Cytologic Features Research Articles

Cytotaxonomical Studies in the Genus <I>Setcreasea</I>

Cytological studies have been done in two species of Setcreasea. In Setcreasm purpurea a somatic chromosome number of 12 has been observed and in S. brevifolia an aneuploid number of 2n = 25 has been found. Three major types of chromosomes have been observed m the karyotypes of both taxa. The cytological situation in the two taxa has been observed to, be similar to that of Tradescantia. Meiotic behaviour in S. purpurea is regular while in S. brevifolia it is irregular. The irregularity in the latter taxon is doubtless connected with aneuploidy and structural hybridity. The finding of diploid pollen grains in S. purpurea and S. brevifoliacould have been due to the failure of the chromosomes or chromatids to go to different poles, disturbance in spindle formation, or possibly to a complete failure of cell wall development. Many cases have been found of abnormal cvtokinesis in pollen grain formation. Polyploidy, structural hybridity and hybridization has been considered to be playing major role in evolutionary tendencies in Setcreasea.In view of the cytological and morphological characteristics, it has been suggested that the genus is related to Zebrina and its relationship with Cyanotis is remote. Taking all these factors into consideration, it appears that Setcreasea will be in more natural systematic position if separated widely from Cyanotis and placed near Zebrina.

Cyto- and Histopographic Assessment of CPA3-Positive Testicular Mast Cells in Obstructive and Non-Obstructive Azoospermia

Infertility is an important personal and society disease, of which the male factor represents half of all causes. One of the aspects less studied in male infertility is the immunological testicular microenvironment. Mast cells (MCs), having high potential for regulating spermatogenesis due to fine-tuning the state of the integrative buffer metabolic environment, are one of the most crucial cellular subpopulations of the testicular interstitium. One important component of the MC secretome is proteases that can act as proinflammatory agents and in extracellular matrix (ECM) remodeling. In the testis, MCs are an important cell component of the testicular interstitial tissue (TIT). However, there are still no studies addressing the analysis of a specific MC protease—carboxypeptidase A3 (CPA3)—in cases with altered spermatogenesis. The cytological and histotopographic features of testicular CPA3+ MCs were examined in a study involving 34 men with azoospermia. As revealed, in cases with non-obstructive azoospermia, a higher content of CPA3+ MCs in the TIT and migration to the microvasculature and peritubular tissue of seminiferous tubules were observed when compared with cases with obstructive azoospermia. Additionally, a high frequency of CPA3+ MCs colocalization with fibroblasts, Leydig cells, and elastic fibers was detected in cases with NOA. Thus, CPA3 seems to be of crucial pathogenetic significance in the formation of a profibrogenic background of the tissue microenvironment, which may have direct and indirect effects on spermatogenesis.

Diagnostic Biomarkers in Renal Cell Tumors According to the Latest WHO Classification: A Focus on Selected New Entities

The fifth edition of the World Health Organization (WHO) classification for urogenital tumors, released in 2022, introduces some novelties in the chapter on renal epithelial tumors compared to the previous 2016 classification. Significant changes include the recognition of new disease entities and adjustments in the nomenclature for certain pathologies. Notably, each tumor entity now includes minimum essential and desirable criteria for reliable diagnosis. This classification highlights the importance of biological and molecular characterization alongside traditional cytological and architectural features. In this view, immunophenotyping through immunohistochemistry (IHC) plays a crucial role in bridging morphology and genetics. This article aims to present and discuss the role of key immunohistochemical markers that support the diagnosis of new entities recognized in the WHO classification, focusing on critical topics associated with single markers, in the context of specific tumors, such as the clear cell capillary renal cell tumor (CCPRCT), eosinophilic solid and cystic renal cell carcinoma (ESC-RCC), and so-called “other oncocytic tumors”, namely the eosinophilic vacuolated tumor (EVT) and low-grade oncocytic tumor (LOT). Their distinctive characteristics and immunophenotypic profiles, along with insights regarding diagnostic challenges and the differential diagnosis of these tumors, are provided. This state-of-the-art review offers valuable insights in biomarkers associated with novel renal tumors, as well as a tool to implement diagnostic strategies in routine practice.

