Journal of Cytology
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   Table of Contents - Current issue
Coverpage
July-September 2018
Volume 35 | Issue 3
Page Nos. 131-194

Online since Thursday, July 12, 2018

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REVIEW ARTICLE  

Functional state of cells during their life and on their journey toward inactivity and death: Search for morphological evidence in thyroid fine needle aspiration smears p. 131
Dilip K Das
DOI:10.4103/JOC.JOC_43_18  
Synthesis and storage of thyroglobulin as well as synthesis of thyroid hormones and their release into the circulation are important functions of thyroid, which were studied in fine needle aspiration (FNA) smears from thyroid lesions. Evidence of thyroglobulin synthesis was demonstrated in neoplastic and nonneoplastic follicular cells, especially in Hürthle cells, in the form of colloid inclusions. Whereas the pinocytic vesicles containing colloid at the luminal end of in nonneoplastic and neoplastic follicular cells indicated engulfment of colloid for synthesis of thyroid hormones (T3and T4), the marginal vacuoles (MVs) (fire-flare appearance) at the basal aspects of follicular cells suggested their release on way to the interfollicular capillaries. The morphological evidence of secretary activity could also be demonstrated in medullary thyroid carcinoma (MTC) in the form of azurophilic granules, marginal vacuoles, and intracytoplasmic lumina (ICL) with secretions; the secretory material, likely to be amyloid, present in MTC cells, and their release to the extracellular space was confirmed by positive immunocytochemical staining for calcitonin. It was found that nuclear grooves and related intranuclear cytoplasmic inclusions (INCIs) in papillary thyroid carcinoma (PTC) possibly represent an initial step of a degenerative process leading to formation of inactive cerebriform nuclei. Based on observation regarding formation and release of precursor substances for psammoma bodies (PBs), it was also suggested that PBs may not represent a process of dystrophic calcification over infarcted/dead papillae but suggest an active biological process, which leads to inhibition of growth of neoplastic cells and acts as a barrier against spread of PTC.
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ORIGINAL ARTICLES Top

Role of squash cytology in intraoperative diagnosis of spinal lesions p. 139
Mousumi Kar, Moumita Sengupta, Saurav Sarkar, Saikat Bera, Chhanda Datta, Uttara Chatterjee, Samarendra Nath Ghosh
DOI:10.4103/JOC.JOC_11_17  
Background: Squash cytology for intra operative diagnosis of central nervous system (CNS) tumors is an immensely important modality. Though its role in brain lesions is unquestionable and has been proven in a number of studies, its utility for spinal lesions is still a grey zone. Aims: To assess the diagnostic accuracy of squash preparation in spinal lesions and its statistical significance (sensitivity, specificity, positive predictive value, negative predictive value) following histological confirmation. Materials and Methods: A total of 57 cases of spinal tumors were taken. May-Grunewald-Giemsa staining (MGG) and Hematoxylin-Eosin (H&E) were done in each one of them. Rest of the tissue was processed for histological diagnosis and results were compared. Results: In our study, histology was taken as the gold standard. By comparing the results, squash preparation had sensitivity of 95.75%, specificity 80.0%, positive predictive value (PPV)95.74%, and negative predictive value (NPV) 80.80%. Schwannoma was found to be the most prevalent tumor in the spine (17/57) in our study, followed by meningioma (13/57). Diagnostic accuracy for schwannoma was fairly high i.e. 92.3%, followed by meningioma (82.35%). Highest diagnostic accuracy was documented in intradural, extramedullary compartment. Conclusion: Inspite of having pitfalls and various limitations in case of spinal lesions, squash preparation is a rapid and easy method with fairly high diagnostic accuracy. So it can be reliably used as an intraoperative diagnostic tool in spinal lesions.
