Highly well differentiated hepatocellular carcinoma and benign hepatocellular lesions. Can they be distinguished on fine needle aspiration biopsy?

OBJECTIVE: To determine whether highly well differentiated hepatocellular carcinoma can be distinguished from benign hepatocellular lesions on fine needle aspiration biopsy (FNAB). STUDY DESIGN: Ninety-five FNABs from 88 patients with hepatic masses/diffuse conditions were reviewed according to new cytologic criteria established by Takenaka et al. They were classified into well-, moderately and poorly differentiated hepatocellular carcinomas (W-, M- and P-HCC) and benign aspirates and histologically verified. RESULTS: There were 21 W-HCC, 39 M-HCC, 10 P-HCC, 3 problematic and 22 benign aspirates. The most useful criteria for diagnosing highly W-HCC were architectural features on the smears/cell block sections, including hypercellularity; arborescent, cohesive clusters; broad trabeculae; transgressing and peripheral endothelium; and cytologic details of small, monotonous hepatocytes with nuclear crowding, decreased cytoplasm, increased nuclear/cytoplasmic ratio, atypical naked nuclei and tumor giant cells. Well-defined cytoplasmic borders, abundant thick and monotonous cytoplasm, eccentric nuclei, thick nuclear membranes, irregular nuclear contours, increased chromatin density, irregular chromatin distribution and macronucleoli were not always detectable in highly W-HCC. In fact, some of them were seen in dysplastic hepatocytes. Deficient reticulin patterns and diffuse sinusoidal CD34 reactivity were helpful. CONCLUSION: Experience, attention to architectural and cytologic details in smears/cell blocks and clinicopathologic correlation should reduce the number of indeterminate reports. However, there will always remain some cytohistologically challenging cases.     

Fine needle aspiration cytology of apocrine carcinoma of the breast. Review of cases in a three-year period

OBJECTIVE: To describe the fine needle aspiration cytology findings of apocrine carcinoma of breast and correlate them with the histologic appearance. STUDY DESIGN: The author reviewed the fine needle aspiration cytology findings of two cases of pure apocrine carcinoma of the breast in the files of Pamela Youde Nethersole Eastern Hospital during a three-year period, 1998-2000. RESULTS: The cytologic findings in both cases were similar. The smears were of moderate to high cellularity, consisting of predominantly dispersed or loosely cohesive tumor cells in a focally granular background. The carcinoma cells contained abundant, dense to granular cytoplasm; round or oval and sometimes eccentrically located nuclei; a smooth nuclear outline; evenly dispersed chromatin; and solitary macronucleoli. The cell borders were mostly discrete. In contrast to benign apocrine cells, the malignant cells showed nuclear overlapping, more frequent nuclear pleomorphism, increased nuclear/cytoplasmic ratios and occasional mitotic figures. Histologic examination of the excised specimens showed extensive, solid apocrine carcinoma in situ with focal stromal invasion. CONCLUSION: Apocrine carcinoma, a subtype of breast carcinoma characterized mainly by its cytologic features, needs to be distinguished from benign apocrine lesions or other eosinophilic and granular cell tumors of the breast. Recognition of the subtle cytologic differences renders a definitive preoperative diagnosis possible.     

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 adult perineal rhabdomyosarcoma: a case report

BACKGROUND: Adult perineal soft tissue sarcomas are rare. Fewer than 30 cases have been reported, and all were diagnosed after surgical resection by histologic examination. Below we report a case in which the diagnosis was established preoperatively by fine needle aspiration (FNA). CASE: A 27-year-old man presented with a firm, midline, perineal mass. Magnetic resonance imaging showed a 3-cm, enhancing mass that was considered neoplastic. FNA biopsy, followed by cytologic examination, revealed moderately cellular aspirates composed of discohesive, small, blue cells with scant cytoplasm, high nuclear/cytoplasmic ratios and pleomorphic nuclei with irregular nuclear contours; uniform, hyperchromatic chromatin; and occasional mitotic figures. Frequent naked nuclei and scattered cells with more abundant, dense cytoplasm and eccentric nuclei were also noted. The diagnosis of rhabdomyosarcoma was favored on FNA and was corroborated by immunohistochemical stains for desmin, myogenin and CD56. Upon surgical resection, the diagnosis of alveolar rhabdomyosarcoma was confirmed histologically and immunophenotypically. CONCLUSION: FNA is a useful tool in diagnosing soft tissue lessions of the perineum, including rare primary tumors, such as adult rhabdomyosarcoma. In this case, early identification avoided incisional biopsy and directed appropriate extirpative surgery and reconstruction considerations.     

