Cytologic features of pancreatic adenocarcinoma with “vacuolated cell pattern.” report of a case diagnosed by endoscopic ultrasound‐guided fine‐needle aspiration

The “vacuolated cell pattern” has only been recently described as a distinct morphologic variant of pancreatobiliary adenocarcinoma. Herein, we report the endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA) cytologic features of a case of pancreatic adenocarcinoma with “vacuolated cell pattern” occurring in a 60‐year‐old man. The aspirate smears and cell block sections from the EUS‐FNA of a 23.5 mm hypoechoic pancreatic head mass were highly cellular, showing variably‐sized crowded three‐dimensional cell clusters, flat sheets, and numerous highly atypical single cells. The background was bloody and showed necrotic debris, but no discernible mucus. The most striking feature of the aspirate was the presence of numerous very large (20–50 µm) vacuoles, occupying the entire cytoplasm, pushing the nuclei to the side and indenting them, that imparted a cribriform appearance to the sheets of neoplastic cells. The non‐vacuolated neoplastic cells were large, had abundant dense (squamoid) cytoplasm, irregularly contoured hyperchromatic nuclei, and prominent macronucleoli. Histologic evaluation of the pancreatectomy specimen showed a “vacuolated cell pattern” adenocarcinoma composed of poorly formed glands, solid sheets, and infiltrating single cells with pleomorphic nuclei and large cytoplasmic vacuoles. To our knowledge, this is the first report describing the cytologic features of this rather uncommon morphologic variant of pancreatic adenocarcinoma. Recognition of this morphologic variant of pancreatic adenocarcinoma in ESU‐FNA samples allows its differentiation from primary and metastatic signet‐ring cell carcinomas. Diagn. Cytopathol. 2014;42:302–307. © 2014 Wiley Periodicals, Inc.     

The oncocyte that went places: Diagnosis with EUS‐guided FNA

Although uncommon, Hurthle cell neoplasms have a characteristic histologic and cytologic features which often aid in the diagnosis of these lesions. In fine needle aspiration biopsies, determining malignant potential on cytologic features is challenging unless other evidence of malignancy (such as metastases) are known. The role of EUS‐guided FNA in diagnosing superior mediastinal masses has been described previously. It's role in evaluating subcarinal metastases from lung cancer primaries have also heen studied. However we describe metastatic thyroid Hurthle cell carcinoma to the subcarina diagnosed through EUS‐guided FNA combining the unique cytologic features o Hurthle cell neoplasms and the versatility ofthe endoscopic ultrasound to reach a diagnosis in this unusual neoplasm. Diagn. Cytopathol. 2013;41:977–979. © 2011 Wiley Periodicals, Inc.     

Endobronchial ultrasound‐guided fine‐needle aspiration cytology of bronchial low‐grade mucoepidermoid carcinoma: Rapid on‐site evaluation of cytopathologic findings

Bronchial mucoepidermoid carcinoma (MEC) is rare, comprising about 0.2% of primary lung tumors. Endobronchial ultrasound (EBUS) guided fine‐needle aspiration (FNA) cytology is an integral tool in the diagnosis and staging of malignant lung tumors. Rapid on‐site evaluation (ROSE) has been proven useful as a guide for assessing the adequacy and accuracy of the FNA samples. Therefore, comprehensive knowledge of diagnostic cytomorphologic findings of MEC is critical for ROSE. We reported a 46‐year‐old woman with 6 weeks of cough productive of yellow sputum that did not improve on antibiotics. A chest CT demonstrated a well‐circumscribed nodule in the right lower lobe bronchus that extended into the lung parenchyma. EBUS‐guided FNA was performed to obtain diagnostic materials. The ROSE of cytology specimen revealed numerous tight clusters of cells with well‐defined, but scant cytoplasm. These cells were relatively small and bland with high N/C ratio, resembling benign ductal cells. Neither cilia nor intranuclear inclusions were noted. Focal extracellular metachromatic mucinous materials were also noted. A preliminary diagnosis of “low‐grade epithelial neoplasm, favor low grade MEC” was rendered. The definitive diagnosis was confirmed by both cytology and core biopsy. EBUS‐guided FNA cytology can be a reliable method for the diagnosis of bronchial low grade MEC. The cyto‐morphology of ROSE can indicate the diagnosis of low grade MEC and direct the appropriate follow‐up triage of the specimen.Diagn. Cytopathol. 2013;41:1096–1099. © 2012 Wiley Periodicals, Inc.     