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Cervicouterine cancer screening – TruScreen™ vs. conventional cytology: Pilot study p. 143
JE Salazar-Campos, A González-Enciso, R Díaz-Molina, ME Lara-Hernández, J Coronel-Martínez, C Pérez-Plasencia, D Cantú de León
DOI:10.4103/JOC.JOC_111_17  
Introduction: Cervicouterine cancer (CC) is a health problem worldwide and is the fourth most common cancer in women, with a greater proportion of individuals affected by advanced stages of the disease in developing countries. Objective: To determine the sensitivity and specificity of the TruScreen™ opto-electronic device vs. conventional cytology in CC screenings. Methodology: This is a prospective observational study that included individuals who presented for the first time at the Dysplasia Clinic of the Instituto Nacional de Cancerología from March 1 through April 30, 2016, and those referred due to abnormal conventional cytology. The patients were evaluated with the TruScreen™ device, conventional cytology, colposcopy and, if necessary, cervical biopsy. The results were analyzed by descriptive statistics as well as the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the TruScreen™, using conventional cytology as the standard. Results: Thirty-two patients were included who met the inclusion criteria. The average age of the patients was 40 years (range, 23–61 years). For the diagnosis of high-grade intraepithelial lesions, the TruScreen™ device showed a 43% sensitivity, a 92% specificity, a PPV of 60%, and a NPV of 85%, whereas evaluation via cervical biopsy exhibited a 33% sensitivity, an 86% specificity, a 33% PPV, and an 86% NPV. The Kappa agreement index of the TruScreen™ with the colposcopies was 0.70. Conclusions: TruScreen™ demonstrated low sensitivity and high specificity compared with conventional cytology, which had a high NPV.
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Correlative study of cytological features in grading of invasive breast carcinoma p. 149
Anamika Sinha, Satyajit S Gill
DOI:10.4103/JOC.JOC_2_18  
Context: Fine-needle aspiration cytology (FNAC) is a proven diagnostic technique for establishing the benign or malignant character of breast lesions. Several cytological grading systems have been proposed for grading of carcinoma breast, with results similar to histologic grades. Aims: This study sought to evaluate the prognostic value of FNAC in invasive ductal carcinoma of breast by correlating it with histological grade. Settings and Design: Tertiary care hospital, retrospective analytical study. Patients and Methods: One hundred and fifty cases of breast carcinoma that underwent modified radical mastectomy consequent to an FNAC diagnosis were included in the study. Robinson's grading system and Elston–Ellis modification of Scarff–Bloom–Richardson grading system were used to assign cytologic and histologic grades, respectively. Statistical Analysis: The cytological grades were correlated with the histological grades using χ2-test and Spearman's rank correlation coefficient. The individual features of the cytological grades were correlated with the histological grades using Kappa coefficient and χ2-test. Values were considered significant at P < 0.05. Results: A statistically significant association was observed between cytologic and histologic grades (r = 0.97; P < 0.01) with sensitivity and specificity, respectively, of 100% and 93.95% for cytological grade 1, 100% and 100% for cytological grade 2 and 100% and 100% for cytological grade 3. Also, a positive correlation was found between each feature of the cytologic grade and the histologic grade (P < 0.05). Among these, a better correlation was demonstrated by cytological features like cell uniformity (Kappa coefficient = 0.50) and appearance of nucleoli (Kappa coefficient = 0.52). Conclusions: Robinson's cytologic grading system is a reliable grading method on FNAC smears of cases of carcinoma breast. It correlates well with Elston–Ellis modification of Scarff–Bloom–Richardson grade in invasive ductal carcinoma of breast.