EXPLORING CYTOLOGICAL ASPECTS OF SOCKET HEALING OPTIMIZATION AFTER ATYPICALREMOVAL OF THE THIRD LOWER MOLAR

This study aims to investigate the cytological characteristics of socket healing after atypical removal of the lower third molar, utilizing osteoplastic synthetic material in conjunction with platelet-rich gel and plasma enriched with thrombocyte factors, to enhance local osteogenesis. Materials and Methods For this comparative clinical study, smears of alveolar content were collected following atypical extraction of the lower third molar. Cell elements were quantified for cytological analysis. Data collection utilized a template developed in Microsoft Excel version 16.34. Statistical processing was performed using RStudio 2023.03.1 Build 446 (Posit Software, PBC). Smears were air-dried, fixed in a 1:1 mixture of alcohol and acetone for 5 minutes, stained first with May-Grünwald’s methylene blue (15 minutes), followed by Romanowsky-Giemsa’s azure-eosin stain (30 minutes). Smear images were captured with the Leica morpho densitometric complex: DM 1000 microscope, DFC-320 camera, images were obtained in jpg format at 400x magnification. Results The study encompassed 30 patients divided into control and experimental groups. Cytological analysis was conducted on the 2nd, 5th, and 10th days of post- operation. In both groups, on the 2nd day, alveolar smears showed the presence of erythrocytes (n = 6) and neutrophils (n = 2). On the 5th day, the experimental group exhibited neutrophils (n = 3) and abundant cocci microflora (n = 6). On the 10th day, epitheliocytes (n = 8) primarily indicated proliferation. Conclusions The obtained results underscore the effectiveness of employing osteoplastic synthetic material in combination with plateletrich gel and plasma enriched with thrombocyte factors for enhancing local osteogenesis following atypical removal of the third molar. This approach demonstrates significant elevation in epithelialization activity, fibroblastic activity, and other markers of the reparative process in comparison to the control group.

Criteria for melanocytic lesions in LC-OCT.

Line-field confocal optical coherence tomography (LC-OCT) is an emerging diagnostic tool with imaging depth reaching ~400 μm and a novel three-dimensional (3D) cube providing cellular resolution. As far as we are aware, there are only a limited number of papers that have reported diagnostic criteria for melanocytic lesions using this technique, and none of them have been multicentric. Our aim was to establish the diagnostic criteria for melanocytic lesions using LC-OCT and identify the most significant architectural and cytologic features associated with malignancy. A retrospective evaluation of 80 consecutive melanocytic lesions from a prospective multicentric data set spanning three European centres was conducted. We excluded facial, acral and mucosal lesions from the study. Dermoscopic and LC-OCT images were evaluated by a consensus of four observers. Multivariate logistic regression with backward elimination was employed. The main melanoma diagnostic criteria include detecting >10 pagetoid cells in 3D acquisition, irregular 3D epidermal architecture, disrupted dermoepidermal junction (DEJ) and clefting. Significant risk factors were irregular 3D epidermal architecture, >10 pagetoid cells, dendritic cells at DEJ without underlying inflammation. Novel malignancy criteria in vertical view were DEJ disruption and clefting around atypical melanocyte nests. Exclusive melanoma features were epidermal nests, epidermal consumption, dense dermal nests with atypia. Protective features in the absence of any malignancy indicators were DEJ ring pattern, cobblestone, elongated rete ridges (vertical), well-defined DEJ and wave pattern (vertical). A series of diagnostic criteria for the identification of melanocytic lesions with LC-OCT have been established. Validation of these criteria in clinical practice through future studies is essential to further establish their utility.

Ameloblastic Carcinoma With Orbital Invasion

Ameloblastic carcinomas are malignant tumors arising from the odontogenic epithelium and defined as having features of ameloblastic differentiation in addition to cytological features of malignancy. Orbital involvement is rare and generally involves invasion of the orbital floor, apex, or soft tissue. This report describes an advanced presentation of ameloblastic carcinoma with orbital invasion and provides a review of the literature. A 58-year-old male presented with a 2-year history of a mid-facial mass, causing intracranial invasion and distortion of most skull foramina, nasopharynx, nasal cavity, and both orbits. Notably, there was an en-plaque pattern of circumferential tracking of the tumor along both orbital walls without invasion beyond the extraconal space, causing compression of the orbital apex and proptosis. Histology demonstrated nests of ameloblastic carcinoma and the advanced tumor was deemed nonresectable, with treatment being palliative.

