Genomic profiling of pleomorphic rhabdomyosarcoma reveals a genomic signature distinct from that of embryonal rhabdomyosarcoma.

Pleomorphic rhabdomyosarcoma (PRMS) is a rare and highly aggressive sarcoma, occurring mostly in the deep soft tissues of middle-aged adults and showing a variable degree of skeletal muscle differentiation. The diagnosis is challenging as pathologic features overlap with embryonal rhabdomyosarcoma (ERMS), malignant Triton tumor, and other pleomorphic sarcomas. As recurrent genetic alterations underlying PRMS have not been described to date, ancillary molecular diagnostic testing is not useful in subclassification. Herein, we perform genomic profiling of a well-characterized cohort of 14 PRMS, compared to a control group of 23 ERMS and other pleomorphic sarcomas (undifferentiated pleomorphic sarcoma and pleomorphic liposarcoma) using clinically validated DNA-targeted Next generation sequencing (NGS) panels (MSK-IMPACT). The PRMS cohort included eight males and six females, with a median age of 53 years (range 31-76 years). Despite similar tumor mutation burdens, the genomic landscape of PRMS, with a high frequency of TP53 (79%) and RB1 (43%) alterations, stood in stark contrast to ERMS, with 4% and 0%, respectively. CDKN2A deletions were more common in PRMS (43%), compared to ERMS (13%). In contrast, ERMS harbored somatic driver mutations in the RAS pathway and loss of function mutations in BCOR, which were absent in PRMS. Copy number variations in PRMS showed multiple chromosomal arm-level changes, most commonly gains of chr17p and chr22q and loss of chr6q. Notably, gain of chr8, commonly seen in ERMS (61%) was conspicuously absent in PRMS. The genomic profiles of other pleomorphic sarcomas were overall analogous to PRMS, showing shared alterations in TP53, RB1, and CDKN2A. Overall survival and progression-free survival of PRMS were significantly worse (p < 0.0005) than that of ERMS. Our findings revealed that the molecular landscape of PRMS aligns with other adult pleomorphic sarcomas and is distinct from that of ERMS. Thus, NGS assays may be applied in select challenging cases toward a refined classification. Finally, our data corroborate the inclusion of PRMS in the therapeutic bracket of pleomorphic sarcomas, given that their clinical outcomes are comparable.

Pitfalls in Salivary Gland Cytology.

BACKGROUND: Salivary gland lesions possess diagnostic challenges on fine needle aspiration (FNA) material. They are relatively uncommon, yet present with a wide spectrum of cytomorphology. Herein, we review common salivary gland neoplasms, their cytomorphologic features, their diagnostic pitfalls, and ancillary studies helpful in achieving an accurate diagnosis. SUMMARY: There are many cytomorphologic overlaps between benign and malignant salivary gland entities. Moreover, metaplasia, cystic changes, and degenerative changes are common findings adding to diagnostic dilemmas. These complicating factors contribute to a minute risk of malignancy in salivary gland lesions that are interpreted as benign on FNA. In rare cases, even malignant salivary gland neoplasms are misinterpreted as benign on aspirated material due to the many cytomorphologic overlaps. For example, benign and malignant neoplasms containing stroma such as myoepithelioma and adenoid cystic carcinoma may be misinterpreted as pleomorphic adenoma. Moreover, diagnosis of salivary gland neoplasms with basal cell features can be confusing on FNA materials; for example, basal cell adenoma can be misinterpreted as adenoid cystic carcinoma. Mucoepidermoid carcinomas have many different appearances on aspirated material due to variable amounts of mucin, degree of nuclear atypia, cellular content, and squamous metaplasia. Acinic cell carcinoma exhibits large cells with abundant cytoplasm on FNA, which can be mistaken for oncocytic cells in oncocytoma or Warthin tumor. Salivary duct carcinoma shows distinct features of malignancy and thus can be mistaken for secondary tumors involving the salivary glands or other malignant salivary gland tumors. The presence of tumor-associated lymphocytes is another underlying cause of misdiagnosis, especially when considering the differential diagnosis of an an intraparotid lymph node. Ancillary studies such as immunohistochemistry and molecular studies are gaining more attention to be utilized on FNA cases. PLAG1 immunostaining, CD117 , DOG1, mammaglobin, and androgen receptor (AR) are examples of commonly used immunostains in diagnosis of salivary gland lesions. MYB gene fusion , rearrangements of the MAML2 gene, ,and ERBB2/HER2 are examples of molecular alterations useful in diagnosis of salivary gland neoplasms. In conclusion, the aim of salivary gland cytology is to differentiate benign entities from the malignant ones and to prevent unnecessary aggressive treatments.

