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Introduction: Benign peripheral nerve tumors (BPNTs) are a heterogenous group of soft tissue tumors that include a variety of nerve sheath tumors, granular cell tumor (GCT), and ganglioneuroma. Only a few large studies exist on cytopathology and diagnostic accuracy using fine-needle aspiration (FNA) biopsy for this set of neoplasms., Materials and Methods: Both surgical and cytopathology files were searched for cases of BPNT. FNA biopsy was performed using standard techniques., Results: Eighty-nine cases from 88 patients (male:female = 1:1; age range: 16-85 years, mean age, 51 years) met inclusion criteria. FNA sites included extremities (58, 65%), head/neck (14, 16%), deep (9, 10%), and trunk (8, 10%). Aspirates were from primary neoplasms in all but one instance. There were 65 schwannomas, seven neurofibromas, seven perineuriomas, seven GCTs, and three ganglioneuromas/neuromas. Aspirates of schwannoma, GCT, neurofibroma (NF), and perineurioma (PN) were correctly diagnosed in 86%, 100%, 29%, and 0% of cases, respectively. Five tumors (6%) were interpreted as either a specific sarcoma or suspicious for sarcoma. Remaining aspirates were classified as spindle cell neoplasm, salivary gland neoplasm, and nondiagnostic. Cytologic features for schwannoma, NF, PN, and ganglioneuroma showed spindle cell-dominant smears arranged mainly in syncytial clusters. GCT aspirates contained a population of epithelioid cells harboring coarsely granular cytoplasm and bare nuclei. Immunohistochemical (IHC) staining in 55 (62%) cases showed S-100 expression in 95%., Conclusion: FNA biopsy coupled with IHC is reliable in correctly classifying schwannoma and GCT, but less so for NF. Perineurioma can be mistaken for sarcoma., (© 2023 American Cancer Society.)

The classification of salivary gland tumors is ever-evolving with new variants of tumors being described every year. Next-generation sequencing panels have helped to prove and disprove prior assumptions about tumors' relationships to one another, and have helped refine this classification. Adenoid cystic carcinoma (AdCC) is one of the most common salivary gland malignancies and occurs at all major and minor salivary gland and seromucous gland sites. Most AdCC are predominantly myoepithelial and basaloid with variable cribriform, tubular, and solid growth. The luminal tubular elements are often less conspicuous. AdCC has largely been characterized by canonical MYB fusions, with MYB::NFIB and rarer MYBL1::NFIB. Anecdotal cases of AdCC, mostly in nonmajor salivary gland sites, have been noted to have unusual patterns, including squamous differentiation and macrocystic growth. Recently, this has led to the recognition of a subtype termed "metatypical adenoid cystic carcinoma." Another unusual histology that we have seen with a wide range of architecture, is striking tubular hypereosinophilia. The hypereosinophilia and luminal cell prominence is in stark contrast to the vast majority of AdCC that are basaloid and myoepithelial predominant. A total of 16 cases with tubular hypereosinophilia were collected, forming morular, solid, micropapillary, and glomeruloid growth, and occasionally having rhabdoid or Paneth-like cells. They were subjected to molecular profiling demonstrating canonical MYB::NFIB (5 cases) and MYBL1::NFIB (2 cases), as well as noncanonical EWSR1::MYB (2 cases) and FUS::MYB (1 case). The remaining 6 cases had either no fusion (3 cases) or failed sequencing (3 cases). All cases were present in nonmajor salivary gland sites, with seromucous glands being the most common. These include sinonasal tract (7 cases), laryngotracheal (2 cases), external auditory canal (2 cases), nasopharynx (1 case), base of tongue (2 cases), palate (1 case), and floor of mouth (1 case). A tissue microarray of 102 conventional AdCC, including many in major salivary gland sites was examined for EWSR1 and FUS by fluorescence in situ hybridization and showed that these novel fusions were isolated to this histology and nonmajor salivary gland location. In summary, complex and striking tubular hypereosinophilia and diverse architectures are present within the spectrum of AdCC, particularly in seromucous gland sites, and may show variant EWSR1/FUS::MYB fusions., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: The fine-needle aspiration (FNA) cytopathology of pleomorphic hyalinizing angiectatic tumor (PHAT) is the subject of a very limited number of reports. We undertook a review of our FNA experience with this neoplasm., Materials and Methods: A search was made of our files for PHAT FNA cases with histopathologic confirmation. FNA biopsy smears and cell blocks were performed and examined using standard techniques., Results: Two primary cases of histologically proven PHAT [both male, ages 56 and 60 years] met study inclusion. FNA sites included buttock and foot. A misdiagnosis of sarcoma was made in each case. Ancillary immunohistochemical testing performed in 1 case suggested angiosarcoma. Cytologic smears showed only modest cellularity with a dual population of bland spindle cells and isolated large pleomorphic cells, many harboring nuclear pseudoinclusions. Smear background was clean, and mitoses absent., Conclusions: The imitative cytopathology of PHAT with a pleomorphic sarcoma remains a pitfall in FNA specimens. Awareness of this entity and its lack of hypercellularity, necrosis, and cohesive groups of atypical cells in smears should assist the cytopathologist in avoiding a misdiagnosis of malignancy., (Copyright © 2022 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2022 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

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., (© 2023 S. Karger AG, Basel.)

Introduction: In children and adolescents, most sarcoma subtypes have a simple karyotype with a single genetic alteration; cytologic findings combined with ancillary testing can lead to a specific diagnosis. The goal of this study was to review the use of fine-needle aspiration in conjunction with immunohistochemistry and molecular studies as a part of an integrated, multidisciplinary diagnostic workup for bone and soft tissue sarcomas in this population., Materials and Methods: We searched for cases aged ≤18 years old with a malignant bone or soft tissue tumor that had corresponding cytology specimens from 3 institutions. Clinical data, cytologic findings and diagnoses, histologic diagnoses, and ancillary testing were documented., Results: Of 99 cases, 55% were male with a mean age of 12 years. Ninety-four cases (95%) had a specific histologic diagnosis, and 84 cases (85%) were primary neoplasms. Ninety-four cases (95%) had a malignant cytologic diagnosis, and 71 cases (72%) had a specific cytologic diagnosis concordant with the histologic diagnosis. Among primary tumors with a specific histologic diagnosis, a specific cytologic diagnosis was made in 63 cases (79%). After excluding osteosarcoma, 74% of the tumors (n = 50) had molecular studies. Specific genetic alterations supporting a definitive diagnosis were found in 42 cases (84%), the majority of which were demonstrated using Fluorescence In Situ Hybridization (n = 33, 79%)., Conclusions: We found that fine-needle aspiration in conjunction with core needle biopsy, immunohistochemistry, and molecular studies allowed cytopathologists to accurately classify sarcomas in a pediatric age group., (Copyright © 2022 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Kaposi sarcoma (KS) is a rare low-grade angioproliferative neoplasm associated with human herpesvirus 8 (HHV-8) infection with multiple clinical subtypes and varying histopathologic patterns. Histologically, many different variants of KS have been reported, yet all can be difficult to recognize and must be differentiated from other vascular tumors. In this report, we studied fourteen cases of a newly described variant of KS reminiscent of a well-differentiated angiosarcoma (angiosarcoma-like KS). All cases showed a diffuse, ill-defined infiltrative dermal-based lesion composed of numerous anastomosing vascular channels of varying caliber lined by a single layer of endothelium with minimal pleomorphism. The vascular proliferation ramified through the dermis and dissected the collagen bundles along with infiltration into the subcutaneous fat and around skin appendages. All cases showed expression of vascular markers (CD31, CD34, and ERG) and were positive for HHV-8. None showed the classic histopathology associated with KS. Without clinical guidance these tumors can be difficult to recognize as KS, creating significant diagnostic challenges. Our study expands on a rare histologic variant of KS that ought to be considered in the differential diagnosis of any cutaneous well-differentiated angiosarcoma. Awareness of this variant of KS is of important for proper diagnosis and management of these patients; thus, careful attention to the histomorphology and clinical history can help lead the pathologist to the correct diagnosis., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Pleural effusions can present a diagnostic challenge as they are not always caused by malignancy in patients with a history of typical visceral primaries., Material and Methods: At 2 major academic medical centers, we have identified several cases in which salivary gland neoplasms metastasized to pleural effusions in patients who have been aggressively managed with various treatment modalities including chemotherapy, radiation, and/or surgical excision., Results: Herein, we present a range of primary salivary gland tumors that metastasized to serous effusions and characterize their cytomorphology, immunoprofiles, and clinical courses. Our case series shows that many tumor types metastasize to pleural effusions and they present unique diagnostic challenges in each case. We found that metastasis of a salivary gland neoplasm to a pleural effusion is a late-stage event and is often associated with poor prognosis., Conclusions: This series serves as a resource to demonstrate the cytomorphologic and immunohistochemical features of malignant pleural effusions due to salivary gland neoplasms and draws attention to poor prognosis in cases of salivary duct carcinoma, mucoepidermoid carcinoma and adenoid cystic carcinoma., (Copyright © 2022 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Myxoid tumors of the soft tissue encompass a group of heterogenous tumors that are characterized by the presence of abundant extracellular myxoid or chondromyxoid matrix material. Fine needle aspiration (FNA) is variably used for diagnosing primary, recurrent, and metastatic myxoid soft tissue tumors. The spectrum of myxoid soft tissue tumors encountered in practice ranges from benign lesions such as simple ganglion cysts to high-grade malignant sarcomas such as myxofibrosarcoma. These myxoid tumors have clinical, cytologic, and histologic overlap. Therefore, making an accurate diagnosis by FNA alone is challenging. Despite this challenge, using a systematic cytomorphologic approach and ancillary studies, an accurate diagnosis is feasible in the majority of cases. This article provides a systematic approach to diagnosing myxoid soft tissue tumors by FNA along with a review of the literature., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Mucoepidermoid carcinoma (MEC) is the most common salivary gland (SG) malignancy. In this study, the author undertook analysis of a large collection of MEC cytologic cases., Materials and Methods: Cytopathology files were searched for MEC cases with histopathologic confirmation. Fine-needle aspiration (FNA) smears used standard technique., Results: Seventy-six cases (63 patients [M:F = 1:1; age range, 23-87 years; mean age, 58 years]) met inclusion criteria. Aspirates were primary (54 [71%]), metastatic (18 [24%]), and locally recurrent (4 [5%]). FNA sites included parotid gland (49 [64%]), regional lymph nodes (11 [14%]), submandibular gland (5 [7%]), inner canthus of eye (2 [3%]), and lung (2 [3%]); and single specimens from palate, jaw, shoulder, paranasal sinus, floor of mouth, ear canal, and effusion. Cytologic diagnoses included MEC (30 cases [39%]), suspicious for MEC (16 [21%]), non-MEC carcinoma (9 [12%]), suspicious for malignancy (SM) (2 [3%], malignant (M) (1 [1%]), SG and/or suspicious SG neoplasm (7 [8%]), atypical (3 [5%]), nonneoplastic (5 [6%]), nondiagnostic (2 [3%]), and benign SG neoplasm (1 [1%]). A total of 26% of low-grade (LG) cases were diagnosed as malignant in contrast to 87% malignant in high-grade (HG) cases. Cytomorphology depended on tumor grade. LG MEC contained intra- and/or extra-cellular mucin and more uniform cell and/or nuclear morphology, whereas cytologic atypia, anisonucleosis, and keratotic cells were more typical of HG tumors., Conclusion: A malignant (M) or suspicious for malignancy (SM) cytologic interpretation was made in 76% of mucoepidermoid carcinoma (MEC) cases. In contrast to high-grade MEC (97% identified as M/SM), only 59% of low-grade (LG) MEC cases were interpreted as such, illustrating the continued diagnostic challenge posed by LG MEC using fine-needle aspiration biopsy., (© 2022 American Cancer Society.)

