Dysembryoplastic neuroepithelial tumor. Features distinguishing it from oligodendroglioma on cytologic squash preparations

OBJECTIVE: To evaluate the diagnostic usefulness of intraoperative cytologic preparations from dysembryoplastic neuroepithelial tumor (DNTs). STUDY DESIGN: We reviewed squash preparations from 17 DNTs and compared them to those from 12 oligodendrogliomas and the histology of frozen sections from the same tumors. RESULTS: The floating neurons and extracellular mucin typical of DNT were more easily demonstrated in cytologic preparations than in frozen sections. Cytologically, oligodendroglialike cells of DNT were distinguished from oligodendrogliomas by larger nuclei with frequent nuclear indentation and multiple, small nucleoli, while oligodendrogliomas consistently showed nuclear roundness of tumor cells with 1 or 2 occasional nuclei. The presence of eosinophilic granular bodies in the background was an ancillary sign of DNT. CONCLUSION: The cytologic features of squash preparations of DNT are fairly characteristic and reliable for the correct intraoperative diagnosis of DNT, helping to determine the appropriate neurosurgical procedure.     

Cytologic characteristics of subependymal giant cell astrocytoma in squash smears: morphometric comparisons with gemistocytic astrocytoma and giant cell glioblastoma

OBJECTIVE: To evaluate the squash smear features of subependymal giant cell astrocytoma (SEGA) in comparison with gemistocytic astrocytoma and giant cell glioblastoma. STUDY DESIGN: We compared the squash smear features of 3 cases of SEGA, 9 cases of gemistocytic astrocytoma and 3 cases of giant cell glioblastoma with the morphometric findings. RESULTS: SEGA had, on average, a 15.84 +/- 5.03-microm nucleus, 33.22 +/- 12.05-microm cytoplasm and 0.50 +/- 0.12 nuclear/cytoplasmic ratio in squash smears. In addition, SEGA showed hairlike processes distributed along the squash direction like strap cells. While the gemistocytic astrocytoma had several tumor cells showing a vertically located nucleus, the tumor cells of SEGA showed nuclei oriented mainly in parallel. CONCLUSION: These squash cytologic features of SEGA can be very helpful in the differential diagnosis by excluding mimics.     

Cytomorphologic characteristics, differential diagnosis and utility during intraoperative consultation for medulloblastoma

OBJECTIVE: To study the cytologic findings that differentiate LC/A and non-LC/A (NLCA) types. STUDY DESIGN: Cytologic smears, prepared during intraoperative consultation (IOC) of 43 cases of pure histologic type, defined as > 80% of the tumor being composed of 1 of 3 major histologic types--classic, nodular and LC/A--were reviewed and graded semiquantitatively (0-3+) for 14 cytologic features: cellularity, nuclear streaming, endothelial proliferation, necrosis, lymphoglandular bodies, rosette formation, apoptosis, nuclear cannibalism, pleomorphism, macronucleoli, paranuclear inclusions, cytoplasmic vacuoles, mitoses and multinucleation. The grades were compared between the 2 histologic groups, LC/A vs. NLCA, as well as between the preparation methods, squash vs. touch (TP). Values of p < 0.05 were accepted as statistically significant. RESULTS: "Cell wrapping" (cannibalism), pleomorphism, macronucleoli, apoptosis, mitoses and cytoplasmic vacuoles were more significantly observed in LC/A than in NLCA. CONCLUSION: Intraoperative cytologic evaluation of these cytologic parameters allows distinction between LC/A and NLCA, which can be prognostically useful during IOC. Rosette formation, the histologic hallmark of classic medulloblastoma, is not a discriminator. Given the fewer artifacts and sufficient cellularity, TP is the preferred method of cytologic preparation.     