Cytopathology of primary sclerosing mucoepidermoid carcinoma with eosinophilia of the thyroid: a multi-institutional case series and review of literature.

INTRODUCTION: Sclerosing Mucoepidermoid Carcinoma with Eosinophilia (SMECE) of the thyroid is an extremely rare tumor that exhibits unique histologic characteristics and is nearly always associated with lymphocytic thyroiditis (LT). However, the cytomorphologic and clinicopathologic characteristics of SMECE have only been described in rare case reports. MATERIALS AND METHODS: Authors' institution laboratory information systems were searched for records of SMECE between 2012 and 2023. Literature review was performed using keywords "Sclerosing mucoepidermoid carcinoma with eosinophilia", "thyroid", and "cytopathology" to search through institution electronic library databases for relevant articles. RESULTS: A total of 19 cases were identified, 3 unpublished in the authors' archives and 16 in the literature which had fine needle aspiration (FNA) material or cytologic features available for review, and were comprised of 3 males and 16 females. The common cytomorphologic characteristics of SMECE included fragments or loose clusters of intermediate-type epidermoid cells in a background of prominent LT and eosinophils. Overt keratinization, mucinous cells, and extracellular mucin were not commonly encountered, resulting in diagnostic challenges, especially if eosinophils associated with epithelial cell clusters were rare. The cases were reported as "Nondiagnostic" (1 case), "Atypia of Undetermined Significance" (4 cases), "Suspicious for Malignancy" (3 case), or "Malignant" (11 cases). CONCLUSIONS: The clinical course of SMECE of the thyroid varied and distinct cytomorphologic characteristics in a subset of patients who experienced aggressive disease raises the possibility of different prognostic grades. Cases with keratinized squamous cells and necrosis mimic anaplastic (undifferentiated) thyroid carcinoma, but the clinical history and radiologic findings can be helpful to exclude this diagnosis.

Cytopathology of mesenchymal tumors of the thyroid gland: analysis of 12 cases from multinational institutions with review of the literature.

INTRODUCTION: Mesenchymal tumors of the thyroid gland are extremely rare. We report the cytomorphologic characteristics of 12 mesenchymal tumors occurring in the thyroid gland and highlight the diagnostic difficulties encountered in their cytologic evaluation. MATERIALS AND METHODS: The cytopathology and surgical pathology archives from 5 large institutions were searched for thyroid mesenchymal tumors that had an FNA available for review. Clinicopathologic and cytomorphologic characteristics for each case were evaluated. RESULTS: Twelve cases of mesenchymal tumors occurring in the thyroid were identified in our search. Patient age ranged from 28 to 84 years (median, 60 years). The cases occurred in 7 women and 5 men. The tumor size ranged from 1.4 to 14 cm (median, 3.3 cm). The tumors were as follows: hemangioma (n = 4; 33.3%), angiosarcoma (n = 2; 16.7%), schwannoma (n = 2; 16.7%), solitary fibrous tumor (n = 2, 16.7%), metastatic synovial sarcoma (n = 1, 8.3%) and metastatic pleomorphic rhabdomyosarcoma (n = 1, 8.3%). The cytomorphologic features of the tumors were similar to those of their counterparts occurring in different sites. An accurate diagnosis was achieved in six primary thyroid mesenchymal cases (60%). Five patients (41.7%) underwent total thyroidectomy, and 3 patients received partial thyroidectomy (25%). Three patients (25%) did not receive a thyroidectomy and subsequent surgical information was not available in 1 case (8.3%). CONCLUSIONS: Mesenchymal tumors of the thyroid are extremely uncommon. Cytologic diagnosis of these tumors is often challenging due to the morphologic overlap with diverse epithelial and non-epithelial thyroid lesions. Ancillary studies such as immunohistochemistry and molecular studies are essential for accurate diagnosis.

Fine needle aspiration of bone lesions: A tertiary care centre experience.

