Cytomorphometry of large cell carcinoma of the lung

A computerized morphometry system was used to evaluate criteria for the cytologic diagnosis of large cell carcinoma (LCC) and poorly differentiated adenocarcinoma of the lung. There were 143 cells measured in six cases of LCC (five sputums and one bronchial washing) and 61 cells in four cases of adenocarcinoma (all sputum samples). Cellular and nuclear areas were significantly larger in adenocarcinoma whereas nucleolar area was greater in LCC, producing a higher nucleolar/nuclear area ratio in LCC. Cellular and nuclear form factors were smaller in LCC while the minor axis was longer in adenocarcinoma, resulting in a smaller axial ratio in adenocarcinoma. These data indicate that adenocarcinoma cells are larger and have a more rounded shape and less nucleolar material, as compared to the smaller, more ellipsoid and convoluted cells of LCC, which have more nucleolar area. A logistic regression identified cellular area, nucleolar/nuclear area ratio and cellular and nuclear form factors as significant contributors to the discrimination of LCC from adenocarcinoma, with a positive predictive value of 92%. Morphometry may therefore be helpful in the differential cytologic diagnosis of adenocarcinoma and LCC.     

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.     

Choroid plexus carcinoma. Report of a case with cytopathologic differential diagnosis

The cytopathologic features of choroid plexus carcinoma in the cerebrospinal fluid of a 13-month-old male infant were reviewed and compared with those of other small-cell malignant neoplasms of childhood and young adulthood involving the central nervous system. The cytologic features of the choroid plexus carcinoma (tight spatial clusters and isolated anaplastic cells with striking nuclear lobulation) were distinct from those of lymphoma, leukemia, neuroblastoma, ependymoma and pineal germinoma. However, the cells had a striking resemblance to those of anaplastic ependymoma and metastatic adenocarcinoma.     

Diagnosis of cervical chordoma by fine needle aspiration biopsy

A case of cervical chordoma diagnosed by fine needle aspiration (FNA) is presented. The cytologic criteria for differentiating chordoma from chondrosarcoma and metastatic adenocarcinoma, the main diagnostic problems, include the finding of physaliferous cells and the presence of bland nuclear features. Significantly, chordomas lack true signet-ring cells. FNA of these rare midline vertebral neoplasms, which produce pain and spinal cord compression, can greatly facilitate diagnosis and optimal treatment.     

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.     

Colon carcinoma metastatic to the lung. Cytologic manifestations and distinction from primary pulmonary adenocarcinoma.

Based upon a review of cytologic specimens obtained from 46 patients, the morphologic characteristics of metastatic colon carcinoma and primary pulmonary adenocarcinoma were compared and contrasted. A monoclonal antibody (D-14) reported to be helpful in identifying colorectal carcinoma was also evaluated. Colon brushings and washings from 10 patients with colonic carcinoma and a variety of respiratory tract cytology samples from 16 and 20 patients with metastatic colonic and primary pulmonary adenocarcinomas, respectively, formed the basis of this review. The presence of well-formed glands and dirty necrosis was significantly more characteristic of colon carcinoma. Other cytologic features and D-14 staining were not sufficiently distinctive to allow a separation from primary pulmonary adenocarcinoma.     

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.     

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.     

Cytologic findings of ascites from patients with ovarian dysgerminoma

The cytomorphologic observations of ascites from three patients with ovarian dysgerminomas are presented. As compared with those in adenocarcinoma, the cytologic findings in this rare malignant ovarian tumor showed more cells lying isolated or in sheetlike arrangements, fewer cells with discrete cytoplasmic vacuoles, less frequent thickening of the nuclear membrane and more frequent multinucleolation.     