Cytologic features of pancreatobiliary neoplasm of duodenum

Small intestinal adenomas are uncommon. Majority of these occur in the region of the ampulla of Vater. Adenomas of the ampulla can be further subdivided into two types—intestinal and pancreatobiliary. While intestinal adenomas are more frequent, pancreatobiliary adenomas are rare. There is limited literature regarding the role of endoscopic ultrasound‐guided fine needle aspiration (EUS‐FNA) in the diagnosis of ampullary/peri‐ampullary neoplasms. Here, we describe the cytologic features of a pancreatobiliary neoplasm of the duodenum that was sampled by EUS‐FNA. The aspirate was cellular and revealed cells with moderately abundant oncocytic cytoplasm. The nuclei were round with fine chromatin and focally prominent nucleoli. Although the concurrent biopsy showed no high‐grade dysplasia or invasive carcinoma, the EUS and imaging findings were highly suspicious for invasion. A broad differential diagnosis is under consideration for a duodenal mass that encompasses neoplasms of the biliary tract, pancreas, duodenum, and ampulla of Vater. To our knowledge, cytologic features of a pancreatobiliary neoplasm of the duodenum have not been previously reported. Our case highlights the features seen on cytology with histologic correlation in the hopes of elucidating features to better characterize these lesions.     

Diagnosis of metastatic pancreatic mesenchymal tumors by endoscopic ultrasound‐guided fine‐needle aspiration

Involvement of the pancreas by metastatic sarcoma is rare, and can prove challenging to differentiate from sarcomatoid carcinomas which occur more commonly. The endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA) technique has been successfully used for the diagnosis of pancreatic carcinomas whether primary or metastatic, and is now considered the most effective noninvasive method for the identification of pancreatic metastases. However, to date very few reports detail the diagnosis of mesenchymal neoplasms by EUS‐FNA. Herein, we report a series of four patients who underwent EUS‐FNA of the pancreas, where the diagnosis of metastatic sarcoma was made based on morphology and ancillary studies. The cases include metastases of leiomyosarcoma, liposarcoma, alveolar rhabdomyosarcoma, and solitary fibrous tumor. The history of a primary sarcoma of the chest wall, mediastinum, and respectively lower extremity was known for the first three of these patients while in the case of the solitary fibrous tumor a remote history of a paraspinal “hemangiopericytoma” was only elicited after the EUS‐FNA diagnosis was made. We conclude that EUS‐FNA is efficient and accurate in providing a diagnosis of sarcoma, even in patients without a known primary sarcoma, thus allowing institution of therapy without additional biopsies. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.     

Endoscopic ultrasound‐guided fine needle aspiration (EUS‐FNA) of mediastinal lymph nodes: Experience from region with high prevalence of tuberculosis

Utility of EUS‐FNA in diagnosing granulomatous lesions of mediastinum in regions with high prevalence of tuberculosis has not yet been evaluated. In the present study, utility and limitations of EUS‐FNA of mediastinal lesions from a tertiary care center with high prevalence of tuberculosis were studied. All cases where EUS‐FNA had been performed to diagnose mediastinal lymphadenopathy from January 2006 to December 2008 were retrieved from the files of cytopathology laboratory. These were reviewed by the cytopathologist. Two hundred and eighty one EUS‐FNA aspirates from 269 patients were evaluated. Satisfactory aspirates were available in 259 cases. A cytological diagnosis of granulomatous lymphadenitis was rendered in 206 cases. Of these, tuberculosis could be established as an etiology in 76 cases and sarcoidosis in 7 cases only. In remaining 123 cases the etiology of granulomatous lymphadenitis could not be established and clinical correlation was suggested. Malignancies were diagnosed or suspected in 24 and 5 cases, respectively. The study highlights that the dilemma of tuberculosis versus sarcoidosis persists in regions with high prevalence of tuberculosis. However, EUS‐FNA is useful in diagnosing unsuspected malignancies and confirming the presence of granulomatous lymphadenitis. Diagn. Cytopathol. 2013; 41:1019–1022.© 2011 Wiley Periodicals, Inc.     