Characteristics of tumour vessels in cytological squash smears of astrocytic tumours

S. Sato, Y. Sato, K. Marutsuka, H. Takeshima and Y. Asada Characteristics of tumour vessels in cytological squash smears of astrocytic tumours Objective: Smear preparations are useful tools from which to diagnose brain tumours intraoperatively. Although vascular proliferation is histologically a key feature of high‐grade astrocytoma, the characteristics of tumour vessels in smear preparations have not been determined. Methods: We examined the density and morphological parameters (area, width, nuclear layer and branches of vessel wall) of tumour vessels in squash smears of 43 primary astrocytomas (grade II diffuse astrocytomas, n = 9; grade III anaplastic astrocytomas, n = 13; grade IV glioblastomas, n = 21) and normal brain tissues (n = 11). Results: Vessel density and all morphological parameters were significantly higher in grade IV than in the other grades of tumours and in normal brain tissue. Vessel area, width and nuclear layer were greater in grade III than in normal brain tissue. The sensitivity and specificity of these vessel parameters for astrocytomas were 75–100% and 82–100%, respectively. Conclusions: Tumour vessel evaluations from squash smears provide useful information for the intraoperative diagnosis and grading of astrocytic tumours.     

Cytomorphology of subependymal giant cell astrocytoma.

The cytomorphology of three subependymal giant cell astrocytomas (SEGA) is described. The tumors occurred in the left lateral ventricle of three males with tuberous sclerosis. The often-polarized spindle and epithelioid tumor cells possessed dense eosinophilic cytoplasm, eccentric nuclei and visible, occasionally prominent nucleoli. In addition, they displayed thick or hairlike processes and had a distinct tendency to form cohesive clusters as well as pseudorosettes. Occasional binucleate and multinucleate cells, as well as "strap" cells and nuclear cytoplasmic inclusions, were further features of this unique tumor. In cytologic terms the principal differential diagnostic considerations include gemistocytic astrocytoma, giant cell glioblastoma and ependymoma. Since, in isolation, SEGA may represent a "forme fruste" of tuberous sclerosis and since patients with tuberous sclerosis may have brain tumors other than SEGA, it is of diagnostic importance to recognize the cytomorphologic features of this essentially benign brain tumor.     

Cytologic findings of medulloblastoma in crush smears

OBJECTIVE: To describe the cytologic findings of medulloblastomas on intraoperative crush preparation smears and compare them with the findings of other central nervous system tumors. STUDY DESIGN: The intraoperative crush preparation smears of 19 cases of medulloblastoma were studied (6 undifferentiated type and 13 well-differentiated type). The findings were compared with those of a control group consisting of 31 astrocytomas, 22 ependymomas, 18 oligodendrogliomas, 27 meningiomas, 17 schwannomas, 17 pituitary adenomas, 3 lymphomas, 5 hemangioblastomas, 5 chordomas and 11 metastatic tumors. RESULTS: Medulloblastomas revealed clusters and isolated small, round malignant cells with hyperchromatic nuclei and indistinct cytoplasm. Typical Homer-Wright rosettes were seen in the well-differentiated type, but they were poorly formed in the undifferentiated type. Tumor cannibalism, target inclusions, cytoplasmic vacuoles and prominent multiple nucleoli were noticed frequently in the undifferentiated type. The control group (metastatic tumors and high grade astrocytomas) rarely showed tumor cannibalism or multiple nucleoli. CONCLUSION: Smears of the undifferentiated type of medulloblastomas frequently revealed tumor cannibalism, cytoplasmic vacuoles, target inclusions and prominent multiple nucleoli. These findings have been rarely reported. The prognosis of the undifferentiated type of medulloblastoma was poor.     

Cytologic features of subependymal giant cell astrocytom: a review of 7 cases

OBJECTIVE: To describe the cytologic features of subependymal giant cell astrocytoma (SEGA) on smears and analyze cytomorphologic parameters that may help in reaching the diagnosis of SEGA. STUDY DESIGN: Cytologic smears of 7 cases of SEGA were reviewed and graded semi-quantitatively for 11 cytologic features: clustering, cytoplasmic fibrillary processes (fibrillarity), cellularity, small prominent nudcleoli, binucleation or multinucleation, "strap cells", spindle-shaped cells, mitoses, intranuclear inclusions, nuclear atypia and perivascular palisading/pseudorosettes. Corresponding histologic sections were also reviewed. RESULTS: The study included 5 male and 2 female patients with an average age of 8.3 years (range, 3-16) at surgery. Cytologic examination revealed loosely cohesive clusters of large cells possessing round to oval nuclei with no or minimal atypia; fine, evenly distributed chromatin; and abundant eosinophilic cytoplasm enmeshed in abundant thin, hairlike processes. Predominant features included hypercellularity, cell clustering, and fibrillarity. Binucleation or multinucleation; small, prominent nucleoli; and strap cells were often seen. Although common in histologic sections, perivascular palisading/pseudorosettes and spindled astrocytic cells were rarely noted on smears. CONCLUSION: The cytologic features of SEGA are highly characteristic and thus are of great use in supporting a diagnosis of SEGA and in excluding mimics, primarily gemistocytic astrocytoma and ependymoma.     

