Cytomorphologic Findings Research Articles

Utility of The Paris System for Reporting Urinary Cytology in patients with HPV-positive urinary tract carcinoma.

Human papillomavirus (HPV)-positive urinary tract carcinomas (UTCas) have distinct morphology and molecular features with potential treatment implications. Cytomorphologic analysis of these tumors on urine cytology specimens has not yet been reported. The authors evaluated the cytomorphologic findings of HPV-positive UTCa on urine cytology using The Paris System for Reporting Urinary Cytology (TPS) criteria. HPV-positive cases were identified by a retrospective review of surgical specimens that had UTCa confirmed by HPV in situ hybridization. Cases that had concurrent urine cytology were reviewed using TPS. Cytomorphologic features of high-grade urothelial carcinoma (HGUC) were evaluated as well as the presence of atypical squamous cells (ASCs) and basaloid features. Sixteen cytology specimens from eight patients with HPV-positive UTCa were included. On original diagnosis, none of the cytology specimens were suggested to be HPV-associated. TPS diagnostic criteria identified eight cases with at least atypical findings, including five HGUC cases, one case that was suspicious for HGUC, and two atypical urothelial cases. Common cytomorphologic features included basaloid clusters (six of eight cases; 75%) and ASCs (four of eight cases; 50%) that matched the corresponding surgical specimens. Most cases exhibited urothelial cell hyperchromasia (seven of eight cases; 88%), and hypochromasia was a frequently observed variant (four of eight cases; 50%), either alone or in addition to hyperchromasia. HPV-positive UTCa can be identified reliably as HGUC by using TPS criteria; however, these cases may not be recognized as HPV-associated. The presence of basaloid cells or ASCs can help suggest screening for HPV in urine specimens. Larger scale studies are warranted to validate cytomorphologic differences and determine the impact of HPV infection on clinical outcomes for patients with UTCa.

Cytomorphological findings in confirmed cases of tubercular lymphadenitis.

Tuberculosis (TB) remains a major health problem, especially in the developing countries. Fine-needle aspiration cytology is the first line of investigation for tubercular lymphadenitis as it is easy to perform, less invasive, quick, and economical. The typical cytopathological features of tuberculosis TB include epithelioid cell granulomas with Langhans giant cells and caseous necrosis. The present study aimed to evaluate the cytomorphological features of newly diagnosed cases of tubercular lymphadenitis confirmed by GeneXpert. This was a retrospective study in which all fine-needle aspirates from newly diagnosed cases of tubercular lymphadenitis confirmed by GeneXpert over a 1-year period from July 2022 to July 2023 were included in the study. The May-Grunwald-Giemsa stained smears from these aspirates were categorized into three patterns-epithelioid cell granulomas with necrosis, epithelioid granulomas without necrosis, and necrosis only. The granulomas were further categorized into well-formed, ill--formed, and splintered. The background of the aspirate which included a reactive lymphoid background, lymphocytes, eosinophils, and neutrophils was tabulated for all the cases. Out of the three cytomorphological patterns, epithelioid granulomas with necrosis were the most predominant (67.5%), followed by necrosis only (20.8%) and granulomas without necrosis (11.6%). An acid-fast bacilli (AFB) positivity of 53.3% (64 cases) was seen on the Ziehl-Neelsen stain. Well-composed, poorly formed, and splintered granulomas were seen in 55 (57.9%), 42 (44.2%), and 21 (22.1%) cases, respectively. Neutrophils were the most common background population (42, 35%) followed by lymphocytes (36, 30%). Reactive lymphoid cells and eosinophils were seen in 12 (10%) and 3 (2.5%) cases, respectively. Fine-needle aspiration cytology is a rapid inexpensive minimally invasive test for tubercular lymphadenitis as epithelioid cell granulomas along with caseous necrosis are highly suggestive of TB. However, manual acid-fast AFB detection has a low sensitivity as is illustrated in the present study where only AFBwas demonstrated in only 53.3% of cases.