Ultrasound and cytological characteristics of NIFTP tumors compared to papillary carcinomas

Ultrasound and cytological characteristics of NIFTP tumors compared to papillary carcinomas

Clinicopathological characteristics of mucinous carcinoma of the breast.

Objective: To highlight clinicopathological differences between Pure Mucinous Carcinoma (PMC) and Mixed Mucinous Carcinoma (MMC) of the breast. Study Design: Descriptive Retrospective study. Setting: Private Lab in Faisalabad, Pakistan. Period: January 2017 to December 2022. Methods: FNAC smears diagnosed with Mucinous Carcinoma fulfilling the inclusion and exclusion criteria were carefully examined for features such as cellularity, extracellular mucin (ECM), nuclear pleomorphism, plasmacytoid cells, macrophages, and myxovascular fragments (MVFs). The diagnosis was confirmed by histopathology and were characterized in to PMC and MMC. Immunohistochemistry slides were evaluated according to established protocols. Statistical analysis was performed using SPSS (p < 0.05). Results: The study analyzed 16 FNAC cytological samples with subsequent histopathological confirmation. These cases were derived from a pool of 712 female breast carcinoma cytology cases over a five-year duration. The predominant age group was 40 to 50 years, with the left breast and upper outer quadrant being the most common site. Distinct cytological characteristics, particularly the significant presence of extracellular mucin in PMC, were observed. Tumor grade and lymph node involvement emerged as crucial prognostic factors. MMC exhibited a high Ki-67 index, indicating increased cellular proliferation. Conclusion: Pure mucinous carcinomas (PMCs) are uncommon breast tumors with distinguished cytologic features. It is clinically and genetically distinct from mixed mucinous carcinoma (MMC) and other types of breast cancer. An important prognostic factor is lymph node involvement, and PMCs often have a low proliferation rate and a more favorable long-term prognosis. Therefore, the identification of PMC through FNAC holds significant diagnostic and clinical importance.

Abstract PO4-25-08: Secretory breast carcinoma (SBC) in an 8-year-old male: Report of an exceptionally rare case with review of clinicoradiologic and pathomolecular findings of SBC in the male pediatric population

