Grading pancreatic adenocarcinomas on fine needle aspiration cytology. The outstanding issues.

OBJECTIVE: The three-tier grading scheme described in "The Papanicolaou Society of Cytopathology (PSC) System for reporting Pancreaticobiliary Cytopathology" (TPSCRPBC) which remained unchanged following the WHO Reporting System for Pancreaticobiliary Cytopathology (WRPBC) was evaluated on pancreatic adenocarcinomas (PACs) reported on endoscopic ultrasound-guided fine needle aspiration cytology (EUS-FNAC). METHODS: The Papanicolaou and May Grunwald Giemsa-stained smears from 116 cases of PACs were graded using the three-tier grading scheme laid down by TPSCRPBC/WRPBC. Cases exhibiting multiple grades were assigned primary, secondary and tertiary grades. Each case was assigned a grade score, either by adding the primary and secondary grades, by adding the primary and tertiary grades when the tertiary grade was 3 or by doubling the grade when only one grade existed. Necrosis was estimated semi-quantitatively. The inter-observer reproducibility in grading was evaluated using Kappa and Kendall's tau-c. Correlations between the various grades, the stage of the tumour and the amount of necrosis were assessed using Spearman rho and Kendall's tau-b. RESULTS: 31.89% of cases showed one grade, and 68.11% showed at least two grades. 16.38% showed three grades. The two commonest grade scores were 3 and 5. The inter-observer reproducibility for grading and grade scoring was satisfactory. A positive correlation was noted between the grades and the amount of necrosis. No significant correlation was found between the grades, grade scores and the stage of the tumours. CONCLUSIONS: The TPSCRPBC/WRPBC grading scheme can be suitably applied to PACs with good inter-observer reproducibility. Cases often show multiple grades in the same tumour.

Non-Association of Driver Alterations in PTEN with Differential Gene Expression and Gene Methylation in IDH1 Wildtype Glioblastomas.

During oncogenesis, alterations in driver genes called driver alterations (DAs) modulate the transcriptome, methylome and proteome through oncogenic signaling pathways. These modulatory effects of any DA may be analyzed by examining differentially expressed mRNAs (DEMs), differentially methylated genes (DMGs) and differentially expressed proteins (DEPs) between tumor samples with and without that DA. We aimed to analyze these modulations with 12 common driver genes in Isocitrate Dehydrogenase 1 wildtype glioblastomas (IDH1-W-GBs). Using Cbioportal, groups of tumor samples with and without DAs in these 12 genes were generated from the IDH1-W-GBs available from "The Cancer Genomics Atlas Firehose Legacy Study Group" (TCGA-FL-SG) on Glioblastomas (GBs). For all 12 genes, samples with and without DAs were compared for DEMs, DMGs and DEPs. We found that DAs in PTEN were unassociated with any DEM or DMG in contrast to DAs in all other drivers, which were associated with several DEMs and DMGs. This contrasting PTEN-related property of being unassociated with differential gene expression or methylation in IDH1-W-GBs was unaffected by concurrent DAs in other common drivers or by the types of DAs affecting PTEN. From the lists of DEMs and DMGs associated with some common drivers other than PTEN, enriched gene ontology terms and insights into the co-regulatory effects of these drivers on the transcriptome were obtained. The findings from this study can improve our understanding of the molecular mechanisms underlying gliomagenesis with potential therapeutic benefits.

Cholangiocarcinoma: A diagnostic dilemma on cytology.

