Gastrointestinal stromal tumors: Cytomorphologic spectrum in fine needle aspiration smears.

Objective: To study the variation in the cytologic features of gastrointestinal stromal tumors (GISTs) at different sites targeted by different modalities. Study design: Cytologic smears of 9 cases of gastrointestinal stromal tumors were reviewed with their histopathologic follow-up. Immuno-cytochemistry was performed where possible. Results: The study includes eight males and one female patient with an age range of 42 to 71 years. There were four classical cases of gastrointestinal stromal tumors that showed tight cellular bundles and fascicles of slender spindle cells with scant cytoplasm. The cytological features of three recurrent and one malignant case included moderately to markedly pleomorphic, plump spindle to ovoid cells with variable chromatin pattern and variable pale blue to vacuolated cytoplasm, present in loose clusters and singly. There was one case with classical gastrointestinal stromal tumor cytology but myxoid stroma. All other cases were confirmed with either CD117 immunostain and/or histopathology. Benign mucosal fragments from stomach or duodenal mucosa were observed in smears obtained by endoscopic ultrasound - fine needle aspiration (EUS FNA). Conclusion: The variability in cytologic features in GIST implies that a diagnosis of gastrointestinal stromal tumor should be rendered on cytology only in conjunction with immune-cytochemistry result of CD117.

Comparative evaluation of smear cytology & hybrid capture II for the diagnosis of cervical cancer.

BACKGROUND & OBJECTIVES: There is no ideal screening method for cervical cancer in India with the role of human papilloma virus (HPV) detection yet to be established. This study was undertaken to compare the diagnostic accuracy of HPV testing by hybrid capture II (HC-II) with conventional cervical smear cytology for squamous intraepithelial lesions (SIL). METHODS: This prospective study was conducted at New Delhi during 2003-2004 with patients selected from the gynaecology out patients of the All India Institute of Medical Sciences. Initial screening by a questionnaire and per-speculum examination were used to select high-risk patients. Patients, in whom conventional cytology, HC-II test and colposcopy-directed biopsy were done, formed the basis of this study. RESULTS: Of the 133 patients included in the study, incidence on biopsy of low grade SIL (L-SIL) was 6.77 per cent, high grade SIL (H-SIL) was 8.27 per cent and carcinoma was 3.00 per cent. Sensitivity and specificity of cytology for detection of H-SIL and above lesions was 93.33 and 83.49 per cent while for HC-II it was 93.33 and 90.83 per cent, respectively. HC-II had higher diagnostic accuracy of 91.13 per cent versus 84.68 per cent for cytology. Kappa for HC-II was higher (0.67) than cytology (0.52). Among patients diagnosed to have atypical squamous cells (ASC-US & ASC-H) and L-SIL, HC-II helped to select patients who had significant lesions on biopsy. INTERPRETATION & CONCLUSION: The main utility of HC-II is in the triage of patients with cytology smear diagnosis of ASC-US, ASC-H or L-SIL, for referral to colposcopic examination. HC-II alone has the best diagnostic accuracy but owing to high cost it is unsuitable for general screening in developing countries. Combining HC-II with cytology will refer smaller numbers for colposcopy,improving efficient utilization of available resources.

Evaluation of adjunctive tests for cervical cancer screening in low resource settings.

BACKGROUND: Visual inspection of cervix after application of acetic acid (VIA) is an effective screening tool for cervical cancer in low resource settings, but its low specificity leads to high referral rates. Adjunctive testing may overcome this drawback. AIMS: This pilot study was aimed to assess test performances of VIA, human papillomavirus (HPV) testing and Pap smear, individually and in simulated combinations, to determine the probable best screening option. SETTING AND DESIGN: Gynecology outpatient department (OPD); cross-sectional study. MATERIALS AND METHODS: One hundred women with complaints of irregular vaginal bleeding or discharge, post coital bleeding or unhealthy cervix on examination underwent Pap smear, HPV testing, VIA, colposcopy and biopsy, if indicated, in this screening order. STATISTICAL ANALYSIS: Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for each of the tests with a biopsy result of > or =HSIL taken as the gold standard. Simulated parallel and sequential combinations for VIA/Pap, VIA/HPV and HPV/Pap were calculated and compared with individual test performance. RESULTS: Prevalence of abnormal Pap smears was 5%, VIA positive 51% and HPV positive 16%. Sensitivity and specificity of VIA were 100% and 53.3% respectively. For HPV and Pap tests corresponding figures were 85.7%, 89.7% and 50%, 98.9% respectively. The best simulated combination with a balance of sensitivity and specificity was of VIA followed by HPV testing (sensitivity 85.7%, specificity 95.4%). CONCLUSION: Addition of HPV testing to VIA can increase the specificity of VIA, thereby reducing the referral rates without compromising the sensitivity of the test.