BACKGROUND: Bone fine needle aspiration (FNA) presents several diagnostic challenges including limited sample material, reduced ability to assess the architecture, and lack of a standardised reporting system. The aim of our study is to present our experience regarding bone FNA. METHODS: We performed a 6-year retrospective search of our archives to identify all FNA cases of bone lesions. Available data regarding patients' demographics, cytopathology, and surgical pathology were recorded. The FNA cases were then grouped into five categories (atypical, neoplasm-benign, neoplasm of unknown malignant potential, suspicious for malignancy, and malignant) and the risk of malignancy (ROM) was calculated. RESULTS: A total of 341 FNA cases performed in 337 patients (M = 173, F = 164; mean age = 57.2 years) were identified. The iliac crest was the most commonly biopsied site (n = 134). The adequacy of bone FNA was 77.4%. The sensitivity and specificity regarding the nature of the lesion were 96.5% and 100%, respectively. The overall diagnostic accuracy of bone FNA was 77%. The accuracy of bone FNA for non-metastatic bone lesions including non-neoplastic lesions was 74%, while the diagnostic accuracy of bone FNA for a metastatic disease was 83.5%. The diagnostic accuracy for primary neoplastic lesions was 70%. The frequency (n,%) of cytomorphological categories were as follows: atypical (30, 8.8%); neoplasm-benign (6, 1.8%); neoplasm of unknown malignant potential (18, 5.3%); suspicious for malignancy (4, 1.2%); and malignant (145, 42.5%). The ROM in these categories was respectively as follows: 51.7%, 0%, 46.7%, 100%, and 99.1%. CONCLUSION: FNA is a sensitive and specific technique for the diagnosis of bone lesions. In most instances, an accurate diagnosis can be achieved if adequate material, ancillary studies, and radiological correlation are available.

Fine-Needle Aspiration of Sarcomas Metastatic to Lymph Nodes: A Cytomorphologic Study over a 10-Year Period.

INTRODUCTION: Metastasis of sarcomas to lymph nodes is an uncommon event in its natural history. We aimed to present our experience with fine-needle aspiration (FNA) of metastatic sarcomas to lymph nodes over a 10-year period. MATERIAL AND METHODS: The cytopathology archives were searched for FNA of lymph nodes involved by metastatic sarcomas. Available clinicopathologic data were recorded. All slides were retrieved and reviewed. RESULTS: Thirty-three lymph nodes, from 30 patients, with metastatic soft tissue sarcomas were identified. The lymph node metastases occurred in 16 males and 14 females (median age, 56 years). The size of the lymph nodes ranged from 1.2 to 7.5 cm (median size, 2.9 cm). The inguinal lymph nodes were the most commonly involved nodes, followed by thoracic and cervical neck nodes. The most common metastatic soft tissue sarcoma encountered was Kaposi sarcoma (n = 7, 23.3%), followed by angiosarcoma (n = 6, 20%) and rhabdomyosarcoma (n = 6, 20%). The most common site of primary soft tissue sarcoma was the head and neck (n = 8, 26.6%), followed by lower extremity (n = 7, 23.3%). The initial diagnosis of sarcoma was established in 6 cases. Seventen patients had metachronous involvement of lymph nodes, while the remaining patients had synchronous involvement. Seventen patients died of disease, and the survival after lymph node metastasis ranged from 1 to 43 months. CONCLUSION: FNA is an accurate and effective method in the diagnosis of metastatic sarcoma to lymph nodes. Knowledge of clinical findings and primary tumor diagnosis along with careful assessment of the cytomorphology is extremely helpful for an accurate diagnosis of metastases.

Synovial sarcoma: cytopathology of 51 cases highlighting the application of ancillary molecular testing.

