An alternative to the diagnostic dilatation and curettage--endometrial cytology.

Endometrial aspiration cytology has been shown by multicentre prospective studies to be an acceptable and valuable method of assessing the endometrium. A retrospective study was undertaken over three years'' routine use of the Isaacs cell sampler. In 86% of the cases suitable endometrium was obtained, with experience of the technique being the important factor. When compared with histological findings, all 11 cases of malignancy were confirmed, including one ovarian adenocarcinoma. Of the cytological reports of endometrial hyperplasia, 78% were confirmed by the histological findings, with the remainder showing minor degrees of cystic hyperplasia or normal endometrium. In no case was a more abnormal lesion present on histological examination than had been suggested by cytological findings. The use of progestogens in reversing hyperplasia is seen to be effective, though the long term benefit remains uncertain. It is concluded that with an experienced cytologist, Isaacs endometrial aspiration should be used routinely for the primary investigation of dysfunctional uterine bleeding and postmenopausal bleeding.     

Value of cytology for detecting endometrial abnormalities in climacteric women receiving hormone replacement therapy.

Over six months 113 endometrial specimens from 110 menopausal women receiving hormone replacement therapy were examined by two cytologists and two histopathologists. Specimens were obtained by aspiration with the Isaacs cell sampler immediately before Vabra suction curettage, both procedures being performed in the outpatient department without anaesthetic. The histologists agreed with each other on the classification of 85 specimens (75.2%) and the cytologists agreed on the classification of 44 (38.9%). In only 15 cases (13.3%) did all four observers agree. Of the three cases of cystic or adenomatous hyperplasia detected histologically, only one was diagnosed by cytology. Furthermore, both cases of adenocarcinoma escaped detection by cytology, though a third case--later confirmed-"was suspected by one cytologist alone. Use of the Isaacs endometrial cell sampler cannot be advocated for routine screening of women with climacteric symptoms receiving hormone replacement therapy. Efforts should be made to establish the correct dose and duration of treatment with an oestrogen-progestogen preparation in order to avoid over-stimulating the endometrium and the need for regular screening for endometrial abnormalities.     

Endometrial assessment with Isaacs cell sampler.

The value of the Isaacs endometrial cell sampler in the cytologic assessment of the endometrium was studied in 121 unanaesthetised patients aged over 40. Satisfactory aspirates for cytological diagnosis of endometrial state were obtained in 111 patients (91%) whereas endometrial specimens for histological diagnosis were obtained in only 89 patients (79%). In only four out of 83 cases were there diagnostic discrepancies between the aspirates and the curettings. It is concluded that the technique is safe, quick, comfortable, and reliable for assessing endometrial state. It should therefore prove valuable for screening, particularly in the management of menopausal women requiring oestrogen treatment.     

The Isaacs Endometrial Cell Sampler. An evaluation in 100 patients with postmenopausal bleeding

The Curity Isaacs Endometrial Cell Sampler was used to obtain cytologic material from 100 consecutive patients presenting with postmenopausal bleeding. It was followed by uterine curettage to obtain material for histology. Satisfactory endometrial aspiration smears were obtained from 92 patients, whereas curettage yielded endometrial tissue in only 48. Of 17 patients with histologic confirmation of malignancy, 7 had smears diagnosed as showing malignancy, and 7 had smears showing hyperplastic changes; 3 of the aspiration smears were judged to be unsatisfactory for cytologic evaluation. All the carcinomas were found in the hyperplastic, malignant or unsatisfactory smears. This technique is worthy of further study.     

Prospective study of combined use of bronchial aspirates and biopsy specimens in diagnosis and typing of centrally located lung tumours.

