Significance of collagenous and mucinous spherulosis in breast cytology specimens

S. Hata, N. Kanomata, Y. Kozuka, M. Fukuya, E. Ohno and T. Moriya
Significance of collagenous and mucinous spherulosis in breast cytology specimens Objective: Spherulosis of the breast is a rare but distinct benign morphological entity. As there are few cytological reports of breast spherulosis, the significance of spherulosis among cytological specimens is unclear. The objective was to document cytological aspects of spherulosis. Methods: A total of 3491 consecutive breast fine needle aspiration cytology (FNAC) samples and 69 nipple discharge cytology samples were reviewed. Papanicolaou‐stained slides with or without Romanowsky staining were analysed. The corresponding 1926 histological specimens were also reviewed. Results: We detected 17 cases of collagenous spherulosis (CS) and/or mucinous spherulosis (MS) among 3560 breast cytology specimens (0.48%). All samples were from women, who varied in age from 22 to 69 years. CS and/or MS were present in 15 of 3491 FNAC specimens (0.43%) and in two of 69 nipple discharge cytology specimens (2.9%). Corresponding histological specimens were available for 14 of the 17 specimens. Of the 14 specimens, 12 consisted of intraductal papilloma, one of fibroadenoma, and one of fibrocystic change. There was no spherulosis among the 1251 cytological specimens of malignant diseases. Conclusions: Cytological evidence of spherulosis is a good indicator of intraductal papilloma.     

Significance of nipple discharge clinical patterns in the selection of cases for cytologic examination

The cytodiagnostic significance of the clinical patterns (types and sites) of nipple discharges was studied in 5,305 cytologically examined discharges from 3,687 women in a consecutive series of 50,181 self-referred women in whom 1,062 breast cancers were detected. The clinical patterns were correlated with cytologic and histologic results in both the whole series and in 119 biopsied cases, and the relative risk of association with breast cancer was calculated for each pattern. As a whole, aside from the pattern, cases with nipple discharges showed a higher relative risk (48.5) than did asymptomatic cases, but a bloody nipple discharge was by far more frequently associated with cancer than was any other pattern, being present in 70% of the cancer cases and in almost all cancer cases with suspicious cytologic findings in the discharge smear. The presence of a nipple discharge, being associated with a higher risk of breast cancer, is an indication for a careful physical examination; systematic cytologic examination should be limited only to bloody discharges. Since cancer is rare in cases with nonbloody discharges and is difficult to detect in cytologic smears of such discharges, systematic cytologic examination of all nipple discharges would not be cost-effective.     

Evaluating the accuracy of uterine cancer screening with the regional cancer registration system

OBJECTIVE: To evaluate the effectiveness of uterine cancer screening by analyzing the accuracy of cervical and endometrial cytodiagnoses as screening methods. STUDY DESIGN: During the year of April 1, 1991-March 31, 1992, 186,161 and 5,697 women underwent cervical and endometrial cytodiagnoses, respectively, and their cytodiagnostic results were computer registered at the Miyagi Cancer Society. By comparison of these examinees with 753 cancer patients who were registered at the regional cancer registry between 1991 and 1993, 133 individuals who were assumed to be identical between the two systems were selected, and of these cases, 83 patients, including test-positive cases, were found within one year. The sensitivity and specificity of each screening method were investigated. RESULTS: Regarding examinees diagnosed as having cancer by the same month in the following year after diagnosis on screening as false negative, the sensitivity, specificity and false negative rates of cervical cytodiagnosis were 94.7%, 98.9% and 5.3%, respectively, and those of endometrial cytodiagnosis were 83.3%, 96.7% and 16.7%, respectively. CONCLUSION: In comparison with the accuracy of cancer examinations for other organs performed by the health care administration, the accuracy of cervical and endometrial cytodiagnoses was sufficient to designate them screening methods.     

