Reticulin fiber staining of crush preparations for the rapid differentiation between schwannomas and meningiomas

The use of reticulin fiber staining of cytologic crush preparations for the rapid differentiation of schwannomas and meningiomas of the cerebellopontine angle was studied. As in paraffin-embedded sections, the reticulin stain demonstrated distinctly different patterns in the two types of tumors. Schwannomas showed extremely numerous, uniformly delicate straight fibers in a streaming or interlacing pattern in cellular areas and less dense, more wavy or curly fibers in degenerative areas. Fibroblastic meningiomas showed a few loose fibers of variable thickness in a root-like tangle while meningotheliomatous meningiomas showed no fibers, except in areas of fibrovascular stroma; both types showed small scattered round structures made up of reticulin fibers. These findings suggest that reticulin staining of crush preparations should be performed as an adjunct to routine cytologic staining of crush preparations and the study of frozen sections in making the intraoperative diagnosis of these tumors.     

Cytology of meningiomas and neurilemomas in crush preparations. A useful adjunct to frozen section diagnosis

Twenty-three meningiomas and 14 neurilemomas were studied by frozen section and crush-preparations techniques. These two types of tumors displayed distinctive cytologic pictures, permitting a correct identification in all cases. Six cases of deeply seated and unusually located meningioma and neurilemoma with equivocal or erroneous frozen section diagnoses were correctly diagnosed cytologically in the crush preparations.     

Use of monoclonal antibodies to glial fibrillary acidic protein in the cytologic diagnosis of brain tumors

Monoclonal antibodies were used to immunocytochemically demonstrate glial fibrillary acidic protein (GFAP) in 174 smear preparations of brain tumor tissue in order to investigate the presence and distribution of GFAP in a variety of intracranial tumors and to evaluate the value of this technique in the cytodiagnosis of brain tumors. GFAP-positive cells were found in the astrocytic tumors and in some of the oligodendrogliomas, ependymomas and medulloblastomas. In contrast, schwannomas, meningiomas, a primary lymphoma, a hemangiopericytoma pituitary adenomas, germinomas and metastatic tumors were negative for GFAP. The cytodiagnostic accuracy of the 174 brain tumors was raised from 90.8% to 97.1% when GFAP-immunoperoxidase staining was employed to aid the routine cytologic diagnosis. These findings indicate that immunoperoxidase staining for GFAP can be successfully applied to cytologic specimens and is a useful adjunct to routine cytologic diagnosis.     

Intraocular tumors. A cytopathologic study

The cytologic characteristics and histopathologic correlates of common ocular tumors were examined using (1) cytologic and histologic specimens prepared from enucleated eyes with retinoblastoma and melanoma, (2) cytologic specimens prepared from clinically obtained intraocular fluids from eyes with lymphoma, metastatic adenocarcinoma and retinoblastoma and (3) cytologic specimens prepared from orbital aspirates and cerebrospinal fluids from a patient in whom retinoblastoma had spread to the orbit and central nervous system. Retinoblastoma cells occurred singly and in clusters and were associated with abundant necrotic debris and portions of capillaries with perivascular tumor infiltrates. Melanoma cells frequently had prominent nucleoli and variable amounts of fine cytoplasmic pigmentation and were found individually and in groups. Lymphoma cells were noncohesive, with scant cytoplasm. Metastatic intraocular adenocarcinoma cells had well-defined borders, multiple nucleoli and vacuolated cytoplasm. In general, the cellular morphology in the cytologic and tissue preparations of the intraocular tumors correlated well with each other. The findings suggest that common primary and metastatic intraocular tumors can be differentiated in cytologic preparations.     

Cytologic features of secretory meningioma

OBJECTIVE: To describe the cytologic features of secretory meningioma on crush preparations. STUDY DESIGN: In five cases, the diagnosis of secretory meningioma was made and crush preparations were available. In each case, crush preparations were made at the time of intraoperative consultation from an open biopsy specimen or stereotactic biopsy. RESULTS: Hematoxylin and eosin-stained crushes showed the presence of clusters of cohesive cells containing variable numbers of inclusions among less cohesive typical meningothelial cells. In two cases, the inclusions were especially prominent. Inclusions varied in size from 3 to 40 microns, had a well-defined rim and contained finely granular or hyaline material and a central core. CONCLUSION: Secretory meningiomas demonstrate distinct cytologic features on crush preparations. Recognition of these inclusions is important since their prominence in some stereotactic smear preparations may lead to diagnostic problems.     

