Intranuclear Cytoplasmic Inclusions Research Articles

A logistic model for thyroid lesions.

A stepwise logistic regression analysis was performed in 27 cases of papillary carcinoma thyroid (PC), 20 follicular neoplasms (FN), 30 cases of Grave's disease (GD), and 40 cases of colloid adenomatous goitre (CAG). The three most important variables in predicting PC were papillary clusters, dense cytoplasm, and intranuclear cytoplasmic inclusions, whereas the predictors of FN were high cellularity combined with a prominent acinar pattern. A few cases of GD and CAG showed a cytologic overlap with PC and FN, respectively. Regression analysis established high cellularity, fire flare appearance, and epitheloid granulomas as reliable predictors of GD, whereas abundant colloid with or without foam cells and follicles associated with colloid (FAC) were important variables in CAG.

Cytomorphology of Metastatic Melanoma—Use of S‐100 Protein In the Diagnosis of Amelanotic Melanoma

The cytomorphological features of cells from 52 cases of metastatic melanoma obtained by fine needle aspiration cytodiagnosis were studied. Morphologically, 11, 19 and 22 cases were classified as spindle, epithelial, and mixed cell types of metastatic melanoma respectively. There were 34 melanotic and 18 amelanotic melanomas. Besides melanin, the presence of intranuclear cytoplasmic inclusions, eosinophilic macronucleoli and giant cells were helpful in the diagnosis of a melanoma. Where attempted, staining for S-100 protein was positive in all the 19 cases (eight amelanotic and 11 sparsely pigmented melanomas). In addition eight cases of metastatic tumour where a differential diagnosis of poorly differentiated carcinoma or large cell lymphoma was entertained, were also studied for localization of S-100 protein and all were found to be negative. Electron microscopy was performed in five cases and showed the presence of melanosomes and/or premelanosomes.

Thyroid tumors: Cytomorphology of papillary carcinoma

Of 2,012 fine-needle aspirations (FNA) of the thyroid performed by the authors between the years 1984 and 1988, a detailed cytomorphologic analysis of 95 cases diagnosed as neoplastic on histology and/or cytology and those that received an equivocal cytodiagnosis is presented. Discussed are papillary carcinomas (28 correctly diagnosed on FNA and two false positives). In most of the cases of papillary carcinoma, the cytologic features were characteristic enough to enable accurate tumor typing. Follicular cells with dense cytoplasm, well defined cell margins, and presence of papillary clusters were the most consistent features observed. Intranuclear cytoplasmic inclusions, though characteristic, were found in only 66.6% of cases. In cystic papillary carcinomas (seven cases) study of the cyst wall as well as the cyst contents enabled an accurate cytodiagnosis. Two cases of multinodular goiter with papillary hyperplasia could not be distinguished with certainty from papillary carcinoma on cytologic grounds.

Occult thyroid cancer discovered by fine‐needle aspiration cytology of cervical lymph node: A report of three cases

Three cases of occult thyroid cancer measuring 10, 6, and 3 mm in diameter were discovered by fine-needle aspiration cytology of cervical lymph nodes. In these three cases, thyroid tumors were not palpable, and scintigraphic, echographic, and soft-tissue radiologic examinations demonstrated no abnormalities of the thyroid glands. Cytologically, the presence of intranuclear cytoplasmic inclusions, nuclear grooves, and colloid was characteristic in aspirated materials. Histologically, all three cases were diagnosed as papillary carcinoma. Fine-needle aspiration cytology of cervical lymph node was very useful to find occult carcinoma of the thyroid gland.

Fine-needle aspiration in hepatocellular carcinoma. Combined cytologic and histologic approach

Cytologic features of fine-needle aspiration (FNA) of hepatocellular carcinoma (HCC) have not been well documented. Most previous reports described only the the morphologic features of the tumor cells without considering the sinusoidal stroma. Cytohistologic correlation on tissue from the same aspirate has rarely been done. This report describes the cytologic patterns of 50 cases of HCC in terms of histologic pattern observed in cell blocks prepared from the same aspiration specimen and classified according to the World Health Organization (WHO) classification. Tumors were classified according to the predominant pattern. Thirty-two cases gave the trabecular pattern. Smears could be subdivided into a central-sinusoidal pattern (23 cases) and a peripheral-sinusoidal pattern (nine cases). One case gave the pseudoglandular pattern. Seventeen cases gave the compact pattern with inconspicuous sinusoids. In all cases sinusoids were easily recognized in cell block sections. Other cytologic features such as intranuclear cytoplasmic inclusions, eosinophilic globules, and bile secretion could be seen in both smears and cell blocks. Mallory's hyalin and ground glass inclusions were only recognized in cell blocks. More attention should be paid to the sinusoidal stroma for diagnosis of HCC in FNA; cell blocks should be more widely utilized to this effect; cytologic patterns could be classified according to the WHO histologic classification.