Background: Pleomorphic liposarcoma (PLPS) is the least common but most aggressive of all forms of liposarcoma (LPS). Its diagnosis relies on the recognition of pleomorphic lipoblasts (PLBs), whose numbers vary considerably. Because few large fine-needle aspiration (FNA) biopsy studies exist, the authors review their experience with PLPS., Methods: The authors' cytopathology files were searched for PLPS with histopathologic verification. FNA biopsy smears were performed via standard techniques., Results: Twenty cases from 20 patients (male/female ratio, 2.3/1; age range, 22-77 years; mean age, 58 years) met the inclusion criteria. All had tissue confirmation. Biopsy sites included the following: thigh (11 [55%]), upper extremity (4 [20%]), axilla (2 [10%]), neck (1 [5%]), chest wall (1 [5%]), and mediastinum (1 [5%]). Aspirates were from primary (17 [85%]), locally recurrent (2 [10%]), and metastatic neoplasms (1 [5%]). The FNA diagnoses were PLPS (10 [50%]), myxofibrosarcoma (4 [20%]), LPS (2 [10%]), sarcoma (2 [10%]), and high-grade malignant neoplasm (2 [10%]). Smears showed thick cell clusters and dissociated single forms. Pleomorphic, epithelioid, and bizarre cell/nuclear shapes were common. PLBs were absent, rare, or unnoticed in 45%. In 25%, smears dominated by myxoid stroma were diagnosed as high-grade myxofibrosarcoma or myxoid LPS. Ancillary testing performed in 5 cases had limited diagnostic efficacy., Conclusions: FNA biopsy of PLPS, although able to successfully recognize malignancy, suffers from a sampling bias due to an inability to capture or recognize PLBs in a significant proportion of cases secondary to the heterogeneous composition of this neoplasm., (© 2022 American Cancer Society.)

Background: Although usually recognized as malignant, fine-needle aspiration (FNA) biopsy of salivary duct carcinoma (SDC) has been confused with other primary salivary gland (SG) neoplasms. This article undertook an analysis of a large collection of SDC FNA cases to assess diagnostic accuracy, specificity, and cytopathology., Methods: Cytopathology files were searched for SDC with histopathologic validation. FNA biopsy smears were performed using standard techniques., Results: Seventy cases from 56 patients (M:F, 1.9:1; age range, 26-92 years; mean age, 65 years) met inclusion criteria. All had tissue confirmation of SDC. FNA sites included: parotid gland (42, 60% cases), neck (10), submandibular gland (7), pre-/post-auricular area (5), face/cheek (3), mediastinal lymph nodes (2), and clavicle (1). Aspirates were from primary (52, 74%), metastatic (12, 17%), and locally recurrent (6, 9%) neoplasms. FNA diagnoses included: SDC (19, 27%), favor/suspicious for SDC (7, 10%), high-grade carcinoma (11), adenocarcinoma (9), carcinoma (6), malignant (6), SG neoplasm (5), atypia (3), SDC versus another malignancy (2), and pleomorphic adenoma (2). Large polygonal cells in groups and single forms showed cribriforming, variable necrosis, pseudopapillae, and oncocytic change. Androgen receptor staining was positive in all cases., Conclusions: FNA biopsy is accurate and reliable in classifying SDC as a malignant neoplasm, but much less so for identification as a specific tumor type. Using the Milan system, 86% of aspirates were classified as either malignant or suspicious for malignancy. A recurring pitfall includes sampling error in cases of SDC ex pleomorphic adenoma., (© 2022 American Cancer Society.)

Background: Mesenchymal neoplasms of the parotid gland (PG) and para-pharyngeal (PP) space are distinctly uncommon. Fine-needle aspiration (FNA) biopsy experience with nonlipomatous neoplasms from this site is reviewed., Methods: Cytopathology and surgical pathology files were examined for mesenchymal PG and PP space neoplasms. FNA biopsy was performed using standard technique., Results: Twenty-two PG and/or PP aspirates from 20 adults (male:female = 1.1:1; age range, 19-84 years, mean age, 50 years) and a 10-week-old infant met inclusion criteria. Biopsy sites included PG (17, 77%) or PP space (5, 23%). Five of 6 malignant neoplasms (83%) were called malignant cytologically. Only 7 of 11 (63%) benign neoplasms were recognized as a benign neoplasm. None of 5 solitary fibrous tumor (SFT) cases were correctly recognized. Conversion to the Milan classification showed 8 (36%) FNA cases diagnosed as benign neoplasm, 6 (27%) malignant neoplasm, 4 (18%) neoplasm of uncertain malignant potential, 2 (9%) nondiagnostic, and single cases of suspicious for malignancy and nonneoplastic. There was 1 false-positive and no false-negative FNA diagnoses. Ancillary testing in 10 (45%) aspirates helped substantiate a correct specific diagnosis in 3 malignant and 3 benign cases., Conclusions: FNA biopsy of nonlipomatous mesenchymal SG neoplasms is particularly challenging. Less than half (9 of 11, 41%) had specific FNA diagnoses that correctly matched the tissue diagnoses or clinical outcome. Accurate Milan categorization was superior for malignant neoplasms (5 of 6, 83%) in contrast to benign neoplasms (7 of 11, 63%), or neoplasms of uncertain malignant potential (SFT) (2 of 5, 40%)., (© 2022 American Cancer Society.)

