Cytologic Features Research Articles

Fine‐needle aspiration and effusion cytology of thoracic SMARCA4–deficient undifferentiated tumor and SMARCA4‐deficient non–small cell lung carcinoma: A multi‐institutional experience with 27 patients

AbstractBackgroundThoracic switch/sucrose nonfermentable–related, matrix‐associated, actin‐dependent regulator of chromatin, subfamily A, member 4 (SMARCA4)–deficient (SD) malignancies, including SD undifferentiated tumor (SD‐UT) and SD non–small cell lung carcinoma (SD‐NSCLC), have been recently described. The cytologic features of these neoplasms in fine‐needle aspiration (FNA) and effusion specimens have rarely been reported in the literature. This study aimed to describe and compare the spectrum of cytologic, immunohistochemical, and clinical features of these high‐grade malignancies recently encountered at the participating institutions.MethodsThis study documented clinical and imaging characteristics of tumors from 27 patients. Sixteen cytomorphologic features and immunohistochemical findings were compared between SD‐UT and SD‐NSCLC samples.ResultsTwenty three FNAs, two bronchial brushings, and two pleural fluids were evaluated, including 17 SD‐UT cases (mean patient age, 70 years) and 10 SD‐NSCLC cases (mean patient age, 62 years). Both malignancies presented with large thoracic masses and/or hilar/mediastinal lymphadenopathy. All SD‐UT cytologic samples had a discohesive or mixed cohesive–discohesive architecture, and most (13 of 17) showed predominant rhabdoid or mixed rhabdoid–epithelioid features. Most SD‐NSCLC cytologic samples (nine of 10) were either cohesive or mixed cohesive–discohesive and had a predominantly epithelioid morphology (eight of 10). Keratins and claudin‐4 were negative or focally positive in SD‐UT samples, whereas they were diffusely positive in SD‐NSCLC samples. Both malignancies were negative for TTF‐1 and p40/p63 and showed loss of expression of SMARCA4.ConclusionsAlthough there is considerable clinical and cytopathologic overlap between SD‐UT and SD‐NSCLC, some key features allow for their distinction. SD‐UT is mostly discohesive with rhabdoid or mixed rhabdoid–epithelioid features, whereas SD‐NSCLC often has cohesive epithelioid morphology. The combination of clinical presentation, cytomorphology, and immunohistochemistry is essential for a definitive diagnosis.

Artefacts in tissue processing: A review

An artificial feature in tissue sections that is self-colored and unrelated is called an artefact. This has been an age long cause of misinterpretation that leads to misdiagnosis. It can result in alteration of normal morphologic and cytologic features that may occur as a result of the way the tissue has been handled, right from the time the biopsy, which is surgically obtained till the entire histopathological procedures of fixation, processing, embedding, sectioning and staining are performed on it. This article reviews the common artefacts encountered during tissue processing.

Fine needle aspiration cytology diagnoses of follicular thyroid carcinoma: results from a multicenter study in Asia

Background: This study was designed to compare diagnostic categories of thyroid fine needle aspiration cytology (FNAC) and incidence of thyroid tumors in the multi-institutional Asian series with a special focus on diagnostic category IV (suspicious for a follicular neoplasm) and follicular thyroid carcinomas (FTCs). Methods: Distribution of FNAC categories, incidence of thyroid tumors in resection specimens and cytologic diagnoses of surgically confirmed follicular adenomas (FAs) and FTCs were collected from 10 institutes from five Asian countries and were compared among countries and between FAs and FTCs. Results: The frequency of category IV diagnoses (3.0%) in preoperative FNAC were significantly lower compared to those in Western countries (10.1%). When comparing diagnostic categories among Asian countries, category IV was more frequent in Japan (4.6%) and India (7.9%) than in Taiwan (1.4%), Korea (1.4%), and China (3.6%). Similarly, incidence of FAs and FTCs in surgical resection specimens was significantly higher in Japan (10.9%) and India (10.1%) than in Taiwan (5.5%), Korea (3.0%), and China (2.5%). FTCs were more commonly diagnosed as category IV in Japan (77.5%) than in Korea (33.3%) and China (35.0%). Nuclear pleomorphism, nuclear crowding, microfollicular pattern, and dyshesive cell pattern were more common in FTCs compared with FAs. Conclusions: Our study highlighted the difference in FNAC diagnostic categories of FTCs among Asian countries, which is likely related to different reporting systems and thyroid cancer incidence. Cytologic features such as nuclear pleomorphism, nuclear crowding, microfollicular pattern, and dyshesive cell pattern were found to be useful in diagnosing FTCs more effectively.

