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.     

Exfoliative cytology of multiple endobronchial granular cell tumor

A multicentric endobronchial granular cell tumor (GCT) in a 50-year-old man was diagnosed by the cytologic study of bronchial lavage specimens. The paraffin-embedded sections contained small clusters of medium-sized round tumor cells that had eccentric nuclei without nucleoli and eosinophilic finely granulated cytoplasm, which was positive with the periodic acid-Schiff stain. These cells were distinguishable from the macrophages and bronchial and squamous cells also found in the specimens. The excised tumors histologically mimicked a squamous cell carcinoma. Since 10% of all GCTs occur in the lung, where a multiple presentation can especially mimic a metastatic malignant process, it is important that the possibility of a granular cell tumor be considered in the screening of exfoliative cytologic specimens from the lung.     

Cytologic features of granulosa cell tumors in fluids and fine needle aspiration specimens

OBJECTIVE: To describe the cytologic features of granulosa cell tumors in fluids and fine needle aspiration specimens, with histologic confirmation. STUDY DESIGN: Histologically confirmed granulosa cell tumors, 6 adult type and 1 juvenile type, were identified. All patients had local recurrences or metastases. Eleven specimens from 7 patients, including cytologic samples, cell blocks and histology, were reviewed. Inhibin immunostaining was performed on cell blocks to aid identification of this group of tumors in the cytologic and histologic samples. RESULTS: The patients were 22-72 years old. Sites included ovary and peritoneum; there were pelvic recurrences and metastatic lesions in the spleen, liver, perirectum and cervical lymph node. Cytologic features of adult granulosa cell tumors included 3-dimensional clusters, resettes loose monolayers and individual cells. Other features were Call-Exner bodies, vacuolated cytoplasm, exuberant capillaries associated with papillarylike fronds, a second population of elongated theca cells, and prominent or rare nuclear grooves. In juvenile granulosa cell tumor the features observed were monolayers, loosely cohesive sheets, single cells, occasional larger pleomorphic cells with nuclear clefting and nuclear protrusions, vacuolated cytoplasm, finely granular chromatin and frequent mitoses. The overall cytologic and histologic correlation was good. Inhibin was focally positive in one peritoneal fluid, correlating with the focal pattern of staining seen on histology. CONCLUSION: A definitive cytologic diagnosis of granulosa cell tumor can be made based on the above criteria. Aggressive tumors are discohesive and show pleomorphism and nuclear protrusions. Inhibin stain may be helpful in identifying granulosa cell tumors in cell block specimens.     

Cytologic diagnosis of primary adenocarcinoma of Bartholin's gland. A case report.

The cytologic and histologic findings in an extremely rare case of adenocarcinoma of Bartholin's gland are described. The tumor cells in scraping and fine needle aspiration smears were in clusters. The nuclei were oval to oblong, and some cells had a peripherally displaced nucleus. The chromatinic material was slightly increased, and some nuclei had prominent nucleoli. The cytoplasm was basophilic and abundant. Microcalcifications and psammoma bodies were numerous. The tentative diagnosis was primary adenocarcinoma of Bartholin's gland, based on the cytologic findings and location of the tumor. Similar findings were noted in the biopsy and surgical specimens.     

Specific tumor markers in diagnostic cytology. Immunoperoxidase studies of carcinoembryonic antigen, lysozyme and other tissue antigens in effusions, washes and aspirates

