Novel CRTC1::MRTFB(MKL2) Gene Fusion Detected in Myxoid Mesenchymal Neoplasms With Myogenic Differentiation Involving Bone and Soft Tissues.

Appropriate classification of fusion-driven bone and soft tissue neoplasms continues to evolve, often relying on the careful integration of morphologic findings with immunohistochemical, molecular, and clinical data. Herein, we present 3 cases of a morphologically distinct myxoid mesenchymal neoplasm with myogenic differentiation and novel CRTC1::MRTFB (formerly MKL2) gene fusion. Three tumors occurred in 1 male and 2 female patients with a median age of 72 years (range: 28-78). Tumors involved the left iliac bone, the right thigh, and the left perianal region with a median size of 4.0 cm (4.0-7.6 cm). Although 1 tumor presented as an incidental finding, the other 2 tumors were noted, given their persistent growth. At the time of the last follow-up, 1 patient was alive with unresected disease at 6 months, 1 patient was alive without evidence of disease at 12 months after surgery, and 1 patient died of disease 24 months after diagnosis. On histologic sections, the tumors showed multinodular growth and were composed of variably cellular spindle to round-shaped cells with distinct brightly eosinophilic cytoplasm embedded within a myxoid stroma. One tumor showed overt smooth muscle differentiation. Cytologic atypia and mitotic activity ranged from minimal (2 cases) to high (1 case). By immunohistochemistry, the neoplastic cells expressed focal smooth muscle actin, h-caldesmon, and desmin in all tested cases. Skeletal muscle markers were negative. Next-generation sequencing detected nearly identical CRTC1::MRTFB gene fusions in all cases. We suggest that myxoid mesenchymal tumors with myogenic differentiation harboring a CRTC1::MRTFB fusion may represent a previously unrecognized, distinctive entity that involves soft tissue and bone. Continued identification of these novel myxoid neoplasms with myogenic differentiation will be important in determining appropriate classification, understanding biologic potential, and creating treatment paradigms.

Cytomorphology of metastatic colonic MXD4::NUTM1-rearranged sarcoma.

This report describes the cytologic features of a recently described MXD4::NUTM1-rearranged colonic sarcoma metastatic to the midclavicular soft tissue. Thirteen years ago, a 65-year-old woman presented with a cecal mass and subsequent liver mass. The cecal mass was diagnosed as malignant undifferentiated spindled and epithelioid neoplasm based on morphology and lack of tumor immunoreactivity with a panel of epithelial, smooth muscle, skeletal, melanoma, hematologic, and GIST markers. The liver mass showed morphologic and immunophenotypic similarity to the epithelioid component of the patient's cecal mass, albeit devoid of the spindled component. Fine needle aspiration of the midclavicular soft tissue mass showed singly scattered to clustered epithelioid to rhabdoid tumor cells with centrally to eccentrically located nuclei, prominent nucleoli, and moderate eosinophilic cytoplasm. Immunohistochemical stains performed on the concurrent biopsy showed the tumor cells were positive for NUT and negative for all other additional markers with retained normal expression of SMARCA2 and SMARCA4. Next-generation sequencing showed the presence of MXD4::NUTM1 gene fusion. Due to the identical cytomorphologic findings with the epithelioid component of the patient's prior cecal and liver masses, the tumor was deemed as consistent with a NUTM1-rearranged sarcoma. To our knowledge, this case represents the first reported cytologic features of a NUTM1-rearranged sarcoma on fine needle aspiration. Familiarity with the cytologic features, inclusion of this entity in the differential diagnosis of tumors with epithelioid and/or rhabdoid morphology, and performance of ancillary tests (immunohistochemistry and molecular) will be helpful in arriving at the right diagnosis.

Are there specific cytologic features that can predict BRAFV600E mutational status of papillary thyroid carcinoma in fine-needle aspiration specimens?

