title: Two different types of carcinoid tumors of the lung: immunohistochemical and ultrastructural investigation and their histogenetic consideration.
abstract: Carcinoid tumors have been an interesting clinical and pathological entity for pathologists because of their unique histopathologic pattern of "Zellballen" (cell ball) and the hormones they produce demonstrable by histochemical and biochemical methods, including immunohistochemistry, and the presence of cytoplasmic dense-core particles demonstrable by electron microscopy. Since carcinoid tumors were established as an entity more than a century ago by Oberndorfer, who was credited with coining the term "carcinoid," meaning carcinoma-like tumors, tumors presenting with similar characteristics have been reported in most of parenchymal organs, including lungs.   Carcinoid tumors in the lungs usually occur as bronchocentric tumors and present with typical histopathologic characteristics of carcinoid tumors, but they may present with significant variation in their cellular compositions, in contrast to the midgut carcinoid tumors. In the latter, tumor cells are quite similar to enterochromaffin granule containing crypt cells, which are regarded as their progenitor cells. Currently, a similar histogenetic explanation is applied to all carcinoid tumors occurring elsewhere.   The bronchus is one of the most common anatomic sites in which the carcinoid tumors occur. However, bronchial carcinoid tumors differ from the midgut counterparts in microscopic appearance, showing more variability in cellular shape and composition from the classical form of midgut carcinoid tumors.   In the lungs, neuroendocrine cells (NEC) are normally found in two different ways. Firstly, they are found as randomly scattered single cells (Kultchitsky cells) similar to enteric counterparts, and, secondly, they are found in aggregates known as "neuroepithelial bodies" (NEB) usually found in the branching point of bronchi. Interestingly, they keep a close anatomic relationship with parasympathetic nerve structures and even form synapses. NEB are usually found in the early stage of fetal development and are claimed to play an important role in the branching of bronchi and regeneration of bronchial epithelial cells following tissue injury. They are claimed to play an important function as a chemoreceptor apparatus related to oxygen tension of the breathing air.   To test the hypothesis that histopathologic variability found in bronchial carcinoids may be related to the fact that lungs are endowed with more than one type of NEC, the author reviewed 36 cases of bronchial carcinoids and found 8 cases in which tumor cells varied significantly from typical carcinoids in cell shape and arrangement. Tumor cells tend to be spindly with frequent presence of S-100-positive sustentacular cells. The latter was designated as type II carcinoid and the rest as type I.   Ultrastructurally, tumor cells in type I exhibited features more typical for epithelial cells. The tumor cells were usually polygonal, forming closely packed cell masses, and cell membranes were closely apposed with frequent primitive cell junctions. The membrane-bound dense-core granules were of variable size and appearance and larger than those seen in type II in which the size of granules ranged from 160 to 350 nm. In 2 cases of type I, frequent cells contained myelin bodies similar to those found in type II alveolar cells. In 14 cases of type I tumors, tumor cells formed lumens into which microvilli were converging. In 5 cases, some areas showed increased cell size exceeding the usual limit of pathologist's comfortable range of small cells. In 2 cases, the tumor contained areas of adenocarcinoma.   Tumor cells in type II were rather oblong and closely packed without any intercellular spaces and the majority of tumor cells contained dense-core granules typical for so-called P granules. These cells seem to give out slender cell processes containing a few dense-core granules. In rare foci, groups of thin cell processes aggregate where profiles of processes cut at different angles can be seen. In such areas one can recognize the profiles of microtubules in many of them. In one tumor, which was previously reported by the author (Ultrapath 2001;25:207), microtubule-containing dendrites were common, as seen esthesioneuroblastomas. They appeared similar to dendrites of neurons. In addition to these chief cells, there were variable numbers of agranulated cells usually found at the periphery of cell balls bordering the interstitium. Some of these cells contained large aggregates of polymorphic dense bodies. However, no definite premelanosomes were found in our series.   The results indicate that there exist at least two different types of carcinoid tumors in the lungs and their immunohistochemical and ultrastructural characteristics are quite different. The type I tumors are quite similar to those found in the midgut and their histogenesis might be similar. The type II tumors showed rather definite neural features in their immunophenotypic and ultrastructural characteristics, which is difficult to explain by the same histogenesis applied to type I. We postulate that type II tumors have a different histogenesis from type I. They may derive from NEC of neuroepithelial bodies rather than Kultchitsky cells. In this regard, it is interesting to note the similarity between neuroepithelial bodies of the lungs and olfactory bulbs in their cellular composition and anatomic arrangement of epithelial cells and nerves, and the similarity between tumors they produce, bronchial carcinoid tumors in our type II and olfactory neuroblastomas.   It is concluded that there are two types of bronchial carcinoid tumors having two different histogenetic pathways. Detailed analysis of the ultrastructural characteristics is the best and definite means to differentiate two types of pulmonary carcinoid tumors.
authors: Department of Pathology, Deaconess Hospital, University of Oklahoma, College of Medicine, Oklahoma City, Oklahoma 73112, USA. kyungwhanmin@yahoo.com
authors: Kyung-Whan
authors: KW
authors: Min
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D002276:Carcinoid Tumor / Q000737:chemistry / Q000145:classification / Q000175:diagnosis* / Q000648:ultrastructure; D004847:Epithelial Cells / Q000737:chemistry / Q000648:ultrastructure; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000737:chemistry / Q000145:classification / Q000175:diagnosis* / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D046568:Neuroepithelial Bodies / Q000737:chemistry / Q000648:ultrastructure; D011237:Predictive Value of Tests
chemical_list: D014408:Biomarkers, Tumor