INTRODUCTION: Among sarcomas, synovial sarcoma (SS) is defined by its unique SS18 cytogenetic translocation. Fine needle aspiration (FNA) biopsy is in a key position to exploit this uniqueness for diagnostic purposes. MATERIALS AND METHODS: Our cytopathology files were searched for examples of SS with histopathologic verification. FNA biopsy, imprint smears, and core needle biopsy (CNB) were performed using standard techniques. RESULTS: Fifty-one cases from 49 patients (male/female ratio, 1:1; age range, 12-79 years; mean age, 40 years) met the inclusion criteria. Of the 51 cases, 44 (86%) were FNAs, 6 were cytology imprints, and 1 was pleural fluid. Eleven aspirates had concurrent CNB. All cases had tissue confirmation. The biopsy sites included extremities (n = 24; 47%), trunk (n = 12; 24%), lung (n = 8; 16%), head or neck (n = 6; 12%), and pleural fluid (n = 1; 2%). The aspirates were from primary (n = 36; 71%), metastatic (n = 12; 24%), and recurrent (n = 3; 5%) neoplasms. The cytologic diagnoses were SS (69%), suspicious for SS (12%), malignancy (10%), spindle cell neoplasm (4%), and malignancy other than SS (6%). In general, smears and imprints contained dense cell aggregates and single cells composed of a monotonous population having fusiform, rounded, or ovoid banal nuclei and scant cytoplasm. Poorly differentiated SS showed both large epithelioid cell and small cell cytomorphology. When performed, SS18 immunohistochemical and genetic testing was positive in all 19 FNA and 3 CNB cases. CONCLUSIONS: When coupled with appropriate ancillary testing, FNA biopsy allows for a specific, accurate diagnosis of SS in most cases.

Degenerative atypia in benign thyroid nodules: a potential diagnostic pitfall on fine-needle aspiration.

INTRODUCTION: Benign (B) follicular lesions of the thyroid are among the most encountered specimens on fine needle aspiration (FNA). Although FNA and The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) remain highly accurate, minimally invasive and robust tools in triaging thyroid nodules, false positive (FP) diagnoses may still occur. Endocrine-type degenerative atypia can cause diagnoses of suspicious for malignancy (SFM) or malignant (M), resulting in overtreatment and exposure to undue surgical risk in patients. MATERIALS AND METHODS: We performed a multi-institutional retrospective clinicopathologic correlation of benign thyroid nodules with degenerative atypia on FNA. Review of cytologic material was conducted to identify potential cytomorphologic features which may have prompted these diagnoses. RESULTS: Among 342 patients with benign thyroid nodules harboring degenerative atypia, 123 had available preceding FNA cytopathology. TBSRTC nondiagnostic, B, atypia of undetermined significance, follicular neoplasm, SFM, and M, comprised 3.3%, 49.6%, 30.1%, 13.0%, 2.4%, and 1.6% of cases. Among patients with FP diagnoses (SFM and M), 100% underwent total thyroidectomy, and 40.0% underwent additional neck lymph node dissections. Among remaining patients, 61.0%, 39.0%, and 0% underwent lobectomy, thyroidectomy, and lymph node dissection. The number of patients who underwent total thyroidectomy was significantly different (P = 0.03) between those with FP nodules and those without. CONCLUSIONS: We demonstrate that 4.1% of nodules harboring endocrine-type degenerative atypia may be given FP diagnoses on initial FNA. Such atypia may be indistinguishable from that of Graves' Disease, dyshormonogenic goiter, and radiation therapy. FP diagnoses of degenerative atypia can expose patients to undue surgical procedures and risks.

Myxoid Soft Tissue Tumors: A 20-Year Experience on Fine Needle Aspiration with Application of the Proposed WHO Reporting System for Soft Tissue Cytopathology.

INTRODUCTION: Myxoid soft tissue tumors represent a heterogenous group of neoplasms. The study presented our experience on cytopathology of myxoid soft tissue tumors on fine needle aspiration (FNA) and aimed to apply the recently proposed WHO system for reporting soft tissue cytopathology. MATERIAL AND METHODS: We performed a 20-year retrospective search of our archives to identify all FNAs performed on myxoid soft tissue lesions. All cases were reviewed, and the WHO reporting system was applied. RESULTS: 129 FNAs performed in 121 patients (62 males; 59 females) showed a prominent myxoid component, accounting for 2.4% of all soft tissue FNAs. The FNAs were performed on 111 (86.7%) primary tumors, 17 (13.2%) recurrent tumors, and one (0.8%) metastatic lesion. A spectrum of non-neoplastic and neoplastic lesions including both benign and malignant neoplasms was identified. Overall, the most common tumors identified were myxoid liposarcoma (27.1%), intramuscular myxoma (15.5%), and myxofibrosarcoma (13.1%). The sensitivity and specificity of FNA regarding the nature of the lesion (benign vs. malignant) were 98% and 100%, respectively. When the WHO reporting system was applied, the frequency of the categories was as follows: benign (7.8%), atypical (34.1%), soft tissue neoplasm of uncertain malignant potential (18.6%), suspicious for malignancy (3.1%), and malignant (36.4%). The risk of malignancy calculated in each category was as follows: benign (10%), atypical (31.8%), soft tissue neoplasm of uncertain malignant potential (50%), suspicious for malignancy (100%), and malignant (100%). CONCLUSION: A diverse group of non-neoplastic and neoplastic lesions can show a prominent myxoid component on FNA. The WHO reporting system for soft tissue cytopathology is easily applicable and appears to correlate well with the malignant potential of myxoid tumors.