Cytomorphological Profile of Graves' Disease and its Co-relation with anti-TPO Antibody

Objective: Thyroid diseases are major health problems in our society, which are manifested by alteration in hormone secretion, enlargement of the thyroid gland. FNAC plays a significant role in the diagnosis of thyroid lesions due to its simplicity and low cost and with a diagnostic accuracy rate of 92%. This study was designed to cytomorphological profile of Graves’ disease and its co relation with anti TPO antibody. Materials and Methods: This is a prospective analytical study of fifty patients with clinically enlarged thyroid gland presenting at STG Hospital, Haldwani, Nainital during Oct 2019 to Oct 2022. FNAC smears of these patients were studied and correlated with cytomorphological findings of different types, grades of thyroiditis and hormone level of T4, T3 and T.S.H. Results: Females were mostly affected by thyroid diseases than males. Female patients were 39 (78%) and male patients were 11 (22%). In the present study, patients were in the age group of 13 to 74 years of age. High T3 levels were noted in 80% high T4 levels were found in 90%. Low TSH level was found in only 64%, normal TSH level found in 34% and 2% presented with high TSH level. 34 patients (68%) found high anti-thyroid peroxidase antibody titre >34 U/ml. Cytomorphology revealed moderate to high cellularity in 88% cases, mild to moderate nuclear atypia in 86% and presence of marginal vacuoles in 82%. Lymphocytic infiltrate found in 24% cases and epithelioid cell granuloma in 14% cases. Conclusion: Thyroid cytology proves to be a reliable, simple, and cost-effective first-line diagnostic procedure with high patient acceptance and with rare, usually easily treated and not life-threatening complications. We recommend further studies with a larger population to validate our study. Keywords: Thyroiditis, Graves' Disease, Malignancy Goiter, Histopathology

Comparison of cytomorphology and histomorphology in myelodysplastic syndromes.

Gold standard for the establishment of the diagnosis of myelodysplastic syndromes (MDS) are cytomorphological features of hematopoietic cells in peripheral blood and bone marrow aspirates. There is increasing evidence that bone marrow histomorphology not only aids in the diagnosis of MDS but can provide additional prognostic information, particularly through assessment of fibrosis and cellularity. However, there is only sparse data on direct comparison between histological and cytomorphological findings within the same MDS patient cohort. Therefore, we performed such an analysis under exceptionally well-standardized conditions. We reexamined biopsy material of 128 patients from the Düsseldorf MDS registry who underwent bone marrow trephine biopsy (in addition to bone marrow aspiration) at the time of diagnosis, addressing the following items: a. Analysis of concordance of diagnoses made by histology and cytomorphology b. Analysis of additional information by histology with regard to the diagnosis and prognosis. The respective biomaterials were available at our institution and had been processed according to unchanged protocols between 1992 and 2010. Fresh histopathological sections were obtained from the tissue blocks, stained under identical conditions and re-assessed by a designated expert pathologist (C.B.) without knowledge of the previous histopathological report or the respective cytomorphological diagnosis. The latter, likewise, was uniformly made by the same expert cytomorphologist (U.G.). Histopathology of bone marrow trephine biopsies reliably captured the diagnosis of MDS. Assignment to the diagnostic WHO subgroup was not entirely concordant with cytomorphology, mainly due to incongruences between the proportion of CD34-positive cells on histopathology and the cytomorphological blast count. Histopathology provided additional diagnostic and prognostic information with high diagnostic and prognostic significance, such as fibrosis. Likewise, histopathology allowed more reliable estimation of bone marrow cellularity.

Cytomorphology of metastatic colonic MXD4::NUTM1-rearranged sarcoma.

This report describes the cytologic features of a recently described MXD4::NUTM1-rearranged colonic sarcoma metastatic to the midclavicular soft tissue. Thirteen years ago, a 65-year-old woman presented with a cecal mass and subsequent liver mass. The cecal mass was diagnosed as malignant undifferentiated spindled and epithelioid neoplasm based on morphology and lack of tumor immunoreactivity with a panel of epithelial, smooth muscle, skeletal, melanoma, hematologic, and GIST markers. The liver mass showed morphologic and immunophenotypic similarity to the epithelioid component of the patient's cecal mass, albeit devoid of the spindled component. Fine needle aspiration of the midclavicular soft tissue mass showed singly scattered to clustered epithelioid to rhabdoid tumor cells with centrally to eccentrically located nuclei, prominent nucleoli, and moderate eosinophilic cytoplasm. Immunohistochemical stains performed on the concurrent biopsy showed the tumor cells were positive for NUT and negative for all other additional markers with retained normal expression of SMARCA2 and SMARCA4. Next-generation sequencing showed the presence of MXD4::NUTM1 gene fusion. Due to the identical cytomorphologic findings with the epithelioid component of the patient's prior cecal and liver masses, the tumor was deemed as consistent with a NUTM1-rearranged sarcoma. To our knowledge, this case represents the first reported cytologic features of a NUTM1-rearranged sarcoma on fine needle aspiration. Familiarity with the cytologic features, inclusion of this entity in the differential diagnosis of tumors with epithelioid and/or rhabdoid morphology, and performance of ancillary tests (immunohistochemistry and molecular) will be helpful in arriving at the right diagnosis.