Cytologic hallmarks and differential diagnosis of papillary thyroid carcinoma subtypes

Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy, characterized by a range of subtypes that differ in their cytologic features, clinical behavior, and prognosis. Accurate cytologic evaluation of PTC using fine-needle aspiration is essential but can be challenging due to the morphologic diversity among subtypes. This review focuses on the distinct cytologic characteristics of various PTC subtypes, including the classic type, follicular variant, tall cell, columnar cell, hobnail, diffuse sclerosing, Warthin-like, solid/trabecular, and oncocytic PTCs. Each subtype demonstrates unique nuclear features, architectural patterns, and background elements essential for diagnosis and differentiation from other thyroid lesions. Recognizing these distinct cytologic patterns is essential for identifying aggressive subtypes like tall cell, hobnail, and columnar cell PTCs, which have a higher risk of recurrence, metastasis, and poorer clinical outcomes. Additionally, rare subtypes such as diffuse sclerosing and Warthin-like PTCs present unique cytologic profiles that must be carefully interpreted to avoid diagnostic errors. The review also highlights the cytologic indicators of lymph node metastasis and high-grade features, such as differentiated high-grade thyroid carcinoma. The integration of molecular testing can further refine subtype diagnosis by identifying specific genetic mutations. A thorough understanding of these subtype-specific cytologic features and molecular profiles is vital for accurate diagnosis, risk stratification, and personalized management of PTC patients. Future improvements in diagnostic techniques and standardization are needed to enhance cytologic evaluation and clinical decision-making in thyroid cancer.

Acute myeloid leukemia with peripheral lymph node involvement in dogs: A retrospective study of 23 cases.

Acute myeloid leukemia (AML) can infiltrate extramedullary tissues, such as the liver, spleen, and lymph nodes and can be difficult to differentiate from lymphoma in cytologic and histologic specimens. Our goal was to identify cytologic features that would support a diagnosis of AML in peripheral lymph node aspirates, for which we used the term extramedullary AML (eAML). Medical records of 23 dogs with a diagnosis of AML and archived lymph node aspirate smears from 2016 to 2024 were reviewed across 4 institutions. Inclusion criteria included ≥50% myeloid blasts plus differentiating myeloid cells in lymph node smears, confirmation of myeloid lineage by flow cytometric analysis, and complete medical records. Peripheral lymphadenopathy was the reason for presentation (9/23, 39%) or was found incidentally on physical examination (14/23, 61%). Most dogs were bi- or pancytopenic (18/23, 78%), with blasts identified in blood smears of 18 dogs (78%). Initial lymph node aspirate interpretations included hematopoietic neoplasia (8/21, 38%), AML (6/21, 29%), lymphoma (5/21, 24%), lymphoid hyperplasia (1/21, 5%), and granulocytic precursor infiltrates (1/21, 5%). On lymph node smear review, cytologic features supporting an eAML were differentiating granulocytes, blasts with myeloid features or promonocytes, dysplastic changes in myeloid cells, and retention of residual lymphocytes. The median survival was 22 days (range = 1-360 days), and 69% of 16 dogs given chemotherapy or glucocorticoids lived for 30 days or more. Our study highlights the importance of hemogram results and lymph node aspirate smear examination for morphologic features of myeloid differentiation to help diagnose eAML in lymph node smears.

Case Series of Thermal Cautery Artifact in Urine Cytology: An Uncommon Finding but a Potential Pitfall.

Therapeutic modalities used in bladder lesions/neoplasms (electrocautery, fulguration, and laser) could produce morphologic alterations leading to diagnostic challenges. While often seen on histology, they can present in urine cytology as atypia or even raise the concern for malignancy. Herein, we present clinicopathologic findings of four patients with cautery artifact in urine cytology. The authors' lists and a computerized search of urine cytology with features of thermal cautery artifact were collated. Slides and clinicopathologic variables (prior specimens, concurrent and follow-up surgical specimens, age, sex, manner of urine collection, cystoscopy, and treatment procedure during cystoscopy) were reviewed. Four cases were identified. Procedures performed during cystoscopy included laser therapy (n = 2), postbiopsy cauterization (n = 1), and fulguration (n = 1). All cases showed spindled cells with delicate bipolar cytoplasm, "cigar-shaped" nuclei, smooth to slightly irregular nuclear membranes, and arranged singly and loosely cohesive to lamellar stacks. Few atypical well-preserved, undistorted cells were identified in 2/4. The concurrent biopsies showed superficial cellular fragments with thermal artifact (n = 1) and rare atypical cells (n = 2). Follow-up biopsies in two cases had high-grade urothelial carcinoma both of which were diagnosed as atypical urothelial cells on cytology. Thermal cautery artifact in urine cytology is rare and can be seen following laser, electrocautery, and fulguration. The spindling artifact can render some degree of difficulty in assessing for the presence of urothelial atypia both in cytology and biopsy. Familiarity with these cytologic features, knowledge of the treatment procedure, attention to the cytologic findings of well-preserved cells and repeat sampling in cases with atypical urothelial cells in patients with history of malignancy is essential.