OBJECTIVE--To determine the diagnostic accuracy of examining bronchial secretions in pulmonary cytopathology and whether cytology and histopathology can complement each other in routine practice among lung specialists. DESIGN--A prospective study comparing 1225 cytological and biopsy results, conducted during 1987-93. Tumours were confirmed by histopathology, imaging techniques, or clinical outcome and imaging techniques combined. SETTING--11 lung or internal medicine units, France. SUBJECTS--1128 patients (874 men; 254 women) aged 65.3 (SD 13.7) years who underwent fibreoptic bronchoscopy for various pulmonary symptoms. RESULTS--Exact concordance between cytological and biopsy results was obtained in 1036/1187 (87.3%) satisfactory specimens. In all 574 lung tumours were diagnosed. One case (0.08%) was a false positive cytological diagnosis in a patient with tuberculosis. Patients with lung cancer were more likely to have positive cytological results than positive biopsy results (P < 0.001). Agreement in tumour typing was observed in 375/424 (88.4%) cases, when non-small cell carcinomas, small cell carcinomas and undifferentiated carcinomas were separated. In the 11 patients with squamous cell carcinomas in situ, eight (72.7%) of the carcinomas were diagnosed cytologically as squamous cell. Unsatisfactory material was obtained in only 20 (1.6%) and 19 (1.6%) cases by cytology and biopsy respectively. Examinations had to be repeated in 86 (7.6%) patients. CONCLUSIONS--Examination of bronchial secretions complements histopathology in both diagnosing and typing lung tumours and could be performed more systematically in patients undergoing fibreoptic bronchoscopy.     

Efficacy of the Isaacs Endometrial Cell Sampler in the cytologic detection of endometrial abnormalities

The efficacy of the Isaacs Endometrial Cell Sampler to obtain specimens for cytologic examination to detect both hormonal disturbances and precursors of malignancy of the endometrium was assessed in 120 symptomatic women. Correlation of the cytologic results with the histologic diagnosis on curettage specimens showed a diagnostic accuracy of 96.3%. The cytologic criteria for diagnosing samples obtained with the Isaacs device are presented.     

Fine needle aspiration cytology of palatine tonsils: a study of 112 consecutive adult tonsillectomies

M. J. Ashraf, N. Azarpira, B. Nowroozizadeh, M. Shishegar, B. Khademi, A. Faramarzi, S. B. Hashemi, A. Hakimzadeh and E. Abedi
Fine needle aspiration cytology of palatine tonsils: a study of 112 consecutive adult tonsillectomies Objective: To study fine needle aspiration cytology (FNAC) findings of tonsillar lesions with histological controls and to assess its role in the diagnostic evaluation of tonsillectomy specimens. Methods: This study consisted of 112 cases that required tonsillectomy, comprising 55 (49.1%) men and 57 (50.9%) women. The ages ranged between 20 and 62 years. The clinical diagnosis in 101 cases was chronic tonsillitis, whereas 11 were suspected of neoplasia. FNAC was performed before tonsillectomy under general or local anaesthesia or on fresh specimens using a 21‐G needle. The smears were stained using Wright–Giemsa and Papanicolaou methods. Histological examination was carried out on surgical specimens of all cases and, when required, immunohistochemistry was performed on histological sections. The diagnostic outcomes between FNAC and surgical biopsy were compared. Results: In this study, 106 cases were diagnosed as chronic tonsillitis/follicular hyperplasia, four cases as non‐Hodgkin’s lymphoma, one as Hodgkin’s lymphoma and one as monophasic synovial sarcoma. All malignant cases were diagnosed by FNAC, but synovial sarcoma was incorrectly diagnosed as squamous cell carcinoma. Five cases clinically suspected of neoplasia were correctly diagnosed as chronic tonsillitis on cytology. Conclusion: Tonsillar aspiration is a safe procedure and is useful in the evaluation of tonsillectomy specimens. However, ancillary tests on cytological material are often needed when neoplasia is suspected and would help clinical management and allow histological examination of cases diagnosed cytologically as lymphoma.     