EUS‐FNA diagnosis of pancreatic serous cystadenoma with the aid of cell blocks and α‐inhibin immunochemistry: A case series

Serous cystadenoma (SCA) is an uncommon benign pancreatic neoplasm that is most often managed conservatively with follow‐up rather than surgical excision. Therefore, to avoid the serious complications of pancreatic surgery, SCA should be diagnosed accurately at the preoperative level. Preoperative SCA diagnosis requires a multimodal diagnostic approach that includes imaging, cystic fluid biochemical analysis and/or endoscopic ultrasound fine‐needle aspiration (EUS‐FNA). In this brief report, we describe six EUS‐FNA cases from five patients that were reported as “benign, consistent with serous cystadenoma”. Samples were hypocellular, composed of loose clusters and single cuboidal, bland‐looking cells among epithelial sheets representing gastrointestinal contamination. Cell blocks were prepared and all six FNA cases revealed cuboidal cells with a positive α‐inhibin immunophenotype, consistent with a diagnosis of SCA. As EUS‐FNAs of SCA commonly result in non‐diagnostic interpretations, cell block preparations with subsequent immunochemistry can increase their diagnostic accuracy and guide patient management.     

Mediastinal ganglioneuroma diagnosed by transesophageal endoscopic ultrasound guided fine needle aspiration (EUS‐FNA)

Ganglioneuromas are rare benign tumors that arise from the sympathetic nerve fibers and represent the final maturation stage of neuroblast tumors. The most common sites of involvement in the body include posterior mediastinum, followed by retroperitoneum, adrenal gland, and soft tissues of the head and neck. In the mediastinum, this tumor is most frequently located in posterior compartment, together with other neurogenic tumors. The reports of mediastinal ganglioneuroma diagnosed by fine needle aspiration (FNA), especially endoscopic ultrasound‐guided FNA (EUS‐FNA) are very sparse. We describe the clinical, radiologic, cytologic, gross and histologic features of mediastinal ganglioneuroma diagnosed by transesophageal endoscopic ultrasound‐guided fine needle aspiration.     

NAB2‐STAT6 gene fusion and STAT6 immunoexpression in extrathoracic solitary fibrous tumors: the association between fusion variants and locations

Solitary fibrous tumor (SFT) is a rare mesenchymal neoplasm harboring NAB2‐STAT6 fusion, which drives STAT6 nuclear relocation. For extrathoracic SFTs, the clinical relevance of this molecular hallmark remains obscure. We assessed STAT6 immunoexpression for 61 extrathoracic SFTs exclusive of the meninges and head and neck, and 25 had analyzable RNAs to distinguish fusion variants by RT–PCR. The immunohistochemical and molecular findings were correlated with clincopathological features and disease‐free survival (DFS). Twenty‐eight males and 33 females had SFTs in the body cavities (n = 31), extremities (n = 17), and trunk (n = 13), categorized into 53 non‐malignant and 8 malignant tumors. The vast majority (n = 57, 93%) exhibited distinctive STAT6 nuclear expression, including malignant ones. The common fusion variants were NAB2ex6‐STAT6ex16/17 in 13 SFTs and NAB2ex4‐STAT6ex2 in 8, while miscellaneous variants were detected only in 4 SFTs in the limbs and trunk but not in any body cavity‐based cases (P = 0.026). The worse DFS was univariately associated with malignant histology (P = 0.04) but unrelated to tumor size, location, or fusion variant. Conclusively, extrathoracic SFTs mostly harbor NAB2ex6‐STAT6ex16/17, followed by NAB2ex4‐STAT6ex2. Miscellaneous variants are significantly rare in SFTs within the body cavities. The clinical aggressiveness of extrathoraic SFTs is associated with malignant histology but unrelated to the NAB2‐STAT6 fusion variants.     