Cytomorphological and histomorphological features of lung adenocarcinoma with epidermal growth factor receptor mutation and anaplastic lymphoma kinase gene rearrangement.

Lung cancer is among the lethal and most prevalent oncological diseases globally. It is known that two types of mutations, namely anaplastic lymphoma kinase (ALK) gene rearrangement and epidermal growth factor receptor (EGFR) gene mutation, are responsible for the development of lung adenocarcinoma. The present study aimed to investigate the differences in the frequency of clinical, cytomorphological and histomorphological features of ALK and EGFR-positive lung adenocarcinomas. The present retrospective study comprised 101 patients diagnosed with lung adenocarcinoma. Based on the molecular findings, the patients were categorized into three groups as follows: The ALK-rearranged group (n=28), the EGFR group (n=42) and the negative group (n=31). The clinical features analyzed included sex, age, smoking status and disease stage. The cytomorphological and histomorphological features examined encompassed the following: Cell cluster size, the arrangement of tumor cells, the size of nuclei, nuclear atypia, the visibility of nucleoli, the presence of necrosis, intracytoplasmic vacuoles, signet ring cells, stromal characteristics and the presence of inflammatory infiltrate presence. The results indicated that the female sex was more prevalent in the EGFR group, but statistically significant differences (P<0.05) were observed between the EGFR and negative group. A significantly greater percentage of non-smokers was identified in the EGFR group compared with the ALK group (P<0.01). The majority of patients with confirmed ALK or EGFR mutations received onco-specific treatment. Focal and abundant necrosis was significantly less common in cytological samples in the EGFR group than in the other groups (21.43 vs. 57.14 and 51.61%, combined, P<0.01). No significant differences were observed in other cytomorphological features between the groups. Intracytoplasmic vacuoles, signet ring cells and cells with visible nucleoli were significantly more frequent in histological specimens of the ALK group (P<0.01). The predictive model composed of these features or combined with sex and smoking habits exhibited statistically significant differences for mutation status as a criterion (P<0.01). Collectively, the findings of the present study confirmed that, in addition to clinical characteristics, certain cytological and histological features of lung adenocarcinoma are associated with the mutational status of the tumor.

Viability and diagnostic potential of tissues obtained through cryobiopsy

BackgroundTransbronchial lung cryobiopsy is primarily used for diagnosing interstitial lung diseases and tumors, providing larger tissue samples with reduced tissue crushing than traditional biopsies. However, freezing during cryobiopsy may damage cells, potentially affecting diagnostic methods that require live cells, such as flow cytometry (FCM). We aimed to determine the extent of freezing-related cell damage in cryobiopsies using cells cultured in vitro. MethodsTo investigate the relationship between freezing duration and sample volume, Jurkat cells underwent freezing for durations ranging from 2 to 6 s, with 1-s intervals, using either 1-mm- or 1.7-mm cryoprobes. FCM was conducted to assess both cell viability (2, 4, and 6 s) and cell-surface molecule expression (3 and 6 s) over varying freezing times. Additionally, we describe a clinical case involving a 70-year-old man suspected of malignant lymphoma, in which tissue samples were obtained via both forceps biopsy and cryobiopsy methods to compare the pathological and cytological features between the methods. ResultsHarvested cell count increased with freezing duration, with a notable increase in viable cell percentage. Moreover, cells distant from the cryoprobe exhibited higher survival rates under milder freezing conditions. FCM revealed significantly higher marker expression levels in viable cryobiopsy samples than in non-viable samples. The clinical case demonstrated that cryobiopsy yields a significant proportion of live cells (>90%), with cytological findings consistent with those of non-frozen samples. ConclusionsCryobiopsy may be beneficial for histopathological diagnosis, providing sufficient viable cells for FCM, and can be used for diagnosing malignant lymphomas and other pulmonary conditions.

The clinicopathologic significance of psammoma bodies in cytology specimens: A series of 78 cases.