BACKGROUND: BRAFV600E mutation is the most common molecular alteration found in papillary thyroid carcinoma (PTC) and has been linked to recurrent disease or possibly more aggressive behavior. Some studies have reported sickle-shaped nuclei (SSN) and plump pink cells (PPC) to be predictive markers of BRAF mutation in FNA cytology. We aimed to evaluate the reproducibility of the aforementioned cytologic features. METHODS: A computerized search for diagnosed PTC surgical pathology cases tested for BRAFV600E mutation by Sanger DNA sequencing was performed. Blinded to BRAF results, the corresponding cytology was reviewed for presence of SSN and PPC. Classic nuclear PTC (CNPTC) features, cystic change, and psammoma bodies were also evaluated. The results were correlated with BRAFV600E mutational status and histologic subtypes. RESULTS: Study cohort consisted of 113 cases (74 BRAFV600E mutated, 39 BRAFV600E wild type). SSN and combined CNPTC /SSN had positive predictive value of 74% and 75%, respectively. CNPTC showed 92% sensitivity and 20% specificity. Psammoma bodies had 92% specificity and 5% sensitivity. The presence of combined PPC/SSN showed 80% specificity, 27% sensitivity, and diagnostic accuracy of 45%. CNPTC was seen in 60/61 (98%) SSN and 45/45 (100%) PPC. There was no significant statistical association between SSN, PPC, and CNPTC with specific histologic subtypes and BRAF mutational status. CONCLUSION: CNPTC is sensitive but not specific for BRAF mutational status. SSN, PPC, and CNPTC are not predictive markers for the presence of BRAF mutation or histologic subtypes. Additional studies may be needed to further corroborate these findings.

Secondary somatic glioblastoma arising from a mature ovarian cystic teratoma in a patient with underlying Li-Fraumeni syndrome.

•First report of a secondary somatic glioblastoma arising from MCT-MT in a patient with underlying Li-Fraumeni syndrome.•The rarity of glioblastoma arising from MCT-MT warrants investigation for underlying genetic predisposition.•Glioblastomas arising from MCT-MT appear to exhibit wild type IDH gene status.•Advanced-stage glioblastoma arising from MCT-MT exhibits aggressive behavior and requires adjuvant therapy.•Optimal adjuvant therapy regimen for glioblastoma arising from MCT-MT remains unknown.

ZC3H7B-BCOR Fusion High-grade Endometrial Stromal Sarcoma With Morphologic Features of Low-grade Endometrial Stromal Sarcoma. A Case Report and Review of Literature.

High-grade endometrial stromal sarcomas with ZC3H7B-BCOR fusion are rare. They are predominantly located in the endomyometrium, with morphologic features characterized as haphazardly arranged fascicles of spindle cells with mild to moderate atypia, abundant myxoid matrix, high mitotic index, and tongue-like/pushing patterns of myometrial invasion. Furthermore, conventional or variant low-grade endometrial stromal sarcomas are often not present. Clinically, they present at a higher stage and are associated with worse prognosis compared with low-grade endometrial stromal sarcoma. Given the limited number of reported cases, we describe the case of a ZC3H7B-BCOR fusion high-grade endometrial stromal sarcoma initially diagnosed on the hysterectomy specimen as low-grade endometrial stromal sarcoma based on an endometrial stromal tumor showing tongue-like myometrial and lymphovascular invasion, minimal cytologic atypia, low-mitotic activity (0-1/10 high-power field), round/spindle cell component and immunohistochemical stain results (positive for CD10, estrogen receptor, progesterone receptor, and focally positive for cyclin D1). At the time of pathologic diagnosis, she was Stage Ia and managed conservatively. Subsequent molecular analysis revealed a ZC3H7B (exon 10)- BCOR (BCL-6 corepressor) (exon 7) gene fusion. On follow-up, she showed no evidence of disease at 37 months from the time of diagnosis. This case report expands the morphologic spectrum of ZC3H7B-BCOR fusion high-grade ESS, which includes an intramural location, morphologic and immunophenotypic features similar to LG-ESS, as well as the presence of round and spindle cell components. This case also underscores the value of molecular analysis in the proper classification of ESS.

Undifferentiated component of dedifferentiated endometrial carcinoma presenting as a "small round cell" malignancy in a mediastinal lymph node, mimicking small cell carcinoma.

