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.     

Crush cytology of melanocytoma of the spinal cord. A case report

BACKGROUND: Primary melanocytic neoplasms of the central nervous system are rare. There is no previous report on the intraoperative crush cytology of these neoplasms. CASE: A melanocytoma occurred in a 65-year-old woman who presented with back pain, and weakness and numbness of the right lower extremity. Magnetic resonance imaging revealed an enhancing mass in the conus medullaris. The tumor was subtotally removed. Crush smears revealed dispersed and perivascular aggregates of monotonous oval or spindle tumor cells with round or oval, uniform nuclei; small nucleoli; and long cytoplasmic processes. Some tumor cells contained fine or coarse cytoplasmic brown pigments. The pigments were easier to discern in the crush smears than in the frozen sections. CONCLUSION: Crush cytology appears to be helpful, alone or in conjunction with frozen sections, in the intraoperative diagnosis of meningeal melanocytoma.     

Fine needle aspiration cytology of dedifferentiated acinic cell carcinoma of the parotid gland: a case report

BACKGROUND: Dedifferentiation of acinic cell carcinoma (ACC) to undifferentiated carcinoma occurs rarely and entails a poor prognosis. Most cases of dedifferentiation occur as recurrences of a previously excised ACC. More rarely the neoplasm presents with areas of well-differentiated ACC coexisting with dedifferentiated ones. CASE: An 85-year-old man presented with 2 nodular areas in the right parotid area. Fine needle aspiration of both nodules was performed. In both cases cytology revealed a double epithelial component in similar proportions. The first one corresponded to cohesive groups of small to intermediate-sized, polygonal cells with round, monomorphic nuclei. They were distributed in small and larger, branching groups with acinic morphology. Intermixed with this population, irregular groups of larger, pleomorphic cells with irregular nuclei, prominent nucleoli and scarce cytoplasm were present. In addition, smears showed an abundant lymphoid background. A cytologic diagnosis of "salivary carcinoma with coexisting areas of acinic cell differentiation and high grade, undifferentiated carcinoma" was given. Histopathology revealed a well-differentiated ACC with areas of high grade undifferentiated carcinoma (dedifferentiated ACC). CONCLUSION: The current case expands the cytomorphologic spectrum of ACC. Cytology may permit the preoperative recognition of dedifferentiation, allowing a more sound therapeutic approach.     

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.     

Cytology of desmoplastic medulloblastoma in imprint smears: a report of 2 cases

BACKGROUND: Desmoplastic medulloblastoma is a rare subtype of medulloblastoma with astroglial differentiation. The cytomorphologic features in intraoperative imprint smears from 2 cases of desmoplastic medulloblastoma are described. CASE REPORTS: A 22-year-old man and 27-year-old woman with a cerebellar tumor underwent craniotomy and tumor resection. The imprint cytologic smears contained cellular zones and nodular hypocellular areas containing astroglial and oligodendrogliallike elements. The cytology was misinterpreted as glial tumors, while the final histologic diagnosis in both cases were desmoplastic medulloblastoma. CONCLUSION: Desmoplastic medulloblastoma shows distinctive cytology in intraoperative smears. However, the occurrence of this rare type in adults and the presence of astroglial elements in imprint smears may cause a cytologic misinterpretation as gliomas.     

Morphologic spectrum of hepatocellular carcinoma in fine needle aspiration biopsies

The light microscopic features of fine needle aspiration smears from 52 primary hepatocellular carcinomas were reviewed. Cytologic grading of these tumors, which indicated three grade I, 29 grade II and 20 grade III carcinomas, was compatible with grading done by histologic examination. In addition to the general cellular characteristics, other cytologic features observed in the smears included bile (48% of the cases), large cytoplasmic vacuoles (23%), small cytoplasmic vacuoles (46%), eosinophilic cytoplasmic inclusions (8%), basophilic cytoplasmic inclusions (48%) and intranuclear cytoplasmic inclusions (71%). The significance of these features is briefly discussed.     

Fine needle aspiration cytology of neuroendocrine tumors of the pancreas. A cytologic, immunocytochemical and electron microscopic study.