Fine needle aspiration diagnosis of transitional cell carcinoma metastatic to the brain. A case report

BACKGROUND: Transitional cell carcinoma (TCC) rarely metastasizes to the brain. In this case, aspiration of a cystic brain lesion was performed and a cytologic diagnosis made. To the best of our knowledge, this is the first reported case of TCC metastatic to the brain diagnosed by fine needle aspiration. CASE: A 72-year-old male with a past medical history of invasive TCC, colonic adenocarcinoma and prostatic adenocarcinoma presented with a large, right, temporal, cystic mass. Fine needle aspiration was performed intraoperatively, and a cytologic diagnosis of metastatic TCC was rendered and confirmed by subsequent tissue examination. CONCLUSION: Intraoperative fine needle aspiration of cystic tumors can be useful in identifying the primary site. The cytologic features of intracerebral metastatic TCC can differ significantly from those observed in urinary tract specimens of high grade TCC. A predominance of large fragments of malignant cells with numerous mitotic figures and apoptotic bodies was seen in the former. The background showed high grade, single transitional cells similar to those observed in urinary tract samples of TCC.     

Quantitative ultrastructural study of nuclei from exfoliated benign and malignant mesothelial cells and metastatic adenocarcinoma cells

Various approaches, including morphometric image analysis, are currently being used to improve the distinction between diffuse mesothelioma and metastatic adenocarcinoma of the serous membranes. Since exfoliated cells of malignant mesotheliomas were thought to have nuclear profile contours with greater irregularity than the similar profiles in metastatic adenocarcinoma cells in pleural effusions, this and other nuclear parameters were measured in ultrastructurally examined preparations from three cases of reactive mesothelial hyperplasia, seven examples of diffuse mesothelioma and three cases of metastatic adenocarcinoma (with primaries in the ovary, esophagus and prostate). Contrary to the subjective impression, the nuclei in metastatic adenocarcinomas actually had a mean nuclear contour index greater than that found in diffuse mesotheliomas; statistically, the difference was not significant. Likewise, such other nuclear parameters as nuclear area, condensed chromatin area and contour index, percentage of condensed chromatin and number of condensed chromatin clumps per nuclear profile did not discriminate between malignant mesotheliomas and adenocarcinomas metastatic to pleural surfaces. These morphometric results quantitate the similarities in nuclear size, nuclear shape and condensed chromatin arrangement in these two types of tumor and explain why the cytopathologist has such great difficulty in distinguishing between exfoliated mesothelioma and adenocarcinoma cells in most cases.     

Fine needle aspiration of adenoid cystic carcinoma metastatic to the lung. Cytologic features and differential diagnosis

Two examples of adenoid cystic carcinoma metastatic to the lung, one from a Bartholin's gland and the other from a submandibular gland, were sampled by fine needle aspiration. Although the cytologic features of adenoid cystic carcinoma have been well described, it is easy to confuse adenoid cystic carcinoma with other more common primary small-cell neoplasms of the lung; to determine distinguishing features, we compared the cytomorphology of adenoid cystic carcinoma with well-differentiated adenocarcinoma, small-cell undifferentiated carcinoma and carcinoid tumor of the lung. The differential features distinguishing adenoid cystic carcinoma from these other neoplasms include: (1) tight, globular, honey-comb arrangements of cells lacking true nuclear molding; (2) acellular chunks of basal lamina material, which alone may suggest adenoid carcinoma; and (3) the extension of a solid core of basal lamina material beyond a sievelike cellular meshwork. The morphologic expression of metastatic adenoid cystic carcinoma is so distinctive as to permit a definite diagnosis.     