Abstract Secretory breast carcinoma (SBC) is a rare and distinct disease, comprising approximately 0.01% of all breast carcinomas. This is a case of an 8-year-old boy who presented with a 1.5-year history of a non-tender, slowly enlarging left subareolar mass, not associated with nipple discharge. Serologic workup revealed minimally elevated prolactin with normal-range FSH, LH, estradiol and testosterone, as well as normal-range beta-hCG, LDH and AFP. Ultrasound showed a circumscribed solid hypoechoic lesion with internal arterial vascularity, favoured to represent a sebaceous cyst. Excisional biopsy was performed, and histologic examination revealed the classic intra- and extracellular secretory material typically seen in SBC. Immunohistochemical (IHC) stains for mammaglobin, S-100 and high molecular weight keratin (CK5) were positive. ER was positive, though not strong staining, and PR and HER2 were negative. A screen for NTRK fusions with pan-TRK IHC was positive. No skin, perineural or lymphovascular invasion was identified. RNA-based NGS demonstrated ETV6-NTRK3 fusion and confirmed the diagnosis of SBC. The patient underwent mastectomy and SLNB, which showed no residual tumor and no positive lymph nodes. A full metastatic work-up was not performed and the patient did not receive neoadjuvant therapy. First described as “juvenile breast carcinoma,” SBC has since been recognized to occur across a wide age range, with most cases occurring in adults. SBC in male pediatric patients is exceptionally rare, with fewer than 20 cases reported in the literature. In this demographic, SBC is usually detected clinically as a subareolar mass not associated with nipple discharge, and appears as a well-circumscribed mass on imaging, mimicking benign entities. SBC is usually detected at a low stage, treated surgically, and follows a clinically indolent course with excellent outcomes. Positive axillary nodes have been identified in a few male children, who subsequently underwent chemo- and/or radiotherapy, with no recorded recurrences in these cases. Distant metastases are an extremely uncommon feature of SBC and have not been reported in the pediatric male population; however, due to the rarity of this diagnosis, particularly in this demographic, robust long-term follow-up data are still lacking. The name “secretory” derives from the histologic appearance of the dense eosinophilic secretory material seen in tumor lumina and bubbly material in the cytoplasm of tumor cells. Similar to the cytologic characteristics of other translocation-driven neoplasms, SBC shows minimal pleomorphism. Mitoses are absent or rare. IHC stains are typically positive for S-100 and high molecular weight keratins and negative for ER, PR, and HER2. Despite the immunophenotypic similarities to triple negative/basal-like carcinomas (TNBC/BLC) the molecular relationship between SBC and TNBC/BLC is unclear. Though initially defined by its distinctive secretions on histology, SBC is now chiefly characterized by a balanced translocation, t(12;15)(p13;q25), resulting in oncogenic ETV6-NTRK3 fusion. Recent cases have demonstrated this using a variety of molecular techniques, including FISH, RT-PCR, and in our case, RNA-based NGS. This translocation also characterizes non-breast secretory carcinomas and has been identified in several other neoplasms, including pediatric mesenchymal tumours and adult acute myeloid leukemia. The rarity of SBC, particularly in the male pediatric population, underlines the necessity of this case report. Additionally, this case highlights the importance of considering SBC as a potential diagnosis in male children presenting with a breast mass, even in the presence of benign imaging characteristics. Table 1: Clinicoradiologic and pathomolecular characteristics of SBC in pediatric males AND, axillary node dissection; CT, chemotherapy; ER, estrogen receptor; FISH, fluorescence in situ hybridization; LE, local excision; MRM, modified radical mastectomy; nd, no data; NED, no evidence of disease; NGS, next-generation sequencing; NS, nodal sampling; PA, periareolar; PR, progesterone receptor; RA, retroareolar; RM, radical mastectomy; PCR, polymerase chain reaction; RT, radiotherapy; SA, subareolar; SLNB, sentinel lymph node biopsy; SM, simple mastectomy; WLE, wide local excision *Not reported as strong staining Table 2: Immunohistochemical phenotype of secretory breast carcinoma EMA, epithelial membrane antigen; ER, estrogen receptor; PR, progesterone receptor *Not reported as strong staining Table 3: Laboratory investigations AFP, alpha fetoprotein; FSH, follicle stimulating hormone; hCG, human chorionic gonadotropin; LDH, lactate dehydrogenase; LH, luteinizing hormone Citation Format: Rebecca Brassington, Svetlana Silverman, Ioana Bratu. Secretory breast carcinoma (SBC) in an 8-year-old male: Report of an exceptionally rare case with review of clinicoradiologic and pathomolecular findings of SBC in the male pediatric population [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-25-08.

Myoepithelial Tumors of Bone with EWSR1::PBX3 Fusion: A Spectrum from Benign to Malignant

The EWSR1::PBX3 fusion gene, commonly associated with cutaneous syncytial myoepitheliomas, is also found in myoepithelial tumors (METs) of bone and soft tissue. These tumors typically demonstrate benign histology and favorable outcomes. This study examines six previously unreported intraosseous METs harboring the EWSR1::PBX3 fusion, focusing on their histopathologic characteristics, immunophenotype, clinical and radiographic profiles, and patient outcomes. The cohort comprised five males and one female, aged 25 to 65 years (median age 31), with tumors located in the proximal tibia (three cases), distal radius (two cases), and ilium (one case), and sizes between 3.2 to 12.2 cm (median size 3.9 cm). Imaging showed osteolytic lesions with varying degrees of cortical involvement and soft tissue extension in three cases. Histologically, four tumors showed mainly uniform oval-to-spindled cells in syncytial or fascicular arrangements within a collagenous matrix, displaying either bland nuclear features or mild atypia, and low to slightly elevated mitotic activity (≤1 per 10 HPF in three cases and 6 per 10 HPFs in one), classifying them as benign or atypical METs. In contrast, two tumors exhibited pronounced nuclear atypia with ovoid, spindled, epithelioid and round cells, hyperchromatic nuclei, inconspicuous nucleoli, increased N/C ratios, high mitotic rates (17 and 19 per 10 HPFs), and extensive necrosis. Both tumors behaved aggressively-one patient underwent amputation after neoadjuvant chemotherapy and radiation, while the other died with the disease. Immunohistochemically, the tumors consistently expressed EMA and S100, but lacked keratin (AE1/AE3) expression. Our study demonstrates that bone METs with EWSR1::PBX3 fusions encompass a histologic continuum from benign to malignant, with benign/atypical METs mirroring their cutaneous analogs in morphology and malignant variants distinguished by heterogenous cytologic and architectural features, pronounced nuclear atypia, and high mitotic rates.

