Centchroman: is unsupervised long-term use warranted? Case report.

OBJECTIVES: Centchroman (Ormeloxifene) is a synthetic non-steroidal compound used as an oral and a post-coital contraceptive. It is currently under trial for treatment of breast cancer and postmenopausal osteoporosis. Centchroman has been reported to induce only minimal side effects and no hormonal imbalance. CASE: A young woman who used centchroman for a long time in an unsupervised fashion presented with menorrhagia, which was controlled with norethisterone. Her massively enlarged uterus showed extensive decidual changes in a hyperplastic endometrium, and diffuse microglandular cervical hyperplasia. CONCLUSIONS: The case suggests a prominent oestrogenic effect of centchroman on the uterus. This could be a significant adverse effect related to prolonged therapy. Lengthy intake of centchroman requires medical surveillance and long-term studies are needed.

Cartilaginous metaplasia in uterine leiomyoma.

INTRODUCTION: Leiomyoma is the most common tumor in the uterus. A spectrum of histologic variants have been noted, however, metaplasia in the leiomyoma is a rare phenomenon. Adipose metaplasia being most commonly reported. Cartilaginous metaplasia in leiomyoma is very rare. MATERIALS AND METHODS: We report first case of pure cartilaginous metaplasia in a uterine leiomyoma. CONCLUSION: Cartilaginous areas although rare, may appear in uterine leiomyoma.

Tissue reaction patterns in respiratory infections: a practical approach to a cytological diagnosis.

Infection of the respiratory tract, particularly indolent and chronic disease can be a diagnostic dilemma. Infections associated with immunosuppressive states often require an accurate early diagnosis because it impacts outcome. A wide variety of specimens, such as, sputum, bronchoalveolar lavarge (BAL), transthoracic or transbronchial fine needle aspiration (FNA) can be employed. Cytopathology is diagnostic when the causative organism can be identified failing which, direction can be given to further investigation by examination of the tissue reaction patterns. Three types of reactions seen in lung infections act as clues to the diagnosis: (a) necrosis, (b) inflammatory reactions, and (c) epithelial changes with little inflammation. Identification of tissue reaction types limits the diagnostic possibilities and facilitates the diagnostic process.

Awareness of authorship criteria and conflict: survey in a medical institution in India.

CONTEXT: Assignment of appropriate authorship on a scientific paper is important for researchers and the public; inappropriate authorship may generate conflict. OBJECTIVES: To determine the extent of: (a) awareness of criteria for authorship and acknowledgment among researchers in a medical institution, (b) conflict concerning authorship issues in the research environment, and (c) their interrelationship. DESIGN AND SETTING: A questionnaire self-administered by the faculty in a teaching hospital in India in March 2006. MAIN OUTCOME MEASURES: Rate and level of awareness of International Committee of Medical Journal Editors (ICMJE) Uniform Requirements for Manuscripts Submitted to Biomedical Journals, or other rate and level of awareness of international published authorship criteria; rate and type of authorship conflict. RESULTS: Ninety-five teaching faculty were contacted; 77 responded. Fifty respondents (65%) reported that they were aware that authorship criteria existed, but only 34 (44%) correctly identified a source. Overall, 30 (39%) respondents reported conflict over authorship issues relating mainly to ownership of data, gift authorship, and issues like academic competition, personality differences, intellectual passion, or order of authorship. There was no difference between number of authorship criteria correctly identified by respondents who reported conflict compared with those who did not (P = .78). CONCLUSIONS: There was poor awareness of criteria for authorship and acknowledgement among the faculty in research publications. Conflict over authorship issues existed in the research environment, but was not influenced by the level of awareness.

Algorithm for cytological diagnosis of nonneoplastic lesions of the salivary glands.