The role of morphometry in the cytology of well-differentiated hepatocarcinoma and cirrhosis with atypia

A morphometric study was performed on 200 nuclei per case in six well-differentiated hepatocarcinomas and in six cirrhoses with cytologic atypia, using samples obtained by fine needle aspiration (FNA) biopsy of the liver. The parameters measured were the nuclear area, the nuclear perimeter and the maximum nuclear diameter. The nuclei of well-differentiated hepatocarcinomas could be distinguished from those of cirrhoses on the basis of the larger size and greater anisonucleosis of the former. A statistical analysis (using a two-sided t-test) of the means of the parameters showed significant differences between the two diagnostic groups. These results suggest that morphometric analysis can help in the differential diagnosis between well-differentiated hepatocellular carcinoma and cirrhosis with cytologic atypia in FNA biopsy samples.     

ASCUS, mature metaplastic type. Cytologic diagnosis and follow-up

OBJECTIVE: To study the cytologic criteria for follow-up of mature metaplastic cells within the atypical squamous cells of undetermined significance (ASCUS) category. STUDY DESIGN: Squamous epithelial abnormalities between January 1994 and June 1997 at our institution totaled 2,632 and included squamous carcinoma (1), high grade squamous intraepithelial lesions (278), low grade squamous intraepithelial lesions (875) and ASCUS (1,478). From the ASCUS group, 134 (9.06%) were metaplastic; 89 were selected for review. Criteria for case selection were follow-up with tissue biopsy or at least two Pap smears and no previous epithelial abnormality. Patients ranged from 27 to 70 years of age. Parameters tabulated included number of abnormal cells per slide, their architecture, cell size, shape, cytoplasmic hue and texture, nuclear size and contour, chromatin pattern and nucleoli. Additionally, specimens were reviewed for hormonal status and inflammation. The findings were correlated with follow-up data. RESULTS: Cells generally appeared single or in loose, monolayered sheets of three to seven cells per group. The cells were well demarcated, polygonal or oval and ranged from 11 to 30 microns with cyanophilic or eosinophilic thickened cytoplasm. The round to oval nuclei with slight irregularity showed a minimally increased nuclear/cytoplasmic ratio with stippled chromatin. Upon review, 69 smears were confirmed as ASCUS-M. Follow-up revealed 42 with benign findings, 9 with persistent ASCUS/ASCUS-M and 18 with low grade squamous intraepithelial lesions. CONCLUSION: In mature metaplastic cells with minimal atypia in patients with no previous or concurrent dysplasia, the follow-up details were similar to those described for ASCUS-superficial/immediate squamous cells. These patients could be followed conservatively.     

Epithelial-myoepithelial carcinoma of the salivary gland. Fine needle aspiration cytologic findings

A case of epithelial-myoepithelial carcinoma of the salivary gland in a 78-year-old patient is presented. Fine needle aspiration cytologic smears showed a moderate number of tumor cells arranged in three-dimensional, well-outlined clusters reminiscent of the ball-like structures of adenoid cystic carcinoma. The nuclei were small and monotonous, with finely granular chromatin and small nucleoli. A large number of cells showed abundant clear cytoplasm; however, in some of the clusters the cytoplasms were very scant, again mimicking adenoid cystic carcinoma. Fragments of pale homogeneous acellular material, isolated or surrounding the cellular clusters, were another conspicuous finding.     

Accuracy of cytology vs. microbiopsy for the diagnosis of well-differentiated hepatocellular carcinoma and macroregenerative nodule. Definition of standardized criteria from a study of 100 cases

OBJECTIVE: To determine the accuracy of ultrasound (US)-guided fine needle aspiration (FNA) for the diagnosis of well-differentiated hepatocellular carcinoma (wd HCC) and macroregenerative nodule (MRN) and to identify the most useful cytologic and histologic criteria to distinguish between those two diagnoses. STUDY DESIGN: Cytologic and histologic specimens of 50 wd HCC and 50 MRN were reviewed blindly and the diagnosis compared to the final clinical diagnosis. Twenty-eight cytologic and 25 histologic criteria were examined and subjected to statistical analysis. RESULTS: Among 100 cases studied, the final diagnosis was available for 43. In those 43 cases, combining analysis of cytologic and histologic specimens, the sensitivity of US-guided FNA was of 75% and the specificity 100%. Cytologic analysis was better than isolated histologic analysis, with a sensitivity of 75% vs. 68%, respectively. Sensitivity of cytologic diagnosis was lower for smaller nodules and for those located in poorly accessible hepatic segments. With the use of stepwise logistic regression analysis, four cytologic features (increased nuclear/cytoplasmic ratio, cellular monomorphism, nuclear crowding, loss of bile duct cells) and four histologic features (increased nuclear/cytoplasmic ratio, decreased Kupffer cells, cellular monomorphism, increased trabeculae thickness) were identified as predictive of HCC.     

