Computer-assisted grading of adenocarcinoma in prostatic aspirates

Conventional cytologic grading of fine needle aspirates of prostatic adenocarcinoma has been shown neither to be reproducible nor to correlate well with histologic grading. This study developed a tumor grade classification based on computerized cytomorphometric features and compared the results to conventional grading of companion tissue sections. The image analysis system evaluated architectural features of the aspirates (mainly cell cluster features and interrelationships) as well as nuclear features. Thirty-five prostatic adenocarcinomas (8 well, 19 moderately and 8 poorly differentiated) were evaluated. Discriminant functions based on data collected at medium and high resolution distinguished between aspirates from low-grade (well-differentiated) and high-grade (poorly differentiated) adenocarcinomas with 81% accuracy. Moderately differentiated cancers could not be classified as a distinct group. This study suggests that accurate grading of prostatic adenocarcinoma in fine needle aspirate smears requires the evaluation of medium-resolution features related to specimen cellularity and uniformity or crowding of cell clusters as well as of high-resolution features of nuclear area, perimeter and coarseness of chromatin texture. These findings are compared to those of other schemes for the cytologic grading of prostatic aspirates.     

Cytology of prostatic carcinoma. Quantification and validation of diagnostic criteria

The validity of diagnostic criteria for the cytologic differentiation between benign and malignant cases and between normal (hyperplastic) and inflammation-activated (prostatitis) prostatic cells was tested by means of semiautomated image analysis and cytophotometry. The following criteria were found to have significant differences between benign and malignant prostatic cells: nucleoli (number, size and size variability), regularity of nuclear arrangement, anisonucleosis, nuclear size, nuclear polymorphism and dissociation of cells. The following criteria were found to be invalid for the detection of prostatic cancer cells: nuclear-cytoplasmic ratio, hyperchromasia and anisochromasia. the cytologic diagnosis of prostatic cancer was achieved by observing a variable constellation of at least three of six pathognomically altered diagnostic criteria. No fixed pattern of diagnostic criteria was found either for prostatic cancer cells in general or for the different malignancy grades.     

DNA measurement errors with a scanning microdensitometer in cytologic and histologic samples of breast cancers

The influence of various DNA measurement errors using a commercially available scanning microdensitometer was evaluated on Feulgen-stained cytologic and histologic samples prepared from paraffin blocks containing invasive ductal breast cancers. The overall average total measurement error was 5.5% for the cytologic specimens and 10.9% for the 4 micron histologic sections. Components of the error included microscopic adjustment variation and focussing errors (3.5% and 1.1%, respectively, for both cytologic and histologic samples) and background intensity estimation errors (3.0% for the cytologic samples and 10.0% for the histologic samples). Measurements of the integrated optical density had a minimal error of 0.5% and an average error of 1.0%. Limitations due to the histologic architecture and/or heterogeneous cell population gave rise to large differences in the selection of nuclei when differently sized scanning masks were used. To improve the reproducibility, masks used should be based on the individual cell size, and background intensity values should be carefully estimated in the vicinity of the selected cells. Overall, the cytologic tumor samples were preferable to the histologic samples for static DNA measurements. It was easier to select cells suitable for measurement in the cytologic samples, and the cytologic measurements were less time consuming and produced a smaller measurement error.     

前列腺泡沫状腺癌1例报告并文献复习

目的探讨前列腺泡沫状腺癌(prostatic foamy gland carcinoma)的临床病理特点、鉴别诊断、治疗及预后。方法观察1例前列腺泡沫状腺癌的组织学、免疫组化,并复习前列腺泡沫状腺癌相关文献。结果前列腺泡沫状腺癌的临床表现与经典型前列腺癌相似。镜下瘤细胞以其具有黄色瘤样胞浆为特征。核的异型性不明显,也常缺乏明显增大的核仁,但有结构异常、浸润性生长方式和基底细胞层消失。其假良性细胞学表现使之易被误诊为良性病变,或者使肿瘤的Gleason分级被低估。结论前列腺泡沫状腺癌是一种有侵袭性生物学行为的特殊组织学类型前列腺癌。     

Fine needle aspiration cytologic findings of breast mucinous neoplasms: differential diagnosis between mucocelelike tumor and mucinous carcinoma