BACKGROUND: Cholangiocarcinoma is a relatively rare form of adenocarcinoma which may resemble adenocarcinoma of pancreatobiliary origin or adenocarcinomas from many other sites in the body. As a result, its diagnosis relies mainly on clinical history and morphology. CASE: A 64-year-old male with cirrhosis and worsening liver failure underwent fine needle aspiration of a radiologically detected liver mass. Cytological material showed a monomorphic population of cells arranged singly and in clusters, reminiscent of a neuroendocrine tumour (NET). Cell block morphology added to the diagnostic dilemma by showing a delicate vasculature among the tumour cells. Immunohistochemistry on the cell block revealed that cells were positive for CK7 and CK19 and negative for synaptophysin and chromogranin, thereby pointing towards a pancreatobiliary origin for the tumour and excluding an NET. CONCLUSION: In the case of liver aspirates, even when encountering confusing morphological entities, it is imperative to keep in mind the possibility of a rare neoplasm such as cholangiocarcinoma. In the absence of core needle biopsy, cell block sections prepared from aspirated material can provide appreciable immunohistochemistry results to resolve the diagnostic dilemma.

Endoscopic Ultrasound-Guided Fine Needle Aspiration Cytology of Pancreatic Adenocarcinomas Revisited. A Detailed Cytological Analysis.

BACKGROUND: Early detection of pancreatic adenocarcinomas is essential for improving survival. In this regard, endoscopic ultrasound-guided fine-needle aspiration cytology (EUS-FNAC) has established itself as the method of choice for its ability to target lesions smaller than those which could be targeted by the traditional imaging methods like transabdominal ultrasound. Identifying these tumors correctly on FNA may be challenging because pancreatic adenocarcinomas may show a wide range of morphological features and the presence of contaminants from the gastrointestinal tract may show up as potential pitfalls. This study presents detailed cytomorphological analyses of 59 cases reported as pancreatic adenocarcinomas on smears and cell blocks. The clinical and histopathology follow-up data wherever available have also been presented. MATERIALS AND METHODS: EUS-FNAC smears and cell blocks from cases reported as pancreatic adenocarcinomas were retrospectively evaluated with individual assessments of a range of features related to cellularity, cellular arrangement, cytoplasmic qualities, and nuclear features. Aspirates from peripancreatic lymph nodes, histopathology sections, and clinical records were reviewed wherever available. RESULTS: Nonneoplastic cells like pancreatic ductal cells and acinar cells, duodenal, and gastric epithelia were detected along with neoplastic cells showing a wide range of variations in different cytomorphological characters. Often, a mixture of features was noted in the same case. Cell block preparations served as useful adjuncts since they made it possible to render unequivocal diagnoses of malignancies in cases where smears were hypocellular. CONCLUSION: The study creates a useful knowledge base of cytomorphological features of pancreatic adenocarcinomas.

Fine-Needle Cytological Characteristics of Carcinoma Breast with Medullary or Medullary-like Features Masquerading as Dendritic Reticulum Cell Sarcoma: An Attempt to Explore the Reasons for Erroneous Cytologic Interpretation.

BACKGROUND: Infiltration of tumors by dendritic reticulum cells (DRC) reflects the host immune defense mechanism. We observed three breast carcinomas cases with dense tumor-infiltrating DRC and lymphocytes in fine-needle aspiration (FNA) smears, leading to cytodiagnosis or differential diagnosis of dendritic reticulum cell sarcoma (DRCS). An attempt was made to find out the reason behind such an erroneous interpretation. MATERIALS AND METHODS: Between 2009 and 2014, two cases were diagnosed as DRCS of the female breast by FNA cytology and in one case possibility of DRCS was considered along with medullary breast carcinoma (MBC). We compare and contrast the cytomorphological features of these three cases with those of nine cytologically diagnosed MBC. RESULTS: Cases diagnosed as DRCS or MBC showed singly dispersed tumor cells, nuclear pleomorphism, bare nuclei, prominent nucleoli, and presence of lymphocytes. There was no significant difference between the two groups for discohesive clusters, syncytial clusters, plasma cells, neutrophils, foamy histiocytes, and necrosis. However, there was significant difference for presence of cohesive clusters (0% DRCS and 100% MBC, P = 0.00485), severe degree (+++) of pleomorphism (100% DRCS vs. 11.1% MBC, P = 0.01818), +++ DRC (P = 0.04697), and DRC with ++ to +++ enlarged nuclei (P = 0.03333), and pleomorphic nuclei (P = 0.00833). Two of the three cytologically diagnosed DRCS cases proved to be MBC or MBC-like and one as invasive ductal carcinoma. Six of nine cytologically diagnosed MBC cases with histology proved to be invasive breast carcinomas. CONCLUSION: Criteria for cytodiagnosis MBC need a fresh look. Cases with numerous dendritic cells possibly represent MBC.