Background: The cytopathology of a giant cell tumor of soft tissue (GCT-ST), a fibrohistiocytic neoplasm distinct from other giant cell-rich soft tissue tumors, is rarely reported. The authors report their experience with a series of 4 GCT-ST fine-needle aspiration (FNA) biopsy cases and compare them with a set from giant cell tumors of bone (GCTBs)., Methods: The authors' cytopathology files were searched for GCT-ST examples with histopathologic confirmation. FNA biopsy smears were performed and examined with standard techniques., Results: Four cases of GCT-ST presenting as a primary soft tissue mass from 4 patients (3 males and 1 female; age range, 28-75 years, mean age, 53 years) were retrieved. FNA sites included the anterior tibia, buttock, shoulder, and upper back. Three cases were interpreted as suspicious for sarcoma radiographically. The specific diagnoses were atypical giant cell tumor of tendon sheath, suspicious for GCT-ST, atypical myxoid lesion with giant cells, and benign with osteoclast-like giant cells (OLGCs). No case was interpreted as malignant. Aspirates consisted of mononuclear polygonal cells, spindled fibroblast cell clusters, and large OLGCs to the near exclusion of other cell types. OLGCs possessed 10 or more nuclei per cell. A comparison with GCTB aspirates and single case reports from the literature showed comparable cytomorphology., Conclusions: GCT-ST FNA smears mimic those of GCTBs containing a limited population of uniform spindle cell clusters, single dispersed polygonal cells, and cytologically banal OLGCs. GCT-ST should be considered in the differential diagnosis of aspirates containing numerous osteoclast-like giant cells., (© 2021 American Cancer Society.)

Introduction: Soft tissue myoepithelioma (STM), a rare mesenchymal neoplasm morphologically analogous to its more common salivary gland (SG) counterpart, is the subject of single case reports regarding its fine-needle aspiration (FNA) biopsy. To our knowledge, ours is the first case series of STM., Materials and Methods: A search was made of our pathology databases for cases diagnosed as STM. FNA biopsy smears and cell blocks were performed using standard techniques., Results: Seven cases were retrieved from 4 men and 3 women (M:F = 1.3:1; age range: 25-79 years, x = 54 years). All but 1 presented as a primary neoplasm. Six aspirates were from the extremities, and 1 from the abdominal wall. Mean tumor size was 5.7 cm. Cytologic diagnosis of STM or suspicious for STM was made in 3 cases (43%). Remaining FNA diagnoses were spindle cell neoplasm/lesion (2), spindle cell sarcoma (1), and extraskeletal myxoid chondrosarcoma (1). Three cases were composed primarily or solely of uniform spindle cells, 3 primarily of uniform epithelioid cells with plasmacytoid features, and 1 case a mixture of these 2 cell types. Myxoid/chondromyxoid stroma was relatively abundant except in the single hypocellular example. Immunohistochemical (IHC) testing performed in 71% was nonspecific, but positive with S-100 in 4 of 5, EMA in 3 of 3, calponin in 2 of 2, and keratin in 1 of 3 examples., Conclusion: FNA biopsy smears of STM are remarkably similar cytomorphologically to their SG equivalent. However, STM can be misidentified principally as extraskeletal myxoid chondrosarcoma, thus requiring a relatively broad IHC panel for a specific diagnosis., (Copyright © 2021. Published by Elsevier Inc.)

Background: Although largely readily recognizable in tissue sections, acinic cell carcinoma (ACC) remains diagnostically problematic in fine-needle aspiration (FNA) cytopathology. The authors undertook an analysis of a large series of ACC aspirates, including acinic cell carcinoma with high-grade transformation (ACC-HGT)., Methods: The authors searched their cytopathology files for ACC cases with histopathologic confirmation. FNA biopsy was performed according to standard techniques., Results: Fifty FNA biopsy cases of ACC (including 36 of parotid origin [72%]) from 41 patients (female to male ratio, 1.4:1; age range, 23-84 years; average, 54 years) met the study inclusion requirements. Primary neoplasm aspirates were most common (72%), and they were followed by recurrent tumors (16%) and metastases (12%). A precise cytologic diagnosis was made for 64%. Three of 9 ACC-HGT cases (33%) were correctly interpreted as such; 98% of conventional ACC cases were correctly graded as low-grade. With the Milan classification system, 74% fit into the malignant category. Ancillary testing was performed for only 36%. Conventional ACC had moderately to highly cellular smears; monotonous cells in aggregates and single forms; rounded nuclei; and microvacuolated, finely granular, oncocyte-like, or nonspecific cytoplasm. ACC-HGT smears contained larger nuclei, high nuclear to cytoplasmic ratios, coarse nuclear chromatin, and a loss of cytoplasmic granules/vacuoles., Conclusions: A correct diagnosis of ACC via FNA biopsy was made in almost two-thirds of the cases. With the Milan classification, 84% of the cases would have been classified as malignant or suspicious for malignancy. An absence of conventional serous acinar cell morphology in some cases as well as an absence of ancillary immunohistochemistry testing in almost two-thirds of the cases prevented even better diagnostic performance., (© 2021 American Cancer Society.)

Introduction: The cytopathology and diagnostic accuracy of salivary gland (SG) polymorphous adenocarcinoma (PAC) is the subject of a limited number of reports. We undertook a review of our experience with fine needle aspiration (FNA) biopsy and PAC., Materials and Methods: A search was made of our cytopathology files for PAC cases that also had histopathological confirmation. FNA biopsy smears and cell-blocks were performed and examined using standard techniques., Results: Eight FNA biopsy cases of histologically proven PAC from 7 patients [F:M = 1.3:1, age 39-75 years, mean = 58] met study inclusion. Metastatic aspirates were most common (4), followed by 3 primary cases and 1 locally recurrent neoplasm. Primary FNA sites included hard palate (1 case), lip (1), and lateral tongue (1); all metastatic sites were in the neck. A precise cytologic diagnosis was made in 38% of cases; however, when applying the Milan classification system, 100% could be categorised as either malignant or of uncertain malignant potential. Ancillary immunohistochemical testing performed in 44% of the cases was non-specific. Cytologic smears showed cellular uniformity and structural variety of cell groups with tubular, branching, cribriform, and convex patterns as well as variable, but occasionally abundant globular myxoid stroma leading to confusion with adenoid cystic carcinoma., Conclusion: The imitative cytopathology of PAC with other SG neoplasms as well as its infrequency in routine FNA biopsy practice makes specific interpretation difficult, but using a classification system allows for appropriate patient management. Molecular testing in future specimens holds promise for enhancing diagnostic accuracy., (© 2021 John Wiley & Sons Ltd.)