Bilateral adrenal gland enlargement secondary to histoplasmosis mimicking adrenal metastases: Diagnosis with EUS‐guided FNA

While adrenal gland histoplasmosis has been previously diagnosed by fine needle aspiration utilizing the percutaneous approach, EUS‐FNA has not been employed in the diagnosis of this infection affecting both adrenal glands. We report a patient with massive bilateral adrenal enlargement due to histoplasmosis that was diagnosed by EUS‐FNA. Trans‐duodenal and trans‐gastric fine needle aspiration biopsy of both adrenal glands was performed. Rapid onsite cytopathologic evaluation (ROSE) revealed epithelioid histiocytes, singly and in clusters consistent with granulomas. Apparent intracytoplasmic inclusions suggestive of organisms were visible. A Gomori Methenamine Silver stain (GMS) revealed abundant small intracellular budding yeasts, morphologically consistent with Histoplasma; the patient was admitted for amphotericin B intravenous infusion. His fever abated on the second day after amphotericin B was started. His urine Histoplasma antigen was positive. Fungal cultures from both adrenal EUS‐FNA samples grew Histoplasma capsulatum. After a one week hospital stay, he was discharged home on itraconazole 200 mg po bid for one year. Four months after initiation of treatment, his urine Histoplasma antigen was undetectable. Nine months after initial diagnosis, the patient regained his energy level, and returned to work with complete resolution of his initial symptoms. This case highlights that EUS‐FNA with ROSE can be a highly effective tool in the diagnosis of uncommon infections of the adrenal glands. Diagn. Cytopathol. 2010. © 2009 Wiley‐Liss, Inc.     

Intriguing Case: Solitary Fibrous Tumor of the Mediastinum

A 62-year-old woman presented with an asymptomatic anterior mediastinal mass. Clinically considered to be a thymoma, the tumor was solid, firm, and composed of hypocellular dense collagen and cytologically bland, spindled fibroblastlike cells growing in a patternless pattern. There was no apparent connection to pleura or pericardium, yet the clinicopathologic features clearly fit with solitary fibrous tumor (SFT) of mediastinum. SFTs occur most commonly in pleura but have been reported in other locations, including the mediastinum, where aggressive behavior has been more common when these tumors are compared to those occurring in pleura. Although it is difficult to predict behavior for all cases of SFT occurring in the mediastinum by cytologic features alone, morphologic criteria for benign and malignant forms have been described. Roughly half the malignant forms will progress, yet the single most important indicator of clinical outcome is whether the tumor can be initially totally excised.     

Intriguing Case: Solitary Fibrous Tumor of the Mediastinum

A 62-year-old woman presented with an asymptomatic anterior mediastinal mass. Clinically considered to be a thymoma, the tumor was solid, firm, and composed of hypocellular dense collagen and cytologically bland, spindled fibroblastlike cells growing in a patternless pattern. There was no apparent connection to pleura or pericardium, yet the clinicopathologic features clearly fit with solitary fibrous tumor (SFT) of mediastinum. SFTs occur most commonly in pleura but have been reported in other locations, including the mediastinum, where aggressive behavior has been more common when these tumors are compared to those occurring in pleura. Although it is difficult to predict behavior for all cases of SFT occurring in the mediastinum by cytologic features alone, morphologic criteria for benign and malignant forms have been described. Roughly half the malignant forms will progress, yet the single most important indicator of clinical outcome is whether the tumor can be initially totally excised.     

Solitary fibrous tumor of the mediastinum.

A 62-year-old woman presented with an asymptomatic anterior mediastinal mass. Clinically considered to be a thymoma, the tumor was solid, firm, and composed of hypocellular dense collagen and cytologically bland, spindled fibroblastlike cells growing in a patternless pattern. There was no apparent connection to pleura or pericardium, yet the clinicopathologic features clearly fit with solitary fibrous tumor (SFT) of mediastinum. SFTs occur most commonly in pleura but have been reported in other locations, including the mediastinum, where aggressive behavior has been more common when these tumors are compared to those occurring in pleura. Although it is difficult to predict behavior for all cases of SFT occurring in the mediastinum by cytologic features alone, morphologic criteria for benign and malignant forms have been described. Roughly half the malignant forms will progress, yet the single most important indicator of clinical outcome is whether the tumor can be initially totally excised.     