Anaplastic large cell lymphoma: Report of two cases with rare patterns (carcinomatous and sarcomatous) in fine needle aspiration cytology and histopathology.

Anaplastic large cell lymphoma (ALCL) is a non-Hodgkin lymphoma of T-cell or null-cell lineage with variable cytomorphology. We report two rare ALCL cases with carcinomatous and sarcomatous patterns, respectively, in fine needle aspiration (FNA) cytology and histopathology. The first case was a 56-year-old man with enlarged left inguinal lymph node. FNA smears showed a malignant small round cell tumor with nuclear molding. In addition, there were large bi-nucleated and multinucleated cells with wreath-like arrangement of nuclei. ALCL and small cell (neuroendocrine) carcinoma were the possibilities considered. Immunocytochemical studies on FNA smears showed positive reaction for leukocyte common antigen (LCA) and negative results for cytokeratin (CK) and chromogranin. Histopathological examination of the lymph node showed features of ALCL with following immunohistochemical staining results: LCA+, CD30+, CD45RO+, CD20-, CD3+ (weak), and Alk1-. During review of sections, areas resembling a small cell anaplastic carcinoma were observed. The second case was a 24-year-old woman with right cervical lymphadenopathy. FNA smears showed an ALCL with highly atypical large cells including bi-nucleated and donut shaped cells, which were positive for CD30, EMA, and Alk-1 protein, and negative for CD20, CD3, and CK. Histopathological examination corroborated the cytodiagnosis of ALCL, and with positive immunohistochemical staining for CD30, EMA, Alk-1 protein+, BCL6+, and Ki67+ (40% cells) and negative results for CD20, CD10, CD3, CD5, CD15, BCl2, CD79a, and CD68. Sarcomatous components were noticed during review of cytologic and histopathological specimen. Awareness about these unusual cytomorphological patterns in ALCL may be of help in proper diagnosis of this neoplasm.

The applicability of Papanicolaou Society of Cytopathology system on reporting endoscopic ultrasound-guided fine needle aspiration cytology specimens of pancreatic lesions in situations with limited availability of ancillary tests. Experience at a single laboratory.

INTRODUCTION: The Papanicolaou Society of Cytopathology (PSC) system of reporting pancreatobiliary cytology is a standardised reporting nomenclature that uses a six-tiered scheme of diagnostic categories utilising routine microscopy and ancillary tests such as biochemical and molecular analysis of cyst fluids and immunochemistry. The objective of this study was to determine the applicability of the PSC system on endoscopic ultrasound-guided fine needle aspiration cytology samples reported at the cytopathology laboratory, Mubarak Al Kabeer Hospital, in Kuwait with special emphasis on situations with limited availability of ancillary tests. METHODS: In total, 132 cases of endoscopic ultrasound-guided fine needle aspiration cytology samples from pancreatic lesions were categorised according to PSC system guidelines after examining the glass slides and reviewing the clinical, imaging and ancillary test findings. These review diagnoses were compared with the diagnoses rendered during initial reporting. Correlation with histopathology reports was done wherever available. RESULTS: In 23 (17.42%) of 132 cases, re-categorisation was necessary between initial and reviewed diagnoses. In 16 cases, re-categorisations were because of non-analogous categories between initial and reviewed diagnosis. In the remaining seven, they were due to identification of newer cytomorphological and imaging findings or because of issues arising from unavailability of sufficient material for ancillary investigations. CONCLUSION: All cases could be categorised using the PSC system with a moderate number of re-categorisations between initial and reviewed diagnoses. In certain circumstances, limited availability of ancillary tests, resulted in non-diagnostic categories whereas in other such circumstances, diagnostic categories could be assigned with certain conceptual modifications to the PSC guidelines.

