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Introduction: Urinary cytology (UrCy) is highly sensitive to diagnosing high-grade urothelial carcinoma (HGUC) but cannot predict muscularis propria invasion. Further, the atypical urothelial cell category (AUC) may have variable outcomes. Image morphometry (IM) may be a valuable adjunct technique in this setting. Hence, we evaluated IM in the AUC and HGUC categories to improve the diagnostic performance. Materials and Methods: The following six nuclear parameters were evaluated by IM on 3150 cells: nucleo-cytoplasmic (N:C) ratio, nuclear area, diameter, perimeter, standard deviation of the nuclear area (SDNA; pleomorphism) and integrated density (ID; nuclear chromasia), using the ImageJ software, in three cohorts based on the histopathology outcome: 20 cases of AUC – benign non-neoplastic outcome (AUC-B); 22 cases of HGUC Muscle invasive (HGUC-MI) and 21 cases of HGUC non-muscle invasive (HGUC-MF). Results: A retrospective analysis of urine cytology. The patient’s ages ranged from 36 to 85 years, with a mean age of 60.6. The male-to-female ratio was 5.4:1. A total of 20 cases of AUC-B and 43 cases of HGUC were selected for IM analysis. HGUC cases had higher nuclear parameters than AUC-B, and HGUC-MI had higher SDNA, ID, diameter, and area than HGUC-MF. SDNA and ID predict muscularis propria invasion in HGUC. Conclusions: Image morphometry successfully differentiates HGUC cases from benign non-neoplastic ones and might help to identify muscularis propria invasion in HGUC using a combination of nuclear parameters.

Background: Mucormycosis is a fungal infection that can affect multiple organs. The role of fine-needle aspiration cytology (FNAC) in its diagnosis is not well documented. Aim: The objective of this study was to describe the detailed cytomorphologic features of mucormycosis on FNAC samples. Materials and Methods: A retrospective analysis of all cases diagnosed as mucormycosis on FNAC between January 2014 and July 2021 was performed for detailed cytomorphological evaluation and correlation to clinical data and microbiological studies wherever available. FNA was computed tomography-guided (n = 38), ultrasonography-guided (n = 31) or palpation-guided (n = 12), and slides were reviewed in two cases. Results: A total of 83 cases of mucormycosis were evaluated. An immunocompromised setting was observed in 48 cases. The most common site of FNA was the lung (n = 57) followed by liver, soft tissue, palate, mediastinum, orbital/ocular region, and lymph node. Isolated renal involvement, a unique feature, was seen in seven cases. The aspirates were necrotic to pus-like or blood-mixed particulate. Broad, nonseptate, foldable, ribbon-like fungal hyphae showing right-angled branching were seen. The tissue reaction was predominantly necro-inflammatory (n = 36), bland necrotic (n = 22), mixed inflammatory (n = 16), suppurative (n = 5), necrotizing granulomatous (n = 3), and granulomatous (n = 1). Immunocompromised patients showed mixed inflammatory responses more frequently. Fungal culture was positive for Rhizopus species in 2/13 cases and molecular testing in two additional cases corresponding to Rhizopus and Syncephalastrum spp. Conclusion: FNA provides quick and conclusive diagnosis of mucormycosis from varied anatomic sites enabling prompt institution of therapy. The tissue response is variable and to some extent dependent on the immune status of the patient.

Abstract Background Cancer progression can be promoted by chronic inflammation. Local immune response may be associated with favourable or unfavourable prognosis of Papillary Thyroid Carcinoma (PTC). Regulatory T (Treg) cells and T helper 17 (Th17) cells exert opposing function and their balance may have a vital role in promotion of tumor growth. Treg cells in tumor microenvironment (TME) may promote tumor progression and reduced survival of patients. Whereas, Th17 cells can promote or inhibit tumor progression depending on phenotypic characteristics of tumor. In this study, we aimed to analyse the kind of immune response developed and its prognostic impact in future therapeutics. Methods Cytometric Bead Array (CBA) analysis of pro and anti-inflammatory cytokines (IFN-gamma, IL-2, IL-6, IL-17 A, TNF-alpha and IL-4, IL-10) was done in 15 PTC irrespective of Lymphocytic Thyroiditis (LT) and 16 Hashimoto’s Thyroiditis (HT) cases. Immunohistochemical expression of FoxP3 and IL-17 A was studied in 27 cases of PTC with LT. Whereas, quantitative gene expression of both was analysed in 10 cases. Results All the pro-inflammatory cytokines showed mild elevation in PTC with LT. On IHC, IL-17 A expression was observed in 74% PTC with LT. Whereas, FoxP3 was present in only 40% cases. Also, IL-17 A expression was significantly associated with age group (> 45 years), tumor size ≤ 1 cm and disease progression. Conclusions Increased expression of cytokines suggested correlation between inflammatory factors and progression of thyroid tumors. Along with this, the balance between IL-17 A and FoxP3 may play an important role in PTC development, prognosis and future management.