Stereotactic biopsy and cytological diagnosis of solid and cystic intracranial lesions

Cytological smears from 115 consecutive cases of stereotactic biopsies of intracranial lesions were reviewed. Ninety-five lesions were solid and 20 cystic. Material from 90 solid and 13 cystic lesions was sent both for cytological and histological examination. In 66 of the solid lesions, the cytological diagnosis was confirmed by histology (five were benign lesions and 61 malignant tumours: 56 primary brain tumours, three metastases and two lymphomas). In 24 cases with discrepant cytology and histology, the histology was inconclusive or insufficient in 14 cases, while cytology established the diagnosis of astrocytoma grade II (seven cases), metastases (two cases), gliosis (one case) and benign (four cases). Necrosis of tumour type was observed cytologically in six patients representing glioblastoma (two cases), anaplastic astrocytoma (one case), lymphoma (one case) and normal brain (two cases) histologically. Three cases reported cytologically as benign were primary brain tumour (two cases) and gliosis (one case). One smear of a glioblastoma was insufficient for cytological diagnosis. Cystic lesions were cytologically benign in 17 cases and malignant in three cases. Histology from the cyst wall confirmed the malignant diagnosis in three cases and showed tumour in six more cases, a benign process (two cases), changes induced by radiotherapy for arteriovenous malformation (one case) and insufficient material (one case). In conclusion, cytology from solid brain lesion allows an accurate diagnosis and subtyping of tumours in a majority of cases, and can thus be used to choose type of therapy. In cystic brain tumours, however, examination of the cystic fluid, is often inconclusive and a biopsy from the cyst wall should be performed if there is clinical or radiological suspicion of tumour.     

Evaluation of aspiration cytology of ovarian masses with histopathological correlation

T. Sood, U. Handa, H. Mohan and P. Goel
Evaluation of aspiration cytology of ovarian masses with histopathological correlation Objectives: To evaluate the efficacy and diagnostic accuracy of fine needle aspiration cytology (FNAC) in distinguishing non‐neoplastic and neoplastic ovarian lesions and to determine reliable cytological criteria for typing neoplastic ovarian masses into benign and malignant tumours and their subtypes. Methods: FNAC was performed on 50 patients diagnosed as having an ovarian mass clinically and/or ultrasonographically. Detailed history, clinical examination and ultrasound findings in each case were recorded. The cytological diagnoses were categorized as neoplastic and non‐neoplastic and further into benign and malignant neoplasms. These cytological diagnoses were then compared subsequently with the histopathological diagnoses. Results: The study material consisted of 57 aspirates from 50 patients. A comparison of cytological findings with the histological diagnosis was possible in 53 aspirates; in the remaining four cases (7%) the smears were acellular. On cytology, 31 lesions were diagnosed as neoplastic and 22 as non‐neoplastic. The overall sensitivity of cytology in diagnosing neoplastic and non‐neoplastic ovarian lesions was 93.9% and the specificity was 100%. The positive predictive value was 100% and negative predictive value 90.9%. The overall diagnostic accuracy was 96.2 %. Conclusion: FNAC of ovarian masses is a minimally invasive procedure that can differentiate neoplastic from non‐neoplastic ovarian lesions. It may help avoid unnecessary operations and preserve the reproductive ability in young patients. Furthermore, it also enables a satisfactory sub‐categorization of ovarian tumours, which facilitates the choice of appropriate therapy.     