Karyometric features of low and high grade glial tumors as compared with their MRI appearance

OBJECTIVE: To compare the results of a magnetic resonance imaging (MRI) grading designed to identify low and high grade gliomas with karyometry used as a tool to grade primary brain tumors. STUDY DESIGN: A consecutive series of 23 primary brain tumors was selected for this study. The neuroradiologist, not knowing the histologic diagnoses, divided the cases into low and high grade categories on the basis of the following 7 features: border sharpness, heterogeneity without contrast, cavitation, contrast enhancement, hypervascularity, mass effect and perifocal T2 hyperintensity. To each feature was given a numerical value, ranging from 1 to 3. All the cases were reviewed and classified by the same pathologist, blinded to the MRI diagnosis. Two hundred nuclei per case were recorded, and 93 karyometric features related to nuclear area, total optical density and chromatin distribution were analyzed for each nucleus. Statistical analysis included discriminant analysis, Kruskal-Wallis test, nonsupervised learning algorithm P-index and Beale statistic. RESULTS: Ten cases were classified as low grade on the basis of their MRI features. The corresponding histopathologic diagnoses were: grade 2 astrocytoma in 2 cases and grade 2 oligodendroglioma in 8 cases. An MRI diagnosis of high grade tumor was made in 13 cases. In 10 cases it was confirmed by the histopathologic diagnosis (3 grade 3 astrocytomas, 1 grade 3 oligodendroglioma and 6 glioblastomas). In the remaining 3 cases the histologic examination revealed a low grade tumor, 1 grade 2 astrocytoma and 2 grade 2 oligodendrogliomas. For the purposes of the karyometric analysis the cases were allocated to the low or high grade category according to their histologic diagnosis (13 cases low grade and 10 cases high grade). Nuclei from low and high grade tumors showed clearly different karyometric characteristics. The oligodendroglioma nuclei had abnormality values close to the low grade standard, while the astrocytoma nuclei were a highly dispersed group with characteristics indicative of a higher degree of nuclear abnormality than the oligodendroglioma nuclei. The results of karyometric analysis showed that grade 2 tumors, corresponding to the low grade group, form a rather distinct category from grade 3 and 4 tumors belonging to the high grade group. CONCLUSION: The results of MRI grading based on a series of features that are routinely assessed by the neuroradiologist to reach a final diagnosis correlate highly with the histopathologic diagnosis. Karyometry can be a useful adjunct to histologic grading.     

Cytologic characteristics of intracytoplasmic refractile eosinophilic granular bodies in anaplastic oligodendroglioma: a case report

BACKGROUND: Oligodendrogliomas, which have a relatively better prognosis than tumors of the astrocytic lineage, have few morphologic clues for diagnosis. CASE: To address this problem, eosinophilic refractile inclusions were examined cytologically in the tumor of a 59-year-old man, using surgical materials for rapid diagnosis. Cytologic, histologic, and immunohistochemical findings were compatible with the refractile eosinophilic inclusions found in oligodendroglial tumors. The tumor cells presented a sheet-like epithelial pattern, forming no overlapping cell clusters, with an ill-defined cytoplasmic membrane, and nuclei that appeared to be naked, approximately 2 times the size of a red blood cell (approximately 7 microm) in diameter. It was easier to examine the cells and inclusions by cytologic preparations than by histology. CONCLUSION: The inclusions were thought to be a diagnostic clue for oligodendrogliomas, especially on cytology, and cytology was more useful than histology.     

