Pembrolizumab induced pericardial tamponade: A case report.

Key Clinical Message: The occurrence of a large pericardial effusion is not a commonly noted adverse event associated with pembrolizumab and our report demonstrates that a rapid development can be diagnosed with close monitoring and triage to acute medical settings. Abstract: Pembrolizumab is an immune checkpoint inhibitor used in various types of cancers. Pericardial tamponade is a rare side effect reported in only very few case reports. Early recognition and therapeutic intervention is vital in all cases. We report a case of a 54-year-old male with Stage 3 lung adenocarcinoma who developed cardiac tamponade secondary to pembrolizumab and subsequently required pericardial window.

Cardiac Amorphous Tumour (CAT) Presenting with Thrombocytopenia.

Cardiac calcified amorphous tumour (CAT) is a rare non-neoplastic lesion with only a few cases reported in literature. We present an interesting case of CAT that was associated with unexpectedly low platelet count. A 40-year man presented with shortness of breath on exertion. Echocardiogram showed a mobile mass within the right atrium. Mass was surgically excised. His platelet count varied from 26,000/ul to 54,000/ul before surgery, which increased postoperatively. Histopathological examination revealed amorphous mass of eosinophilic fibrin with dense calcification. No morphologic evidence of myxoma was seen and the final diagnosis of CAT of the heart was rendered. CAT is a rare cardiac lesion with an excellent prognosis after complete surgical removal. The microscopic examination is the only tool for definitive diagnosis.

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.

Cercariform cells: another cytologic feature distinguishing solid pseudopapillary neoplasms from pancreatic endocrine neoplasms and acinar cell carcinomas in endoscopic ultrasound-guided fine-needle aspirates.

BACKGROUND: Solid pseudopapillary neoplasm (SPPN) is a rare tumor of unknown origin that occurs predominantly in the body or tail of the pancreas in young women. The authors recently identified cercariform (Greek: tailed) cells, similar to those described in urothelial carcinomas, as a consistent cytologic feature in ultrasound-guided fine-needle aspiration (EUS-FNA) samples from SPPNs. The objective of the current multi-institutional study was to define the value of these cells in the differential diagnosis of SPPN with other neoplasms characterized cytologically by the presence of monotonous, uniform cells in pancreatic aspirates: pancreatic neuroendocrine tumors (Pan-NETs) and acinar cell carcinomas (ACCs). METHODS: The files of 4 academic hospitals were searched for SPPNs, Pan-NETs, and ACCs that were diagnosed by EUS-FNA. The slides were reviewed, and several cytologic features were recorded semiquantitatively to identify discriminating features between SPPNs, Pan-NETs, and ACCs. RESULTS: From the analysis of 18 SPPNs, 4 ACCs, and 20 Pan-NETs, the following cytologic features were identified as common to all 3 neoplasms: single cells and rosettes/acinar cell groups, round-to-plasmacytoid cells, pale-to-granular cytoplasm, fine vacuoles, and binucleated cells. Papillary structures, cercariform cells, large cytoplasmic vacuoles, reniform nuclei, hyaline globules/magenta-colored material, and degenerative features (cholesterol crystals, calcifications, foam cells, or giant cells) were significantly more common in SPPNs. Prominent nuclear grooves were encountered in only 4 of 18 SPPNs. CONCLUSIONS: The current results indicated that the presence of cercariform cells is another useful clue for the cytologic diagnosis of SPPN in challenging cases.

Follicular lymphoma transformed to "double-hit" B lymphoblastic lymphoma presenting in the peritoneal fluid.

