[Ultrastructural phenotypes of tumor cells of endocrine-cellular neoplasms of hepatopancreatoduodenal organs and their role in determining the degree of malignancy and prognosis of these diseases]. / Ul'trastrukturnye fenotipy opukholevykh kletok éndokrinno-kletochnykh novoobrazovanii organov gepatopankreatoduodenal'noi zony i ikh znachenie v opredelenii stepeni zlokachestvennosti i prognoza étikh zabolevanii.

78 tumors of the hepatopancreoduodenal system were studied clinically, cytologically and ultrastructurally. Hormonal disturbances were observed in 36% of the patients. The 5-year survival after radical surgery did not depend on the tumor size, tumor cell atypia or metastases to the regional lymph nodes. The prognosis was worse when the tumor was located in the liver. Ultrastructural features of the tumor cells were reliable criteria of the malignancy degree and tumor prognosis. The prognosis, recurrence-free interval and survival improve with an increase in the number of ultrastructurally differentiated cells and organoids in cytoplasm, and with a reduction in nuclear polymorphism and number of dark cells. The degree of histologic and ultrastructural differentiation of tumor cells may not coincide.

[Mucinous breast carcinomas with neuroendocrine differentiation]. / Mutsinozni kartsinomi na g'rdata s nevroendokrinna diferentsiatsiia.

Mucinous breast carcinomas, denominated also gelatinous, mucoid and colloid (collomas), represent a heterogeneous group of neoplasms. More than half of them exhibit signs of neuroendocrine differentiation. Eighteen mucus producing carcinomas of the breast are subjected to morphological study. On the ground of demonstrating argyrophilia by the methods of Grimelius and Churukian--Shenk, and presence of secreting granules during electron microscopic study, they are assigned under the heading apudomas, i.e. tumors of the diffuse endocrine system, or the so-called APUD-system. The important practical implications of demonstrating neuroendocrine cells with a special reference to the biological patterns of this particular type of tumors are discussed.

Cartinoid tumor of the middle ear and mastoid.

Primary cartinoid tumors in the middle ear and mastoid are rare. They are also very difficult to distinguish from adenomas and adenocarcinomas, using conventional histological stains. We present clinical, histological, immunohistochemical and ultrastructural findings of a cartinoid tumor in the middle ear and mastoid in a 40-year-old male. A soft tumor was revealed in the posterior mesotympanum and mastoid cavity, and a radical tympanomastoidectomy was performed. The tumor cells were stained by chromogranin A, and neurosecretory granules were confirmed with electron microscopy. We also review 20 previously reported cases in regard to their presentation, symptoms, signs, tumor extension, treatments, and histopathology.

[Neuroendocrine system and its tumors]. / Neuroendokrines System mit seinen Tumoren.

The original classification of neuroendocrine tumours proposed by Pearse was based on a common embryologic origin in the neuroectoderm. The term, carcinoid, literally means carcinoma-like, was coined in 1907 to describe the histologic similarity of these tumors to carcinomas on the one hand and their generally indolent biologic behaviour on the other hand. Neuroendocrine tumours represent a group with complex biological, histological, ultrastructural and immunocytochemical properties. This concept was replaced by another classification based on results of modern techniques (electron microscopy, immunocytochemistry, molecular and DNA analyses). This permits a more reliable classification of tumours, that can be used to determine their biological behaviour and prognosis.

[Apudoma: a rare case of the laryngeal tumor]. / W sprawie rzadkiego przypadku guza krtani--apudoma.

The authors present the problem of endocrine function of some neoplasmatic tumors based on their own very rare case of the larynx apudoma. They pay attention to the value of some modern diagnostic methods including radioimmunological determination of the serum peptide hormone levels and some specific immunofluorescence assays with monoclonal antibodies.

[Application of electron microscopy in the diagnosis of neoplasms].

The majority of neoplasms can be diagnosed by light microscopy, but in some cases the diagnosis remains ambiguous due to poor differentiation, even though special stainings have been employed. This paper presents 34 cases of neoplasms in which the tumors were diagnosed by electron microscopy. This includes distinguishing (1) anaplastic carcinoma from lymphoma; (2) anaplastic carcinoma from amelanotic melanoma; (3) APUDoma from other tumors; (4) different mesenchymal tumors. The diagnoses of 4 cases of malignant melanoma, 11 cases of APUDoma, 7 cases of poorly differentiated carcinoma or anaplastic carcinoma, 2 cases of non-Hodgkin's lymphoma, 9 cases of mesenchymal tumors and 1 cases of other tumors have been resolved by electron microscopy. It is obvious that in some cases, electron microscopy can be of help in establishing a correct diagnosis.