Nipple discharge cytology in mass screening for breast cancer

Since 1977 mass screening for breast cancer has been conducted in Miyagi Prefecture, Japan; inspection, palpation and cytologic examination of any nipple discharge are part of the initial screening procedures. Among 149,681 subjects examined, 404 cancer cases and 63 papilloma cases were detected. The nipple discharges from 20,537 women were examined cytologically; of the 61 cancer cases, the smears were positive in 18 cases, suspicious in 7, negative with atypical findings in 12 and negative in 24. Ten of the cancer cases were detected exclusively by the cytologic examination of a nipple discharge. In eight of these ten cancer cases, there was no other initial evidence of the primary tumor. The cytologic diagnosis of discharges without blood from 28 cancer cases was positive or suspicious in 10 cases and negative in 18. Thirty-seven of the papilloma cases were initially detected only by the cytologic examination of a nipple discharge; neither physical examination nor mammography showed any abnormal findings.     

Critical evaluation of the cytodiagnosis of fibrogastroendoscopic samples obtained under direct vision

The reliability and efficiency of the cytodiagnosis of fibrogastroendoscopic biopsy samples obtained under direct vision in 676 cases during a five-year period were reviewed. The critical evaluation showed a cytodiagnostic sensitivity of 93.54%, a specificity of 98.79%, a false-negative rate of 6.46%, a false-positive rate of 1.21%, a predictive value of a positive result of 98.01%, a predictive value of a negative result of 96.00%, a prevalence rate of 38.91%, an overall diagnostic accuracy of 96.75% and a chi-square value of 5.50 (P less than .05). These results were comparable to those obtained by histologic study in the same cases; the combined use of both cytology and histology to analyze the samples obtained gave the best results. These findings reemphasize the important role of fibrogastroendoscopic cytodiagnosis in establishing the existence of gastric cancer and shows that the technique is accurate and efficient. The types of statistics useful for assessing such data are discussed.     

Repeated Nipple Fluid Aspiration: Compliance and Feasibility Results from a Prospective Multicenter Study

BackgroundDespite intensive surveillance, a high rate of interval malignancies is still seen in women at increased breast cancer risk. Therefore, novel screening modalities aiming at early detection remain needed. The intraductal approach offers the possibility to directly sample fluid containing cells, DNA and proteins from the mammary ductal system where, in the majority of cases, breast cancer originates. Fluid from the breast can non-invasively be obtained by oxytocin-assisted vacuum aspiration, called nipple fluid aspiration (NFA). The goal of this feasibility study was to evaluate the potential of repeated NFA, which is a critical and essential step to evaluate its possible value as a breast cancer screening method.MethodsIn this multicenter, prospective study, we annually collected nipple fluid for up to 5 consecutive years from women at increased breast cancer risk, and performed a questionnaire-based survey regarding discomfort of the aspiration. Endpoints of the current interim analyses were the feasibility and results of 994 NFA procedures in 451 women with total follow-up of 560 person years of observation.ResultsIn this large group of women at increased risk of breast cancer, repetitive NFA appeared to be feasible and safe. In 66.4% of aspirated breasts, nipple fluid was successfully obtained. Independent predictive factors for successful NFA were premenopausal status, spontaneous nipple discharge, smaller breast size, bilateral oophorectomy and previous use of hormone replacement therapy or anti-hormonal treatment. The procedure was well tolerated with low discomfort. Drop-out rate was 20%, which was mainly due to repeated unsuccessful aspiration attempts. Only 1.6% of women prematurely declined further participation because of side effects.ConclusionsRepeated NFA in women at increased breast cancer risk is feasible and safe. Therefore, NFA is a promising method to non-invasively obtain a valuable source of potential breast cancer specific biomarkers.     

Cytology of nipple discharge in florid gynecomastia

OBJECTIVE: To determine the cytomorphologic spectrum of nipple discharge in florid gynecomastia. STUDY DESIGN: During a 22-year period (July 1979-June 2001), nipple discharge from nine males with breast lesions were examined. Smears from four of these cases with histologically documented gynecomastia were reviewed along with the tissue sections. RESULTS: In the three patients with florid gynecomastia the smears were cellular, with numerous benign ductal cells and papillary fragments along with foam cells and inflammatory cells. Epithelial atypia was mild in two cases and moderate in one. One of the three cases had an associated breast lump that showed features of florid gynecomastia on fine needle aspiration cytology. The biopsy from this case showed cystic hyperplasia of the breast similar to that in women with an intraductal papilloma. One case of simple gynecomastia on histology showed two fragments of benign ductal cells with occasional apocrine and foam cells. CONCLUSION: Nipple discharge in florid gynecomastia may pose problems in identification as the cellularity and atypia may lead to a misdiagnosis of carcinoma.     