Currently the clinicopathologic significance of psammoma bodies in cytology specimens are not completely understood, including types of cytology specimens and pathologic conditions frequently associated with this unique cytologic feature. In this study, we undertook a retrospective approach to review the specimen types, cytology preparations, patient characteristics, organs or tissues involved and differential diagnoses in cytology specimens with the finding of psammoma bodies. Cytology cases with the finding of psammoma bodies from January 2004 to December 2022 were retrieved from our institution's pathology databases, and their clinicopathological features were reviewed. A total of 78 cytology specimens with the finding of psammoma bodies were recorded in our CoPath system. The mean age at diagnosis was 59 years. The patient group showed female gender predominancy (90%). FNA specimens comprised about 38.5% of total cases. Other common specimen types were body cavity fluids (38.5%), including pleural effusion and peritoneal fluid, and about 20.5% of the cases were pelvic washing performed during gynecologic surgeries. Most cytology cases with psammoma bodies had a malignant diagnosis (69%). About 18% of the cases were in the indeterminate diagnostic categories, with 12% suspicious for malignancy and 6% of the cases with atypical cells. About 5% of cases were placed in the neoplastic category, while 8% of cases were negative for malignancy. About 79% of peritoneal cytology with psammoma bodies were neoplastic and mostly gynecologic tumors. Pleural fluids with psammoma bodies were very likely to be malignant and involved by serous carcinoma (15 of 16 cases, 94%). Papillary thyroid carcinoma was the second most common malignancy in our series, present in about 53% of thyroid cytologies with the finding of psammoma bodies. Our study showed that psammoma bodies in cytology preparations were more often associated with malignancies in our study of 78 cytology specimens (69%). The most sampled location in our study was peritoneal cavity, followed by pleural cavity, thyroid, lymph nodes, neck masses, and omentum. The clinicopathologic value of psammoma bodies in predicting malignancy varies depending on locations and specimen types.

Evaluation of Ascitic Fluid Cytology in a Tertiary Hospital in South-Western Nigeria: A 7-year Retrospective Study

Background: Ascites is the pathological accumulation of fluid within the peritoneal cavity of varied etiology. Various abnormalities can be detected through cytological analysis of ascitic fluid. Ascitic fluid cytology (AFC) is a rapid and cost-effective means of evaluating ascites to establish its nature and cause. Aim: To evaluate ascitic fluid cytological findings over a seven-year period and to correlate the cytological features with the clinical profile of the patients. Materials and Methods: This was an observational retrospective study conducted in a healthcare facility in south-western Nigeria. The reports of AFC tests performed from January 1, 2016 to December 31, 2022 were retrieved to obtain the following information for analysis: Age, Gender, Tribe, Year of the test, Provisional diagnosis, and Cytological diagnosis. Results: The data of a total number of 121 patients were analyzed; 61 males (50.4%) and 60 females (49.6%) with a mean (±SD) age of 51.51 ± 15.22. Decompensated cirrhosis was the commonest clinical diagnosis 65 (53.7%) followed by hepatocellular carcinoma 11 (9.1%). Ascitic fluid cytological findings showed 45 (37.2%) were positive for malignant cells; 46 (38.0%) were negative for malignant cells; 13 (10.7%) were suspicious for malignancy; 9 (7.4%) were acellular smears; and 8 (6.6%) were inflammatory smears. The ascitic fluid of only 4 out of 11 patients with hepatocellular carcinoma tested positive for malignant cells, giving a sensitivity of 36.4%. Conclusion: AFC remains very useful in the diagnostic work-up of patients with ascites but should not be completely relied upon in confirming a malignancy, other additional diagnostic investigations should be deployed.

Clinical and cytological characteristics of serous effusions in 69 cases of lymphoma patients.

To explore the value of cell morphology, immunophenotype, and gene alterations of serosal effusion in the diagnosis of lymphoma. Serosal effusion of 69 cases of lymphoma patients were collected, including 36 cases with malignant effusion and 33 cases with nonmalignant effusion. Ordinary cytology, liquid-based cytology, cellblock, and immunocytochemical staining were performed in each case, some cases were detected by fluorescence in situ hybridization for C-MYC, BCL2, and BCL6 gene translocations. T/B cell ratio in malignant and nonmalignant serosal effusions was analyzed and compared by flow cytometry (FCM)and immunohistochemical (IHC), respectively. The prognostic value of serous effusion in diffuse large B-cell lymphoma (DLBCL) was investigated and another 20 DLBCL cases without effusion were successively selected as control. The number of naive lymphocytes, apoptotic bodies, and mitotic figures were more common in malignant effusions compared with nonmalignant effusions (p < .01). The top three lymphomas in malignant effusion were DLBCL (19/36, 52.8%), mantle cell lymphoma (MCL) (4/36, 11.1%, 3 blastoid variant) and high-grade B-cell lymphoma (HGBL) (4/36, 11.1%). T/B cell ratio by FCM analysis ranged from 0.00 to 0.55 (mean 0.084) in malignant effusion, and 2.58 to 984.00 (mean 249.9) in nonmalignant effusion. The difference was significant (p = .017). The T/B cell ratio by IHC analysis ranged from 0.02 to 3.00 (mean 0.200) in malignant effusion, and 2.00-100.00 (mean 34.10) in nonmalignant effusion. The difference was significant (p = .017). In the effusions involving DLBCL, most effusions were present at the time of diagnosis (57.9%); single pleural effusions were more common (36.8%). The median overall survival times of patients with malignant effusion, nonmalignant effusion and DLBCL without serous effusion were 11, 17, and 23 months respectively (p = .04). Three patients of HGBL died, and the overall survival times were 5, 8, and 9 months, respectively. The cytomorphological characteristics combined with immunophenotype, FCM, gene rearrangement, and other tests can diagnose and classify patients with effusion as the first symptom. The T/B cell ratio is less than 1 by FCM or IHC suggesting a malignant serosal effusion. The presence of malignant effusion in DLBCL patients is an important clue for poor prognosis.