Fine‐needle aspiration of gastric leiomyoblastoma metastatic to the subcutis

Leiomyoblastomas are rare tumors, and there have been few reports on their fine-needle aspiration (FNA) cytologic morphology. We herein describe the FNA features of a gastric leiomyoblastoma with subcutaneous metastasis. The cells had eosinophilic cytoplasm and oval eccentric nuclei, occasionally with intranuclear cytoplasmic inclusions. An organoid pattern was obvious in cell block sections. The tumor was positive for vimentin but negative for desmin, S-100 protein, and the common epithelial markers. The histogenesis is discussed, as are reasons why this tumor is better termed epithelioid mesenchymal tumor.

Fine‐needle aspiration cytology of sacrococcygeal chordoma

The fine-needle aspiration cytology (FNAC) of four cases of chordoma that were diagnosed preoperatively is presented. One of the cases showed anaplastic components along with the classical features of chordoma; this is probably the second case diagnosed with these features on FNAC. The cytologic features of classical chordoma include conspicuous extracellular matrix in the background. Polygonal cells, dissociated and in small groups, were identified in all cases. Physaliphorous cells were also prominently found in these cases. In addition, the case with anaplastic features showed very bizarre cells with profound multinucleation and the presence of intranuclear cytoplasmic inclusions. The diagnosis of chordoma was possible because of a high index of suspicion on clinical grounds and the use of special staining for confirmation.

Hyalinizing trabecular adenoma of the thyroid. A report of three cases with immunohistochemical and ultrastructural studies

We have studied three examples of benign thyroid tumours which conform to the lesion recently described as hyalinizing trabecular adenoma. The prominent feature of this trabecular epithelial lesion is the extracellular deposition of an eosinophilic material that does not show the features of amyloid; the epithelial cells may be elongated, sometimes radially arranged around the eosinophilic material. All three tumours showed positive immunocytochemical staining for thyroglobulin, keratin, chromogranin and neuron-specific enolase. One tumour showed isolated cells with immunoreactivity for somatostatin, argyrophil cytoplasmic granularity with the Grimelius technique, and ultrastructurally demonstrable cytoplasmic electron-dense endocrine granules. The hyaline extracellular material in all three tumours showed strong immunoreactivity for both type IV collagen and laminin. Previous radiation may be important in the causation of this tumour, and it shows a frequent association with severe thyroiditis. We conclude that the main histological feature of this lesion, the hyaline material, is due to the overproduction of a basement membrane-like material by the neoplastic follicular cells. The presence in one tumour of evidence of endocrine differentiation may reflect the potential for follicular cells to show biphasic differentiation, a feature which may be more frequent than has been previously recognized. Several of the other features of this tumour--for example the frequent intranuclear cytoplasmic inclusions--may lead to diagnostic problems, and the entity deserves wider recognition.

A histopathological, immunohistochemical and ultrastructural study of intranuclear cytoplasmic inclusions in thyroid papillary carcinoma

Intranuclear cytoplasmic inclusions (ICI) in 38 cases of thyroid papillary carcinoma were studied histopathologically, immunohistochemically, and ultrastructurally in order to examine the frequency of ICI and their relationship to both the histological structure and cytological findings in thyroid papillary carcinoma. The fine-structure and biochemical state of ICI were also studied. ICI occurred in all 38 cases. ICI occurrence ranged from one in several microscopic fields to more than ten per field. The number of ICI divided by the number of nuclei on the microscopic photographs ranged from 0.013 to 0.116. The frequency of ICI was strongly influenced by the state of nuclear chromatin and pleomorphism, but was not influenced by a pattern of papillary or follicular tumour growth. Immunohistochemically, 10-30% of ICI revealed strong thyroglobulin (Tg), which was ascertained by immunoelectron microscopy. Neither T3 nor T4 was detected in ICI (with some exceptions). Some ICI showed keratin and vimentin. PAS-positive ICI were observed. Ultrastructurally, enlarged r-ER, many Golgi vesicles and small vesicles (diameter of 300-500 nm) and sacs were observed in ICI. These findings suggested increased protein synthesis and/or protein accumulation. Abundant secondary lysosomes, showing degradation of ICI, and bundles of condensed intermediate filaments were also detected. The character and genesis of ICI are discussed.