Grading Cytologic Epithelial Atypia in Pancreatic Mucinous Cysts Predicts Patient Survival: Correlation With Histologic, Molecular, and Clinical Follow-Up

Cytologic examination of epithelial cells in cyst fluids from pancreatic mucinous cysts is the optimal method for identifying high-grade atypia (HGA), which may represent histologic high-grade dysplasia (HGD) or invasive carcinoma, and thereby classify the cyst as high risk, warranting surgical resection. Cytologic features of HGA were previously described at our institution in 2013 and implemented thereafter, but performance of grading with these criteria has not yet been reported. In total, 1322 pancreatic cyst fluid specimens (2014-2021) were identified; all pathology reports and relevant clinical data were reviewed in detail; and 230 unique cysts (217 patients) contained neoplastic mucinous epithelium. Of the 230 cysts, 178 had low-grade atypia (LGA), and 52 had HGA; 97 cysts had histologic follow-up: 77 (79%) were resections and 20 (21%) were diagnostic surgical biopsies only. Moreover, 92 (95%) were confirmed neoplastic mucinous cysts, 3 were adenocarcinomas, and 2 were benign entities. Among histologically confirmed neoplastic mucinous cysts, 58 had low-grade dysplasia (LGD); 34 had HGD, of which 14 also had invasive carcinoma. A significantly higher proportion of cysts with HGA (63%) demonstrated at least HGD on follow-up compared with that of those with LGA (26%, P < .001). The sensitivity and specificity of HGA for accurately classifying a high-risk cyst were 54% and 81%, respectively. Of the 230 cysts, 146 (64%) cysts had corresponding next-generation sequencing results; 31% of HGA cysts harbored a high-risk mutation (TP53, CDKN2A, and/or SMAD4) vs 7% of LGA cysts (P < .001). Among cysts without histologic confirmation, 25% of HGA cysts had high-risk mutation vs 7% of LGA cysts. The grade of cytologic atypia was predictive of overall survival and recurrence-free survival (P < .001 and P = .020, respectively). Implementation of cytological criteria for HGA in pancreatic mucinous cysts has relatively low sensitivity but modest specificity for classifying a high-risk cyst. Although high-risk mutations were more commonly found in cysts with HGA, their frequency is overall low. Thus, evaluating the degree of cytologic atypia, which is predictive of patient survival, provides significant value and informs patient outcomes.

Atypical glandular cells and predictive features of malignancy in Pap smears: A retrospective monocentric study.

The introduction of cytological screening with the Papanicolau smear significantly reduced cervical cancer mortality. However, Pap smear examination can be challenging, being based on the observer ability to decode different cytological and architectural features. This study aims to evaluate the malignancy rate of AGC (atypical glandular cells) category, investigating the relationships between cytological and histological diagnosis. Eighty-nine patients, diagnosed as AGC at cytological evaluation and followed up with biopsy or surgical procedure at Policlinico Gemelli Hospital, Rome, Italy, were included in the study. The cytopathological architectural (feathering, rosette formation, overlapping, loss of polarity, papillary formation, three-dimensional formation) and nuclear (N/C ratio, nuclear enlargement and hyperchromasia, mitoses, nuclei irregularity, evident nucleoli) features of AGC were evaluated. Statistical analyses were performed to assess cyto-histological correlation and determine the relevance of architectural and nuclear features in the diagnosis of malignancy. Of the 89 AGC patients, 48 cases (53.93%) were diagnosed as AGC-NOS and 41 (46.07%) were diagnosed as AGC-FN, according to the Bethesda classification system. The follow-up biopsies or surgical resections revealed malignancy in 46 patients (51.69%). The rates of malignancy for AGC-NOS and AGC-FN were 35.41% and 70.73% respectively. Furthermore, analysing cytopathological features, we found that both architectural and nuclear criteria were statistically significant (p < 0.05). Only overlapping, nuclear irregularity and increased N/C ratio were not found to be statistically significant for detecting malignancy. Cytological diagnosis of glandular lesions remains a valid tool, when appropriate clinical correlation and expert evaluation are available.

