Metastatic spindle-cell carcinoma. Cytologic features and differential diagnosis

Fine needle aspiration biopsies of tumors can yield a variety of spindle cells derived from several types of neoplasms. Among these is a rare lesion known as a "spindle-cell carcinoma" or "pseudosarcoma," which may represent a transformation of a preexisting squamous-cell carcinoma that has been subjected to radiotherapy or solar damage. The cytologic, histologic and ultrastructural features of a case of metastatic spindle-cell carcinoma of the rib subjected to fine needle aspiration are presented, and other spindle-cell tumors that should be considered in the differential diagnosis are discussed.     

Fine needle aspiration cytology of malignant mesothelioma

The results of fine needle aspiration (FNA) cytology in 19 cases of malignant mesothelioma are presented. Adequate material for a diagnosis of malignancy was obtained in 17 cases, and in 8 cases a specific diagnosis of mesothelioma could be made. In four other cases, the findings were either consistent with or suggestive of mesothelioma; in four, accurate distinction from other neoplasms was not possible, and in two cases, adenocarcinoma was suggested. The spectrum of cytologic findings ranged from neoplasms of purely epithelial appearance through more pleomorphic biphasic neoplasms to anaplastic tumors. A combination of epithelial-like cell clusters, pavement-like sheets of epithelial cells with well-defined cell borders and prominent cell separation, dispersed angular cells with dense cytoplasm and some spindle-cell forms was the most specific cytologic pattern for mesothelioma. In four neoplasms, ultrastructural examination of aspirated material provided the additional evidence for a definitive diagnosis. The identification of hyaluronic acid within intracytoplasmic vacuoles, either in smears or in cell blocks, confirmed the diagnosis in three tumors. Only in one case, with a strong clinical background suggesting mesothelioma, was the cytologic preparation sufficient for diagnosis without ancillary diagnostic methods. FNA is of particular value in the diagnosis of pleural mesothelioma in patients who do not present with a pleural effusion. Obtaining material for cell block preparations, cytochemistry or ultrastructural study is generally necessary for definitive tumor typing.     

Fine needle aspiration cytology of pancreatoblastoma with immunocytochemical and ultrastructural studies

The cytologic features of a pancreatoblastoma (infantile adenocarcinoma), a rare pancreatic neoplasm of childhood, are described. Fine needle aspiration (FNA) under ultrasound guidance produced a hypercellular specimen consisting of numerous oval-to-cuboidal cells that had a moderate amount of granular cytoplasm. Spindle-shaped, elongated and triangular-shaped epithelial cells were also seen, along with smaller cells that had a higher nuclear/cytoplasmic ratio and a denser cytoplasm. In addition, there were abundant fragments of stroma present, including some surrounded by epithelial cells. Immunoperoxidase studies performed on the aspirated material revealed positive staining of the epithelial cells for cytokeratin (AE1/3), including high and low molecular weight cytokeratin, carcinoembryonic antigen, neuron-specific enolase and alpha-1-antitrypsin. Ultrastructural examination demonstrated epithelial cells containing either large electron-dense zymogen granules in the range of 400 nm to 600 nm or small dense neuroendocrine granules measuring from 100 nm to 200 nm. This finding, in concert with the immunocytochemical studies, supported a "blastemal" cell origin with bidirectional differentiation for this unusual pancreatic neoplasm and enabled a specific preoperative diagnosis of pancreatoblastoma to be made. The differential diagnosis of pancreatoblastoma from other pediatric neoplasms involving the pancreas, including neuroendocrine tumors and neoplasms of acinar cell derivation, is presented. We believe that the FNA cytologic findings can lead to a correct diagnosis of pancreatoblastoma, especially when coupled with immunocytochemical and ultrastructural studies performed on the aspirated material.     

Primary cilia in gastric Gastrointestinal Stromal Tumours (GISTs): an ultrastructural study

Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal (non‐epithelial) neoplasms of the human gastrointestinal (GI) tract. They are thought to derive from interstitial cells of Cajal (ICCs) or an ICC progenitor based on immunophenotypical and ultrastructural similarities. Because ICCs show primary cilium, our hypothesis is based on the possibility that some of these neoplastic cells could also present it. To determine this, an exhaustive ultrastructural study has been developed on four gastric GISTs. Previous studies had demonstrated considerable variability in tumour cells with two dominating phenotypes, spindly and epithelioid. In addition to these two types, we have found another cell type reminiscent of adult ICCs with a voluminous nucleus surrounded by narrow perinuclear cytoplasm with long slender cytoplasmic processes. We have also noted the presence of small undifferentiated cells. In this study, we report for the first time the presence of primary cilia (PCs) in spindle and epithelioid tumour cells, an ultrastructural feature we consider of special interest that has hitherto been ignored in the literature dealing with the ultrastructure of GISTs. We also point out the frequent occurrence of multivesicular bodies (MVBs). The ultrastructural findings described in gastric GISTs in this study appear to be relevant considering the critical roles played by PCs and MVBs recently demonstrated in tumourigenic processes.     