Gastrointestinal stromal tumors in fine-needle aspiration biopsies.

Gastrointestinal stromal tumors (GISTs), although rare, are the most common mesenchymal neoplasms of the gastrointestinal tract. Their potential for malignancy underscores the significance of identifying them through cytomorphologic findings and pertinent immunohistochemical markers. GISTs can emerge anywhere along the gastrointestinal tract with a predilection for the stomach. The clinical manifestations vary from nonspecific abdominal symptoms to incidental discovery during diagnostic interventions for unrelated signs and symptoms. Cytologically, GIST aspirates contain spindle or epithelioid cells with immunoreactivity for CD117/c-KIT, DOG-1, and CD34. Molecularly, KIT or PDGFRA mutations are prevalent, guiding targeted therapy with tyrosine kinase inhibitors. Distinct subtypes like succinate dehydrogenase-deficient GISTs pose challenges, often affecting younger individuals and displaying unique features. Histologically, GISTs are graded by mitotic rates, aiding prognostication. Distinguishing GISTs from similar entities is pivotal, necessitating attention to their immunostaining patterns for making an accurate diagnosis and molecular alterations for effectively planning treatment. Common differential diagnoses include leiomyoma, schwannoma, and solitary fibrous tumor. This article presents a classic GIST case and showcases relatively simple diagnostic clues for identifying similar lesions that may occur in diverse locations.

Understanding cytomorphologic changes in Pap tests of transgender men on testosterone therapy

Abstract Introduction/Objective Pap test findings in transgender men on testosterone therapy can often lead to misdiagnosis of dysplasia, especially in the setting of a positive HPV test. We reviewed relevant literature to analyze the cytomorphological nuances and applicable correlations to subsequent pathology in Pap tests of transgender men on testosterone therapy. Methods/Case Report We searched peer-reviewed journals on PubMed, synthesizing five articles published from 2018-2022 that specifically address cytomorphological findings on cervical Pap tests and biopsy results in transgender men on testosterone therapy. Results (if a Case Study enter NA) Various cytological changes, such as small parabasal-type cells and transitional cell metaplasia (TCM) can be mistaken for dysplasia in transgender men. In fact, these changes are representative of atrophy due to testosterone, as such findings have been observed in patients undergoing tamoxifen therapy. Small parabasal-type cells are described as clusters or sheets with intermittent nuclear enlargement and hyperchromatic nuclei, whereas TCM comprises flat sheets of cells with oval to spindle-shaped nuclei, powdery chromatin, and prominent nuclear grooves. Relevant clinical history can often help clarify cytologic diagnoses, as Pap tests that show atrophic changes can be misinterpreted as being abnormal. In several cases described in the literature, original diagnoses of atypical squamous cells of undetermined significance (ASCUS) were re-interpreted as atrophic changes after eliciting a history relevant for testosterone therapy. Small parabasal-type cells found on cytology have correlated with sections of the ectocervix that have groups of small hyperchromatic cells attached to the surface of atrophic cervical epithelium or areas of TCM. These cells may be mistaken for endometrial cells, especially in patients over 45 years old. Distinguishing atrophic changes from dysplasia on surgical pathology may modify cytologic diagnoses. Conclusion Transgender men on testosterone therapy often retain their cervix, necessitating ongoing cervical cancer screening. However, Pap test results from these individuals often exhibit atrophic changes through the presence of small parabasal-type cells and TCM. Differentiating between atrophy and dysplasia can pose a diagnostic challenge, especially in the setting of positive HPV testing or inflammation. Continued analyses into these cytomorphological nuances will assist providers in refining their diagnostic approaches and providing personalized care to transgender men.

Cytomorphology of mesenchymal lesions in a tertiary care centre and its correlation with histopathology.