[Ultrastructural analysis in differential diagnosis of tumors].

Ultrastructures of 25 tumors were analyzed by electron microscopy (EM). Of the 25 cases, there were 9 amine precursor uptake and decarboxylation tumors (APUD) (2 carotid body tumor, 2 medullary carcinoma of thyroid and 5 carcinoid) in which the dense core granules of different sizes were seen in the cytoplasm. 4 cases of malignant melanoma were identified by EM basing on the premelanosome and melanosome in the cells. In 4 carcinomas from different locations, 2 had mucous secretory granules in the cytoplasm and junction complex between the tumor cells. The diagnosis was finally confirmed as adenocarcinoma. The other 2 cases were identified as epidermoid carcinoma or anaplastic carcinoma as desmosome and tonofilaments were found. 4 cases of malignant lymphoma without any cell junction complex were identified. Moreover, there were several cases of mesenchymal cell tumors, such as leiomyoma, rhabdomyosarcoma, chordoma and Schwannoma confirmed by their special organelles. This study shows that the ultrastructural analysis is valuable in the differential diagnosis and classification of tumors.

[Electron-microscopic study of neuroendocrine tumors of the lung]. / Elektronno-mikroskopicheskoe issledovanie neiroéndokrinnykh opukholei legkogo.

An electron-microscopic study was made of carcinoids, malignant carcinoids and small-cell lung cancer. These neoplasms are shown to represent one histogenetic group--neuroendocrine tumours (apudomas) of the lung. One can distinguish 3 main structural forms among them, i.e. epithelioid, sarcoma-like and symplastic. According to the ultrastructural criteria the neoplasms mentioned can be classified by their differentiation degree, as well, intermediately and poorly differentiated variants. This classification correlates well enough with the catamnesis of patients and may serve for prognosis of the disease.

[Lung apudomas]. / Apudomy legkikh.

As a result of a complex morphological examination of 140 cases of lung neoplasms, 24 apudomas (17.11%) and 3 carcinomas (2.14%) were identified. The latter consisted of histologically-heterogeneous lesions containing endocrine cells in combination with epidermoid or glandular cells. Clinical symptoms as well as cytologic, histological, histochemical and electron microscopic characteristics of the tumors were studied. Most of those tumors were poorly-differentiated, histologically identical to various types of small-cell lung carcinoma, or--less frequently--solid lesions and other types of tumor. The above tumors can be detected by special diagnostic procedures.

[Neuroendocrine (Merkel cell) skin cancer. Electron microscopic study]. / Rak kozhi iz neiroéndokrinnykh kletok Merkeliia. Elektronno-mikroskopicheskoe issledovanie.

The study is concerned with the results of light and electron microscopic examination of 2 cases of neuroendocrine (Merkel cell) carcinoma of the skin. Both patients developed multiple widely-distributed intra- and subcutaneous nodules. Histologically, tumors were mostly trabecular. Electron microscopic examination revealed neuroendocrine secretory granules, small bundles of intermediate fibers, a well-defined Golgi complex and a relatively high level of vesicular structures. There were some basal membrane fragments. It is suggested that they originate from polypotential epithelial stem cells.

[Malignant tumors of the uterus characterized by endocrine differentiation]. / Zlokachestvennye opukholi matki, kharakterizuiushchiesia éndokrinnoi differentsirovki.

Widely varying numbers of endocrine cells were identified in 12 out of 64 cases of uterine cancer in the course of histochemical and electron microscopic examination. Some neoplasms had morphologic features of apudoma of various degree of differentiation, the remaining ones (adenocarcinoma and adenosquamous carcinoma) were identified as tumors of endocrine origin if their cells contained certain specific metabolites most reliably detectable by the argyrophilic method after Grimelius and electron microscopy. The results of the study and literature data suggest that both endocrine and epithelial cells originate from multipotential epithelial stem cells.

New immunocytochemical observations with diagnostic significance in cutaneous neuroendocrine carcinoma.