Interpreting a Diagnosis of Atypical Squamous Cells of Undetermined Significance in Cervical Cytology and its Association with Human Papillomavirus: A retrospective analysis of 180 cases in Kuwait.

OBJECTIVES: Atypical squamous cells of undetermined significance (ASC-US) represent a diagnostic challenge during cervical cytology. This study aimed to review and identify high-risk human papillomavirus (HR-HPV) genotypes among previously diagnosed ASC-US cases in Kuwait. METHODS: This retrospective study analysed 180 cases diagnosed as ASC-US between June 2017 and May 2018 at the Mubarak Al-Kabeer Hospital, Kuwait. Cervical specimens were assayed to determine the presence of HR-HPV DNA; subsequently, positive cases underwent genotyping and were categorised into three groups (HPV 16, HPV 18/45 and other HR-HPV types). RESULTS: In total, ASC-US was confirmed in only 105 cases (58.3%), with the remaining cases reclassified as negative for intraepithelial lesions or malignancy (NILM; 32.2%) and epithelial cell abnormalities (ECA; 9.4%). Of these, HR-HPV DNA was present in 20 ASC-US (19%), one NILM (1.7%) and six ECA (35.3%) cases. There were 62 Kuwaiti and 43 non-Kuwaiti women with confirmed ASC-US; of these, three (4.8%), six (9.7%) and four (6.5%) Kuwaitis and one (2.3%), one (2.3%) and five (11.6%) non-Kuwaitis had HPV 16, both HPV 16 and 18/45 and other HR-HPV genotypes, respectively. Of those with HR-HPV DNA, the NILM case had the HPV 18/45 genotype, while the six ECA cases had the HPV 16 (n = 1), both HPV 16 and 18/45 (n = 1) and other HR-HPV (n = 4) genotypes. CONCLUSION: Overall, HR-HPV DNA was present in 19% of ASC-US cases compared to 1.7% of NILM cases initially misdiagnosed as ASC-US. Re-review of cervical cytology diagnoses may reduce unnecessary costs associated with HR-HPV genotyping.

Human papillomaviruses other than 16, 18 and 45 are the major high risk HPV genotypes amongst women with abnormal cervical smear cytology residing in Kuwait: Implications for future vaccination strategies.

OBJECTIVES: The study was undertaken to determine the prevalence of different high risk HPV (HR-HPV) genotypes amongst women residing in Kuwait with epithelial abnormalities in cervical smears and to detect any difference in the distribution of these genotypes between Kuwaiti and Non-Kuwaiti women or between the cytological diagnosis groups. MATERIALS AND METHODS: Thinprep specimens from women with epithelial abnormalities on cervical smears were subjected to Aptima HR-HPV assay and those found to be HR-HPV positive were genotyped using the Aptima HPV genotyping assay into three groups (i) HPV 16, (ii) HPV 18/45 and (iii) others. RESULTS: HR-HPV was found in 229 (30.57%) of the 749 cases with epithelial abnormalities. Of the 116 cases subjected to further genotyping, the non-16, 18, 45 genotype accounted for the most prevalent group accounting for 62.93% of the cases, followed by HR-HPV 16 (31.04%) cases and HPV 18/45 (6.03%) of cases. There was no significant difference between Kuwaiti and non-Kuwaiti women nor was any difference noted between the various cytological diagnosis group. CONCLUSION: Most HR-HPV infections amongst women residing in Kuwait with epithelial abnormalities are due to HPV types other than the 16, 18 and 45. As HPVs 16 and 18 are considered to be the most prevalent HR-HPV genotypes worldwide, causing invasive cancer, the findings of this study is significant from an epidemiological standpoint. It should also be taken into account before undertaking any HPV vaccination program since the available HPV vaccines protect against HR-HPVs 16 and 18 only.

An attempt to understand glioma stem cell biology through centrality analysis of a protein interaction network.