Use of monoclonal antibodies to glial fibrillary acidic protein in the cytologic diagnosis of brain tumors

Monoclonal antibodies were used to immunocytochemically demonstrate glial fibrillary acidic protein (GFAP) in 174 smear preparations of brain tumor tissue in order to investigate the presence and distribution of GFAP in a variety of intracranial tumors and to evaluate the value of this technique in the cytodiagnosis of brain tumors. GFAP-positive cells were found in the astrocytic tumors and in some of the oligodendrogliomas, ependymomas and medulloblastomas. In contrast, schwannomas, meningiomas, a primary lymphoma, a hemangiopericytoma pituitary adenomas, germinomas and metastatic tumors were negative for GFAP. The cytodiagnostic accuracy of the 174 brain tumors was raised from 90.8% to 97.1% when GFAP-immunoperoxidase staining was employed to aid the routine cytologic diagnosis. These findings indicate that immunoperoxidase staining for GFAP can be successfully applied to cytologic specimens and is a useful adjunct to routine cytologic diagnosis.     

Comparison of smears and cell blocks in the fine needle aspiration diagnosis of recurrent gynecologic malignancies.

A retrospective, seven-year study was conducted to evaluate the value of cell blocks as an adjunct to smears in the fine needle aspiration (FNA) diagnosis of recurrent gynecologic malignancies. Eighty-four FNAs were performed on patients with previously diagnosed malignancies of the cervix (39 cases), ovary (27), uterus (14), vulva (2) and vagina (2). Material for the preparation of cell blocks was available in all cases. Smears and cell blocks were reviewed separately, and the findings were categorized as positive, negative, suspicious or unsatisfactory. Identical smear and cell block results were reported in 71 (84.5%) of the 84 cases (45 positive, 20 negative, 1 suspicious and 5 unsatisfactory). In 12 cases (14.3%) the smear was superior to the cell block in detecting malignant cells; while all 12 smears were positive, 8 cell blocks were negative, and 4 were suspicious. In no case was the cell block positive with a negative smear; in one (1.2%) the cell block was positive and the smear suspicious. The results of this study indicate that the additional study of cell blocks is of little benefit in the FNA cytodiagnosis of recurrent disease in patients with documented gynecologic malignancies.     

Evaluation of the Cost Effectiveness of Establishing A Fine Needle Aspiration Cytology Clinic In A Hospital Out-Patient Department

In an attempt to reduce the number of inadequate smears processed by our laboratory and the false negative rate of fine needle aspiration cytodiagnosis, we have introduced a fine needle aspiration cytology service where aspirates are taken by the cytopathologist in a clinic. In the 12 month period since the introduction of this service, the number of inadequate smears fell sharply. Nine per cent of the specimens were inadequate compared with 43% of specimens from other sources. The establishment of the clinic resulted in a threefold reduction in the cost of diagnosing breast lesions.     

Ultrasound-guided fine needle aspiration cytology in the diagnosis and management of thyroid nodules