Diagnosis and grading of non-Hodgkin's lymphomas on fine needle aspiration cytology.

Fine needle aspiration cytology (FNAC) enjoys popularity among clinicians worldwide, as a first line of investigation in all patients with lymphadenopathy and is preferred over biopsy because of its minimally invasive nature and cost-effectiveness. Although non-Hodgkin's lymphomas (NHL) are conventionally diagnosed and graded on biopsy specimens, it may be useful to be able to not only diagnose but also grade these cases on FNAC smears. The WHO and REAL classifications forming the basis of treatment in some centres rely on clinical features, immunocytochemistry and cytogenetics, which are beyond reach of most centres in the developing countries. This study therefore is aimed at diagnosing and grading NHLs on morphological parameters. The cytologic grading accuracy is compared with the histologic grades assigned according to the International Working Formulation (IWF) system which relies solely on morphological features, most important of which is cell size. Ninety five cases were retrieved over a 3 year period (May 2000 to April 2003). These were (i) cases where a cytological diagnosis of NHL or suspicious of NHL was made and corresponding histological sections available and (ii) cases where a diagnosis of NHL was made in histology and corresponding FNAC smears were available irrespective of the cytological diagnosis. The diagnostic accuracy of FNAC for NHLs was determined using histology as the gold standard. Cases were also graded on FNAC smears using a three tier grading system based upon cell size into low, intermediate and high grades. Cytologically assigned grades were correlated with the corresponding histological grades (IWF) to determine grading accuracy. An accurate diagnosis of NHL was thus possible in 67/95 (70.5%) cases. Overall accurate grading was seen in 65/95 (68%) cases using cytological criteria. Accurate cytologic grading was possible in 14/15 (93.33%) low grade, 11/18 (61.11%) intermediate and 40/62 (64.5%) high grade non Hodgkin's lymphomas. Kappa statistics revealed a very good agreement between cytological and histological grades for low grade NHL. The kappa scores for intermediate and high grade NHLs indicated moderate agreement. Using the two-tier system grading the kappa value for high grade lymphomas improved to 0.72, indicating good concordance. This study highlights the utility of FNAC as a morphological tool for diagnosing and grading NHLs in a significant number of cases. This modality may assist clinicians in management of cases of NHLs, especially in centres working within the constraints of limited availability or non availability of ancillary techniques.

Value of scoring system in classification of proliferative breast disease on fine needle aspiration cytology.

Fine-needle aspiration (FNA) cytology is successful in identification of benign and malignant breast lesions, but its role in proliferative breast lesions which increase cancer risk is poorly defined. We have analyzed the cytomorphologic features of proliferative breast lesions in conjunction with cytologic scoring system proposed by Masood et al and with histopathology. Sixty two patients (14 cases of fibroadenoma, 15 cases of fibroadenoma with atypia, 11 cases of proliferative breast disease (PBD), 8 cases of PBD with atypia and 14 cases of carcinoma) diagnosed on routine FNA were subjected to scoring following Masood's criteria. All cases with the cytologic diagnosis of fibroadenoma were confirmed on histology. Of 11 cases of PBD on FNA, 10 were PBD without atypia on histology. One case, which showed atypical hyperplasia on histology, was missed by both the scoring system and cytomorphology and one case was over-diagnosed as PBD with atypia by the scoring system. FNA cytology correctly identified all the carcinoma cases, while the scoring system under-diagnosed 2 cases as PBD with atypia. Hence, in cases not suspected to be atypical or confirmed to be cancer on routine cytology, scoring added no information over and above cytomorphology and was not useful. All fourteen cases of fibroadenoma with atypia suspected on routine cytology were fibroadenoma on histology. Scoring system correctly placed 11/14 of these cases as PBD without atypia. Similarly 3/8 cases thought to be PBD with atypia were correctly placed as PBD without atypia by scoring. Only 2/8 cases thought to be PBD with atypia on cytology were confirmed to have atypical hyperplasia on histology. Scoring improved the diagnostic yield to 2/5. Hence, in cases of fibroadenoma or PBD, suspected on FNAC to have cytological atypia, Masood scoring gives additional information by eliminating benign cases and improving diagnostic yield. Application of scoring in a step-wise manner, on atypical aspirates, can help in selection of cases suitable for biopsy.

