Cytological diagnosis of lymphoepithelial carcinoma: Simple yet confusing.

Lymphoepithelial carcinoma (LEC) of salivary glands are rare tumours and present as gradually progressing painless masses. LECs have good prognosis and accurate differentiation from secondary tumours and nasopharyngeal carcinoma is essential to dictate management. We present a case of an elderly male presenting with a parotid swelling diagnosed as LEC on fine needle aspiration cytology and confirmed on histopathology and immunohistochemistry.

High-grade transformation in adenoid cystic carcinoma: Can it be diagnosed on cytology? A cytohistological correlation.

Adenoid cystic carcinomas (ADCC) are distinctive salivary gland neoplasms with characteristic histomorphology. The diagnosis of dedifferentiation/high-grade transformation (HGT) indicates poor prognosis and is most often made on histopathology. We present a case of ADCC arising from a minor salivary gland tumor exhibiting HGT, reaching up to the submandibular gland and having lymph node metastases, suspected on fine-needle aspiration cytology. The index case highlights the awareness of the entity of the HGT of salivary gland tumors and raises suspicion for cytological diagnosis.

Digital Examination of LYmph node CYtopathology Using the Sydney system (DELYCYUS): An international, multi-institutional study.

BACKGROUND: After a series of standardized reporting systems in cytopathology, the Sydney system was recently introduced to address the need for reproducibility and standardization in lymph node cytopathology. Since then, the risk of malignancy for the categories of the Sydney system has been explored by several studies, but no studies have yet examined the interobserver reproducibility of the Sydney system. METHODS: The authors assessed interobserver reproducibility of the Sydney system on 85 lymph node fine-needle aspiration cytology cases reviewed by 15 cytopathologists from 12 institutions in eight different countries, resulting in 1275 diagnoses. In total, 186 slides stained with Diff-Quik, Papanicolaou, and immunocytochemistry were scanned. A subset of the cases included clinical data and results from ultrasound examinations, flow cytometry immunophenotyping, and fluorescence in situ hybridization analysis. The study participants assessed the cases digitally using whole-slide images. RESULTS: Overall, the authors observed an almost perfect agreement of cytopathologists with the ground truth (median weighted Cohen κ = 0.887; interquartile range, κ = 0.210) and moderate overall interobserver concordance (Fleiss κ = 0.476). There was substantial agreement for the inadequate and malignant categories (κ = 0.794 and κ = 0.729, respectively), moderate agreement for the benign category (κ = 0.490), and very slight agreement for the suspicious (κ = 0.104) and atypical (κ = 0.075) categories. CONCLUSIONS: The Sydney system for reporting lymph node cytopathology shows adequate interobserver concordance. Digital microscopy is an adequate means to assess lymph node cytopathology specimens.

The cytological diagnosis of Pneumocystis jiroveci pneumonia in bronchoalveolar lavage.

Objectives: Immunosuppressed individuals are more prone for opportunistic infections. Pneumocystis jiroveci pneumonia (PJP), previously known as Pneumocystis carinii pneumonia (PCP), is the most common opportunistic infection affecting people living with HIV. As PJP can cause life threatening serious infection to a patient, treatment should not be delayed for these cases. To study clinico-cytomorphological spectrum of PJP. Material and Methods: We analysed the clinical and detailed cytological features of 15 patients with PJP who were diagnosed on examination of bronchoalveolar lavage (BAL) fluid. Results: The mean age of the patients was 38.4 years (range 13 - 61 years). A total of seven patients were HIV positive; five patients were post renal transplant, and one patient was a known case of acute leukaemia on immunosuppression. Presence of foamy alveolar casts (FACs) was the distinctive feature and was noted in 14 out of 15 cases. We detected 14 out of 15 cases accurately in BAL fluid cytology. Conclusion: BAL cytology is one of the important modes of investigations which can detect PJP infection. The history of fever, cough, immunosuppression, bilateral haziness in the radiography of lung and the characteristic alveolar cast indicate the possibility of PJP infection. Cytology can provide early diagnosis and can reduce the mortality of immunocompromised patients.

Mismatch Repair Deficiency in Adult Granulosa Cell Tumors: an Immunohistochemistry-based Preliminary Study.