A step-wise logistic regression analysis of hepatocellular carcinoma an aspiration biopsy study

Fine needle aspiration biopsy (FNAB) has become a popular method to diagnose mass lesions of the liver. Although several reports have listed FNAB criteria to be used to diagnose both primary and metastatic tumors of the liver, none have separated key cytologic criteria from secondary criteria. We reviewed the FNAB smears from 35 patients with proven hepatocellular carcinoma and 74 patients with proven metastatic tumors in the liver. All specimens were coded as to the presence or absence of the following variables: polygonal cells with centrally placed nuclei; well-defined, granular cytoplasm; large nucleoli; small cytoplasmic vacuoles; large cytoplasmic vacuoles; bile; polymorphonuclear leukocytes; malignant cells separated by sinusoidal vessels; endothelial cells surrounding tumor cell clusters; multinucleated tumor giant cells; basophilic intracytoplasmic inclusions; eosinophilic intracytoplasmic inclusions; and intranuclear cytoplasmic inclusions. A step-wise logistic regression analysis was performed on the data to determine the variables predictive of hepatocellular carcinoma. The statistical analysis selected polygonal cells with centrally placed nuclei, malignant cells separated by sinusoidal capillaries, and bile as the key cytologic criteria for hepatocellular carcinoma. Endothelial cells surrounding tumor cell clusters and intranuclear cytoplasmic inclusions were selected as secondary criteria by this analysis.

A light and electron microscopical study of intranuclear cytoplasmic invaginations in interstitial cell tumours of dogs

Intranuclear cytoplasmic invaginations, so-called “pseudoinclusions”, were seen in all 7 interstitial cell tumours identified among 32 consecutive canine testicular tumours examined. The proportion of cells with intranuclear cytoplasmic invaginations varied from less than 1 per cent to 15 per cent. Similar “pseudoinclusions” were not seen in any other canine testicular tumours examined; this finding might be helpful in differential diagnosis, especially in less differentiated tumours. Histologically, the cytoplasmic invaginations appeared as round, eosinophilic, clearly demarcated intranuclear inclusions and stained with periodic acid-Schiff. Affected nuclei were enlarged. The process of progressive cytoplasmic invaginations into the nucleus and replacement of most of the nuclear volume of the neoplastic interstitial cells with cytoplasmic material was examined by transmission electron microscopy. Two or more cytoplasmic invaginations were sometimes present within a single nucleus. The nuclear membrane could be followed continuously around the cytoplasmic invaginations and nuclear pores were present in the membrane covering invaginations. The invaginations contained smooth and rough endoplasmic reticulum, vesicles, lipid vacuoles, myelin figures and disrupted membranous profiles. Bundles of interwoven cytoplasmic filaments were among the organelles seen in the invaginations in one tumour. Possible reasons for the formation of intranuclear cytoplasmic inclusions are discussed and maintenance of the normal ratio of nuclear surface to nuclear volume is suggested as the mechanism promoting formation of inclusions in interstitial cell tumours.

Oral mucosal cytomegalovirus as a manifestation of the acquired immune deficiency syndrome

Cytomegalovirus (CMV) infection presenting as a painful palatal gingival ulcer was one of the initial clinical manifestations of the acquired immune deficiency syndrome (AIDS) in a male homosexual patient. The diagnosis of oral CMV infection was established when large intranuclear and smaller cytoplasmic CMV inclusions were observed in endothelial cells at the base of the mucosal ulcer. The identification of intranuclear and intracytoplasmic herpes-type viral particles in the infected cells was confirmed by electron microscopy. Cytoplasmic viral particles coexisted with paranuclear dense bodies resembling lysosomes. These features are characteristic of CMV-infected cells. A review of the Engish-language literature disclosed only three previously reported cases of CMV infection involving the oral mucous membranes. A vasculitis associated with the CMV-infected endothelial cells appears to be the underlying mechanism responsible for development of the oral ulcer. CMV should be considered a possible causative agent when oral ulcers are detected in immunocompromised patients. Likewise, the finding of CMV in oral ulcers should alert one to the possibility of an immunocompromised state.

Loss of intracellular peroxidase and anaplastic change of differentiated carcinoma of human thyroid gland.