Perivascular Epithelioid Cell Tumor (PEComa) of Pancreas Diagnosed Preoperatively by Endoscopic Ultrasound‐Guided Fine‐Needle Aspiration

Perivascular epithelioid cell tumors (PEComas) of the pancreas are extremely rare mesenchymal tumors and to our knowledge, only 17 cases have been reported in the English literature to date. We report our experience with a new case of primary pancreatic PEComa diagnosed preoperatively by endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA) complemented by tissue cell block and immunohistochemistry. The patient was a 54‐year‐old female whose chief complaint was intermittent severe right upper quadrant abdominal pain. Computed‐tomography (CT) imaging revealed a mass between the head and the body of the pancreas. EUS‐FNA smear preparation was obtained but was nondiagnostic. However, examination of the tissue cell block showed sheets of epithelioid cells with abundant eosinophilic cytoplasm and immunohistochemistry studies revealed positivity for both melanocytic (HMB‐45 and Melan‐A) and smooth muscle markers (actin and desmin). A diagnosis of PEComa was made and an uncomplicated middle pancreatectomy was performed. Our case and review of the literature demonstrates that EUS‐FNA complemented with tissue cell block increases cellular yield, improved preoperative diagnostic accuracy, and may assist the surgeon in planning conservative surgical management. Diagn. Cytopathol. 2017;45:59–65. © 2016 Wiley Periodicals, Inc.     

Fine‐needle aspiration cytology of epithelioid malignant peripheral nerve sheath tumor: A case report and review of the literature

The epithelioid variant of malignant peripheral nerve sheath tumor (eMPNST) is an extremely rare soft tissue neoplasm comprising less than 5% of all MPNSTs. It is distinguished cytomorphologically from a conventional MPNST by the presence of polymorphous round epithelioid cells arranged in loose clusters with or without spindled tumor cells. These features pose a diagnostic challenge because the differential diagnosis involves a variety of mesenchymal and non‐mesenchymal tumors including epithelioid sarcoma, sclerosing epithelioid fibrosarcoma, malignant rhabdoid tumor, chordoma, metastatic carcinomas, and melanoma. Thus, it may become imperative to perform immunochemical stains on cell blocks of FNA aspirates to arrive at definitive diagnosis. Reports describing the cytologic features of eMPNST are rare. Herein, we report a case of eMPNST with focus on cytomorphologic and cytoimmunochemical features and differential diagnosis. Diagn. Cytopathol. 2016;44:226–231. © 2015 Wiley Periodicals, Inc.     

The cytologic diagnosis of epithelioid myxofibrosarcoma: A case report

The epithelioid variant of myxofibrosarcoma is a rare but recently described entity. We report a case of an elderly woman who presented with a slowly enlarging mass of the right lower extremity. Fine-needle aspiration (FNA) cytology revealed a malignant epithelioid neoplasm. The smears of the aspirate material were highly cellular and contained a dominant population of cells with uniform round-to-oval nuclei and cytoplasmic vacuolization, arranged in loosely cohesive aggregates and linear arrays within a myxoid background. A second minor population of cells consisted of aggregates of bland spindled cells. On resection, the neoplasm proved to be an epithelioid myxofibrosarcoma. To our knowledge, the cytologic features of epithelioid myxofibrosarcoma have not previously been documented. Herein, we discuss the cytologic features of epithelioid myxofibrosarcoma as seen on FNA biopsy and its distinction from other epithelioid neoplasms of soft tissue. Diagn. Cytopathol. 2012. ? 2011 Wiley Periodicals, Inc.     

Cytopathologic diagnosis of esophageal glomus tumor presenting as an incidental posterior mediastinal mass in an 80‐year‐old male

Endoscopic ultrasound guided fine‐needle aspiration (FNA) of the upper gastrointestinal tract presents a diagnostic challenge to cytopathologists due to the broad differential diagnosis and morphologic overlap between various entities in this location. We report here an incidentally discovered case of esophageal glomus tumor presenting as a posterior mediastinal mass in an 80‐year old male. Glomus tumor is a rare soft tissue neoplasm with bland epithelioid morphology and cytoplasmic granularity. Literature review reveals only 6 published cases of esophageal glomus tumor in the general pathology literature. To our knowledge, this is the first report in the English literature to describe FNA cytology of an esophageal glomus tumor. This rare case presentation provides the opportunity to review the differential diagnosis for lesions of the upper gastrointestinal tract and their appearance on FNA in order to clarify an entity that is uncommon in everyday cytology practice. Diagn. Cytopathol. 2014;42:705–710. © 2013 Wiley Periodicals, Inc.     