We report the fine needle aspiration cytology findings in six cases of neuroendocrine tumor of the pancreas. Three cases were from the pancreas, two from hepatic metastases and one from a peripancreatic lymph node metastasis. The cytologic features that permitted a preoperative diagnosis of pancreatic neuroendocrine tumor were: a cellular aspirate; numerous isolated cells and irregular, loose, dyshesive cellular aggregates; minimal nuclear pleomorphism; infrequent mitoses; fine, evenly dispersed nuclear chromatin with occasional inconspicuous nucleoli; a scant-moderate amount of granular, amphophilic, well-defined cytoplasm; clustering of tumor cells around segments of capillaries; and rosette formation. The differential diagnosis includes cells derived from normal pancreatic acini, islet cell hyperplasia, acinic cell carcinoma, well-differentiated pancreatic adenocarcinoma, metastatic small cell undifferentiated carcinoma of the lung, pancreatic small cell anaplastic carcinoma and malignant lymphoma. The application of immunocytochemistry to cytologic smears can be easily and reliably performed to confirm the neuroendocrine nature of the tumor and identify the specific type of polypeptide hormone or hormones produced by these tumors. Four aspirates showed immunoreactivity for chromogranin, and one was positive for gastrin. Cells of a lipid-rich neuroendocrine tumor were negative for chromogranin; however, the tissue section contained neuron specific enolase, and neurosecretory granules were demonstrated by electron microscopy.     

Spindle cell malignant melanoma metastatic to the breast from a pigmented lesion on the back. A case report

BACKGROUND: Tumors metastatic to the breast are quite unusual (1.2% of all tumors). Malignant melanoma is an exception and is one of the principal metastasizing tumors, described mainly as a primary tumor. There are 5 different cytologic patterns; the spindled pattern is very uncommon, more difficult to diagnose and can be confused with a wide range of sarcomatous lesions. Nevertheless, there are some cytologic features that allow differentiation from similar tumors. CASE: A 30-year-old woman presented with a firm, deep, nontender mass in the upper outer quadrant of the right breast. Fine needle aspiration cytology was performed, and the aspiration smears showed spindle-shaped neoplastic cells arranged singly or in clusters with marked nuclear atypia. Melanin pigment was sometimes seen in the cytoplasm of some cells. Pathologic study of the breast tumor corroborated the diagnosis, and later study revealed lymph node metastases and relapse in the breast area and on a scar on the back. Two years earlier, biopsy of a pigmented lesion on the back was diagnosed as a cellular blue nevus. CONCLUSION: The cytologic features of spindle cell melanoma are distinctive. The presence of atypical fusiform cells with elongated cytoplasm; enlarged nuclei, some of them binucleated or multinucleated; prominent nucleoli; intranuclear cytoplasmic inclusions; and melanin pigment can help to diagnose these unusual metastases to the breast. This case was the first of malignant metastatic melanoma with the spindled pattern in which the diagnosis was made by fine needle aspiration cytology.     

Medullary thyroid carcinoma. Rare cytologic findings

OBJECTIVE: To describe some rare cytologic findings in medullary thyroid carcinoma. STUDY DESIGN: Review of the fine needle aspiration smears from 15 cases of medullary thyroid carcinoma that were confirmed on histologic sections. The ages ranged between 31 and 67 years; 10 were female and 5 male. Thirteen were sporadic forms, and two were familial forms. RESULTS: Eight cases were classified as pleomorphic cell type and seven as monomorphic cell type. The smears revealed round, oval, triangular, polygonal and spindle-shaped cells, intracytoplasmic red granules, occasional intranuclear inclusions, amyloid, binucleated and multinucleated cells, and thick, granular chromatin. CONCLUSION: The rare cytologic findings in this study were grape cells, cytoplasmic nippling, elongated cytoplasmic processes, carrot-shaped nuclei, nuclear buddings, mast cell-like cells and a Burkitt's lymphoma-like appearance. These findings were rarely reported before.     

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.     

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.     

Aspiration cytology of the oncocytic variant of papillary adenocarcinoma of the thyroid gland

OBJECTIVE: To study the cytologic features of the oncocytic variant of papillary adenocarcinoma of the thyroid gland to distinguish this subtype from other oncocytic lesions of the thyroid. STUDY DESIGN: We reviewed the smears from aspiration biopsies of 6 proven cases of oncocytic variant of papillary adenocarcinoma and compared their cytologic features with smears from 19 oncocytic follicular neoplasms (11 adenocarcinomas and 8 adenomas). Smears were stained with a modified Giemsa stain (Diff-Quik). RESULTS: All smears were cellular. Colloid was variable but more abundant in cases of the oncocytic variant of papillary adenocarcinoma. The cells in papillary adenocarcinoma had round to ovoid, overlapped nuclei; prominent intranuclear inclusions; and "grooves." Nucleoli were generally absent. In oncocytic follicular neoplasms, the cells had round nuclei and prominent nucleoli. Nuclear inclusions and grooves were seen but were not as prevalent as in papillary adenocarcinomas. CONCLUSION: The oncocytic variant of papillary adenocarcinoma of the thyroid gland can be distinguished from other oncocytic lesions by fine needle aspiration biopsy, whereas the absence of prominent nucleoli in oncocytes favors the diagnosis of an oncocytic papillary adenocarcinoma.     