Cytologic evaluation of low grade transitional cell carcinoma and instrument artifact in bladder washings

OBJECTIVE: To identify key cytologic features for the separation of low grade transitional cell carcinomas (TCCs) from nonneoplastic lesions in bladder washings. STUDY DESIGN: The cytomorphologic features of 95 bladder washing specimens showing papillary fragments, which included 50 low grade TCCs and 45 nonneoplastic lesions, were reviewed retrospectively. RESULTS: Bladder washings from low grade TCCs showed papillary and irregular groups of cells with ragged borders, cytoplasmic homogeneity and subtle nuclear changes, such as increased nuclear/cytoplasmic ratio and irregular nuclear border. Bladder washings after instrumentation from nonneoplastic lesions of the bladder showed cellular specimens with cohesive, ball-shaped and papillary clusters with smooth borders lined with a denser-staining cytoplasmic collar. Reactive urothelial cells often displayed loose aggregates with irregular borders but no cytoplasmic collar. CONCLUSION: In bladder washing cytology, nuclear changes and cytoplasmic homogeneity play a major role in the diagnosis of carcinoma.     

Voided urine cytology of papillary renal cell carcinoma and renal calculus: report of a case with emphasis on the importance of cytologic screening in high-risk individuals

BACKGROUND: Preoperative diagnosis of cases of renal calculus complicated with papillary renal cell carcinoma (RCC) by image analysis is usually difficult. CASE: A 50-year-old man who had a past history of renal calculus suffered from macrohematuria and abdominal pain for one month was admitted to our hospital. Ultrasonographic examination revealed a 4-cm tumor shadow in the right kidney; it was hypovascular in arteriography. Papillary cell clusters with abundant cytoplasm were found by the cytologic examination of voided urine. Their nuclei were oval and situated eccentrically in the cytoplasm. The nuclear/cytoplasmic ratio was increased. Fine, granular chromatin was distributed evenly, and the nuclear membrane was thin and nearly smooth. Several small nucleoli were evident. All these findings were indicative of a diagnosis of papillary RCC. Histology of nephrectomy specimens confirmed the diagnosis. CONCLUSION: Voided urine cytology can be useful for screening and follow-up of patients with papillary RCC.     

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.     

Unusual cytologic findings in low grade papillary transitional cell carcinoma

OBJECTIVE: To describe cases of low grade papillary transitional cell carcinoma (LG-pTCC) with a low nuclear cytoplasmic (N/C) ratio and unusual cytologic patterns with many isolated, single neoplastic cells. STUDY DESIGN: We defined the following unusual cytologic findings as "isolated, single cell pattern": (1) numerous single cells sometimes with a few flat cell clusters; (2) very low N/C ratio; (3) angulation of cytoplasmic contour; (4) pale, homogeneous cytoplasm; (5) hyperchromatic nuclei with an uneven contour; (6) monotonous cytologic appearance; and (7) clear background. We studied 2,956 cytologic specimens of voided urine from 114 LG-pTCC patients at our university hospital during a 10-year period. RESULTS: Thirty-six specimens had the isolated, single cell pattern. The isolated, single cell pattern showed less celllular atypia than does the typical pattern of LG-pTCC. On histology the cases with the isolated, single cell pattern showed a papillary structure with an erosive surface and were composed of mildly atypical neoplastic cells with very low N/C ratios. CONCLUSION: Some LG-pTCCs show many single, atypical transitional cells.     

Fine needle aspiration cytology of metastatic hepatic adrenocortical carcinoma mimicking hepatocellular carcinoma: a case report

BACKGROUND: Adrenocortical carcinoma (AC) is a rare neoplasm, usually considered one of the most morbid and lethal human tumors. It occurs primarily in children and young adults and often presents with advanced and/or metastatic disease. CASE: A 9-year-old boy with a previous diagnosis of adrenocortical carcinoma underwent computed tomography (CT)-guided fine needle aspiration (FNA) for preoperative investigation of a hepatic mass. All smears revealed abundant groups of cells surrounding an interconnective, thin-walled, central vascular core. These cells showed finely vacuolated, large cytoplasm with eccentrically placed nuclei. Occasionally, cells underwent a sudden, marked increase in size, with prominent atypia. Multinucleated, atypical giant cells and high mitotic rate were also evident. The cytologic findings resembled the previous histologic adrenocortical carcinoma features. CONCLUSION: The cytologic features of metastatic hepatic adrenocortical carcinoma may mimic those of hepatocellular carcinoma. However, the presence of atypical multinucleated and pleomorphic cells with microvacuolated cytoplasm and eccentric nuclei as well as the absence of naked nuclei and endothelial linings yield the diagnosis of adrenocortical carcinoma. Nevertheless, other space-occupying liver lesions in children must also be considered. This case demonstrates the usefulness of CT-localized FNA biopsy in hepatic masses in children, and discusses the possible cytologic differential diagnosis.     