Exploring cytologic features and potential diagnostic challenges of metastatic NUT carcinoma to the parotid gland: A case report and a comprehensive literature review.

NUT carcinoma (NC) is a highly aggressive, poorly differentiated carcinoma that harbors a t(15:19) translocation, leading to the fusion of the NUTM1 gene. While the upper aerodigestive tract along the midline (head, neck, thorax, and mediastinum) is commonly reported as the primary site of NC, subsequent cases have emerged in diverse locations. Achieving a definitive diagnosis based solely on morphology is challenging; however, it can be achieved using immunohistochemistry (IHC) specific to the NUT antibody or by demonstrating the characteristic BRD4::NUTM1 fusion. Accurate and timely diagnosis can potentially inform patient management and guide treatment. While histologic documentation of NC is commonly found, there is a limited description of its cytologic features. A 39-year-old male with a history of sinonasal squamous cell carcinoma (SCC) presented with a right parotid mass aspirated via fine needle aspiration cytology (FNA). Histologic examination of the previous sinonasal pathology reviewed at our institution revealed sheets of primitive-appearing, monotonous, undifferentiated cells with distinct, prominent nucleoli. Additionally, there were foci of abrupt keratinization, accompanied by a notable neutrophilic infiltrate. The initial diagnosis of SCC was reclassified to NC and confirmed through NUT IHC and molecular testing. Although the parotid FNA initially suggested the possibility of a variety of small round blue cell tumors, it exhibited morphological similarities to the sinonasal tumor, leading to the diagnosis of metastatic NC. Cytomorphologic features of NC are limited and can overlap with various small round blue cell tumors. Correct classification is especially pivotal in the era of targeted therapy, considering the ongoing development and evaluation of BET inhibitors targeting BRD4.

Comparative assessment of morphological, cytological, and reproductive characteristics of the spontaneous mixoploid ‘MM 2×/4×’ and its diploid counterpart ‘Miss Manilla’ in Bougainvillea (Bougainvillea × buttiana Honlttum & Standl.)

Polyploidization-triggered chromosome multiplication typically leads to improved agronomic and ornamental characteristics in plants. However, mixoploidy may sometimes occur in spontaneous and artificially induced polyploidization events, and the deficiency of basic information about mixoploidy limits its application in breeding. In this study, the ploidy stability of spontaneous mixoploidy Bougainvillea × buttiana ‘Miss Manila’ (‘MM 2×/4×’) was validated through chromosome counting and flow cytometry analysis. Compared with its diploid counterpart ‘MM 2×’, ‘MM 2×/4×’ exhibited significantly larger size in the morphological characters related to leaf, bract, thorn, and perianth tube. The average length, width, and density of stomata in ‘MM 2×/4×’ were also significantly larger than in ‘MM 2×’, while the stomatal density of mesophyll cells decreased. The anthers of ‘MM 2×/4×’produced both 1n and 2n pollen grains, which in vitro germinated reached 8.92 %, significantly higher than ‘MM 2×’ (0.36 %). The seed setting rate of the crossing combinations ‘MM 2×/4×’ × ‘Chitra’, ‘Chitra’ × ‘MM 2×/4×’ and ‘MM 2×/4×’ × ‘Bixi’ were 65.47 %, 32.36 %, and 53.17 %, respectively, and the ploidy levels among different offspring individuals of the same genetic population are relatively consistent. While ‘MM 2×’ could not be hybrid with either the tetraploid ‘Chitra’ or diploid ‘Bixi’. Therefore, the mixoploid ‘MM 2×/4×’ partially restored the fertility of gametes and might be employed for both ploidy breeding directly and creating hybrid segregation populations in bougainvillea for trait genetic dissection.

Clinicopathologic Features and Cytologic Correlation of ALK-Rearranged Papillary Thyroid Carcinoma: A Series of Eight Cases.

