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.     

Potential of the learning vector quantizer in the cell classification of endometrial lesions in postmenopausal women

OBJECTIVE: To investigate the potential of artificial neural networks for cell identification in endometrial lesions from postmenopausal women. STUDY DESIGN: The study was performed on cytologic material obtained by the Gynoscann endometrial cell samplerfrom 12 cases of atrophic endometrium, 48 cases of hyperplasia without cytologic atypia (18 cases of simple hyperplasia and 30 cases of complex hyperplasia), 12 cases of hyperplasia with cytologic atypia (complex atypical hyperplasia) and 48 cases of adenocarcinoma (30 cases of well-differentiated, 12 cases of moderately differentiated and 6 cases of poorly differentiated carcinoma). From each case approximately 100 cells were examined using a custom image analysis system. A learning vector quantizer (LVQ) identified the collected data. RESULTS: Investigation of cells from Endometrial Alterations with LVQ proved that according to the nuclear characteristics, as expressed by morphometric and textural measures, the endometrial cells from postmenopausal women may be identified as belonging to one of thefollowing three groups: atrophy, hyperplasia without cytologic atypia (simple and complex hyperplasia) and malignant neoplastic lesions (atypical complex and adenocarcinoma). CONCLUSION: The role of nuclear morphologic features in the cytologic diagnosis of endometrial alterations was confirmed. The overlap in thefeature space observed indicates that cell characteristics do not form strictly separate clusters. Thatfact explains the difficulty that morphologists have with the reproducible identification of cells from endometrial lesions in postmenopausal women. Application of LVQ offers a good classification at the cell level and promises to be a powerful toolfor classification on the individual patient level andfor the clarification of the natural history of endometrial pathology.     

Genetic alterations in presumptive precursor lesions of breast carcinomas.

The hypothetical multistep model of breast carcinogenesis suggests a transition from normal epithelium to invasive carcinoma via intraductal hyperplasia (without and with atypia) and in situ carcinoma. These presumptive precursor lesions are currently defined by their histological features, and their prognosis is imprecisely estimated from indirect epidemiological evidence. Cytogenetic and molecular-genetic analysis of these lesions give evidence for an accumulation of various genetic alterations during breast tumorigenesis. Using immuno-histochemistry overexpression of the c-erbB-2 oncogene was found in ductal carcinoma in situ (DCIS), but not in atypical intraductal hyperplasia (AIDH) and intraductal hyperplasia (IDH). An expression of mutant p53 tumor suppressor gene as well as expression of cyclin D1 was identified in DCIS. In IDH lesions loss of heterozygosity (LOH) at various loci could be identified, and comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH) studies delivered evidence for DNA amplification on chromosomal region 20q13 in the early stage of IDH.However, little is currently known about genetic alterations in those premalignant lesions, and the chronology of genetic alterations and histopathological changes during carcinogenesis is mainly undiscovered.     

Clinical and cytologic features of papillary neoplasms of the breast

OBJECTIVE: To compare the cytologic features benign and malignant papillary breast lesions. STUDY DESIGN: We reviewed the clinical and cytologic features in 29 cases of intraductal papilloma and 26 cases of atypical papilloma or papillary carcinoma that had been diagnosed by histologic examination. The diameter of the mass was examined as a clinical feature. The cytologic features evaluated were as follows: bloody background, row of tall columnar cells, naked bipolar nuclei, hemosiderin-laden macrophages, myoepithelial cells, single scattered atypical cells, cellularity, nuclear atypia, nuclear grade, apocrine metaplasia, eosinophilic cytoplasmic granules, papillary clusters, small papillae, cell balls and large sheets. RESULTS: Of the features evaluated, the diameter of the mass, naked bipolar nuclei and cell balls differed significantly between benign and atypical or malignant papillary neoplasms. The average diameter of a benign papillary neoplasm was 1.8 cm, and that of an atypical or malignant papillary neoplasm was 2.2 cm (p = 0.042). Naked bipolar nuclei were found in 27 cases of benign papillary neoplasm (93.1%) versus 19 cases of atypical or malignant papillary neoplasm (73.1%) (p = 0.050). Cell balls were found in 14 (48.3%) and 21 (80.8%) cases, respectively (p = 0.012). All 6 cases in which cell balls were present and naked bipolar nuclei were absent proved to be atypical or malignant papillary neoplasms. Of 17 cases in which cell balls were absent and naked bipolar nuclei present, 13 (76.5%) were benign papillary neoplasms. CONCLUSION: Most cytologic features overlapped in benign and atypical or malignant papillary neoplasms. Although they were not pathognomonic, naked bipolar nuclei and cell balls were cytologic features that differed significantly between benign and atypical or malignant papillary neoplasms. When papillary neoplasms of the breast are suspected in a cytologic smear, the combination of clinical examination, mammography and cytologic features should be considered to make the correct diagnosis.     

