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Aims: NUTM1‐rearranged sarcoma is an emerging entity that differs from NUT carcinoma at the molecular level, with most of the former tumours harbouring fusions involving genes in the MYC‐associated factor X dimerization (MAD) transcription family (MXD1, MXD4, MXI1 [or MXD2], and MGA). MGA::NUTM1 is one of the most recently described novel gene fusions associated with NUTM1‐rearranged sarcoma. Herein we describe the clinicopathologic features of three sarcomas with an MGA::NUTM1 fusion. Methods and results: The three study patients were male, with an age range of 10–28 years. The tumour sites were deep soft tissue of the thigh, the chest wall, and the pelvis. All three tumours were aggressive, with multiple recurrences and metastases. Histologically, the tumours were composed of monotonous spindle, round, or epithelioid cells in variably hyalinized stroma and prominent aggregates of amianthoid fibre‐like collagen or collagen rosettes. Mitotic activity was relatively low (5–12 mitotic figures per 10 hhpf). All tumours tested expressed NUT, with one tumour having S100 protein expression and two tumours having CD99 and CD56 expression. The genetic breakpoints were MGA exon 21, MGA exon 22, and NUTM1 exon 3. Conclusion: MGA::NUTM1 sarcoma often exhibits hyalinized stroma with amianthoid fibre‐like collagen or collagen rosettes in the presence of monotonous round, epithelioid, or spindle cell morphology. NUT immunohistochemistry and molecular testing can help confirm the diagnosis. [ABSTRACT FROM AUTHOR]

Introduction: Benign sebaceous salivary gland (SG) neoplasms represent approximately 0.2% of all salivary gland neoplasms. Not only are fine needle aspiration (FNA) biopsy findings of sebaceous adenoma (SA) and sebaceous lymphadenoma (SLA) limited, but their findings are also rarely compared with one another. Materials and Methods: Our cytopathology files were searched for examples of benign sebaceous SG neoplasms with concomitant histopathological verification. FNA biopsy and cell collection were performed using standard technique. Results: One case each of parotid SA and parotid SLA showed markedly dissimilar cytomorphology. The SA case was composed of a repetitive population of profusely multivacuolated polygonal cells with single and multiple nuclei, and was specifically recognised cytologically as a sebaceous neoplasm due to its characteristic cytoplasmic vacuolisation. The SLA case, however, was characterised by smears filled primarily with lymphocytes and only scant widely scattered basaloid cell clusters. A non‐specific diagnosis of basaloid neoplasm was rendered. In retrospect, recognition of sebaceous differentiation was limited to rare cell groups. Conclusion: Though nominally, epidemiologically, and to a degree histopathologically analogous, the cytopathology of SA and SLA are markedly dissimilar, reflecting the dominant cell component in each. With FNA biopsy, a specific interpretation is more likely for SA than SLA due to the overwhelming obscuring lymphoid population in the latter. [ABSTRACT FROM AUTHOR]

Introduction: Pleomorphic dermal sarcoma (PDS) is an uncommon cutaneous mesenchymal neoplasm. It is cytomorphologically identical to atypical fibroxanthoma (AFX), but differs due to its invasion beyond the dermis. We undertook an examination of our experience with fine needle aspiration (FNA) biopsy cytology of PDS. Materials and Methods: Our cytopathology files were searched for examples of PDS with concomitant histopathological verification. FNA biopsy smears and cell collection were performed using standard techniques. Results: Seven cases of PDS were retrieved from four different patients (M:F, 1:1; age range: 63–88 years; mean age = 78 years). All patients (57%) presented with a primary tumour with one having an FNA biopsy of two local recurrences and a single distant metastasis. Five aspirates were from the extremities and two from the head/neck. Tumours ranged from 1.0 to 3.5 cm (mean, 2.2 cm). Specific cytological diagnoses were pleomorphic spindle/epithelioid sarcoma (3 cases), PDS (2), AFX (1), and atypical myofibroblastic lesion, query nodular fasciitis (1). Immunohistochemical (IHC) staining from FNA‐generated cell blocks in two cases showed non‐specific staining with vimentin in both cases; positive CD10, CD68, and INI‐1 staining in one case; and smooth muscle actin expression in the other. Multiple negative stains were performed in both of these cases to exclude malignant melanoma, carcinoma, and specific forms of sarcoma. Cytopathology consisted of a mixture of spindle, epithelioid, and bizarre pleomorphic cells. Conclusion: Coupled with ancillary IHC stains, FNA biopsy can help recognise PDS as a sarcomatous cutaneous neoplasm, but is unable to distinguish PDS from AFX. [ABSTRACT FROM AUTHOR]

Introduction: Atypical spindle cell/pleomorphic lipomatous tumour (ASPLT) is an infrequently appreciated benign lipomatous neoplasm newly accepted into the most recent WHO classification of soft tissue tumours. Materials and Methods: Our cytopathology files were searched for examples of ASPLT and spindle cell/pleomorphic lipoma (SCPL) having histopathological verification. Conventional fine needle aspiration (FNA) biopsy smears were performed using standard techniques. Results: Eleven patients including three cases of ASPLT and eight of SCPL (M:F = 4.5:1; age range: 39‐97 years, mean age = 60 years) met the inclusion criteria. FNA biopsy sites included extremity (5, 45%), trunk (3, 27%), and head/neck (3, 27%). All aspirates were from primary neoplasms. FNA diagnoses of ASPLT cases were spindle cell lipomatous neoplasm, fibrotic low‐grade SC neoplasm, and myxoid lipomatous neoplasm. Eight SCPL cases were diagnosed as spindle cell neoplasm (3), spindle cell lipoma (SCL) (1), pleomorphic lipoma (1), suspicious for SCL (1), benign adipose tissue (1), and benign spindle cells and connective tissue (1). Ancillary testing in two ASPLT cases showed positive CD34 and negative MDM2 immunostain in one, and negative FISH results for MDM2 and DDIT3 in another. Conclusion: ASPLT is a novel lipomatous neoplasm simulating primarily SCPL and atypical lipoma/well‐differentiated liposarcoma. Diligent cytomorphological observation, clinical information, and ancillary testing may allow for its specific recognition using FNA biopsy. [ABSTRACT FROM AUTHOR]

