Pitfalls in fine needle aspiration cytology.

A review of pitfalls encountered in fine needle aspiration cytology (FNAC) of all organs and tissues and based mainly on the author's 35-year experience of diagnostic FNAC in clinical practice is presented. Diagnostic difficulties are usually related to deviations from common cytological criteria that may occur in some lesions. Others are due to the effects of the sampling procedure or of the preparation of samples. A few basic rules are proposed, which may help to avoid some of the diagnostic pitfalls.     

Role of fine needle aspiration cytology in diagnosis of pleomorphic adenomas

Role of fine needle aspiration cytology in diagnosis of pleomorphic adenomas This retrospective study was carried out to review the cases diagnosed as pleomorphic adenoma in major or minor salivary glands and determine the difficulties encountered on typing this tumour on fine needle aspiration cytology (FNAC). Over a 19‐year period (1982–2000) 488 pleomorphic adenomas were diagnosed on FNAC from different sites (parotid – 372 cases, submandibular – 95 cases; oral cavity – 21 cases). Histology was available in 232 cases. Twenty‐nine cases where a histological diagnosis of pleomorphic adenoma was made but the cytological diagnosis was variable were also reviewed. In 216 of the 232 cases a good cytohistological correlation was available. On review only 4 of the 16 cases initially diagnosed as pleomorphic adenoma on FNAC where the histology revealed a different tumour were categorized as pleomorphic adenoma, while 3 each were classified as adenoid cystic carcinoma and benign tumour ?type, and 2 each were diagnosed to be muco‐epidermoid carcinoma, monomorphic adenoma and acinic cell carcinoma. On review of the FNAC smears from 29 cases where a histological diagnosis of pleomorphic adenoma was available while the cytological diagnosis was variable, only 11 (38%) were categorized as pleomorphic adenoma. In the majority of the remaining cases the cytological diagnosis did not alter markedly, 7 of 10 cases where the tumour could not be typed on cytology initially could not be typed even on review. In conclusion, FNAC is an ideal, fairly accurate preoperative procedure for the diagnosis of pleomorphic adenomas. Certain diagnostic problems occur in differentiating pleomorphic adenomas from adenoid cystic carcinoma, monomorphic adenoma and mucoepidermoid carcinoma. Carcinoma ex‐pleomorphic adenoma is difficult to identify on FNAC and in our series all 4 such cases on histology were considered benign on cytology.     

Scrape cell-block technique for fine needle aspiration cytology smears

An inconclusive diagnosis on fine needle aspiration cytology (FNAC) may be due to poor spreading and presence of thick tissue fragments despite aspiration of adequate material. Repeat aspiration may not be possible especially when aspirates of deep seated organs have been obtained by image guided techniques. We have resorted to a 'scrape cell-block' (SCB) technique in such cases. In this technique the cellular material on the slides which had already been fixed and stained, was carefully removed by scraping following destaining and then processed as a cell block. SCB interpretation was then compared with the smear diagnosis and histological diagnosis, wherever available. A total of 27 cases were studied. In 12 cases SCB slides added information to the FNAC smears. In 14 cases SCB did not offer any additional information. SCB was inconclusive in one case. Final histological correlation was available in eight cases and the SCB diagnosis was confirmed in six cases, whereas in two cases SCB failed to identify the tumour. Immunocytochemistry (ICC) was done in one case. SCB is a useful technique to make the best use of the available material when reaspiration is difficult.     

Fine needle aspiration of focal liver lesions

Fourteen percutaneous fine needle aspirates (FNAs) of focal liver lesions performed under ultrasound guidance at the Sultan Qaboos University Hospital (SQUH), Oman, between January 1991 and October 1992, are presented. Ten of these were cytologically diagnosed as hepatocellular carcinomas (HCC). the patients' ages ranged from 50 to 70 years and eight of these were males. the important diagnostic cytological criteria of HCC were found to be increased nucleocytoplasmic (N/C) ratio, trabecular pattern, atypical naked nuclei, bile production by malignant hepatocytes and absence of bile duct epithelium. Carcinoembryonic antigen (CEA) positivity of bile canaliculi by cross-reaction with biliary glycoprotein I (BGP I) made possible the differentiation of HCC from metastases. We stress the importance of cell blocks as these often constitute microbiopsies. Ultrasound-guided FNA of focal liver lesions is recommended as a simple, easy and quick procedure.     