Benign mesenchymal tumours of the tongue: A report of adult-type rhabdomyoma and granular cell tumour with a review of the literature.

The cytomorphological features of benign mesenchymal tumours of the tongue have rarely been reported. Herein, we present the cytomorphological features of adult-type rhabdomyoma, which occurred in the tongue of a female patient, and granular cell tumour (GCT), which occurred in the tongue of a male patient; both patients were in their mid-50s. The cytological features of the adult-type rhabdomyoma case included large polygonal to ovoid cells with abundant and granular cytoplasm with predominantly peripherally located, uniform, round to oval nuclei and small nucleoli. Cross-striation and crystalline intracytoplasmic structures were not seen. The cytological features of the GCT case included large cells with abundant granular pale cytoplasm, small round nuclei and small distinct nucleoli. The cytological differential diagnoses of these tumours overlap; thus, the cytological findings of the different entities included in their differential diagnoses are discussed.

Metastatic sarcomas to pleural effusion: a 10-year large tertiary care center experience with emphasis on clinical features and cytomorphologic characteristics.

INTRODUCTION: Metastatic sarcomas to pleural effusion are extremely rare, accounting for <1% of all malignant pleural effusions. We aim to present our experience with pleural effusion specimens containing metastatic sarcomas over a 10-year period. METHODS: We performed a 10-year retrospective search of cytopathology archives to identify all pleural effusions that were involved by metastatic sarcoma. All available cytopathology and surgical pathology specimens were retrieved and reviewed. RESULTS: Twenty-eight pleural fluids from 22 patients with metastatic sarcoma were identified in our search. The patients' ages ranged from 12 to 73 years. The pleural fluid volumes ranged from 10 to 1500 ml. Rhabdomyosarcoma was the most commonly encountered metastatic sarcoma to pleural effusion (n = 7). Other metastatic sarcomas were as follows: epithelioid angiosarcoma (n = 4), Ewing sarcoma (n = 3), clear cell sarcoma (n = 2), high grade conventional osteosarcoma (n = 2), undifferentiated pleomorphic sarcoma (n = 1), epithelioid sarcoma, proximal type (n = 1), dedifferentiated liposarcoma (n = 1), and conventional chondrosarcoma (n = 1). The time between initial diagnosis and effusion varied from 3 months to 25 years. Two patients are alive with disease at 6 and 21 months of follow-up. All other patients were dead of disease and the survival after a malignant pleural effusion ranged from <1 month to 18 months. CONCLUSIONS: Metastatic bone and soft tissue sarcomas to pleural effusions are rare and their cytologic features can be mistaken for carcinoma, melanoma, or mesothelioma. Careful review of the patient's medical history, comparison of the previous pathology and the use of ancillary studies are crucial for the evaluation of pleural effusions involved by metastatic sarcomas.

Polymethylmethacrylate-induced foreign body reaction presenting as bilateral parotid lesions: A case report of dermal filler adverse reaction diagnosed on fine needle aspiration.

BACKGROUND: Dermal filler injections are being increasingly used as a non-surgical option for facial cosmetic procedures. However, their use has been implicated in multiple adverse events including immediate, early onset, and late onset complications. AIM: We present a case of dermal filler-induced foreign body reaction presenting as bilateral parotid lesions and diagnosed using fine needle aspiration. CONCLUSION: This case elucidate the risk of delayed adverse events in patients with dermal filler injections and stresses the importance of awareness by patients and providers for such events.

Chondroblastoma: Cytomorphologic Analysis of 10 Cases with Review of the Literature.