OBJECTIVE: Adult granulosa cell tumors (AGCTs) are rare ovarian malignant neoplasms; their etiopathogenetic mechanisms remain largely unelucidated. Lately, defects in mismatch repair (MMR) have been implicated in the pathogenesis of AGCTs. Demonstration of MMR deficiency in these tumors can help identify patients potentially eligible for immune checkpoint inhibition therapy. The present study was done to explore the role of MMR deficiency in the etiopathogenesis of AGCTs. METHODS: This was a retrospective study conducted on histopathologically confirmed AGCT cases. MMR protein expression was evaluated by immunohistochemistry (IHC) on tissue microarrays using an antibody panel of MSH2, MSH6, MLH1, and PMS2. RESULTS: Of a total of 40 ovarian AGCTs evaluated for MMR deficiency, none demonstrated loss of expression of any of the 4 MMR proteins. CONCLUSIONS: The results of our preliminary study show that there is no association between MMR deficiency with AGCT. Nevertheless, larger multicenter studies are needed to confirm or refute this observation.

Cytomorphological spectrum of metastatic bone tumors: Experience at a tertiary care center.

Objectives: Bone is a frequent site of metastases and typically indicates a short-term prognosis in cancer patients. The majority of skeletal metastases are due to breast and prostate cancer. Bone metastasis is actually much more common than primary bone cancers, especially in adults. Fine-needle aspiration cytology (FNAC) provides reasonably accurate pre-operative diagnosis in vast majority of cases. This study aims to elicit the cytomorphological detail of various metastatic bone tumors. Material and Methods: A total of 109 cases of tumors metastatic to bone have been included in this study. The details of the cases were available from the archives of the department of cytology. May Grunwald Giemsa and hematoxylin and eosin stained smears were studied and examined for the cytomorphological spectrum. Cell block and immunohistochemistry tests were done, wherever feasible. Results: Among 109 patients, the mean age was 54.52 years. There was male preponderance with 90 males and 19 females. The most common site of metastases was in the vertebra (82 cases), and 76 cases were in the dorsolumbar region. The most common type of tumor metastasizing was adenocarcinoma. Conclusion: FNAC is a very useful, economical procedure. There are characteristic cytological features of the metastatic lesions and the basic diagnostic categorization of the malignant tumors is possible on FNAC. Regarding the primary source clinical history, radiological features of the primary tumor, if any, and immunocytochemistry may be needed.

Contrast-enhanced ultrasound of solid pancreatic head lesions: a prospective study.

OBJECTIVE: To evaluate the role of contrast-enhanced ultrasound (CEUS) in the differential diagnosis of solid pancreatic head lesions (SPHL). METHODS: This prospective study comprised consecutive patients with SPHL who underwent CEUS evaluation of the pancreas. Findings recorded at CEUS were enhancement patterns (degree, completeness, centripetal enhancement, and percentage enhancement) and presence of central vessels. In addition, time to peak (TTP) and washout time (WT) were recorded. The final diagnosis was based on histopathology or cytology. Multivariate analysis was performed to identify parameters that were significantly associated with pancreatic ductal adenocarcinoma (PDAC). RESULTS: Ninety-eight patients (median age 53.8 years, 59 males) were evaluated. The final diagnosis was PDAC (n = 64, 65.3%), inflammatory mass (n = 16, 16.3%), neuroendocrine tumor (NET, n = 14, 14.3%), and other tumors (n = 4, 4.1%). Hypoenhancement, incomplete enhancement, and centripetal enhancement were significantly more common in PDAC than non-PDAC lesions (p = 0.001, p = 0.031, and p = 0.002, respectively). Central vessels were present in a significantly greater number of non-PDAC lesions (p = 0.0001). Hypoenhancement with < 30% enhancement at CEUS had sensitivity and specificity of 80.6% and 67.7%, respectively, for PDAC. There was no significant difference in the TTP and WT between PDAC and non - PDAC lesions. However, the WT was significantly shorter in PDAC compared to NET (p = 0.011). In multivariate analysis, lack of central vessels was significantly associated with a PDAC diagnosis. CONCLUSION: CEUS is a useful tool for the evaluation of SPHL. CEUS can be incorporated into the diagnostic algorithm to differentiate PDAC from non-PDAC lesions. KEY POINTS: • Hypoenhancement and incomplete enhancement at CEUS were significantly more common in PDAC than in non-PDAC. • Central vessels at CEUS were significantly associated with PDAC. • There was no difference in TTP and WT between PDAC and non-PDAC lesions.