Fractal dimension in endometrial carcinoma

OBJECTIVE: To mathematically assess in a pilot study, endometrial glandular margin irregularity in simple hyperplasia, complex atypical hyperplasia and well-differentiated endometrial carcinoma with the help of box counting of fractal dimension and to discriminate these lesions on the basis of box counting of fractal dimension of the gland. STUDY DESIGN: Ten cases each of endometrial simple hyperplasia (without atypia), complex hyperplasia with atypia and endometrial carcinoma (well-differentiated, endometrioid) were assessed in the study. Five fields at 20 x magnification from each case were randomly selected, and the glands were outlined with the help of a pointer. Using the box counting method, the fractal dimension of each case was measured. RESULTS: Mean fractal dimension in simple hyperplasia, complex atypical hyperplasia and endometrial carcinoma was, 0.899 +/- 0.13, 0.932 +/- 0.042 and 0.939 +/- 0.02, respectively. Statistical analysis showed that the fractal dimension of glands of simple hyperplasia were significantly different from that of complex atypical hyperplasia and endometrial carcinoma (P = .041 and .013, respectively, ANOVA). However, there was no significant difference in fractal dimension between glands of complex hyperplasia and of endometrial carcinoma (P = .659, ANOVA). CONCLUSION: This study provides mathematical (objective) assessment of the measurement of glandular margin irregularities in simple hyperplasia, complex atypical hyperplasia and endometrial carcinoma. Fractal dimension of gland margin may have diagnostic potential in the future.     

Benign mucocele-like lesion of the breast: how to differentiate from mucinous carcinoma before surgery.

The aim of the study was to improve the pre-operative diagnosis of mammary mucinous lesions. All mucinous lesions detected by fine needle aspiration (FNA) and confirmed by histological examination were reviewed by cytological findings, mammographic appearances and sonographic findings. Twenty aspirates had corresponding pathology, including 12 mucinous carcinomas, two mucocele-like lesions (MLL) with atypical ductal hyperplasia, three MLL with ductal hyperplasia and three simple MLL. Simple MLL and mucocele-like with ductal hyperplasia showed scant cellularity, no or rare intact single tumour cells, monolayered arrangement and absence of nuclear atypia. In contrast, most mucinous carcinomas showed higher cellularity, more single tumour cells, three-dimensional clusters, and mild to marked nuclear atypia. However, MLL with atypical ductal hyperplasia showed cytological features overlapping with mucinous carcinoma. MLL had a non-specific mammographic appearance and showed a cystic lesion on sonography. Mucinous carcinoma appeared as a solid mass on sonography and as a distinct nodule on mammography. Based on the combination of FNA cytology and image findings, benign MLL can be correctly distinguished from mucinous carcinoma before surgery.     

Colorectal cytology in chronic ulcerative colitis

During a period of ten years, 109 colorectal cytology specimens were obtained from 41 patients with chronic ulcerative colitis. There were 28 male and 13 female patients, whose average age was 45 years. All patients were symptomatic and had ulcerative colitis with repeated attacks of profuse diarrhea on the average for 12 years prior to their first cytologic examination. Eight cytology specimens were positive for malignant cells, 35 had atypia, 58 were negative and 8 were unsatisfactory. The malignant cells showed marked anisocytosis, pleomorphism and nuclear hyperchromasia and appeared in loosely cohesive clusters or in single forms in an inflammatory and necrotic background. Subsequent colectomy revealed invasive carcinoma in five patients and carcinoma in situ in two. Smears that were negative or showed atypia contained abundant chronic inflammatory cells. The atypical colonic epithelial cells contained prominent nuclei and formed cohesive clusters. Surgical biopsy and/or segmental resection revealed the presence of polyps, pseudopolyps, polypoid hyperplasia, mucosal atypia and crypt abscesses in patients with atypical and negative cytologic findings. It is concluded that cytologic examination of the colon can play an important role in the examination of patients with ulcerative colitis and allows for the detection of malignant transformation of the colonic mucosa.     