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. When combined with ancillary immunohistochemical staining, FNA cytopathology is capable of accurately diagnosing most benign peripheral nerve neoplasms. Isolated cellular pleomorphism is not uncommon in this tumor category, and should not be mistaken for malignancy. [ABSTRACT FROM AUTHOR]

Objective: Haemoglobin spherulosis (HS) is a rare lesion occurring post‐vitreous haemorrhage that is absent from the cytopathology literature. Methods: We present the fine needle aspiration (FNA) biopsy cytological features of a case of HS occurring in a 73‐year‐old woman. Results: FNA smears of hemorrhagic vitreous fluid showed numerous variably sized smooth glassy spherules ranging from 3‐20 μm. Occasional red cells and a rare lymphocyte were observed, but other cell types were absent. Immunohistochemical staining of a cell block showed diffuse positive staining of spherules with haemoglobin A. Conclusions: HS is a rare lesion that occurs post‐subretinal haemorrhage and may be encountered by pathologists examining ocular cytological specimens. [ABSTRACT FROM AUTHOR]

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.; [ABSTRACT FROM AUTHOR]

Background: Sarcomas constitute a heterogeneous group of tumors with different clinical behaviors and variable responses to systemic therapies. Recent immunotherapy studies with PD1 inhibitors (PD1i) show promising results with use in certain soft-tissue sarcomas; however, the clinical and molecular features that best predict response to PD1i remain unclear.Methods: Demographic, imaging, histologic, and genetic sequencing data was collected for sarcoma patients who received nivolumab or pembrolizumab (PD1i) treatment at our institution between January 1st 2015 and April 23rd 2018. The primary objective was to determine progression-free survival (PFS) in patients with advanced sarcomas receiving PD1i. Secondary objectives included determining overall survival (OS) and assessment of characteristics associated with response to PD1i. Fifty-six patients who were treated with PD1i therapy met inclusion criteria for this study.Results: Partial response towards PD1i treatment was seen in 3 in 26 evaluable patients, but no complete responses were observed (overall response rate 11.5%). Within this group of patients, the 90 day PFS was found to be 48.8%. In patients in whom PD1 expression was known, there was a statistically significant positive correlation between expression of PD1 and longer PFS and OS rates. Patients that were treated with more than four cycles of PD1i therapy were also more likely to have a greater OS.Conclusions: This study suggests activity of PD1i in a pretreated cohort of advanced sarcoma patients, particularly for the subset of patients with PD1 positive tumors. Our results highlight the importance of further research to better target the optimal patient population and markers of response. [ABSTRACT FROM AUTHOR]

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. A large cohort of patients with acinic cell carcinoma (ACC) demonstrates that cytologic grading into a low‐grade type (conventional) and a high‐grade type (carcinoma with high‐grade transformation) is clinically acceptable. However, diagnostic specificity for primary cases of ACC with fine‐needle aspiration biopsy but without ancillary cotesting remains problematic. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Familial adenomatous polyposis (FAP) is a condition typically caused by pathogenic germline mutations in the APC gene. In addition to colon polyps, individuals with FAP have a substantially increased risk of developing papillary thyroid cancer (PTC). Little is known about the events underlying this association, and the prevalence of somatic "second-hit" mutations in APC is controversial. Methods: Whole-genome sequencing was performed on paired thyroid tumor and normal DNA from 12 FAP patients who developed PTC. Somatic mutation profiles were compared with clinical characteristics and previously sequenced sporadic PTC cases. Germline variant profiling was performed to assess the prevalence of variants in genes previously shown to have a role in PTC predisposition. Results: All 12 patients harbored germline mutations in APC, consistent with FAP. Seven patients also had somatic mutations in APC, and seven patients harbored somatic mutations in KMT2D, which encodes a lysine methyl transferase. Mutation of these genes is extremely rare in sporadic PTCs. Notably, only two of the tumors harbored the somatic BRAF p.V600E mutation, which is the most common driver mutation found in sporadic PTCs. Six tumors displayed a cribriform–morular variant of PTC (PTC-CMV) histology, and all six had somatic mutations in APC. Additionally, nine FAP-PTC patients had rare germline variants in genes that were previously associated with thyroid carcinoma. Conclusions: Our data indicate that FAP-associated PTCs typically have distinct mutations compared with sporadic PTCs. Roughly half of the thyroid cancers that arise in FAP patients have somatic "second-hits" in APC, which is associated with PTC-CMV histology. Somatic BRAF p.V600E variants also occur in some FAP patients, a novel finding. We speculate that in carriers of heterozygous pathogenic mutations of tumor suppressor genes such as APC, a cooperating second-hit somatic variant may occur in a different gene such as KTM2D or BRAF, leading to differences in phenotypes. The role of germline variance in genes other than APC (9 of the 12 patients in this series) needs further research. [ABSTRACT FROM AUTHOR]

Background: Dedifferentiated liposarcomas (DDLPS) are mesenchymal tumors associated with universally poor response to treatment. Genomic amplification of murine double minute 2 (MDM2) is used as a diagnostic biomarker; however, no established biomarkers exist to guide DDLPS treatment. In the largest study of its kind, we report that the extent of MDM2 amplification, not simply the presence of MDM2 amplification, may be biologically important to the actions of DDLPS. Patients and Methods: The distribution of MDM2 amplification in DDLPS was assessed using data from a commercial sequencing laboratory (n = 642) and The Cancer Genome Atlas (n = 57). Data from two retrospective clinical trials (n = 15, n = 16) and one prospective clinical trial (n = 25) were used to test MDM2's utility as a clinical biomarker. in vitro and in vivo assessments were conducted in DDLPS cell lines. Results: Genomic MDM2 amplification follows a highly reproducible log‐normal distribution. In patients with DDLPS treated with complete tumor resection, elevated MDM2 was associated with shortened time to recurrence as measured by genomic amplification (p =.003) and mRNA expression (p =.04). In patients requiring systemic therapy, higher MDM2 amplification was associated with reduced overall survival (p =.04). Doxorubicin treatment of DDLPS cells in vitro demonstrated variable sensitivity based on baseline MDM2 levels, and doxorubicin treatment elevated MDM2 expression. In vivo, treatment with doxorubicin followed by an MDM2 inhibitor improved doxorubicin sensitivity. Conclusion: MDM2 amplification levels in DDLPS follow a reproducible distribution and are associated with clinical outcomes and drug sensitivity. These results suggest that a prospective study of MDM2 as a predictive biomarker in DDLPS is warranted. Implications for Practice: No validated biomarkers exist for treatment selection in dedifferentiated liposarcoma (DDLPS). Although murine double minute 2 (MDM2) is currently used for diagnosis, the clinical relevance of MDM2 amplification has yet to be fully assessed. This study found that MDM2 amplification follows a predictable distribution in DDLPS and correlates with clinical and biological outcomes. These data suggests that MDM2 amplification may be a useful biomarker in DDLPS. Patients with advanced dedifferentiated liposarcomas (DDLPS), a soft‐tissue sarcoma characterized by genomic amplification of CDK4 and MDM2, have universally poor outcomes following the limited therapies available. This article reports that the extent of MDM2 amplification, not simply the presence of MDM2 amplification, may be biologically important to the actions of DDLPS. [ABSTRACT FROM AUTHOR]