The ultrastructural aspects of neoplastic myoepithelial cell in pleomorphic adenomas of salivary glands

The purpose of this study has been to establish the major ultrastructural aspects of the myoepithelial cell and the myoepithelial-like cells proliferated in the pleomorphic adenomas of salivary glands. Thus, twelve benign pleomorphic adenomas of salivary glands have been studied by electron-microscopy transmission techniques. Our analysis has proved the proliferation of two major cellular populations, one of ductal type and one of myoepithelial type, which tried to reproduce the tubulo-acinar cytoarchitecture from the normal salivary glands. We have also noticed the key role of the so-called 'modified' myoepithelial cells from the periphery of the proliferating epithelial units in the genesis of the myxoid and chondromyxoid tumoral stromal areas. All these ultrastructural aspects have explained the great histological diversity of these salivary gland neoplasms as well as the key role of the myoepithelial cell in its histogenesis.     

The ultrastructure of metastatic adenocarcinoma in serous fluids. An aid in identification of the primary site of the neoplasm

Identification of the primary sites of metastatic adenocarcinomas is a diagnostic problem, particularly in cases of occult primary neoplasms. We studied the ultrastructural morphology of 16 metastatic adenocarcinomas that presented as effusions to establish organ-specific features that would characterize adenocarcinomas from various sites. The nine cases in which the site of the primary carcinoma was known included seven derived from the breast, one from the ovary and one from the colon. The primary site was unknown in seven cases at the time of presentation. After investigations, the primary site became known in five cases (lung, colon and appendix, one case each, and the ovary in two cases). Ultrastructurally diagnostic features could be detected in gastrointestinal, ovarian, bronchioloalveolar-cell and breast carcinomas. In gastrointestinal carcinomas, the presence of short microvilli with long rootlets was specific for the group. The lamellar inclusions of type II pneumocytes were diagnostic of bronchioloalveolar-cell carcinoma. The microvilli in ovarian carcinomas were long, slender and bushy, as in mesotheliomas; however, the cells lacked the perinuclear condensation of tonofilaments seen in the latter. Breast carcinomas were associated with numerous intracytoplasmic lumina, electron-dense granules and aggregates of small vesicular bodies. We conclude that ultrastructural examination of adenocarcinomas in serious fluids can help to identify the primary site of certain neoplasms or at least shorten the list of possibilities. This may reduce costs and minimize the discomfort patients have to undergo by curtailing extensive invasive investigations in search of unknown primary neoplasms.     

Fine needle aspiration cytology of perineurioma. Report of a case with histologic, immunohistochemical and ultrastructural studies

The fine needle aspiration (FNA) findings are presented for a case of perineurioma, a benign soft tissue tumor composed of perineurial cells, which are epithelial-like and ensheath the endoneurial connective tissue space of nerve fibers. A subcutaneous FNA performed on a posterior thigh mass of a 14-month-old boy produced a specimen consisting of numerous spindle-shaped tumor cells with bipolar cytoplasmic extensions and occasional pseudosignet-ring cells in a prominent myxoid background. Cytologically, a diagnosis of benign myxoid tumor was made. Histologic examination of the resected tumor revealed the characteristic features that have been described for perineurioma; the diagnosis was confirmed with immunocytochemical and ultrastructural studies. Perneurioma should be included in the differential diagnosis of benign myxoid neoplasms seen in FNA biopsy specimens.     

Functional differentiation of the anterior pituitary cells in the fetal pig

Summary The fetal porcine pituitary was investigated by means of ultrastructural immunocytochemistry (1) to identify the first cells synthesizing the adenohypophyseal hormones, (2) to follow their differentiation during fetal development, and (3) to compare their ultrastructural characteristics with those of mature adult cells.The first ACTH-cells, which produced and stored ACTH, -LPH, -MSH, and - and -endorphin in the same granules, were very numerous at day 34 and displayed a uniform morphology. At day 50 and thereafter, until the end of gestation, the ACTH-cells differed in their appearance probably reflecting various stages of differentiation of one cell type. The GH-cells gained rapidly ultrastructural features comparable to those of mature GH-cells. In contrast, in the case of PRL-cells, which appeared only at the end of the gestation period as immature elements containing very small secretory granules, the morphological maturation seemed to take place only after birth. The first cells synthesizing the glycoprotein hormones (LH, LH, FSH and TSH) displayed ultrastructural features of immature cells. At day 50, their ultrastructural organization started to show a different pattern. At the end of gestation, the TSH-cells and the gonadotropic cells displayed the ultrastructural features of mature cells.     