Gynecomastia: cytologic features and diagnostic pitfalls in fine needle aspirates.

OBJECTIVE: To illustrate some of the uncommon cytologic findings of gynecomastia, such as apocrine metaplasia, cellular atypia and foamy macrophages, that can be misinterpreted as evidence of malignancy. STUDY DESIGN: The clinical data and fine needle aspiration (FNA) cytologic material from 100 men with the diagnosis of gynecomastia were retrospectively reviewed. The excisional biopsy slides were available for 16 cases. For comparison, FNA smears from five men with breast lesions other than gynecomastia were studied. RESULTS: The patients ranged in age from 23 to 91 years. Cytologic findings were as follows: cohesive sheets of cells containing 20-1,000 cells (98%); scattered, single, bipolar cells (78%); spindle cells (68%); ductal epithelial atypia (26%); apocrine metaplasia (8%); and foamy histiocytes (12%). In nine cases the atypia was marked, and in two of them the possibility of malignancy could not be ruled out. Surgical follow-up on 16 patients, including the cases with marked atypia, showed gynecomastia. In one case, gynecomastia was associated with intraductal papilloma. No correlation between the underlying etiology and atypical cytologic features of gynecomastia was identified. CONCLUSION: Apocrine metaplasia and epithelial atypia are common findings in gynecomastia. Attention to the cell patterns, the presence of sheets of ductal cells and absence of atypical single cells will point to the correct diagnosis.     

Morphometric image analysis of follicular lesions of the thyroid

OBJECTIVE: To determine the role of image morphometry in distinguishing various follicular lesions of the thyroid in cytologic smears. STUDY DESIGN: Archival fine needle aspiration smears of 10 cases each of follicular hyperplasia, follicular adenoma, follicular carcinoma and follicular variant of papillary carcinoma were used for the study. All cases were histopathologically proven. At least 100 random nuclei from each case were subjected to analysis with an image cytometer. Area, convex area, length, width, perimeter, convex perimeter and roundness of nuclei were measured using a 40 x objective (1 pixel = 0.446 micron). RESULTS: ANOVA showed that all the nuclear variables studied were significantly different (P < .05) in follicular hyperplasia as compared to follicular carcinoma and papillary carcinoma. All nuclear variables except roundness were also significantly different (P < .05) between follicular hyperplasia and follicular adenoma. However, between follicular adenoma, follicular carcinoma and papillary carcinoma there was considerable overlap of nuclear morphometric parameters. CONCLUSION: Image morphometry may help to distinguish nonneoplastic follicular lesions (hyperplasia) from neoplastic lesions (adenomas and carcinomas). However, to distinguish benign from malignant follicular lesions, image morphometry might not improve the accuracy of standard cytologic examination.     

Stereotaxic fine needle aspiration cytology of clinically occult malignant and premalignant breast lesions