Background: Inactivation of DNA mismatch repair (MMR) and the resulting microsatellite instability (MSI) are frequently observed in endometrial, stomach, and colorectal cancers, as well as more rarely in other solid tumor types. The prevalence of MSI in thyroid cancer has not been explored in depth, although recent studies utilizing data from large cancer sequencing efforts such as The Cancer Genome Atlas indicate that MSI is absent or at least very rare in the most common and most well studied histologic subtype, papillary thyroid carcinoma. This study aimed to determine the prevalence of MSI in thyroid cancer by using a large series comprising all major histological subtypes. Methods: A total of 485 thyroid cancer patients were screened for MSI/MMR deficiency, including all major histologic subtypes (195 papillary thyroid carcinoma, 156 follicular thyroid carcinoma [FTC], 50 anaplastic thyroid carcinoma, 65 medullary thyroid carcinoma, and 17 poorly differentiated thyroid carcinomas) by using a combination of polymerase chain reaction–based detection, immunohistochemistry, and next-generation sequencing. Results: A total of four tumors were MSI-high and had loss of MMR protein expression, all of which were from FTC patients. Whole-exome sequencing was performed on two MSI-high FTCs and revealed a hemizygous loss of function mutation in MSH2 in one tumor. Conclusions: Based on these data, it is estimated that the overall prevalence of MSI in FTC is 2.5%, and MSI is either entirely absent or rare in other histology subtypes of thyroid carcinoma. These findings highlight the importance of testing for MSI in FTC. [ABSTRACT FROM AUTHOR]

Background: Human papillomavirus (HPV)–related squamous cell carcinoma (SqCC) of the oropharynx is an epidemiologically and clinically distinct form of SqCC that is associated with an improved prognosis. However, HPV‐related small cell carcinoma of the oropharynx is a rare and newly described variant that is associated with aggressive clinical behavior and poor outcomes. To date, fewer than 2 dozen reports of this entity exist in the literature, and there is no discussion of cytopathologic features. This article reports 6 cases and discusses the salient cytomorphologic findings, ancillary studies, and challenges when this entity is encountered. Methods: Anatomic pathology archives were searched to identify patients with a diagnosis of HPV‐related small cell carcinoma of the oropharynx. Medical records were reviewed to document the following: age, sex, smoking status, other relevant clinical history, primary location, treatment, and clinical outcome. Both p16 and high‐risk HPV in situ hybridization (ISH) studies were positive in at least 1 specimen from each patient. The pathologic diagnoses, cytomorphologic characteristics, immunocytochemical stains, and HPV ISH studies were reviewed and recorded for all available cases. Results: Six patients with 11 cytopathology specimens of HPV‐related small cell carcinoma of the oropharynx were identified. The mean age was 61.3 years, and all patients died with widely metastatic disease (mean, 23 months; range, 12‐48 months). Mixed small cell carcinoma and SqCC components were present in half of the cases. Conclusions: The identification of a small cell component can be reliably performed with cytology preparations and is crucial because this (and not the HPV status) determines the prognosis. Human papillomavirus–related small cell carcinoma of the oropharynx is a rare and newly described entity with an aggressive clinical course. This is one of the first studies of human papillomavirus–related small cell carcinoma of the oropharynx in cytology preparations. [ABSTRACT FROM AUTHOR]

Background: Human papillomavirus (HPV)–related squamous cell carcinoma (SqCC) of the oropharynx is an epidemiologically and clinically distinct form of SqCC that is associated with an improved prognosis. However, HPV‐related small cell carcinoma of the oropharynx is a rare and newly described variant that is associated with aggressive clinical behavior and poor outcomes. To date, fewer than 2 dozen reports of this entity exist in the literature, and there is no discussion of cytopathologic features. This article reports 6 cases and discusses the salient cytomorphologic findings, ancillary studies, and challenges when this entity is encountered. Methods: Anatomic pathology archives were searched to identify patients with a diagnosis of HPV‐related small cell carcinoma of the oropharynx. Medical records were reviewed to document the following: age, sex, smoking status, other relevant clinical history, primary location, treatment, and clinical outcome. Both p16 and high‐risk HPV in situ hybridization (ISH) studies were positive in at least 1 specimen from each patient. The pathologic diagnoses, cytomorphologic characteristics, immunocytochemical stains, and HPV ISH studies were reviewed and recorded for all available cases. Results: Six patients with 11 cytopathology specimens of HPV‐related small cell carcinoma of the oropharynx were identified. The mean age was 61.3 years, and all patients died with widely metastatic disease (mean, 23 months; range, 12‐48 months). Mixed small cell carcinoma and SqCC components were present in half of the cases. Conclusions: The identification of a small cell component can be reliably performed with cytology preparations and is crucial because this (and not the HPV status) determines the prognosis. Human papillomavirus–related small cell carcinoma of the oropharynx is a rare and newly described entity with an aggressive clinical course. This is one of the first studies of human papillomavirus–related small cell carcinoma of the oropharynx in cytology preparations. [ABSTRACT FROM AUTHOR]

