Stefan E. Pambuccian

Atypical teratoid/rhabdoid tumor of the brain: Cytopathologic characteristics and differential diagnosis

Atypical teratoid/rhabdoid tumor (AT/RT) is a highly aggressive neoplasm with a unique cytogenetic profile. Although the clinicopathologic and radiologic features of AT/RT have been described previously, to the authors knowledge the cytomorphologic profile of this tumor has not been studied well.

Significance of benign endometrial cells in papanicolaou tests from women aged ≥ 40 years

The 2001 Bethesda System recommends reporting benign endometrial cells (BECs) in women aged ≥ 40 years and considers these women at risk for endometrial pathology. The current study examines the relative risk of hyperplasia or malignancy conferred by the presence versus the absence of BECs in Papanicolaou (Pap) tests of women aged ≥ 40 years.

Adrenal extranodal NK/T-cell lymphoma diagnosed by fine-needle aspiration and cerebrospinal fluid cytology and immunophenotyping: A case report

The cytologic findings of an extranodal NK/T‐cell lymphoma (NKTCL) presenting as a large adrenal mass with leptomeningeal involvement diagnosed by CT‐guided fine‐needle aspiration and cerebrospinal fluid (CSF) cytology are described. The 65‐year‐old Caucasian patient presented with progressive headache and multiple cranial nerve neuropathies. Magnetic resonance imaging showed leptomeningeal enhancement surrounding the conus medullaris and cauda equine, and a subsequent PET/CT demonstrated a large right adrenal gland mass. Fine‐needle aspiration of the adrenal mass showed occasional large pleomorphic cells with prominent nucleoli, moderate amounts of cytoplasm, and rare large cells with sparse cytoplasmic granules admixed with numerous small lymphocytes. Initial flow cytometry from this sample showed no clonal B‐cell population. Immunoperoxidase stains performed on the cell block/core specimen showed that the large atypical cells were positive for CD2, CD30, CD43 and CD56, TIA‐1, granzyme, and perforin, but for none of the other T‐cell markers used (CD3, CD4, CD5, CD8, CD45RO), which stained the abundant background lymphocytes. A CSF specimen showed similar neoplastic cells and flow cytometry showed an NK‐cell population with aberrant immunophenotype. The cytologic findings of the neoplastic cells and the extensive panel of immunoperoxidase stains allowed the diagnosis of NKTCL, which was confirmed by the subsequent flow‐cytometric immunophenotyping performed on the CSF. This is, to the best of our knowledge, the first case of NKTCL diagnosed by FNA of the adrenal gland and by CSF cytology. Diagn. Cytopathol. 2009.

Endoscopic ultrasound-guided fine-needle aspiration diagnosis of clear-cell pancreatic endocrine neoplasm in a patient with von Hippel-Lindau disease: A case report

The cytologic findings of a clear‐cell pancreatic endocrine neoplasm (PEN) diagnosed by endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA) occurring in a 29‐year‐old man with von Hippel‐Lindau (VHL) syndrome are described. Imaging studies showed multiple pancreatic masses and cysts, a single liver lesion, and pulmonary and renal cysts. Cytologic features of this clear‐cell PEN included the presence of large sheets and rounded clusters of polygonal neoplastic cells with relatively abundant cytoplasm containing numerous, small, sharply‐demarcated vacuoles that occasionally indented nuclei and gave the cells a “frothy” appearance. Mild anisonucleosis was present and nucleoli were visible. Rare single cells and stripped nuclei were seen. Small vessels transgressed tumor cell sheets. These cytologic findings are distinct from those of typical endocrine neoplasms, and bear resemblance to the cytologic features of renal cell carcinoma metastatic to the pancreas. To the best of our knowledge, this is the first detailed report of the EUS‐FNA cytologic findings of a clear‐cell PEN associated with VHL syndrome. We believe that the distinctive and characteristic cytologic features, together with immunohistochemical studies, can allow a preoperative cytologic diagnosis of this highly unusual pancreatic lesion and avoid possible confusion with other clear‐cell neoplasms in the pancreas, particularly metastatic renal cell carcinoma. Diagn. Cytopathol. 2009.