Detection of ALK Gene Rearrangements in Non-Small Cell Lung Cancer by Immunocytochemistry and Fluorescence in Situ Hybridization on Cytologic Samples.

OBJECTIVE: Determination of the molecular status is mandatory for personalized treatment of patients with non-small cell lung carcinoma. The present study was performed to detect anaplastic lymphoma kinase (ALK) rearrangements in pulmonary adenocarcinoma on cytology samples, using immunocytochemistry (ICC) and fluorescence in situ hybridization (FISH) on cell-blocks to assess the diagnostic reliability of these two techniques. MATERIAL AND METHOD: A total of 50 confirmed lung adenocarcinoma cases were included. In all the 50 cases, ICC was performed for ALK protein expression by using the D5F3 clone on Ventana platform. On the basis of ALK protein expression on ICC, the cases were categorized as ALK positive (2+ or 3+ strong cytoplasmic granular positivity) or negative (negative or 1+ cytoplasmic granular positivity). FISH for detection of ALK gene rearrangement was performed in 7 ALK ICC positive cases and 7 ALK ICC negative cases using the Vysis ALK break apart FISH probe kit. RESULTS: Based on ICC, 7(14%) cases were ALK positive and 43(86%) were ALK negative. ALK gene rearrangements in lung adenocarcinoma were more commonly seen in non-smokers (31.25%) as compared to smokers (6.25%). Among the ALK-ICC positive cases, FISH demonstrated break apart signal in 5 cases (ALK- ICC positive); however, no break-apart signals were seen in 2 ALK-ICC positive and all the seven ALK-ICC negative cases. CONCLUSION: Immunocytochemistry on cell- blocks using DF53 clone is a highly sensitive and specific method for the detection of ALK gene rearrangements in lung adenocarcinoma with a greater number of ALK positive cases being detected on ICC as compared to the ALK-FISH.

Fine-Needle Aspiration Diagnosis of Lymphoma Based on Cytomorphology Alone: How Accurate is it? - A Cyto-Histopathology Correlative Study.

CONTEXT: Fine-needle aspiration cytology (FNAC) is a rapid and accurate first-line diagnostic modality in lymphadenopathy. AIMS: To determine the utility of FNAC for the diagnosis of lymphoma and highlight the various pitfalls in morphological interpretation. SETTINGS AND DESIGN: This was a retrospective study of 3 years duration in which cytology diagnosis was compared with the follow-up histopathology diagnosis wherever available. RESULTS: A cytodiagnosis of lymphoma was made in a total of 868 cases (2.8%) out of nearly 33,000 FNAC performed during the study period; 556 (64.1%) cases were diagnosed as non-Hodgkin lymphoma (NHL), 198 (22.8%) as Hodgkin lymphoma (HL), and in 114 (13.1%) cases, a cytological diagnosis of lymphoma without further categorization was given. Histopathological reports were available in 348 cases, with an overall concordance rate of 93.1% (324), which was slightly higher in the HL cases (95.8%) as compared to NHL (91.7%). Twenty-four cases (6.9%) showed discordant cytological diagnosis with subsequent histopathology. The main reasons for the erroneous diagnosis were the over-interpretation of the germinal center cells as atypical lymphoid cells, over-interpretation of immunoblasts with prominent nucleoli as Hodgkin cells, and sheets of monomorphic lymphoid cells interpreted as low-grade lymphoma. CONCLUSION: Cytomorphology alone can make a correct basic diagnosis of lymphoma with a high degree of accuracy. The errors in interpretation can be further reduced by careful attention to the diagnostic pitfalls and common differential diagnoses.

Cytology of peritoneal implants of borderline serous tumor of ovaries in ascitic fluid.