The aim of this study was to formulate an algorithm for the cytologic diagnosis of nonneoplastic enlargements of the salivary gland.Smear cellularity and cytological features such as presence of epithelial cells and types of inflammation were assessed in a retrospective study of 201 aspirates. One hundred and forty-six were inflammatory, 19 were noninflammatory nonneoplastic, and 36 were cystic lesions. Of the cystic lesions, cytological evidence of retention cyst was seen in seven, while two aspirates with only hemosiderin-laden macrophages were hematomas. The remaining 27 defied subclassification. Noninflammatorynonneoplastic lesions included 5 fatty infiltrations, 2 sialadenosis, and 12 normal salivary glands. Forty-two lesions were acute inflammations, 89 were chronic, and 15 were granulomatous. Cytomorphologic patterns identified in samples with acute inflammation were 9 abscesses, 29 acute obstructive sialadenitis, and 4 acute infective sialadenitis. Three aspirates with chronic inflammation were lymphoepithelial lesions, 82 chronic sialadenitis, and 4 lymph node in salivary gland. Fifteen granulomatous lesions were 10 tuberculosis, 3 sarcoidosis, and 2 foreign body granulomas. Using the proposed algorithmic approach, nonneoplastic salivary gland enlargement could be placed into distinct, clinically relevant diagnostic categories.

Metastatic extraocular sebaceous carcinoma with an occult primary.

The cytological diagnosis of sebaceous carcinoma is based on the aspiration of tumor lobules with extensive sebaceous differentiation. However, these tumors may show a spectrum of cells ranging from basaloid to well-differentiated sebaceous. Extraocular sebaceous carcinoma is an uncommon tumor. An occult primary at initial presentation has not been described previously. A 60-yr old woman was referred to the fine-needle aspiration (FNA) clinic with a submandibular mass. The cytological diagnosis was mucoepidermoid carcinoma. Histopathologically, it was a sebaceous carcinoma metastatic to the submandibular lymph node. No primary tumor was identified. Six months later, she presented with a nodule at the angle of her mouth and a recurrence of the submandibular swelling. FNA cytology (FNAC) and histopathologic examination revealed a primary cutaneous sebaceous carcinoma with submandibular lymph node metastasis. A metastatic sebaceous carcinoma in the submandibular region with limited sebaceous differentiation and occult primary is another pitfall in the cytomorphological diagnosis of mucoepidermoid carcinoma.

Cytopathology of chalazia.

Chalazion is a common inflammatory condition of the eyelid, usually treated on the basis of clinical diagnosis alone. Preoperative exclusion of malignancy in chalazia with atypical clinical presentation could prevent unwarranted surgery. This is a retrospective study of aspirates from 16 patients with chalazia having an atypical clinical presentation. Smears were stained with May-Grünwald Giemsa. Two broad patterns of granulomatous inflammation reflecting the spectrum of changes in the course of the disease were seen. Nine smears had mixed-cell granulomas consisting of neutrophils, lymphocytes, plasma cells, macrophages, giant cells, and granulation tissue. Seven smears had suppurating granulomas characterized by epithelioid cell granulomas with numerous neutrophils in a proteinaceous background. Fine-needle aspiration cytology of chalazia with atypical clinical presentation provides a rapid, safe, and reliable means of documenting the diagnosis and excluding malignancy.

Aspiration cytology diagnosis of a primary amyloid tumor of thoracic vertebra: a case report.

Isolated primary amyloid tumor of bone is rare; however, preoperative diagnosis can be rewarding because the prognosis is excellent. There are no clinical or roentgenographic criteria that can establish this diagnosis. There are few previous reports of fine-needle aspiration (FNA) where diagnosis of amyloidoma was made retrospectively. They describe the presence of extracellular hyaline material along with plasma cells and lymphocytes. A 35-year-old female was referred to the FNA clinic with swelling in the right upper chest wall. Radiologic findings revealed a destructive lytic lesion involving the bodies of D1 and D2 vertebrae with extension into surrounding soft tissue. Repeated FNA smears were hypocellular but had abundant homogeneous flocculent material, which stained positive with Congo red. A few plasma cells and foreign-body giant cells were also seen. We conclude that preoperative FNA cytology diagnosis of amyloid tumor is possible. Hypocellular smears with flocculent material, plasma cells, and foreign-body giant cells in absence of granulation tissue should suggest the diagnosis.

Pitfalls in the cytological classification of borderline leprosy in the Ridley-Jopling scale.