Catheterized urine cytology of mucinous carcinoma arising in the renal pelvis. A case report

BACKGROUND: Primary mucinous carcinoma of the renal pelvis is a rare tumor; therefore, criteria for cytologic diagnosis of this tumor have not been established. CASE: An 81-year-old woman suffered from macrohematuria for six months and was found to have a tumor in the right kidney by radiographic examination. Catheterized urine obtained from the right renal ureter was viscous and contained spherical clusters of cells with occasionally vacuolated, lacy and basophilic cytoplasm. In the small to medium-sized nuclei, chromatin was coarse and granular, and the nuclear membrane was thin and nearly smooth. Large nucleoli were evident in some of the nuclei. These findings were consistent with adenocarcinoma possibly of mucinous type. CONCLUSION: Preoperative diagnosis of mucinous carcinoma is possible by cytologic findings of catheterized urine together with clinical data.     

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.     

Diagnostic value of qualitative and quantitative variables in thyroid lesions

Two hundred and thirty-three thyroid lesions were studied by fine needle aspiration (FNA) cytology using standard cytologic criteria available in the literature. These included 114 cases of nodular colloid goitre (NCG), 47 cases of Hashimoto's thyroiditis (HT), 12 follicular adenomas (FAd), five cases of subacute thyroiditis and three cases of thyrotoxicosis among the benign lesions. The malignant lesions seen were 30 cases of papillary carcinoma (PCa), 16 follicular carcinomas (FCa), three cases with double lesions, e.g. papillary carcinoma with coexisting NCG, and three of papillary carcinoma with HT. Emphasis was given to eight qualitative and quantitative (morphometric) variables in these various thyroid lesions. Cell measurements were done using a Visopan Lux projection microscope. The three qualitative variables included type of nuclear membrane (regular/irregular), type of nuclear chromatin and the presence or absence of conspicuous nucleoli. The quantitative variables studied were nuclear diameter, nuclear area, cytoplasmic diameter, cytoplasmic area & N/C ratio. Statistical analysis was performed in order to know whether the standard cytologic criteria used at FNA cytology in the literature (increased cellularity, microfollicles, increased N/C ratio, absence of significant haemosiderin-laden macrophages and scanty colloid) could differentiate a follicular adenoma from a follicular carcinoma. A statistical analysis was also performed to establish the utility of the qualitative and quantitative variables. The results showed that none of the standard cytologic criteria applied could differentiate follicular adenoma from a follicular carcinoma. With regard to qualitative variables, irregularity of nuclear membrane and presence of conspicuous nucleoli were most significant in papillary carcinoma, followed by follicular carcinoma, then by follicular adenoma; these features being hardly evident in nodular colloid goitre and Hashimoto's thyroiditis. A coarse nuclear chromatin was most significant in follicular carcinomas followed by follicular adenomas. It was less obvious in the benign conditions, but more prominent in Hashimoto's thyroiditis compared with a goitre. It was also not obvious in a papillary carcinoma. Of the quantitative variables, all measurements were greatest in PCa > FCa > FAd > NCG = HT. When differentiating follicular adenoma from follicular carcinoma the qualitative variables of significance were the presence or absence of nucleoli, the chromatin pattern and regularity/irregularity of nuclear membrane; the nuclear area was the most important feature among quantitative variables.     

Fine needle aspiration cytology of ductal breast carcinoma with neuroendocrine differentiation. Review of eight cases with histologic correlation