OBJECTIVES: Peritoneal fluid cytology is done routinely in cases with serous carcinoma of ovary. However, morphologic features of borderline serous tumors (BSTs) of ovary in ascitic fluid have been rarely described. The aim of our study was to evaluate the morphologic features of BST with and without ascitic fluid involvement (BST+ and BST-, respectively) and compare with those of serous carcinomas, both in conventional and liquid-based cytology (LBC) smears. MATERIAL AND METHODS: Out of 30 BST cases reported in 3 years, seven cases had BST+. We compared the cytomorphology of seven cases of BST+, seven cases of BST-, and seven cases of serous adenocarcinoma with positive ascitic fluid cytology. Both conventional and LBC smears were studied in all cases and compared. Histopathology of omentum in these cases was also studied. RESULTS: Most cases with BST+ had regular papillary fragment borders with nuclei showing mild-to-moderate pleomorphism, fine nuclear chromatin with small nucleoli as compared with serous carcinomas all of which had irregular borders with moderate-to-severe nuclear pleomorphism, coarse chromatin, and macronucleoli. CONCLUSION: A combination of cytoarchitectural and nuclear features can help in suspecting BST in ascitic fluid. Ascitic fluid cytology together with tissue histology can increase the rate of the detection of peritoneal implants.

Cytomorphological features of cervical small cell neuroendocrine carcinoma in SurePath™ liquid-based cervical samples.

Small cell neuroendocrine carcinoma (SCNEC) of the cervix is a rare, highly aggressive tumour with poor prognosis and high propensity for distant metastases. The cytological features of SCNEC have rarely been described in cervical samples, and to the best of our knowledge, there are no previous reports using SurePath™ liquid-based cytology. In the present report we present the cytomorphological features of histopathologically confirmed cases of cervical SCNEC in SurePath preparations. On cytological examination, all three cases demonstrated variable numbers of tumour cells, ranging from a few dispersed cells and tiny micro-biopsies to large aggregates of small tumour cells with a high nucleus-to-cytoplasmic ratio, stippled chromatin, inconspicuous nucleoli, and scant cytoplasm. Immunocytochemistry for CD56 on the cervical preparation confirmed the diagnosis in one case. The presence of small tumour cells with characteristic stippled/salt-and-pepper type nuclear chromatin were the most consistent cytological features in these cases. Knowledge of these characteristic cytological features can help in suggesting a diagnosis of SCNEC in cervical samples which can then be confirmed by immunocytochemistry.

Steroid Cell Tumor of the Ovary Presenting with Ascites: A Rare Neoplasm in a Postmenopausal Woman.

Steroid cell tumors of the ovary are rare sex-cord stromal tumors, accounting for approximately 0.1% of all ovarian neoplasms. Majority of these tumors are benign, occur in pre-menopausal women and are associated with hyperandrogenism. However, around one-third of cases are malignant and do not present with hormonal manifestations. A 48-year-old post-menopausal woman presented with complaints of gradually increasing progressive abdominal distension over the past 3 months. She had a history of weight gain but denied any symptoms of virilization. On examination, abdominal distension associated with ascites was noted. Serum CA125 level was raised. Contrast-enhanced computed tomography revealed a solid right adnexal mass. Based on the clinical impression of epithelial ovarian malignancy, the patient underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy and infracolic omentectomy. Histopathological examination revealed steroid cell tumor of the not otherwise specified type in the right ovary with the capsular breach. However, all other organs, including the omentum were free of tumor. The index case is unique for its presentation in a post-menopausal woman, association with ascites, elevated CA125 levels and lack of any virilization manifestations. Establishing an early and accurate tissue diagnosis is essential so that appropriate surgical management can be done to prevent the development of metastases in potentially malignant cases.

Application of Indian Academy of Cytologists Guidelines for Reporting Serous Effusions: An Institutional Experience.

BACKGROUND: Recently, the Indian Academy of Cytologists (IAC) has published the guidelines for interpretation and reporting of serous effusions. Till date, there are no studies on its applicability. AIMS: The present study was carried out to assess the feasibility of applying the IAC reporting categories to effusions, determine the frequency, and provide an estimate of the risk of malignancy (ROM) for individual diagnostic categories. MATERIALS AND METHODS: All cases of serous effusion fluids reported in the year 2019 were retrieved from the archives and reassigned as per the IAC diagnostic categories. The clinical and histopathological follow-up information was obtained wherever possible. RESULTS: A total of 1340 effusion samples were received from 1085 patients. There were 561 (51.7%) males and 524 (48.3%) females. Majority were pleural (1066, 79.5%), followed by peritoneal (187, 14%) and pericardial (87, 6.5%) effusions. The age ranged from 7 months to 92 years. There were 35 (2.6%) samples in category 1 (non-diagnostic), 954 (71.2%) in category 2 (benign), 17 (1.3%) in category 3 (atypical), 59 (4.4%) in category 4 (suspicious for malignancy) and 275 (20.5%) in category 5 (malignant). The estimated ROM in serous effusion samples was 20% for category 1, 16.7% for category 2, 50% for category 3, 94.4% for category 4 and 100% for category 5. CONCLUSIONS: The categorization of serous effusion cytology samples as per the IAC diagnostic categories and as per the reporting format developed by the IAC is feasible and the management recommendations are mostly appropriate.