This is a blinded, retrospective, correlative study of classification of leprosy by cytomorphology, clinical examination, and bacterial density. One hundred consecutive adequate aspirates from skin lesions of leprosy were studied. The Ridley-Jopling (R-J) five-group classification system was used. May-Gruenwald-Giemsa (MGG) and Ziehl-Neelsen (Z-N) stains were employed. Complete clinical, cytological, and bacteriological concordance was found in 88 patients. One-step mismatch in classification was seen in 12 patients with cytomorphological features of borderline-borderline (BB/mid-borderline) leprosy. Cytomorphological features of BB leprosy in aspirates from skin lesions should alert the cytopathologist to the possibility that the bacteriological index (BI) may vary widely. Appropriate steps must be taken to ensure accurate reporting of BI.

Fine needle aspiration cytology of leprous neuritis.

OBJECTIVE: To document the cytomorphologic features of leprous neuritis and their correlation with bacterial density. STUDY DESIGN: A partly retrospective, partly prospective study of the fine needle aspiration cytology of enlarged nerves in leprosy. Cytomorphologic features of nerve aspirates from 28 patients were studied. May-Grünwald-Geimsa and Ziehl-Neelsen staining methods were employed. RESULTS: Five cytomorphologic patterns were observed in smears of nerve aspirates in 19 group I patients with concurrent skin and nerve lesions: (1) inflammation composed of epithelioid cell granulomas (5), bacillary index (BI) = 0; (2) epithelioid cell granulomas with necrosis (5), BI = 0-1+; (3) acellular necrosis (5), BI = 0-4+; (4) macrophage granuloma (3), BI = 5-6+; and (5) granulation tissue (1), BI = 1+. In 9 group II patients with pure neuritic leprosy, 3 patterns were seen: (1) epithelioid cell granulomas (5), BI 0-6+; (2) epithelioid granulomas with necrosis (1), BI = 0; and (3) acellular necrosis (3), BI = 0-6+. CONCLUSION: The entire spectrum of leprosy is seen in nerve aspirates. Necrosis is often a prominent feature. Recognition of the range of cytomorphologic patterns and their correlation with BI contribute to accurate calibration of the disease in nerves, resulting in appropriate choice of treatment.

Significance of cytologic criteria in distinguishing small cell from non-small cell carcinoma of the lung.

OBJECTIVE: To study the significance of cytologic features in distinguishing small cell carcinoma (SCC) from non-small cell carcinoma (NSCC). STUDY DESIGN: Prospective study of 76 patients with lung carcinoma. Percutaneous fine needle aspiration and bronchial washings stained with Papanicolaou and May-Grünwald-Giemsa stain were used for categorization of tumors according to the World Health Organization classification. Each tumor was also scored for the presence or absence of standard cytologic criteria used in the diagnosis of SCC. Data were analyzed for sensitivity, specificity and significance using the chi 2 and Fisher exact tests. Undifferentiated and unclassified tumors were examined immunocytochemically for the presence of neuron-specific enolase, epithelial membrane antigen and leukocyte common antigen. Cytologic diagnoses were compared with histopathologic diagnoses. RESULTS: Seventy-six lesions classified on cytomorphology consisted of SCC (15), NSCC (50), non-Hodgkin's lymphoma (1), carcinoid (1) and undifferentiated or poorly differentiated carcinomas (9), 2 of which showed nuclear molding and salt-and-pepper chromatin. Immunocytochemistry and biopsy confirmed the diagnosis of SCC in those two patients. CONCLUSION: Nuclear molding, cell size and scant, basophilic cytoplasm were highly sensitive and specific by univariate analysis for distinguishing SCC from NSCC. Other features, such as salt-and-pepper chromatin, crush artifact and apoptotic bodies, also had significantly high specificity; however, their low sensitivity precluded their usefulness in separating SCC from NSCC. Thus, morphologic evaluation plays a major role, while immunocytochemistry can make a limited contribution in differentiating SCC from NSCC.

Exploring the links between quality assurance and laboratory resources. An audit-based study.