Background: Nodular fasciitis (NF) is a clonal, self‐limited proliferation that has only rarely been described in the parotid gland. Because of its potential to mimic benign and malignant parotid neoplasms clinically, radiographically, and cytomorphologically, NF is often managed with unnecessary surgery, which is associated with a risk for significant surgical complications. The purpose of this study is to present the clinical and cytomorphologic findings for NF of the parotid gland by fine‐needle aspiration (FNA). Methods: The pathology archives of the authors' respective institutions were searched for salivary gland FNA cytology specimens with a confirmed diagnosis of NF. The clinical history, pathologic diagnosis, cytomorphologic findings, and immunocytochemical results were recorded. Results: A total of 15 cases were identified; the average age was 37 years, and 10 patients (66.7%) were female. Five cases (33.3%), all treated surgically, showed recurrence within an average timeframe of 1.6 months. Only 3 cases (20.0%) were classified as definitive, probable, or suggestive of NF. On average, smears were composed of predominantly single (69.2%), spindled cells (100.0%) with short unipolar (76.9%) and/or bipolar processes (38.5%), round (61.5%) or elongated (84.6%) nuclei, and inconspicuous nucleoli (53.8%). In 69.2%, a tissue‐culture appearance was shown, and 76.9% contained myxoid stroma. In 46.2%, a minimal amount of cytologic atypia was shown. Conclusions: Keeping NF in the differential for any bland, single, spindled cell proliferation with elongated cytoplasmic processes and bland nuclei may prompt the clinician to consider more conservative management in the correct clinical context. Nodular fasciitis is a clonal, self‐limited proliferation that has only rarely been described in the parotid gland. This study characterizes the clinical and cytomorphologic findings of nodular fasciitis of the parotid gland by fine‐needle aspiration to facilitate better preoperative recognition of this entity. [ABSTRACT FROM AUTHOR]

Sinonasal tract (SNT) alveolar rhabdomyosarcoma (ARMS) are frequently misdiagnosed, especially in adults. Fifty-two adult (≥18 years) patients with SNT ARMS were reviewed and characterized by immunohistochemistry and molecular studies. Twenty-six females and 26 males (18-72 years; mean 43.2 years), presented after a short duration (mean 2.6 months) with a large (mean 5.5 cm) destructive nasal cavity mass, involving multiple contiguous paranasal sites (n = 46) and with cervical adenopathy (n = 41). The tumors showed an alveolar, nested to solid growth pattern below an intact, but often involved (n = 9) epithelium with frequent necrosis (n = 37), destructive bone invasion (n = 30), and lymphovascular invasion (n = 25). The neoplastic cells were dyshesive and dilapidated, with crush artifacts. Rhabdoid features (n = 36) and tumor cell multinucleation (n = 28) were common. Mitotic counts were high (mean 17/10 HPFs). The neoplastic cells showed the following immunohistochemical positive findings: desmin (100%), myogenin (100%), MYOD1 (100%), MSA (96%), SMA (52%), CAM5.2 (50%), AE1/AE3 (36%); other positive markers included S100 protein (27%), CD56 (100%), synaptophysin (35%), and chromogranin (13%). Overall, 54% show epithelial marker reactivity. Molecular studies showed FOXO1 translocations (81%) with PCR demonstrating PAX3 in 72.7% tested. Patients presented with high stage (IV 24; III 26) and metastatic disease (lymph nodes n = 41; distant metastases n = 25) (IRSG grouping). Surgery (n = 16), radiation (n = 41) and chemotherapy (n = 45) yielded an overall survival of 36.1 months (mean; range 2.4-286); 18 alive without disease (mean 69.6 months); 7 alive with disease (mean 11.0 months); 1 dead without disease (63.7 months); and 26 dead with disease (mean 18.5 months). SNT ARMS frequently present in adults as a large, destructive midline mass of short symptom duration, with high stage disease. The alveolar to solid pattern of growth of cells with rhabdoid-plasmacytoid features suggests the diagnosis, but epithelial immunohistochemistry markers are present in 54% of cases, leading to misdiagnosis as carcinomas if muscle markers are not also performed. Overall survival of 36.1 months is achieved with multimodality therapy, but 64% have incurable disease (16.9 months). Mixed anatomic site (p = 0.02) was a significant adverse prognostic indicator, while stage (0.06) and tumor size >5 cm (0.06) approached marginal significance. [ABSTRACT FROM AUTHOR]

Background: The retinoblastoma (RB) transcriptional corepressor 1 protein functions to slow cell-cycle progression. Inactivation of RB by reduced expression and/or hyperphosphorylation allow for enhanced progression through the cell cycle. Murine models develop medullary thyroid carcinoma (MTC) after generalized loss of RB. However, RB expression in MTC has only been evaluated in a small number of tumors, with differing results. The objective of this study was to determine whether reduced expression of RB and/or overexpression of hyperphosphorylated RB predict MTC aggressive behavior. Methods: Formalin-fixed, paraffin-embedded primary thyroid tumors and lymph node metastases from MTC patients were evaluated for calcitonin, RB, and phosphorylated RB (pRB) expression by immunohistochemistry. Two expert pathologists evaluated the slides in a blinded manner, and the immunohistochemistry results were compared to disease-specific survival as a primary endpoint. Results: Seventy-four MTC samples from 56 patients were analyzed in this study, including 51 primary tumors and 23 lymph node metastases. The median follow-up time was 6.75 years after surgery (range 0.64-24.30 years), and the median primary tumor size was 30 mm (range 6-96 mm). Sixty-six percent of cases were classified as stage IV. RB nuclear expression was diffusely present in 88% of primary tumors and 78% of lymph node metastases. Nuclear pRB expression was present in 22% of primary tumors and 22% of lymph node metastases. On univariate analysis, reduced RB (<75% tumor cell staining) trended with lower MTC-specific survival for primary tumor and metastatic nodes (primary tumor hazard ratio = 3.54 [confidence interval 0.81-15.47], p = 0.08; and lymph node hazard ratio = 4.35 [confidence interval 0.87-21.83], p = 0.05). For primary tumors, multivariable analysis showed that low nuclear RB expression was independently associated with worse disease-specific ( p = 0.01) and overall ( p = 0.02) survival. pRB levels were not associated with survival for either primary tumor or lymph node metastases. Conclusions: Reduced RB expression is associated with decreased patient survival in univariate and multivariable analyses, independent from patient age at surgery or advanced TNM stage. Future studies involving larger MTC patient populations are warranted to determine if lower RB expression levels may serve as a biomarker for aggressive disease in patients with MTC. [ABSTRACT FROM AUTHOR]