Anaplastic lymphoma kinase (ALK) gene fusions are rare in papillary thyroid carcinoma (PTC) but may serve as a therapeutic target. This study aims to evaluate the preoperative cytologic findings and clinicopathologic features of a series of eight ALK-rearranged PTCs from our pathology archives and consultations. All cases were confirmed by ALK D5F3 immunohistochemistry and six with additional targeted RNA-based next-generation sequencing (NGS). The original fine-needle aspiration (FNA) cytology diagnosis included the Bethesda System (TBS) category II in three (37.5%), TBS III in two (25%), TBS V in two (25%), and TBS VI in one (12.5%). Six cases had available FNA cytology and were reviewed. The cytologic features showed microfollicular architecture as well aslimited or reducednuclear elongation and chromatin alterations in all six. Nuclear grooves and pseudoinclusions were absent in two cases, rarely or focally noted in three, and frequently found in one. Two cases initially diagnosed asTBS II, showing microfollicular architecture without well-developed nuclear features, were revised to TBS III (with architectural atypia only). For histologic correlations, four were infiltrative follicular variant PTCs, three as classic subtype PTC with predominant follicular growth, and one as solid/trabecular subtype PTC. All eight cases demonstrated reducedPTC nuclear features with respect to nuclear elongation and chromatin alterations compared to thosetypically identified in "BRAF-like" PTCs. The NGS testing revealed EML4::ALK fusion in three, STRN::ALK fusion in two, and ITSN2::ALK fusion in one. In conclusion, although ALK-rearranged PTCs have been associated with neutral gene expression profile from a BRAF-RAS scoring perspective, the "RAS-like" nuclear features were more commonly identified in this series, resulting in frequent indeterminate diagnosis of preoperative FNA.

A case of pancreatic PEComa with prominent inflammatory cell infiltration: the inflammatory subtype is a distinct histologic group of PEComa

BackgroundPEComa is a mesenchymal tumor that can occur in various organs including the uterus and soft tissues. PEComas are composed of perivascular epithelioid cells, and angiomyolipoma (AML), clear cell sugar tumor (CCST), and lymphangiomyomatosis (LAM) are considered lesions of the same lineage as tumors of the PEComa family. Histologically, a common PEComa shows solid or sheet-like proliferation of epithelioid cells. This is accompanied by an increase in the number of dilated blood vessels. Here, we report a case of pancreatic PEComa with marked inflammatory cell infiltration.Case presentationA 74-year-old male patient underwent an appendectomy for acute appendicitis. Postoperative computed tomography and magnetic resonance imaging revealed a 30 × 25 mm non-contrast-enhanced circular lesion in the tail of the pancreas. The imaging findings were consistent with a malignant tumor, and distal pancreatectomy was performed. Histologically, most area of the lesion was infiltrated with inflammatory cells. A few epithelioid cells with large, round nuclei, distinct nucleoli, and eosinophilic granular cytoplasm were observed. Spindle-shaped tumor cells were observed. Delicate and dilated blood vessels were observed around the tumor cells. Immunohistochemically, the atypical cells were positive for αSMA, Melan A, HMB-45, and TFE3. The cytological characteristics of the tumor cells and the results of immunohistochemical staining led to a diagnosis of pancreatic PEComa.ConclusionsA histological variant known as the inflammatory subtype has been defined for hepatic AML. A small number of tumor cells present with marked inflammatory cell infiltration, accounting for more than half of the lesions, and an inflammatory myofibroblastic tumor-like appearance. To our knowledge, this is the first report of pancreatic PEComa with severe inflammation. PEComa is also a generic term for tumors derived from perivascular epithelioid cells, such as AML, CCST, and LAM. Thus, this case is considered an inflammatory subtype of PEComa. It has a distinctive morphology that is not typical of PEComa. This histological phenotype should be widely recognized.

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.

Molecular analysis using SalvGlandDx improves risk of malignancy estimation and diagnosis of salivary gland cytopathology: An exploratory multicenter study.