Liquid-based Cytological Features of Adenocarcinoma Not Otherwise Specified, Extrauterine Adenocarcinoma, and Other Malignant Neoplasms of The Uterine Cervix: A 5-year Single-institutional Experience With 30 Consecutive Patients.

The adenocarcinoma (ADC) and other malignant neoplasm (OMN) terminologies of The Bethesda System represent various histological types of uterine and extrauterine malignancies. This study aimed to clarify the incidences of ADC not otherwise specified (ADC-NOS), ADC extrauterine (ADC-EXT), and OMN in our institution and describe their characteristic cytomorphological features. We searched the database to identify all patients diagnosed with carcinoma, including those diagnosed through cervical liquid-based cytology (LBC), between January 2019 and December 2023. The electronic medical records and all available slides were reviewed. Overall, 30 of the 149,197 (0.02%) patients were diagnosed with ADC-NOS, ADC-EXT, and OMN. All three groups included various histological types of both gynecological and non-gynecological origin. More than two-thirds (23/30; 76.7%) were of uterine origin, but seven patients had metastatic carcinoma of extrauterine organ origin, including the ovary, lung, stomach, breast, colon, urethra, and pancreas. In all patients, the cytological features were concordant with the histological features. In LBC, ADC-NOS does not only encompass uterine cervical tumors, but also various types of extrauterine malignancies. ADC-EXT and OMN also represent both extrauterine and uterine tumors. Awareness of the morphological features observed in LBC samples of non-gynecological malignancies may be helpful in obtaining the correct diagnosis.

Clinical and cytological characteristics of malignant pericardial effusion and estimation of the rate of progression until its evacuation by pericardiocentesis

Abstract Introduction Pericardial effusion (PE) is a complication of neoplastic processes that worsens the prognosis and can lead to symptomatic presentations requiring pericardiocentesis (PC). There is limited literature regarding the evolution of PE from its onset to the need for PC, characteristics of these patients, progression rate of PE, and potential accelerating factors. Purpose This study aims to: i) Analyze the baseline characteristics of patients undergoing PC; ii) Evaluate the correlation between PE appearance and cytology; iii) Analyze the progression rate until PC performance. Methods This retrospective observational study includes patients with active neoplasia and significant symptomatic PE treated with PC at our hospital from 01/01/2010 to 06/30/23, with subsequent follow-up until 10/31/23. Clinical characteristics related to neoplastic processes and PE diagnosis were analyzed, including PE appearance, cytology, and computed tomography scans performed as neoplasia follow-up prior to PC. Results A total of 75 patients were included, with 6 excluded because of non-malignant conditions (2 acute pericarditis-related PE, 3 purulent PE, and 1 chylous PE). The remaining 69 patients had a median age of 59 years, with 55.1% being male. Lung neoplasm was most frequent (63.8%, with 84% adenocarcinoma), followed by lymphomas/lymphoid leukemia (7.3%), upper digestive tract (7.3%), and breast cancer (7.3%). 52.2% of PEs undergoing PC were diagnosed simultaneously with neoplasm (70.45% associated with pulmonary neoplasms); 43.5% had ECOG 1, and 89.9% had metastases (excluding PE) at PC. Cardiac tamponade was present in 27.5%, with percutaneous pericardiostomy added in 21.7%. PE appearance was sero-haematic in 49.3%, haematic in 36.2%, and serous in 14.5%. Cytology showed mostly positive results (69.2%: 50% in serous PE and 71.93% in haematic/sero-haematic PE). The median time from the last CT scan prior to PE to PC was 5 months (160 days, range: 24-943 days). PC recurrence was observed in 30.4% of cases. Follow-up mortality was 82.6%, higher in breast, renal, digestive, thymoma, and genital neoplasms (100%), with hematological neoplasms having the lowest mortality (40%), followed by pulmonary neoplasms (79.5%). Mortality was higher in patients with more lines of treatment at PC and with a higher number of metastases. The median time from PC to death was 2 months (68.5 days, range: 1 day-2007 days). Conclusions The most common neoplastic PE was associated with lung adenocarcinoma, though a variety of neoplasms were observed. Half of PEs were diagnosed concurrently with neoplasm diagnosis. Cytology sensitivity was not high, and PE appearance did not adequately predict outcomes. The median time from the last CT scan prior to PE to PC was 5 months, potentially guiding echocardiographic follow-up once PE is observed on CT. Overall mortality was high (82.6%), except for onco-hematological PE.Iconographic summary of malignant PE

Cytologic features of gastric-type endocervical adenocarcinoma: Three cases report and literature review.