Fine needle aspiration cytology of solitary fibrous tumours of the pleura

OBJECTIVE: To analyse fine needle aspirates from solitary fibrous tumour (SFT) of the pleura and to elucidate the cytological features unique to these tumours and differential diagnostic findings of benign and malignant SFTs. METHODS: Fine needle aspiration (FNA) cytology slides from eight cases of SFT of the pleura, including six benign and two malignant SFTs, were reviewed. The subsequent histological slides were also examined. RESULTS: Cytological diagnoses from six histologically proven cases of benign SFTs were low-grade sarcoma (one), non-small cell carcinoma (one), malignant tumour (1) and benign (three). Two cases of malignant SFTs were cytologically diagnosed as malignancy. The aspirates showed a varying degree of cellularity. Most smears were composed of single, scattered fusiform cells, and irregular loose aggregates of oval to spindle cells intimately admixed with dense collagenous stroma. Two malignant SFTs had a greater number of cells in clusters, and displayed mitotic activity, without significant cytological atypia. CONCLUSIONS: The diagnosis of SFT may be suggested by a combination of cytological and radiological findings. The precise determination of malignancy for SFT, however, is not usually straightforward on the basis of cytological features alone. The findings of highly cellular clusters and mitotic activity in the FNA cytological smear can help differentiate malignant from benign SFTs.     

Criteria for the cytologic assessment of hyperplasias in endometrial samples obtained by the Endopap Endometrial Sampler

The Endopap Endometrial Sampler was used in 1,465 women, either just before endometrial biopsy or curettage (in 760 symptomatic patients) or as an office procedure (in 705 women). The samples were inadequate for interpretation in only 8.7% of the cases. Although all malignant lesions were identified by this screening technique, about one-fourth were initially classified cytologically as hyperplasia. Endometrial hyperplasias presented the greatest difficulties in interpretation, with only slightly over half of the proven cases correctly assessed on the endometrial sample. In an attempt to improve the accuracy of the cytologic diagnosis of hyperplasias, ten morphologic features were examined retrospectively in 207 cases. Five of the criteria were shown to provide an increased probability of correctly diagnosing endometrial hyperplasias on the cytologic sample: (1) the overlapping of cells in the glandular clusters or sheets, (2) the presence of nucleoli, (3) anisokaryosis, (4) granularity of chromatin and (5) the presence of sheets of stromal cells. The more of these criteria observed in a given case, the better was the chance of cytologically identifying a hyperplasia in the Endopap sample.     

Does Microhistology Improve the Cytological Diagnosis of Liver and Pancreatic Tumours?

Guided percutaneous fine needle aspiration cytodiagnosis of the liver, retroperitoneum and pancreas was performed in 197 patients. In 42 cases, material left after the smears were prepared was embedded in paraffin wax for histological examination. Six liver tumours and seven pancreatic tumours were identified in this material. In two cases the diagnosis of liver cell carcinoma was made only after microhistological examination. Re-examination of the cytological material in both cases disclosed features of liver cell carcinoma which were underestimated in the first examination and diagnosed only broadly as cancer cells. On the other hand, in another case cancer cells were present only in the smear and absent in the microhistological preparation. Diagnosis of pancreatic tumours was generally not improved by microhistological examination. In one case cancer cells were present only in the cytological material. In another case a cytological diagnosis of suspected cancer was confirmed as adenocarcinoma by microhistology. The diagnosis of non-neoplastic material in the remaining 29 cases were identical by cytopathology and microhistology. It is concluded that the microhistology of needle aspirate material complements cytological examination and can refine diagnosis although it increases cost.     

Aspiration and cytological evaluation of idiopathic bone cavities of the jaw

The idiopathic bone cavity (IBC) is an intraosseous pseudocyst devoid of epithelial lining. Clinically, IBCs of the jaw are asymptomatic and normally found in routine radiographic exams. Although the literature regarding the content of IBCs is controversial, the final diagnosis is usually aided by the discovery of an empty cavity upon surgical exploration. The aim of this study was to perform cytological and histological analysis of IBC contents. Cytological analysis of nine cases of IBC was performed after puncture and processed by the cell block technique. Histological analysis was performed in six cases in which it was possible to collect enough material by curettage of bone walls. Remarkably, cell block analysis revealed the presence of fibrin, often arranged as a net; erythrocytes; and inflammatory cells, with a predominance of lymphocytes as well as some macrophages and neutrophils. Histological analysis showed the presence of scant connective tissue, bone trabeculae, hemorrhagic foci, and hemosiderin. Only two cases presented scattered multinucleated giant cells. Cytological evaluation of IBC content by the cell block technique might represent a useful diagnostic tool, especially in cases in which there is no available material for curettage in the cavity.     