INTRODUCTION: Chondroblastoma (CB) is a rare, benign cartilage-producing tumor, typically affecting the epiphysis of long bones in skeletally immature individuals. There have been only limited case reports describing the cytomorphologic features of this tumor, and thus the cytopathologic diagnostic criteria are controversial. Herein, we report the cytologic findings of 10 CB cases, discuss the diagnostic criteria and critical differential diagnosis, along with a comprehensive review of the literature. METHODS: We performed a retrospective search of our cytopathology and surgical pathology databases for cases diagnosed as CB that had corresponding cytology specimens from four large medical institutions. All available cytopathology specimens were retrieved and reviewed. Clinicopathologic and radiologic data were recorded. RESULTS: Ten cases were retrieved from 8 patients aged 15-42 years (mean, 24 years), five of whom were males. Eight cases represented primary tumors while 2 cases were recurrences. Three cases occurred in the femur, two cases occurred in the humerus, while 1 case occurred in each of the glenoid, talus, and proximal phalanx of the 3rd toe. The cytologic diagnosis of CB was achieved in 7 cases. The neoplastic mononuclear cells were present in all cases and their cytologic features were similar. These cells displayed round to oval eccentric nuclei, evenly distributed chromatin, and inconspicuous nucleoli; few of which had nuclear indentations. Multinucleated giant cells were present in 9 cases (90%). Fragments of chondromyxoid matrix were present in 4 cases on cytologic preparations (40%). Cell blocks were available in 8 cases. Mononuclear and multinucleated giant cells were present in all adequate cell blocks and their cytologic features were identical to those seen in the smears. The chondroid matrix was present in only three of the adequate cell blocks (43%). CONCLUSION: We concluded that with the appropriate clinical and radiologic setting, the diagnosis of CB can be achieved on cytology if characteristic chondroblasts are present. The presence of chondromyxoid matrix is a helpful clue but is not necessary for the diagnosis. As in surgical pathology, cytologic evaluation of bone tumors should be interpreted in conjunction with clinical and radiologic findings.

Pancreatoblastoma in an elderly woman: A case report simulating a pancreatic neuroendocrine tumour with emphasis on cytomorphological features.

Pancreatoblastoma (PB), a rare malignant epithelial neoplasm, is the most common pancreatic neoplasm of childhood. It is exceptionally rare in the adult population and its occurrence is limited to case reports. Although the neoplastic cells of PB can have a number of different directions of differentiation, PB is defined by the combination of neoplastic cells with acinar differentiation and squamoid morules. We report a case of a female patient in her 70s who presented with elevated creatinine level, concerning a kidney disorder, and was found to have an abdominal mass on CT scan. Fine needle aspiration (FNA) showed cellular smears with numerous 3-dimentional clusters of acinar cells and scattered squamoid morules. A cell block showed sheets of cells, some of which formed acini. Numerous squamoid morules were noted and were highlighted by nuclear labelling with antibodies to B-catenin in the cell block. The FNA diagnosis was rendered as "carcinoma with acinar differentiation, favour pancreatoblastoma." Subsequent histological findings confirmed the PB diagnosis. Next generation sequencing detected a CTNNB1 mutation. Given the wide usage of FNA in the preoperative diagnosis of pancreatic masses, the cytopathologist needs to be aware of the morphological features of PB and its cytological differential diagnosis, even in an elderly patient. The differential diagnosis includes acinar cell carcinoma, pancreatic neuroendocrine tumour, and solid pseudopapillary neoplasm. In conclusion, the cytological finding of neoplastic cells with acinar differentiation combined with squamous morules and/or mesenchymal elements in the smears and more commonly in the cell blocks appears to be the most specific finding for the diagnosis of PB.

Chordoma: analysis of 47 fine-needle aspiration biopsy, cytologic imprint, and small biopsy specimens.