Fine needle aspiration cytology of metastatic malignant rhabdoid tumor

The diagnosis and management of pediatric neoplasms using fine needle aspiration (FNA) has been neglected as compared to neoplasms occurring in adults. A case of metastatic malignant rhabdoid tumor diagnosed by FNA cytology is presented, and the cytologic morphology, which to our knowledge has not previously been reported, is described. The ultrastructural findings in the histologic specimen are also depicted. This case demonstrates the feasibility and need for further exploration of the use of FNA in pediatric oncology.     

Ultrastructure of adult T-cell leukemia/lymphoma

Eighteen cases of adult T-cell leukemia/lymphoma (ATLL) in Japan were analyzed by electron microscopy and compared with 5 cases of B-lymphoma and well-established groups of T-lymphomas (4 cases of T-lymphoblastic lymphoma and 2 cases of Sézary syndrome). Five hundred cells in each case, categorized ultrastructurally as to the cellular size and nuclear shape, showed an essentially pleomorphic cellular distribution in ATLL in remarkable contrast with the monomorphism of B-"histiocytic", B-well-differentiated lymphocytic, and T-lymphoblastic lymphomas. Some B-lymphomas and Sézary syndrome also showed pleomorphism. Cases of ATLL were classified according to the predominant cells and degree of nuclear irregularity, which delineated a spectrum of node-based, peripheral T-cells neoplasms probably encompassing T-immunoblastic sarcoma, T-zone lymphoma, as well as multilobated T-cell lymphoma. The characteristic fine structure of ATLL, in comparison with that of B-lymphomas, included slight to marked nuclear irregularity with convoluted-shape predominance, a specked chromatin pattern of the large cells, prominent lysosomes, and glycogen accumulation in addition to the difference in cellular distribution. Although T-lymphoblastic lymphoma and Sézary syndrome shared some of these features, the ultrastructural differentiation of ATLL from them seems to be possible.     

Cytologic features of well-differentiated sclerosing liposarcoma in aspirated samples

The histologic, cytologic and ultrastructural features of two cases of a rare variant of liposarcoma, the well-differentiated sclerosing type, are presented. These tumors are characterized by lipoblasts (in different stages of development), atypical fibroblasts, multinucleated floret cells, lipocytes and delicate, dispersed collagen. The differential diagnosis includes other types of liposarcoma and three benign lipomatous lesions: the pleomorphic lipoma, the atypical lipoma and the spindle cell lipoma. The latter three neoplasms are composed of fibroblasts, lipocytes and coarse collagen and may have typical lipoblastlike or fibroblastic cells. Given the difficulty in distinguishing these lesions, both cytologically and histologically, the clinical presentation and the tumor location become essential in rendering the diagnosis of sclerosing liposarcoma.     

Immunocytochemical characterization of two thyroid medullary carcinoma cell linesin vitro

Summary The immunocytochemical characterization of cell lines originating from thyroid medullary carcinoma, i.e. human TT cells and rat rMTC 6-23 cells, was undertaken. The immunocytochemical studies were supplemented by ultrastructural studies, including ultrastructural immunocytochemistry, and by radioimmunological estimation of calcitonin secretion to the medium. In rMTC 6-23 cells (subcultures 24 to 30), no hormone presence was demonstrated immunocytochemically, which corresponded to the absence of secretory granules at the ultrastructural level. Of various proteins sought, only neuron-specific enolase could be demonstrated. Nevertheless, the cells secreted calcitonin into the medium. TT cells (passages 145 to 160) produced secretory granules. The granules contained calcitonin, calcitonin gene-related peptide, somatostatin, neurotensin, met-enkephalin, leu-enkephalin, gastrin releasing peptide, parathyroid hormone-related protein, functional proteins of the chromogranin group and synaptophysin. Other functional proteins found in the cytosol of TT cells included non-specific enolase, calbindin and tyrosine hydroxylase. Receptor for calcitriol was localized in the cell nucleus. Marker proteins were localized in the cytosol (carcinoembryonic antigen) and in the cell skeleton (-tubulin, cytokeratin). Following changes in ionized calcium levels in the medium, changes in calcitonin secretion and in immunocytochemical detectability of some hormones and functional proteins were observed. TT cells demonstrated the expression of numerous hormones and functional proteins associated with calcitonin secretion. Further, the cells in their ultrastructure, immunocytochemical and secretory characteristics, resemble more closely normal parafollicular cells of the thyroid and, in our opinion, represent a more appropriate model for functional studies.     