The immunoperoxidase technique was used to identify specific tumor markers in exfoliated cells in fine needle aspirates and body fluids. Carcinoembryonic antigen (CEA) and lysozyme staining was evaluated in cytocentrifuge preparations from 42 malignant effusions and aspirates and 16 benign effusions. Reactive mesothelial cells were negative for CEA and lysozyme or showed faint peripheral cytoplasmic staining. Malignant cells from 50% of the adenocarcinomas studied were positive for CEA. All tumors studied were negative for lysozyme. These staining patterns are helpful in the differential diagnosis of reactive mesothelial and adenocarcinoma cells, a frequent diagnostic dilemma. Moreover, demonstration of specific tumor antigens (e.g., prostatic acid phosphatase, calcitonin and immunoglobulin) helped define the origin of metastatic malignancy in selected cases. Estrogen receptor activity was also identified in tumor cells using this technique. Immunoperoxidase was helpful in the evaluation of malignant cytologic specimens from patients with more than one tumor. Interpretation of staining patterns is discussed, with reference to the limitations of the technique. Immunoperoxidase methods maintain cytologic detail, are readily adaptable to diagnostic cytology and increase the specificity of cytologic diagnosis.     

Identification of types and primary sites of malignant tumors by examination of exfoliated tumor cells in serous fluids. Comparison with the diagnostic accuracy on small histologic biopsies

The accuracy of identification of tumor type and primary site of malignant tumors by examination of exfoliated tumor cells was cytologically studied in 448 malignant effusions from 366 patients for whom the primary tumor site had been confirmed by histology. Ninety-seven corresponding small biopsies from metastases were separately reviewed histopathologically. In four fluids, the cells were too scanty or too poorly preserved for tumor typing. The cytologic tumor typing was performed with nearly 100% accuracy in the remaining 444 fluids, except for those of intermediate-cell anaplastic carcinomas (0 of 3) and poorly differentiated squamous (epidermoid) carcinomas (1 of 5). Adenocarcinoma was correctly identified in 98% of 285 fluids, large-cell carcinoma in 97% of 108 fluids, oat-cell carcinoma in 94% of 16 fluids, well-differentiated (keratinizing) squamous carcinoma in 100% of 3 fluids, malignant lymphoma in 100% of 22 fluids and sarcoma in 100% of 2 fluids. The criteria and the failures are discussed at length. In the investigation of the accuracy of cytologic and histologic diagnoses with respect to the primary tumor site, tumors with variable sites of origin (sarcomas and lymphomas) and those with usually singular sites of origin (e.g., small-cell anaplastic carcinoma of the lung) were excluded, leaving 387 cytologic and 83 histologic specimens available for review. The breast as a primary site was correctly identified in 70% of both the cytologic and histologic specimens; the primary cytodiagnostic criteria included a uniform cell pattern, finely granular chromatin, dense cytoplasm and cell balls with smooth borders. Ovarian primaries were correctly identified in 70% of the fluids and 83% of the biopsy samples on the basis of very irregular clusters of large pleomorphic tumor cells, large nucleoli and psammoma bodies. Lung primaries, identified in 50% of the fluids and 29% of the biopsy samples, showed quite variable cell patterns, most often including large pleomorphic cells with or without mucus formation and prominent multinucleation. Gastric cancers of the diffuse type were accurately identified in 52% of the corresponding fluids, which showed mainly isolated cells with dense cytoplasmic rims, occasional signet-ring cells, "embryo-shaped" nuclei, marked hyperchromasia and densely granular chromatin.(ABSTRACT TRUNCATED AT 400 WORDS)     

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.     

Fine needle aspiration cytologic findings in metastatic basaloid squamous cell carcinoma of the head and neck.

Basaloid squamous cell carcinoma of the head and neck is a variant of squamous carcinoma the cytomorphology of which has not been examined previously. The cytologic features of metastatic basaloid squamous cell carcinoma in fine needle aspiration specimens from nine patients are described. The primary tumors, when known, were located in the base of the tongue, tonsil, epiglottis, nasopharynx, hypopharynx and false vocal cord. Each neoplasm had large fragments or clusters of crowded cells and scattered single cells in the cytologic smears. The cells had round or oval, hyperchromatic nuclei that often had single, small nucleoli. The nuclei usually were small or medium sized, but six tumors had a few cells the nuclei of which were large and pleomorphic. The cytoplasm was typically scant, and only three cases had occasional keratinized cells. Necrosis was present in six neoplasms. Three neoplasms, originally diagnosed as small cell undifferentiated carcinoma, contained numerous single cells and small clusters of cells with nuclear molding. On review, however, smears from these neoplasms also contained a few large fragments of tightly cohesive cells with larger, vesicular nuclei. Another basaloid squamous cell carcinoma had been interpreted elsewhere as an adenoid cystic carcinoma because of the presence of pseudoglandular structures with stromal cores. Although the cytologic features of basaloid squamous cell carcinoma may mimic those of other poorly differentiated carcinomas in fine needle aspiration specimens, they are sufficiently distinctive that a diagnosis of this variant of squamous cell carcinoma can be suggested for a patient whose primary neoplasm is located in the upper aerodigestive tract.     