INTRODUCTION: Fine-needle aspiration (FNA) and small tissue biopsy of chordoma have been reported in several small series, but no large series exists. We undertook an examination of 47 cases (with concurrent core needle biopsy in a subset) to analyze diagnostic accuracy, cytomorphology, and immunohistochemistry. MATERIALS AND METHODS: Our cytopathology files were searched for examples of chordoma with histopathologic verification. FNA biopsy smears and core needle were performed using standard techniques. RESULTS: Forty-seven cases of chordoma were retrieved from 44 patients [M:F; 1.8:1; age range 5-81 years; mean age 55 years]. Twenty-seven presented with primary, 10 with locally recurrent, and 7 with metastatic tumors. Two aspirates were from the appendicular skeleton, 2 from the trunk, 1 from neck lymph node, and 42 aspirates (89%) from axial and peri-axial skeleton and surrounding soft tissues. Four were cytologic touch imprints while the remainder were FNA biopsy specimens. Specific cytologic diagnoses were chordoma/consistent with chordoma (44 cases, 94%), suspicious for chordoma (2), and malignant neoplasm (1). Along with a single case of benign notochordal tumor misdiagnosed as chordoma, our diagnostic accuracy was 91%. Concurrent tissue biopsy was performed in 51% of cases. Immunohistochemical staining of tumor in 29 (62%) cases showed expression of brachyury in 23 of 24 (96%) instances. Cytopathology consisted of cellular smears populated by large cells possessing enormous amounts of vacuolated and non-vacuolated cytoplasm with an abundant background myxoid/chondromyxoid stroma. CONCLUSIONS: FNA and small tissue biopsy specimens show a very high degree of diagnostic accuracy in recognition of chordoma.

Cytopathology of rare gastric mesenchymal neoplasms: A series of 25 cases and review of literature.

BACKGROUND: Gastrointestinal stromal tumour (GIST) is the most common mesenchymal neoplasm arising in the stomach. However, a number of other rare mesenchymal neoplasms do occur at this anatomic site, which often presents a diagnostic challenge for cytopathologists on endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). Our study aims to selectively present the clinico-radiological and cytopathological characteristics of these rare "non-GIST" neoplasms, as well as their differential diagnoses. MATERIAL AND METHODS: We performed a 20 year retrospective search in the cytopathology database of our two large medical institutions for non-GIST mesenchymal neoplasms arising in the stomach and diagnosed on EUS-FNA. Data regarding the patients' demographics and radiological findings were analysed. All available cytopathology specimens were reviewed. The cytomorphological characteristics and the accompanying immunohistochemical stains, when available, were subsequently analysed. RESULTS: Twenty-five cases of gastric mesenchymal tumours were selectively included in the study after excluding all cases of GIST (n = 113) diagnosed on FNA. These cases included 10 leiomyomas (40%), eight schwannomas (32%), five glomus tumours (20%), one perivascular epithelioid cell neoplasm, and one desmoid tumour. The specimen cellularity was variable and ranged from hypocellular to highly cellular. Most smears were composed of spindle cells with a few showing epithelioid morphology. Cell blocks were available in 20 cases and a range of immunohistochemical ancillary studies were performed. DOG-1, c-KIT, smooth muscle actin (SMA), and S100-protein were the most common immunomarkers done. CONCLUSION: Our study highlights important cytomorphological characteristics of rare mesenchymal neoplasms arising in the stomach. In the appropriate clinical setting and with the help of immunohistochemistry, an accurate diagnosis of these neoplasms can be achieved.

Label Cleaning Multiple Instance Learning: Refining Coarse Annotations on Single Whole-Slide Images.

Annotating cancerous regions in whole-slide images (WSIs) of pathology samples plays a critical role in clinical diagnosis, biomedical research, and machine learning algorithms development. However, generating exhaustive and accurate annotations is labor-intensive, challenging, and costly. Drawing only coarse and approximate annotations is a much easier task, less costly, and it alleviates pathologists' workload. In this paper, we study the problem of refining these approximate annotations in digital pathology to obtain more accurate ones. Some previous works have explored obtaining machine learning models from these inaccurate annotations, but few of them tackle the refinement problem where the mislabeled regions should be explicitly identified and corrected, and all of them require a - often very large - number of training samples. We present a method, named Label Cleaning Multiple Instance Learning (LC-MIL), to refine coarse annotations on a single WSI without the need for external training data. Patches cropped from a WSI with inaccurate labels are processed jointly within a multiple instance learning framework, mitigating their impact on the predictive model and refining the segmentation. Our experiments on a heterogeneous WSI set with breast cancer lymph node metastasis, liver cancer, and colorectal cancer samples show that LC-MIL significantly refines the coarse annotations, outperforming state-of-the-art alternatives, even while learning from a single slide. Moreover, we demonstrate how real annotations drawn by pathologists can be efficiently refined and improved by the proposed approach. All these results demonstrate that LC-MIL is a promising, lightweight tool to provide fine-grained annotations from coarsely annotated pathology sets.

Atypia of undetermined significance in the Milan System for Reporting Salivary Gland Cytopathology: Cystic versus non-cystic masses.

