% der Patienten typische Herde nachgewiesen werden (Durchschnittsalter 34 Jahre). An Hodengrundkrankheiten findet man vor allem tubuläre Atrophien (58%) oder Kryptorchismus (22% der Fälle mit Gefäß Veränderungen). Die histochemischen Reaktionen lassen vermuten, daß der Hauptteil der eingelagerten Substanz aus Lipoiden, besonders Lecithinen besteht. Daneben sind auch Mukopolysaccharide abgelagert. Elektronenoptisch handelt es sich vorwiegend um fein granuläre Depots mit Vakuolen und seltenen Myelinfiguren. In späteren Stadien ist subendothelial ferner elastinartiges Material zu sehen, an der Peripherie der Herde sind Kollagenfasern nachweisbar. Die pathogenetische Bedeutung dieser arteriolären Hyalinoseherde und ihre Ursache sind unklar.

Testicular seminomas may occur in various forms, of which the classical and spermatocytic are distinct, the anaplastic or atypical seminomas, however, less clearly defined. Lately, a separate group of particular clinical significance, comprising seminomas with syncytiotrophoblastic giant cells (STGC), has been specified. Although this type of seminoma had been recognized morphologically long ago, recent investigations have shown its ability to secrete HCG, a fact that raises serious difficulties in its differential diagnosis with combined seminomas and choriocarcinomas. Two cases of seminomas with STGC are presented and pertinent clinical and morphologic problems discussed.

Histological examination of numerous biopsies from mature testes, repeatedly showed irregularities of the elastin staining in the tunica propria of the seminiferous tubules. Even when abundant elastic fibers were visible by light microscopy, no elastic fibers were demonstrable in the electron microscope in ultrathin sections of testicular tubules embedded in Epon and contrasted with phosphotungstic acid (PTA). In 43 biopsies from 22 men aged 17–39 years (19 investigations of sterility and three patients with hypogonadotropic hypogonadism) we therefore checked for the occurrence of elastic fibers in the wall of the seminiferous tubules. Matrix loci of elastic fibers could indeed be demonstrated by electron microscopy using PTA and potassium permanganate (KMnO4), but only after embedding in araldite. Under these conditions, light and electron microscopic findings agreed with each other. The appearances of moderate and severe testicular tubular atrophy differed slightly from one another with regard to the amount of elastin. In the “Sertoli cells only syndrome”, elastic fibers were demonstrable only outside the hyalinized inner layer. In the Klinefelter syndrome, only “uncertain” elastin loci were present, but greatly increased microfibrils were to be seen using the electron microscope. No elastic elements and only very sparse microfibrils were present in the tunica propria of the tubules of young men with hypogonadotropic hypogonadism.