OBJECTIVE: To investigate and rectify the problems related to Ziehl-Neelsen (Z-N) staining in a cytology laboratory in the context of quality assurance. STUDY DESIGN: An audit based quality assurance study of 1,421 patients with clinical diagnoses of tubercular lymphadenopathy who underwent fine needle aspiration cytology. Data from 8 months were audited (group 1). Laboratory practices related to selection of smears for Z-N staining were studied. A 2-step corrective measure based on results of the audit was introduced for 2 months (group 2). Results were subjected to statistical analysis using the chi 2 test. RESULTS: Of 1,172 patients in group 1,368 had diagnoses other than tuberculosis. Overall acid-fast bacillus (AFB) positivity was 42%. AFB positivity in 249 patients in group 2 was 89% (P < .0001). CONCLUSION: Several issues in the laboratory are linked to quality assurance. Solving everyday problems can have far-reaching benefits for the performance of laboratory personnel, resources and work flow.

Cytology of testicular changes in leprosy.

OBJECTIVE: To study the changes in testicular aspirates and semen of patients with leprosy. STUDY DESIGN: A prospective study of 56 patients in the reproductive-age group, with no record of treatment for leprosy. Both Ridley-Jopling and WHO classification systems were used. Skin and/or nerve biopsies were performed for documentation of the diagnosis. Semen analysis and fine needle aspirates of the testes were performed. Smears from the testicular aspirates were stained with May-Grünwald-Giemsa and Ziehl-Neelsen stain. RESULTS: Five patients were unable to produce an ejaculate. Abnormal semen analysis and/or testicular aspirates were seen in 24 (42.8%) patients. Eleven had oligospermia and eight azoospermia. Abnormalities in testicular aspirates ranged from hypospermatogenesis (4) through maturation arrest (1) and atrophy (11). Two patients had hydrocoele, and two had associated microfilariae. Three patients with multibacillary leprosy had type 2 reaction. Mycobacterium lepre was demonstrable in testicular aspirates from all patients with multibacillary and in three with paucibacillary leprosy. CONCLUSION: Abnormal semen analysis and/or testicular aspirates occur in a very high percentage of patients with leprosy. While this is expected for multibacillary disease, the high incidence in the paucibacillary form was surprising. With the rapid elimination of leprosy, fertility-related disability might emerge as a major problem in these people.

Implementation of the bethesda system for reporting thyroid cytopathology: interobserver concordance and reclassification of previously inconclusive aspirates.

Standardized diagnostic terminology was introduced by the Bethesda System for Reporting Thyroid Cytopathology (BSRTC) in an effort to bring uniformity to the reporting of thyroid cytopathology, provide more defined categories to enable clinical management, and minimize the number of inconclusive cases. Previous studies indicate that the BSRTC is a reliable and valid reporting system for thyroid cytology. This study was conducted to compare the concordance between observers with varying cytopathology experience when using the BSRTC, and to assess the impact on the number of inconclusive reports. A retrospective study was conducted in two parts. In the first part 415 thyroid aspirates were reviewed independently by three observers with different experience levels. The aspirates were reclassified according to BSRTC and agreement scores were calculated using kappa statistics. In the second part 39 inconclusive aspirates signed out previously, were recategorized according to BSRTC. Agreement level between the three observers using the BSRTC was strong (Fleiss' kappa score = 0.6561). Inconclusive cases could be categorized further with BSRTC; there was significant reduction in the number of inconclusive diagnoses (P < 0.001). Strong interobserver agreement with BSRTC indicates the ease with which the new system can be applied in regular reporting. Significant reduction in the number of inconclusive diagnoses results in better communication with the clinician and improved risk assessment for thyroid aspirates.

Clinical audit of repeat fine needle aspiration in a general cytopathology service.

BACKGROUND: The few studies on repeat aspiration focussed on accuracy of diagnosis following repeat. Numbers and documented reasons for repeat remain unaddressed. AIM: To study factors associated with requests for repeat fine needle aspiration cytology (FNAC). SETTINGS AND DESIGN: Metropolitan hospital, clinical audit. MATERIALS AND METHODS: Audit of 5104 FNAC in 10 months. STATISTICAL ANALYSIS USED: Univariate, and multivariate binary logistic regression. RESULTS: Seven hundred and six patients (13.8%) were advised repeat aspirates. Three hundred and twelve of these were actually repeated (44.1%). Carryover of actually repeated aspirates to subsequent months averaged 10.8 (34.2%). Maximum numbers of repeat requests were from thyroid 76/415 (18.3%), followed by lymph node 310/1856 (16.7%), and from breast 86/716 (12.0%). Outcome of actually repeated aspirates were: Diagnostic 181/312 (58.0%), and non-diagnostic 131/312 (41.9%). Reasons for repeat were inadequate aspirates 370/706 (52.4%), non-diagnostic descriptive reports 309/706 (43.7%); in 27/706 (3.8%), no reason was mentioned. CONCLUSIONS: Inadequate aspirates, non-diagnostic descriptive reports, and FNAC/FNAB from thyroid, lymph nodes, and breast contribute to repeats. We suggest steps to reduce the number of repeat aspirates to eliminate extra work.