The term "Atypia" has been employed to describe a wide spectrum of cytomorphologic features associated with reactive/inflammatory processes as well as those suspicious for neoplasms in cytology. Similar to other cytopathology reporting systems, the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) has reserved the atypical category for cytology specimens lacking quantitative and/or qualitative cytomorphologic features to be diagnosed with confidence as either non-neoplastic or neoplastic. In MSRSGC, the atypical category is associated with a risk of malignancy and recommendation for clinical management. In this review, we discuss the value of atypical diagnostic category of MSRSGC in both cystic and non-cystic salivary gland lesions by evaluating our institutional case cohort.

Application of the Milan System for Reporting Salivary Gland Cytopathology in pediatric patients: An international, multi-institutional study.

BACKGROUND: Pediatric salivary gland fine-needle aspiration (FNA) is uncommon with a higher frequency of inflammatory lesions and a small proportion of malignancies. This international, multi-institutional cohort evaluated the application of the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) and the risk of malignancy (ROM) for each diagnostic category. METHODS: Pediatric (0- to 21-year-old) salivary gland FNA specimens from 22 international institutions of 7 countries, including the United States, England, Italy, Greece, Finland, Brazil, and France, were retrospectively assigned to an MSRSGC diagnostic category as follows: nondiagnostic, nonneoplastic, atypia of undetermined significance (AUS), benign neoplasm, salivary gland neoplasm of uncertain malignant potential (SUMP), suspicious for malignancy (SM), or malignant. Cytology-histology correlation was performed where available, and the ROM was calculated for each MSRSGC diagnostic category. RESULTS: The cohort of 477 aspirates was reclassified according to the MSRSGC as follows: nondiagnostic, 10.3%; nonneoplastic, 34.6%; AUS, 5.2%; benign neoplasm, 27.5%; SUMP, 7.5%; SM, 2.5%; and malignant, 12.4%. Histopathologic follow-up was available for 237 cases (49.7%). The ROMs were as follows: nondiagnostic, 5.9%; nonneoplastic, 9.1%; AUS, 35.7%; benign neoplasm, 3.3%; SUMP, 31.8%; SM, 100%; and malignant, 100%. Mucoepidermoid carcinoma was the most common malignancy (18 of 237; 7.6%), and it was followed by acinic cell carcinoma (16 of 237; 6.8%). Pleomorphic adenoma was the most common benign neoplasm (95 of 237; 40.1%). CONCLUSIONS: The MSRSGC can be reliably applied to pediatric salivary gland FNA. The ROM of each MSRSGC category in pediatric salivary gland FNA is relatively similar to the ROM of each category in adult salivary gland FNA, although the reported rates for the different MSRSGC categories are variable across institutions.

Ancillary studies on cell blocks from fine needle aspiration specimens of salivary gland lesions: A multi-institutional study.

BACKGROUND: Ancillary studies are commonly performed on cell blocks prepared from fine-needle aspiration (FNA) specimens. There are limited studies in application of ancillary studies on cell blocks from salivary gland (SG) FNAs. This multi-institutional study evaluates the role of ancillary studies performed on cell blocks in the diagnosis of SG lesions, and their impact on clinical management. METHOD: The electronic pathology archives of three large academic institutions were searched for SG FNAs with ancillary studies performed on cell blocks. The patient demographics, FNA site, cytologic diagnosis, ancillary studies, and surgical follow-up were recorded. If needed, the cytologic diagnoses were reclassified as per the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC). RESULTS: 117 SG FNA cases were identified including 3, 10, 11, 6, 23, 4, and 60 cases in MSRSGC categories I, II, III, IVa, IVb, V, VI, respectively with surgical follow-up available ranging from 27% to 100% within each category. Ancillary studies including histochemistry, immunocytochemistry (IHC), and in situ hybridization (ISH) were beneficial in 60%-100% of cases in each category. Risk of malignancy was 100% in both the suspicious for malignancy (V) and malignant (VI) categories. Ancillary studies improved diagnosis in 60% of non-neoplastic cases (II, 6/10), 100% of benign neoplasm cases (IVa, 6/6), and 98.3% of malignant cases (VI, 59/60). CONCLUSION: Judicious and case-based ancillary studies performed on SG FNA cell blocks with sufficient material can improve the diagnostic yield by further characterization of the atypical/neoplastic cells, particularly in MSRSGC categories IVa-VI.