BackgroundLymphocytic thyroiditis (LT) is frequently seen in the tumor microenvironment (TME) of papillary thyroid carcinomas (PTCs). However, the characteristic of these tumor-infiltrating lymphocytes (TILs) is not well understood.ObjectiveWe aim to define the TME of PTC cases by characterizing the TILs.DesignThis is a cross-sectional observational study.PatientsWe enrolled 29 PTC (23 having concurrent LT), 14 LT, and 13 hyperplastic nodules with LT (HN) patients from January 2016 to December 2020.MeasurementsImmunohistochemical (IHC) expression of CD8, FoxP3, PD-1, and PD-L1 was studied in PTC with LT and compared with HN. PD-1 and PD-L1 expression was correlated at the mRNA level by quantitative real-time PCR. Immunophenotyping of TILs was done in FNAC samples of PTC and LT by flow cytometry.ResultsIHC revealed the presence of CD8+ cytotoxic T lymphocytes (CTLs) and FoxP3+ T regulatory cells (Tregs) in 83% and 52% of PTC with LT cases, respectively. Flow cytometric analysis of the PTC samples revealed a significant abundance of CTL compared with Treg and a higher CTL with lower Treg counts compared with LT. On IHC, PD-1 positivity was noted in 56.5% of PTC with LT cases, while intermediate PD-L1 positivity was found in 70% of the cases. There was a significant upregulation of PD-1 mRNA in PTC with LT. A significant correlation was noted with PD-L1 expression with lymph node metastasis and presence of Treg cells.ConclusionsIncreased expression of PD-1 and PD-L1 in the TME of PTC may provide a potential molecular mechanism for tumor survival despite the predominance of CTLs, possibly through their inactivation or exhaustion.

Perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal uterine tumor and the histological variant, sclerosing PEComa is exceedingly rare. Sclerosing PEComas preferentially occur in the retroperitoneum and occurrence in the uterine corpus is seldom seen. These tumors pose a diagnostic challenge and need distinction from morphological mimickers such as epithelioid smooth muscle tumors, endometrial stromal sarcoma, and metastatic carcinoma. Accurate diagnosis can be established coupling histomorphology with immunostaining. The distinction from other entities is of prime importance considering the therapeutic and prognostic implications. Herein, we describe a case of uterine sclerosing variant of PEComa with diagnostic difficulties and key to diagnose this entity.

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.

Background: In the modern era, immunocytochemistry (ICC) is an essential part of investigations. There is now an increasing workload of ICC in laboratories. Automated immunostaining platform may help the laboratories to deal with such a rising burden of ICC. Summary: In this brief review article, we have described the various aspects of automated ICC, particularly the benefits, limitations, types of the system, working manner, and comparison of different commercially available systems.

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.

Cytological examination plays an important role in the initial work-up of the serous cavity effusion fluids to find out the possible etiology as benign or malignant. Among malignant effusions, cytology is helpful in determining the exact type, site, and stage of the tumor. However, for reporting effusion cytology specimens, there is no consistent and reproducible reporting system. Aims: The aim of these guidelines is to provide a standardized format for effusion cytopathology right from sample receipt to its ultimate report sign-out for implementation in all cytopathology laboratories. The Indian Academy of Cytologists in consultation with experts across the country has prepared guidelines pertaining to collection, preparation, and diagnostic categories of effusion specimens to reduce reporting variability. The guidelines are made keeping in mind the different areas of practices in India, especially low- and medium-resource settings. The guidelines are broadly divided into essential, optimal, and optional categories for best usage and appropriate allocation of the precious specimens. In referral centers or well-established setups, essential ancillary techniques can be done for accurate and final diagnosis. By adhering to and implementing these uniform guidelines, it is hoped that clinical patient care and management in India will improve and be of uniformly good quality by enabling and facilitating good laboratory practices.