Undifferentiated/dedifferentiated endometrial carcinoma is an uncommon malignant neoplasm of the endometrium that can present as a diagnostic challenge, especially in a metastatic setting. We present a case of a 70-year-old woman with a prior endometrial biopsy diagnosed as endometrioid carcinoma, FIGO Grade 2. Chest computerized tomography showed moderate to severe centrilobular emphysema with a 3 mm nodule in the right upper lobe and posterior mediastinal lymphadenopathy. Fine needle aspiration smears of the mediastinal lymph node showed predominantly single and loosely cohesive tumor cells with scant basophilic cytoplasm, prominent nuclear streaking, and molding. Inconspicuous nucleoli and mitotic figures were present. Immunohistochemical (IHC) stains showed the tumor cells were positive for CD56 and synaptophysin but negative for AE1/AE3, CAM5.2, CK7, CK20, TTF-1, INSM1, chromogranin, CD99, HMB45, SOX10, EBV-LMP1, and desmin. Flow cytometry was negative for lymphoma. Based on the overall cytologic findings and significant smoking history, a small cell carcinoma could not be excluded. Similar morphologic findings were identified on the corresponding lymph node biopsy. Because of the history of endometrial carcinoma, additional IHC stains (PAX 8, ER, and EMA) were done but were negative. However, the mismatch repair proteins revealed loss of MLH1 and PMS2 with retained MSH2 and MSH6 nuclear expression. Hence, a metastatic undifferentiated component of a dedifferentiated carcinoma from the patients' endometrial primary was favored and subsequently confirmed on the hysterectomy specimen.

Ectopic adrenal cortical tissue presenting as gastrohepatic ligament "lymph node" diagnosed by fine-needle aspiration: A case report.

Ectopic adrenal cortical tissue has been reported in several locations, most often involving the retroperitoneal fat close to the adrenal gland. The reported cases presenting adjacent or proximal to the stomach are rare and mostly diagnosed on histology. To our knowledge, the cytologic features of ectopic adrenal cortical tissue diagnosed on fine needle aspiration are not well documented in the cytology literature. We describe the cytologic features of ectopic adrenal cortex which initially presented on imaging study as an enlarged gastrohepatic ligament "lymph node" on a patient with gastric signet ring cell carcinoma. The aspirates showed small clusters and cords of uniform cells with abundant vacuolated to densely compact cytoplasm, occasionally stripped nuclei, and delicate frayed cytoplasmic membranes dispersed in a bubbly, vacuolated background. Immunohistochemical stains performed on the corresponding cell block showed these cells were positive for SF-1 and negative for PAX 8. The corresponding biopsy showed similar findings in addition to immunoreactivity to inhibin. Because the cytologic features of ectopic adrenal cortical tissue especially on unusual sites could easily mimic malignant neoplasms, familiarity with the cytologic features in conjunction with immunohistochemical stains are key in arriving at the correct diagnosis and avoiding misdiagnosis.

Revisiting the cytologic features of autoimmune pancreatitis: An institutional experience.

BACKGROUND: Autoimmune pancreatitis (AIP) is a known mimicker of pancreatic ductal adenocarcinoma both clinically and radiologically. In this study, the authors present their institutional experience in diagnosing AIP on cytology and correlate results with the histologic findings. METHODS: A 14-year computerized search for patients who had histologically confirmed AIP with concurrent or prior cytology was performed. Clinical data, cytology findings, and surgical pathology results were reviewed for analysis. RESULTS: Eighteen patients were identified. The patients showed a male predominance, with a mean age of 59 years. Jaundice, weight loss, and abdominal pain were the most common clinical presentation. Five of 12 patients who were tested for serum immunoglobulin G4 had elevated levels. Cytologic findings of 16 cases that were available for review showed markedly inflamed fibrous stroma (54%) and cytologic atypia (50%). The final cytologic diagnoses were suspicious for adenocarcinoma (n = 1), atypical (n = 8), and benign/negative (n = 9). The corresponding surgical pathology diagnoses were classified as type 1 (n = 10), type 2 (n = 6), and AIP, not otherwise specified (n = 2). All type 2 AIP cases had at least atypical cytologic diagnoses, with one called suspicious for adenocarcinoma and another called adenocarcinoma at the time of rapid on-site evaluation. In contrast, eight of 10 type 1 AIP cases were negative/benign, and two of 10 were atypical. In these two atypical cases, the possibility of AIP was raised because of the presence of inflamed stroma. CONCLUSION: AIP is a pitfall in cytology because moderate-to-marked atypia can be present, especially in type 2 AIP. Because atypia can be severe, the presence of cellular fibrous stroma with lymphocytic stromal infiltrates and the integration of serum immunoglobulin G4 levels could be helpful in avoiding diagnostic overcall in AIP.