Ultrasound-guided fine needle aspiration of ovarian masses: Assessment of diagnostic accuracy and risk stratification using a categorical reporting system.

INTRODUCTION: The present study was undertaken to assess the accuracy of fine needle aspiration cytology (FNAC) and cell-block immunocytochemistry, and to estimate the risk of malignancy, using a categorical reporting system, in the diagnosis of ovarian masses. METHODS: This was a 5-year retrospective study of FNAs of ovarian masses. The cytological diagnoses were categorised as inadequate, non-neoplastic, benign neoplasms, indeterminate for malignancy, suspicious for malignancy and malignant neoplasms. The cytology was correlated with the corresponding histopathology to assess the diagnostic accuracy and risk of malignancy associated with each diagnostic category. RESULTS: Of a total of 66 703 FNAs performed during the study period, 580 (0.9%) were performed on ovarian masses. Of these, 40 (6.9%) were reported as non-neoplastic; 76 (13.1%) as benign neoplasms; 14 (2.4%) as indeterminate for malignancy, 48 (8.3%) as suspicious for malignancy, 337 (58.1%) as malignant neoplasms and 65 (11.2%) as inadequate for interpretation. Immunocytochemistry (ICC) was performed on 99 (17%) aspirates. Subsequent histopathology was available in 208 (35.8%) cases. On cyto-histopathological correlation, 183 (88%) were concordant and 25 (12%) were discordant. The overall sensitivity, specificity, positive and negative predictive values and diagnostic accuracy for diagnosing ovarian malignancy were 88.4%, 85.7%, 96.8%, 60.0% and 88% respectively. Risk of malignancy for each category was 80%, 0%, 4.5%, 66.7%, 88.5% and 98.5% respectively. CONCLUSIONS: Ultrasound-guided FNAC has high specificity and diagnostic accuracy for preoperative diagnosis of ovarian malignancies and hence is a valid diagnostic procedure in certain clinical situations. Reporting using a categorical system imparts uniformity and also provides the clinicians with an associated risk of malignancy to guide further management.

Assessment of risk of malignancy by application of the proposed Sydney system for classification and reporting lymph node cytopathology.

BACKGROUND: Fine-needle aspiration cytology (FNAC) is one of the most commonly used techniques for evaluating lymphadenopathy. Recently, the Sydney system was proposed for assessing the performance, classification, and reporting of lymph node (LN) cytopathology. The present study was conducted to assess the risk of malignancy associated with each of the diagnostic categories of the proposed Sydney system. METHODS: This was a 2-year retrospective study of LN-FNAs; cytologic diagnoses were categorized by the proposed Sydney system. Cytological diagnoses were correlated with the corresponding histopathological diagnoses to assess diagnostic accuracy and risk of malignancy for each diagnostic category. RESULTS: Of 23,335 FNAs during the study period, 6983 (30%) were performed on LNs. Of these, 289 (4.1%) cases were reported as nondiagnostic/inadequate (L1); 3397 (48.6%) were reported as benign (L2); 33(0.5%) as atypical cells of undetermined significance (L3), 96 (1.4%) as suspicious for malignancy (L4) and 3168 (45.4%) as malignant (L5). Subsequent histopathology was available for 618 (8.8%) cases. On cytohistopathologic correlation, 552 (89.3%) were concordant and 66 (10.7%) discordant. The overall sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy of LN-FNA were 79.9%, 98.7%, 98.4%, 83.1%, and 89.3%, respectively. The risk of malignancy was 27.5% for the nondiagnostic category, 11.5% for the benign, 66.7% for the atypical, 88% for the suspicious, and 99.6% for the malignant categories. CONCLUSIONS: FNAC has high diagnostic accuracy for the diagnosis of various LN pathologies. Application of the proposed Sydney system can help in achieving uniformity and reproducibility in cytologic diagnoses and also help in risk-stratification on cytology.