Cytologic diagnosis of a metastatic oligodendroglioma in a pleural effusion. A case report

BACKGROUND: Extraneural metastasis of oligodendroglioma is extremely rare and is diagnosed primarily by biopsy or autopsy and very occasionally by fine needle cytologic examination. We report a case of metastatic oligodendroglioma diagnosed by cytologic examination of a pleural effusion. Such a diagnosis has not been reported before. CASE: A 64-year-old woman developed anemia and bilateral pleural effusion 7 years after an operation for an oligodendroglioma over the left frontal lobe. Cytologic examination of the pleural effusion showed aggregates of atypical polygonal cells containing round, hyperchromatic nuclei and scanty, granular cytoplasm in Liu's and Papanicolaou stain and cell blocks. Immunohistochemical staining of the tumor cells revealed a positive reaction for antibodies to glial fibrillary acidic protein, S-100 and Olig2. Pleural biopsy confirmed the cytologic diagnosis of pleural effusion. A pathologic fracture of the right humeral and femoral bones was noted 1 month later, and the specimen also showed infiltrating oligodendroglioma cells in bone tissue. CONCLUSION: To the best of our knowledge, this is the first metastatic oligodendroglioma diagnosed by pleural cytology. Fine needle cytology can provide a reliable and rapid way to detect an extracranial metastatic oligodendroglioma in different organs.     

Fine needle aspiration cytology of desmoplastic malignant melanoma. A case report

The cytologic features of a recurrent desmoplastic malignant melanoma (DMM) examined by fine needle aspiration biopsy are reported. Cytologic examination revealed multiple microtissue fragments as well as smaller, dissociative aggregates composed predominantly of spindle-shaped neoplastic cells with hyperchromatic nuclei, small but prominent nucleoli and no cytoplasmic pigment or intranuclear pseudoinclusions. The tumor cells exhibited weak cytoplasmic staining for S-100 protein. To the best of our knowledge, this is the first reported case report describing the cytologic findings of DMM. Problems in differential diagnosis are discussed.     

Granular-cell tumor of the breast. A cytologic, immunohistochemical and ultrastructural study of two cases

Two primary granular-cell tumors of the breast are reported. Cytologically and histologically, these tumors had the classic features of small, eccentrically located nuclei and numerous periodic acid-Schiff-positive cytoplasmic granules. The characteristic cytologic features were best appreciated in touch imprints, not in frozen sections. Immunohistochemically, the tumors demonstrated diffuse cytoplasmic staining for S-100 protein but negative staining for myoglobin. The significance of these immunohistochemical staining characteristics, particularly in evaluating the possible histogenesis of these tumors, is discussed. The ultrastructural features of these two tumors are also presented and compared to findings reported by other investigators.     

Cytologic findings in carotid body tumors

OBJECTIVE: To describe the cytologic findings in 13 cases of carotid body tumors (CBTs) and discuss the differential diagnoses. STUDY DESIGN: Cytologic smears were obtained from 13 cases of carotid body tumors by fine needle aspiration. All tumors were clinically suspected and later confirmed by arteriography or color Doppler ultrasonography. The cytomorphologic findings are described. RESULTS: The smears revealed hypercellularity, a bloody background, isolated and clusters of round to oval cells with indistinct cytoplasm, reticular chromatin, no prominent nucleoli, giant bare nuclei, anisocytosis, acinar structures and plasmacytoid cells. These findings suggested metastatic tumors. CONCLUSION: The cytologic diagnosis of CBTs is very difficult. The aspiration findings can be easily mistaken for those of metastatic tumors. However, when used with clinical and color Doppler findings, fine needle aspiration plays an important role in the preoperative diagnosis and management of CBTs.     