The use of p63 as an effective immunomarker in the diagnosis of pulmonary squamous cell carcinomas on de-stained bronchial lavage cytological smears

M. Uke, B. Rekhi, D. Ajit and N. A. Jambhekar
The use of p63 as an effective immunomarker in the diagnosis of pulmonary squamous cell carcinomas on de‐stained bronchial lavage cytological smears Objectives: A diagnosis in pulmonary onco‐cytopathology primarily necessitates distinguishing small cell carcinoma (SCLC) from non‐small cell carcinoma (NSCLC), which includes squamous cell carcinoma and adenocarcinoma. Lately, p63 antibody has been used for distinguishing squamous cell carcinoma from SCLC and adenocarcinoma. We present an analysis of p63 expression in cytological smears from 100 bronchial lavage specimens comprising 51 cases of SCLC and 49 cases of NSCLC. Methods: A single Papanicolaou‐stained conventional smear was de‐stained and re‐fixed with cold acetone and methanol for immunocytochemical staining with p63 antibody. Staining results were graded as 0 (nil), 1+ (focal), 2+ (moderate, diffuse) and 3+ (strong, diffuse). Results: Out of 100 cases, 21 were cytologically diagnosed as squamous cell carcinoma. Twenty of these showed 2+ or 3+ p63 positivity, whereas one, which was adenocarcinoma on histology, showed 1+ staining. Of seven cases cytologically diagnosed as adenocarcinoma, six showed no p63 staining, whereas one, which was squamous cell carcinoma on histology, showed 1+ staining. All 48 cases cytologically diagnosed as SCLC were confirmed as such on histology and showed no p63 staining. Four cases were cytologically designated as poorly differentiated carcinomas, of which three showed no p63 staining and one showed 3+ staining. The former three were found to be SCLC on histology while the latter was squamous cell carcinoma. The remaining 20 cases were cytologically designated as NSCLC. Of these, eight showed no p63 staining, whereas 10 showed 1+ and two showed 2+ staining. The former eight were adenocarcinoma on histology and the latter two were squamous cell carcinoma. The 10 cases that showed 1+ p63 staining were adenocarcinomas (n = 5), squamous cell carcinoma (n = 4) and NSCLC, not otherwise specified (n = 1). Positive staining was seen in normal basal cells, which acted as an internal control. Overall sensitivity of p63 for squamous cell carcinoma was 100% and specificity was 90.4%. Conclusions: p63 immunostaining on processed cytology smears can be used to help identify squamous cell carcinoma. Its diffuse expression was specific for squamous cell carcinoma while focal staining was also seen in adenocarcinoma.     

Management of Women With A Cervical Smear Showing A Mild Degree of Dyskaryosis: A Review of Policy

Three hundred and thirty-seven women who presented for the first time with a cervical smear showing a mild degree of dyskaryosis were followed for a minimum period of 3 years and 9 months. Of the 305 women with complete cytological and histological records, 178 were biopsied and 127 remained on cytological follow up. In the biopsied group one case of microinvasive squamous cell carcinoma was diagnosed within 1 year of the patient's first abnormal smear. A further 24% showed cervical intraepithelial neoplasia (CIN) I, 17% showed CIN II and 29% showed CIN III. The overall regression rate for the group of 305 women was 34%. Our results indicate that cytological surveillance is acceptable provided that biopsy is advised when dyskaryosis persists. No major modifications to laboratory policy are indicated and in approximately 34% of cases an unnecessary hospital referral would be avoided.     