Signet ring adenocarcinoma metastatic to the bronchus and mimicking goblet cell hyperplasia. A case report

BACKGROUND: Goblet cells in the lower respiratory tract are metaplastic bronchial epithelial cells usually associated with asthma or chronic bronchitis. Goblet cells acquire their name by a tendency to distend with mucus, with subsequent distortion in cell shape. Due to similarity of shape, metaplastic goblet cells and signet ring cells can be easily confused in cytologic samples. CASE: A 55-year-old male with a history of gastrointestinal adenocarcinoma underwent brushing, washing and biopsy of a bronchial lesion. The bronchial wash and brush samples showed a very cellular specimen, with large aggregates of distended columnar cells. These were arranged in long strips, thick bundles and occasional three-dimensional aggregates. Some aggregates contained numerous rounded cells with markedly distended cytoplasm. The rounded cells were slightly larger than the distended columnar cells. These cells had a relatively large but innocuous-appearing nucleus displaced to the periphery of the cell. The corresponding bronchial biopsy revealed signet ring adenocarcinoma, presumably metastatic from the gastrointestinal primary. CONCLUSION: Signet ring adenocarcinoma, either primary or metastatic, can be difficult to diagnose in cytologic and histologic specimens. There are numerous mimics of signet ring cells, both benign and neoplastic. In respiratory cytologic specimens, one of the benign imposters is goblet cell metaplasia.     

Cytology of angiosarcoma in effusions

The cytologic and immunocytochemical findings in pleural effusions from three cases of angiosarcoma are presented. In two of the cases, the primary lesion was on the scalp; in the third case, an angiosarcoma of the small intestine developed after radiotherapy for Hodgkin's disease. Single malignant cells and small clusters of cells were seen in cytologic preparations from two cases while only single cells were seen in preparations from one case. The malignant cells had delicate, finely vacuolated cytoplasm with distinct borders. No specific morphologic features were noted. Immunoperoxidase studies revealed binding of Ulex europaeus and reactivity for vimentin in all three cases and expression of Factor VIII-related protein in two of the cases but no expression of epithelial markers. The clinical history and immunoperoxidase studies are necessary to distinguish angiosarcoma from metastatic adenocarcinoma and other malignancies in effusions.     

Prostatic carcinoma cells in urine specimens

Between January 1985 and March 1990, the Cytology Laboratory of Hanover General Hospital examined cytologic preparations from four patients which revealed cells consistent with prostatic adenocarcinoma. In three of these cases, malignant cells were positive for prostatic-specific antigen. A fifth patient's specimen contained prostatic-specific antigen positive cells compatible with prostatic origin, but without overtly malignant features. All five patients had high grade prostatic adenocarcinoma (Gleason's Grade 8–10), and urinary tract symptoms. the most useful cytologic features indicating prostatic origin were large and often multiple nucleoli.     

Distribution of silver-stained interphase nucleolar organizer regions as a parameter to distinguish neoplastic from nonneoplastic reactive cells in human effusions

The distribution of interphasic nucleolar organizer regions (NORs) was studied in cytologic preparations of human serous effusions in order to differentiate malignant cells from nonmalignant reactive cells. The study was carried out on 80 cases of metastatic adenocarcinoma, 10 cases of mesothelioma, 10 reactive pleural effusions and 5 peritoneal washings. Visualization of NORs at the light microscopic level was obtained using a silver-staining technique for acidic proteins selectively associated with NORs. The morphologic data were also statistically evaluated by means of an automated image analyzer. The quantity of silver-stained NORs was higher in cancer cells (both mesothelioma and adenocarcinoma) than in reactive mesothelial cells. Moreover, NORs were more irregularly distributed within the nucleoli and were more variably sized in cancer cells than in reactive mesothelial cells.     