Giant invasive pituitary adenoma extending into the sphenoid sinus and nasopharynx: report of a case with intraoperative cytologic diagnosis

BACKGROUND: Invasive pituitary adenomas involving the skull base are difficult to distinguish from other, more aggressive tumors. Intraoperaive diagnoses are crucial for deciding the course of treatment. CASE: A large mass extending from the sella turcica to the sphenoid sinus and nasopharynx was identified in a 42-year-old male. Because of the lack of endocrine abnormalities and lack of an apparent rise in pituitary hormones, preoperative diagnoses included chordoma, chondrosarcoma, meningioma and pituitary adenoma. Tumor fragments were easily squeezed into a thin layer of cells for cytologic specimens. Uniform, round tumor cells were arranged in minimally cohesive cell sheets and possessed regular, ovoid nuclei with a fine chromatin pattern and granular cytoplasm with prominent Golgi areas. The cytologic features indicated a probable diagnosis of pituitary adenoma and excluded other possibilities. Immunohistochemical demonstration of prolactin and ultrastructural features established the final diagnosis of prolactinoma. With the administration of bromocriptine, a large reduction in tumor size occurred. As compared to frozen sections, cytologic preparations are more effective for the intraoperative diagnosis of pituitary adenomas. Such neoplasms should always be included in the differential diagnosis of tumors involving the skull base.     

Cytologic features of ovarian tumors of low malignant potential in peritoneal fluids

The distinction of ovarian tumors of low malignant potential (OTLMP) from invasive ovarian carcinomas has significant therapeutic and prognostic implications. This study was undertaken to define the cytologic features of OTLMP in peritoneal fluids and to compare them with the cytologic features of invasive carcinomas. Peritoneal fluids from 13 patients with OTLMP and 10 patients with invasive ovarian carcinoma contained neoplastic cells and were reviewed with attention to papillary fragment morphology, cellular pleomorphism and cytoplasmic and nuclear characteristics. Cytologic preparations from patients with OTLMP contained large, cohesive papillary fragments with smooth borders. The neoplastic cells were relatively small and uniform, with high nuclear-cytoplasmic (N/C) ratios (greater than 1:2), few intracytoplasmic vacuoles and inconspicuous nucleoli. Mitotic figures were rare. Peritoneal fluids from patients with invasive ovarian carcinoma contained smaller discohesive papillary fragments with irregular borders. The neoplastic cells were relatively large and pleomorphic, with low N/C ratios (less than or equal to 1:2), abundant intracytoplasmic vacuoles and prominent nucleoli; most preparations contained many single cells and mitotic figures.     

Cytodiagnosis of central neurocytoma in intraoperative preparations

OBJECTIVE: To assess the cytologic features in smear preparations of 3 central neurocytomas. STUDY DESIGN: Three patients with central neurocytoma underwent intraoperative frozen section diagnoses, and the cytologic evaluations are presented. RESULTS: The smears typically showed cellular tumors composed of isomorphous, round cells. The tumor cells showed ill-defined cytoplasm oval nuclei with finely granular chromatin and micronucleoli. A fibrillary matrix in the background was noted in all cases. The tumor in the 20-year-old patient exhibited numerous giant cells with phyagocytosed hemosiderin granules between small, round tumor cells. Permanent sections, immunohistochemistry and electron microscopy confirmed that all cases were central neurocytomas. CONCLUSION: Central neurocytomas can be diagnosed reliably using combined cytologic preparations and frozen sections. The appearance of numerous macrophages that phagocytose hemosiderin between neoplastic cells should also be considered characteristic of the cytomorphology of central neurocytomas.     

Differential protein expression in human gliomas and molecular insights

Gliomas are the most common of the primary intracranial tumors with astrocytomas constituting about 40%. Using clinically and histologically assessed astrocytomas, we have studied their protein profiles using a two-dimensional gel electrophoresis-mass spectrometry approach and identified differentially expressed proteins which may be useful molecular indicators to understand these tumors. Examination of the protein profiles of 27 astrocytoma samples of different grades revealed 72 distinct, differentially expressed proteins belonging to various functional groups such as cytoskeleton and intermediate filament proteins, heat shock proteins (HSPs), enzymes and regulatory proteins. Based on the consistency of their differential expression, 29 distinct proteins could be short-listed and may have a role in the pathology of astrocytomas. Some were found to be differentially expressed in both Grade III and IV astrocytomas while others were associated with a particular grade. A notable observation was underexpression of Prohibitin, a potential tumor suppressor protein, Rho-GDP dissociation inhibitor, Rho-GDI, a regulator of Rho GTPases and HSPs as well as destabilization of glial fibrillary acidic protein, GFAP, major protein of the glial filaments, in Grade III malignant tumors. We attempt to explain glioma malignancy and progression in terms of their combined role.     