Crush preparations of lesions of the central nervous system. A useful adjunct to the frozen section

A series of 32 cases in which crush preparations were used in addition to frozen sections for the rapid diagnosis of lesions of the central nervous system (CNS) is presented. The cytopathologic features in crush preparations of astrocytomas, glioblastomas multiforme and a pituitary adenoma are described. Excellent preservation of cellular detail was seen in the crush preparations. Frozen sections lacked cytologic detail but provided a better view of the tissue architecture. The crush preparations yielded the correct diagnosis in 29 of the 32 cases. In the other three, a secondary component of the neoplasms (oligodendroglioma and fibrosarcoma) was identified only in the paraffin sections. Use of both frozen sections and crush preparations is recommended for all cases in which an immediate diagnosis of a CNS lesion is required.     

Intraoperative cytodiagnosis of metastatic brain tumors confused clinically with brain abscess. A report of three cases

BACKGROUND: Cystic lesions of the brain may have diverse etiologies, ranging from true cysts to malignant tumors with cystic degeneration. Preoperative determination of the exact nature of them as well as intraoperative diagnosis may be sometimes difficult or even impossible. Sensitivity and specificity of diagnosis will be improved by introducing new methods or combining traditional procedures. CASES: Three metastatic brain carcinomas with primary sites of breast, pancreas and prostate presented as cystic lesions and were confused clinically with abscess. Intraoperative frozen section was not revealing. Cytologic study of sediments of aspirated fluid uncovered malignant cells. CONCLUSION: When combined with frozen section, intraoperative cytologic studies in the form of crush preparation, fine needle aspiration or evaluation of aspirated fluid in cystic lesions (as in our cases) can improve diagnostic accuracy by detecting important diagnostic features that otherwise may be missed.     

Scratch cytologic findings on surgically resected solitary fibrous tumors of the pleura

OBJECTIVE: To ascertain the cytologic characteristics of solitary fibrous tumors of the pleura (SFTPs) on smear preparations. STUDY DESIGN: Fine needle aspiration cytology (FNAC) was initially attempted preoperatively in five cases, but the specimens were inappropriate for interpretation because only a few tumor cells were obtained. Therefore, scratch smears made at the time of operation were used. Papanicolaou and immunocytochemical staining was performed in all 10 cases, 2 of which were malignant. RESULTS: As expected, cellular tumors yielded more cells. The cytologic appearance was variable, showing spindle/bipolar, dendritic/stellate and intermediate cells. Atypical cells reminiscent of sarcoma were also present in cellular, benign tumors. Highly atypical epithelioid cells were obtained in two malignant cases. Immunocytochemically, the tumor cells were positive for CD34 and vimentin and negative for cytokeratin, regardless of histologic differences and cell shape. CONCLUSION: It seems difficult to diagnose SFTPs with certainty by FNAC, partly because the cell morphology of SFTPs resembles a wide variety of heterogeneous groups of spindle cell tumors and partly because only a few tumor cells were available in the FNAC specimens in the present study. However, a cytologic diagnosis of SFTP is possible if cytologic preparations yield CD34-positive cells with spindle/bipolar or dendritic/stellate morphology.     