The positive impact of cytological specimens for EGFR mutation testing in non‐small cell lung cancer: a single South East Asian laboratory’s analysis of 670 cases

B. Pang, D. Matthias, C.W. Ong, A.N. Dhewar, S. Gupta, G.L. Lim, M.‐E. Nga, J.E. Seet, A. Qasim, T.‐M. Chin, R. Soo, R. Soong and M. Salto‐Tellez The positive impact of cytological specimens for EGFR mutation testing in non‐small cell lung cancer: a single South East Asian laboratory’s analysis of 670 cases Objectives: To compare the rejection rates of non‐small cell lung cancer (NSCLC) samples obtained by differing sampling methods for testing by Sanger sequencing for epidermal growth factor receptor (EGFR) mutations. To assess the association between unsatisfactory outcomes and the quantity of DNA extracted from cytological versus histological samples. Methods: Six hundred and seventy NSCLC samples referred to our centre from 2008 to 2010 were reviewed as a consequence of sample rejection, presence of EGFR mutations, cytological versus histological sampling methods, DNA quantity and the unsatisfactory genotyping rate. Results: Eighty samples were rejected for testing in similar proportions of histological and cytological samples (11.9% versus 10.9%) usually (n = 75) because the amount of cellular material was judged insufficient in small biopsies or cytology samples. The remaining 590 samples on which EGFR testing was attempted yielded 51 (8.6%) unsatisfactory test outcomes caused by failure of the polymerase chain reaction (PCR) (n = 47 cases), uninterpretable Sanger chromatograms (n = 3 cases) and insufficient DNA extracted for PCR (n = 1 case). The difference in rates of unsatisfactory outcomes between cytological samples (seven of 147 samples or 4.7%) versus tissue samples (44 of 443 samples or 9.9%) was clinically relevant but not statistically significant (Mann–Whitney test; P < 0.081). There was no association between the concentration of DNA extracted and the likelihood of an unsatisfactory analysis; which was similar in all types of sections (large and small) while 0% of 37 cytology slides were unsatisfactory. Conclusions: Utilizing cytology samples for EGFR testing avoids unnecessary patient re‐biopsing and yields a clinically superior satisfactory rate to the overall satisfactory rate of tissue biopsies of NSCLC. The quality rather than quantity of DNA extracted may be a more important determinant of a satisfactory result.     

Urine cytology evaluation in cases of uretero-ileal cutaneous diversion

Cytological examination of urine from the ileal conduit in cases of bladder cancer treated by radical surgery can be an important and effective follow-up procedure. A total of 19 patients (18 males and one female) on whom radical cystectomy for cancer was performed were studied. Three urine specimens were examined in each case using routine cytological methods. Three cases of recurrent carcinoma (mainly of papillary type) were diagnosed cytologically before any clinical evidence of disease. the cytological examination of urine at 3-6 month intervals after cystectomy for bladder carcinoma is considered advisable in all cases, since the recurrence rate of transitional cell neoplasms in the upper urinary tract after cystectomy for transitional carcinoma is quite high.     

Papillary neoplasms of the breast: clues in fine needle aspiration cytology

Papillary neoplasms of the breast include a wide spectrum of mammary lesions. The differential diagnosis of benign and malignant lesions can be problematic not only cytologically, but also histopathologically. Aspiration smears can demonstrate that cytological differentiation is feasible. A retrospective study of 30 cases of papillary tumour of the breast, 15 papillary carcinomas and 15 papillomas, was performed to find the cytological differences between the pathologies. Cytological samples of papillary carcinomas were characterized by an abundance of cellular material, three-dimensional papillary clusters without fibrovascular connective tissue cores, small papillae arranged in cell balls, tall columnar cells and isolated naked nuclei. Numerous haemosiderin-laden macrophages were seen. There were no eosinophilic bipolar cytoplasmic granules, bipolar naked nuclei or apocrine metaplasia. In the papillomas there was less material; the papillae had cohesive stalks surrounded by columnar cells in a honeycomb pattern. We also found fewer small papillae and isolated columnar cells. In addition, the presence of apocrine metaplasia and bipolar naked nuclei was noted. We suggest that papillary carcinoma of the breast can be diagnosed by cytology and differentiated from papilloma.     

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.