Immunocytochemical detection of mycobacterial antigen in extrapulmonary tuberculosis.

The aim of the study is to determine whether immunostaining for mycobacterial antigen can contribute to the cytological diagnosis of extrapulmonary tuberculosis (EPTB). The study was carried out on aspirated material of lymph nodes, and other accessible sites, from 65 patients with clinical diagnosis of tuberculosis (TB). Twenty patients, diagnosed by fine-needle aspiration, with non-tuberculous granulomas served as controls. The diagnosis of TB was based on the demonstration of acid-fast bacilli (AFB), culture positivity for Mycobacterium tuberculosis (M. tuberculosis), or response to treatment with standard anti-tubercular therapy. Immunostaining was done using polyclonal antibody to mycobacteria. AFB positivity by Ziehl Neelsen (ZN) staining was 21%, 65.38%, and 68% respectively in Pattern 1 (granulomas alone), in Pattern 2 (granulomas with necrosis), and in Pattern 3 (necrosis alone). Overall AFB positivity was 56.92%. Twenty-eight of 65 cases were negative for AFB on direct smear. Culture was positive in 46% (13/28). Sensitivity and specificity of immunostaining were 96.92% (63/65) and 95%, respectively. Immunoreactivity was seen in 26 (92.8%) of 28 cases which were negative by ZN staining. Except in the case of leprosy, in which cross reactivity was seen, there was no immunoreactivity in the control group. Immunocytochemistry (ICC) had high sensitivity (96.2%) and specificity (95%) in the diagnosis of EPTB. ICC may be a useful adjunct to evaluation of cytomorphology and ZN staining.

Mentoring for first year medical students: humanising medical education.

New entrants are vulnerable to the challenges of the medical course; mentoring programmes are known to offer support. This paper evaluated the experiences of students and faculty enrolled in a new mentoring programme. After needs analysis of students and faculty, a small-group mentoring programme for new medical students was initiated. Fifty-five volunteer faculty mentors were allocated two-three students each. At year-end, feedback using an open-ended questionnaire, revealed that there was no contact in one-third of the cases; the commonest reasons cited were lack of mentee initiative, time and commitment. Supportive mentors were appreciated. Over 95% of respondents believed that mentoring was a good idea; many believed the mentee benefitted; mentors also reported improved communication and affective skills; 60 (77.0%) mentees wanted to mentor new students the following year. Thus, mentoring of first-year students by faculty was effective, when contact occurred, in making the mentee feel supported. Mentoring may be a means of honing the affective domain and humanitarian instincts of medical faculty and students.

Cytokeratin-20 immunocytochemistry in voided urine cytology and its comparison with nuclear matrix protein-22 and urine cytology in the detection of urothelial carcinoma.

This study was done on 59 subjects (42 urinary bladder carcinoma patients and 17 non-neoplastic controls). Urine cytology and bladder chek NMP22 test was done on all cases. CK20 immunostaining was performed on archived papanicolaou stained urine cytology smears in 34 cases (27 bladder carcinoma and 7 negative controls). Results of all three tests (cytology, NMP22, and CK20 immunostaining) were compared with histopathology to evaluate the accuracy of individual test. The combination of cytology and NMP22 was compared with combination of cytology and CK20 immunostaining for detection of bladder carcinoma. NMP22 had sensitivity of 92.9% and specificity of 70.6%, as compared with voided urine cytology (sensitivity of 76.2% and specificity of 76.5%) and CK20 immunostaining (sensitivity of 70.4% and specificity of 71.4%). Combination of cytology and NMP22 gave better results (sensitivity of 88.1% and specificity of 88.2%) than combination of cytology and CK20 immunostaining or any other test in isolation.