Fine needle aspiration diagnosis of malignant lymphoma with confirmation by immunoperoxidase staining

Cytospin preparations of fine needle aspirates in 14 cases of suspected lymphoma were studied by immunoperoxidase techniques. The combination of cytologic smears and immunoperoxidase studies resulted in a working diagnosis in 13 of the 14 cases. The immunologic markers in conjunction with the cytologic appearance of the aspirates were reliable and consistent in differentiating between malignant and benign lymphoproliferative lesions and in determining the B-cell or T-cell nature of the process.     

Endocyte endometrial smears in the cytodiagnosis of endometrial carcinoma

The cytologic diagnosis of endometrial cancer using material obtained with the Endocyte endometrial sampler was assessed for 874 patients. The samples obtained were smeared directly on slides for fixation and staining; the smears were more difficult to assess than cervicovaginal smears, however, due to the presence of blood, the small size and density of the cells and the flattened three-dimensional architecture of the tissue fragments obtained. Only 8.2% of the samples were classified as inadequate; repeat sampling in some of those cases produced diagnostic material. All 12 cases of carcinoma (including one case in a woman less than 40 years of age) were diagnosed by cytology as malignant; however, the original cytologic sample in one of those cases was inadequate. For the diagnosis of benign versus malignant, cytology had a sensitivity of 92%, a specificity of 100% and predictive value of 100%. Cytology also diagnosed as suspicious the smears from 5 of 13 cases of endometrial hyperplasia and 2 of the 9 cases of endometrial polyps. The cytologic findings for benign and malignant samples are described and illustrated in detail. Relative to other endometrial sampling devices, the Endocyte is inexpensive and was easily used by the gynecologist and well tolerated by the patients, with no complications and minimal discomfort.     

Giant cystic metaplastic carcinoma of the breast: a case report with diagnosis by fine needle aspiration

BACKGROUND: Breast cysts are mainly benign and are reported in association with fibrocystic disease and phyllodes tumor. Rarely have cystic changes been reported to occur in malignant tumors. They are usually small but large in rare cases. Giant breast cysts are very rare, and only a few cases have been reported. CASE: A 37-year-old woman presented with a rapidly growing breast mass. Mammography showed a huge, well-circumscribed cystic mass (17 x 16 x 16 cm) suggestive of a benign lesion. Cytologic examination revealed a highly cellular tumor composed of malignant cells of various sizes and shapes in a necrotic background. The smears were diagnosed as positive for malignancy and suggested metaplastic carcinoma. Mastectomy was performed, and histologic study confirmed the cytologic diagnosis. CONCLUSION: This is the first reported case of a breast cyst of this size. Clinically the cyst was confused with a benign lesion. The fine needle aspiration aided the diagnosis and planning of treatment.     

Morphometric analysis of borderline atypia in prostatic aspiration biopsy specimens.

In a prior study of 411 fine needle aspirates of the prostate (FNAPs), we identified a subset of 50 (12%) aspirates in which the findings were designated cytologically atypical. These equivocal cases formed a heterogeneous group composed of both histologically benign and malignant proliferations in which cutting needle biopsy was necessary to further delineate the nature of the abnormality. In an attempt to define quantitative and morphologic criteria for the separation of these proliferations into benign and malignant categories and to reduce the need for diagnostic cutting needle biopsies, we performed a cytomorphometric analysis of smears from 12 FNAPs (6 histologically proven benign and 6 histologically proven malignant) with equivocal cytologic atypia. We were unable to define any cytomorphometric criteria that accurately subdivided these cases into benign and malignant categories.     

Malignant melanoma in fine needle aspirates and effusions. An immunocytochemical study using monoclonal antibodies

The value of monoclonal antibodies (MAbs) for the immunodetection of keratin, vimentin and two melanoma-associated antigens recognized by NKI/C3 and NKI/Bteb for the diagnosis of malignant melanoma has been previously established on histologic preparations. In the present study, cytologic preparations from 20 fine needle aspirates and effusions from patients with malignant melanoma were evaluated using these antibodies. Twenty of 20 smears were negative for keratin, and 20 of 20 smears were positive for vimentin. Positivity for NKI/C3 was seen in 12 of 12 cases studied, and for NKI/Bteb in 12 of 13 cases. These results indicate that a panel of MAbs consisting of anti-keratin, anti-vimentin, NKI/C3 and NKI/Bteb is useful for a more accurate diagnosis of malignant melanomas on cytologic preparations. The expression of these antigens in melanoma cells in cytologic smears can be a valuable aid in the detection of primary (noncutaneous) and metastatic melanomas by fine needle aspiration.     