Introduction: Chondromyxoid fibroma is a rare bone tumor characterized by immature myxoid mesenchymal tissue showing early primitive cartilaginous differentiation. There have been limited case reports describing the cytologic features of chondromyxoid fibroma. Herein, we reported cytologic features of chondromyxoid fibroma on fine-needle aspiration (FNA)., Materials and Methods: We performed a retrospective search in our cytopathology and surgical pathology database for cases diagnosed as chondromyxoid fibroma that had corresponding cytology specimens from three medical institutions. All available cytopathology specimens were reviewed., Results: Eight cases were retrieved from patients aged 16-77 years (mean, 51 years), and M:F ratio of 1.7:1. Seven tumors (88%) were primary, and most (62%) occurred in flat bones. Cytologic diagnoses were made in 6 cases with cytologic slides not available to review in 1 case. All cases showed metachromatic matrix in the background, while hyaline cartilage fragments were absent. All cases had two cell populations comprising oval to round cells and stellate to spindle cells. The spindle to stellate cells were more commonly embedded in matrix material. Moderate atypia (hyperchromasia and moderate anisonucleosis) was present in 4 cases (80%), while no mitotic figure was present in all cases., Conclusions: Our study highlights common cytologic features of chondromyxoid fibroma, including the presence of the spindle or stellate cells embedded in matrix material. Hyaline cartilage is uncommon and, if present, diagnostic considerations should include enchondroma or low-grade chondrosarcoma. A specific cytologic diagnosis primarily using FNA samples can be challenging but possible when evaluated in conjunction with clinical and radiologic data., (Copyright © 2021 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Introduction: Myxofibrosarcoma is one of the more common sarcomas encountered in adults., Materials and Methods: A search was made of our cytopathology and surgical pathology databases for cases diagnosed as myxofibrosarcoma (MyxoFS). FNA biopsy smears and cell block were performed and examined using standard techniques., Results: Sixty-six cases were retrieved from patients aged 40 to 94 years (mean: 67 years), with a male:female ratio of 1.4:1. Forty-seven (71%) were primary neoplasms, 13 (20%) locally recurrent, and 6 (9%) metastasis. Lower extremity was the most common site 38 (58%) cases, followed by upper extremity and trunk (each 13 [20%] cases), 1 head/neck, and 1 pleural-based mass. Forty-two (64%) cases were specifically/correctly diagnosed as MyxoFS. Thirteen (20%) were diagnosed as undifferentiated pleomorphic sarcoma (UPS), 3 (4.5%) as myxoid neoplasm, 2 (3%) as myxoid sarcoma, and 1 (1.5%) sarcoma, not otherwise specified. As most were examples of high-grade (HG) MyxoFS, cytomorphology contained pleomorphic and spindled cells set in a variable amount of myxoid stroma. Arborizing capillaries were common, and pseudolipoblasts were uncommon. All cases interpreted as UPS were HG MyxoFS histologically. Five (7.5%) cases-pleomorphic liposarcoma (3), solitary fibrous tumor (1), and atypical lipoma (1)-were mistakenly diagnosed. Ancillary immunohistochemistry played a minor role in diagnostic assessment., Conclusion: MyxoFS was accurately interpreted using FNA biopsy in about two thirds of cases. One fifth were misinterpreted as UPS due to the absence/near absence of myxoid stroma, which varies considerably in the definition of this neoplasm., (Copyright © 2021 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Introduction: Advances in the genetics of soft tissue neoplasia have allowed for the diagnostic recognition of specific tumor types from small biopsy specimens, including those procured using the fine needle aspiration (FNA) biopsy technique. Extraskeletal myxoid chondrosarcoma (EMC) is a malignant mesenchymal neoplasm characterized by NR4A3 and, less specifically, by EWSR1 gene rearrangements. A series of EMC cytologic specimens was examined to demonstrate the diagnostic value of incorporating fluorescence in situ hybridization (FISH) testing in cytologic cases of suspected EMC., Materials and Methods: A search was made of our cytopathology and surgical pathology databases for cases diagnosed as EMC. FNA biopsy cytology, exfoliative cytology, imprint cytology, and FISH analysis were performed and examined using standard techniques., Results: A total of 16 cases of EMC were retrieved from 15 patients (male/female ratio, 2.8:1; mean age, 62 years). Of the 15 patients, 10 were new patients with primary tumors, 2 had locally recurrent tumors, and 4 had metastases. The sites included the extremities in 10 cases, the trunk in 4, serous effusion in 1, and a mediastinal lymph node in 1 case. The specific cytologic diagnoses were EMC (14 cases; 88%), suspicious for EMC (n = 1), and malignant cells (n = 1). All cases for which FISH testing was successfully used were specifically recognized as EMC. Aspirates and imprint smears consisted of uniformly rounded cells set in an opaque myxoid/chondromyxoid stroma (less abundant and more diaphanous in the effusion sample), sometimes arranged in short anastomosing cords. FNA of 1 case of an EMC cellular variant mimicked a malignant small rounded cell tumor., Conclusion: EMC can be added to the growing list of soft tissue neoplasms that are specifically recognizable using cytopathology, coupled with judicious application of ancillary molecular testing., (Copyright © 2020 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Introduction: Second primary nonlymphoid malignancies (SPNLM) have long been recognized as a complication of chronic lymphocytic leukemia (CLL)., Materials and Methods: A search was made of our cytopathology database for cases of CLL that also contained a SPNLM., Results: Seventeen cases from 13 known CLL patients [M:F = 2.3:1; age range: 47-77 years, x = 67 years] met criteria for this study. SPNLMs consisted of different forms of metastatic carcinoma (10 patients) and malignant melanoma (3). Of 16 FNA biopsies and 1 pleural fluid, 82% had ancillary testing; 35% had the specimen subdivided for both flow cytometry (FCM) and immunohistochemistry (IHC). Lymph node was the most common site for FNA biopsy (12), followed by face (2), and soft tissue (2). Squamous cell carcinoma was the most common SPNLM (6), followed by melanoma (3), and there were single cases of adenocarcinoma, large cell neuroendocrine carcinoma, Merkel cell carcinoma, and papillary thyroid carcinoma. A correct specific cytologic diagnosis was made in 15 (88%) cases., Conclusions: Cytopathology is highly proficient in recognizing SPNLM in CLL patients. Utilization of cytologic material for FCM and IHC is feasible, and extremely helpful in achieving diagnostic accuracy., (Copyright © 2021 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Introduction: Perivascular epithelioid cell tumor (PEComa) is a family of rare mesenchymal tumors consisting of histologically and immunohistochemically distinctive perivascular epithelioid cells. Relatively little is known about the cytopathology of extra-renal PEComas. Because of a considerable range of morphology and their rarity, accurate cytologic classification can be challenging. We evaluated cytologic characteristics and diagnostic pitfalls of extra-renal PEComas on fine-needle aspiration (FNA)., Materials and Methods: We performed a retrospective search in our cytopathology and surgical pathology database for cases diagnosed as PEComa that had corresponding cytology specimens from 3 medical institutions. All available cytopathology specimens were reviewed. We evaluated cytologic characteristics and recorded histologic diagnoses and immunohistochemical stains., Results: Seven FNA specimens from 6 patients were identified, and cytologic diagnoses were made in all cases as follows: PEComa (4 cases), most consistent with PEComa (1 case), malignant neoplasm (1 case), and hepatocellular carcinoma (1 case). Most specimens were moderately to highly cellular. Cell distribution occurred as tissue fragments with background proliferating capillaries. Most smears were composed of epithelioid cells showing mild to moderate anisonucleosis, abundant eosinophilic cytoplasm, well-defined borders, intranuclear pseudoinclusions, and prominent nucleoli. A combination of myoid and melanocytic markers was expressed in 6 cases except 1 case, which was called hepatocellular carcinoma., Conclusions: This was the largest FNA series for extra-renal PEComas to date. Our study highlights some common cytomorphologic characteristics of PEComa with which cytopathologists should be familiar. In the right clinical and radiologic context, and with the aid of immunohistochemistry, a definitive diagnosis can be achieved., (Copyright © 2021 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Introduction: Unlike epithelial malignancies, mesenchymal neoplasms arising within the tubular gut are less often encountered in endoscopic ultrasound-guided (EUS) fine-needle aspiration biopsies (FNABs). Nonetheless, preoperative diagnosis of such neoplasms has important therapeutic and prognostic value. We report our experience with this category of neoplasms from the past decade., Materials and Methods: We performed a 10-year retrospective search at our respective institutions to identify EUS-guided FNAB cases of mesenchymal neoplasms arising from the tubular gut wall and closely adjacent structures. Cytopathologic diagnoses were compared to corresponding surgical pathology (SP) when available. Cases with either no confirmatory cell block (CB) immunohistochemical (IHC) staining, or no SP were excluded., Results: Two-hundred eighty-two cases (M:F = 1:1; age range: 25-94 years, mean age = 60 years) of EUS-guided FNAB from the tubular gut met our criteria. Onsite adequacy was performed on nearly all cases. Case numbers: 209 gastrointestinal stromal tumors (GIST), 58 smooth muscle neoplasms, and 15 miscellaneous neoplasms. Of these, 188 (67%) had SP follow-up. We found that 258 (91%) aspirates had a correct specific diagnosis, 3 (1%) were nondiagnostic, 18 (6%) had indeterminate diagnoses, and 3 (1%) had incorrect diagnoses (2 leiomyosarcomas mistaken as leiomyoma, and 1 fibrosclerotic lesion mistaken as inflammatory pseudotumor). Of 94 cases with no SP, all had a specific cytologic diagnosis based on confirmatory IHC staining from the CB including 61 GISTs, 29 smooth muscle neoplasms, and 4 miscellaneous tumors., Conclusion: This study endorses the clinical utility of EUS-guided FNAB in the diagnosis of tubular gut mesenchymal neoplasms. A definitive and accurate diagnosis is possible in over 90% of cases, chiefly when cytomorphology is coupled with optimal cellularity and IHC from a concurrent CB. EUS-guided FNAB diagnosis of mesenchymal tubular gut neoplasms may play an important role in determining neoadjuvant therapy as targeted therapy evolves., (Copyright © 2020 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Fine needle aspiration (FNA) cytology is a sparsely used diagnostic method in the evaluation of mediastinal sarcomas in most medical centers worldwide with most literature citations regarding this category of malignancies consisting of small series and individual case reports. Most of these published studies highlight vascular sarcomas such as epithelioid hemangioendothelioma, and angiosarcoma, various subtypes of liposarcoma including well-differentiated liposarcoma, myxoid liposarcoma, and pleomorphic liposarcoma, malignant peripheral nerve sheath tumor, and sarcomas of uncertain differentiation, primary synovial sarcoma and the Ewing sarcoma family of tumors. This paucity of cytopathology reports regarding mediastinal sarcomas is in marked contrast to the almost daily application of endobronchial ultrasound (EBUS)-guided FNA biopsy for sampling mediastinal lymph nodes and mediastinal masses for primary and metastatic carcinomas which, of course, are considerably more common that any type of sarcoma in this location. EBUS, endoscopic ultrasound-guided (EUS) needle biopsy, and percutaneous image-guided biopsy using either core needle, fine-needle, or both can serve a potentially useful role for diagnostic sampling of mediastinal sarcomas, be they primary or metastatic. This review catalogues much of the published data regarding FNA cytopathology and its application to mediastinal sarcomas. An attempt is made to primarily highlight case series rather than individual case reports; however, due to the paucity of these, case reports are cited and discussed where appropriate., Competing Interests: Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/med-20-30). The series “Mediastinal Sarcomas” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare., (2020 Mediastinum. All rights reserved.)