Objectives: Granular cell tumors are rare neoplasms of neural origin. Despite the mesenchymal nature of these tumors, they rarely occur in the soft tissue, and as a result, this subset is not well characterized. We present the largest case series to date comprising 50 patients with benign and atypical soft tissue granular cell tumors in an effort to better define the pathologic features in this subset of lesions.Methods: All cases of soft tissue granular cell tumors from the Ohio State Medical Center and the Medical College of Wisconsin over a 10-year period were reviewed for histologic and clinical findings.Results: The most common location was the upper extremity. The mean age was 38.6 years, and the mean size of the tumor was 2.1 cm. An infiltrative growth pattern was seen in 58.8% of cases, and positive margins were found in 68.2%. Eleven (21.6%) cases showed evidence of cytologic atypia and fulfilled the criteria for a diagnosis of atypical giant cell tumor. Two of 11 patients with long-term follow-up experienced local recurrence.Conclusions: Compared with granular cell tumors overall, the soft tissue subset shows a larger average size and higher propensity for incomplete resections, with atypical features being relatively common. Our findings suggest that soft tissue granular cell tumors may be slightly more aggressive than their dermal or organ-confined counterparts. [ABSTRACT FROM AUTHOR]

BACKGROUND Nodular fasciitis (NF) is a benign, self-limited, fibroblastic/myofibroblastic proliferation that is diagnostically challenging, often mimicking a malignant process due to its rapid growth clinically and its high cellularity, mitotic activity, and variable/nonspecific cytomorphologic findings. Herein, the authors report what to their knowledge is the largest and first multi-institutional study of the cytomorphologic characteristics of NF by fine-needle aspiration (FNA). METHODS The pathology archives at The Johns Hopkins Hospital, The Ohio State University Wexner Medical Center, and Emory University Hospital were searched for soft tissue FNA cytology specimens of masses confirmed to be NF. The clinical history, actual FNA diagnosis, and cytomorphologic features were recorded by the authors. RESULTS A total of 34 patients were identified, 33 of which had material available for review. The mean age of the patients was 40 years (range, 1-80 years); 18 patients (52.9%) were male. The mean duration of symptoms was 3.75 months. Four cases (11.8%) and 2 cases (5.9%) were signed out as NF and 'malignant neoplasm, NOS [not otherwise specified],' respectively. On average, cases were hypercellular (mean, 3.27/4). Thirty cases (90.9%) contained spindled morphology, whereas 30 cases (90.9%) and 28 cases (84.4%) contained cells with unipolar and curved cytoplasmic tails, respectively. Eccentric, ovoid, and spindled/elongated nuclei were observed in 31 cases (93.9%), 30 cases (90.9%), and 29 cases (87.9%), respectively. Nineteen cases (57.6%) lacked atypia. CONCLUSIONS In the current study, the diagnosis of NF was suggested in nearly 40% of cases. Combining the clinical presentation with the most commonly described cytomorphologic features will appropriately triage the majority of cases, although uncertainty will remain in a significant number of cases. Cancer Cytopathol 2017;125:20-29. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Nodular fasciitis (NF) is a benign, self-limited, fibroblastic/myofibroblastic proliferation that is diagnostically challenging, often mimicking a malignant process due to its rapid growth clinically and its high cellularity, mitotic activity, and variable/nonspecific cytomorphologic findings. Herein, the authors report what to their knowledge is the largest and first multi-institutional study of the cytomorphologic characteristics of NF by fine-needle aspiration (FNA).Methods: The pathology archives at The Johns Hopkins Hospital, The Ohio State University Wexner Medical Center, and Emory University Hospital were searched for soft tissue FNA cytology specimens of masses confirmed to be NF. The clinical history, actual FNA diagnosis, and cytomorphologic features were recorded by the authors.Results: A total of 34 patients were identified, 33 of which had material available for review. The mean age of the patients was 40 years (range, 1-80 years); 18 patients (52.9%) were male. The mean duration of symptoms was 3.75 months. Four cases (11.8%) and 2 cases (5.9%) were signed out as NF and "malignant neoplasm, NOS [not otherwise specified]," respectively. On average, cases were hypercellular (mean, 3.27/4). Thirty cases (90.9%) contained spindled morphology, whereas 30 cases (90.9%) and 28 cases (84.4%) contained cells with unipolar and curved cytoplasmic tails, respectively. Eccentric, ovoid, and spindled/elongated nuclei were observed in 31 cases (93.9%), 30 cases (90.9%), and 29 cases (87.9%), respectively. Nineteen cases (57.6%) lacked atypia.Conclusions: In the current study, the diagnosis of NF was suggested in nearly 40% of cases. Combining the clinical presentation with the most commonly described cytomorphologic features will appropriately triage the majority of cases, although uncertainty will remain in a significant number of cases. Cancer Cytopathol 2017;125:20-29. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Papillary thyroid cancer (PTC) is reported to be highly heritable in epidemiological studies. Genome-wide association studies (GWAS) have uncovered several variants associated with PTC predisposition. It remains unknown whether these variants might contribute to better clinical stratification of PTC patients. Methods: In order to assess the usefulness of germline genetic analyses in the management of PTC patients, the genotypes of five variants (rs965513, rs944289, rs116909374, rs2439302, and rs966423) were determined in 1216 PTC patients and 1416 controls. Additionally, the expression of seven genes located close to GWAS variants ( PTCSC3, MBIP, NKX2-1, FOXE1, DIRC3, PTCSC2, and NRG1) were measured in 73 PTC paired tumor/normal tissues, respectively. Next, the association was analyzed between the genotypes of the germline variants and the levels of gene expression with clinical/pathological features such as age, sex, TNM staging, multifocality status, extrathyroidal expansion, and MACIS score. Results: The risk allele of rs965513 was associated with larger tumor size ( p = 0.025) and extrathyroidal expansion (odd ratio [OR] = 1.29, p = 0.045). The variant rs2439302 showed association with lymph node metastasis (OR = 1.24, p = 0.016), and multifocality status of the tumor (OR = 1.24, p = 0.012). The expression of MBIP was associated with T stage ( p = 0.010). MBIP and PTCSC3 displayed lower expression in PTC tissue in males than in females ( p = 0.025 and p = 0.036, respectively). NKX2-1 displayed lower expression in patients with N1 stage ( p = 0.040). Conclusions: The studied germline risk alleles predisposing to PTC were associated with a more aggressive course of the disease reflected by larger tumor diameter, higher multifocality rate, and more advanced N stage at the time of diagnosis. These results show that germline variants not only predispose to PTC but also might impact its clinical course. However, these associations were only moderate, and further large multi-ethnic studies are required to evaluate the usefulness of these germline variants in the clinical stratification of PTC patients. [ABSTRACT FROM AUTHOR]