Biological networks can be analyzed using "Centrality Analysis" to identify the more influential nodes and interactions in the network. This study was undertaken to create and visualize a biological network comprising of protein-protein interactions (PPIs) amongst proteins which are preferentially over-expressed in glioma cancer stem cell component (GCSC) of glioblastomas as compared to the glioma non-stem cancer cell (GNSC) component and then to analyze this network through centrality analyses (CA) in order to identify the essential proteins in this network and their interactions. In addition, this study proposes a new centrality analysis method pertaining exclusively to transcription factors (TFs) and interactions amongst them. Moreover the relevant molecular functions, biological processes and biochemical pathways amongst these proteins were sought through enrichment analysis. A protein interaction network was created using a list of proteins which have been shown to be preferentially expressed or over-expressed in GCSCs isolated from glioblastomas as compared to the GNSCs. This list comprising of 38 proteins, created using manual literature mining, was submitted to the Reactome FIViz tool, a web based application integrated into Cytoscape, an open source software platform for visualizing and analyzing molecular interaction networks and biological pathways to produce the network. This network was subjected to centrality analyses utilizing ranked lists of six centrality measures using the FIViz application and (for the first time) a dedicated centrality analysis plug-in ; CytoNCA. The interactions exclusively amongst the transcription factors were nalyzed through a newly proposed centrality analysis method called "Gene Expression Associated Degree Centrality Analysis (GEADCA)". Enrichment analysis was performed using the "network function analysis" tool on Reactome. The CA was able to identify a small set of proteins with consistently high centrality ranks that is indicative of their strong influence in the protein protein interaction network. Similarly the newly proposed GEADCA helped identify the transcription factors with high centrality values indicative of their key roles in transcriptional regulation. The enrichment studies provided a list of molecular functions, biological processes and biochemical pathways associated with the constructed network. The study shows how pathway based databases may be used to create and analyze a relevant protein interaction network in glioma cancer stem cells and identify the essential elements within it to gather insights into the molecular interactions that regulate the properties of glioma stem cells. How these insights may be utilized to help the development of future research towards formulation of new management strategies have been discussed from a theoretical standpoint.

Contribution of immunocytochemical stainings for galectin-3, CD44, and HBME1 to fine-needle aspiration cytology diagnosis of papillary thyroid carcinoma.

In cytology practice some papillary thyroid carcinoma (PTC) cases have indeterminate diagnoses and overlapping cytological features with benign lesions. This study was undertaken to find out if immunocytochemistry using Galectin-3, CD-44 and HBME-1 could be of help in such situations. Forty-six cases consisting of 22 malignancy (PTC) cases, 7 suspicious of (S/O) PTC, 1 follicular neoplasm, 5 follicular lesion of undetermined significance (FLUS), and 11 benign (colloid goiter) cases diagnosed by FNA were included in this study. Staining reactions were graded in a sliding scale of -, 1+, 2+, 3+, and 4+. In an assessment of 100 cells, each cell with weak, and moderate to strong positive reaction were assigned a score of 1 and 4, respectively. Staining reaction of ≥+2 and scores >100 were considered positive. Frequency of cases with ≥+2 reaction, and scores >100 for each of Galectin-3, CD-44, and HBME-1 were significantly higher in PTC or combined PTC and S/O PTC cases as compared with FLUS and benign cases taken together (P = 0.01744 to 0.00000). When the cases were compared according to histological malignant and benign diagnoses, the difference was also significant in respect of ≥+2 reaction, and scores >100 for Galectin-3 and CD44 (P = 0.04923 to 0.00947); however, there was no significant difference, when these parameters for HBME1 were compared. Galectin 3, CD 44, and to some extent HBME 1 are useful immunocytochemical parameters with potential to support FNAC diagnosis of PTC, especially in situations with difficult differential diagnoses.

Kikuchi-Fujimoto disease in fine-needle aspiration smears: a clinico-cytologic study of 76 cases of KFD and 684 cases of reactive hyperplasia of the lymph node.