Morphologic and immunocytochemical evaluation of 220 fine needle aspirates of malignant lymphoma and lymphoid hyperplasia

A total of 220 fine needle aspiration (FNA) specimens from 212 patients with clinically suspected or previously histologically confirmed lymphoma were evaluated by cytology in conjunction with immunophenotyping analysis of the aspirate; the results were compared with the histologic diagnosis made on previous or current accessions of lymph node or extranodal tissue. Smears of the aspirates were stained with the Diff-Quik and Papanicolaou stains while immunoperoxidase staining using antibodies against kappa and lambda immunoglobulin light chains and Leu-4 was routinely performed on Cytospin preparations. Where indicated, additional marker studies (including T-200, Leu-1, Leu-2a, Leu-3a + 3b, Leu-M1, B1, Leu-12, IgM, CALLA and TdT) were performed. For the non-Hodgkin's lymphomas, specimens were classified by the cytologic characteristics of the neoplastic cells according to the International Working Formulation scheme. The combination of cytologic smears and immunoperoxidase studies resulted in a diagnosis of lymphoma in 173 cases (79%). The remaining aspirates were interpreted as suspicious for lymphoma (7%), benign (10%) or inadequate for diagnosis (4%). Of the 15 suspicious aspirates, 5 proved to be Hodgkin's disease and 2 to be T-cell lymphoma by subsequent biopsy. The cause of failure in the nine inadequate aspirates were necrosis (3 cases), sclerosis (2 cases) and faulty technique (4 cases). In the cases that had concurrent tissue biopsies, no false-positive diagnoses were rendered. These results indicate that FNA used in association with immunocytochemistry is a reliable tool for establishing the diagnosis and classification of the majority of cases of lymphoma. Optimal immunoglobulin light-chain ratios for defining monoclonality in FNA specimens of B-cell lymphomas are proposed.     

Cytology of bronchial gland carcinoma

The cytologic findings in two adenoid cystic and three mucoepidermoid carcinomas of the bronchial tree are reported. In one case of adenoid cystic carcinoma, the diagnosis was made on a fragment of tumor tissue exfoliated in the patient's sputum. In the other case, brushing and aspirated materials yielded large clusters of small cells arranged around cystlike spaces containing globular basophilic mucuslike material. Fine needle aspirates from the two low-grade mucoepidermoid carcinomas showed clusters of malignant squamous cells containing mucus-secreting cells. The high-grade mucoepidermoid cancer yielded malignant squamous and glandular cells in aspirates.     

Decisive role of intermediate filament typing of tumor cells in the differential diagnosis of difficult fine needle aspirates

Thirty-six diagnostically difficult fine needle aspirates from enlarged lymph nodes and malignant soft tissue tumors, containing tumor cells with scanty or no obvious light microscopic features indicative of their differentiation, were assessed by a panel of six cytopathologists. Their diagnoses were recorded and then compared with the definitive diagnosis established by combining the cytologic findings with the results of intermediate filament typing of tumor cells in the smears using monoclonal antibodies specific for each filament type. The results show that use of these antibodies can markedly improve the accuracy of the cytologic diagnosis of tumor type as well as revise or prevent erroneous cytologic diagnoses in difficult cases. This pertains especially to the differential diagnoses of carcinoma versus malignant lymphoma, carcinoma versus malignant melanoma, carcinoma versus sarcoma and squamous carcinoma versus carcinoma of simple epithelia. Intermediate filament typing of tumor cells in aspirates as an objective histogenetic criterium makes the differential diagnosis of the difficult aspirates much more reliable and reproducible, provided that appropriate questions are asked, monoclonal antibodies with well-defined specificities are used and the antigenicity of the intermediate filaments in smears is preserved.     