Crush cytology of Rosai-Dorfman disease of the central nervous system. A report of 2 cases

BACKGROUND: Rosai-Dorfman disease (RDD) of the central nervous system (CNS) is rare. There is no previous report on intraoperative crush cytology of this disorder. CASES: A 70-year-old man presented with headache and was found to have 2 intracranial extraaxial masses. A 62-year-old man presented with cauda equina syndrome secondary to a mass lesion in the sacral canal. The crush smears, prepared intraoperatively from a small portion of the biopsy specimen in each case, showed scattered lymphoid aggregates in a lighter background with a loose admixture of lymphocytes, plasma cells, usual histiocytes and RDD histiocytes. The RDD histiocytes contained single but sometimes multiple nuclei that were larger and more hyperchromatic than those of the usual histiocytes. Many RDD histiocytes had voluminous, pale pink cytoplasm. Lymphophagocytosis by RDD histiocytes was observed. The findings in the crush smears reflected the histology of the lesions. The lymphophagocytosis and nuclear details in the RDD histiocytes were more visible in the crush smears than in the frozen sections. CONCLUSION: Crush cytology appears useful, alone or in conjunction with frozen sections, in the intraoperative diagnosis of CNS RDD.     

Cytologic findings in calcifying epithelial odontogenic tumor: a case report

BACKGROUND: Calcifying epithelial odontogenic tumor (CEOT), or Pindborg's tumor, is a rare, benign, odontogenic neoplasm first described by Pindborg in 1955. It is most commonly seen in the fourth and fifth decades of life, usually arises in the mandibular premolar-molar areas and accounts for approximately 1% of all intraosseous odontogenic tumors. This report describes the cytologic findings in a case of CEOT. CASE: A 62-year-old woman was referred to the ear, nose and throat clinic with a right maxillary mass. The fine needle aspiration (FNA) smears showed numerous calcifications; amorphous, eosinophilic material; and clusters of round epithelial cells embedded in a bloody background. The smears were diagnosed as suspicious for malignancy. Maxillectomy was done. The histologic sections were diagnosed as CEOT. CONCLUSION: FNA findings of calcifying epithelial odontogenic tumor have been described rarely. The clusters of epithelial cells with prominent nucleoli are mistaken for features of a malignant tumor.     

Fine needle aspiration cytology of the Ewing's sarcoma family of tumors

OBJECTIVE: To study the cytomorphologic features of the Ewing's sarcoma (ES) family of tumors. STUDY DESIGN: During a period of eight years (1990-1997), 123 soft tissue tumors and 65 bone tumors were evaluated by fine needle aspiration cytology (FNAC); 14 cases were diagnosed as in the ES family of tumors. The ages of the patients ranged from 8 to 30 years. All the cases were histologically confirmed. RESULTS: Of 14 cases of the ES family of tumors, 7 were ES, 3 extraosseous ES (EOE), 2 peripheral primitive neuroectodermal tumor (PPNET) and 2 Askin tumor. Cytologically, smears from all the cases showed round tumor cells with a high nuclear/cytoplasmic ratio. On detailed examination, subtle differentiating features were observed. The cells in ES had finer nuclear chromatin in comparison to those of PPNET and Askin tumor, and punched-out clear cytoplasmic vacuoles were present. PPNET showed nuclear molding, unipolar cytoplasmic tags and Homer-Wright rosettes. Histologically, all cases of ES and EOE and one case of Askin tumor showed periodic acid-Schiff-positive inclusions. CONCLUSION: FNAC features coupled with clinical findings enable a rapid diagnosis of the ES family of tumors, from which treatment modalities can be determined.     

Imaging of pediatric brain tumors using somatostatin analogue 111Ih-DTPA-D-Phe1-octreotide

Malignant solid tumors and leukemias are the second most common causes of death in childhood. The most frequent pediatric solid tumors are brain tumors. Brain tumors, especially medulloblastoma should be treated by surgery, irradiation and chemotherapy. However, chemotherapy has only moderate effect. Pediatric brain tumors, especially medulloblastomas, express somatostatin receptors. The aim of this study was the investigation of the expression of somatostatin receptors in pediatric brain tumors for diagnostic and therapeutic purpose. Fifty-six scintigraphic imagings (111In-DTPA-D-Phe1-octreotide) made in 45 children treated with brain tumor at the Unit of Oncology of the 2nd Department of Pediatrics, Semmelweis University. The diagnosis was medulloblastoma in 21 cases (46.7%). MRI scans have been performed parallel with the Octreoscan images. Octreoscan images were positive in 27 of 56 (48.2%) cases. The 27 positive Octreoscan images consisted of 16 medulloblastomas, 4 ependymomas, 4 astrocytomas and 3 glioblastomas. In 37 (66.1%) cases the results of Octreoscans were the same as those of the MRI scans. However, in 19 scans (33.9%) the outcome was different. Octreoscan imaging is not suitable for differential diagnosis in pediatric brain tumors, including medulloblastomas. Isotopes specifically binding to the somatostatin receptors (111In-DTPA-D-Phe1-octreotide) can be applied in medulloblastomas for diagnosis and follow-up treatment. In Octreoscan-positive tumors the Octreoscan images establish the opportunity to somatostatin analogue and/or specifically targeted radiation therapies.     