OBJECTIVE: To examine the accuracy of fine needle aspiration cytology (FNAC) in the diagnosis of thyroid nodules and compare the inadequacy rates for ultrasound-guided and freehand FNAC. METHODS: A retrospective study of 434 patients with thyroid nodules who underwent diagnostic FNAC over a 2-year period. Cytological diagnoses have been compared with the histological assessment of resection specimens in 69 cases. RESULTS: The inadequacy rate was significantly lower from ultrasound guided FNAC (24/373 cases, 6.4%) than from freehand FNAC (8/61 cases, 13.1%) (P = 0.043). Seventy-six percentage of patients had a non-neoplastic cytological diagnosis and, after multidisciplinary review, the patients were reassured and assigned to clinical follow-up. Sixty-seven patients had a resection for cytological appearances consistent with non-neoplastic disease (n = 34), suspicious of follicular neoplasia (n = 23), or suspicious of malignancy (n = 10), and two patients had resections following inadequate cytology with ultrasound appearances suspicious of a neoplasm. The overall accuracy of FNAC analysis for malignancy was 97.0%, with sensitivity 83.3%, specificity 98.0%, positive predictive value 71.4% and negative predictive value 98.4%. The overall accuracy of FNAC analysis for the prediction of neoplasia was 97.5%, with sensitivity 80.5%, specificity 97.8%, positive predictive value 89.2% and negative predictive value 95.9%. Difficulties in cytological diagnosis were associated with lymphoid infiltrates and with degenerative changes in follicular adenomas. CONCLUSION: Ultrasound-guided FNAC has a significantly lower yield of inadequate aspirates than palpable FNAC. The ability of FNAC to predict neoplasia in 89% patients and to exclude neoplasia in 95.9% patients makes an important contribution to the multidisciplinary assessment of patients.     

Fine needle aspiration cytology of salivary gland lesions: advantages and pitfalls

Fine needle aspiration cytology (FNAC) was performed on 52 patients with salivary gland lesions. A definitive cytodiagnosis was possible in 45 cases: a sensitivity of 89% and a specificity of 94% was achieved. The pitfalls of FNAC of salivary gland lesions are reflected by the false positive and false negative rates which were 4%. Errors of cytodiagnosis are due to the morphological variability of these tumours which make sampling and interpretation difficult.     

Papillary breast lesions diagnosed on cytology. Profile of 65 cases

OBJECTIVE: To analyze the cytologic features of nipple discharge and fine needle aspiration (FNA) cytologic smears from breast lesions reported as showing papillary features and to correlate them with histopathologic features. STUDY DESIGN: The study group consisted of FNA smears and/or nipple discharge smears from 65 breast lesions diagnosed on cytology as duct papilloma, papillary lesion, fibrocystic condition, fibroadenoma, papillary neoplasm or papillary carcinoma. Cytomorphologic features assessed included cellularity, cell pattern (clusters, papillary, 3-dimensionality, etc.) and cell characteristics (monomorphism, pleomorphism, apocrine change, plasmacytoid features). Histological material was available for review and cytohistologic correlation in all cases. RESULTS: Forty-six specimens were FNA smears, and 16 were nipple discharge smears; in 3 cases FNA and nipple discharge cytologic smears were available for review. Cytologic study could predict the presence of a papillary pattern in all neoplasms with pure or focal papillary differentiation. There was an overlap in cytomorphologic features between papillary and nonpapillary benign lesions as well as between benign and malignant papillary neoplasms. Frank blood in the aspirate, cell dissociation and atypia, however, were more frequent in the last. CONCLUSION: Overlap of cytologic features in nonneoplastic and neoplastic benign papillary lesions and between benign and malignant papillary neoplasms necessitates histologic evaluation in all cases diagnosed as papillary on cytology. Since 49.2% of lesions showing papillary features on cytology prove to be malignant, all cases reported as papillary on cytology should be excised urgently for histologic assessment.     

Diagnostic value of nucleolar organizer regions (AgNORs) in brush biopsies of suspicious lesions of the oral cavity.

OBJECTIVE: The aim of this retrospective study was to report on the diagnostic accuracy of AgNOR-analysis as an adjunctive diagnostic tool of conventional oral exfoliative cytology taken from suspicious lesions in our clinic. STUDY DESIGN: Cytological diagnoses obtained from brush biopsies of macroscopically suspicious lesions of the oral mucosa from 75 patients (final diagnoses: 53 histologically proven squamous cell carcinomas, 11 leukoplakias and other inflammatory oral lesions) and from 11 patients with normal mucosa as a negative control group were compared with histological and/or clinical follow-ups. Five smears were doubtful and seven suspicious for tumor cells in the cytologic report. Number of AgNOR's were counted in 100 squamous epithelial cell-nuclei per slide after silver-restaining. RESULTS: Sensitivity of our cytological diagnosis alone on oral smears for the detection of squamous carcinomas was 92.5%, specificity 100%, positive predictive value was 100% and negative 84.6%. The best cut-off value of the mean number of AgNOR dots per nucleus distinguishing benign from malignant cells was 4.8. The percentage of nuclei with more than three AgNORs had a cut-off level of 70%. Applying these methods to twelve doubtful or suspicious cytological diagnoses we were able to correctly establish the diagnosis of malignancy in ten cases of histologically proven cancers and to reveal benignity in two histologically proven cases. Thus we achieved a positive and negative predictive value of 100% each. CONCLUSIONS: Smears from brushings of visible oral lesions, if clinically considered as suspicious for cancer, are an easily practicable, non-invasive, painless, safe and accurate screening method for detection of oral cancerous lesions. We conclude that AgNOR-analysis may be a useful adjunct to other methods in routine cytological diagnosis of oral cancer that can help to solve cytologically suspicious or doubtful cases.     