OBJECTIVE: To report the cytologic findings of mucocelelike tumor and mucinous carcinoma. STUDY DESIGN: All mucinous neoplasms diagnosed by fine needle aspiration and confirmed by histologic examination were reviewed to detect the cytologic findings helpful for the differentiation. The cytologic findings were correlated with the histologic findings. RESULTS: Cytologically, mucinous carcinomas were highly cellular and showed many single epithelial cells and variably formed epithelial cell clusters in abundant extracellular mucin. Malignant cells exhibited round, atypical nuclei; granular chromatin; and small nucleoli. Mucocele like tumor showed low cellularity with scanty, monolayered, small sheets of epithelial cells and abundant, extracellular mucin. Myoepithelial cells were present within the epithelial cell sheets. Tumor cells were usually small, with uniform, round nuclei; fine chromatin; and absence of nucleoli. CONCLUSION: Cytologic findings of mucocelelike tumor and mucinous carcinoma were different in cellularity, shape of cell clusters and nuclear features, although mucocelelike tumors having a carcinoma component were similar to mucinous carcinoma. Awareness of the cytologic findings of breast mucinous neoplasms is important to make a specific diagnosis.     

Clinical and cytologic features of papillary neoplasms of the breast

OBJECTIVE: To compare the cytologic features benign and malignant papillary breast lesions. STUDY DESIGN: We reviewed the clinical and cytologic features in 29 cases of intraductal papilloma and 26 cases of atypical papilloma or papillary carcinoma that had been diagnosed by histologic examination. The diameter of the mass was examined as a clinical feature. The cytologic features evaluated were as follows: bloody background, row of tall columnar cells, naked bipolar nuclei, hemosiderin-laden macrophages, myoepithelial cells, single scattered atypical cells, cellularity, nuclear atypia, nuclear grade, apocrine metaplasia, eosinophilic cytoplasmic granules, papillary clusters, small papillae, cell balls and large sheets. RESULTS: Of the features evaluated, the diameter of the mass, naked bipolar nuclei and cell balls differed significantly between benign and atypical or malignant papillary neoplasms. The average diameter of a benign papillary neoplasm was 1.8 cm, and that of an atypical or malignant papillary neoplasm was 2.2 cm (p = 0.042). Naked bipolar nuclei were found in 27 cases of benign papillary neoplasm (93.1%) versus 19 cases of atypical or malignant papillary neoplasm (73.1%) (p = 0.050). Cell balls were found in 14 (48.3%) and 21 (80.8%) cases, respectively (p = 0.012). All 6 cases in which cell balls were present and naked bipolar nuclei were absent proved to be atypical or malignant papillary neoplasms. Of 17 cases in which cell balls were absent and naked bipolar nuclei present, 13 (76.5%) were benign papillary neoplasms. CONCLUSION: Most cytologic features overlapped in benign and atypical or malignant papillary neoplasms. Although they were not pathognomonic, naked bipolar nuclei and cell balls were cytologic features that differed significantly between benign and atypical or malignant papillary neoplasms. When papillary neoplasms of the breast are suspected in a cytologic smear, the combination of clinical examination, mammography and cytologic features should be considered to make the correct diagnosis.     

Fine needle aspiration cytology of retroperitoneal paraganglioma with lipofuscin pigmentation

The cytologic features observed in fine needle aspiration smears and cell blocks from a retroperitoneal paraganglioma are described. The aspirate contained clusters of uniform cells of medium size, with ill-defined borders, round nuclei and evenly dispersed chromatin. An unusual feature was the presence of cytoplasmic pigment, which proved to be lipofuscin by histochemical staining and electron microscopy. The histologic and ultrastructural findings, as well as the results of histochemical and immunodiagnostic staining, are also presented.     

Cytologic diagnosis of the papillary variant of renal-cell carcinoma

The papillary variant of renal-cell carcinoma is characterized by distinctive histologic, clinical and angiographic features. A study was undertaken to delineate the cytologic features of this tumor as it is encountered in cellular samples. Cytologic specimens containing tumor cells from eight patients who underwent resection for papillary renal-cell carcinoma were examined and compared to corresponding cytologic samples obtained from ten other patients who had nonpapillary renal-cell carcinoma. The cytologic appearance of papillary renal-cell carcinoma, which is deceptively benign, is marked by distinctive papillary structures that often resemble branched chains. The cells are usually small and contain uniform nuclei; numerous macrophages with foamy cytoplasm are often found in the background. These cytologic features were not observed in the cellular specimens from the nonpapillary renal carcinomas. We conclude that papillary renal-cell carcinoma can be confidently recognized in cytologic specimens.     