Malignant effusions secondary to metastatic thyroid carcinomas: A review of 15 cases.

BACKGROUND: Malignant effusions secondary to thyroid carcinomas are rare, and publications on this topic are limited. This study presents a large cohort of thyroid carcinomas involving effusion cytology. METHODS: A 20-year computerized search for fluid cytology diagnosed with thyroid malignancy was performed. The following data were collected: patients' demographics, clinical findings, and histologic diagnoses. The cytology slides and ancillary tests were reviewed. RESULTS: Among 47,593 specimens, 15 thyroid carcinomas involving the pleural fluid from 11 patients were found. There were six males and five females with a mean age of 72 years. Ten patients with available follow-up died of their disease. Papillary thyroid carcinoma (PTC) was the only histologic type. Ten cytology cases were available for review. The cytologic findings common to all cases were nonspecific (clusters/three-dimensional architecture, enlarged irregular nuclei, and scant to abundant to vacuolated cytoplasm). The classic PTC features were not present in all cases (fine/powdery chromatin [80%], micronucleoli [70%], nuclear grooves [50%], papillary-like architecture [40%], psammoma bodies [40%], and pseudo-nuclear inclusions [20%; present on the cell block only]). In 11 of the 15 cases, the diagnosis was rendered with immunohistochemical stains performed on the cell block (paired box 8, thyroid transcription factor 1, and thyroglobulin). In four of the 15 cases, the cytologic diagnosis was made after a comparison with prior surgical pathology or fluid cytology. CONCLUSIONS: PTC is the most common histologic type of thyroid malignancy involving pleural effusion. Because the cytologic findings are nonspecific and classic PTC features are not always present, the clinical history in conjunction with immunohistochemical stains is helpful in arriving at the correct diagnosis.

Bone and soft tissue sarcomas in cerebrospinal fluid and effusion: A 20-year review at our institution.

BACKGROUND: The literature on bone and soft tissue sarcomas (BSTSs) involving effusions and cerebrospinal fluid (CSF) is very limited. METHODS: A computerized search for fluid cytology with a sarcoma diagnosis from 2000 to 2020 was performed. All available cases, including the clinical follow-up, were reviewed. RESULTS: A total of 57 fluids specimens from 36 BSTSs were identified (9 rhabdomyosarcomas, 6 angiosarcomas, 5 epithelioid hemangioendotheliomas, 3 dedifferentiated liposarcomas, 2 chondrosarcomas, 1 extraskeletal myxoid chondrosarcoma, 3 Ewing sarcomas, 2 undifferentiated sarcomas, 3 osteosarcomas, 1 synovial sarcoma, and 1 hybrid low-grade fibromyxoid sarcoma/sclerosing epithelioid fibrosarcoma). There were 22 males and 14 females. The age range was 4 to 82 years (median, 45 years). Sites of involvement included pleural fluid (n = 38), peritoneal fluid (n = 14), and CSF (n = 5). Twenty-four cytology cases were available for review. The cytologic features were nonspecific and ranged from dyshesive to clusters of round, epithelioid, pleomorphic, and occasionally spindle-shaped malignant cells that could easily mimic other non-BSTS malignant tumors. The diagnosis of BSTS was made by comparison with a prior specimen and/or ancillary studies (molecular or immunohistochemical stains). The prognosis was poor because 95% of the patients died of their disease. CONCLUSIONS: The incidence of BSTS in fluid cytology is extremely rare, and it can have cytologic features similar to those of non-BSTS malignancies. Although, in most cases, a comparison with a prior known BSTS specimen may suffice, the use of ancillary studies is extremely helpful in arriving at the correct diagnosis. However, in cases with no known prior malignancy, including BSTS in the differential diagnosis is prudent for preventing misdiagnosis.