Diagnosis of salivary gland neoplasms is challenging, especially on cytological specimens acquired by fine-needle aspiration. The recently implemented standardized Milan system for reporting salivary gland cytopathology provides an estimated risk of malignancy (ROM); yet, for two of the categories, the diagnosis of the lesion remains unclear. However, a precise diagnosis is desirable for optimal patient management, including planning of surgery and imaging procedures. Cytological specimens (n=106) were subjected to molecular analysis using the SalvGlandDx panel. The risk of malignancy was calculated for each detected alteration based on the diagnosis of the resection specimen. By taking into account the molecular alterations, their associated ROM, the clinical and cytological features, and the current literature, the Milan category was evaluated. Of n=63 technically valid cases, 76% revealed a molecular alteration. A total of 94% of these molecularly altered cases could be assigned to a different Milan category when additionally taking molecular results into account. In only 2% of the salivary gland neoplasms of uncertain malignant potential, in which a molecular alteration was detected, the classification remained salivary gland neoplasms of uncertain malignant potential. Molecular analysis of cytological specimens provides a benefit in classifying salivary gland neoplasms on fine-needle aspiration. It can improve the ROM estimation and thus help to assign cases of formerly unknown malignant potential to clearly benign or malignant categories.

A cytomics-on-a-chip platform and diagnostic model stratifies risk for oral lichenoid conditions

ObjectivesA small fraction of oral lichenoid conditions (OLC) have potential for malignant transformation (MT). Distinguishing OLCs from other oral potentially malignant disorders (OPMD) can help prevent unnecessary concern or testing, but accurate identification by non-expert clinicians is challenging due to overlapping clinical features. In this study, the authors developed a cytomics-on-a-chip tool and integrated predictive model for aiding the identification of OLCs. Study DesignAll study subjects underwent both scalpel biopsy for histopathology and brush cytology. A predictive model and OLC Index comprising clinical, demographic, and cytologic features was generated to discriminate between subjects with lichenoid (OLC+) (N=94) and non-lichenoid (OLC−) (N=237) histologic features in a population with OPMDs. ResultsThe OLC Index discriminated OLC+ and OLC− subjects with area under the curve (AUC) of 0.76. Diagnostic accuracy of the OLC Index was not significantly different from expert clinician impressions, with AUC of 0.81 (p=0.0704). Percent agreement was comparable across all raters, with 83.4% between expert clinicians and histopathology, 78.3% between OLC Index and expert clinician, and 77.3% between OLC Index and histopathology. ConclusionThe cytomics-on-a-chip tool and integrated diagnostic model have the potential to facilitate both the triage and diagnosis and risk stratification of patients presenting with OPMDs and OLCs.

Severe Conjunctival and Corneal Epithelial Dysplasia: A Case Series

Ocular surface squamous neoplasia (OSSN) are among the most frequent non-pigmented malignancies of the ocular surface. They have a wide range of histological characteristics - ranging from mild epithelial dysplasia to invasive carcinoma of the squamous cells of the cornea. They may be restricted to the conjunctiva or also involve the cornea. As there are no leading symptoms in the early stages, diagnosis may be very delayed in patients who do not receive regular ophthalmological treatment. The present case series describes clinical and histological data on OSSN and includes clinical and histological data on OSSN, including possible clinical presentations, important risk factors, special histological and cytological features and therapeutic options. Retrospective case series of patients with histologically confirmed severe epithelial dysplasia of the conjunctiva and cornea consistent with OSSN who presented to the Department of Ophthalmology in Basel University Hospital. The analysis covered demographic data, symptoms, diagnostic testing (photo documentation, brush biopsy), treatment and cytological and/or histological material and findings. We report on five patients aged between 41 and 92years at the time of diagnosis. The histological findings in all patients included severe epithelial dysplasia, but with a heterogenous clinical presentation. In all cases, the lesion started in the conjunctiva, but traversed the limbus and extended to the cornea. The primary treatment was always surgical removal. In one patient, this had to be repeated several times due to recurrent metaplasia and was complemented by subsequent mitomycin C therapy. The clinical outcome ranged between total restitution of the original state to inevitable enucleation. The clinical presentation of OSSN is highly heterogenous, so that the initial diagnosis is difficult. There are no official guidelines for treatment, so that the treatment of choice varied between clinics. Regular ophthalmological follow-ups are recommended, even after complete surgical excision. Possible relevant concomitant diseases and risk factors must be identified before therapy.