Introduction: Low-grade fibromyxoid sarcoma (LGFMS) is a rare fibroblastic tumor characterized by a prolonged clinical course and malignant biological behavior. Given its deceptively bland cytomorphology, a diagnosis can be quite challenging notably on fine-needle aspiration (FNA). In an attempt to shed light on some of the distinctive cytomorphologic characteristics, this study was conducted to review all cases of LGFMS in our database, correlating available clinical data, immunohistochemical findings, and molecular analysis., Materials and Methods: This series included 20 FNAs from 18 patients with a histologically confirmed LGFMS diagnosis from 3 large academic institutions. Detailed cytomorphologic analysis for each case was documented in conjunction with corresponding clinical characteristics and provided ancillary testing., Results: Out of 14 adequate FNA samples, 9 (64.2%) demonstrated a mixture of fibrous and myxoid pattern; the majority of cases were composed of deceptively bland tumor cells with rare nuclear pleomorphism and nuclear membrane irregularities. A MUC4 immunostain was performed on 5 specimens; all tested positive (100%). FUS rearrangement was detected in 4 out of 5 cases (80%). Follow-up information revealed 5-year recurrence in 1 case and metastatic disease in 2 cases, to the lung/pleura (8 years) and fourth rib (1 year), respectively., Conclusions: The presence of bland spindle cells and associated with myxoid matrix material, in the appropriate clinical setting, can suggest LGFMS and direct additional confirmatory testing. A definitive diagnosis of LGFMS on FNA requires adequate sampling, familiarity with key cytomorphologic features, acquisition of diagnostic material for a cell block preparation and ancillary testing, and clinicoradiologic correlation., (Copyright © 2020 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Introduction: As a rare soft tissue malignancy, epithelioid sarcoma (EpS) is infrequently subjected to cytopathologic analysis. With the exception of a few series, the cytology literature regarding EpS is largely limited to single case reports. Our purpose was to evaluate our experience with EpS, and review the literature regarding its cytopathology., Materials and Methods: A search was made of our cytopathology and surgical pathology databases for cases diagnosed as EpS. Fine-needle aspiration biopsy smears and imprint smears were performed and examined using standard technique. Effusion samples were processed using liquid-based slides., Results: Twenty cases of EpS were retrieved from 10 patients (M:F 1:1; mean age = 36 years). One patient had 5, 1 patient had 3, and 3 patients had 2 separate specimens. All patients had prior or subsequent tissue confirmation of EpS; all were of the classic/distal type. Seven were new patient cases, 7 were locally recurrent, and 6 were metastases. Sites included lower extremity (8 cases), upper extremity (4), trunk (4), serous effusion (2), scalp (1), and mediastinum (1). Specific cytologic diagnosis were EpS (13 cases), sarcoma not otherwise specified (5), and malignant neoplasm (2). All cases where cell-block SMARCB-1 staining was used were specifically recognized as EpS. Cytomorphology was composed primarily of epithelioid/plasmacytoid cells having eccentrically positioned nuclei, moderate cytoplasm, and variable nuclear pleomorphism., Conclusion: The cytopathology of EpS is somewhat variable, morphologically non-specific, and mimics that of other neoplasms with epithelioid features. Ancillary immunostaining is necessary for a specific diagnosis in newly encountered patients., (Copyright © 2020 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Introduction: Xp11.2 translocation-associated RCC (Xp11RCC) defined by molecular alterations involving TFE3 genetic rearrangements constitutes a large percentage of primary renal neoplasms in children, but less than 4% of adult cases. Fewer than 10 single case reports constitute the English cytopathology literature regarding this neoplasm. Our objective is to describe and illustrate the cytopathology of this uncommon renal neoplasm from a series of 5 cases using cytologic imprints, effusion specimens, and fine-needle aspiration (FNA) cytology., Materials and Methods: Review was made of our cytopathology and surgical pathology databases. FNA biopsy smears and imprint smears were performed using a standard technique. Effusion samples were processed using liquid-based slides., Results: Five cytologic specimens from 4 patients with histopathologically confirmed Xp11RCC were identified (mean age: 36 years) over a period of 7 years. All cases contained large cells with voluminous amounts of vacuolated cytoplasm arranged in non-descript clusters and as single forms. A "tigroid" pattern consisting of linear strips of detached cytoplasm was seen in both imprint smear cases and the single FNA case. Psammomatous calcifications, true papillary structures, and hyaline globules were absent in all cases. Four examples were diagnosed as Xp11RCC, but 3 represented metastatic disease, and 1 was diagnosed using both cytology and core needle tissue histopathology. The remaining case was diagnosed nonspecifically as a clear cell malignant neoplasm., Conclusions: The cytopathologic features of Xp1RCC are relatively nonspecific, and overlap with other renal cell carcinoma subtypes. A definitive diagnosis is only possible with ancillary immunohistochemistry with or without additional TFE3 fluorescence in situ hybridization., (Copyright © 2020 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Context: Beyond squamous carcinoma, a variety of diagnostically challenging neoplasms arise within various head and neck sites. This is particularly the situation with neoplasms where little cellular cytoplasm is present to assist the pathologist in categorizing such lesions., Objective: To highlight diagnostic pitfalls that accompanying neoplasms composed primarily of 'cytoplasmically-poor' cells. These pitfalls include morphologic and immunohistochemical traps that emerge from this class of neoplasms., Data Sources: Selection of pathologic specimens from the author's personal files, and literature review., Conclusions: Interpretative pitfalls regarding the histopathology and immunophenotype of small 'cytoplasmically-poor' neoplasms are a diagnostic hazard in head and neck surgical pathology practice, and require knowledge of histomorphologic plasticity and aberrant immunophenotyping., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Pseudomyogenic hemangioendothelioma (PHE) is an uncommon mesenchymal tumor of intermediate malignant potential with characteristic clinicopathologic and genetic features. Although bone involvement accompanies nearly one-fourth of reported cases of soft tissue PHEs, primary intraosseous PHE is rare. Herein, we report five cases of primary intraosseous PHEs. Male to female ratio was 4:1, with an average age of 28 years (age range, 5-44 years). Radiologically, tumors presented as lytic lesions in the proximal femur (two), diaphysis of the tibia (one), distal radius (one) and vertebrae (one). Multifocal lesions were observed in four cases. Histopathologic examination revealed plump spindle cells and prominent nucleoli. New bone formation was noted in three cases. Immunohistochemically, all tumors were positive for CD31 and negative for CD34. Pan Cytokeratin (CK) (AE1/3) was positively expressed in all, except a single tumor, in which CK7 and Cam5.2 were expressed. INI1/SMARCB1 was completely retained in all tumors. A single patient underwent surgical resection. During follow-up, two cases showed no evidence of disease within two and five years, respectively. Differential diagnosis of a PHE of bone includes osteoblastoma, epithelioid angiosarcoma, metastatic carcinoma, metastatic rhabdomyosarcoma, and epithelioid sarcoma. Caution must be exercised as pan CK (AE1/3) might not be expressed; therefore, the use of other cytokeratins, such as Cam5.2 is recommended. Awareness of such an entity in bone is the key to the diagnosis., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Ancillary testing is absolutely integral to the correct recognition and classification of lymphoid neoplasms as procured with the fine-needle aspiration (FNA) biopsy technique. In patients with a newly diagnosed lymphoid neoplasm, immunophenotyping with flow cytometry, immunohistochemistry, or both is a standard that is currently expected by oncologists before any form of therapy is initiated. This is often the case also for patients with recurrent/relapsed disease. The cellular material obtained with FNA is perfectly suited to meet this demand. That said, the exceptional complexity of modern-day lymphoma classification often precludes definitive subclassification in a subset of lymphomas for a variety of reasons with the FNA biopsy technique, even with the application of ancillary tests. These include a requirement for definitive knowledge of the nodal architecture (eg, Hodgkin lymphoma), of the histologic grade via the counting of cells per microscopic field (follicular lymphoma), and of molecular findings (often unobtainable because of limitations of cellularity). The application of molecular tests to lymph node aspirates continues to evolve but is still largely confined to specialized medical centers. The intent of this article is to briefly review the diagnostic approach and algorithm for handling lymph node aspirates at the authors' own laboratory. This article highlights what the authors and others consider to be essential ancillary tests and discusses their respective advantages and shortcomings. It lists limited and extended antibody panels and molecular tests that the authors have found helpful not only for correctly recognizing lymphoma with FNA cytopathology but also for subtyping lymphomas whenever possible., (© 2018 American Cancer Society.)