Lymphomas showing both MYC/8q24 rearrangement and IGH@BCL2/t(14;18)(q32;q21), also referred to as "double-hit" or "dual-hit" lymphomas (DHL) are rare B-cell malignancies with a germinal center B-cell immunophenotype and heterogeneous cytologic and histologic features. Such lymphomas may arise de novo or through transformation of follicular lymphomas and are classified either as "B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL)" (most commonly), DLBCL, or, rarely, as B-lymphoblastic lymphoma. We report a case of B-lymphobastic lymphoma arising through transformation of follicular lymphoma diagnosed on peritoneal fluid cytology, flow cytometry, and cytogenetic studies in a 53-year-old man who presented with abdominal pain, shortness of breath, night sweats, extensive lymphadenopathy, pleural effusion, and ascites. Cytologic examination of the ascitic fluid showed two distinct populations of neoplastic lymphoid cells, a predominant population of larger cells with fine powdery ("blastic") chromatin, visible to prominent nucleoli and occasional small cytoplasmic vacuoles and a less numerous population of smaller cells with centrocytic morphology. Flow cytometry also showed two distinct monotypic B-cell populations, both expressing CD10, and TdT-positivity was demonstrated immunohistochemically. Fluorescence in situ hybridization (FISH) demonstrated both MYC rearrangement and IGH/BCL2 gene fusion and cytogenetic analysis showed a complex karyotype including both t(14;18)(q32;q21) and t(8;22)(q24.1;q11.2). Since DHL pursue an aggressive clinical course, respond poorly to therapy, and have a poor outcome, it is important to suspect the diagnosis when encountering neoplastic lymphoid cells that are difficult to classify in effusion cytology specimens and to order the appropriate immunophenotyping and cytogenetic studies.

Endoscopic ultrasound-guided fine-needle aspiration diagnosis of large cell neuroendocrine carcinoma of the gallbladder and common bile duct: report of a case.

Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) allows a reliable and accurate diagnosis of neoplasms of the gallbladder and bile ducts. We report the cytopathologic findings of a case of large cell neuroendocrine carcinoma (LCNEC) of the gallbladder and extrahepatic bile ducts in a 67-year-old woman who presented with progressive abdominal pain and jaundice. EUS-FNA of the mass involving the common bile duct and of a porta hepatis lymph node showed abundant cellularity with tumor cells arranged singly and occasionally in tight and loose clusters and rosette-like structures in a background showing extensive necrotic debris. The tumor cells were predominantly plasmacytoid, showed a moderate amount of focally vacuolated cytoplasm and large round to oval hyperchromatic nuclei with prominent nucleoli, numerous mitoses, and apoptotic bodies. The differential diagnosis included poorly differentiated adenocarcinoma, lymphoma, melanoma, and poorly differentiated neuroendocrine carcinoma (NEC), large cell type. The tumor cells were strongly and diffusely positive for cytokeratin AE1/AE3, CD56, synaptophysin, and chromogranin and showed a very high proliferative fraction on Ki67 staining, supporting the diagnosis of a high-grade NEC. Due to the large size of the neoplastic cells, moderate amounts of cytoplasm and prominent nucleoli, a diagnosis of LCNEC was made on the EUS-FNA sample. Despite the prompt institution of chemotherapy, the patient died shortly thereafter and the diagnosis was confirmed at autopsy. This is to our knowledge the first case of LCNEC of the gallbladder and bile ducts diagnosed by EUS-FNA.

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.

Large platelet aggregates in endoscopic ultrasound-guided fine-needle aspiration of the pancreas and peripancreatic region: a clue for the diagnosis of intrapancreatic or accessory spleen.

Intrapancreatic and intraabdominal accessory spleens (IPIASs) are rarely encountered in endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) biopsies. However, as incidentally discovered IPIAS can mimic a benign or malignant pancreatic neoplasm on imaging studies, a definitive diagnosis made by EUS-FNA can avert an unnecessary surgical intervention or additional radiologic follow-up. We report five cases of intrapancreatic splenules and one case of accessory spleen (AS) in which a definitive diagnosis was made on EUS-FNA. Previously recognized FNA cytomorphologic features of splenic tissue, including ASs and splenosis, are endothelial cells and polymorphous lymphocytes admixed with neutrophils, eosinophils, plasma cells, histiocytes, and lymphoglandular bodies. We describe the additional finding of abundant large platelet aggregates as another distinguishing feature of splenic tissue on FNA. In all six cases, large platelet aggregates were identified along with polymorphous lymphoid cells, lymphoglandular bodies, loose aggregates of endothelial cells and scattered or aggregated bland spindle cells. A review of 10 consecutive cases of EUS-FNA-sampled benign intraabdominal lymph nodes showed that the presence of large platelet aggregates, three-dimensional aggregates of lymphoid cells and of bland slender spindle cells and the absence of follicular germinal cell components (tingible body macrophages and lymphohistiocytic aggregates) are useful in differentiating IPIASs from reactive lymph nodes. Immunoperoxidase stains were useful to confirm a suspected IPIASs by showing CD31-positive acellular flocculent material, consistent with large platelet aggregates and a rich CD8-positive endothelial cell network between CD45-positive lymphoid cells and CD68-positive histiocytes in all six cases.