Extracellular hyaline material in association with other cytologic features in aspirates from collagenous spherulosis and adenoid cystic carcinoma of the breast

OBJECTIVE: To reevaluate breast aspirates showing extracellular hyaline material (EHM) and globules to assess if clinicoradiologic and cytologic features could help in differentiating between benign and malignant lesions, especially collagenous spherulosis (CS) and adenoid cystic carcinoma (ACC). STUDY DESIGN: Fine needle aspiration was performed on 884 patients with breast lumps. The cytomorphologic features of 6 cases showing EHM, including classic hyaline globules (HGs), were analyzed in detail. Three cases also had hemorrhagic nipple discharge. Tissue diagnosis (4) and mammography (6) were available. RESULTS: Aspirate smears revealed high cellularity composed of monolayers: clusters of uniform, small cells; EHM; and HGs surrounded by similar cells. Benign naked nuclei and stromal fragments (4), nuclear pleomorphism (3), apocrine cells (2), foam cells (2), naked HGs (2) and spindle cells in proximity to HGs were also seen (4). Nipple discharge smears showed foam cells, erythrocytes (3) and epithelial cell clusters with hyaline material (1). The cytologic diagnosis was CS (4) and ACC (2). Histopathology confirmed the diagnosis of CS (2) and ACC (1). CONCLUSION: There may be a morphologic overlap between the cytomorphologic features of CS and ACC, leading to diagnostic errors. The presence of EHM and HGs in association with bland cellular features should be interpreted with caution to avoid erroneous diagnoses. Histopathology is mandatory in these cases because of their different prognostic implications.     

Phyllodes tumor of the breast. A cytohistologic study of 80 cases

OBJECTIVE: To study the cytologic features of phyllodes tumor (PT) of the breast and determine the accuracy of their subclassification in fine needle aspirates. STUDY DESIGN: Eighty cases of histologically diagnosed PT between 1982 and 1997 with a previous fine needle aspiration (FNA) were evaluated. The FNA smears of each case were reviewed without knowledge of the initial cytologic diagnosis and subclassified into benign, borderline or malignant PT. RESULTS: Benign PTs were characterized by a dimorphic mixture of stromal and epithelial cells. The stromal fragments showed mild to moderate cellularity with absent to minimal pleomorphism and no mitosis. There were occasional, if any, single stromal cells. Borderline PTs had stromal fragments with moderately cellular stroma exhibiting moderate pleomorphism. Two additional features were the presence of single stromal cells and an occasional mitosis in the stromal fragments/single cells. Aspirates from malignant PT were very cellular, with a high stromal/epithelial ratio and marked stromal cellularity. The stromal cells were highly pleomorphic, with frequent mitosis and atypical single stromal cells in the background. Fifty-seven of the 80 histologically documented cases (71.3%) were diagnosed as PT on FNA (40 benign, 10 borderline and 7 malignant). In 81% (46 of 57 PTs), good cytohistologic correlation (32 benign, 8 borderline and 6 malignant) was observed. In another eight cases, one grade differentiation between cytologic and histologic grade was observed. Six of the nine malignant PTs on histology were correctly subclassified on cytology. There were one false positive and two false negative cases. CONCLUSION: Cytologic diagnosis and grading of PT on FNA is possible. Special care should be undertaken in interpreting phyllodes fragments, cellularity of stroma, pleomorphism and mitosis. Single stromal cells are also important morphologic criteria for subclassification. Multiple-site aspiration is advisable to avoid diagnostic errors.     

Brushing cytology in biliary tract obstruction

During a period of eight years (1980 to 1987), cytologic samples were obtained by brushing and reverse screw devices from 54 patients undergoing transhepatic cholangiography for evaluation of obstructive jaundice. Eight patients were excluded from this study, seven for inadequate follow-up and one because of unsatisfactory cytologic material. Of the remaining cases, 32 were cytologically diagnosed as adenocarcinomas; all but one patient proved to have malignant disease by histologic examination and/or through clinical follow-up. These included 21 pancreatic carcinomas, 6 bile duct carcinomas, 1 ampullary carcinoma, 1 gallbladder carcinoma and 2 metastatic carcinomas. In one case, the diagnosis of malignancy was found to be in error upon review of the cytologic smears. Of 14 patients with negative cytologic diagnoses, 7 were found to have malignant neoplasms and 7 had benign diseases. These findings indicate that, while a positive cytologic diagnosis is a reliable indicator of a malignant biliary obstruction, a negative result does not exclude malignancy.     