Urine cytology findings in patients with biopsy-confirmed urothelial carcinoma in situ with plasmacytoid features.

BACKGROUND: Urine cytology is an important screening tool in the diagnosis of high-grade urothelial carcinoma. Diagnosis in urine samples follows criteria outlined by The Paris System for Reporting Urinary Cytology (TPS). However, cytologic characteristics of the recently described urothelial carcinoma in situ with plasmacytoid features (P-CIS) have not been described, and it is unknown whether they conform to TPS criteria for high-grade urothelial carcinoma. This study was aimed at better characterizing possibly unique cytologic features of P-CIS. METHODS: The authors collected urine cytology specimens from patients with subsequent bladder biopsy-proven P-CIS. Specimens were re-reviewed according to the TPS criteria. The proposed cytologic features of P-CIS (eccentric, enlarged, and hyperchromatic nuclei) were evaluated; this included the reproducibility of 3 cytopathologists for the proposed cytologic features. RESULTS: Seventy-four urine specimens from 18 patients with P-CIS-diagnosed bladder biopsies were identified. The TPS diagnoses of the 74 urine cytology specimens were as follows: negative for high-grade urothelial carcinoma (n = 26), atypical urothelial cells (n = 26), suspicious for high-grade urothelial carcinoma (n = 12), and high-grade urothelial carcinoma (n = 10). Only 7 urine specimens met the proposed cytologic criteria for P-CIS, and they had TPS diagnoses of negative for high-grade urothelial carcinoma (n = 1), atypical urothelial cells (n = 3), and high-grade urothelial carcinoma (n = 3). The κ interobserver agreement ranged from poor to fair. CONCLUSION: The features of P-CIS on urine cytology are subtle and infrequently reproducible and often do not meet the TPS criteria for diagnosis as high-grade urothelial carcinoma. In specimens that do not meet TPS criteria for high-grade urothelial carcinoma, P-CIS cytology in isolation would be best classified as atypical urothelial cells.

Cytologic features and immunohistochemical findings of epithelioid hemangioendothelioma (EHE) in effusion: A case series.

BACKGROUND: Epithelioid hemangioendothelioma (EHE) is a rare malignant vascular tumor characterized by WWTR1-CAMTA1, t (1:3) (p36;q25) translocation in 90% of cases. Without prior EHE history, it can mimic other malignant effusions. Recently, CAMTA1 was published as an excellent immunohistochemical surrogate marker for molecular testing for WWTR1-CAMTA1 fusion in surgical specimens. METHODS: A 6-year retrospective search using our computer system was performed for cases diagnosed as EHE on effusion cytology and surgical specimens. The clinical presentation, cytologic findings and immunohistochemical stain results, including CAMTA1 were reviewed. RESULTS: Four pleural and one peritoneal effusions were identified. The median age was 52 years with a female to male ratio of 3:2. Most patients presented with pulmonary symptoms. The cytologic features were non-specific easily mimicking other malignancies; especially in the absence of known prior malignancy. This was exemplified by one of our cases which was initially misdiagnosed as adenocarcinoma. Intracytoplasmic erythrocytes were present only on the cell blocks but not on cytology. The cytology cell blocks from patients with prior EHE confirmed on surgical biopsies stained positive for vascular markers (CD31, ERG) and CAMTA1. CONCLUSION: The features of EHE in effusion are non-specific and a diagnostic pitfall in cytology. In the absence of prior EHE diagnosis, inclusion of this entity in the differential diagnoses and application of immunohistochemical stain panels will be prudent in avoiding a misdiagnosis. However, in cases with prior EHE diagnosis, CAMTA1 could serve as diagnostic marker; especially on limited cytology material. Additional studies will be helpful in supporting our results.

Perigastric solitary fibrous tumor (SFT) diagnosed on fine needle aspiration: A case report and review of literature.