Stereotaxic fine needle aspiration (FNA) cytology was used to study clinically occult (nonpalpable) breast lesions in 114 consecutive patients with mammographically suspicious findings prior to excisional biopsy. The aspirate contained insufficient material for cytologic evaluation in 15 cases (13.2%), which were histologically diagnosed as benign (7 cases), atypical hyperplasia (7 cases) or carcinoma in situ (1 case). The cytologic findings indicated a benign lesion in 77 cases (67.5%), which were histologically diagnosed as benign (71 cases) or atypical ductal hyperplasia (6 cases). The cytologic sample showed atypia in eight cases (7.0%), which were histologically diagnosed as severe atypical ductal hyperplasia (three cases), carcinoma in situ (one case) or proliferative fibrocystic disease (four cases). In the eight cases (7.0%) cytologically interpreted as probably malignant, histology confirmed six invasive carcinomas, one carcinoma in situ and one fibrocystic disease. Of six cases (4.4%) cytologically reported as malignant, five were histologically diagnosed as invasive carcinoma and one as carcinoma in situ. Overall, stereotaxic FNA cytology reported as malignant or probably malignant 14 of the 15 cases with a histologic confirmation of malignancy, for a sensitivity of 93.3%. Cytology correctly identified 78 of the 83 histologically negative cases, for a specificity of 94.0%. The 16 cases histologically diagnosed as ductal hyperplasia, which carries a high risk for subsequent malignancy, were studied in detail in an effort to define histologic and cytologic criteria for this entity. Using selected histologic criteria, 11 of these cases were graded as showing mild-to-moderate atypical hyperplasia and 5 as showing severe atypical hyperplasia. Three of the latter cases were similarly identified by an analogous cytologic grading; the other two cases had insufficient cytologic samples. The total results in this series of 114 cases support the use of stereotaxic FNA cytology in the diagnosis of these nonpalpable breast lesions, examples of which are illustrated. In particular, it may help to raise the low specificity yielded by mammography alone, which would represent a significant advance for the patient in terms of the accuracy, expediency and reduced cost of diagnosing these lesions.     

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

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

A useful immunohistochemical approach to evaluate intraductal proliferative lesions of the breast and to predict their prognosis

An examination was performed on 16 intraductal proliferative breast lesions diagnosed as intraductal papillomas (IP) or usual ductal hyperplasia (UDH), which were followed up for more than 3 years. An immunohistochemical marker panel combining myoepithelial markers, high-molecular-weight keratin (HMWK) and neuroendocrine markers was used. Two of 11 IP cases were re-evaluated as atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS). These cases developed breast cancer after the first operation. One IP case showed repeated recurrences. None of the other IP and UDH cases had breast cancer or recurrence. The ADH, DCIS and the recurrent IP showing a solid growth lacked myoepithelia, but the recurrent IP expressed HMWK, immunohistochemically. Interestingly, these three lesions were weakly positive for neuroendocrine markers. All other IPs and UDHs, including lesions having solid components, were negative for neuroendocrine markers, and most of them were positive for myoepithelial markers and/or HMWK. A combination of the above immunohistochemical markers seems useful to evaluate intraductal proliferative lesions and to predict their prognosis. In particular, intraductal proliferative lesions with solid components exhibiting positivity for neuroendocrine markers should be followed up carefully to monitor breast cancer risk or recurrence.     

Cytologic study of noninvasive intraductal papillary-mucinous carcinoma of the pancreas

OBJECTIVE: To examine the cytologic features of noninvasive intraductal papillary-mucinous carcinoma (IPMC) in an attempt to differentiate it cytologically from hyperplasia, invasive IPMC and invasive ductal adenocarcinoma (IDA). STUDY DESIGN: Tumor samples from 23 patients clinically diagnosed with a mucin-producing tumor of the pancreas, including 10 cases of hyperplasia, 10 noninvasive IPMCs and 3 invasive IPMCs, and tumor samples from 21 patients with IDA, were examined cytologically. Cytologic specimens were obtained in various ways, such as by fine needle aspiration, imprint, brushing, vinyl tube aspiration and aspiration from a cannula at endoscopic retrograde cholangiopancreatography. RESULTS: Cytologically, all 10 noninvasive IPMCs exhibited clearly defined cytoplasmic boundaries (+1, ++4, ++ and mainly small nuclei (++7, +++3), with nuclear size and cytoplasm similar to those of hyperplastic cells, and irregular chromatin distribution (+2, ++8) and prominent nucleoli (-2, +4, ++3, +++1), all atypical nuclear features similar to those of invasive IPMC or IDA. There also were small papillary cohesive clusters (-1, +2, ++4, +++3) and euchromatin (+1, ++1, +++8), which were found only in IPMCs. CONCLUSION: The cytologic features of small, malignant nuclei and small papillary cohesive clusters are suggestive of noninvasive IPMC. Furthermore, the addition of clearly defined cell borders and euchromatin and the presence of some goblet cells are more strongly suggestive of noninvasive IPMC.     