Diagnostic accuracy and cytomorphological spectrum of Wilms tumour in fine needle aspiration biopsy cytology samples supplemented with cell blocks.

OBJECTIVE: Paediatric malignant renal neoplasms are subjected to neoadjuvant chemotherapy as per Societe Internationale d'Oncologie Pediatrique; International Society of Pediatric Oncology (SIOP) protocol. An accurate tissue diagnosis is required prior to institution of chemotherapy, and hence the aim of this study was to evaluate the diagnostic accuracy of fine needle aspiration biopsy cytology (FNABC) along with cell block histology. MATERIALS AND METHODS: A retrospective audit of all paediatric renal neoplasms diagnosed by FNABC between 2015 and 2019 was performed. Histopathology correlation was done wherever available. WT cases were subjected to detailed cytomorphological evaluation. RESULTS: A total of 121 cases of paediatric renal neoplasms including 109 WT, four clear cell sarcoma, one malignant rhabdoid tumour and three mesoblastic nephroma were evaluated. The age range was 4 weeks to 8 years. FNABC samples were adequate for diagnosis in 120 of 121 cases (99.18%) and a definitive cytological diagnosis was achieved in 117 cases (96.7%). The specificity and sensitivity for a cytopathological diagnosis of WT were 98.7% and 97.4%, respectively. On detailed cytomorphological analysis of 68 histopathology-proven WT, 40 (58.8%) cases were triphasic, 23 (35.3%) were biphasic and four were composed of blastema only. The corresponding cell blocks provided additional information over the conventional smears in 23 (33.8%) cases, with epithelial or mesenchymal elements recognised and evidence of rhabdomyoblastic differentiation. CONCLUSION: FNABC along with cell block histology is highly accurate for diagnosis of WT and other malignant paediatric renal neoplasms and is recommended as the technique of choice in centres with cytopathology expertise for establishing a cellular diagnosis prior to commencement of neoadjuvant chemotherapy.

Lymphoreticular malignancies in serous effusions: Cytomorphologic, flow cytometric and immunocytochemical analysis.

INTRODUCTION: Involvement of body fluids by lymphoreticular malignancies (LRM) is rare and often associated with poor prognosis and decreased overall survival. The present study was conducted to analyze the characteristic cytomorphologic, flow cytometric and immunocytochemical features of LRMs in serous effusions. MATERIALS AND METHODS: This was a three-year retrospective study. A total of 218 effusion samples, reported as involved by lymphoreticular malignancies, on cytology, were reviewed. All the cases wherein the cytological diagnosis was confirmed by flow cytometric (FCM) and/or immunocytochemical (ICC) studies were retrieved and studied in detail. FCM and/or ICC were performed in a total of 51/218(23.4%) samples, including 30 pleural (58.8%), 18 peritoneal (35.3%), and 3 pericardial fluid (5.9%) samples. RESULTS: The cytomorphologic diagnoses included infiltration by non-Hodgkin lymphoma (NHL;n = 27), infiltration by LRM (n = 19), infiltration by chronic lymphocytic leukemia (CLL;n = 2), Hodgkin's lymphoma (HL;n = 1) and suggestive of infiltration by LRM (n = 2). FCM and/or ICC confirmed the diagnoses as infiltration by T-cell lymphoblastic lymphoma in 18; mature B-cell NHL in 10; Burkitt lymphoma in 7; diffuse large B-cell lymphoma in 4; follicular lymphoma, T- cell NHL and CLL in 2 samples each and hairy cell leukemia, plasmablastic lymphoma and HL in 1 sample each. 94.1% concordance was noted between the initial and final cytologic diagnosis. CONCLUSIONS: Involvement of body fluids and effusions by LRMs, though rare, carries an immense prognostic significance and hence the prompt detection is crucial. Detection of these malignancies by cytologic examination of effusions is challenging yet potentially useful and the least invasive method available to establish an early diagnosis.