Microfilariae of Wuchereria bancrofti in cytologic smears

Microfilariae of Wuchereria bancrofti were observed in cytologic material in 35 cases. The material included cervicovaginal smears (17 cases), effusions (14), urine (2), bronchial washings (1) and ovarian cyst fluid (1). The initial diagnosis was made from the cytologic smear in all cases; none had clinical filariasis. Symptomatic vaginal bleeding in 9 of the 17 cases with microfilaria-positive cervicovaginal smears was reflected in the large numbers of red blood cells found in the smear. Blood eosinophilia was present in 11 of 19 cases investigated. Eosinophils were seen in the smears in 20 cases. In the majority of the cases of effusions with microfilariae the effusions were malignant. Significant adherence of inflammatory cells and macrophages to microfilariae was present in 7 of the 35 cases. The significance of these findings is discussed.     

Atypical glandular cells of undetermined significance favor endometrial origin. Criteria for separating low grade endometrial adenocarcinoma from benign endometrial lesions

OBJECTIVE: To evaluate cytologic criteria for separating atypical glandular cells of undetermined significance favor endometrial origin (AGUS-EM), on Papanicolaou-stained (Pap) smears into favor benign and favor malignant categories. STUDY DESIGN: All patients who had a Pap smear diagnosis of AGUS-EM, not further qualified, followed by tissue follow-up were identified from the surgical pathology and cytopathology files from January 1992 through December 1996. The Pap smears were scored blindly for the presence or absence of 40 cytologic criteria, and univariate analysis was performed to determine which criteria were most indicative of malignancy by tissue follow-up. RESULTS: The presence of an atrophic smear, nuclear size greater than twice that of an intermediate cell nucleus and absence of clusters with irregular borders were highly indicative of adenocarcinoma, although other criteria were also helpful in identifying malignancy. CONCLUSION: There are no combinations of cytologic criteria that definitely separate AGUS-EM cases into those with benign or malignant findings on follow-up. However, some isolated criteria were useful in the differential diagnosis in a [table: see text] significant number of cases.     

Fine needle aspiration cytology of breast fibroadenoma. A cytohistologic correlation study of 405 cases.

OBJECTIVE: To evaluate the cytohistologic correlation of breast fibroadenoma (FA) in order to assess the value of cytology in the conservative management of this lesion. STUDY DESIGN: A retrospective analysis of all aspirates diagnosed as FA or fibroadenomatous lesion (n = 1,549) for which a histologic follow-up study was available (n = 362). Forty-three aspirates, including 14 nonrepresentative smears, from histologically proven FAs with a different cytologic report were also included in the study. RESULTS: Cytohistologic agreement was present in 287 of the 362 cytodiagnoses. Lack of correlation was observed in 75 cases. Most diagnostic errors accumulated in the older patient group. The sensitivity of the cytologic diagnosis of FA was 86.9% (90.8% excluding nonrepresentative cases), with a positive predictive value of 79.3%. In 43 cases a histologic diagnosis of FA was given after previous erroneous (n = 29) or nonrepresentative cytodiagnoses (n = 14). The specificity of the cytologic diagnosis of FA reached 93.8%, with a negative predictive value of 96.3% (97.5% excluding nonrepresentative cases). Regarding malignancy, five tumors were diagnosed as FA and were malignant. No false positive diagnoses of malignancy were given, but nine aspirates were included in the category "suspicious for carcinoma." CONCLUSION: FA of the breast remains a diagnostic challenge for the cytopathologist. A considerable amount of benign breast lesions can mimic FA on cytology, and such diagnostic categories as "fibroadenomatous lesion" or "consistent with FA" are associated with low diagnostic accuracy. While the cytologic requisites for entering a program of conservative management of FA are established, it seems that strict diagnostic criteria should be applied even at the expense of diminishing sensitivity.     

Serial fine needle cytology in the diagnosis of esophageal cancer

OBJECTIVE: To describe a method of registering local spread of cancer in the esophageal wall through serial endoscopic fine needle aspiration (FNA), to evaluate FNA as a diagnostic tool as compared to histologic biopsies and brush cytology, and to investigate cytologic appearances of aspirates and correlate them with survival STUDY DESIGN: Fifty-two patients with esophageal cancer were investigated with serial FNA every second centimeter from the upper esophageal sphincter aborally down to the level of macroscopic tumor. Histologic biopsies and brush cytologies were then performed. RESULTS: Of investigated cases, 33% showed malignant or suspect malignant cells from macroscopic tumor, at > or = 4 cm orally, as did 3 of 12 patients at 14 cm. FNA was more sensitive than brush cytology in establishing the diagnosis. A high ratio between the numbers of benign and malignant cells in aspirates from gross tumor tissue correlated with shorter survival (P < .03). CONCLUSION: Serial FNA can demonstrate local microscopic tumor spread in the wall of the esophagus in vivo in esophageal cancer patients. FNA is also a useful adjunct in establishing the diagnosis. Finally, evaluations of tumor cytology may have prognostic value.     