Role of fine needle aspiration cytology in evaluation of paediatric lymphadenopathy

Fine needle aspiration cytology (FNAC) in children has been slow to gain acceptance as compared with its use in adults. The aim of this retrospective study is to determine the utility of FNAC in diagnosing paediatric lymphadenopathy. Six hundred and ninety-two paediatric lymph nodes were aspirated during the period from January 1996 to June 2001. Aspirated material in 32 cases (4.6%) was deemed inadequate for cytological diagnosis. In the remaining cases, 62.2% were reactive lymphadenopathy, 25.2% tuberculous lymphadenitis, 6.3% acute suppurative lymphadenitis, nine cases revealed malignancy (seven lymphoma, two metastatic deposits) and one case had Langerhan's cell histiocytosis. No significant complications were encountered in any of the cases. FNAC emerged as a safe and reliable diagnostic procedure in paediatric age group obviating the need for excision biopsy.     

Pitfalls in the diagnosis of Wegener's granulomatosis on fine needle aspiration cytology

OBJECTIVE: To review the clinical and pathological findings in six suspected cases of Wegener's granulomatosis (WG) and highlight the diagnostic difficulties faced by the cytopathologist. METHODS: Retrospective review of records of the Cytopathology Department to identify patients who underwent image-guided transthoracic pulmonary fine needle aspiration cytology (FNAC) for pulmonary lesions of suspected WG and those who were subsequently confirmed to have WG. Detailed evaluation of cytomorphological features was carried out. RESULTS: A total of six cases were identified in whom the initial procedure to obtain a pathological diagnosis was transthoracic FNAC. In one case, atypical squamous cells on cytology initially suggested a diagnosis of squamous cell carcinoma while in another a diagnosis of WG was made on cytology; however, a subsequent lung biopsy revealed silicosis. CONCLUSION: Acute inflammation and necrosis are the most consistent cytopathological findings in WG. In selected cases FNAC can provide supportive pathological evidence to establish a diagnosis of WG.     

Audit of fine needle aspiration cytology of 120 renal lesions

Solid renal masses in 120 patients were assessed by percutaneous fine needle aspiration cytology, performed under radiographic guidance. Follow-up was obtained in all but seven cases. Diagnostic sensitivity for 83 tumours in the series was 91.6%, while two false positive reports resulted in a specificity of 93.8%. Positive and negative predictive values were 97.4% and 81.1% respectively. One advantage of the procedure was the ability to cell type neoplasms accurately, which enabled administration of pre-operative chemotherapy in childhood tumours, and selection of appropriate surgical procedures in adults. The technique offered a non-surgical means of confirming primary renal tumours in patients presenting initially with distant metastases, and documenting renal secondaries in cases with malignancy at other sites. The diagnosis of benign or inflammatory lesions permitted institution of definitive therapy.     

The role of micronucleus scoring in fine needle aspirates of ductal carcinoma of the breast