Fine needle aspirate smear morphology in metastatic melanoma

Cytologic smear preparations of fine needle aspirates obtained from 71 patients with biopsy-proven metastatic malignant melanoma were morphologically analyzed. Cell diameter, percentage of cells lying individually, smear cellularity, mitotic rate, percentage of cells with nuclear inclusions and number of giant cells were quantitated. Qualitative estimates of degree of pigmentation, background composition, presence of macrophages, presence of contaminating blood, cell shape, amount and appearance of cytoplasm, prominence of Golgi apparatus, reactivity with the antibody NKI/C-3 and eccentricity of the nuclei were made. While eccentric nuclei, cytoplasmic vacuoles, intranuclear inclusions, high cellularity and cells with abundant cytoplasm were found frequently in smears from malignant melanomas, the presence of reactivity with NKI/C-3, pigment, giant cells, a bloody background and a lack of cell cohesion were the features most commonly associated with smears obtained from patients harboring metastatic melanoma.     

Malignant melanoma of mediastinum misdiagnosed as a spindle cell thymoma in a fine needle aspirate: a case report

BACKGROUND: Malignant melanomas in the medastinum are extremely rare. Both primary melanomas and metastatic lesions from a primary elsewhere can occur in the mediastinum. Aspiration biopsy of a melanoma at this unusual site may pose problems in diagnosis. CASE: A 35-year-old woman presented with an anterior mediastinal mass. Cytologic smears were hemorrhaghic and revealed a loosely dispersed population of spindle cells with prominent nucleoli. In view of the location, the possibility of spindle cell thymoma was suggested on cytology. Subsequent histology revealed a malignant melanoma. CONCLUSION: This case stresses that the cytopathologist should keep in mind the remote differential diagnosis of a malignant melanoma while evaluating spindle cell neoplasms of the mediastinum, especially in tumors with prominent cell dispersal and with cells that have prominent nucleoli even without melanin pigment. Accurate diagnosis helps in evaluating patients and avoids unnecessary surgery when the lesion represents a metastasis to the mediastinum from a primary elsewhere.     

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.     

Cytologic findings with histologic correlation in 43 cases of mammary intraductal adenocarcinoma diagnosed by aspiration biopsy

OBJECTIVE: To review the cytologic and subsequent histologic findings in intraductal mammary adenocarcinoma (ductal adenocarcinoma in situ) (DCIS) to evaluate the role of aspiration biopsy (AB) in identifying and grading the disease. STUDY DESIGN: AB smears and tissue sections from 43 women with pure DCIS who underwent preoperative AB were reviewed. Smears were assessed for cellularity, cellular arrangement (including dissociation, nuclear size and pleomorphism), and presence of nucleoli and necrosis. RESULTS: Of the 43 cases, 22 were high grade (HG) DCIS, 7 cases were intermediate grade (IG), and 14 cases were low grade (LG). Cytologic findings of HG DCIS was as follows: high cellularity (22/22), clusters of pleomorphic cells with large nuclei and increased nuclear/cytoplasmic ratios (22/22), single cells (20/22), prominent nucleoli (22/22) and necrosis (diffuse in 15/22, focal in 7/22). All LG cases had moderately to highly cellular smears with cohesive, 3-dimensional sheets of uniform, small cells with inconspicuous nucleoli arranged around a central lumen, forming "punched-out" spaces. Single cells were prominent in 2 of 14 cases. IG DCIS showed intermediate features between LG and HG DCIS: 3-dimensional sheets with punched-out spaces, abundant single cells, moderate pleomorphism and focal necrosis. CONCLUSION: HG DCIS is easily identifiable on AB smears; however, distinction from invasive carcinoma may not be possible. The cytologic diagnosis of LG DCIS is difficult, and 50% of our cases were called atypical on AB. Recognition of cohesive cellular arrangements with crowding and punched-out spaces is crucial as single cells and prominent atypia are often lacking.