Introduction: Gout may manifest with crystal-induced arthropathy and/or soft tissue tophi. Demonstration of monosodium urate (MSU) crystals is necessary to establish the diagnosis. Despite the fact that alcohol is an ideal fixative to preserve MSU crystals, very few fine-needle aspiration (FNA) cases of gout have been published., Materials and Methods: A retrospective review was performed for FNA cases diagnosed as tophaceous gout. Samples included unstained smears or smears stained with Diff-Quik or Papanicolaou stain, and formalin-fixed paraffin-embedded cell block stained with hematoxylin and eosin (H&E)., Results: We identified 22 FNA cases involving 18 men and 4 women. Only 7 patients had a clinical history of gout and 5 were taking gout medication. At least 4 patients presented with a clinical diagnosis of rule out sarcoma. All had soft tissue masses from either upper (n = 5) or lower (n = 17) extremities. Extracellular polarizing needle-shaped crystals with negative birefringence were present and visible on unstained, Diff-Quik, or Papanicolaou-stained conventional smears as well as in H&E-stained cell blocks in all cases., Conclusions: Our study demonstrates that MSU crystals are readily detectable under polarization on direct smears with or without staining. FNA cytology can serve as an alternative to core needle biopsy or synovial biopsy in not only confirming a diagnosis of tophaceous gout, but also in eliminating a diagnosis of soft tissue sarcoma in those patients where clinical and/or radiologic features were concerning for malignancy., (Copyright © 2018 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

In this article, we report a case of transformation of a benign giant cell tumor (GCT) of the calcaneus into an epithelioid angiosarcoma. The patient presented to our service in 2003 and was followed until 2014. Transformation occurred 11 years after curettage, cryotherapy, cementation, and a well-documented disease-free interval. Longitudinal radiographs, magnetic resonance imaging, and histopathology were evaluated by the same medical team. There are only a few case reports and case series of malignancy associated with GCT of bone. To our knowledge, this case report is the first to describe an assessment of the transformation of a benign GCT of bone into an epithelioid angiosarcoma. Orthopedic surgeons, radiologists, oncologists, and pathologists should be aware of the potential for transformation of benign GCTs to high-grade sarcomas after a long disease-free interval., Competing Interests: Authors’ Disclosure Statement: The authors report no actual or potential conflict of interest in relation to this article.

Introduction: Herpes simplex virus (HSV) infection can be diagnosed in pulmonary cytology specimens. We sought to determine the clinical significance of this finding., Methods: Our medical records were searched for cases of HSV infection diagnosed in cytology specimens and the results compared with those in the literature., Results: In our sample, 9 patients had HSV inclusions. All patients had pulmonary disease, 8 of 9 had multi-organ system disease, and 8 of 9 had been treated with either steroids or chemotherapy. Patients were either not treated with antiviral therapy (6 of 9) or treated for oral with or without cutaneous disease only (3 of 9). Two patients died; pulmonary infection was confirmed in only 1 patient. Compared with prior series, the number of cases with 10 or fewer cells with inclusions was significantly higher (89% versus 17%, P < 0.001)., Conclusions: Compared with prior series, most patients with HSV inclusions in pulmonary cytology specimens have fewer cells with inclusions, have oral and or cutaneous disease as well, and are not treated for pulmonary HSV. Nevertheless, this finding is associated with a risk of death, from both pulmonary infection and/or comorbid disease., (Copyright © 2017 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Introduction: Controversy remains as to whether image-guided fine-needle aspiration (FNA) biopsy coupled with appropriate ancillary techniques has clinical utility in the diagnosis of deep-seated lymphomas., Materials and Methods: A retrospective search (20 years) was performed to identify FNA cases with a definitive or indeterminate lymphoma diagnosis for deep-seated locations. The FNA diagnosis was compared with corresponding surgical pathology (SP) and clinical follow-up. The application of ancillary tests was also evaluated., Results: A total of 121 cases from 118 patients were recovered. Among 95 of 121 (79%) aspirates that had a definitive lymphoma diagnosis, 50 lacked SP follow-up. Most (82%) represented possible recurrent lymphoma, and thus therapy proceeded based on the FNA results alone. Additionally, 44 of 95 (46%) had an FNA diagnosis concordant with corresponding SP and 1 case was discordant. Of 44 with concordant SP diagnosis, 25 had further lymphoma subtyping that was concordant with SP. There were 26 of 121 (21%) with indeterminate diagnosis on FNAs. Of these, SP confirmed a diagnosis of lymphoma in 81%. Indeterminate cytologic diagnoses were due either to absent/inconclusive flow cytometry (FC) (11 of 21) or Hodgkin lymphoma (10 of 21). Of 121 cases, 93 utilized FC, 53 utilized cell-block immunohistochemical stains, and 29 utilized molecular testing as part of FNA work-up., Conclusions: FNA plays an important role in the diagnosis/clinical management of deep-seated non-Hodgkin B cell lymphoma (NHL), particularly for recurrence. The addition of ancillary techniques, particularly FC, markedly increases NHL diagnostic accuracy and subclassification. Our study is one of the few large series examining the clinical utility of FNA in the setting of deep-seated lymphomas., (Copyright © 2017 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Papillary Thyroid Carcinoma (PTC) displays one of the highest familiality scores of all cancers as measured by case-control studies, yet only a handful of genes have been implicated until now. Variants in microRNAs have been associated with the risk of several cancers including PTC but the magnitude of this involvement is unclear. This study was designed to test to what extent genomic variants in microRNAs contribute to PTC risk. We used SOLiD technology to sequence 321 genomic regions encoding 427 miRNAs in one affected individual from each of 80 PTC families. After excluding variants with frequency ≥ 1% in 1000 Genomes Phase 1 (n = 1092) we detected 1978 variants. After further functional filtering steps 25 variants in pre-miRs remained. Co-segregation was observed for six out of 16 tested miRNA variants with PTC in the families, namely let-7e, miR-181b, miR-135a, miR-15b, miR-320, and miR-484. Expression of miR-135a and miR-181b was tested in normal thyroid and tumor tissue from patients that carry the variants and a decrease in expression was observed. In vitro assays were applied to measure the effect of the variants on microRNAs' maturation. Four out of six variants were tested. Only the let-7e and miR-181b variants showed an effect on processing leading to lower levels of mature miRNA. These two variants were not detected in 1170 sporadic PTC cases nor in 1404 controls. Taken together, our data show that high penetrance germline sequence variants of miRNAs potentially predispose to a fraction of all PTC but are not common.