S. Samanta, P. Dey and R. Nijhawan The role of micronucleus scoring in fine needle aspirates of ductal carcinoma of the breast Aims and objectives: Micronucleus (MN) scoring was carried out in benign (fibroadenoma) and malignant (infiltrating ductal carcinoma) breast lesions to evaluate the role of MN as a biomarker in breast carcinomas. We also compared MN scores among different cytological grades of breast carcinoma. Materials and methods: A total of 31 archival cases of fibroadenoma (FA) and 40 cases of infiltrating ductal carcinoma (IDC) were selected. The best May‐Grünwald–Giemsa (MGG) stained fine needle aspiration cytology (FNAC) smear of each case was selected. The MN scoring was carried out independently by two observers on 1000 epithelial cells in oil immersion magnification (100× objective). The MN scores in FA and IDC were compared. The IDC cases were graded and the MN scores in different cytological grades of IDC were compared. Results: The mean MN scores (± standard deviation) in FA and IDC were 0.6 (± 1.1) and 13.6 (± 12.8), respectively, which were significantly different (P < 0.0001). There were seven grade 1, 13 grade 2, and 20 grade 3 IDCs. The mean MN scores (± standard deviation) of grade 1, 2 and 3 IDC were 4.3 (± 2.3), 11.95 (± 9.2) and 21.1 (± 16.7), respectively. An analysis of variance (anova ) test showed a significant difference in MN score between all the grades of IDC (P < 0.05). However, there was no significant difference between fibroadenoma and grade 1 IDC. The Pearson’s correlation coefficient showed positive correlations between MN scoring in the different grades of IDC. Conclusions: MN scoring on routinely stained smears of IDCs was significantly higher than in fibroadenoma and was relatively easy, reliable and reproducible. As MN scoring of grade 1 IDC was similar to fibroadenoma, a larger study should be conducted to compare grade 1 IDC with other benign breast lesions.     

Fine needle aspiration cytology in a case of florid gynaecomastia

A case of gynaecomastia examined by fine needle aspiration cytology is reported. The pitfalls in trying to obtain a cytological diagnosis in the florid proliferative stage of the disease are detailed together with an account of the natural history.     

Standardization of fine needle aspiration cytology of the breast – comparison of Auto Cyto Fix and conventional smears

In Japan, there are some problems with fine needle aspiration (FNA) cytology of the breast, such as insufficient smeared cells, air-drying artefact and excessive erythrocytes. Liquid-based cytology has been found to solve these problems. Equipment for such preparations has been developed, but can be expensive to purchase and operate. We developed Auto Cyto Fix 1000 (ACF), which is inexpensive and automatically smears and fixes cells. The purpose of this study was to compare the various cytological features of conventional and ACF specimens. We evaluated whether the ACF method would be able to replace the conventional method. Forty-eight FNA specimens of breast were studied. All specimens were prepared by the direct smeared (DS) and ACF methods and evaluated for unsatisfactory cell collection, air-drying artefacts, background findings and epithelial cell findings. Although ACF specimens were prepared using the cells remaining in the needle and syringe after preparing DS specimens, the cellularity of two of the ACF specimens was better than that of the corresponding DS specimens. ACF specimens never showed air-drying artefact. Unlike DS specimens, which have many erythrocytes in the background, erythrocytes were filtered out and the background of ACF specimens was clean. We believe that many problems attributable to conventional FNA specimen preparation have been solved in this study. Preparation using the ACF apparatus can reduce running costs and can be used to prepare FNA specimens of the breast for cytological examination as an alternative to the conventional method.     

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.     

Role of fine needle aspiration cytology in the diagnosis of soft tissue tumours and tumour-like lesions

In this study, we evaluated the usefulness of fine needle aspiration cytology (FNAC) in the diagnosis of soft tissue tumours. We have also assessed the various pitfalls of FNAC of soft tissue tumours. This was a retrospective study and here we analysed only 82 histopathology proven cases of FNAC of soft tissue tumours diagnosed in a five and half year period. On histopathological examination, 55 of these cases were malignant and 27 were benign. There was a total of 15 recurrences and histopathology was available prior to FNAC in only eight of these cases. Therefore, excluding these eight cases, malignant tumours were primarily diagnosed by FNAC in 47 cases. The sensitivity, specificity and positive predictive value of FNAC in diagnosis of soft tissue tumours were 91.5%, 92.5% and 95.5%, respectively. Only 22 of 47 cases (46.8%) were correctly categorized. There were two false-positive and four false-negative cases. One case each of fibromatosis and schwannoma were reported as sarcoma. False-negative cases were fibrosarcoma (1), malignant nerve sheath tumour (2) and haemangiopericytoma (1). FNAC was very useful in distinguishing benign from malignant soft tissue tumours. However, it was not so effective in exact categorization of tumours.     