OBJECTIVE: To describe the fine needle aspiration cytology findings of ductal breast carcinoma with neuroendocrine differentiation and correlate them with the histologic appearance. STUDY DESIGN: We reviewed the cytologic features of eight cases of ductal carcinoma with neuroendocrine differentiation in the files of Pamela Youde Nethersole Eastern Hospital during the three-year period 1998-2000. Immunohistochemical study for neuroendocrine markers was performed, with ultrastructural correlation. RESULTS: All cases showed similar cytologic features. The smears were of moderate to high cellularity with predominantly dispersed or loosely cohesive tumor cells. The carcinoma cells were mostly of low cytologic grade. They possessed round and relatively uniform, eccentric nuclei; finely stippled chromatin; sometimes small, distinct nucleoli; and discrete cell borders. Abundant eosinophilic and focally granular cytoplasm was a common finding. In some of the cases there was accentuation of staining in the paranuclear region; it correlated with aggregates of dense core neurosecretory granules seen ultrastructurally. Mucoid substance was seen in the background in some of the aspirates. Histologic examination of the tumors showed invasive ductal carcinoma with an organoid growth pattern and sometimes mucinous component. The neuroendocrine differentiation was confirmed immunohistochemically. CONCLUSION: Although this subtype of ductal carcinoma probably carries no significant prognostic value per se, it has distinct cytologic features, rendering preoperative diagnosis possible. Recognition of this entity is important in order to avoid the misdiagnosis of neuroendocrine tumor metastatic to the breast.     

Cytologic criteria of cystic papillary carcinoma of the thyroid

OBJECTIVE: To establish differential cytologic criteria between benign and malignant thyroid cysts. STUDY DESIGN: The study was a retrospective, transverse, analytic, comparative one of 3 groups of patients with nonfunctional thyroid nodules subjected to fine needle aspiration biopsy (FNAB) and surgical resection of the lesions, with histologic study as the diagnostic gold standard. Fifteen cases of cystic papillary carcinomas (group 1) with initial false negative diagnoses, 42 goiters accompanied by cystic degeneration (group 2) and 15 noncystic papillary carcinomas (group 3) were studied. Independent variables were age and sex; dependent variables were the presence of tridimensional fragments, papillae, anisonucleosis, nuclear bars, pseudoinclusions, powdery chromatin, cytoplasmic vacuoles, metaplastic cytoplasm, psammoma bodies, autolysis, multinucleated giant cells, spindle cells, colloid, monolayered laminae and macrophages in FNAB specimens. Statistical analysis was performed by central tendency measures and the chi 2 test. RESULTS: The chi 2 test revealed a statistically significant difference between group 2 and the groups with papillary carcinoma based on the presence of tridimensional fragments, anisonucleosis, nuclear bars, pseudoinclusions, powdery chromatin, cytoplasmic vacuoles, metaplastic cytoplasm and autolysis. CONCLUSION: The above cytologic characteristics must be searched for systematically in the FNAB of every cystic lesion of the thyroid to rule out the presence of cystic papillary thyroid carcinoma and to decrease the rate of false negative results.     

Comparative cytologic features of adenocarcinoma in situ of the uterine cervix

The cytologic findings in 30 cases of adenocarcinoma in situ (AIS) and related lesions of the cervix were compared with those in 13 cases of cervical invasive adenocarcinoma and 8 cases of cervical nonneoplastic conditions that mimicked AIS cytologically. Although there was considerable overlap, the presence of large cells with irregular nuclei and uneven chromatin distribution in smears containing no normal endocervical cells helped to distinguish invasive adenocarcinoma from AIS. The presence of "feathering," rosettes, mitotic figures and very crowded nuclei with scant cytoplasm and without cilia helped distinguish AIS from benign conditions.     

Cytodiagnosis of classic lobular carcinoma and its variants.

The well-known cytologic features of lobular carcinoma traditionally consist of modest cellularity and small, atypical cells lying singly or in small groups. However, lobular carcinoma is a common pitfall in the cytodiagnosis of breast lesions. Knowledge of its varied histologic appearance can help to prevent diagnostic difficulties. Among 55 consecutive cases of breast needle aspirates with histologic follow-up, 9 lobular carcinomas were identified. The surgical material was examined for the following histologic variants: (1) classic, (2) solid, (3) alveolar, and (4) mixed; it was correlated with the cytologic findings. Pure, classic lesions were the most likely cause of false-negative diagnoses. Two of nine lobular carcinomas were diagnosed as benign due to scant cellularity and cell smallness. Four of nine were cytologically misclassified as ductal type due to more abundant cellularity and larger cells. This could be attributed to the predominant alveolar or solid patterns present in three cases. Only three of nine were accurately classified as lobular carcinoma, and all had a significant classic histologic element. Another important feature that is highly suggestive of lobular carcinoma is the presence of cytoplasmic vacuoles. They were overlooked in three of four cases. This study suggested that the traditional cytologic features of lobular carcinoma are present only in tumors with a predominantly classic histologic pattern. Awareness of the variant patterns and their cytologic features, including more abundant cellularity, larger cells and clusters, and cytoplasmic vacuoles, will aid in correct classification.