Introduction: Controversy remains as to whether Ki-67 labeling on endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) cell blocks (CBs) can be used to grade pancreatic neuroendocrine neoplasms (PanNENs) reliably and what would be the best methodology for doing so., Materials and Methods: A retrospective search identified cases with both EUS-FNA and correlating surgical pathology (SP) available. 58 CBs (>100 tumor cells) were identified. Ki-67 labeling on CB was counted using both manual count (MC) and digital image analysis (DIA, ImmunoRatio software). The grades determined on CB were compared with those on corresponding SP reports (kappa statistics). The correct grading rates between MC and DIA were compared (McNemar's test). Total tumor cell number (TTCN, cutoffs: 500 and 2000) was used as a stratification factor (chi-square tests for trend)., Results: Of 58 cases, the SP grade distribution was 31 grade 1, 23 grade 2, and 4 grade 3. Overall, the grading concordance of CB MC and SP was higher than that of CB DIA and SP (McNemar's P-value = 0.022). Compared with SP, CB MC correctly graded 69% (40 of 58) [κ = 0.44 (95% CI: 0.21, 0.66)]; CB DIA correctly graded 55% (32 of 58) [κ = 0.19 (95% CI: 0.04, 0.42)]. Grade 1 tumors had the highest concordance. Although the correct grading rate improved as TTCN increased, no statistical significance was found., Conclusion: Although Ki-67 labeling on CB can be used to grade PanNENs, limitation exists, particularly for grade 2 tumors. The method of counting makes a difference: MC is more accurate than DIA. The major reasons of discordance include non-tumor cell contamination and insufficient sampling., (Copyright © 2016 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Introduction: Primary thyroid lymphoma is a rare neoplasm accounting for 1% to 5% of thyroid malignancies. We study the efficacy of fine-needle aspiration (FNA) in diagnosing thyroid lymphoma., Methods: Pathology databases from our three institutions were searched for thyroid FNA biopsies having a diagnosis of lymphoma or atypical lymphoproliferative cells, or a corresponding tissue diagnosis of thyroid lymphoma having a prior FNA biopsy., Results: Sixty-eight cases were retrieved from 64 patients; 67 cases with histologic confirmation. Forty-six specimens were from women (68%), ages 21 to 87 years (mean = 60). Forty-seven aspirates were diagnosed as lymphoma (n = 29) or suspicious (n = 18) for lymphoma (sensitivity = 73%), 11 atypical, 7 benign, 2 unsatisfactory, and 1 suspicious for carcinoma. Follow-up surgical diagnoses included diffuse large B-cell lymphoma (n = 43), classical Hodgkin lymphoma (5), chronic lymphocytic leukemia (5), and other cases (11). Only 12 of 64 patients (13 specimens) had a known diagnosis of lymphoma prior to FNA. Light chain restriction was detected in 34 specimens (by flow cytometry [FCM] in 32 cases or polymerase chain reaction, in 2 cases). FCM was polyclonal (n = 7) or inconclusive (2) with 25 cases not having FCM performed or not having enough viable cells for evaluation. Four cases showed lymphocytic thyroiditis on surgical follow-up with 2 of these cases having a small monoclonal lymphoid population detected by FCM., Conclusions: Diffuse large B-cell lymphoma was the most common lymphoma in this series (63%). The sensitivity of FNA with the optional use of FCM was 71% with a specificity of 99%., (Copyright © 2016 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Introduction: Application of fine-needle aspiration (FNA) biopsy to soft tissue tumors remains underutilized in North America. Myxoid liposarcoma (LPS), the second most common subtype of LPS, is characterized primarily by t(12;16)(q13;p11) which is amenable to FISH analysis using a break-apart probe for DDIT3. Little is known regarding FISH testing for DDIT3 on cytologic specimens. We report our FNA experience with myxoid LPS and application of this molecular probe., Materials and Methods: Specimens retrieved from our cytology database used search codes for myxoid LPS. Tissue files were searched for any cases with corresponding FNA biopsies. FNA biopsy was performed using a standard technique., Results: From 24 FNA cases of myxoid LPS (mean age = 52 years), a specific diagnosis was made in 87.5%. Two cases were diagnosed as spindle/round cell neoplasm, and 1 as suspicious for myxoid LPS. There were 2 false positive diagnoses and no false negatives. Nearly all cases arose in the extremities; thigh being most common. Principal cytologic features consisted of discrete myxocellular microfragments, a plexiform capillary pattern, and variable number of univacuolated lipoblasts. Uniformly banal ovoid nuclei were randomly scattered within myxocellular microfragments. FISH analysis for DDIT3 rearrangement from unstained smears and/or cell-block was positive in 13 cases, and unsuccessful in 3, with no false positive/false negative results., Conclusion: Myxoid LPS is diagnosable in a high percentage of cases using FNA biopsy alone. Confirmatory FISH analysis for DDIT3 is not only possible, but also valuable for correctly recognizing this neoplasm., (Copyright © 2016 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Background: The purpose of this study was to further define the impact of primary surgery in the management of oropharyngeal squamous cell carcinoma (SCC)., Methods: Two hundred ninety-six patients with oropharyngeal SCC treated with primary surgery were included. Multivariable analysis and recursive partitioning analysis (RPA) identified predictors of survival and gastrostomy tube presence., Results: Multivariable analysis identified that HPV negativity (p = .0002), presence of extranodal extension (p = .0025), and advanced T classification (p = .0081) were independent predictors of survival. For HPV-positive patients, surgical approach (p = .0111) and margin status (p = .0287) were significant predictors of survival. For HPV-negative patients, extranodal extension (p = .0021) and advanced T classification (p = .0342) were significant predictors of survival. Smoking status and advanced neck disease did not impact survival, and the addition of adjuvant chemotherapy did not confer survival benefit in HPV-positive or HPV-negative subgroups., Conclusion: Independent predictors of survival are unique in patients with oropharyngeal SCC treated with primary surgery. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1794-E1802, 2016., (© 2015 Wiley Periodicals, Inc.)

Background: Anaplastic thyroid carcinoma (ATC) is relatively rare. A correct pathologic diagnosis is mandatory to exclude less aggressive entities, and guide management. We describe our experience with the fine needle aspiration (FNA) cytomorphology of ATC and potential mimics., Materials and Methods: Cytology files were searched to recover all cases of ATC/suspicious for ATC. Surgical pathology files were searched for ATC cases having corresponding cytology. FNA was performed using standard technique., Results: Of 59 FNA cases, 34 were correctly diagnosed as ATC (or possible ATC); 22 were false negative, and 3 false positive. All but 2 patients were confirmed by tissue biopsy or clinical course. Of 56 true ATC cases [51 patients (mean age: 69 years) (F:M ratio: 1.24:1)], 40 were primary, 11 metastatic, 4 recurrent, and 1 indeterminate. Carcinoma not otherwise specified (6), malignant not otherwise specified (5), differentiated thyroid cancer (3), atypical (2), suspicious for neoplasm/malignancy (2), and unsatisfactory (4) constituted the false negative diagnoses. Smear cellularity and cell distribution were variable. Malignant cells were mostly epithelioid, but accompanied by pleomorphic, spindle, and multinucleated forms. Differentiated thyroid carcinoma was diagnosed in 5 cases. Background necrosis and/or inflammation were common (80%). Three false positive cases included 1 example each of melanoma, Hürthle cell carcinoma, and metastatic squamous carcinoma. Where follow-up was possible, 91% of patients were dead of disease., Conclusion: A FNA diagnosis of ATC/probable ATC was made in 34 out of 56 cases (sensitivity: 61%). Problematic cases were associated with incomplete sampling, lack of cell block immunostaining, uncertainty of anatomic site, and overlapping morphologic features with non-ATC malignancies., (Copyright © 2016 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Evaluation of deep-seated lymphomas by fine-needle aspiration (FNA) can be challenging due to their reduced accessibility. Controversy remains as to whether FNA and ancillary techniques can be used to diagnose deep-seated lymphomas reliably and sufficiently for clinical management. Most published studies are favorable that endobronchial ultrasound (EBUS)/endoscopic ultrasound (EUS)-FNA plays an important role in the diagnosis of deep-seated lymphomas. The addition of ancillary techniques, particularly flow cytometry, increases diagnostic yield. While subclassification is possible in a reasonable proportion of cases, the reported rates of successful subclassification are lower than those for lymphoma detection/diagnosis. The diagnostic limitation exists for Hodgkin's lymphoma, grading of follicular lymphoma, and some T-cell lymphomas. The role of FNA in deep-seated lymphomas is much better established for recurrent than primary disease. It remains unclear whether the use of large-sized-needle FNA or a combination of core needle biopsy and FNA improves subclassification. It is important for cytopathologists to have considerable understanding of the WHO lymphoma classification and develop a collaborative working relationship with hematopathologists and oncologists. As EUS/EBUS-FNA techniques advance and sophisticated molecular techniques such as next- generation sequencing become possible, the role of FNA in the diagnosis of deep-seated lymphomas will possibly increase., (© 2016 S. Karger AG, Basel.)

Objectives: Epithelioid hemangioendothelioma (EHE) and epithelioid angiosarcoma (EAS) are rare vascular neoplasms that share many morphological characteristics on histology but demonstrate different clinical behavior. Given the many reported clinical and morphological features shared between EAS and EHE, we examined all cases of EAS and EHE diagnosed primarily on fine needle aspiration (FNA) at our three institutions that were confirmed by a tissue diagnosis., Study Design: A total of 29 cases from 25 patients were identified: 15 EHE from 11 patients and 14 EAS from 14 patients., Results: Many cytomorphological features existed on a spectrum that overlapped considerably between EAS and EHE cases. Common features between the two entities include epithelioid morphology and eccentrically placed nucleus. Intracytoplasmic lumens (ICL), a morphological feature that may suggest vascular origin, can be found in both entities but are not always present., Conclusions: Given the general absence of vascular cytomorphological features, such as ICL, the proper classification of these tumors depends on the successful use of immunoperoxidase markers such as factor VIII-related antigen, ERG, or CD31 as well as a high index of suspicion. The distinction between EAS and EHE on FNA alone is treacherous at best., (© 2014 S. Karger AG, Basel.)