Plasma cell tumours: cytomorphological features in a series of 12 cases diagnosed on fine needle aspiration cytology

U. Handa, S. Chhabra and H. Mohan
Plasma cell tumours: cytomorphological features in a series of 12 cases diagnosed on fine needle aspiration cytology Objective: Plasma cell tumours represent autonomous proliferation of plasma cells and can manifest as multiple myeloma, monoclonal gammopathy of undetermined significance, variants of plasma cell myeloma or plasmacytoma. Methods: We report 12 cases of plasma cell tumours, which were initially diagnosed as plasmacytoma on fine needle aspiration cytology (FNAC). The patients were further subjected to bone marrow examination, serum electrophoresis, urine examination for Bence–Jones proteins, and x‐ray examination of the skeleton. Results: The cytological smears from all cases were cellular and showed numerous plasma cells in varying degrees of maturity. Subsequent to investigations, five cases were labelled as multiple myeloma with secondary extramedullary plasmacytoma, three as solitary bone plasmacytoma and two as primary extramedullary plasmacytoma. In the remaining two cases, bone marrow and urine examination findings were not available, so a conclusive diagnosis of multiple myeloma or solitary plasmacytoma could not be made. Conclusion: The study highlights the role of FNAC in the diagnosis of plasma cell tumours. Subsequent work‐up and follow‐up of these patients is important to rule out the presence of multiple myeloma.     

Diagnosis of skeletal lymphoma and myeloma by radiology and fine needle aspiration cytology

Diagnosis of skeletal lymphoma and myeloma by radiology and fine needle aspiration cytology From 1986 to 1998, all patients referred to Karolinska Hospital because of a skeletal destruction of unknown origin routinely underwent radiographic examination and fine needle aspiration cytology (FNAC). Among these, there were 83 patients with solitary lesions of the bone diagnosed and treated for myeloma (plasmacytoma) or non-Hodgkin's lymphoma. Review of the series showed that myeloma could not be distinguished radiographically from lymphoma. Nor could low and high grade lymphoma lesions be discriminated by radiographic appearance. The diagnostic utility of plain radiography in the two conditions seems to be confined to the mere detection of a destructive bone lesion and visual guidance for FNAC. The latter aspect, however, is crucial for the application of FNAC to bone lesions. Review of the cytologic specimens obtained by FNAC showed that they allowed a conclusive diagnosis in all 40 myeloma cases and in 41 of 43 lymphoma cases. In 32 of the 40 myeloma cases, the FNAC material could be used for immunocytochemistry, which disclosed kappa or lambda light chain restriction, corroborating the cytomorphological diagnosis. Thirty-eight lymphomas were characterized immunologically and in 35, a light chain restriction could be demonstrated. Our results show that the use of FNAC in the diagnosis of primary myeloma and lymphoma of bone obviates the need for other diagnostic modalities, including open biopsy. A combined approach based on radiology and FNAC, performed as an out-patient procedure, offers rapid and accurate diagnosis of myeloma and lymphoma among patients with radiographically unclassified destructive bone lesions.     

Peripheral endothelial cells are not reliable in differentiating primary benign and malignant hepatocellular lesions in fine needle aspirates of the liver

The distinction of hepatocellular carcinoma (HCC) from benign lesions of the liver in fine needle aspiration (FNA) specimens can be problematic. In an attempt to separate well-differentiated HCC from benign hepatocellular lesions, the presence of tissue fragments displaying peripheral endothelial cells (PE) has been proposed in a previous study as a useful feature in favour of malignancy. In this study, we evaluated slides from 59 cases of liver masses undergoing FNA (19 HCC, 40 benign) and evaluated them for the presence of tissue fragments containing PE. We found that 90% of cases of HCC contained tissue fragments in which PE were either focally present or abundant. However, 68% of cases containing only benign hepatocytes also contained tissue fragments in which PE were at least focally present. In addition, it appears that within the group of benign lesions, the presence of PE was related to the overall cellularity of the specimen rather than the specific nature of the lesion. Thus, the presence of PE in tissue fragments does not, in isolation, appear to be a useful morphological feature for the separation of benign and malignant hepatocellular lesions in FNA material.     