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Role of p16/Ki-67 Dual immunostaining in detection of cervical cancer precursors p. 153
Diya Das, Moumita Sengupta, Keya Basu, Mona Tirkey, Chhanda Datta, Uttara Chatterjee
DOI:10.4103/JOC.JOC_4_17  
Background: Pap-smears-based cytology and human papilloma virus testing have their own limitations in detecting cervical precancerous lesions, and still need further standardization. Co-expression of p16ink4a and Ki-67 can be used as additional biomarker. Aims: To study the role of liquid-based cytology and the dual immunostaining for p16/Ki-67 in predicting the presence of significant lesion in cases of mild cytological atypia. Materials and Methods: A prospective, cross-sectional study was performed in the Department of Pathology, in collaboration with Department of Obstetrics and Gynecology over 15 months including 545 patients. Immunocytochemistry followed by colposcopy-guided biopsy were performed in 52 cases with epithelial abnormalities. Results: Thirty-five cases (67%) were dual-stain positive among the cases with epithelial abnormalities. In the ASC-US and LSIL group, the sensitivity and specificity of the immunostaining in diagnosing CIN2+ lesions were 100 and 70% and 87.5 and 100%, respectively. p16/Ki-67 positivity also increased with cytological severity which in turn corresponded with histological findings: it reached from 33% in ASC-US to 100% in both HSIL and SCC categories. Conclusion: This dual immunostaining may potentially be a useful tool in the triage of the ASC-US and the LSIL group, considering the high sensitivity and specificity values.
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Can fine needle aspiration cytology be used as a “Proxy Gold Standard” to Diagnose tuberculous mastitis? p. 159
Meherbano M Kamal, Hemant R Kulkarni, Manjiri M Makde, Radha Munje
DOI:10.4103/JOC.JOC_72_17  
Objective: To assess the performance of fine needle aspiration cytology (FNAC) in the diagnosis of tuberculosis mastitis. Materials and Methods: Diagnostic test performance evaluation using two methods—as compared to an alloyed gold standard as well as in the absence of a gold standard. Alloyed gold standard combined the results of acid fast bacilli in cytology smears, histopathological confirmation, and response to treatment. Bayesian estimation of test parameters was done in the absence of the gold standard. Results: FNAC was carried out in 6,496 consecutive cases of breast lump and 104 cases of granulomatous mastitis were detected. Both methods of test parameter estimation identified a high specificity of FNAC for the diagnosis of tuberculosis mastitis (98.9% and 98.4%, respectively). Estimation of sensitivity was falsely high (100%) using the alloyed gold standard because of a workup bias and falsely low (8.41%) using the Bayesian estimation because of low prevalence. Likelihood ratios by both methods suggested that FNAC has good discriminatory capability. Conclusion: In situations where prevalence of tuberculosis is high and where facilities for histopathological evaluation do not exist, FNAC can offer an optional alternative to base the therapeutic decision for starting antitubercular treatment.
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SYMPOSIUMS Top

Contribution of immunocytochemistry to the diagnosis of usual and unusual lymphoma cases p. 163
Dilip K Das
DOI:10.4103/JOC.JOC_42_18  
Some of the limitations of fine needle aspiration (FNA) in the cytodiagnosis of lymphoma include problems encountered in differentiating reactive hyperplasia from low-grade non-Hodgkin lymphoma (NHL), lower cytodiagnostic accuracy for NHL with a follicular (nodular) pattern and nodular sclerosis type of classical Hodgkin lymphoma (HL), and overlapping morphological features between T-cell-rich B-cell lymphoma (TCRBCL), anaplastic large cell lymphoma (ALCL), and HL. Immunocytochemistry may be of help in such situations. The B-cell lymphomas such as small lymphocytic lymphoma/CLL, follicular lymphoma (FL), mantle cell lymphoma (MCL), MALT lymphoma, Burkitt lymphoma (BL), and diffuse large B-cell lymphoma (DLBCL) have pan-B-cell markers (CD19, CD20, CD22, CD23, and CD79a). The FL (centrocytic), MCL, and MALT lymphoma can be differentiated with the use of a panel consisting of CD5, CD10, and CD23. In addition, FL is BCL2+ and MCL is BCL2+ as well as cyclin D1+. The DLBCL is BCL6+ in 60–90% cases. Besides pan B-cell marker, the immunocytochemical profile of BL includes CD10+, BCl6+, EBV±, and Ki67+ (100% cells). TCRBCL, a rare variant of DLBCL can be immunocytochemically differentiated from anaplastic large cell lymphoma (CD45+, CD30+, CD15‒, T±, B‒, EMA+, ALK1±) and classical HL (CD30+, CD15+, CD45‒, B‒, T‒, EMA‒). Unlike classical HL, the nodular lymphocytic predominant HL has a phenotype that includes LCA+, CD20+, CD79a+, CD15‒, and CD30‒. Whereas the immature neoplastic cells of T-lymphoblastic lymphoma (LBL) are CD3+, CD20‒, and Tdt+, the rarely encountered mature T-CLL/T-PLL are immunophenotypically CD3+, CD4+, CD5+, CD7+, CD8‒, CD20‒, CD23‒, and Tdt‒.