Ultrastructural localization of endogenous peroxidase (peroxidase) in differentiated thyroid carcinoma was studied in 2 cases of follicular carcinoma and 12 of papillary carcinoma. The reaction product for the enzyme was observed in cancer cells which had a round and smoothly-contoured nucleus and rather few number of microvilli (positive cells) and the product localized mainly in the rough-surfaced endoplasmic reticulum and perinuclear cisternae. The positive cells resembled normal follicular cells in localization sites of the reaction product and ultrastructural features. On the contrary, in cancer cells having an irregularly-outlined nucleus with or without intranuclear cytoplasmic inclusion and many microvilli, no reaction product was visualized (negative cells). The positive cells were frequently found in 2 follicular carcinomas and 2 papillary carcinomas. Only a few number of positive cells presented in 2 papillary carcinomas. The remaining 8 papillary carcinomas were composed only of negative cells. Histologically, follicles with colloid were frequently found in carcinomas with abundant positive cells, whereas they were few in number in carcinomas containing only negative cells. These findings suggest that loss of peroxidase activity in cancer cells of follicular cell origin correlates with anaplastic change of the cancer cells.

Cytological Findings in Medullary Carcinoma of the Thyroid

In six cases of medullary carcinoma of the thyroid rather characteristic findings were seen in cytological specimens obtained by aspiration or imprint. The roundish-polygonal or spindle-shaped cells were predominantly disseminated, but occasionally arranged in small groups. The nuclei were frequently found in an excentric position; binuclear cells were sometimes encountered. In addition, five of the six cases showed intranuclear cytoplasmic inclusions which were also investigated by electron microscopy in specimens of two cases. Such inclusions in aspiration biopsies of the thyroid have so far been regarded, as characteristic for papillary carcinoma. In smears as well as in histological sections amyloid and calcitonin could be demonstrated by congo red staining and by immunocytochemistry, respectively. The cytomorphology of the tumor cells, their pattern of arrangement, and the peculiar nuclear inclusions make up a combination of findings that may justify the diagnosis of medullary carcinoma in aspiration biopsies. In smears the diagnosis can already be confirmed when (immuno-) cytochemical methods are applied to smear preparations.

Tumours of the anterior uvea. II. Intranuclear cytoplasmic inclusions in malignant melanoma of the iris.

Intranuclear cytoplasmic inclusions have been described previously in both human and animal tissue. So far as we are aware they are described in detail for the first time in this paper in 60 cases of malignant melanoma of the iris, usually in spindle cells. The light microscopic appearances are described, and electron microscopic studies of selected cases show clearly the genesis of these inclusions by cytoplasmic invagination of the nuclear membrane. Their significance is discussed. It is of interest that we have seen identical inclusions in malignant melanomas of the ciliary body, choroid, and conjunctiva but have not as yet reported our findings.

Cytologic Study of Intranuclear Cytoplasmic Inclusions of the Thyroid Gland

Light microscopic studies were performed to evaluate the intranuclear cytoplasmic inclusions of the thyroid on 102 patients with thyroid disease during the period of from 1971 to 1977. The patients consisted of 35 patients with adenoma, 8 with hyperthyroidism, 5 with chronic thyroiditis, 12 with cyst, 31 with papillary carcinoma, 9 with follicular carcinoma, one with medullary carcinoma and one with anaplastic carcinoma. Normal cytology of the thyroid gland was studied on seven of them.The following results were obtained.(1) By the Papanicolaou method the inclusions were stained light bluish or greenish gray, and by the Giemsa method, light reddish-brown. They were mostly round in shape, but were clearly differentiated from degenerative vacuoles for the following features they invariably contained some fine structures and were demarcated by athick and relatively distinct border. By the Papanicolaou, Giemsa, Azan and PAS methods the inclusions were stained in a similar manner to their cytoplasma. By Shorr's and Mann's methods, however, they appeared quite different from nucleoli. The mean diameter of the inclusions was about half a nucleus.(2) The inclusions were detected in 26 of the 31 patients with papillary carcinoma, one of the 9 patients with follicular carcinoma and one of the one with medullary carcinoma. On the other hand, they were never found in the other histological types of thyroid disease or in the normal thyroid gland in this series.(3) In the cases of thyroid carcinoma with the inclusions, the ratio of number of carcinoma cells having the inclusions to the number of whole carcinoma cells ranged from 0.48 to 4.01% on the Papanicolaou-stained smears and from 0.29 to 3.87% on the Giemsa-stained smears. The higher this ratio, the more frequently was encountered cellular atypism such as nuclear enlargement, anisonucleosis, abnormal appearance of chromatin, polychromasia of nuclei, nucleolar abnormalities and increased nucleo-cytoplasmic ratio.(4) It may be concluded that the existence of the inclusions is of significant diagnostic value in indicating malignancy in cytodiagnosis of thyroid disease.