Aims and Objectives: The aim of this work was to study the application of Modified Millipore technique (MMT) as a liquid-based tool to have multiple monolayer cellular smears for the routine cytology and Immunocytochemistry. Materials and Methods: In this study, we included 32 effusion fluid samples and 30 fine-needle aspiration cytology (FNAC) samples. From each of the samples, at first routine conventional smear was prepared. The residual samples were processed by MMT to make multiple smear preparation. Both the conventional and MMT of the monolayer cells were evaluated. The various cytomorphological features including the cellularity, background information, nuclear morphology, and cytoplasmic preservation were compared in these two techniques. Result: There were a total of 15 cases of fluid samples and 27 cases of FNAC. Statistical analysis of Mann–Whitney U test showed that the monolayer preparation by MMT and liquid-based cytology of fluid and FNAC smears are of same quality (P > 0.01). Conclusion: Monolayer preparation by MMT is cheap and effective. This technique can be used in routine laboratory for multiple monolayer cell preparations.

Chorioangioma is the most common benign non trophoblastic tumor of the placenta. It is a rare presentation with incidence of 0.6-1% of all pregnancies. It is associated with feto maternal complications like polyhydramnios, cervical incompetence, preterm labor, increased rate of cesarean delivery, abruptio placentae, malpresentation, postpartum hemorrhage, fetal growth restriction, fetal anemia, fetal thrombocytopenia, non immune hydrops, fetal cardiac failure, cerebral embolism, cerebral infarction, intrauterine fetal and neonatal death. Ultrasound is the gold standard for diagnosis . Here we present a case of giant chorioangioma of 6 * 5 cm with complication of polyhydramnios, preterm labor, abruptio placenta and placenta previa successfully managed with good maternal and fetal outcome.

Extramammary Vulval Paget’s Disease (VPD) is rare neoplasm of post-menopausal women. In relatively young perimenopausal patients, it can cause both diagnostic dilemma and therapeutic challenges. Majority of VPD is of non-invasive variety. Among invasive Paget’s disease, only 20% cases show invasion more than 1 mm. The present report describes a unique case of an invasive extra-mammary VPD with depth of invasion more than 4 mm presenting at a relatively young perimenopausal lady. Only 14 cases of VPD has been treated with primary radiotherapy in literature till date. We report this case to be the 15th case where radiotherapy was solely used to treat an invasive VPD.

Objective: To distinguish fibrolamellar hepatocellular carcinoma (FL-HCC) variant from the conventional hepatocellular carcinoma (HCC) by cytology, immunocytochemistry, and morphometry. Study Design: Retrospective detailed cytomorphological, immunocytochemical, and morphometric analysis was performed in 6 cases of FL-HCC reported on fine needle aspiration. Cell block immunocytochemistry (CB-ICC) for CK7 and CD68 was performed in four cases. Morphometry was carried out with Cell A software. Area of the cell, nucleus and nucleolus was measured in 50 nuclei per case in 6 cases each of FL-HCC and HCC. Results: The mean age of patients with FL-HCC was 19 years and all had normal serum alpha-fetoprotein levels. Fine needle aspiration smears showed large polygonal cells with abundant cytoplasm, vesicular nucleus and prominent nucleolus, associated with variably cellular fibrous stromal fragments. Intranuclear inclusions, cytoplasmic eosinophilic inclusions, and bile were also noted. FL-HCC showed strong membrano-cytoplasmic CK7 positivity and cytoplasmic granular and canalicular positivity for CD68. In contrast, HCC showed weak focal positivity for CK7 and only canalicular CD68 positivity. Morphometry revealed that FL-HCC cells were 2.19 times the size of HCC. Conclusion: CK7 immunocytochemistry on cell blocks is useful for confirming and distinguishing it from HCC.

Treatment strategy of Cervical Intraepithelial Neoplasia-3 (CIN 3) in background of High Grade Squamous Intraepithelial Lesion (HSIL) is very different amongst the pregnant and non-pregnant women. This case report highlights the approach of diagnosis and management of CIN 3 in pregnancy. A 32-year-old woman, Fourth Gravida one Live issue and previous 2 Abortion (G4P1021), was diagnosed to have cervical intra-epithelial neoplasia (CIN 3) in pregnancy at 20+1 weeks period of gestation. The decision to continue pregnancy was made. She was followed with LBC and colposcopy 12 weekly during the pregnancy. Her pregnancy was uneventful. She delivered vaginally a live born girl, 2.74 kg at 38+4 weeks. In the postpartum period repeat, Liquid Based Cytology (LBC) and colposcopy-directed biopsy were done. The LBC revealed HSIL while biopsy was suggestive of CIN 3. Cone biopsy was done and histopathology report revealed CIN 3 with margins and tips of cone free of tumour. Thus, in this patient neither progression nor regression was noted with conservative approach and definitive management was deferred until the post-partum period. The aim of this article is to highlight the approach of diagnosis and management of CIN 3 in pregnancy.