Kikuchi-Fujimoto disease (KFD) is cytologically characterized by a polymorphous lymphoid cell population, abundant karyorrhectic debris and histiocytes, many of which are crescentic (Kikuchi histiocytes). As per reviewed literature, KFD may be confused with tuberculosis, lymphoma, and reactive hyperplasia of lymph nodes (RHLN). Since RHLN was found to be a major challenging factor during routine cytodiagnosis of KFD in our material, we tried to find out the differentiating clinico-cytologic features between 76 KFD and 684 RHLN cases seen in Kuwait. 63.2% of KFD were in 3rd and 4th decades of life as compared to 40.2% of RHLN (P = 0.0002). Male to female ratio was 1: 2.45 for KFD and 1:1.09 for RHLN (P = 0.0022). Kuwaiti:non-Kuwaiti ratio was 1:2.04 for KFD and 1.31:1 for RHLN (P < 0.0001). Capillary networks was present in 71.1% of KFD smears and 52.6% of RHLN (P = 0.0023). Tingible body macrophages and dendritic reticulum cells were detected in 17.1% and 22.4%, respectively, in KFD as opposed to 50.1% and 58.8%, respectively, in RHLN (P < 0.0001). Kikuchi histiocyte count ranged from 2 to 36% in KFD and was ≥10% in 31 (40.8%). Rare Kikuchi histiocytes were detected in 16 (2.3%) of RHLN cases but in none of them the count exceeded 1%, whereas their count was >1% in all KFD cases (P < 0.0001). Thus, KFD cases differed significantly from RHLN in respect of age and sex distribution, Kuwaiti:non-Kuwaiti ratio, and cytomorphologic features such as capillary networks, Kikuchi histiocyte count, dendritic reticulum cells, and tingible body macrophages.

T-cell-rich B-cell lymphoma (TCRBCL): limitations in fine-needle aspiration cytodiagnosis.

Exclusive reports on fine needle aspiration (FNA) cytodiagnosis of T-cell-rich B-cell lymphoma (TCRBCL) are scarce in literature. This report reflects the diagnostic difficulties associated with cytodiagnosis of this rare variant of diffuse large B-cell lymphoma. The study is based on 11 cases with age ranging from 16 to 63 years and a median of 50 years. Male to female ratio was 6:5. Ten cases presented with lymphadenopathy and one had lymphadenopathy as well as extranodal solid tumor. The initial cytodiagnosis was suggestive of TCRBCL in one case, TCRBCL/Hodgkin's lymphoma (HL) in three cases, TCRBCL/HL/anaplastic large cell lymphoma (ALCL) in two cases, TCRBCL/ALCL in one case, and TCRBCL/non-Hodgkin lymphoma (NHL) T-cell/ALCL in one case. There was also a cytologically diagnosed HL case, which on review turned out to be HL/TCRBCL. Histopathological diagnosis was HL in all these nine cases. There were two histologically diagnosed TCRBCL cases during this period, with cytodiagnoses of NHL other than TCRBCL in one and HL in the other. While highlighting the difficulties associated with the cytodiagnosis of TCRBCL, this study conveys a word of caution that adequate immunocytochemical studies should be performed before diagnosing this rare neoplasm with a varied cytomorphology.

Papillary thyroid carcinoma: how much should the surgeon read from fine needle aspiration cytology reports?

OBJECTIVE: During routine fine needle aspiration cytodiagnosis of papillary thyroid carcinoma (PTC), a number of cases are diagnosed as suspicious; or it is suggested that PTC or a neoplasm be ruled out by histopathology. Since these diagnostic labels are likely to put the clinicians in a difficult situation while planning the management, this study aims to find out how much the surgeon should read from these reports. MATERIALS AND METHODS: The patients were divided into two groups. Group A included 38 cases diagnosed as PTC or suspicious of PTC. Group B included 40 cases in which it was suggested that PTC/a neoplasm to be ruled out and non-neoplastic lesions with one or more cytologic features of PTC. The two groups were compared with clinical, imaging and cytomorphologic features. RESULTS: A significant difference was observed with respect to age between Group A and Group B (P<0.001). The frequency of the following five cytologic features was significantly higher in Group A: papillary formation (P<0.001), psammoma bodies (P=0.054), fine nuclear chromatin (P=0.010), frequent nuclear grooves (P<0.001) and intra-nuclear cytoplasmic inclusion (P<0.001). Three or more of the five cytologic features were also reported in significantly higher number of Group A cases (P<0.001). Majority (81.8%) of the cases with subsequent histology in Group A were confirmed as PTC as opposed to 7.7% in Group B (P<0.001). CONCLUSIONS: Thus, cases with definitive cytodiagnosis of PTC and suggestive of PTC (Group A) should be taken much more seriously by the surgeons as compared to Group B cases.