Diagnostic schemes for fine needle aspirates of breast masses

A comparison was made of four statistically based schemes for classifying epithelial cells from 243 fine needle aspirates of breast masses as benign or malignant. Two schemes were computer-generated decision trees and two were user generated. Eleven cytologic characteristics described in the literature as being useful in distinguishing benign from malignant breast aspirates were assessed on a scale of 1 to 10, with 1 being closest to that described as benign and 10 to that described as malignant. The original computer-generated dichotomous decision tree gave 6 false negatives and 12 false positives on the data set; another tree generated from the current data improved performance slightly, with 5 false negatives and 10 false positives. Maximum diagnostic overlap occurred at the cut-point of the original dichotomous tree. The insertion of a third node evaluating additional parameters resulted in one false negative and seven false positives. This performance was matched by summing the scores of the eight characteristics that individually were most effective in separating benign from malignant. We conclude that, while statistically designed, computer-generated dichotomous decision trees identify a starting sequence for applying cytologic characteristics to distinguish between benign and malignant breast aspirates, modifications based on human expert knowledge may result in schemes that improve diagnostic performance.     

Kimura's disease. Diagnosis by aspiration cytology

OBJECTIVE: To characterize the cytologic features of Kimura's disease and distinguish the differentiating features from those of other conditions with similar cytologic findings. STUDY DESIGN: In eight cases of Kimura's disease the cytologic features were correlated with the histologic findings. RESULTS: The cytologic features included a polymorphous lymphoid population with an admixture of significant numbers of eosinophils, fragments of collagenous tissue, endothelial cells and occasional polykaryocytes. CONCLUSION: Various conditions, both benign and malignant, may mimic Kimura's disease clinically and on smears. These have to be ruled out before making a diagnosis of Kimura's disease. The cytologic features of Kimura's disease have to be interpreted in the appropriate clinical setting in order to make a correct preoperative diagnosis.     

Prospective comparative cytologic study of direct peritoneal smears and lavage fluids in patients with epithelial ovarian cancer and benign gynecologic disease

Direct peritoneal samples obtained by scraping or brushing (with a Cytobrush) were compared to peritoneal lavages (washings) for the cytologic evaluation of patients with gynecologic disease. The direct samples were obtained during laparotomy or laparoscopy, following saline lavage if that was performed, and were immediately smeared on glass slides and fixed in 95% alcohol. Only 9 of the direct peritoneal samples taken from 64 patients with benign gynecologic disease were unsatisfactory for cytologic interpretation while 19 of the 33 lavage specimens simultaneously collected from these patients were considered unsuitable for analysis (P less than .001). Two direct smears from cases with benign histology were reported as suspicious. Nineteen patients with epithelial ovarian cancer also had cytologic specimens collected by direct sampling and by washing. The direct smears were positive for malignancy in 12 cases, suspicious in 4 cases and negative in 3 cases while the lavage samples were positive in 9 cases, suspicious in 4 cases, negative in 4 cases and unsatisfactory in 2 cases. These results indicate that direct peritoneal sampling is a simple and reliable alternative to peritoneal lavage and produces a significantly lower incidence of unsatisfactory specimens.     

Aspiration cytology of tubular breast carcinoma

The cytologic features in smears of fine needle aspirates from 34 tubular breast carcinomas were studied. Uniform and bland epithelium in cohesive clusters dominated all specimens; two-thirds also showed some degree of cellular dissociation. Characteristic (but not quite pathognomonic) angular epithelial clusters with a tubular structure occurred in about 50% of the smears. Sparsely occurring atypical nuclei and/or cytoplasmic vacuoles, similar to those seen in lobular cancer, were found in half of the cases. Although a lack of myoepithelial cells was apparent in the majority of the smears, one-fourth of them showed a quite prominent myoepithelial component. Various combinations of atypical features resulted in a picture that was considered diagnostic of malignancy in 50% of the cases; the remaining specimens showed less pronounced atypia. Other pitfalls associated with the cytologic diagnosis of tubular carcinoma are discussed, and the importance of basing the management of small breast lesions on the mammographic as well as on the cytologic findings is emphasized.