Utility of galectin 3 expression in thyroid aspirates as a diagnostic marker in differentiating benign from malignant thyroid neoplasms.

Galectin-3 is a 31kD beta-galactoside binding lectin, which is known to be expressed in various neoplasms including thyroid tumors. This study was conducted to study the role of galectin-3 in differentiating benign from malignant thyroid nodules onfine needle aspirates (FNAC). Galectin-3 immuocytochemistry was performed in 70 cases with adequate smears. The cytology diagnosis of these cases was: papillary carcinoma (25), follicular neoplasm (16), adenomatous goiter (20), hyperplastic nodule (5), medullary carcinoma (5) and anaplastic carcinoma (1). Galectin-3 positivity was seen in 80% of papillary carcinomas, 37.5% offollicular neoplasms and in 60% of benign nodules. The single case of anaplastic carcinoma was positive but all the cases of medullary carcinoma were negativefor galectin-3. Three of thefollicular neoplasms that were diagnosed on histology as carcinoma were positive on cytology and one case offollicular adenoma was also positive. Our study shows that galectin-3 is strongly expressed in smears of papillary carcinoma. However, since it is also expressed in a variety of benign lesions, its role as a pre-surgical markerfor differentiating benignfrom malignant thyroid nodules is limited.

Diagnosis of Pneumocystis pneumonia by bronchoalveolar lavage cytology: experience at a tertiary care centre in India.

BACKGROUND: Diagnosis of Pneumocystis pneumonia requires morphological demostration of P. carinii (now re-named as P. jiroveci). Although bronchoalveolar lavage (BAL) fluid cytology constitutes a formidable tool for detecting this infection, few studies on the utility of BAL cytology in diagnosing PCP are available from India. The present study reports the clinical spectrum, cytomorphological features and the utility of BAL cytology in diagnosing Pneumocystis infection from a tertiary care centre in India. METHODS: Retrospective study of 13 patients with PCP, diagnosed on examination of BAL fluid. RESULTS: The mean age of the patients was 41.2 years. One patient had human immunodeficiency virus (HIV) infection, while the other 10 were renal transplant receipients on immunosuppressive therapy. The immune status of two patients was unknown. Fever, cough and shortness of breath were the main presenting symptoms. Radiological diagnosis of Pneumocystis pneumonia was offered in only one case. Foamy alveolar casts were present in all cases. Silver methanamine stain enhanced the rounded, helmet or cleft forms of sporozoites. Inflammatory infiltrate was mainly polymorphonuclear. CONCLUSIONS: BAL cytology, thus, constitutes a useful diagnostic modality for morphological documentation and reliable diagnosis of Pneumocystis pneumonia in an immunocompromised host. Pneumocystis pneumonia appears to be a common opportunistic infection in renal transplant receipients in India.

Pseudoangiomatous stromal hyperplasia of the breast-cytological features of two cases and review of literature.

Pseudoangiomatous stromal hyperplasia (PASH) of the breast is a lesion characterized on histology by the presence of anastomosing slit like spaces embedded in a hyalinized fibrous stroma. Till date, the cytological features of PASH have been described in only 12 cases, of which two cases were diagnosed on aspiration cytology as suspicious for carcinoma and in one case, for phyllodes tumor. We describe the FNAC findings of two of our cases of PASH. The first case was diagnosed as a phyllodes tumor and the other case as a benign proliferative breast disease, possibly a fibroadenoma. A review of the published literature on cytology of PASH shows the morphological variations that can exist in the cytology smears of this lesion. FNAC findings of PASH are non-specific, and the role of FNAC in PASH is to confirm the benign nature of the lesion, rather than provide a definitive pre-surgical diagnosis.