A hypothesis and theoretical model speculating the possible role of therapy mediated neoplastic cell loss in promoting the process of glioblastoma relapse.

Tumor recurrence is considered to be one of the biggest culprits, behind the poor prognosis of glioblastomas. Using published facts on primary glioblastomas, with special reference to cancer stem cells and their recently described heterogeneity, a hypothesis is being proposed that speculates the possible role of therapy mediated neoplastic cell loss in promoting the process of relapse in these tumors. The mechanisms by which such a phenomenon could be functional has been integrated into a double version theoretical model, which envisages glioblastomas as neoplasms comprising of multiple, differentially regulated and dynamically distinct neoplastic compartments (named as active and back-up compartments in this article) supported by their own complement of cancer stem cells, wherein therapy mediated cell loss, which mainly affects the size of the active compartment, results in abrogating the inhibitory effect of the active compartment on the back-up compartment, thereby leading to the activation of the back-up compartment. This activation contributes towards tumor recurrence. The possibility of the existence of such a phenomenon could have strong implications on management and prognosis of these tumors. This article aims to provoke discussion and generate new ideas for further research.

Grading of soft tissue sarcomas on fine-needle aspiration cytology smear.

In this present study we have attempted to grade soft tissue sarcomas on fine-needle aspiration cytology (FNAC) material and then subsequently correlated our findings on histology section.A total of 44 cases of primary soft tissue sarcomas (STS) were graded and correlated with the subsequent histopathology sections.FNAC successfully diagnosed 40 cases and four cases were reported as benign. There were 11 grade I, 32 grade II and one grade III cases on histopathology. Out of the 11 grade I cases, only three cases were graded correctly on cytology. On FNAC, 31 sarcomas were diagnosed correctly as grade II tumors and one case was under diagnosed as benign. There was a single case of grade III sarcoma on histopathology which was correctly diagnosed and graded on FNAC.In majority of the STS it is possible to grade on FNAC. Grade I STS is relatively difficult to grade than grade II STS.

Proximal-type epithelioid sarcoma in the groin presenting as a diagnostic dilemma.

Epithelioid sarcoma is an uncommon soft-tissue sarcoma typically presenting as a subcutaneous or deep dermal mass in the distal extremities of young adults. Lately, a 'proximal' subtype has been described, which occurs in the pelvic and genital areas of somewhat older individuals and tends to behave more aggressively than the conventional subtype. The correct diagnosis of this subtype is essential, since this tumor can be easily mistaken for other malignant tumors that exhibit epithelioid morphology. We report a case of proximal-type epithelioid sarcoma that presented as an inguinal mass in a 47-year-old man. Histologically, the tumor consisted of diffuse sheets of epithelioid cells with scattered rhabdoid morphology. By immunohistochemistry, the neoplastic cells expressed cytokeratin, epithelial membrane antigen, vimentin, CD34, CD99 and showed complete loss of nuclear INI1 protein expression. Fluorescence in situ hybridization was considered borderline for 22q deletion. We present this case to emphasize the importance of diagnosing this uncommon tumor and the role of INI1 immunohistochemistry in establishing the diagnosis.

Hodgkin's lymphoma: diagnostic difficulties in fine-needle aspiration cytology.