Nuclear grooves in cytologic preparations. A study of the utility of this feature in the diagnosis of papillary carcinoma

The sensitivity and specificity of nuclear grooves and inclusions for papillary carcinoma was investigated in 32 touch preparations and 69 fine needle aspiration cytologic preparations of the thyroid. Ultrastructurally, these grooves and inclusions are cytoplasmic invaginations into the nucleus. Overall, 100% of the papillary carcinomas contained nuclear grooves while only 70% contained inclusions. Grooves, however, could be seen in 70% of nonpapillary neoplasms and in 56% of nonneoplastic conditions of the thyroid, albeit generally fewer in number and often not as distinct. Inclusions were present in 13% of nonpapillary neoplasms and were absent in nonneoplastic conditions. Some nuclei on cytologic preparations contain lines that are probably artifacts of chromatin alignment and do not represent true nuclear grooves. Since such lines may be indistinguishable from true grooves, grooves should be used cautiously and in conjunction with other criteria in the diagnosis of papillary carcinoma.     

Cytology of primary pulmonary mucoepidermoid and adenoid cystic carcinoma. A report of four cases

BACKGROUND: Mucoepidermoid and adenoid cystic carcinomas are very rare primary pulmonary neoplasms that can be classified under the broader heading of salivary gland-like neoplasms (SGN). Both entities need to be considered in the cytologic differential diagnosis of lung tumors. We reviewed cytologic findings in primary pulmonary neoplasms diagnosed at our institution during the time period 1981 to the present along with outside consultation cases. CASES: Three cases of primary mucoepidermoid carcinoma and one case of primary adenoid cystic carcinoma of the lung were diagnosed based on cytology during the period examined. Patient ages were 16, 25, 47 and 78 years, respectively. The mucoepidermoid cytology specimens were composed of three cell types, mucinous, squamous and intermediate cells, at times associated with extracellular mucin. The adenoid cystic carcinoma consisted of small, uniform cells with dark nuclei, scant cytoplasm and associated, acellular balls of basement membrane material. CONCLUSION: The differential diagnosis for primary pulmonary neoplasms needs to include the rare SGN. Cytologic features of adenoid cystic carcinoma are diagnostic; those of mucoepidermoid carcinoma are at least suggestive.     

Chordoid glioma of the third ventricle: Report of a case with cytologic features and utility during intraoperative consultation

BACKGROUND: Chordoid glioma is a rare, low grade neoplasm with a unique chordoid appearance as well as distinct clinicopathologic and immunohistochemical features. Its cytologic features have not been described. CASE: A 42-year-old woman with recent-onset amnesia and confusion underwent magnetic resonance imaging, which revealed a 5-cm mass lesion arising in the third ventricle. Intraoperative squash smears showed cellular sheets as well as nests and strands of epithelioid tumor cells with bland nuclei and polygonal to elongated cytoplasm in a mucinous background. Binucleation was commonly seen. The tumor was intimately admixed with a benign lymphoplasmacytic infiltrate and scattered Russell bodies. Histologically, the tumor cells were arranged in a syncytium with prominent lymphoplasmacytic infiltrates and scattered small foci of necrosis in a mucinous matrix. The foremost differential diagnosis was chordoid meningioma. Immunohistochemically, the tumor cells were positive for glial fibrillary acid protein (GFAP), vimentin, epithelial membrane antigen, CD34, neuron-specific enolase and CK-7 and negative for synaptophysin, S-100 protein, neurofilament, and estrogen and progesterone receptors. CONCLUSION: Intraoperative smear cytology in this case of chordoid glioma revealed distinctive cytologic features, reflecting the unique histologic pattern. Cytologic features, such as binucleation, absence of intranuclear pseudoinclusions and GFAP immunoreactivity, are particularly helpful in differentiating chordoid glioma from chordoid meningioma.