Cervical gastric-type adenocarcinoma shows gastric differentiation, and the tumor cell morphology appears benign and unrelated to human papillomavirus, which makes cervical gastric-type adenocarcinoma highly susceptible to misdiagnosis as normal glandular epithelium in cytologic diagnosis. We present 3 cases of gastric-type adenocarcinoma, with the first being a 57-year-old female with abnormal uterine bleeding and fluid drainage. The second patient was a 63-year-old female, and the third was a 59-year-old female with irregular vaginal bleeding after menopause. The 3 patients were diagnosed with cervical gastric-type adenocarcinoma by combining their history, clinical data, cytopathology, histopathology, and immunohistochemistry. Patient 1 underwent total hysterectomy and adnexectomy, but refused radiotherapy and chemotherapy. Patient 2 received a chemotherapeutic regimen, and patient 3 was treated with traditional Chinese medicine. Patient 1 was followed-up for 9 months and is currently in good general condition, while patients 2 and 3 were not followed-up. The "drunken honeycomb" cell arrangement is diagnostically important in liquid-based cytology, especially when three-dimensional spheroids are present, and may be a characteristic cytological finding of well-differentiated cervical gastric-type adenocarcinoma.

Cytological Characteristics of the Eye Conjunctiva in Dogs with Atopic Dermatitis

Atopic dermatitis is a chronic, pruritic inflammatory skin disease affecting approximately 10% of dogs worldwide. The disease typically manifests at an early age, causing pruritus and secondary skin lesions in specific anatomical regions. The pathophysiology of canine atopic dermatitis (CAD) remains incompletely understood, but recent research suggests a complex interplay between skin barrier dysfunction, allergic sensitisation, and microbial dysbiosis. Despite the well-established association between atopic dermatitis and conjunctivitis, the prevalence of conjunctivitis in dogs with CAD is often underestimated in clinical practice due to inadequate recognition of symptoms and a lack of specific diagnostic protocols. This study aimed to analyse the cytological characteristics of the conjunctiva in dogs affected by atopic dermatitis. Samples were collected from 24 dogs diagnosed with CAD and treated at the University Veterinary Hospital, Faculty of Veterinary Medicine, University of Zagreb. Cytological analysis was performed on samples obtained using a cytobrush. The results revealed the presence of inflammatory cells in all samples, with lymphocytes most prevalent (87.5%). A mild degree of conjunctival metaplasia was observed in all dogs, regardless of the type of inflammatory cells and the severity of conjunctivitis. These findings suggest that atopic dermatitis may induce changes in the conjunctiva that are not necessarily correlated with the intensity of the inflammatory response. The presence of lymphocytes, along with eosinophils in some cases, underscores the diagnostic value of conjunctival cytology in dogs with CAD. Furthermore, the increased density of goblet cells suggests similarities in the pathophysiology of ocular allergies in dogs and humans, opening avenues for further research to better understand and treat these conditions. This study highlights the importance of an interdisciplinary approach in the diagnosis and treatment of atopic dermatitis, including regular ophthalmologic examinations as part of standard clinical practice.