Cytology of metastatic cervical squamous cell carcinoma in pleural fluid: Report of a case confirmed by human papillomavirus typing

Cervical squamous cell carcinomas are rarely the cause of malignant effusions. Their identification can be relatively easy when keratinizing atypical squamous cells are present, but may be very difficult when only nonkeratinizing malignant cells are present. We present the case of a 47‐year‐old woman who presented with a large left pleural effusion after having recently completed chemoradiation therapy for stage IIB cervical squamous cell carcinoma. Cytologic examination of the fluid showed a uniform population of single atypical cells with finely vacuolated cytoplasm, ectoendoplasmic demarcation, cell‐in‐cell arrangements, and short rows of cells with intervening “windows,” all features reminiscent of mesothelial cells. No keratinization or three‐dimensional cell clusters were identified. A panel of immunohistochemical stains was performed on the cell block material, and the atypical cells were positive for cytokeratin 5/6, p63, and p16 but not for cytokeratin 7, calretinin, WT1, or Ber‐EP4 or TTF1. These findings were consistent with metastatic squamous cell carcinoma. HPV DNA determination and typing by PCR confirmed the presence of HPV16 in an aliquot of pleural fluid. This is to our knowledge the first reported case of pleural fluid involved by metastatic squamous cell carcinoma where HPV DNA testing was used to confirm the origin of the metastasis. Despite its rarity, metastatic nonkeratinizing squamous cell carcinoma should be considered when a single cell population of large atypical cells is found in effusions. Immunoperoxidase stains and HPV testing can be performed to establish the diagnosis and confirm the origin from a cervical primary. Diagn. Cytopathol. 2009.

Epithelioid angiosarcoma of the kidney: a diagnostic dilemma in fine-needle aspiration cytology.

Epithelioid angiosarcomas (EAS) of kidney are rare and aggressive tumors with noncharacteristic imaging features that overlap with those of inflammatory conditions and renal cell carcinoma (RCC). We report the fine‐needle aspiration (FNA) cytology findings of a case of EAS that involved the left kidney of an 83‐year‐old male. The smears and cell block sections showed pleomorphic epithelioid cells with ample cytoplasm, eccentric nuclei, occasional cytoplasmic hyaline globules, and rare intracytoplasmic lumina. Immunohistochemical stains performed on cellblock sections showed that the tumor cells were positive for vimentin, CD31, CD34, Factor VIII, and CD10, but showed no staining for cytokeratins AE1/AE3 and 8/18, HMB45, CD45, smooth muscle actin, and S100. The morphological and immunohistochemical distinction between EAS, primary tumors of the kidney, and other epithelioid and rhabdoid neoplasms is discussed. Diagn. Cytopathol. 2012.

Paracoccidioides brasiliensis in a liquid-based Papanicolaou test from a pregnant woman: report of a case.

With the exception of Candida species, fungal organisms are rarely encountered in the Papanicolaou test and, when encountered, usually represent contaminants rather then infections. We present the case of a healthy 29‐year‐old pregnant female, gravida 1, para 0, who presented for her first prenatal visit at 12‐week gestation and had many large fungal‐like elements with a distinct budding pattern of multiple narrow‐based buds resembling a “ships‐wheel” identified in her routine liquid‐based Papanicolaou test. Based on its characteristic appearance in the Papanicolaou test and the hematoxylin and eosin, periodic acid Schiff and Gomoris methenamine silver stains performed on the cell block made from the residual sample, the fungus was diagnosed as “consistent with Paracoccidioides.” This is the second reported case of Paracoccidioides presenting in a Papanicolaou test and shows that this organism may rarely involve the uterine cervix in the absence of clinical systemic disease. Diagn. Cytopathol. 2008; 36: 557–560.

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. Diagn. Cytopathol. 2013;41:1091–1095.

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. Diagn. Cytopathol. 2013;41:661–672.

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.