Role of fine needle aspiration cytology in the diagnosis of goiter.

Enlargement of the thyroid gland is a common occurrence in most parts of the world especially in the iodine-deficient goiter belt areas. Vast majority of these lesions are benign but they invariably lead to a series of investigations among which FNAC plays a pivotal role. Although many studies have reported diagnostic accuracy of FNAC in detecting neoplasms, there have been few studies where the role of FNAC in the diagnosis of goiter along with their diagnostic pitfalls has been evaluated. The present study was undertaken to assess the accuracy of FNAC in diagnosis of goiter and to highlight its limitations and diagnostic pitfalls. 771 cases over a five-year period were retrieved from the files of Cytopathology Laboratory, Department of Pathology at the All India Institute of Medical Sciences, New Delhi. They included 733 cases where the cytological diagnosis was goiter or suggestive of goiter along with 38 cases in which the histological diagnosis was goiter while the cytological diagnosis was cystic change or neoplasm. FNAC with minimum of two passes were performed in each case and May Grünwald Giemsa and Papanicolaou stains were done. Histology was available in 192 cases. The cytological and histological concordance was determined and the FNAC smears and histological sections in cases showing discordance were reviewed. There was cytological and histological concordance 130/168 (77.38%) cases. In 34 cases (20.23%) no diagnosis could be offered because of cystic change. A false positive cytologic diagnosis of neoplasm was made in 4 cases. Presence of hurthle cell metaplasia, hyperplastic nodules and papillary hyperplasias were responsible for the false positive diagnoses. In 24 cases neoplasms were initially missed on FNAC of which 10 cases could be detected on review while 5 cases were considered unsatisfactory. Sampling errors were mainly responsible for these false negative diagnoses. FNAC is thus an accurate and reliable diagnostic tool for management of goiters provided strict adherence to adequacy criteria are maintained.

Adenomyoepithelioma of the breast: a potential diagnostic pitfall on fine needle aspiration cytology.

Adenomyoepithelioma is a rare myoepithelial cell-rich tumour of the breast. We report a case of adenomyoepithelioma in a 60-year-old female, where it evoked the suspicion of a carcinoma on fine needle aspiration cytology (FNAC) smears and also review the literature on FNAC diagnosis of this rare tumour.

Malignant melanoma of soft parts a diagnostic pitfall in FNA: a case report.

Malignant melanoma of soft parts (MMSP) is a rare tumour with frequent local recurrences and eventual nodal and distant metastasis. It has characteristic clinical features and histologic picture. However, a precise diagnosis of this tumor may be difficult on aspiration material. We report two cases of MMSP which posed a diagnostic dilemma owing to their variable cytomorphological features and make an attempt to review the literature.

Comparative evaluation of grading of breast carcinomas in fine needle aspirates by two methods.

BACKGROUND & OBJECTIVES: Fine needle aspiration (FNA) material is increasingly being used to determine various prognostic parameters in patients with carcinoma breast. It was recommended that cytological grading should be part of all FNA reports of breast carcinoma so that preoperative prognostication could be done on it. However, the most reliable method for cytological grading that closely reflects the most widely used histological grading system is yet to be determined. This study was undertaken to compare results of two cytological grading methods to see which corresponded better to the histological grade. METHODS: In a double-blind study, cytological grading of 52 patients with breast carcinoma was carried out using two different grading systems (Robinson's and Mouriquand's methods) and the grades compared with the histological grading to find out which reflected histological grades more closely. RESULTS: By Robinson's method 28.8, 46.2 and 25 per cent aspirates were graded as I, II and III respectively. Using Mouriquand's grading 9.6, 69.2 and 21.2 per cent aspirates were graded correspondingly. Comparison of the two methods showed a concordance in 40 (76.9%) cases. Both cytological grading systems showed a concordance of 71.2 per cent with the histological grading. Robinson's cytological grading showed a diagnostic accuracy of 80.76 per cent with 77.77 per cent specificity while Mouriquand's method had an accuracy of 84.60 per cent with 33.33 per cent specificity. INTERPRETATION & CONCLUSION: Though the Robinson's and Mouriquand's grading systems were found to have similar concordance with histological grading, Robinson's method was considered better because of its simplicity, and specificity.