Solitary fibrous tumor (SFT) is a mesenchymal tumor initially described in the pleura. When the tumor is located in the pleura and the classic histologic findings are present, the diagnosis of SFT can be straightforward. However, the cytologic diagnosis of perigastric SFT can be challenging due its rarity with only one cytology case report. Another confounding factor is its potential mimicry with other perigastric/gastric mesenchymal tumors. Herein, we report a case of perigastric SFT diagnosed on cytology in conjunction with immunohistochemical stains. The patient is a 79-year-old woman who presented with an enlarging perigastric mass on computerized tomography scan which was highly concerning for a saccular aneurysm. Endoscopic ultrasound (EUS) revealed a 6.6 cm hypoechoic lesion abutting the stomach. An EUS-guided fine needle aspiration was performed. The smears showed singly scattered to clusters of bland spindle cells with scant cytoplasm dispersed in a bloody background. The cell block showed similar spindle cells focally supported by a collagenized stroma. Immunohistochemical stains performed on the cell block showed the tumor cells were positive for CD34, BCL2, and STAT6 and negative for CD117, DOG1, CD31, ERG-ENDO, AE1/AE3, S-100, desmin, and synaptophysin, supporting the diagnosis of solitary fibrous tumor.

Malignancies in Pleural, Peritoneal, and Pericardial Effusions.

CONTEXT.­: The incidence and types of malignancies in effusion cytology are largely limited to studies performed in the 1970s through the 1990s. OBJECTIVE.­: To examine how the incidence of different types of malignancies in effusions has changed with time. DESIGN.­: A computerized search for fluid cytology from 2000 through 2016 (database included age, gender, cytologic diagnosis, and type of malignancy) was performed, and all cases were reviewed. RESULTS.­: Of 30 085 effusion specimens, 3285 (11%) were positive for malignancy (2175 pleural, 955 peritoneal, and 155 pericardial). Of those, 1023 (31%) had known primary sites (648 pleural, 267 peritoneal, and 108 pericardial). Malignancy was more common in females than males in both pleural (15% versus 9%) and peritoneal (14% versus 5%) effusions (P < .001). The most common metastatic tumors in pleural fluid were lung for males and breast for females; in peritoneal fluid, hematolymphoid for males and Müllerian tumors for females; in pericardial fluid, lung for both genders. Among invasive mammary carcinomas, lobular carcinoma tended to metastasize to peritoneal fluid, whereas ductal carcinoma tended to metastasize to pleural fluid (P < .001). Plasma cell neoplasms metastasized to pleural and pericardial but not peritoneal fluid (P = .002). CONCLUSIONS.­: Although pulmonary and Müllerian tumors continue to be the most common origin of metastasis in pleural and peritoneal fluid for males and females, respectively, the frequencies for other malignancies have changed. Familiarity with the more common sites of metastasis in effusion cytology is important, especially in patients with unknown primary, as this will be valuable in judicious triaging of specimens for ancillary studies.

Uterine Inflammatory Myofibroblastic Tumor Showing an Atypical ALK Signal Pattern by FISH and DES-ALK Fusion by RNA Sequencing: A Case Report.

Inflammatory myofibroblastic tumors (IMTs) are spindle cell neoplasms of intermediate (borderline) biologic potential with tendency for local recurrence but low risk of metastasis. They affect children more than adults. The most common sites of involvement are the lung, soft tissue, peritoneum, bladder, and less commonly the gynecologic tract. IMTs are characterized by spindle to epithelioid cells with myofibroblastic differentiation, some degree of smooth muscle differentiation, myxoid stroma and usually associated with brisk lymphoplasmacytic infiltrates. In about half of the cases, IMTs are associated with rearrangements of the anaplastic lymphoma kinase (ALK) gene located at chromosome 2p23. The ALK rearrangement can be detected by immunohistochemistry for ALK protein expression (mostly cytoplasmic with or without perinuclear accentuation) or by fluorescent in situ hybridization (FISH) using dual-color break-apart probes for which the typical pattern is seen as split 3' end (red) and 5' end (green) probe signals in addition to single normal, unsplit red-green signal pair (yellow). Herein we describe a case of uterine IMT initially misdiagnosed intraoperatively as leiomyoma which showed sparse lymphocytic infiltrates, positive ALK expression by immunohistochemistry, a predominantly atypical FISH signal pattern (1 yellow and 1 red signal only) and few typical signal patterns (1 yellow, 1 red, and 1 green signal) in a smaller population of tumor cells. The RNA sequencing showed a recently described DES-ALK fusion transcript in the tumor cells, suggesting an intrachromosomal inversion and deletion as the likely underlying mechanism for the atypical FISH pattern. Familiarity with the unusual morphology and atypical FISH pattern is crucial given that this tumor has an activating ALK rearrangement and may benefit from targeted tyrosine kinase inhibitors in the future.