Clinical and cytologic aspects of primary fallopian tube carcinoma. A report of ten cases

The clinical and cytologic findings in ten cases of primary fallopian tube carcinoma, a very rare malignancy, are presented. All ten patients had vaginal pool (V), cervical (C), endocervical (E) and endometrial aspiration (EA) smears examined preoperatively; peritoneal smears were also prepared from cul-de-sac fluid aspirated during surgery. In the preoperative cytodiagnosis, some of V, C, E and EA smears were positive for malignant cells in six of the ten patients (60%). Examination of the EA smear was the most effective means of discovering this disease. A watery discharge was noted in two patients, both of whom were negative in the preoperative cytodiagnosis. In such patients, it is necessary to repeat the smear examinations. The cytologic appearance of this disease is contrasted to that of endometrial carcinoma.     

Spontaneous Infarction of an Intraductal Papilloma of the Breast: Cytological Presentation On Fine Needle Aspiration

A relatively rare case of spontaneous infarction of an intraductal papilloma of the breast is presented which was considered to be suspicious for malignancy on fine needle aspiration (FNA) cytology. The aspirate revealed several groups of atypical cells featuring a high nuclear-cytoplasmic ratio, coarsely granular chromatin, and somewhat prominent nucleoli. There was abundant necrotic cellular debris in the background. These cellular features were considered evidence of ductal carcinoma of the breast. The correct diagnosis was made by open biopsy which revealed necrosis involving the breast due to infarction of an intraductal papilloma.     

Endoscopic ultrasound‐guided fine needle aspiration of the pancreas: cytomorphological evaluation with emphasis on adequacy assessment,diagnostic criteria and contamination from the gastrointestinal tract1

Objective: Endoscopic ultrasound (EUS)‐guided fine needle aspiration (FNA) has been proved to be safe, efficient and reliable in the diagnosis of pancreatic lesions. This study evaluated specimen adequacy, diagnostic criteria of various pancreatic neoplasms and contamination from the gastrointestinal (GI) tract. Methods: EUS‐guided FNA of the pancreas and subsequent surgical resections performed at the University of California Irvine Medical Center during February 1996–October 2000 were retrospectively selected. Modified Papanicolaou staining method was used for immediate evaluation and cell block prepared. Results: A total of 267 cases were available for review, including 147 (55.1%) positive/suspicious, 10 (3.7%) atypical, 96 (36.0%) negative and 14 (5.2%) unsatisfactory cases. Eighty‐six (58.5%) positive/suspicious cases had histological confirmation and 12 (8.3%) had lymph node or distant metastases by cytology. Three atypical, two negative, and two unsatisfactory cases proved to have adenocarcinoma. Contamination from duodenum, stomach or pancreas was found in 77 positive/suspicious, three atypical and 90 negative cases. The sensitivity, specificity, diagnostic accuracy, positive and negative predictive values were 94.6%, 100%, 95.6%, 100%, 82% respectively. Conclusions: EUS FNA is efficient and accurate in the diagnosis of pancreatic neoplasms in adequate samples. Contamination from the GI tract should be well recognized to avoid misinterpretation.     