It is commonly believed that cytodiagnosis of Hodgkin's lymphoma (HL) is much easier than that of non-Hodgkin lymphoma (NHL). However, recognition of certain NHL subtypes with Reed-Sternberg (R-S)-like cells and results of immunohistochemical studies point to the contrary. To study the limitations of cytology in diagnosis of HL, fine-needle aspiration (FNA) smears of 130 lymphoma or suspected lymphoma cases were reviewed. Initial and reviewed cytodiagnoses were compared with histopathology in 89 cases. Immunocytochemical and immunohistochemical studies were performed in 56 and 59 cases, respectively. Among histologically diagnosed HL cases, definitive cytodiagnosis of HL (initial as well as reviewed) was significantly less frequent than cytodiagnosis of NHL among histologically diagnosed NHL cases (P = 0.0328 and = 0.0001, respectively). On the other hand, cytologically diagnosed HL/NHL cases were significantly more frequent in the former group (P = 0.0001 and = 0.0018, respectively). ALCL and TCRBCL were the two NHL subtypes which created confusion with HL in FNA smears. Twenty-one cytohistological concordant HL cases and equal number of discordant cases were compared. When compared with discordant group, the patients in concordant group were significantly younger (P = 0.045). Hodgkin/Hodgkin-like cells and typical R-S cells were significantly more frequent in FNA smears of the concordant group (P = 0.0478 and = 0.0431, respectively). Immunocytochemical and immunohistochemical studies showed good correlation with histological diagnosis of HL. It is suggested that proper interpretation of cytologic features, together with use of immunocytochemical parameters can help in reducing the margin of error in cytodiagnosis of HL.

Fine-needle aspiration cytologic features of four special types of breast cancers: mucinous, medullary, apocrine, and papillary.

Recognition of special types of breast cancers by fine-needle aspiration (FNA) cytology may have prognostic implications but some difficulties still exist in the ability of cytopathologists to determine the tumor subtypes. Detailed cytomorphological features were studied in the four special and unusual types of breast cancer cases (8 cases of mucinous, 9 medullary, 9 apocrime, and 11 papillary) and compared between themselves and with those of 32 duct cell carcinomas, not otherwise specified (NOS). Papillary carcinomas were also compared with 10 benign papillary lesions. The significance of the differences was determined using Fishers' Exact Test of Probability. In mucinous carcinoma, the frequency of signet ring cells (62.5%), and background pools of mucin (87.5%) were significantly higher than those of duct cell carcinoma (NOS), medullary carcinoma, apocrine carcinoma, and papillary carcinoma (P = 0.0408 to < 0.0001). In medullary carcinomas, lymphomononuclear cell infiltration (100.0%) was observed in significantly higher number of cases than in papillary, mucinous, and apocrine types (P < 0.0001). Further, moderate to marked nuclear pleomorphism (100.0%) and nuclear irregularity (77.8%) was significantly higher than those of mucinous carcinoma and papillary carcinoma (P = 0.0294 to <0.0003). Abnormal apocrine cells and papillary formation, characterizing all the apocrine carcinomas and papillary carcinomas, respectively, were present in significantly lower number in other variants and in duct cell carcinoma (NOS) (P = 0.0002 to <0.0001). Glycogen vacuoles (63.6%) were observed in a significantly higher number of papillary carcinoma as compared to duct cell carcinoma (NOS), apocrine, and medullary carcinomas (P = 0.0047 to 0.0022). The significant parameters differentiating papillary carcinoma and benign papillary lesions were loose cohesive clusters (P = 0.001) and acinar formation by neoplastic cells (P = 0.0237). Histopathology reports available in 36 cases, confirmed the cytodiagnosis of carcinoma in all 35 cases and the benign lesion in one case. Cytological subtyping was confirmed in 13 of 16 special types of carcinomas and all the 15 duct cell carcinoma (NOS). Thus, special and unusual variants of duct cell carcinomas like mucinous, medullary, apocrine, and papillary have specific cytomorphological features, which differentiate them from one another and from duct cell carcinoma (NOS). However, differentiating features between papillary carcinoma and benign papillary lesions were very few in this study.