Fine needle aspiration cytology (FNAC) is a minimally invasive method for sampling a heterogenous lesion. It is one of the first-line investigations in the evaluation of soft tissue tumours. However, the heterogeneity of mesenchymal lesions pose a challenge to the cytological diagnosis. The present study aims at evaluation of the cytomorphological findings of mesenchymal lesions on FNAC along with their histopathological correlation. This was a retrospective study conducted over a period of 1 year from January 2021 to January 2022. All the patients of cytologically diagnosed mesenchymal lesions on their FNA aspirates were included in the study. Cytomorphology of the May Grunwald Giemsa and Papanicolaou stained slides were examined and correlated with clinical and histopathological details wherever available. Out of the 90 patients, 69 (76.7%) were males and 21 (23.3%) were females. Maximum number of cases were in 4-5th decade of life. The lower limb was found to be the most common site (57.8%) for the mesenchymal lesions. Majority of the cases on FNA in our study were found to be benign - 79 (87.8%), while only 11 cases were malignant (12.2%). On cytological examination, spindle cell lesions were most common followed by adipocytic lesions. Based on the cyto-histological correlation, sensitivity, specificity, negative predictive value, positive predictive value and diagnostic accuracy of FNAC in diagnosis of mesenchymal lesion was 78.6%, 100%, 92.5%, 100% and 94.1% respectively. FNAC is a simple and minimally invasive tool that plays an important role in triaging patients with good specificity and sensitivity.

Cytomorphological findings in drug defaulters of tuberculous lymphadenitis.

Tuberculosis (TB) is an important health problem specially in the developing countries. Although effective chemotherapy is available, compliance of patient is a major challenge. The aim of this study was to describe cytomorphological features of drug defaulters on lymph node on fine-needle aspiration cytology (FNAC) and compare it with newly diagnosed cases. A cross-sectional study was done for a period of 18 months, in which all patients having tuberculous lymphadenitis were included after taking detailed history regarding previous anti-TB drug intake. Cytomorphological findings in drug defaulters were evaluated and compared with newly diagnosed cases. There were a total of 150 cases with 120 newly diagnosed and 30 drug defaulters. Splintered epithelioid cell granuloma was seen in 40% of drug defaulters, while it was absent in case of newly diagnosed cases (P < 0.0001). Well-formed epithelioid cell granuloma was most commonly seen in newly diagnosed cases (65.83%) followed by poorly formed granuloma (26.67%). Another significant finding was distribution of eosinophils which were significantly high in case of drug defaulters (56.67%) (P < 0.0001). Cytomorphological findings can help in identification of the drug defaulters on FNAC and thus plan further line of treatment.

False-Positive Atypical Endocervical Cells in Conventional Pap Smears: Cyto-Histological Correlation and Analysis

Introduction: Endocervical glandular atypia is relatively rarely diagnosed by Pap smears. A significant proportion of follow-up histological samples show no premalignant or malignant lesions. The observed cytomorphological findings in premalignant glandular lesions overlap with histologically proven reactive lesions. Methods: A total of 45 conventional Pap smears diagnosed as atypical endocervical cells, not otherwise specified (AEC, NOS) with human papillomavirus (HPV) status available were blindly evaluated in a search for 38 cytomorphological features representing background, architectural, cellular, and nuclear features. Of the cases, 30 represented histologically proven benign changes, and 15 represented histologically proven adenocarcinoma in situ (AIS) or endocervical adenocarcinoma (EAC) cases. The benign biopsies were re-evaluated, and the associations of the cytomorphological features or combinations of them with specific histological features and entities were statistically examined. Results: The most frequent histological findings in the benign group were squamous metaplasia, inflammation, tubal metaplasia, and microglandular hyperplasia. The statistical analysis revealed cytological features associated with squamous metaplastic changes, inflammation, and microglandular hyperplasia. Unfortunately, no cytomorphological feature was sufficiently specific to confidently leave the lesion without follow-up and histological correlation. Degeneration and nuclear crowding were the most salient features that distinguished the instances of glandular atypia with benign follow-up histology from those with histologically proven AIS or EAC (26.7 vs. 60.0%, p = 0.030, and 50.0 vs. 86.7%, p = 0.017). Conclusion: Additional methods besides cytomorphology are required to reliably distinguish smears with AEC, NOS harbouring only benign histological changes from those exhibiting endocervical glandular malignancy.

Cytomorphological findings of Trichophyton rubrum infection in an elderly hypertensive woman.