Qualitative and quantitative analysis of cytologic assessment of astrocytoma, oligodendroglioma and oligoastrocytoma

OBJECTIVE: To evaluate the usefulness of intraoperative cytology for differential diagnoses of astrocytoma, oligodendroglioma and oligoastrocytoma. STUDY DESIGN: Qualitative analysis of cytologic features of the 3 brain tumors was conducted using intraoperative touch or squash preparations that were stained with the Papanicolaou method, targeting the cellular density, cytoplasmic and nuclear profiles and blood vessel morphology. In addition, we attempted a computer-assisted image analysis of tumor cell nuclei and compared the results with qualitative observations. RESULTS: Astrocytomas were characterized by many fibrillary cytoplasmic processes and large, irregular nuclei. Oligodendrogliomas were characterized by small, round nuclei and a fine, delicate capillary network. In both tumors of a higher grade, anaplastic large nuclei and proliferating endothelial cells were noted. Oligoastrocytomas showed combined cytologic profiles of astrocytomas and oligodendrogliomas. Quantitative studies suggested that nuclei of oligodendroglial tumors were significantly rounder than those of astrocytomas. In general, the quantitative results were consistent with the qualitative observations. CONCLUSION; Cytologic evaluation using touch or squash preparations is of great help for intraoperative differential diagnosis of astrocytoma, oligodendroglioma and oligoastrocytoma. Cytologic as well as histologic assessment should be conducted at the intraoperative diagnosis of these tumors.     

Unusual cytologic findings in low grade papillary transitional cell carcinoma

OBJECTIVE: To describe cases of low grade papillary transitional cell carcinoma (LG-pTCC) with a low nuclear cytoplasmic (N/C) ratio and unusual cytologic patterns with many isolated, single neoplastic cells. STUDY DESIGN: We defined the following unusual cytologic findings as "isolated, single cell pattern": (1) numerous single cells sometimes with a few flat cell clusters; (2) very low N/C ratio; (3) angulation of cytoplasmic contour; (4) pale, homogeneous cytoplasm; (5) hyperchromatic nuclei with an uneven contour; (6) monotonous cytologic appearance; and (7) clear background. We studied 2,956 cytologic specimens of voided urine from 114 LG-pTCC patients at our university hospital during a 10-year period. RESULTS: Thirty-six specimens had the isolated, single cell pattern. The isolated, single cell pattern showed less celllular atypia than does the typical pattern of LG-pTCC. On histology the cases with the isolated, single cell pattern showed a papillary structure with an erosive surface and were composed of mildly atypical neoplastic cells with very low N/C ratios. CONCLUSION: Some LG-pTCCs show many single, atypical transitional cells.     

Psammoma bodies in fine needle aspirates from thyroids containing nontoxic hyperplastic nodular goiters

Psammoma bodies present in fine needle aspiration (FNA) smears with typical cytologic features of colloid goiter from five patients raised the possibility of coexistent papillary carcinoma. However, subsequent careful histologic examination of the entire thyroidectomy specimens did not show occult carcinoma in any of the cases. The psammoma bodies were identified in the stroma next to the foci of papillary hyperplasia in each case. They were small, often equal in size to or slightly larger than the follicular epithelial cell nuclei, and could be misinterpreted as epithelial cell nuclei. These findings suggest that the presence of psammoma bodies in an FNA smear cytologically consistent with a colloid goiter should raise the possibility of coexistent papillary hyperplasia or neoplasia. However, because of the strong statistical association of psammoma bodies with malignant thyroid neoplasms, histologic confirmation is mandatory in such cases.     

Automated cell nuclear segmentation in color images of hematoxylin and eosin-stained breast biopsy

OBJECTIVE: To develop an automated, reproducible epithelial cell nuclear segmentation method to quantify cytologic features quickly and accurately from breast biopsy. STUDY DESIGN: The method, based on fuzzy c-mean clustering of the hue-band of color images and the watershed transform, was applied to 39 images from 3 histologic types (typical hyperplasia, atypical hyperplasia, and ductal carcinoma in situ [cribriform and solid]). RESULTS: The performance of the segmentation algorithm was evaluated by visually determining the percentage of badly segmented nuclei (approximately 25% for all types), the percentage of nuclei that remained in clumps (4.5-16.7%) and the percentage of missed nuclei (0.4-1.5%) for each image. CONCLUSION: The segmentation algorithm was sensitive in that a small percentage of nuclei were missed. However, the percentage of badly segmented nuclei was on the order of 25%, and the percentage of nuclei that remained in clumps was on the order of 10% of the total number of nuclei in the duct. Even so, > 600 nuclei per duct, on average, were segmented correctly; that was a sufficient number by which to calculate accurate quantitative, cytologic, morphometric measurements of epithelial cell nuclei in stained tissue sections of breast biopsy.     