AgNOR analysis of atypical ductal hyperplasia and intraductal carcinoma of the breast

OBJECTIVE: To determine the diagnostic and prognostic value of argyrophilic nucleolar organizer regions (AgNORs) in atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS) and microinvasive ductal carcinoma (MDCA) of the breast. STUDY DESIGN: Image analysis of histologic sections from biopsies of 46 breast ADH and DCIS and 18 cases of MDCA. Determination of morphometric features of cell nuclei and nucleolar organizer regions by using AMBA software system. Data were compared with the estrogen receptor/progesterone receptor (ER/PR) content as well as with the growth fraction, determined immunohistochemically. RESULTS: AgNOR number and total AgNOR area increased from ADH to DCIS. The highest values were recorded in cases of DCIS with microinvasion. Differences between ADH and intraductal or microinvasive ductal carcinoma were statistically significant. Within the group of intraductal carcinomas, the lowest values were measured in the solid type and highest values in the comedo type. A correlation was found between AgNOR features and growth fraction but not between these features and ER/PR status. CONCLUSION: Selected AgNOR features are relevant for differentiation between ADH and DCIS as well as between low and high grade DCIS and microinvasive ductal carcinoma. Therefore, objective and reproducible data obtained by AgNOR analysis may allow better evaluation of the prognostic significance of these lesions.     

Automated image morphometry of lobular breast carcinoma

OBJECTIVE: To analyze the role of automated image morphometry (AIM) in distinguishing infiltrating lobular carcinoma (ILC) of the breast from benign, borderline and infiltrating ductal carcinoma (IDC). STUDY DESIGN: Only histopathologically proven lobular carcinoma, ductal carcinoma, borderline lesions and benign breast lesions were selected for the study. There were 19 cases of ILC and 30 cases of IDC, 20 cases of benign lesions (fibroadenoma, 18; fibrocystic disease, 1; and fibroadenosis, 1); 10 cases were borderline lesions (mild epithelial hyperplasia, 3; moderate epithelial hyperplasia, 2; florid epithelial hyperplasia 4; intraductal papillary carcinoma, 1). In all cases hematoxylin and eosin-stained slides were used for AIM. At least 100 cells from each case were subjected to analysis randomly with an image cytometer with Leica Quantimet 600 software (Cambridge, England). Nuclear area, diameter, perimeter, convex perimeter, convex area and roundness were measured in each case with random, unbiased selection of cells and 40 x objectives (one pixel = 0.46 microm). AIM data on the cases were analyzed in relation to final cytologic diagnosis. RESULTS: All the nuclear morphometric features of ILC were much lower than those of IDC and borderline lesions, whereas nuclear morphometric data on ILC were only marginally more than those on benign cases. ANOVA showed that mophometric data were significant (P < .05) in all the variables between ILC and IDC. However, there was no significant difference between ILC, and borderline and benign cases. CONCLUSION: Image morphometry may be useful in distinguishing ILC from IDC on cytologic smears. However, morphometric data may not be helpful in distinguishing benign and borderline lesions from ILC.     

The comedo subtype of intraductal carcinoma. Cytologic characteristics.

Smears from 10 intraductal carcinomas of the comedo type without microinfiltration were compared with smears from 10 similar tumors with suspected or proven microinfiltration and smears from 10 invasive comedo carcinomas. Microinvasive tumors could not be separated from purely intraductal cases unless tumor cell infiltration in mammary fat was seen in the smear. The tumor cells in most of the intraductal cases were shed in cohesive groups and clusters, lying in necrotic cellular debris and with few or no scattered, single, dissociated tumor cells. Smears from invasive comedo carcinomas invariably showed tumor cell clusters and scattered, single, dissociated tumor cells, often with atypia in excess of what was seen in the intraductal cases. Also, in most cases the invasive tumors did not show a background of necrotic cellular debris.     

Pathophysiology and management of endometrial hyperplasia and carcinoma.