Trichophyton is a dermatophytic fungi causing superficial skin infections which affects outermost layer of the epidermis, stratum corneum, and mainly involves feet, groin, scalp, and nails. Invasion into the dermis occurs mainly in immunocompromised patients. A 75-year-old hypertensive female presented with a nodular swelling on the dorsum of right foot for 1 month. The swelling was 1.0 × 1.0 cm and gradually progressive in nature. FNAC revealed many thin filamentous branching and fungal hyphae along with foreign body granulomas and suppurative acute inflammation. The swelling was excised and sent for histopathological examination which confirmed the above findings. Periodic Acid Schiff stain showed fungal hyphae in both cytology smear as well as histopathology section. On fungal culture, microconidia with septate hyphae suggestive of Trichophyton rubrum was seen. Trichophytons mainly affect immunocompromised and diabetic patients, however, may present as nodular lesions without any history of superficial dermatophytosis as seen in the present case. The characteristic cytological picture helped to clinch the diagnosis in this case and facilitated further management.

Cytology of micropapillary mucinous carcinoma: A case report of a clinically and genetically distinct breast carcinoma variant.

Micropapillary mucinous carcinoma (MPMC) is an uncommon histopathological variant of breast cancer accounting for approximately one-fifth of all mucinous breast carcinomas. In contrast to pure mucinous carcinoma, MPMC tends to affect younger women and is associated with decreased progression-free survival, higher nuclear grade, lymphovascular invasion, lymph node metastasis, and positive HER2 status. Typically MPMC histology shows micropapillary architecture with "hobnailing" of cells and reverse polarity. Very few publications document the cytomorphological findings of MPMC. We report a case of MPMC that was suspected in fine needle aspiration cytology (FNAC) and confirmed at histopathology.

Cytologic features of gynecologic germ cell tumors and carcinomas exhibiting germ cell tumor differentiation.

In this study, the authors sought to describe the cytologic features of primary gynecologic germ cell tumors and carcinomas exhibiting germ cell differentiation because little information currently exists. An institutional database search was performed to identify histologically confirmed gynecologic germ cell tumors and carcinomas with germ cell tumor differentiation. Available cytologic material was reviewed by three observers, and morphologic features were recorded in addition to patient age at original diagnosis, primary tumor site, site(s) from which the examined cytologic material was obtained, and the type of examined cytologic preparations. In total, 15 cytologic specimens from 12 women (aged 19-82years) were identified and included touch preparations of core biopsies from various sites (n=6), fine-needle biopsies (n=2), pelvic washings (n=1), ascitic fluids (n=4), pelvic cyst fluid (n=1), and endometrial aspirate (n=1). Of the 12 patients, seven had primary gynecologic germ cell tumors, four had gynecologic (ovarian and endometrial) tumors exhibiting somatic yolk sac tumor-like differentiation, and the remaining patient had an intestinal-type adenocarcinoma arising within an ovarian teratoma. There was morphologic overlap among many of the cases, although cytoplasmic vacuolation/granular cytoplasm was seen in 75% of primary yolk sac tumors or carcinomas with yolk sac tumor differentiation, and dense/squamoid cytoplasm was seen in 100% of teratomatous elements that were sampled. Germ cell tumors and somatic neoplasms exhibiting germ cell tumor differentiation occurring in adult women share some cytologic features and may be difficult to distinguish from one another, although some tumor types showed characteristic cytomorphologic findings.

Identification of Phenotypic Subgroups of Acute Myeloid Leukemia, Defined By Differentiation According to Who 2022 Classification