The distinction of mesothelioma from adenocarcinoma in malignant effusions by electron microscopy

To determine the usefulness of the electron microscopic (EM) differential diagnosis between malignant mesothelioma and metastatic adenocarcinoma in cytologic specimens of serous fluids, we undertook a prospective study of 17 pleural and peritoneal effusions from 14 patients. In the nine effusions identified as malignant by routine cytologic examination, EM correctly diagnosed three mesotheliomas and six adenocarcinomas. EM resolved the differential diagnosis of mesothelioma versus adenocarcinoma in three cases in which routine cytologic examination could not. As with tissue specimens, EM cannot be used to diagnose the malignancy of cytologic specimens; it can, however, reliably identify the origin of cells diagnosed as malignant by routine cytologic examination. We conclude that, when EM is used to evaluate cytologically malignant effusions, it can accurately distinguish mesothelioma from adenocarcinoma. This technique will be diagnostically useful in selected cases and may be helpful in avoiding more invasive procedures as well as delays in diagnosis and therapy.     

The cytopathologic diagnosis of esophageal adenocarcinoma

The diagnostic cytologic features were analyzed in 18 cases of histopathologically proven esophageal adenocarcinoma accessioned at the Johns Hopkins Hospital between 1975 and 1988 for which cytologic material was available. Primary esophageal adenocarcinoma was diagnosed in 15 of 18 cytologic specimens (83%); in 3 cases (17%), carcinoma was suspected, but the changes were nondiagnostic. The most consistent cytologic changes included both architectural features (loss of orientation and nuclear crowding) and criteria of malignancy (high nuclear/cytoplasmic ratios and prominent nucleoli). In the 15 diagnostic cases, the nucleoli were small in 8 and round in 11; in the majority of these cases, the nuclei contained one to three nucleoli. In addition, nuclear and cytoplasmic molding was seen in 9 of these 15 cases, hyperchromasia was present in 8, coarse chromatin clumps were seen in 5, and tissue fragments tended to be multilayered. Review of the three nondiagnostic cases showed that scant material was present in two; the third case had abundant material, but only nondiagnostic changes, suggesting a sampling error. Barrett mucosa was seen in 7 of the 18 cases. These cases show that esophageal adenocarcinoma can be reliably diagnosed on cytologic preparations, based on the consistent architectural features and the usual cellular criteria of malignancy.     

Polymorphous low grade adenocarcinoma of the salivary gland. Diagnosis by fine needle aspiration cytology

OBJECTIVE: To describe the fine needle aspiration cytology findings of polymorphous low grade adenocarcinoma of the salivary gland. STUDY DESIGN: The authors reviewed the cytologic findings of 5 cases of polymorphous low grade adenocarcinoma. All cases were confirmed by histologic examination. RESULTS: All cases showed similar cytologic findings. The smears had high cellularity with a population of mixed epithelial and myoepithelial cells. These cells formed branching papillae, sheets and clusters. The epithelial cells were uniform, with round to ovoid nuclei; absent or inconspicuous nucleoli; and a moderate amount of dense cytoplasm. Occasionally the cells formed spherical structures containing hyaline globules. Myxoid matrix, either dispersed in the background or interspersed with the cellular elements, was also seen often. CONCLUSION: Polymorphous low grade adenocarcinoma should be cytologically differentiated from adenoid cystic carcinoma, monomorphic adenoma and pleomorphic adenoma. Recognition of subtle cytologic features. may be useful in the differential diagnosis.     