Serotonin-producing pancreatic endocrine tumour. Histological, ultrastructural and immunohistochemical study of a case

Serotonin-producing pancreatic endocrine tumours are rare neoplasms which in most cases exhibit malignant biological behaviour. These tumours, in the majority of the well-documented cases, are composed of argyrophil- and argentaffin-positive cells which contain large pleomorphic neurosecretory granules. In contrast, argyrophilic non-argentaffin pancreatic endocrine tumours with tumour cells containing round neurosecretory granules are exceptional. In this study we describe such a tumour not associated with clinical evidence of carcinoid syndrome in a 60-year-old woman. Histological examination revealed tumour extension in pancreatic lymphatic vessels and veins but no evidence of locoregional or distant metastases. Ten months after surgery the patient showed no recurrence of the disease. Immunohistochemistry revealed cytoplasmic serotonin production in the tumour cells which were negative for anti-gastrin, insulin, glucagon, somatostatin, pancreatic polypeptide (PP), vasoactive intestinal peptide (VIP) and ACTH. This study emphasizes the usefulness of combined ultrastructural and immunohistochemical investigations in order to identify and characterize the rare pancreatic endocrine tumours with serotonin production.     

Peritoneal washing cytology. Uses and diagnostic criteria in gynecologic neoplasms

Review of a 20-month experience with 241 peritoneal washes performed on 191 patients showed that the use of these specimens has expanded greatly. Of the 19 patients with neoplastic cells in their peritoneal washing cytology specimens, 12 had primary ovarian neoplasms, 4 had primary uterine cervical neoplasms, 2 had primary endometrial neoplasms, and 1 had mammary carcinoma metastatic to the ovary. Gynecologic oncologists at this institution are now routinely obtaining peritoneal washing cytology specimens whenever there is intraabdominal surgery on patients known to have or suspected of having a pelvic neoplasm. The following criteria were found to be essential to the accurate evaluation of these specimens: (1) cells considered to be malignant should be present both singly and in groups and should be malignant by the usual cytologic criteria, (2) the patients must have or be known to have had a neoplasm whose cells are similar to those in the washing specimen, and (3) the cells considered to be neoplastic must be different from and not confused with reactive mesothelial cells. The last criterion is important because the peritoneal lavage traumatically removes mesothelium, which can appear atypical. These criteria make the cytologic interpretation of most peritoneal washing specimens straightforward; interesting diagnostic problems occur, however, including the evaluation of neoplasms of borderline malignancy, those "spilled" during surgery and second neoplasms found by peritoneal washing cytology.     

Endocrine cells in the prostate gland, urothelium and Brenner tumors. Immunohistological and ultrastructural studies

Endocrine cells are a normal constituent of the prostate gland, prostatic urethra and urinary bladder mucosa. Positive results using immunohistochemical technics were obtained only with antiserotonin antibodies. In normal tissues, there was a close similarity between the distribution of argyrophilic cells (Grimelius) and serotonin-storing cells. Some striking features were the patchy distribution of endocrine cells, the presence of slender cytoplasmic processes occasionally reaching the luminal surface and the paucity of specialized cells in bladder mucosa. It is unlikely that endocrine cells participate in conventional neoplasms of prostate and bladder. Exceptions are lobular hyperplasia, certain adeno-carcinomas of prostate and inverted papilloma of bladder. An ultrastructural study permitted the distinction of two types of endocrine cells characterized by a different morphology of their granules. Another relevant finding was the presence of serotonin-storing cells in Brenner tumors. The latter observation emphasizes the close similarity between this neoplastic epithelium and urothelium. This implies that endocrine cells may be of mesodermal derivation.     

Electron microscopic-cytochemical study of the enzyme activity of energy metabolism in "dark" and "light" neurons of the rat cerebral cortex

The ultrastructural localization of succinate dehydrogenase (SDH) and lactate dehydrogenase (LDH) activity in "dark" and "light" neurons of the intact rat's frontal brain cortex has been studied. The enzymes' activity was detected with using potassium ferricyanide as artificial acceptor of electrons. In the "light" cells SDH activity is localized in the mitochondria and plasma membranes. LDH activity is localized in the mitochondria, plasma membranes and hyaloplasm. SDH and LDH activity was not found in the "dark" cells.     