Background: The recently published WHO classification 2022 has extended genetic findings as the diagnostic basis for acute myeloid leukemia with defining genetic abnormalities (AML-DGA) resulting in 13 such entities leaving only a minority of cases not genetically defined, i.e. AML, defined by differentiation (AML-DBD). Clustering of flow cytometrically (FC) analyzed immunophenotypes may help to identify subgroups within AML-DBD allowing to search for additional genetic abnormalities which in future WHO classifications may qualify for AML-DGA. Aim: To identify subgroups within AML-DBD based on immunophenotypes analyzed by FC and to elucidate their genetic background applying panel sequencing. Methods: In a multicenter study comprising four institutions in North America, Europe and Asia cases with AML-DBD according to WHO 2022 classification were selected which had been diagnosed applying broad antigen panels by FC and broad gene panels by NGS. Expression data by FC on 30 surface and cytoplasmic antigens were collected and rated as negative, dim, partial and bright. Cluster analysis was performed to identify subgrops of cases with similar phenotpyes. Patterns of gene mutations within these subgroups were assessed. Results: A total of 234 AML-DBD were identified and included in the study. Nine antigens were found to be differentially expressed and to contribute to defining subgroups: MPO, CD34, CD11b, CD14, CD36, CD45, CD15, CD64 and CD65. Clustering of cases appyling expression categories of these nine antigens resulted in the identification of seven subgroups with clear differences in the antigen expression patterns (figure, panel A). Groups 1 and 3, different from all other groups, both showed bright expression of MPO and CD34 but only group 3 in addition showed bright CD36 expression (figure, panel B). Groups 2 and 4 also brightly expressed CD34 but showed only dim and no expression, respectively, of MPO. Conversely, groups 5 and 6 showed bright MPO expression with heterogeneous and largely no expression, respectively, of CD34. Group 5 exclusively showed bright expression of CD45 and CD64 in line with a monocytic phenotype. Group 7 was characterized by merely no or dim only expression of the nine antigens found differentially expressed between these seven groups. Interestingly, there has been no clear correlation between these seven groups and cytomorphologic findings besides AML with maturation occuring frequently in groups 1 (51% of cases) and 4 (67%) and AML without maturation in group 7 (57%). NGS revealed mutations in seven genes, which are not used by the WHO 2022 classification to define AML-DGA, to occur at different frequencies among the seven subgroups: DDX41(non germline), DNMT3A, FLT3-ITD, IDH1, IDH2, KMT2A-PTD and NRAS. In groups 1 to 4 20% to 39% of cases showed DDX41 mutations but no cases did so in groups 5 to 7. DNMT3A mutation frequencies varied among all groups between 17% and 44%. FLT3-ITD was found in 50% of group 5 but in only 7% to 28% of other groups. Mutations in IDH1 and IDH2 were found in all groups at frequencies ranging from 17% to 44%. While in the majority of groups frequencies of IDH2 mutations exceeded those of IDH1 mutations this was not the case in groups 3 and 5. KMT2A-PTD were found at a particularly high frequency of 44% in group 7 with other groups showing frequencies between 5% and 33%. NRAS mutations were found overall most infrequently with frequencies in groups ranging from 4% to 17%. Conclusions: Clustering of flow cytometric data revelad seven subgroups of AML-DBD with different antigen expression patterns in nine differentially expressed genes. Results of panel sequencing revealed differences in the genetic background of the seven groups but at the same time showed overlaps in mutation patterns between groups. Following the insights in the genetic basis of hematopoietic neoplasms gained in recent years and its application as principles in the WHO classification 2022 it is anticipated that the seven subgroups of AML-DBD identified in the present study feature additional genetic abnormalities besides the mutations described here. Whole genome and transcriptome sequencing will help identifying these additional abnormalities. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Comparison of Cytomorphology and Histopathology in Myelodysplastic Syndromes (MDS)

Introduction: Bone marrow cytomorphology, cytogenetics and molecular analyses are essential tools for diagnosing a myelodysplastic syndrome. MDS are characterized by dysplastic features of hematopoietic cells and may also show an increased blast cell count. Histopathology can provide additional information on bone marrow fibrosis and cellularity. We analysed correlations and differences between cytomorphological and histopathological findings at diagnosis. Patients and methods: In the Duesseldorf MDS registry, we identified 127 patients with detailed information available on bone marrow cytomorphology, blast count, blood cell counts and clinical features, who also had a bone marrow core biopsy taken at the time of diagnosis. From their formalin-fixed, paraffin-embedded histopathology specimens new sections and stains were made and evaluated by one reviewing pathologist (SB) who assessed a predefined set of features. The pathologist had no knowledge of the cytomorphological findings, except for the information that the specimen was from a "patient with myelodysplastic syndrome". Statistical analyses were performed by SPSS. Procedures were in accordance with the current version of the Helsinki Declaration. Informed consent was obtained from all patients included in the study. Results: The estimation of the percentage of CD34-positive cells by histopathology differed significantly from the cytomorphologically assessed medullary blast count, with a trend towards histopathological underestimation of blast cells (figure 1). Assessment of dysmegakaryopoiesis by histopathology identified 44 cases with dysplastic features, which were deemed inconspicious by cytomorphology. Histopathology yielded a significant positive correlation (p=0.002) between cellularity and degree of dysmegakaryopoiesis, and these two features were also correlated with higher-risk WHO subtypes. Fibrosis and dysmegakaryopoiesis were negatively correlated. Bone marrow cellularity seemed to be overestimated by cytomorphology compared with histopathology. The percentage of erythropoietic cells did not correlate well between cytomorphological and histopathological review. Neither WHO subtype nor medullary blast count showed an association with the proportion of erythropoiesis, regardless of the mode of evaluation. All patients with expanded erythropoiesis also showed signs of dysmegakaryopoiesis. There was no case of cytomorphologically diagnosed MDS that was not confirmed by histopathology, and 48% of MDS diagnoses were identical as to their WHO subtype. However, in 66 cases (52%), the WHO type diagnosed by histopathology differed from the WHO type diagnosed by cytomorphology. The discrepancy was mainly due to differing estimates of medullary blast counts. In our cohort, the degree of fibrosis positively correlated with bone marrow cellularity, a finding that appeared counterintuitive to clinical experience. Increased cellularity also correlated with higher-risk MDS subgroups. Prognosis in terms of overall survival was influenced by the following parameters: Cytomorphologically assessed medullary blast count, bone marrow cellularity, fibrosis, and percentage of erythropoiesis, the latter assessed by histopathology. Patients with of grade 2 or 3 fibrosis had an inferior outcome (figure 2). Conclusions: In our study, histopathology was fully congruent with bone marrow cytology as far as making a diagnosis of MDS is concerned. Histopathology, though, often underestimated the blast count and showed difficulty in identifying the correct MDS type according to the WHO classification. Histopathology is also at a disadvantage regarding evaluation of single cell morphology, with the exception of assessing certain aspects of dysmegakaryopoiesis. A clear advantage of histopathology is its exclusive capability of gauging bone marrow fibrosis and cellularity, both of which are relevant for the diagnosis and prognosis of MDS. We conclude that cytomorphology and histopathology should both be harnessed to optimize the characterization of a patient's myelodysplastic syndrome. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