Endometrial Polyp of the Placental Fetal Membranes: Report of a Case.

Endometrial polyps embedded in the fetal membranes have only rarely been described. A review of the English literature showed only one abstract describing this occurrence and to the best of our knowledge, there have been no other publications of this entity. Herein we present a case of a 37-yr-old woman with a history prior abortion and complicated pregnancy (type 2 diabetes mellitus and preeclampsia) who delivered by cesarean section. Although the placenta did not show hypertensive vasculopathic changes or other pathologic findings, an endometrial polyp embedded within the fetal membranes was present. Recognition of this rarely reported entity is important in order to avoid confusion with a significant neoplastic process.

Fibrous Extracellular Spheroids in an Endoscopic Ultrasound-Guided Pancreatic Fine Needle Aspiration Correlating to a Gyriform Pancreatic Endocrine Tumor with a Unique Cobblestone Pavement Growth Pattern.

Pancreatic neuroendocrine neoplasms (PanNENs) are uncommon tumors. Fine needle aspiration (FNA) samples from PanNENs are typically of high cellularity and lack necrosis. In cytology slides from these tumors, dyscohesive cells are usually reported with variably round to oval to plasmacytoid forms exhibiting coarsely granular chromatin and showing immunoreactivity for synaptophysin. We present an unusual, and to our knowledge not previously described, example of an FNA of a PanNEN with large extracellular fibrous spheroids containing intrinsic fibroblasts and rimmed by small to intermediate sized neoplastic epithelial cells with high nuclear cytoplasmic ratios. The cytomorphology of the PanNEN in this case was in some ways reminiscent of that expected in adenoid cystic carcinomas of the salivary glands that most often contain large extracellular globules of basement membrane material and a somewhat biphasic population of lesional cells. The cytomorphology in this case was found to correlate well with the resection specimen histomorphology of an exaggerated gyriform pattern of growth resulting in a unique cobblestone-pavement like microscopic appearance. Knowledge of this potential cytomorphology will aid the cytology community through recognition and reporting of this previously undescribed pattern in an uncommon disease.

The usefulness of lymphoid enhancer-binding factor 1 and androgen receptor in diagnosing solid pseudopapillary neoplasm of the pancreas on cytopathology.

BACKGROUND: Solid pseudopapillary neoplasm (SPN) is an uncommon tumor that is challenging to diagnose on cytology due to morphologic overlap with other pancreatic neoplasms. Recently, putative diagnostic markers for SPN have been reported in the surgical pathology literature, with nuclear positivity for lymphoid enhancer-binding factor 1 (LEF1) and androgen receptor (AR) identified in >90% and >80% of cases, respectively. In the current study, the authors sought to evaluate the sensitivity and specificity of LEF1 and AR on SPN cytology specimens and available corresponding surgical resection specimens. METHODS: Immunohistochemistry was performed using monoclonal antibodies against LEF1 and AR on 19 SPN cytology cases and 15 corresponding follow-up surgical resection specimens from 2 institutions. To evaluate specificity, the authors stained 23 non-SPN tumors diagnosed on cytology with corresponding surgical specimens (4 acinar cell carcinomas, 9 pancreatic neuroendocrine tumors, and 10 ductal adenocarcinomas). Positivity for LEF1 and AR was defined as any nuclear staining within neoplastic nuclei. RESULTS: LEF1 was found to be positive in 18 of 19 cytology cases (94.7%) and 15 of 15 corresponding surgical resection specimens (100%). AR was positive in 4 of 16 cytology cases (25.0%) and 4 of 15 corresponding surgical resection specimens (26.7%). Among non-SPN tumors, LEF1 demonstrated a specificity of 87% whereas the specificity for AR was 100%. CONCLUSIONS: LEF1 for SPN on cytology material was found to demonstrate a sensitivity of 94.7% and a specificity of 87%. Although AR was found to have a specificity of 100%, its sensitivity was lower (25%). LEF1 could be a valuable immunostain on cytology cell block material for the diagnosis of SPN. However, the same may not hold true for AR.