Fine needle aspiration cytology of parathyroid adenoma. A review of seven cases

The value of fine needle aspiration (FNA) cytology in the diagnosis of parathyroid adenomas was demonstrated by a cytohistologic review of seven cases. The cytologic patterns, which were characterized by numerous, mostly isolated epithelial cells and naked nuclei showing anisokaryosis and multiple nucleoli, were consistent with the histologic findings in this neoplasm, which should be considered in the differential (FNA) diagnosis of masses in the neck region. The only diagnostic problem is its differentiation from follicular thyroid neoplasms.     

Standardized thionin-eosin stain in bronchial cytology. A substitute for hematoxylin-eosin Y staining

A standardized thionin-eosinic acid stain was developed as a quick and highly reproducible staining method for bronchial cytology. Bronchial smears and paraffin-embedded sputum samples were stained with thionin-eosin and with the conventional hematoxylin-eosin Y. Spectral absorption characteristics and staining intensity of thionin-eosin-stained cells were investigated by means of cytophotometry. The staining pattern of thionin-eosin is very close to that of the hematoxylin-eosin stain; the contrast between nucleus and cytoplasm is significantly higher for thionin-eosin. Thionin-eosin can be used for "dye-fixation" of cytologic smears and tissue imprints. Blueing and differentiation (as for hematoxylin-eosin) is not required for thionin-eosin; thus, fixation and staining can be performed within two minutes. The spectral absorption characteristics of thionin-eosin allow reliable automated cytophotometric discrimination of cell nuclei and cytoplasm. The standardized thionin-eosin stain is recommended as a substitute for the hematoxylin and eosin stain in bronchial cytology.     

Immunocytochemical detection of cyclin, a proliferation-associated protein, in cytologic preparations.

Cyclin is a nuclear protein associated with DNA-polymerase delta, whose expression correlates with cell proliferation in vitro. To assess the value of cyclin staining in diagnostic cytology, an anticyclin monoclonal antibody was used to survey cyclin expression in cytologic preparations obtained as "bench top" aspirates from surgically resected specimens. The tissues assayed included carcinomas and normal and benign proliferative tissues of renal, mammary, prostatic and colonic origin. Staining was performed via the avidin-biotin-complex immunoperoxidase method. The staining of tumor cells was nuclear, with sparing of the nucleoli; the results were variable in different areas of a given tumor and varied significantly between tumors of the same histopathologic type. Benign proliferative tissues also showed staining. Nonproliferative tissues, such as renal tubules adjacent to a renal cell adenocarcinoma, were largely, but not entirely, nonstaining. The percentage of cyclin-positive nuclei was sometimes much higher than the typical percentages of tumor cells found in S phase. This observation was confirmed in two cases in which cyclin staining was much greater than the percentage of S-phase cells detected by flow cytometry. This suggests either stabilization of the protein beyond S phase in cells and/or dysregulation of cyclin expression in malignant cells. The viability of unfixed surgically resected tissue may also have affected the detection of cyclin, a problem that should not exist with clinically aspirated tissue fixed immediately after aspiration. These preliminary observations suggest that the selective use of cyclin staining may facilitate cytologic diagnoses. Furthermore, the wide range of cyclin expression within tumors of one histologic type suggests that cyclin expression may serve as a new parameter for investigating tumor behavior and prognosis.     

Cytologic, histologic, DNA ploidy and electron microscopic analyses of a case of vulvar Paget's disease

The cells in a case of multifocal vulvar Paget's disease were studied by cytology, histology, ploidy analysis and electron microscopy. The Paget cells in smears were seen in an isolated or a sheetlike arrangement. The cells had peripherally located nuclei, prominent nucleoli and unevenly distributed melanin granules of various sizes in their cytoplasms. The histologic sections contained multifocal microscopic lesions that were larger than the macroscopic lesion. Paget cells in the histologic sections demonstrated positive cytoplasmic staining with the periodic acid-Schiff, Alcian blue, mucin, glandular cytokeratin, epithelial membrane antigen and carcinoembryonic antigen reactions. The nuclear DNA histogram of the Paget cells in the cytologic smears showed a polyploid pattern, with a sharp peak at 4c; the cells in sheets had a ploidy level between 2c and 4c while a few of the isolated cells had a ploidy level that extended past 8c. Various nuclear DNA patterns were observed in the histologic samples; a recurrent lesion was later found in an area adjacent to the primary lesions that had higher ploidy levels. Ultrastructurally, the Paget cells contained lysosomes and tiny electron-dense secretory granules in their cytoplasms, suggestive of a glandular cell origin. These findings suggest that Paget cells may be derived from the secretory portion of sweat glands.