Molecular Testing Prevents Overdiagnosis of Epithelioid Hemangioma

Abstract Introduction/Objective Epithelioid hemangiomas (EH) are mostly solitary benign vascular tumors commonly involving the dermal and subcutaneous areas of the head and neck. However, reports of multifocality are increasing, specially in same anatomic region. Some reported cases of EH show morphologic features that may mimic malignant vascular tumors such as hemangioendotheliomas or angiosarcomas. However, there are no reported overlaps in the molecular characteristics of these tumors. We describe a multifocal EH with atypical features, suspicious for angiosarcoma, which needed molecular testing to resolve the diagnosis. Methods/Case Report The patient is a previously healthy 42-year-old male with a 5-month history of multiple growing painless penile nodules. Biopsy of one of the nodules was done. Histologic examination showed multifocal dermal- based ill-circumscribed nodules with interspersed inflammatory infiltrates and focal areas of necrosis. Tumor periphery shows vasoformative growth with intraluminal and extravasated red blood cells. Neoplastic cells were large and ovoid with abundant eosinophilic cytoplasm, large vesicular pleomorphic nuclei and prominent nucleoli. Immunohistochemical stains showed strong expression of ERG, FLI-1, and CD31 and negativity for AE1/AE3, CD34, HHV8 and EMA. The morphologic and immunohistochemical features of the specimen showed significant overlap of two primary differential diagnoses - epithelioid angiosarcoma and epithelioid hemangioma. Ultimately, molecular testing revealed ZFP36-FOSB fusion, confirming the diagnosis of EH. Results (if a Case Study enter NA) NA Conclusion Differentiating benign and malignant epithelioid vascular neoplasms can sometimes be challenging. There can be overlap in terms of architectural variety, presence of necrosis, vasoformation, inflammatory cell components and cytologic features, especially in EH with atypical features and epithelioid angiosarcoma (EA). Both of these tumors show positive immunoreactivity for CD31, CD34, FLI1 and ERG, and negativity for most keratins. Currently, the most reliable way to distinguish each tumor is molecular testing, with EH having FOS/FOSB rearrangements and EA with MYC or FLT4 amplification. Benign and malignant epithelioid vascular tumors can be indistinguishable morphologically and immunohistochemically. Molecular tests can help differentiate these neoplasms to better tailor patient management.

Malignant Rhabdoid Tumor masquerading as Neuroblastoma: A rare Case-report

Abstract Introduction/Objective Malignant rhabdoid tumors (MRT) predominantly impact infants and young children, typically occurring around the age of 15 months. While they can emerge from soft tissues throughout the body, but commonly initiate in the kidneys. Neuroblastoma-like characteristics are seldom observed within the varied phenotypes of malignant rhabdoid tumors. Here, we present an exceptionally rare and distinctive subtype of malignant rhabdoid tumor exhibiting features akin to neuroblastoma localized within the unusal parapharyngeal space. Methods/Case Report A 2-month-old female presented to the ED with an enlarging right cervical neck mass. The mother reported a one-week history of upper respiratory tract symptoms and noticed an enlarging mass of her right neck. CT reported a “parapharyngeal abscess with airway compression”. The patient was started on Augmentin with no significant improvement. Repeat CT with contrast demonstrated an enlarging rim-enhancing 3 cm mass involving the right parapharyngeal space, trachea, and right carotid arteries. Laryngoscopy and incisional biopsy of right neck lymph nodes demonstrated a high-grade malignancy with prominent nucleoli, high N/C ratio and scant cytoplasm. The tumor tested positive for CD 99, synaptophysin, and neurofilament, leading to the initial diagnosis of neuroblastoma. However, molecular analysis uncovered the loss of INI-1 on 22q11.2, prompting a reevaluation and a final diagnosis of MRT with neuroblastoma-like characteristics was made. Results (if a Case Study enter NA) NA Conclusion A range of tumors displaying distinct “rhabdoid” cytological features are collectively termed as malignant rhabdoid tumors (MRTs). Conventional immunohistochemistry (IHC) staining for CD99, synaptophysin, neurofilament, and myogenin might suggest neuroblastoma, Ewing sarcoma, or rhabdomyosarcoma. However, the absence of INI-1 expression provides a definitive diagnosis. INI-1 loss, a purported tumor suppressor gene located on chromosome 22q11.2, solidifies the tumor’s classification as malignant rhabdoid tumor (MRT). Additionally, a positive neurofilament stain in MRT is crucial for diagnostic and therapeutic assessments. This differentiation is vital, given the dismal prognosis of MRT with a 5-year survival rate of less than 10%.

A rare case report of hurthle cell adenoma mimicking malignancy

Thyroid lesions are the most common endocrine diseases, occurring in usually all age groups, though accurate diagnosis still remains a challenge, as due to oncocytic potentials of Thyroid cells leads to like indeterminate or suspicious diagnosis. Long standing benign Thyroid lesion shows atypical presentation suspicious to malignancy. Now a days with the help of WHO classification and available advanced diagnostic measures helping to confirm the diagnosis, avoiding overdiagnosis and wrong treatment. Hence this study review the importance of Histopathological study with coordination with immunohistochemistry (IHC) study, where suspicious thyroid malignant lesion finally diagnosed as benign Hurthle cell/ Oncocytic adenoma in Nodular Goitre.: 72 year old female presented huge neck swelling since one year, was reviewed in our departments of Pathology and ENT. Fine needle aspiration cytology (FNAC) features are suspicious of Malignancy, further Histopathological features were studied with co ordance of IHC study. FNAC features, which were suspicious of Malignancy were further studied with Histopathological and IHC studies diagnosed as Hurthle cell/ Oncocytic adenoma in Nodular Goitre. Histopathology remains the cornerstone for the diagnosis of thyroid oncocytic lesions and also in distinguishing between adenoma and carcinoma.