BACKGROUND Chondroblastic osteosarcoma (COS) is a uniformly fatal bone malignancy if not diagnosed and treated appropriately in a timely manner. Fine-needle aspiration (FNA) of osseous lesions is routinely performed in major medical centers. Appropriate characterization of the tumor will significantly influence patient management and outcomes. METHODS A retrospective review of the cytopathology archives of 2 large tertiary care centers for a 15-year period (2001-2015) revealed 17 cases of COS (9 primary, 6 recurrent, and 2 metastatic cases) in 16 patients. Clinical outcome and histopathologic follow-up were reviewed and correlated. RESULTS There were 9 male and 7 female patients (male-to-female ratio of approximately 1:1), ranging in age from 12 to 70 years (mean age, 29.2 years). The classic locations for osteosarcoma were commonly involved, such as the long bones around the region of the knee in 4 cases and the proximal humerus in 1 case. However, other 'nonclassic' sites also were noted to be commonly involved, including the distal tibia or fibula (4 cases), sacroiliac region (4 cases), mandible (3 cases), and skull (1 case). Cytomorphologic characteristics were high cellularity; predominantly discohesive, single cells; small tissue fragments; background osteoid and chondroid matrix; spindled cells and plasmacytoid cells with moderate to abundant basophilic vacuolated cytoplasm and occasional multiple cytoplasmic processes; round to oval nuclei with anisonucleosis; and small to prominent nucleoli. There were scattered binucleated and multinucleated osteoclast-like giant cells. Cases with high-grade morphology demonstrated marked pleomorphism and abundant mitoses. CONCLUSIONS The differential diagnosis of COS includes chondroblastoma, chondrosarcoma, and chondroid chordoma. A definitive diagnosis can be made with clinical and radiological correlation. Cancer Cytopathol 2016;124:493-500. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

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 [ABSTRACT FROM AUTHOR]

Fibrous dysplasia (FD) involving the mid-face may be associated with cystic and other secondary changes that make diagnosis more difficult. We present a case of FD associated with a remote history of blunt facial trauma and extensive cystic changes involving the medial orbit and sinuses. An endoscopic exploration revealed 'stalagmites' along the floor of the cystic cavity that were consistent with dystrophic calcification. This case was unusual given the degree of dystrophic calcification and the presence of sino-orbital stalagmites within the cystic cavity. Radiologic and pathologic features of the stalagmites are characterized. [ABSTRACT FROM AUTHOR]

Background: Physiologic iodide-uptake, mediated by the sodium/iodide symporter (NIS), in the salivary gland confers its susceptibility to radioactive iodine-induced damage following 131I treatment of thyroid cancer. Subsequent quality of life for thyroid cancer survivors can be decreased due to recurrent sialoadenitis and persistent xerostomia. NIS expression at the three principal salivary duct components in various pathological conditions was examined to better our understanding of NIS modulation in the salivary gland. Methods: NIS expression was evaluated by immunohistochemistry in human salivary gland tissue microarrays constructed of normal, inflamed, and neoplastic salivary tissue cores. Cumulative 123I radioactivity reflecting the combination of NIS activity with clearance of saliva secretion in submandibular and parotid salivary glands was evaluated by single-photon emission computed tomography/computed tomography imaging 24 hours after 123I administration in 50 thyroid cancer patients. Results: NIS is highly expressed in the basolateral membranes of the majority of striated ducts, yet weakly expressed in few intercalated and excretory duct cells. The ratio of 123I accumulation between parotid and submandibular glands is 2.38±0.19. However, the corresponding ratio of 123I accumulation normalized by volume of interest is 1.19±0.06. The percentage of NIS-positive striated duct cells in submandibular salivary glands was statistically greater than in parotid salivary glands, suggesting a higher clearance rate of saliva secretion in submandibular salivary glands. NIS expression in striated ducts was heterogeneously decreased or absent in sialoadenitis. Most ductal salivary gland tumors did not express NIS. However, Warthin's tumors of striated duct origin exhibited consistent and intense NIS staining, corresponding with radioactive iodine uptake. Conclusions: NIS expression is tightly modulated during the transition of intercalated to striated ducts and striated to excretory ducts in salivary ductal cells. NIS expression in salivary glands is decreased during inflammation and tumor formation. Further investigation may identify molecular targets and/or pharmacologic agents that allow selective inhibition of NIS expression/activity in salivary glands during radioactive iodine treatment. [ABSTRACT FROM AUTHOR]