A rare case of sebaceous lymphadenoma: Cytohistological correlation of preoperative cytomorphologic findings

We are presenting a case of a 74-year-old female with a parotid gland mass. Fine-needle aspiration (FNA) of the mass demonstrated cohesive groups of epithelial cells with overall bland-appearing nuclei and abundant vacuolated cytoplasm, consistent with sebaceous cells, in a background of polymorphous lymphocytes, scattered histiocytes, and adipose tissue. Immunostains showed that the epithelial cells stain positive for p63, but negative for CD117 and DOG-1. CD3 and CD20 showed a mixture of T- and B-cells. On the PAP-stained slides, there were numerous sac-like structures, consistent with myospherules. These findings were suggestive of neoplasm with sebaceous differentiation. The main differential diagnosis included sebaceous adenoma, sebaceous lymphadenoma, and other benign lesions with sebaceous differentiation. The parotid mass was resected. Histology sections demonstrated a well-circumscribed neoplasm with multicystic epithelial component and surrounding lymphoid infiltrate, consistent with sebaceous lymphadenoma. Sebaceous lymphadenoma (SLA) is a rare benign salivary gland neoplasm that is most commonly seen in the parotid gland. Preoperative FNA diagnosis of sebaceous neoplasms is challenging. To the best of our knowledge, this is the third case of sebaceous lymphadenoma diagnosed preoperatively. In this manuscript, we detail the epidemiological characteristics and histogenesis of sebaceous salivary gland neoplasms, and the cytomorphologic differential diagnosis of SLA with key diagnostic features of each entity.

Cerebrospinal fluid infiltration by chronic myeloid leukaemia: Evaluation of cytomorphological features.

To describe the cytomorphological findings of all cerebrospinal fluid (CSF) cytology samples showing infiltration by chronic myeloid leukaemia (CML) and their correlation with haematological findings. A retrospective analysis of all CSF samples reported as showing infiltration by CML on cytology from January 2014 to December 2021 was performed. A total of 10 cases with positive CSF cytology were evaluated. The mean age of the patients was 34.1 years (range 17-70 years). There were more males than females. All cases were pre-diagnosed cases of CML on haematological investigations. On cytology, the smears showed atypical/immature blast-like cells, with a high nucleo-cytoplasmic ratio, opened-up chromatin, 1-2 conspicuous nucleoli and a scant to moderate amount of agranular to fine granular cytoplasm along with occasional granulocytic precursors. The shortest time interval for CSF positivity in a known case of CML was 5 months, and the longest interval was 11 years. It is extremely uncommon to encounter CML infiltration in CSF. Timely analysis of CSF cytology samples can allow quick diagnosis and alter the patient management protocol.

A roadmap for a comprehensive diagnostic approach to fine needle cytology of lymph node metastases.