Critical role of fine needle aspiration cytology and immunocytochemistry in preoperative diagnosis of pediatric renal tumors

OBJECTIVE: To evaluate accuracy and role of immunocytochemistry (ICC) in cytologic diagnosis of pediatric renal tumors. STUDY DESIGN: Fine needle aspirates from 75 cases of pediatric renal tumors were studied. Radiologic-guided aspirations were performed, with 6-7 smears stained with Papanicolaou and Giemsa stains. Smears were screened without the knowledge of final histologic diagnosis. Subsequently, clinical details, final histology and diagnosis rendered by the original cytologist were noted to judge accuracy of diagnosis by a sensitized cytologist. Five neuroblastomas that entered close differentials for Wilms tumor were also evaluated. ICC studies were also performed after staining. RESULTS: Of 58 Wilms tumors, 5 were misdiagnosed; 3 renal rhabdoid tumors and 1 clear cell sarcoma were missed on cytology. Non-Hodgkin's lymphomas presenting as renal masses were accurately diagnosed on cytology, but primitive neuroectodermal tumors (n = 3) and renal cell carcinomas (n = 2) were not accurately diagnosed. Accuracy rate improved from 65% to 92% on review by a cytologist aware of cytologic features of pediatric renal tumors. CONCLUSION: A good accuracy rate of diagnosis of pediatric renal tumors can be achieved by priming pathologists to typical features of tumors. Immunocytochemistry plays a supportive role in cases with atypical morphology or unusual presentations.     

Cytopathology of thymoma

From 1967 to 1981, 37 cases were diagnosed as thymoma by transthoracic fine needle aspiration biopsy. All were verified histologically, with no false-positive results. The various cytomorphologic patterns of thymoma are presented. All aspirates from the thymomas were reviewed and found to be composed of epithelial elements, with an admixture of lymphocytes in various proportions. There were 13 cases of lymphocytic predominance, 11 of epithelial-cell predominance, 4 of spindle-cell predominance, and 9 of mixed cell types. In the cytologic preparations the epithelial elements from different tumors exhibited different cytologic appearances and were tentatively subclassified into five types: small, intermediate, large, large pleomorphic and spindle shaped. The cytologic features of thymoma observed in aspiration biopsies are sufficiently distinctive from those of other anterior mediastinal tumors to be diagnostic. It appears feasible to investigate an anterior mediastinal mass with percutaneous fine needle aspiration for the purpose of establishing the diagnosis of thymoma prior to median sternotomy or thoracotomy.     

Comparative analysis of electron microscopy and immunocytochemistry in the cytologic diagnosis of malignant small round cell tumors

OBJECTIVE: To compare the contributions of electron microscopy (EM) and immunocytochemistry (ICC) as adjuncts in the cytodiagnosis of malignant small round cell tumors (MSRCT). STUDY DESIGN: This prospective study included 57 cases with a preliminary aspiration diagnosis of MSRCT. The contributions of EM and ICC in arriving at a specific diagnosis were evaluated. RESULTS: The 57 cases included 22 cases of Ewing's sarcoma/peripheral neuroectodermal tumor (PNET), 12 neuroblastomas, 8 Wilms' tumors, 6 rhabdomyosarcomas, 5 lymphomas, 2 retinoblastomas and 1 synovial sarcoma. One case remained unclassified. Electron microscopy was crucial to the diagnosis in 38.4% cases as against 39.2% of cases by ICC. The light microscopic diagnosis was confirmed in 42.3% and 53.5% cases by EM and ICC, respectively. EM and ICC were inconclusive for a specific diagnosis in 19.2% and 7.1% of cases, respectively. Technically unsatisfactory preparations in EM and ICC accounted for 5 and 1 cases, respectively. The overall efficiency in making a diagnosis was 80.7% for EM versus 92.8% for ICC. Aberrant expression of antigens led to difficulties in interpretation of ICC, and EM was particularly helpful. The ultrastructural demonstration of neural differentiation in Ewing's sarcoma/PNET tumors helped place tumors in the PNET category. CONCLUSION: While ICC is the ancillary method of choice in the cytologic diagnosis of MSRCT, EM contributes to the diagnosis and improves diagnostic accuracy.     