Isolated carcinoid tumor metastatic to the thyroid gland: report of a case initially diagnosed by fine needle aspiration cytology

BACKGROUND: Neuroendocrine tumor metastatic to the thyroid gland is rare and may be difficult to differentiate from primary thyroid neuroendocrine tumors, such as medullary thyroid carcinoma (M/ITC). This report describes an unusual case of bronchial carcinoid metastatic to the thyroid diagnosed by fine needle aspiration cytology (FNAC). CASE: A 42-year-old woman with an undiagnosed bronchial carcinoid tumor presented to our clinic with a solitary nodule in the thyroid gland. FNAC of the nodule showed loosely cohesive groups of cuboidal tumor cells with scant, slightly granular cytoplasm; centrally located nuclei with a coarsely granular, salt-and-pepper chromatin pattern and inconspicuous nucleoli. Immunocytochemically the tumor cells were positive for neuron-specific enolase, chromogranin and synaptophysin and negative for thyroglobulin, calcitonin and carcinoembryonic antigen. The cytologic diagnosis of a metastatic neuroendocrine carcinoma was confirmed histologically. CONCLUSION: Metastasis to the thyroid gland may pose a diagnostic problem, particularly with tumors of neuroendocrine origin, as these have similar cytologic features in various organs. The correct preoperative cytologic diagnosis of metastatic carcinoid tumor in patients without a prior history of cancer and differential diagnosis with MTC are crucial because prognosis, workup and treatment are different in each.     

Positive effusion cytology as the initial presentation of malignancy

During a period of four years (1981 to 1984), 641 ascitic, 860 pleural and 47 pericardial fluid specimens were examined cytologically. Of these, 154 ascitic samples, 174 pleural specimens and 10 pericardial effusions, obtained, respectively, from 108, 133 and 7 patients, were found to contain malignant cells. In 7 patients, ascites, and in 18 cases, pleural effusions were the first indication of cancer. None of the positive pericardial fluids was the initial presentation of malignancy. The cytologic findings and follow-up data on these 25 patients are the subject of this study. The most common type of neoplasm in these effusions was adenocarcinoma (86% of the ascitic and 78% of the pleural fluids). Most of the malignant neoplasms in ascitic fluids were derived from ovarian tumors (5 of 7) while those in pleural effusions came mainly from lung tumors (12 of 18). Mammary carcinoma, which was the most common malignant tumor found in cases of pleural effusions, did not present initially with an effusion in any of our cases. The cytologic diagnosis was confirmed in all cases by either biopsy or strong clinical evidence. The prognosis in patients who initially presented with an effusion was poor. All of the patients with an adequate follow-up died within 29 months in cases of ascites and within 19 months in cases of pleural effusions.     

Comparison of the pick-and-smear and Saccomanno methods for sputum cytologic analysis

The two methods of preparing sputum specimens for cytologic study, the (fresh) pick-and-smear technique and the (blended) Saccomanno technique, were compared using 249 consecutive specimens. Two slides were prepared for each specimen by each technique. Of the specimens, 103 showed squamous metaplasia, carcinoma in situ or carcinoma. A semiquantitative rating system (0 to 4+) was used to determine the number of diagnostic cells for each method for those 103 cases. More diagnostic cells were found on the Saccomanno preparations (217) than on the fresh preparations (154). There were 121 diagnostic cells in the Saccomanno preparations versus 95 diagnostic cells in the fresh preparations from 63 squamous metaplasias; 7 versus 3 for the preparations from 5 carcinomas in situ; 64 versus 42 from 28 squamous cell carcinomas; 3 versus 1 from 1 large cell undiffernomas; and 12 diagnostic cells in Saccomanno preparations versus 5 in fresh preparations from 3 small cell cancers. Twelve squamous metaplasias, two carcinomas in situ, four squamous carcinomas, one adenocarcinoma and one small cell cancer had no diagnostic cells on the fresh preparations; four squamous metaplasias and one squamous carcinoma had no diagnostic cells on the Saccomanno preparations. More diagnostic information and fewer false-negative results were achieved with the Saccomanno technique.