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Where to look for AFB in FNA Smears from tuberculous lymph nodes p. 170
Dev Prasoon
DOI:10.4103/JOC.JOC_58_18  
Demonstration of acid fast bacilli (AFB) is essential for the definitive cytodiagnosis of tuberculosis. However, it is not seen in all cases of tuberculosis, being more commonly observed in necrotic lesions. Tuberculosis shows a spectrum of lesions that form a continuum extending from good immunity end with purely granulomatous lesions to poor immunity end with purely necrotic lesions. Each stage has distinctive microscopic picture and determines the chance of finding AFB. AFB yield was the highest (92.7%) in necrotic lesions containing eosinophilic structures (ES).
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Trucut/Core biopsy versus FNAC: Who wins the match? thyroid lesions and salivary gland lesions: An overview p. 173
Nalini Gupta, Parikshaa Gupta, Arvind Rajwanshi
DOI:10.4103/JOC.JOC_18_18  
Thyroid and salivary gland are amongst the most common sites subjected to fine needle aspiration cytology (FNAC) due to easy accessibility of these sites along with high diagnostic accuracy of FNAC. The performance of FNAC can be increased with the use of ultrasonographic guidance and rapid on-site evaluation. Cell block along with immunochemistry and other ancillary techniques further helps in clinching the correct diagnosis in certain diagnostically challenging cases. Core needle biopsy (CNB) is proposed to have a better diagnostic accuracy in certain situations. However, CNB has no definite role as an upfront first-line diagnostic technique for thyroid or salivary gland lesions. We describe role of FNAC and CNB in thyroid and salivary gland lesions with detailed discussion of advantages and disadvantages of both these techniques.
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FNAC Versus CNB: Who wins the match in breast lesions? p. 176
Indranil Chakrabarti
DOI:10.4103/JOC.JOC_35_18  
The triple test lies at the heart of preoperative diagnosis of breast lesions. Raised awareness and self-assessment have significantly increased the rate of detection of breast pathologies. The managing clinicians usually decide the imaging and pathological modalities to the best interest of the patients. Core needle biopsy (CNB), cell-block studies, and fine needle aspiration cytology (FNAC) coupled with rapid on-site evaluation (ROSE) have significantly increased the accuracy of preoperative diagnosis. Immunocytochemistry, immunohistochemistry on cell blocks, and other ancillary studies give confidence to the clinicians to decide the best treatment strategies.
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Trucut biopsy vs FNAC of pelvic tumors-who wins the match? p. 179
Asaranti Kar, Bharat Satapathy, Kaumudee Pattnaik, Prafulla K Dash
DOI:10.4103/JOC.JOC_63_18  
Preoperative pathologic diagnosis of pelvic tumors is mandatory for proper management of patients like neoadjuvant chemotherapy and interval debulking. Currently there are many minimally invasive methods available which include fine-needle aspiration cytology (FNAC) and trucut biopsy, mostly complimentary to each other. FNAC is a cheap, rapid and sensitive method for diagnosis of pelvic tumors. It can be done as an outpatient procedure without complications. But with it, the tissue architecture cannot be seen. Trucut biopsy on the other hand reveals tissue architecture and can help in grading and subtyping of malignant tumors. Trucut biopsy has to be done under image guidance like ultrasound and computed tomography. Patient is administered local anaesthetic and can be discharged safely after 2 hours. Pathologists familiar with histomorphology can give a correct diagnosis easily. But many times sampling errors may occur; especially in large tumors, resulting only in necrosis, hemorrhage and degenerated tissue bits. Also differentiation of borderline from malignant ovarian tumors is very difficult. In case of mixed tumors one component may be missed. Hard tumors like fibromas and leiomyomas yield scanty material and result in inadequate reporting. With FNAC, the overall accuracy rate is estimated to be around 96.3%. With trucut biopsy, adequacy is from 91 to 95% and accuracy is approximately 98% in different studies. When both methods are combined, the adequacy is 100%, diagnostic accuracy 95.5%, sensitivity 94.9% and specificity 100%. Therefore depending on the clinical diagnosis and the location of tumors, either FNAC and/or trucut biopsy can be chosen.