Application of artificial neural network for classification of thyroid follicular tumors

OBJECTIVE: To analyze smears of 197 thyroid follicular tumors (adenoma and carcinoma). STUDY DESIGN: Several types of artificial neural networks (ANN) of various designs were used for diagnosis of thyroid follicular tumors. The typical complex of cytologic features, some nuclear morphometric parameters (area, perimeter, shape factor) and density features of chromatin texture (mean value and SD of gray levels) were defined for each tumor. RESULTS: The ANN was trained by means of cytologic features characteristic for a thyroid follicular adenoma and a follicular carcinoma. At subsequent testing, the correct cytologic diagnosis was established in 93% (25 of 27) of cases. The morphometry increased the accuracy of diagnosis for follicular tumors in up to 97% (75 of 78) of cases. ANN correctly distinguished an adenoma or a carcinoma in 87% (73 of 84) of cases when using color microscopic images of tumors. CONCLUSION: The usage of ANN has raised sensitivity of cytologic diagnosis of follicular tumors to 90%, compared with a usual cytologic method (sensitivity of 56%). The automatic classification of thyroid follicular tumors by means of ANN is prospective.     

Diagnostic cytologic features of an epididymal melanotic neuroectodermal tumor of infancy present in scrotal fluid: a case report

BACKGROUND: The cytologic features of melanotic neuroectodermal tumor of infancy (MNTI) have been described in rare cases only, and these reports have been based solely on direct smears obtained from aspirated tumor material or from touch preparations of resected tumors. CASE: We report, to our knowledge, the first documented case of an epididymal MNTI diagnosed from aspirated hydrocele fluid processed using the ThinPrep system (Cytyc Corp., Boxborough, Massachusetts, U.S.A.). CONCLUSION: Based on a 15 year retrospective review of scrotal fluids submitted for cytologic evaluation to our laboratory, MNTI represented the sole neoplasm that was represented in the fluid and could be specifically diagnosed. Compared to the direct smear evaluation in our case and other published reports, the ThinPrep method enables the recognition of both neuroblast-like cells and larger melanin-containing epithelial cells in scrotal fluid, thereby aiding in the specific diagnosis of MNTI and minimizing the risk of misdiagnosing this tumor as a more aggressive neoplasm.     

Intraoperative cytologic crush preparation findings in craniopharyngioma: a study of 72 cases

OBJECTIVE: To describe the intraoperative crush preparation and the cytologic features of craniopharyngioma and the differential diagnosis. STUDY DESIGN: Twelve cases of craniopharyngioma were diagnosed by crush preparation cytology in the Department of Pathology, Shiraz Medical School, and formed the basis of this study. The patients' ages ranged from 7 to 43 years; 3 were female and 9 male. The cytologic findings together with the histologic findings were studied. RESULTS: All cases had a high yield of cells, consisting of honeycomb sheets of epithelial cells with and without palisading rows of cells, papillary clusters, squamous cell clusters, anucleated squames, calcification, multinucleated giant cells, cholesterol crystals, glandular or rosettelike structures, ciliated columnar cells and spindle cells. The smears were diagnosed as suggestive of craniopharyngioma. Histologic sections confirmed the cytologic diagnoses. CONCLUSION: Intraoperative cytologic crush preparation findings are helpful in the diagnosis of craniopharyngioma, when combined with clinical information. Crush preparation cytology is important in the diagnosis of central nervous system tumors.     

Immunohistochemical detection of nestin in pediatric brain tumors.

Nestin is an intermediate filament protein (IFP) expressed in undifferentiated cells during CNS development and in CNS tumors. Previous studies have arrived at different conclusions in terms of which types of CNS tumors express nestin. In this report we establish an immunohistochemical protocol using antigen retrieval, which significantly enhances staining with two polyclonal anti-nestin antisera, #130 and #4350. The staining pattern was identical for the two nestin antisera and very similar to that of vimentin, while glial fibrillary acidic protein (GFAP), immunoreactivity was absent from 9.5-week-old forebrain. The current study of 20 primary CNS tumors from pediatric patients included seven ependymomas, seven primitive neuroectodermal tumors (PNETs), five pilocytic astrocytomas, and one glioblastoma multiforme (GBM). All these tumors expressed nestin to various extents, in contrast to five brain metastases tested. Strong nestin immunoreactivity was found in malignant primary CNS tumors, whereas benign pilocytic astrocytomas showed low but consistent nestin expression. In all tumors nestin immunoreactivity was confined to the cytoplasm of tumor cells and was co-expressed with astrocyte markers vimentin, GFAP, and S-100. Vascular endothelial cells of all neoplasms also showed marked immunoreactivity for nestin and vimentin, whereas they were negative for GFAP and S-100. In conclusion, antiserum #4350 detected nestin in formalin-fixed, paraffin-embedded tissue sections by heat-induced antigen retrieval immunohistochemistry. Nestin was expressed in both highly malignant and low malignant gliomas, indicating the potential use of nestin as a diagnostic tumor marker in surgical pathology.     