Cytological findings of monophasic synovial sarcoma presenting as a lung mass: report of a case and review of the literature.

Synovial sarcomas are rare malignant mesenchymal tumors that can arise from any anatomic site. Although they are often located at the paraarticular region of the extremities, the incidence of synovial sarcomas in the lungs is rare, with only a few cytology case reports to date. We report a case of synovial sarcoma presenting as a lung mass diagnosed on fine-needle aspiration (FNA) cytology. The patient is a 38-year-old chronic smoker who presented with cough, worsening dyspnea, and weight loss. Computerized tomography of his chest revealed an 8-cm left lower lobe pleural-based mass. An FNA of the lung mass showed cellular smears composed of monotonous population of singly scattered to sheets of bland spindle cells with elongated nuclei, fine chromatin pattern, and scant to moderate amount of delicate cytoplasm. Immunohistochemical stains performed on the cell block showed that the tumor cells were positive for calretinin and focally positive for pancytokeratin, CAM5.2, and smooth muscle myosin heavy chain. The tumor cells were negative for S-100, podoplanin, and CD34. Fluorescence in situ hybridization performed on the cell block demonstrated the presence of SYT (18q11) translocation, supporting the diagnosis of synovial sarcoma.

Metastatic SMARCB1 (INI-1)-Deficient Sinonasal Carcinoma Diagnosed by Endobronchial Ultrasound-Guided Fine-Needle Aspiration (EBUS-FNA): A Potential Diagnostic Pitfall and Review of the Literature.

SMARCB1 (INI-1)-deficient sinonasal carcinoma is a rare entity within the subgroup of poorly differentiated sinonasal tract carcinomas. As there are only two papers describing the cytologic features of this entity, herein we describe the unique cytomorphologic features of a pulmonary metastasis of this tumor and include the differential diagnosis based on tumor location. The patient was a 53-year-old male who initially presented with sinus congestion and vision changes including left-eye proptosis and diplopia. The initial biopsy of the ethmoid-centered sinonasal mass was non-keratinizing squamous cell carcinoma based on strong immunoreactivity with p40 and absence of immunoreactivity for chromogranin, synaptophysin, p16, and EBER. However, the final diagnosis of the surgical resection was amended to SMARCB1 (INI-1)-deficient sinonasal carcinoma after additional immunohistochemical stains were performed. Post-primary resection, follow-up computed tomography imaging revealed significant interval progression of a solitary, initially indeterminate 1-cm lung nodule in the left upper lobe. Endobronchial ultrasound-guided fine-needle aspiration with concomitant core-needle biopsy was performed. Rapid on site evaluation of cytologic smears revealed a hypercellular specimen consisting of sheets of epithelioid cells with very scant to absent cytoplasm, ill-defined cell borders, enlarged fragile nuclei, and areas of nuclear molding. Mitotic figures were present. Other areas showed tumor cells with spindled to elongated nuclei and scant to ill-defined wispy cytoplasm. Both cytology cell block and core-needle biopsy histopathologic material showed the tumor cells to be negative for INI-1 nuclear staining as well as CK5/6, CAM5.2, p40, p63, CK7, AE1/3, and TTF-1. SMARCB1 (INI-1)-deficient sinonasal carcinoma can have a spectrum of morphologies and may mimic "small-round-blue-cell" and spindle-cell tumors on cytology preparations. Given the pulmonary location of the aspirate, familiarity with the cytomorphologic spectrum of SMARCB1 (INI-1)-deficient sinonasal carcinoma, inclusion of this entity within the differential diagnosis, and performance of immunohistochemistry will aid in arriving at the correct diagnosis.