Med. Weter. 71 (5), 264-275, 2015

full text

Madej J.A.
Pathomorphology and pathogenesis of very rare groups of tumors
The paper describes the pathomorphology of very rare neoplastic syndromes in humans and animals, namely mucosa-associated lymphoid tumors (MALTomas), gastro-intestinal stromal tumors (GISTomas), perivascular endothelial tumors (PEComas), multiple endocrine neoplasias (MEN), and neuroendocrine tumors (NETs). Particular attention is devoted to MALTomas of a non-Hodkins lymphoma type, originating from the marginal zone of lymphoid tissue accumulations, as well as to “secondary” lymphomas, originating on the basis of an earlier development involving a chronic lymphocytic inflammatory process, frequently of the type of autoimmune reaction. This group includes classic lymphoma, arising with cooperation of Helicobacter pylori, thyroid lymphoma (in the autoimmune Hashimoto disease), and salivary gland lymphoma (in the autoimmune Sjögren’s syndrome). Interestingly, the abovementioned lymphomas are examples of neoplastic development based on local, rather than systemic, autoimmune processes. Very seldom lymphomas of the MALTomata type can be encountered in the skin, breast, brain, bronchi, thymus, bone marrow, uterine cervix and endometrium, auditory canal, testis, and lymph nodes that drain the alimentary tract. All non-Hodkin lymphomas are malignant and monoclonal with a very differentiated immunofenotype and with karyotypic lesions, which may injure bone marrow, thus leading to anaemia and haemorrhagic diathesis. In MALTomatas, one can note disturbances in function of affected organ due to the chromosomal aberration of the BCL-10 and iMALT1 genes and disturbances in proteins corresponding to them, the role of which is the formation of complexes that control cell death. GISTomata (GISTs) stem from precursor stem cells for myocytes, interstitial Cajal cells, and other mesenchymal cells of the alimentary tract. In such tumors, mutations develop in the c-kit gene, causing a permanent activation of protein KIT, transmembrane type 3 tyrosine kinase, which promotes cell proliferation. As a rule, they represent non-malignant tumors; only occasionally developing pseudocapsules. Both non-Hodkin lymphomas and GISTomata can be classified as tumors of the mesenchymomata type or tumors originating from mesoderm and mesenchyme. PEComata represent another group of mesenchymal tumors, which includes the so-called clarocellular “sugar” tumor of the lungs, characterized by the expression of HMB-45, S-100 protein, and vimentin. Associations are also described between MEN I and MEN II syndromes and tumors originating from neuroendocrine cells, that is, NET type tumors (neuroendocrine tumors), currently included in the DNS (diffuse neuroendocrine system) – the previous APUD system. The markers of net type tumors include neurospecific enolase, synaptophysin, chromogranin A and B, and HVMAT-II (human vesicular monoamine transporter isoform – 2). In MEN I, MEN II syndromes and in fibromatosis, mutations develop in suppressor genes, that is, respectively in MEN I (MEN I), RET (MEN II), NF1 and NF2 (fibromatosis). In addition, the paper suggests new names for a group of tumors involving GALTomas (gut-associated lymphoid tissue) and for ESTomas (endometrial stromal tumors). It describes cases of borderline tumors, non-malignant carcinomas, for which it is difficult or impossible to establish a correct differential diagnosis. A mention is also made of two new suppressor genes of neoplastic development, that is, the alfa-Klotho gene and the BLM I gene, whose loss of function allows the cell to enter the pathway of neoplactic development. The role of the CDH1 gene is also presented as an example of an epigenetic factor in neoplasia.
Key words: MALToma type, GISToma type, PEComa type tumors, MEN syndromes, NETs, borderline tumors (BTs)