Metastatic breast carcinoma in cerebrospinal fluid. A cytomorphometric study

A study was undertaken to quantitate the cellular characteristics of metastatic breast carcinoma in cerebrospinal fluid (CSF). Millipore filters of CSF from 15 patients with metastatic breast carcinoma were reviewed; 50 cells per case were evaluated when available. All cells in all cases shed singly or in loose clusters; tight balls or morulae were absent. All cells had regular, round-to-oval nuclei with finely granular chromatin. The majority of cells in all cases had single or multiple round nucleoli, granular cytoplasm with distinct borders and a mean nuclear-cytoplasmic ratio of close to 0.70. Cellular background, number of tumor cells per case, number and placement of nuclei and nuclear and cytoplasmic diameter varied both within and among the cases. There was significant variation in nuclear and cytoplasmic diameters both within and among the cases of infiltrating ductal carcinoma. Thus, the uniform appearance of the cells was due to consistent cytologic features, not to similarity in cell size. The cytologic profile of metastatic breast carcinoma is sufficiently characteristic to distinguish this tumor from other benign and malignant lesions that shed in the CSF.     

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.     

Glandular lesions of the cervix on thin-layer Pap tests. Validity of cytologic criteria used in identifying significant lesions

OBJECTIVE: To determine the cytologic features that are most helpful in characterizing significant glandular lesions of the cervix observed on the ThinPrep (TP) Pap test (Cytyc Corp., Boxborough, Massachusetts, U.S.A.) and to compare these features with those published for conventional smears. STUDY DESIGN: Thirty-nine TP preparations with cytologic evidence of glandular lesions of the cervix and histologic and/or clinical correlation were studied. These lesions included (1) 11 cases of benign/reactive conditions; (2) 10 cases of adenocarcinoma in situ (AIS), of which 1 had both AIS and carcinoma in situ; (3) 1 case of invasive adenocarcinoma; (4) 15 cases of squamous intraepithelial lesions and squamous cell carcinoma, including 4 with glandular involvement, and (5) 2 cases of adenosquamous cell carcinoma. These cases were reviewed by the first author without knowledge of the histologic diagnosis. Twenty-five previously published cytologic criteria were used to evaluate glandular cells on TP slides. Statistical analysis was performed using Fisher's exact test to determine the significance of the features studied. RESULTS: All glandular lesions had cytologic features on TP similar to those previously described on conventional smears. However, TP slides demonstrated enhanced nuclear features but less-preserved architectural patterns. Reactive lesions showed minimal overlapping without hyperchromasia or mitotic figures and with normal nuclear/cytoplasmic ratios. AIS and invasive adenocarcinoma cases had similar features. Increased cellularity and overcrowding were prominent, whereas feathering, rosettes and cell strips were present but subtle. CONCLUSION: Glandular lesions of the cervix on TP slides shared many of the characteristic features reported for conventional smears. However, nuclear details were more pronounced in TP slides, while architectural patterns, although present, were relatively subtle.     

Columnar cell carcinoma of the thyroid. Fine needle aspiration findings in a case

Columnar cell carcinoma is a recently described rare tumor of the thyroid. The fine needle aspiration cytologic findings of one example are reported. In the smears, the tumor fragments showed papillary and glandular patterns. The tumor cells were columnar and exhibited pseudostratification of the nuclei. The nuclei were oval to elongated and possessed stippled chromatin and inconspicuous nucleoli; occasional ones exhibited longitudinal grooving. It is important to distinguish this tumor from papillary carcinoma of thyroid because of its much more aggressive behavior, from metastatic adenocarcinoma for obvious treatment considerations, and from medullary carcinoma.     

Bronchioloalveolar carcinoma presenting with meningeal carcinomatosis. Cytologic diagnosis in cerebrospinal fluid

The cytologic findings in a 35-year-old patient with bronchioloalveolar carcinoma who initially presented with central nervous system involvement are reported. Following the cytologic diagnosis of carcinomatous meningitis (metastatic adenocarcinoma), an open lung biopsy was performed, which confirmed the presence of a primary pulmonary neoplasm (bronchioloalveolar carcinoma). This case illustrates the importance of the cytologic diagnosis of a clinically unsuspected primary neoplasm. Further, together with three earlier reported cases, it indicates that, in young patients, tumor cells shedding into the cerebrospinal fluid can be the first indication of bronchioloalveolar carcinoma.