Background: In this paper, we have compared the cytomorphologic characteristics of liquid-based preparation (LBP) [SurePath (SP)] cytology and conventional smear (CP) preparations on fine-needle aspiration (FNAC) material by a semi-quantitative scoring system for cases of lymphadenopathy. Materials and Methods: In this prospective study, a total of 52 consecutive cases of FNAC of lymphadenopathy were included. The first pass was used for CP followed by LBP with the help of SP technique. The smears were independently compared and assessed by two observers (PS and PD). Results: The semiquantitative grading was compared in two groups by Wilcoxon signed-rank test. The background information, cell architecture, pleomorphism, nuclear and cytoplasmic details, and three-dimensional structures were significantly different in LBP and CP smears. Conclusions: Liquid-based cytology (LBC) is a relatively simple technique, which exhibits good nuclear and cytoplasmic details with the absence of obscuring background material. Even the number of slides and area per slide to be screened were less than the conventional preparation but caution must be applied to interpret the slides and secure a diagnosis, especially if LBC is the first and only method applied for diagnosis.

Background: Multiple myeloma or plasmacytoma resulting in malignant effusion is rarely described in literature. Aims: In this paper, we have studied the seven rare cases of plasma cell infiltration in effusion fluid. Materials and Methods: We studied six cases of pleural fluid and one case of ascetic fluid. Detailed cytological features, clinical history, bone marrow examinations, serum electrophoresis, and immunofixation data were analyzed. Result: There were two cases of plasmacytoma, four cases of multiple myeloma, and one case of plasmablastic lymphoma. On cytology, all the cases showed excess plasma cells along with mesothelial cells and lymphocytes on effusion cytology smear. Conclusion: Plasma cell rich effusion in cases of plasma cell tumor is rare. However, on cytology these cases do not pose much problem if relevant history is known.

Primary sarcomas of the urinary bladder or prostate are extremely rare entities. The rarity and lack of awareness makes it difficult for the cytologists to detect the spindle cell lesions in urine for malignant cytology. The literature available for the detection of urinary tract sarcomas is little. Here, we report the urine cytology findings of two interesting cases of urinary bladder and prostatic leiomyosarcoma.

Fine-needle aspiration cytology (FNAC) of the breast is a rapid, cost-effective, and sensitive procedure to diagnose breast lesions, and was widely employed to diagnose breast lesions in the past. However, in recent times, core needle biopsy of the breast is gaining popularity and acceptability, although FNAC still looms large. There are some intrinsic disadvantages to FNAC, of which the most important is probably difficulty in classification of a significant percentage of breast lesions. Such lesions are usually denoted by the rubric "grey zone lesions of the breast." This article attempts to review these grey zone lesions and highlight the difficulties in diagnosing them.

Background: Visual image classification is a great challenge to the cytopathologist in routine day-to-day work. Artificial neural network (ANN) may be helpful in this matter. Aims and Objectives: In this study, we have tried to classify digital images of malignant and benign cells in effusion cytology smear with the help of simple histogram data and ANN. Materials and Methods: A total of 404 digital images consisting of 168 benign cells and 236 malignant cells were selected for this study. The simple histogram data was extracted from these digital images and an ANN was constructed with the help of Neurointelligence software [Alyuda Neurointelligence 2.2 (577), Cupertino, California, USA]. The network architecture was 6-3-1. The images were classified as training set (281), validation set (63), and test set (60). The on-line backpropagation training algorithm was used for this study. Result: A total of 10,000 iterations were done to train the ANN system with the speed of 609.81/s. After the adequate training of this ANN model, the system was able to identify all 34 malignant cell images and 24 out of 26 benign cells. Conclusion: The ANN model can be used for the identification of the individual malignant cells with the help of simple histogram data. This study will be helpful in the future to identify malignant cells in unknown situations.