Fine needle aspiration cytology of mucoepidermoid carcinoma of the thymus

Primary mucoepidermoid carcinoma of the thymus developing in an 80-year-old Japanese man is described. This is the third case report of this rare tumour which was diagnosed following fine needle aspiration cytology (FNAC) of a metastatic lesion in the left humerus. FNA showed the typical cytological findings of mucoepidermoid carcinoma, that is the presence of squamous, glandular and intermediate neoplastic cells. Histology at autopsy confirmed these findings.     

Demonstration of oestrogen receptor in symptomatic breast carcinoma, using fine needle aspiration cytology

Oestrogen receptor immunocytochemical assay (ER-ICA) was used to determine oestrogen receptor (ER) content of cells in fine needle aspirate (FNA) specimens from 88 breast carcinomas. In 49 of these the radioligand binding assay for oestradiol was available for comparison. The predictive value of ER-ICA staining for a positive radioligand binding assay (greater than 10 fmol/mg protein) was 95%. Although the predictive value of negative staining was only 66%, 34 out of 37 ER-ICA negative tumours had radioligand binding assays below 60 fmol/mg protein. ER-ICA staining showed a strong positive correlation with age of the patient, positivity being rare before the menopause. There was a weak inverse correlation with tumour grade but none with tumour size or lymph node status. The assessment of ER by immunocytochemistry using FNA cytology is a rapid technique, which may easily be repeated and provides a pre-operative assessment of ER status. It allows confirmation that tumour cells are present in the sample and an assessment of tumour heterogeneity.     

Fine needle aspiration cytology of infantile haemangioendothelioma of the liver: a report of two cases

E. Sigamani, V. K. Iyer and S. Agarwala Fine needle aspiration cytology of infantile haemangioendothelioma of the liver: a report of two cases Background: Fine needle aspiration cytology (FNAC) of infantile haemangioendothelioma of the liver (IHL) has not previously been described because routine use of FNAC is contraindicated due to the risk of bleeding. Methods and materials: Two patients presented with progressively increasing right upper quadrant abdominal mass. The index case was a girl aged two and a half years with a large single mass in the right lobe of the liver. The second was a 3‐month‐old girl in whom ultrasonography revealed multiple hypoechoic lesions in the liver. Ultrasound‐guided fine needle aspiration had been performed on both patients. May‐Grünwald‐Giemsa stained smears from these two patients were reviewed and correlated with histopathology. Results: Both aspirates showed predominantly normal hepatocytes and bile ductules amongst which tumour cells were admixed. The latter were oval to spindle‐shaped with scant cytoplasm and wavy, kinked and indented nuclear outlines. The non‐epithelial character of the tumour cells was apparent and helped to rule out hepatoblastoma. One case showed extramedullary haemopoiesis. The diagnosis of IHL was established on subsequent excision in the first case and a wedge biopsy in the second case. CD34 and factor VIII R antigen were positive in the tumour cells. Conclusion: Radiological diagnosis of IHL is possible in a majority of cases, but sometimes features may overlap with hepatoblastoma and fine needle aspiration may be performed inadvertently. Characteristic kinked nuclei and intermixed normal liver tissue might suggest IHL in the differential diagnosis of a spindle cell vasoformative tumour.     

Fine needle aspiration cytology in non-neoplastic non-toxic recurrent nodular goitre

The aim of the study was to examine whether evaluation of anisokaryosis is helpful in the cytological diagnosis of focal lesions in non-toxic recurrent goitre (NRG) after thyroidectomy for non-malignant goitre. Karyometric analysis was performed in routine cytological smears obtained from 80 females: 40 with focal lesions in non-toxic primary goitre (NPG) and 40 with NRG (postoperative histopathological examination revealed nodular goitre in both groups in all cases). We found that the level of anisokaryosis was significantly (P<0.005) higher in NRG than in NPG. There were no significant differences between the two lesions, in cellular composition or thyroid follicular cell arrangement. Thus, isolated anisokaryosis, a feature of malignancy in patients without a prior thyroidectomy, has limited diagnostic value in recurrent goitre.