An Anaplastic Lymphoma Kinase (ALK) Immunohistochemical Pitfall: ALK-positive Histiocytosis versus Angiomatoid Fibrous Histiocytoma

Abstract Introduction/Objective The 5th Edition WHO classification expanded the histiocytic/dendritic cell neoplasms to include ALK-positive histiocytosis, which can present as multisystem or single-site disease, affecting various age groups. These tumors lack high-grade cytologic features but express ALK by immunohistochemistry, typically indicating ALK locus rearrangements. In this case study, a cutaneous mass initially suspected as ALK-positive histiocytosis was found to be angiomatoid fibrous histiocytoma (AFH) with ALK expression, highlighting the potential diagnostic pitfall due to overlapping histomorphology and ALK expression. Methods/Case Report A previously healthy twelve-year-old boy sought evaluation for a growing and ulcerating mass on his left arm, which developed gradually over a year post-injury. Laboratory tests showed elevated inflammatory markers and mild anemia. A biopsy of the ulcer revealed Staphylococcus aureus infection. Initial histological examination revealed mixed inflammatory infiltrates with focal necrosis, prominent histiocytes, and giant cells. Despite favoring an infectious cause, immunostains were performed. AE1/AE3, ERG, CD34, CD30, S100, SOX10, SMA, and MyoD1 were negative, while INI1 was retained. However, ALK was strongly positive in some histiocytoid cells, suggesting ALK-positive histiocytosis. Surgical resection was subsequently performed to manage the abscess and characterize the lesion. Histologic examination revealed a solid nodule containing spindled and epithelioid cells with a bland histiocytoid appearance, arranged in a compact syncytial growth pattern within the dermis and subcutis. Surrounding the tumor, there was a distinct cuffing of fibrosis with organized lymphoplasmacytic cells. Break apart fluorescence in situ hybridization studies showed rearrangement of EWSR1 but not ALK. The diagnosis of angiomatoid fibrous histiocytoma was rendered. Results (if a Case Study enter NA) NA Conclusion This case highlights the importance of understanding immunohistochemical features, especially those that are unusual and unexpected in rare diseases. With the growing use of minimally invasive sampling techniques, this case study underscores the significance of integrating molecular diagnostics with clinical, histological, and immunophenotypic evaluations to achieve an accurate diagnosis in surgical pathology.

Cardiac Angiosarcoma with Unusual Cytologic Features Causing Cardiac Tamponade in a Young Adult Patient

Abstract Introduction/Objective Cardiac angiosarcoma is a rare endothelial malignancy with poor prognosis, frequent metastasis, and short median survival of only a few months. The disease has a wide age spectrum and can occur in young adult patients. The cytological diagnosis of cardiac angiosarcomas is challenging as cases are rare and its cytology is not extensively described or reported in literature. Here, we describe a rare case of cardiac angiosarcoma with unusual cytologic features. Methods/Case Report Our patient is a 30 year old male presenting with three days of worsening dyspnea and palpitations and was discovered on ultrasound to have large pericardial effusion compressing the right ventricle and causing cardiac tamponade. CT/MRI imaging revealed a 4.5 x 4.3 x 2.6 cm mass inside the right ventricle with extra- cardiac invasion through the pericardium and into the anterior mediastinum. Pericardiocentesis yielded 1.5 liters of hemorrhagic, brown, pericardial fluid with elevated LDH and protein levels. Cytology of the pericardial fluid revealed numerous tumor cells occurring singly or in monolayered, acinar clusters or cohesive spheres containing amorphous, eosinophilic cores made of collagen as evidenced on trichrome stain. The tumor cells possessed hyperchromatic, irregular, variably sized nuclei, prominent nucleoli, and cytoplasmic vacuoles. The tumor cells were positive for vimentin, CD31, and CD34, and showed high Ki67 proliferation index &amp;gt; 50%. A catheter-mediated biopsy of the right ventricular mass revealed spindled and epithelioid tumor cells strongly positive for CD31, CD34, and vimentin, focally positive for Factor VIII and AE1/AE3, and showing high Ki67 proliferation index of roughly 50%. The cytological, histological, and immunohistochemical findings were most consistent with cardiac angiosarcoma as the diagnosis. The patient eventually developed worsening chronic left chest pain and expired from cardiac arrest six months after his diagnosis. Results (if a Case Study enter NA) NA Conclusion We report a rare case of cardiac angiosarcoma with unusual cytologic features, manifesting as acinar clusters and cohesive spheres with collagenous cores that are not typical of malignant endothelial neoplasms. Currently there are no effective, standardized therapies that can significantly prolong survival for this malignancy, and treatment is often palliative. The cytological diagnosis of cardiac angiosarcoma is challenging given the rarity of this disease and the paucity of literature describing its cytology.