Cytologic diagnosis of metastatic germ-cell tumors

The clinical, pathologic and cytologic findings were correlated in 86 cases of metastatic germ-cell tumors. Although the cytologic features of malignant germ-cell tumors are sufficiently characteristic to make specific cytologic diagnosis possible, the diagnostic accuracy can be augmented with cytochemical stains. It was found that due to recent advances in therapy, cytologic detection of metastases does not necessarily indicate a fatal outcome.     

Neuroectodermal ovarian tumors: a brief overview

Primary neuroectodermal tumors of the ovary are rare monophasic teratomas composed exclusively or almost exclusively of neuroectodemal tissue. Approximately 60 neuroectodermal tumors of the ovary have been reported in the literature. These tumors were classified as ependymoma, astrocytoma, glioblastoma multiforme, ependymoblastoma or as primitive neuroepithelial tumors such as medullo-blastoma, medulloepithelioma and neuroblastoma. Most tumors were diagnosed in the third and fourth decades of life, but occasionally they were first discovered in children, adolescents or older women. Microscopically, they are identical to equivalent neuroectodermal tumors of the central nervous system. The review of the literature shows that most patients with clinical stage I and II were treated surgically, whereas those with stage III or IV tumors received additional radiation or chemotherapy, or both. The clinical stage at the time of diagnosis is the most important prognostic parameter of these tumors.     

Cytopathology of the central nervous system. Part I. Utility of crush smear cytology in intraoperative diagnosis of central nervous system lesions

OBJECTIVE: To evaluate the utility of rapid intraoperative crush smear cytologic diagnosis of central and peripheral nervous system lesions and to determine the accuracy and relevance of the accuracy of the intraoperative cytologic diagnosis when compared to the final paraffin section diagnosis. STUDY DESIGN: The crush (squash) smear technique was introduced at Sher-i-Kashmir Institute of Medical Sciences in May 2003. The 8 months of 2003 were used for standardization of the procedure. In 2004, 151 patients with open neurosurgical specimens or stereotactic biopsies were diagnosed intraoperatively by crush smears, and the diagnosis was compared with final diagnosis on paraffin sections of the same tissue samples. No supplementation of frozen sections was used. RESULTS: Of 151 cases, 144 were diagnosed accurately intraoperatively by crush smear cytology when compared with the respective paraffin section diagnoses. The diagnostic accuracy attained was 95.36%. Each case was diagnosed within 10 minutes after receipt of sample. Neurosurgical procedure (open or stereotaxy) did not affect diagnostic accuracy. CONCLUSION: In the expert hands of a pathologist with good exposure neurosurgical specimens, crush smear cytology is an accura and reliable procedure for the intraoperative diagnosis central nervous system tumors.     

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.     

An embryonic origin for medulloblastoma

Medulloblastoma is a common brain tumor of children. Three differentiated cell types are found in medulloblastomas: neurons, glia, and muscle cells. Because of the presence of multiple differentiated cell types these tumors were named after a postulated cerebellar stem cell, the medulloblast, that would give rise to the differentiated cells found in the tumors. We describe a cell line with the properties expected of the postulated medulloblast. The rat cerebellar cell line ST15A expresses an intermediate filament, nestin, that is characteristic of neuroepithelial stem cells. ST15A cells can differentiate, gaining either neuronal or glial properties. In this paper we show that the same clonal cell can also differentiate into muscle cells. This result suggests that a single neuroectodermal cell can give rise to the different cell types found in medulloblastoma. We also show expression of nestin in human medulloblastoma tissue and in a medulloblastoma-derived cell line. Both the properties of the ST15A cell line and the expression of nestin in medulloblastoma support a neuroectodermal stem cell origin for this childhood tumor.