We report the case of a 56-year-old woman who had severe leg pain and whose radiographs initially suggested metastatic carcinoma, lymphoma, osteogenic sarcoma, or adamantinoma. Results of multiple biopsies confirmed a diagnosis of Rosai-Dorfman disease, which typically presents in children and young adults (mean age at onset, 20 years).

Oncocytomas arising in the nasal cavity are quite rare. These entities more commonly occur in the major salivary glands, minor salivary glands, respiratory seromucinous glands, and endocrine organs. Very few cases of oncocytoma in the nasal cavity have been reported, with only 5 diagnosed as malignant. This article describes a case involving an 81-year-old man with a nasal oncocytoma that was completely resected with an endoscopic medial maxillectomy. The diagnostic rationale is discussed, along with a review of the literature.

Background: Metastatic cancer infrequently involves the pancreas. When the pancreas hosts a metastatic tumor, cytopathological evaluation of fine-needle aspirate material is a crucial part of the diagnostic process. In this study, we show two institutions' experience with cytopathological diagnosis of pancreatic metastasis., Methods: Databases of institutional experience at The Johns Hopkins Hospital and Ohio State University Medical Center were queried for cases of metastatic tumors in the pancreas that underwent fine-needle aspiration. Demographic and pathological features were compiled and the cytomorphology was reviewed., Results: Forty-two cases of tumor metastasis to the pancreas were found. Over the time of this review, 5,495 aspirates were performed, and 43% (2,389/5,495) had malignant cytological findings. Thus, the 42 cases of metastatic disease to the pancreas comprised 0.8% of all pancreas aspirates and 1.8% of the malignant ones. Renal cell carcinoma was the most common metastasis, followed by melanoma and non-small cell lung carcinoma. Among the other tumors in this series, 2 cases each of rare metastases such as the fibrolamellar variant of hepatocellular carcinoma and solitary fibrous tumor were also seen., Conclusion: The pancreas is rarely involved with metastatic disease, but when it is involved the most common tumor is renal cell carcinoma followed by melanoma and non-small cell lung cancer. Clinical history and awareness of the primary pancreatic mimickers are necessary for arriving at the correct diagnosis. As conventional pancreatic adenocarcinoma is uncommon in children and young adults, history of other tumors - even ones that usually follow an indolent course - is essential.

Background: Acral myxoinflammatory fibroblastic sarcoma (AMFS) is a rare low-grade sarcoma with somewhat unique morphologic characteristics. While recurrences are relatively common, distant metastases are infrequent. Cytopathologic descriptions of AMFS are limited, prompting the current study., Methods: A retrospective review was performed at two tertiary-care hospitals, and 3 patients with this diagnosis were identified. The cytopathologic and clinical features were reviewed. The following clinical data was collected for each case: age, gender, site of lesion, treatment, and follow-up information., Results: Pertinent cytologic features included large atypical epithelioid cells with occasional macronucleoli and lipoblast-like features in a background of bland spindle cells, myxoid stroma, and inflammation. All patients presented with acral mass lesions. Metastatic disease to an inguinal lymph node was found in 1 patient., Conclusions: AMFS is a low-grade sarcoma which shows some characteristic cytologic features. However, due to the presence of occasional bizarre and pleomorphic giant cells, there can be overlap with higher-grade sarcomas, and correlation with histology, immunohistochemistry, and imaging are required to make this diagnosis., (Copyright © 2013 S. Karger AG, Basel.)

Small cell osteosarcoma may present a challenging primary diagnosis on cytologic assessment owing to its rarity and its morphologic similarity to other small round blue cell tumors. Five cases of small cell osteosarcoma from our cytopathology archives were identified and reviewed and cytologic features elaborated. Three cases were fine-needle aspirations from bony lesions in the classic location for osteosarcoma (2 distal femur and 1 proximal tibia), and 2 aspirations were from metastases. Common cytomorphologic features included relatively small to intermediate cell size, high nuclear/cytoplasmic ratios, round nuclei, minimal anisonucleosis, finely granular nuclear chromatin, fine cytoplasmic vacuoles, and only rare osteoid. Small cell osteosarcoma shares many of the well-described cytomorphologic features of classic osteosarcoma, but the relatively small cells, round hyperchromatic nuclei, and scant osteoid constitute the common denominator. Correlation with radiographic findings and ancillary tests can aid in definitive diagnosis.

Background: The importance of interinstitutional consultation (IC) has been documented across a variety of surgical pathology organ systems. However, to the authors' knowledge, few studies exist regarding this practice within cytopathology and specifically within fine-needle aspiration cytology (FNAC)., Methods: All FNAC cases between September 2002 and January 2007 were reviewed. Original diagnoses and second opinion diagnoses (SODs) were categorized as either no diagnostic disagreement, or minor diagnostic disagreement, or major diagnostic disagreement, and the latter was defined as either a 2-step deviation on a scale of "unsatisfactory, benign, atypical, suspicious, and malignant" or a change in treatment and/or prognosis. Outcome was determined by a review of the electronic medical record., Results: Among 742 FNAC cases from outside laboratories, there were minor disagreements in 132 cases (17.8%) and major disagreements in 69 cases (9.3%) compared with the SODs from the authors' laboratory. Follow-up was available for 60 of 69 major discrepancies. The SOD was supported on follow-up in 65% of major discrepancies, and the initial diagnosis was supported better in 33% of major discrepancies. In 55% of cases in which the original institution diagnosis was supported better, either no case slides were received for examination or the slides contained material that was considered nondiagnostic by the authors. An SOD prompted a change in clinical management in 32 of 742 patients (4.3%). Aspirates that were most prone to change in management or therapy were from the thyroid (13 cases), neck (soft tissue and lymph nodes; 9 cases), salivary gland (2 cases), and liver (2 cases). Of 60 major diagnostic disagreements, board-certified cytopathologists rendered an SOD in 44 cases, and 75% of the diagnoses were supported better by follow-up, whereas pathologists who were not board certified in cytopathology had only 38% of SODs supported., Conclusions: Of 742 FNAC cases, 9.3% had major diagnostic disagreements; and, in 4.3%, patient management and therapy were altered. These results were similar to studies in surgical pathology emphasizing the importance of IC in FNAC. The authors concluded that FNAC IC benefits patient care., (Copyright 2009 American Cancer Society)

Nineteen cases of a distinctive variant of paraganglioma characterized by extensive collagen deposition resulting in a pattern of growth that resembled an invasive malignant neoplasm are described. The patients were 3 men and 16 women, 32 to 69 years of age (mean, 50.5 years). The tumors were located in the carotid body region, parapharyngeal region, and mediastinum. Tumor size ranged from 2 to 6 cm in greatest diameter. Grossly, the tumors were described as rubbery to firm, tan-red, and with extensive areas of sclerosis. Histologic examination showed nests and cords of tumor cells separated by broad bands of fibrous tissue. The tumor cells ranged from round to polygonal with abundant cytoplasm to elongated spindle cells with scant cytoplasm. Nuclear cytomegaly was present focally enhancing the atypical appearance of the tumor cell population in 17 cases. Mitoses were sparse (<1 x 10 HPF), and there was no evidence of necrosis in any of the cases. Foci of vascular and perineural invasion were present in 2 and 4 cases, respectively. The most striking morphologic feature was the presence of irregular cords and bands of hyalinized fibrous tissue that compartmentalized the lesion into irregular nests, islands, or cords of tumor cells, imparting them with an infiltrative appearance. All the tumors showed positive immunostaining for chromogranin, synaptophysin, and monoclonal neuron specific enolase. S-100 protein stains identified a sustentacular cell network, whereas cytokeratin AE1/AE3 was negative in all cases. Clinical follow-up in 14 cases, ranging from 2 months to 20 years (mean follow-up, 6.6 years) showed evidence of local recurrence in 2 cases and the development of a separate tumor in the contralateral neck in 1 case. The remainder of patients were free of recurrence or metastasis following simple local excision. Because of the prominent sclerosis, a diagnosis of an invasive malignant neoplasm was initially considered in the majority of cases. Sclerosing paraganglioma should be included in the differential diagnosis of sclerosing lesions of the head and neck region and mediastinum. Appropriate immunohistochemical stains may be of aid for establishing the correct diagnosis.