BACKGROUND: Margin status is a predictor of outcome for patients with liver malignancies, although what constitutes a negative margin is controversial. Traditionally, the completeness of resection is estimated by surgical histopathology of the resected specimen margin, despite the in situ margin being potentially more important. The true margin is often altered by parenchymal transection techniques. The authors propose that cytologic assessment of the in situ margin is more specific for determining the true margin. METHODS: A total of 84 patients with primary or metastatic liver tumors who were undergoing surgical resection were enrolled in this prospective Institutional Review Board-approved study. Specimen and in situ (patient) margins were assessed using a 'scrape preparation' cytologic technique and compared with traditional surgical histopathology. Patients were followed for assessment of local disease recurrence. RESULTS: Follow-up data were complete for 64 patients for a median of 37 months (range, 12 months-56 months). Twenty patients were excluded because of perioperative death (6 patients; 7%) or a follow-up of < 12 months. Seven patients (12.2%) had positive histopathologic specimen margins, but only 1 was found to be positive by cytology (1.8%). No in situ cytologically positive margins were identified along the cut edge of the liver remnant. The rate of intra- or extrahepatic recurrences was 56.7%, whereas the local recurrence rate was 1.8%. One patient with local recurrence demonstrated simultaneous intra- and extrahepatic disease recurrences and had negative margins by all methods of evaluation. CONCLUSIONS: To the authors' knowledge, the current study is the first to demonstrate that in situ margins can be assessed using cytopathology. This method is quick and can be universally applied. Given the difficulty of accurately assessing margins after hepatectomy, cytopathologic evaluation may be more reflective of the true margin. Cancer (Cancer Cytopathol) 2012. © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND: Among sarcomas, a diagnosis of malignant peripheral nerve sheath tumor (MPNST) is often one of exclusion due to the absence of unequivocally characteristic histopathology, a conclusive immunohistochemical profile, or even a unique chromosomal anomaly. Because of this, the fine-needle aspiration (FNA) cytopathology of MPNST is extremely challenging. In the current study, the authors review their FNA experience with this neoplasm. METHODS: The authors searched their combined departmental cytology files for all lesions signed out as MPNST or suspicious for MPNST, as well as their own surgical pathology files for any cases of MPNST that had corresponding cytology. FNA was performed using standard techniques. RESULTS: A total of 55 cases of MPNST, all with tissue confirmation, and 1 misdiagnosed example of melanoma were retrieved from 52 patients (M:F ratio of 1.5:1; average age, 46 years), 26 of whom had a history of neurofibromatosis type 1 (NF-1). Aspirates were from primary (27 cases), locally recurrent (14 cases), or metastatic (10 cases) MPNST; 4 primary tumor aspirates were of ex vivo specimens. Sites included the extremities (22 cases), trunk/pelvis (22 cases), head and neck (6 cases), and deep-seated masses (6 cases). FNA diagnoses were MPNST (24 patients); consistent with MPNST (5 patients); sarcoma, not otherwise specified (10 patients); atypical (3 patients); spindle cell neoplasm (6 patients); malignant neoplasm (1 patient); and nondiagnostic (3 patients). A definitive diagnosis of either MPNST or consistent with MPNST was issued in 30%, 93%, and 70%, respectively, of primary, locally recurrent, and metastatic lesions. CONCLUSIONS: FNA cytopathology is limited as a diagnostic instrument for the initial diagnosis of MPNST, but is exceedingly accurate and valuable in the recognition of metastatic and locally recurrent MPNST. Cancer (Cancer Cytopathol) 2012. © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND: The current study was conducted to describe the clinical features and presentation, cytomorphological characteristics with histological correlation, and prognosis of patients who undergo fine-needle aspiration (FNA) for postradiation sarcoma (PRS). METHODS: A retrospective review was performed of 13 individual patients who were pooled from the FNA services of 3 academic institutions between 2001 and 2012. Cases were reviewed for the primary tumor, radiation history, latency period, and other distinguishing clinical features. The frequency of the various cytological preparations as well as the use of immunohistochemistry (IHC) on this material were reviewed. The cytopathology diagnosis was compared with the resection diagnosis, and the survival time was reviewed. RESULTS: The median age of the patients was 61 years (range, 35 years-94 years) and no significant gender predilection was noted. The median latency period was 11 years (range, 5 years to > 50 years). Patients generally presented with large tumors (median, 8 cm [range, 3 cm-12 cm]), and the median survival was 14 months (range, 6 months-46 months). Nine of 13 patients died of their disease and 1 was lost to follow-up. The tumors were morphologically heterogeneous. IHC played an important role in excluding other diagnoses in those cases in which sufficient material was available. CONCLUSIONS: PRS is a morphologically heterogeneous entity that can be diagnosed by FNA. It is a diagnosis of exclusion that requires a history of therapeutic radiation and often requires IHC to rule out locally recurrent malignancy. Cancer (Cancer Cytopathol) 2012. © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis: Head and neck solitary fibrous tumors (SFTs) are quite rare, with <200 cases reported in the literature. The purpose of this study was to analyze the diagnostic and therapeutic challenges of this rare disease while reporting the largest head and neck case series. Study Design: Retrospective review. Methods: Between 1991 and 2011, 13 cases of head and neck SFTs from the pathology database were identified. Demographic, clinical, radiologic, and pathologic data were then abstracted and compiled for review. Results: SFT presented nearly equally as asymptomatic slow-growing masses or with local symptoms due to compression. All tumors imaged by computed tomography or magnetic resonance imaging with contrast showed a well-defined strongly enhancing mass. Two patients had evidence of bone erosion on imaging, but no histopathologic features of malignancy. Treatment consisted of surgical resection and in two cases postoperative radiation. Two patients had pathologic findings of malignancy, but are alive without recurrence at 26 and 51 months follow-up. Two patients had recurrence, one with paraspinal disease and grossly positive surgical margins, and another with endoscopic resection and poor margin control. Conclusions: SFTs of the head and neck are exceedingly rare and those with aggressive behavior even more so. Diagnosis is often difficult and not definitive until morphologic and immunohistochemical evaluation is performed. In most cases, complete surgical excision is the only necessary treatment. Although in patients with malignant components or positive surgical margins, adjuvant radiation may be beneficial. Regardless, all patients require close clinical follow-up for several years. Laryngoscope, 2012 [ABSTRACT FROM AUTHOR]

Background: MicroRNA (miR) expression signatures are proposed to be able to differentiate thyroid cancer from benign thyroid lesions. We selected eight miRs (miR-146b, -221, -187, -197, -346, -30d, -138, and -302c) to examine the potential use of miRs to supplement diagnostic cytology in cases designated as 'atypia of undetermined significance.' Methods : miR expression was measured in thyroid fine needle aspiration (FNA) specimens by quantitative polymerase chain reaction. Gene expression analyses and linear discriminant analysis (LDA) were performed in a training sample set ( n=60) to obtain a classification rule to predict FNA cases as benign or malignant. The predictions were cross-validated by comparing with the corresponding histological diagnoses. A validation sample set ( n=68) was further tested with the established four-miR LDA classification rule. Results: A set of four miRs (miR-146b, -221, -187, and -30d) was identified that could differentiate malignant from benign lesions. A four-miR LDA classification rule was obtained and used to predict FNA cases as benign or malignant. For the training sample set, we obtained a diagnostic accuracy of 93.3%, sensitivity of 93.2%, specificity of 93.8%, positive predictive value (PPV) of 0.98, and negative predictive value (NPV) of 0.83. For the validation sample set, we obtained a diagnostic accuracy of 85.3%, sensitivity of 88.9%, specificity of 78.3%, PPV of 0.89, and NPV of 0.78. For the 30 atypia cases in the validation sample set, we obtained a diagnostic accuracy of 73.3%, sensitivity of 63.6%, specificity of 78.9%, PPV of 0.64, and NPV of 0.79. Based on the miR predictions, we classified the atypia cases predicted as 'malignant' into 'high risk' and those predicted as 'benign' into 'low risk' categories. While thyroid carcinomas, particularly papillary thyroid carcinomas (PTCs), were relatively enriched in the high-risk category, this particular miR panel is subject to inaccurate results in follicular neoplasias in atypia cases. Conclusions: We demonstrate that miR amplification from FNA samples is feasible and that the particular four miR profile in this study can identify PTCs. However, further refinement is required for application to FNA cytology of 'atypia of undetermined significance' cases due to low accuracy in classifying follicular neoplasias. [ABSTRACT FROM AUTHOR]