Diagnostic utility of galectin-3 in aspirates of thyroid follicular lesions

OBJECTIVE: To investigate the expression of galectin-3 in various thyroid follicular lesions, including diffuse hyperplasia, nodular hyperplasia, and benign and malignant follicular neoplasms, to clarify the diagnostic utility of galectin-3 in aspirates of follicular lesions. STUDY DESIGN: A total of 146 follicular lesions diagnosed cytologically, obtained from patients who had undergone thyroidectomy for either benign or malignant nodules, were evaluated using Papanicolaou-stained slides and cell blocks with galectin-3 immunostaining. We primarily categorized the aspirated specimens as benign, indeterminate or suspicious for a follicular neoplasm based on cellularity, architectural arrangement of the follicular cells and presence or absence of colloid. Galectin-3 immunostaining was evaluated according to the proportion and intensity of positively stained cells. Cytologic diagnoses were correlated with the results of galectin-3 and categorized into 3 groups (benign, indeterminate for malignancy, suspicious for malignancy) and compared with the corresponding histologic diagnoses. RESULTS: When the histologic diagnoses were compared with the cytologic diagnoses, the accuracy in the distinction between benign and malignant cases was 79.5% except for 8 cytologically and 3 histologically indeterminate cases. Except for 11 indeterminate cases, there were 18 (12.3%) discrepant cases. False positive cases included 8 of 62 (12.9%) nodular hyperplasias and 1 of 42 (2.4%) follicular adenomas. Of 9 false negative cases, 4 minimally invasive carcinomas and 2 widely invasive carcinomas were included. Three follicular tumors of uncertain malignant potential were cytologically categorized as malignant, and all cases showed positivity for galectin-3. CONCLUSION: Galectin-3 could be used as a useful supplementary marker for cytologic diagnosis, although it was not an absolute marker in determining whether a lesion was benign or malignant.     

Value of fine needle aspiration cytology of the breast, with an emphasis on the cytodiagnosis of colloid carcinoma.

The fine needle aspiration (FNA) cytologic evaluation of 6,941 lesions of the breast was reviewed, with an emphasis on the cytodiagnosis of colloid carcinoma. The most common benign breast diseases in this series were fibroadenomas, cysts and fibrocystic conditions. All cases with an FNA diagnosis of suspicious were biopsied; a number of these were found to be carcinoma of the breast. In cases with an FNA diagnosis of carcinoma of the breast, a plan of management was immediately adopted on the basis of that diagnosis. Thirteen cases of colloid (mucinous) carcinoma of the breast were diagnosed by FNA cytology; in all, the cytodiagnosis was confirmed by the subsequent histologic diagnosis. The distinctive cytologic criteria that may be useful for making an FNA diagnosis of colloid carcinoma of the breast are discussed, and the FNA differences between the pure and mixed types of colloid carcinoma are noted.     

乳腺良性肿块与乳腺癌患者的超声弹性成像对比

目的:对比乳腺良性肿块与乳腺癌患者的超声弹性成像,明确超声弹性成像的应用价值。方法:选取2014年5月-2016年1月我院乳腺肿块患者128人次共146例肿块,根据病理结果分为乳腺良性肿块和乳腺癌,比较超声弹性成像与病理结果。结果:128个患者共计肿块146例,99例结节为良性肿块,其中32例为乳腺纤维腺瘤,29例为乳腺增生结节,20例为乳腺脂肪瘤,6例为乳腺血管脂肪瘤,4例为乳腺导管腺瘤,8例为乳腺导管内乳头状瘤;47例肿块为恶性,其中37例肿块为浸润性导管癌,9例肿块为粘液腺癌,1例肿块为硬癌。乳腺良性肿块患者81人次共99例,其中1分43例(43.43%),2分34例(34.34%),3分18例(18.18%),4分4例(4.04%);乳腺癌患者47例,其中3分9例(19.15%),4分20例(42.55%),5分18例(38.30%)。超声弹性成像鉴别乳腺良性肿块与乳腺癌的灵敏度为95.96%,特异性为80.85%,准确度为91.10%,阴性预测值为90.48%,阳性预测值为91.35%。结论:超声弹性成像鉴别乳腺良性肿块与乳腺癌的灵敏度高达95.96%,具有较高准确度,可辅助诊断乳腺疾病。