Scraping Smear Cytology of Nodular Lesions of the Thyroid

In this report an examination was made of the cytomorphologic features of scraping smears from nodular lesions of the thyroid. The series comprised fourty-two cases including seventeen cases of papillary adenocarcinoma, one of follicular adenocarcinoma, one of small cell anaplastic carcinoma, two of papillary adenoma, four of follicular adenoma and sixteen of hyperplastic nodule.The cells derived from papillary adenocarcinoma were arranged in epithelial sheets indicative of papillary structures, and the presence of intranuclear cytoplasmic inclusion bodies and many small intranuclear vacuoles was considered to be important diagnostic aids in recognizing this type of carcinoma. No intranuclear cytoplasmic inclusion bodies were seen in the cases of other types of carcinoma, adenoma and hyperplastic nodule except for one case of papillary adenoma. The cytologic differentiation between adenomas and hyperplastic nodules was impossible with smears.

Proceedings: Acute lower respiratory tract infections in children: observations on aetiology and management.

Intranuclear cytoplasmic inclusions have been described previously in both human and animal tissue. So far as we are aware they are described in detail for the first time in this paper in 60 cases of malignant melanoma of the iris, usually in spindle cells. The light microscopic appearances are described, and electron microscopic studies of selected cases show clearly the genesis of these inclusions by cytoplasmic invagination of the nuclear membrane. Their significance is discussed. It is of interest that we have seen identical inclusions in malignant melanomas of the ciliary body, choroid, and conjunctiva but have not as yet reported our findings.

Intranuclear Crystals and Cytoplasmic Membranous Inclusions, Associated with Infection by Two Brazilian Strains of Potato Virus Y

Two types of inclusions readily detectable under light and electron microscope were found in cells infected with strains Yp and Ynt of the potato virus Y besides the characteristic lamellar inclusions, present in tissues invaded with viruses of this morphological group. The first is an intranuclear isometric crystal, related to the nucleolus, and more conspicuous in later phases of infection. The other, found in the cytoplasm of the cell of all the plants, infected with both strains so far examined, is membranous in nature. It is composed of a pile of closely packed, 10-50 large cisternae, usually bowl shaped. It is suggested that this structure derives from a hypertrophy of the dictyosomes of the Golgi complex.

Fett im nucleolus

Electron microscope studies have demonstrated the presence of compact and vacuolar lipid droplets in the enlarged nucleoli of thioacetamide-damaged liver cells of the rat. The droplets most frequently lie in the outer part of the nucleolus and are tightly held by nucleolar material. It can be shown that the lipid droplets are derived from the cytoplasm. They are taken up into the nucleus by infolding of the nuclear envelope, leading to intranuclear cytoplasmic inclusions. After breaking up of the included nuclear envelope, the droplets enter the nucleoplasm and may penetrate from there into the nucleolus. The driving force for the movement (wandering) of lipid droplets within the nucleoplasm and from the nucleoplasm into the nucleolus is considered to be the oncotic pressure of the chromosomes resulting in the course of thioacetamide-induced nuclear edema. In den vergröβerten Nucleolen Thioacetamid-geschädigter Leberzellen der Ratte wurden elektronenmikroskopisch (kompakte und vakuolisierte) Fettropfen beobachtet. Sie liegen meist in der Peripherie des Nucleolus und werden von der Nucleolarsubstanz fest umklammert. Es läβt sich zeigen, daβ die Fettropfen aus dem Cytoplasma stammen. Sie werden auf dem Wege über Cytoplasmainklusionen in das Kerninnere aufgenommen. Durch Auflösung der eingeschlossenen Kernhülle gelangen sie in das Karyoplasma und dringen von hier aus in den Nucleolus ein. Als treibende Kraft für die Fortbewegung der Fettropfen innerhalb des Karyoplasmas und vom Karyoplasma in den Nucleolus hinein wird der gesteigerte Quellungsdruck der Chromosomen verantwortlich gemacht, der im Zuge der Thioacetamid-bedingten Kernschwellung auftritt.