Endometrial cancer is currently the commonest pelvic malignancy affecting American women, most of whom share the same pathophysiologic basis, that is, unopposed estrogenic stimulation. The initial result of hyperestrogenism is the development of endometrial hyperplasia, which is reversible in most cases by appropriate hormonal therapy. Persistent stimulation eventually leads to atypical hyperplasia with nuclear atypia and invasive carcinoma. Because there is no cost-effective screening method for the detection of endometrial hyperplasia and carcinoma, it is essential to survey the high-risk population with appropriate diagnostic techniques. After diagnosis, therapy should be individualized based on pathologic findings (cell type and histologic grade) and extent of disease (International Federation of Gynaecologists and Obstetricians stage, depth of myometrial invasion, and pelvic and para-aortic lymph node status). Recent studies suggest that sex hormone receptors and nuclear DNA ploidy patterns provide useful prognostic information independent of histologic grade.     

Epithelial atypia in gynecomastia induced by chemotherapeutic drugs. A possible pitfall in fine needle aspiration biopsy.

The clinical, cytopathologic and histopathologic features of a case of gynecomastia induced by chemotherapeutic drugs are described. Fine needle aspiration (FNA) smears showed epithelial atypia, and an erroneous cytologic diagnosis of carcinoma was made. Histopathologic study showed gynecomastia with epitheliosis, papillomatosis and atypical ductal hyperplasia. Review of the FNA smears showed the findings to be more typical of a reparative or regenerative process; these findings had been cytologically overinterpreted, partly due to the lack of adequate clinical information submitted with the aspirate. The possible causes of gynecomastia, the induction of epithelial atypia by cytotoxic chemotherapy and the cytologic features whose recognition may prevent false-positive diagnoses in such cases are discussed.     

Fine needle aspiration of breast lesions in women aged 30 and under

Fine needle aspiration (FNA) biopsies of 1,598 breast masses were performed between 1983 and 1989, and of them, 48 were from women aged 30 and under for whom a cytologic diagnosis was made by FNA and histologic follow-up was available. In 37 (77%) of the cases, both the cytologic and histologic diagnoses were benign. Fibroadenoma (20/37) and fibrocystic changes (14/37) were the most common benign lesions aspirated. Eight (17%) FNAs showed cytologic atypia. Four of these atypical lesions proved to be benign (two fibroadenomas, two fibrocystic changes). Epithelial proliferation in fibroadenomas and fibrocystic changes and cellular stroma in a fibroadenoma mimicking phylloides tumor were the causes of atypia in these biopsies. Four of the eight atypical lesions were shown to be carcinoma at biopsy (three infiltrating duct, one atypical medullary). Low cellularity, epithelial cohesiveness mimicking a fibroadenoma and background lactational changes in a pregnant patient were the causes of the atypical, rather than unequivocally malignant, diagnoses in these cases. In three patients (6%), a diagnosis of carcinoma was made by FNA and confirmed histologically (all were infiltrating duct carcinoma). Although most breast masses in women aged 30 and under are benign, cytologic atypia in a breast fine needle aspirate in this age group warrants a surgical biopsy. Clinical follow-up alone may be appropriate for young women with clinically nonsuspicious breast masses without cytologic atypia.     

Computerized morphometric image analysis of cytologic nuclear parameters in breast cancer

The value of nuclear morphometry in the preoperative fine needle aspiration (FNA) cytologic diagnosis of mammary lesions was investigated and correlated with the lymph node status of the patients. The subjects consisted of four groups of patients: 49 with invasive ductal carcinomas (18 with no positive nodes, 16 with one to three positive nodes and 15 with four or more positive nodes) and 14 patients with benign lesions. The FNA specimens were smeared onto slides and stained by the May-Grünwald-Giemsa technique. The area, perimeter and maximum diameter of 100 randomly chosen nuclei were both measured with the IBAS image analysis system and semiquantitatively estimated with an eyepiece micrometer. For all three parameters, significant differences were found between benign and malignant lesions. The mean nuclear perimeter allowed the morphometric discrimination between all four groups with statistical significance; nuclear area and maximum diameter did not discriminate patients with invasive carcinoma and one to three positive nodes from those with no positive nodes or more than three positive nodes. Morphometry proved to be far superior to eyepiece measurements with respect to accuracy and reproducibility of the results. The results suggest that nuclear perimeter can be used as an additional parameter not only for the FNA cytologic diagnosis of breast cancer, but also for the estimation of patients' prognosis.