Fine needle aspiration cytopathology of bronchial carcinoid tumors: an analytical study of the cells

While frequently considered to originate in a common stem-cell of neuroendocrine origin, bronchial carcinoid tumors and small-cell anaplastic carcinomas differ significantly in their biologic potential and treatment. Patient management is often dependent on the diagnostic specificity of a pulmonary fine needle aspiration specimen. This study evaluated the cellular features in fine needle aspiration samples from seven bronchial carcinoid tumors and four small-cell anaplastic carcinomas of the "intermediate" type. Planimetric measurements were performed on tracings of 1,100 cells. An analysis of specific cytoplasmic and nuclear features was also obtained on 2,200 cells. Significant quantitative and qualitative differences in the cytomorphology of the cells derived from bronchial carcinoid and small-cell anaplastic neoplasms were obtained, clearly demonstrating that differentiation of these neoplasms is possible on a cytopathologic basis in fine needle aspiration samples.     

Ultrastructural visualization of sulphated complex carbohydrates in blood and epithelial cells with the high iron diamine procedure

Synopsis The high iron diamine (HID) method has been found to impart density at the ultrastructural level selectively to sites known to contain sulphated complex carbohydrates. Thus, immature primary granules in rabbit heterophils, immature précrystalloid granules in rabbit eosinophils, all granules of rabbit basophils, mouse and rat mast cells and the nucleoids of -granules of rabbit platelets were stained by HID. Granules of mast cells in rat cervical lymph node varied in the distribution pattern of the HID-reactive component. Mucous droplets within goblets of mouse colonic epithelial cells varied in HID reactivity. Sites known to contain sialomucin but no sulphates, such as mucous cells and apical plasmalemmae in mouse rectosigmoid colon, failed to stain with HID in contrast to their reactivity for dialysed iron at the ultrastructural level. The surface of mast cells and blood cells lacked affinity for HID, indicating that the dialysed iron binding at the surfaces can be attributed to neuraminic acid. HID proved more effective than dialysed iron in visualizing acid mucosubstance in precursor forms of the crystalloid granules in the eosinophil and in mast cell granules. Inclusion of 0.5% glycerol in the HID solution enhanced staining in mouse colon.     

Influence of fasting and stimulation on the rat gastric endocrine cells

Summary The ultrastructure and certain cytochemical parameters of endocrine cells of the rat gastric mucosa during 168 h of fasting were investigated. To some of the fasting animals peroral food or alcohol was administered before decapitation.The EC (enterochromaffin cells) the ECL (enterochromaffin-like cells), D₁ cells, AL (A-like cells) and G cells were identified by means of electron microscopy. Only the EC, ECL, and G cells could be identified by means of light microscopy by an adequate histochemical technique.The ultrastructural picture of the ECL and of the EC cells did not change markedly during the fasting. In the D₁ cells there occurred an agglomeration of secretory granules. Some of them disintegrated and disappeared. In the AL cells an agglomeration of granules during the fasting was also observed. Granules engulfed in lysosomes were often found. The participation of lysosomes in the degradation of granules during the fasting was more marked in the AL cells than in the G cells. The participation of lysosomes was questionable in the EC and D₁ cells, and in the ECL cells no lysosomes were observed. In contradistinction to the G cells of the non-fasting animals, where more than one half of the gastrin granules were empty, the G cells during the fasting were filled with agglomerated dense granules and contained lysosomes with fragments of engulfed secretory granules.Following the administration of food (Larsen's diet) 3 h before sacrificing the dissolution of the content of granules with well preserved membranes was observed (emiocytosis did not take place). The administration of food did not lead to changes in the ultrastructural appearance of the EC cells. The peroral administration of alcohol did not lead to any changes in the ultrastructural appearance of the AL and G cells.     

Several types of mitochondrial ultrastructure in animal cell mitochondria and their relationship to energy production]

Using the mitochondrial suspension of rabit's hepatocytes the interconnection between the ultrastructural reorganization and the power of mitochondria has been studied. Several steady states of these organelles were revealed corresponding to the rest, norm and to the excitement, all being characterized by definite ultrastructural and power-production parameters. It was shown that these physiological states of mitochondria were common to the intact cells. On the basis of the idea on the discrete physiological states of mitochondria, cases of a so-called "variety" of these methods of approach to the study of the interrelation between the structure and function of mitochondria may be used as well for the analysis of some pathological changes of these organelles.