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Tru-cut/core biopsy versus FNAC: Pulmonary tumors p. 183
Deepali Jain
DOI:10.4103/JOC.JOC_73_18  
Primary lung epithelial malignancies are the most common neoplasms among all pulmonary tumors. Lung cancer (LC) is the leading cause of cancer-related mortality for which a histologic or cytologic confirmation of malignancy is required before treatment. Specimen management is an important task for pathologists in the field of LC. Biopsy and fine needle aspiration are comparable. It is desirable to have both for diagnosis and mutation testing to maximize their use for patient care.
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CASE REPORTS Top

Cytodiagnosis of primary thyroid lymphoma coincident with unnoticed papillary thyroid carcinoma: A case report and review of the literature p. 187
Gozde Kir, Billur Cosan Sarbay, Adnan Ozpek
DOI:10.4103/JOC.JOC_180_15  
Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer, whereas primary thyroid lymphoma is very rare. Here, we report a case in which a right-sided nodule measuring 4.3 × 2.2 cm was examined using fine-needle aspiration biopsy. This revealed abundant monomorphic non-cohesive large lymphoid cells without thyroid follicular cells, on which basis acytodiagnosis of lymphoma coincident with lymphocytic thyroiditis was made. Subsequent histologic examination revealed CD45−, CD20+, and Bcl-6 + and cytokeratin-, CD3-, CD5-, and CD30-negative tumor cells arranged diffusely in the whole thyroid coexisting with a separate PTC nodule sized 1.3 × 1.0 cm in the right lobe. The key point exemplified by this case is that a cytodiagnosis of this extremely rare coexistence of PTC and lymphoma can be made by adequate sampling of both nodules preoperatively. In our case, only one nodule formation was sampled, and therefore the coexisting PTC was not detected with cytology preoperatively.
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Cytodiagnosis of coexistence of leukemic infiltration and extramedullary hematopoiesis in a cervical lymph node, in T cell leukemia patient p. 189
Akanksha Bothale, Kalpana Bothale, Sadhana Mahore, Trupti Dongre
DOI:10.4103/0970-9371.232256  
Extramedullary hematopoiesis (EMH) is a compensatory mechanism that occurs when the marrow is unable to maintain sufficient red cell mass. EMH generally occurs in the patients with deficient bone marrow hematopoiesis secondary to either peripheral red cell destruction or marrow replacement. Although EMH is known to occur in agnogenic myeloid metaplasia with myelofibrosis, chronic myelogenous leukemia, thalassemia, and infiltrative disorders, such as lymphomas, it is rare in acute leukemias. EMH is most commonly seen in the liver and spleen as a diffuse lesion. The involvement of lymph nodes in leukemia and EMH is known; however, to the best of our knowledge, the occurrence of both in the same lymph node has been reported in a single case report. Our case may be the second most rare case of coexistence of infiltration by leukemic lymphoblasts and EMH in the same lymph node detected on FNAC. EMH should be considered in the differential diagnosis of patients with bone marrow disorders and mass lesions in extramedullary sites.
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LETTER TO EDITOR Top

Cytological diagnosis of an uncommon tumor of the minor salivary gland – Basal cell adenoma p. 193
Premila Desousa Rocha, RG Wiseman Pinto, Rajika Bhat, Durva Prabhugaonkar, Adora Fernandes
DOI:10.4103/JOC.JOC_184_17  
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