Rapid staining using toluidine blue: a reliable method for quick diagnosis in ultrasound-guided aspiration cytology.

Rapid staining of ultrasound guided aspirates is an accepted procedure for evaluation of adequacy and rapid diagnosis (RD). We have assessed the reliability of Toluidine blue stain in this regard, which has not been previously reported. 295 ultrasound guided aspirates performed over a 13 month period were studied. 59 aspirates were inadequate for RD. 103 cases were called malignant on RD of which 101 were confirmed, and 2 cases were considered highly suspicious on final diagnosis. Of 34 cases considered suspicious on RD, 32 were either signed out as malignant or considered highly suspicious while 2 cases were benign. Of 56 cases considered benign on RD, 49 were confirmed, 2 were suspicious for malignancy and 5 cases had inadequate material on final diagnosis. All 43 inflammatory lesions on RD were confirmed. The overall sensitivity for a malignant/suspicious for malignancy diagnosis was 98.54% on RD while specificity was 97.99%. Sensitivity and specificity for an inflammatory condition was 100%. Toluidine blue staining is not only a reliable method for rapid staining and diagnosis, it also permits preservation of cytological material by destaining and restaining with permanent stains.

Cytomorphology of polymorphous low grade adenocarcinoma--diagnosis and pitfalls.

Polymorphous Low Grade Adenocarcinoma (PLGA) arises characteristically in the minor salivary glands. Histological diagnosis of this tumour has improved following awareness and well characterized histologic features. However cytologic diagnosis is difficult. Ten cases of PLGA were identified on review of 61 cases of palatal salivary gland tumours aspirated over a 17 year period. Seven of these had been diagnosed as salivary gland tumours but had not been further characterized, while two cases had been diagnosed as adenoid cystic carcinoma initially. In only one case a differential diagnosis between pleomorphic adenoma and PLGA had been considered. Cytologic diagnosis of PLGA is difficult but possible if an attempt is made to identify specific cytologic criteria.

Fine needle aspiration cytology of epithelioid variant of schwannoma--a diagnostic dilemma.

Epithelioid variant of schwannoma is a rare type of benign nerve sheath tumor which has an aggressive clinical course in comparison to the conventional schwannoma. We report one such case in a 53 year old female with an aspirate from a swelling in the nape of the neck. It posed a diagnostic dilemma because of its cellularity numerous groups of plump epithelioid cells along with multinucleated cells. The cells were lying in a myxoid stroma, coming singly and in nests and cords thus mimicking an epithelial tumor. The initial cytologic diagnosis of possibly a skin adnexal tumor was rendered. This case highlights the diagnostic pitfall encountered in the aspiration cytology of neurogenic tumors.

Aspiration cytology for diagnosis of tuberculosis--perspectives in India.

Tuberculosis (TB) a common cause of mortality can readily be diagnosed by fine needle aspiration. The technique is a simple, cost effective, out patient procedure with a high diagnostic accuracy both in adults and children. The diagnostic morphologic findings comprise of epithelioid cell granulomas and giant cells with or without necrosis. Often an acute inflammatory exudate is obtained. Stain for acid fast bacilli immensely augments diagnosis especially in cases where necrosis or an inflammatory exudate is obtained. Culture studies on aspirated material are time consuming though diagnosis is enhanced. PCR can be applied to detect mycobacterial DNA and has been applied on aspirated material and found to be more sensitive in the detection of tuberculosis. In children TB of lymph nodes is readily identified and so also from other sites such as bone and soft tissues. In children FNAC also plays a role in detection of BCG adenitis, infection with atypical mycobacteria and co-existing infections such as HIV and AIDS.