BACKGROUND: B-cell lymphomas with concurrent IGH-BCL2 and c-MYC rearrangements (so-called 'double-hit lymphomas' [DHL]) are a relatively rare, recently described category in the 2008 World Health Organization classification of hematopoietic neoplasms. Response to chemotherapy and survival are poor. METHODS: The authors reviewed files of cytogenetically documented DHL to identify cytologic features that would allow its possible recognition. RESULTS: Twelve fine-needle aspirates (FNAs), 2 pleural fluids, and 1 touch imprint of cytogenetically proven DHL were uncovered. Primary DHL was correctly recognized in 3 of 12 FNA cases using Ki-67 staining coupled with a positive bcl-2 result as the basis for performing fluorescence in situ hybridization (FISH) analysis of c-MYC and IGH-BCL2 rearrangements. Remaining FNAs and non-FNA cases were diagnosed as non-Hodgkin lymphoma, B-cell lymphoma, or atypical lymphocytosis. Ten cases had cell block material available. All cases had high cellularity with a dissociated smear pattern and background lymphoglandular bodies. Cell size ranged from intermediate to large. Nuclei were predominantly rounded or slightly irregular in contour; 4 FNAs had markedly cleaved nuclei. Some nuclei harbored discrete but small nucleoli, whereas in others coarse chromatin and indistinct or multiple small nucleoli existed. A variable number of mitotic figures, tingible body macrophages, and background apoptotic cells were also present. CONCLUSIONS: No specific cytomorphologic feature(s) were found to reliably identify DHL using FNA or exfoliative cytology. A high Ki-67 proliferation index and positive bcl-2 staining (on cytospin slides or cell block material) of cases not conforming to typical Burkitt lymphoma morphology should prompt FISH analysis for c-MYC and/or IGH-BCL2 rearrangements to identify DHL, particularly if tissue biopsy is not expected. Cancer (Cancer Cytopathol) 2011;. © 2011 American Cancer Society [ABSTRACT FROM AUTHOR]

A 17-year-old male presented to us following a hyperflexion injury to his right knee sustained while playing soccer. Immediately after the traumatic event, he developed a large, tense knee effusion. Physical examination revealed limited range of motion. MRI revealed a lobulated mass in the posteromedial aspect of the knee joint. The mass was excised and sections submitted to pathology. A pathologic, microscopic, and immunohistochemical characteristics revealed the final diagnosis of fibroma of tendon sheath in the knee. At 12 months followup, the patient reported no subjective symptoms, such as pain or limitation of athletic activities and has full range of motion. Additionally, he has demonstrated no signs of recurrence. We report a case of fibroma of the tendon sheath originating from the synovial membrane of the joint capsule of the knee. [ABSTRACT FROM AUTHOR]

The article discusses a study on the reliability of fine-needle aspiration (FNA) for high-grade sarcoma (HGS). The researchers examined their cytopathology database from March 2001 to January 2007, and determined all FNA cases diagnosed as HGS. It was found out that a cytopathologic diagnose of HGS was accurate in 88 of 97 cases with follow-up. Moreover, a FNA biopsy diagnose of HGS seems to be clinically reliable in a number of cases when used in collaboration with the orthopedic team.

BACKGROUND. Extraskeletal myxoid chondrosarcoma (EMC) is a rare soft-tissuesarcoma rarely subjected to cytologic analysis. With the exception of a few small series, the cytology literature of EMC is largely limited to single-case reports. The purpose was to evaluate the cytomorphology of 8 EMC cases as obtained by imprint/scrape cytology and fine-needle aspiration (FNA) biopsy, to review the literature,and to demonstrate the utility of cytogenetic analysis in the diagnosis of EMC.METHODS. The cytology files were reviewed for all soft-tissue lesions signed out aschondrosarcoma, myxoid sarcoma, and EMC, and the tissue files for any cases ofEMC that had corresponding cytopathology. FNA was performed using a standardtechnique. Scrape preparations were performed from tissue sent fresh to the laboratory for either frozen section or for special studies such as electron microscopy ortissue banking.RESULTS. Eight cases of EMC were retrieved from 4 men and 3 women (medianage 5 62 years). One patient had 2 separate cytologic specimens 4.5 years apart. Allpatients had subsequent tissue confirmation of the diagnosis of EMC. Five individuals presented as new patients, and 2 had a prior diagnosis of EMC. Sites included4masses from the foot/ankle, 2 from the calf, 1 wrist mass, and 1 buttock mass. Fivepatients were diagnosed from FNA biopsy, whereas 3 were diagnosed using scrapeslides. Five cases were correctly and categorically diagnosed by the cytologicmethod as EMC, 1 as chondrosarcoma favor EMC, 1 as sarcoma favor EMC, and 1as myxoid spindle/epithelial neoplasm. Cytologic features ranged from hypocellularto highly cellular smears composed primarily of rounded cells set in an abundantmyxoid stroma that varied from opaque to semitransparent and lacked vascularityor necrosis. Smears showed cells in short, sometimes anastomosing cords, but alsoas single cells and nondescript cell clusters. Cells displayed a monotonous uniformity in nuclear diameter and cell size. Bland nuclei with evenly dispersed chromatindisplayed variably sized nucleoli, and a moderate amount of infrequently vacuolated cytoplasm. Tissue fragments of variable size were found in 5 of 5 FNA cellblocks. Fluorescence in situ hybridization (FISH) analysis using the EWSR1 probeshowed a positive 22q12 translocation in 2 of 3 FNA cases that were tested. Onecase with negative FISH results on the cytologic preparation showed a positivetranslocation using the same technique in the subsequent resection specimen.CONCLUSIONS. A confident cytologic diagnosis of EMC depends on the presence ofa uniform, round to oval cell population often arranged in cords and set in an abundant myxoid/chondromyxoid background and arising in the appropriate clinicalcontext. If positive, FISH testing (of paraffin cell blocks or cytospin preparations) isconfirmatory when coupled with this cytomorphology. [ABSTRACT FROM AUTHOR]