Fine needle cytology (FNC) is widely used as a first-line procedure in the diagnostic algorithm of lymphadenopathies. In a metastatic setting, a first-line diagnostic approach identifies non-haematopoietic malignancy; however, cytopathologists could also provide a second diagnostic level, identifying the origin of the primary tumour. This paper outlines a comprehensive and practical approach to the cytological diagnosis of lymph node metastases. Cytological diagnoses of lymph node metastases performed over a 10-year period were selected and divided into two groups. The first group, labelled "oncological," comprised patients with a previous history of malignancy; the second group, labelled "naïve," included patients with no relevant history. Pathology records were retrieved to record microscopic findings, namely, background appearance, group architecture, and specific cell features; data from cell block (CB) preparations were also collected. Overall, 982 cases were selected: 497 cases (50.61%) in the naïve group, and 485 (49.39%) in the oncological group. Overall, a second diagnostic level was achieved in 834/982 cases (84.92%); cases diagnosed as carcinoma not otherwise specified were more frequent in the naïve group than in the oncological group (17.51% vs. 8.04%, P &lt; 0.01). Notably, although CB material was available in only 44.87% of the naïve cases, we were able to achieve a second diagnostic level thanks to the integration of clinical and cytomorphological findings, plus lymph node topography, in 82.49% of the cases. Our results confirmed that in a metastatic setting, FNC can reliably lead to the identification of the origin of the primary tumour.

Dysmegakaryopoiesis and Transient Mild Increase in Bone Marrow Blasts in Patients With Aplastic Anemia Treated With Eltrombopag May Be Signs of Hematologic Improvement and Not Portend Clonal Evolution.

Eltrombopag, a thrombopoietin-receptor agonist, stimulates hematopoiesis in patients with acquired aplastic anemia (AA). Cytomorphologic changes in bone marrow after eltrombopag administration are still unclear. This study examined the effect of eltrombopag on cytomorphologic findings using data from prior phase 2 studies (E1201 and E1202). Microscopic examinations were performed in 31 patients with AA (E1201 [n = 21], E1202 [n = 10]). The relationship between hematologic improvement and morphologic findings was also investigated. In 5 patients (E1201 [n = 3], E1202 [n = 2]), the bone marrow blast count increased after initiation of eltrombopag treatment compared with screening values. The blast count was less than 5%, and the increase in bone marrow blasts was transient in all 4 patients who had bone marrow examinations at follow-up. In 8 patients (E1201 [n = 5], E1202 [n = 3]), dysplastic forms of megakaryocytes were found in the bone marrow following treatment initiation. Dysmegakaryopoiesis of 10% or more was found in 3 patients. None of the patients revealed micromegakaryocytes. Ten patients showed an increase in bone marrow blasts and/or dysmegakaryopoiesis following treatment initiation. Nine of 10 patients showed hematologic improvement in 1 or more lineages. Dysmegakaryopoiesis without micromegakaryocytes and a transient increase of less than 5% in bone marrow blast count may be signs of hematologic improvement with eltrombopag for patients with AA.

Cytomorphological spectrum of solitary fibrous tumour: revisited.

Solitary fibrous tumour (SFT) is a tumour of mesenchymal origin. Its diagnosis on cytology is challenging, owing to variation in cellularity, sparsely distributed cellular and stromal components. Cytomorphological findings for this type of tumour have rarely been described in the literature-only a few case reports and the occasional case series have been presented thus far. We present the cytomorphological features of SFT with special emphasis on immunochemical findings. We present cytological data from eight cases of histopathologically proven SFTs. The cytomorphological features, immunochemical markers and differential diagnostic entities on fine needle aspiration cytology are discussed. Fine needle aspiration was performed at various anatomical sites. Cytology smears showed variable cellularity, with tumour cells arranged in loose clusters and as singly scattered cells. Interlacing fascicles with palisading of cells was noted. The cells were predominantly spindle to elongated, having moderate cytoplasm with elongated wavy nuclei. These nuclei had fine to coarse chromatin, with inconspicuous to prominent nucleoli. There was prominent, metachromatically staining, amorphous to fibrillary, collagenous to myxoid matrix material associated with the tumour cells. Other findings included intranuclear pseudo-inclusions, multinucleated giant cells and atypical mitoses. Cytological diagnoses offered varied from 'spindle cell neoplasm' to 'spindle cell sarcoma' or 'suggestive of sarcoma'. Immunocytochemistry (ICC) performed on cell block sections showed positivity for STAT6, CD34 and Bcl-2. Cytological diagnosis of SFT can be challenging. A careful search for characteristic cytomorphological features is diagnostically helpful. The cytomorphology should be interpreted with caution, with an appropriate ICC panel, including STAT6 and CD34.