Archiv für pathologische Anatomie und Physiologie und für klinische Medicin

 Mixed medullary-follicular carcinomas (MMFC) of the thyroid are rare tumours showing the morphological and immunochemical properties of both parafollicular and follicular cell lineages. Their recognition is based on a classical WHO definition, although several other patterns have been described in recent years. We investigated 11 cases of MMFC by immunohistochemistry and in situ hybridization (ISH) to analyse the structural features, the immunophenotypic profile and the calcitonin (CT) and thyroglobulin (TG) gene expression of the neoplasm. Histologically, 10 cases had mixed parafollicular and follicular cell populations in the primary tumour and 1 only in the lymph node metastasis. All cases were immunoreactive for CT (in medullary areas) and TG (in follicular areas and also in the solid component of 8/11 cases). These findings were confirmed by ISH analysis. Combined ISH and immunostaining showed that most cases had separate CT and TG gene expression, although rare cells with concurrent CT and TG gene expression were identified in 2 tumours. We conclude that (a) MMFC display heterogeneous morphological patterns and are a special type of thyroid tumour undergoing divergent differentiation; (b) in MMFC, CT and TG genes are generally not simultaneously expressed by the same cell, although dual expression of CT and TG was present in rare neoplastic elements; and (c) the origin of MMFC, whether they are derived from the ultimo-branchial body or result from neoplastic transformation of different cell populations following common oncogenic stimuli, is unclear.

Malignant tumors invade and metastasize. They consist of cancer cells, evolving through genetic and epigenetic modulation, mixed with tumor-associated host cells, emerging from resident or bone marrow-derived precursors. These cells establish ecosystems to activate cellular programs for local invasion and distant metastasis. Characteristic of such malignancy-related activities is communication inside ecosystems between cells, ligands, receptor protein complexes, and signaling pathways as well as between ecosystems comprising the primary tumor, lymph node and distant metastasis, bone marrow and blood and lymph circulation. Complexity is another characteristic, resulting from: heterogeneity of the cell populations; the numbers of promoter and suppressor genes, their levels of regulation, and the pleiotropic activities of their products; biological redundancy of the molecular mechanisms underpinning invasion-related activities. Clinical attention is paid to putative new targets, namely host cells, individual molecules and their signaling pathways, as well as the effects of current treatment on invasion and metastasis.

Die Morphologie und Fermenthistochemie der Nebennierenrinde bei primärem Aldosteronismus wird an Hand von 10 Fällen dargestellt. Einschließlich des charakteristischen solitären Adenoms lassen sich 5 Formvarianten unterscheiden: Die Restrinde außerhalb der Adenome zeigt meist eine Atrophie der Zona fasciculata. Die 3-β-Hydroxysteroid-Dehydrogenase ist in der breiten Zona glomerulosa nur schwach aktiv. In 4 Fällen mit Normo- oder nur geringer Hypokalämie, aber niedrigem Renin wird eine mikronoduläre Hyperplasie ohne Adenom gefunden. Diese Fälle stellen klinisch und biochemisch eine Sondergruppe von Mineralcorticoidsyndromen dar, deren Ätiologie unbekannt ist. Kennzeichnend für die mikronoduläre Hyperplasie ist die spongiocytäre Umwandlung der Glomerulosazelle.