The presence and distribution of cytokeratins, actin, neurofilament protein, neuron-specific enolase, S-100 protein, and different neuropeptides were studied immunohistochemically by the peroxidase-antiperoxidase immunoenzyme method or the avidin-biotin-peroxidase technique in 10 patients with primary cutaneous neuroendocrine carcinoma. In all cases of cutaneous neuroendocrine carcinoma, immunoreactivity for neuron-specific enolase, cytokeratin, and neurofilament was identified. No staining was found after incubation with antibodies to S-100 protein, actin, and other tested neuropeptides. The cytoplasmic cytokeratin and neurofilament immunoreactivity was particularly strong in perinuclear areas, sometimes showing an annular pattern or displaying a discoid profile. The diagnosis of cutaneous neuroendocrine carcinoma may be reliably made by the immunocytochemical demonstration of neuron-specific enolase and intermediate filaments (cytokeratin, neurofilament protein) by conventional microscopy. Cutaneous neuroendocrine carcinoma has morphological, immunological, and histogenetic similarities to carcinoid neoplasms of the gut. We favor the concept that cutaneous neuroendocrine carcinoma is derived from, or differentiates toward, dermal neuroendocrine cells.

Hepatocellular carcinoma with carcinoid features.

A primary hepatic neoplasm with histologic features suggestive of both hepatocellular carcinoma and carcinoid tumor was studied by light microscopy, electron microscopy, and immunocytochemistry. These methods revealed areas of hepatocellular carcinoma, areas of carcinoid tumor, and mixed areas within the same cell. This case provides one more example of the coexistence of carcinoma and carcinoid in the same neoplasm and thereby supports the hypothesis that a malignantly transformed stem cell can differentiate in both epithelial and amine precursor uptake and decarboxylation (APUD) directions.

Metastasizing APUD cell tumours of the human gastrointestinal tract. Light microscopic and karyometric studies.

A total of 11 metastasizing gastrointestinal APUD cell tumours from biopsy and autopsy files were reclassified according to Soga and Tazawa as well as to WHO Histologic Classification of Tumours. The much higher proportion of APUD cell tumours in autopsies (11 cases from 1000 autopsies in comparison with 22 cases from 22 000 biopsies) demonstrate that the majority of them will not be discovered during the patient's life. EC cell carcinoids (type A) predominate in both non-metastasizing and metastasizing gastrointestinal APUD cell tumours. Metastases from EC cell carcinoids occurred only in regional lymph nodes and in the liver. The APUD cell tumours originating in the pancreas represent the most frequently metastasizing gastrointestinal carcinoids. Besides in the liver and in regional lymph nodes metastases from pancreatic APUD cell tumours were seen in the skin, the brain and the skeleton. One case with two (pancreatic, bronchial) competitive primary APUD cell tumours and a skin metastasis was studied by means of automated cell image analysis. Cell populations of these three tumour sites were characterized by morphometric and densitometric nuclear parameters. It could be demonstrated that the skin metastasis consisted of a cell population, which occurred as a subpopulation in the primary tumour of the bronchus. The results of karyometric investigations supported the hypothesis that single components of tumours can metastasis selectively.

Bronchial carcinoid with fibrillary inclusions related to cytokeratins: an immunohistochemical and ultrastructural study with subsequent investigation of 12 foregut APUDomas.

A bronchial P cell carcinoid, which was negative for all hormones immunocyto chemically tested, showed a globular intracytoplasmic inclusion in almost every cell. The inclusions were not clearly distinguishable using the haematoxylin- eosin- safran procedure; they were best demonstrated with the Masson trichrome stain and the Grimelius technique and were easily detected in 1 micron thick Epon sections as target-like structures. On electron microscopy, they were found to be composed of filamentous aggregates entrapping a few endosecretory granules, which showed degenerative changes. The filaments, 8-10 nm in diameter, lacked any periodicity; they were randomly dispersed in the central area and arranged in broken concentric swirls at the periphery of the inclusions. The globules lacked the tinctorial properties of amyloid, but showed a strong immunostaining for keratin-like proteins. A systematic investigation of 12 APUDomas of bronchial or duodenopancreatic origin, using both light and electron microscopy, identified a few filamentous bodies in one case, a somatostatin cell tumour of ampulla of Vater. In both cases, the structures appeared similar to those previously reported in growth hormone cell pituitary adenomas as well as in a few bronchial or gut carcinoids. Whatever their nature, morphological data suggest that they are related to abnormalities in the secretory function, involving the Golgi apparatus, the endosecretory granules and the microtubular microfilamentous system.