Evidence‐based evaluation of the risks of malignancy predicted by thyroid fine‐needle aspiration biopsies

A National Cancer Institute (NCI) “Thyroid Fine‐Needle Aspiration (FNA) State of the Science Conference” recently proposed standardized nomenclature and “risks of malignancies” associated with various diagnostic categories. We evaluated the evidence levels of the data used by NCI to predict malignancy risks and whether those estimates had clinical validity in our patient population. Eight hundred seventy‐nine patients underwent thyroid FNA during 2006. FNA diagnoses were translated into NCI diagnostic categories, and 2‐year follow‐up retrospective information was obtained. Four percentages of malignancies were calculated for each diagnostic category using follow‐up information from FNA, thyroidectomy, both, and all patients as denominators. 95% confidence intervals (CI) were estimated for all proportions, and results were analyzed with chi‐square statistics. “Relative risk” calculations were performed using the percentage of malignancies in the entire population under study as a denominator. Most of the studies cited by the NCI provided incomplete and variable level III evidence based mainly on surgical follow‐up. Among our patients, the percentages of malignancies calculated with follow‐up data from all patients as the denominator were similar to the “risk estimates” proposed by the NCI, but estimates based on surgical follow‐up overestimated the probability of thyroid malignancy for patients with FNA diagnosis of “benign” and “follicular lesions of undetermined significance” (FLUS). Relative risk and 95% CI calculations suggested that the NCI classification could be simplified into three categories: “benign,” “FLUS + neoplasm,” and “suspicious + malignant.” Diagn. Cytopathol. 2010. © 2009 Wiley‐Liss, Inc.     

Endobronchial ultrasound‐guided transbronchial needle aspiration diagnosis of mediastinal lymph node metastasis of mucinous adenocarcinoma: Arborizing stromal meshwork fragments as a diagnostic clue

Endobronchial Ultrasound‐Guided Transbronchial Needle Aspiration (EBUS‐TBNA) is a reliable and accurate method for the diagnosis of mediastinal metastases in patients with pulmonary and extrathoracic neoplasms. We report the cytopathologic findings of a case of metastatic signet‐ring cell carcinoma with abundant extracellular mucin production in the mediastinal lymph nodes of a 41‐year‐old woman, who presented with nausea, abdominal pain, and weight loss. Imaging studies showed a renal mass, numerous lung nodules, and mediastinal and retroperitoneal lymphadenopathy. EBUS‐TBNA of level 4R and 7 lymph nodes showed abundant, thick, “clean” mucus with entrapped ciliated bronchial cells, rare histiocytes, and fragments of cartilage. No neoplastic cells could be identified in Diff‐Quik®‐stained smears during the rapid on‐site evaluation, but rare signet‐ring cells were identified in the Papanicolaou‐stained smears and cellblock sections. A distinctive feature of the aspirates was the presence of large branching (arborizing), “spidery” stromal fiber meshwork fragments. These stained metachromatically (magenta) with Romanowsky‐type stains and cyanophilic to orangeophilic with Papanicolaou stains and showed occasional attached bland spindle cells, but had no capillary lumina or CD31‐staining endothelial cells. The tumor cells were strongly and diffusely positive for CEA, CDX2, CK7, CK20, and MUC2, supporting the diagnosis of a metastatic signet‐ring cell adenocarcinoma, most likely of gastrointestinal origin. We believe that the presence of the large spidery stromal fiber fragments is a useful clue to the presence of a mucinous neoplasm in EBUS‐TBNA and allows the differentiation of the neoplastic mucus from contaminating endobronchial mucus. Diagn. Cytopathol. 2013;41:896–900. © 2012 Wiley Periodicals, Inc.