Roberto Logrono

Fine‐needle aspiration of thyroid nodules: A study of 4703 patients with histologic and clinical correlations

The Papanicolaou Society of Cytopathology recently proposed 6 diagnostic categories for the classification of thyroid fine‐needle aspiration (FNA) cytology. Using these categories, the experience with FNA from 2 institutions was studied with emphasis on cytologic‐histologic correlation, source of errors, and clinical management.

Clinical Impact of On-Site Cytopathology Interpretation on Endoscopic Ultrasound-Guided Fine Needle Aspiration

OBJECTIVES:Endoscopic ultrasound-guided fine needle aspiration (EUS-guided FNA) is becoming a preferred modality for diagnosing and staging GI and mediastinal malignancies. Although experts advocate on-site cytopathology assessment for tissue sample adequacy, there are few data to support this claim. Our goal was to determine whether on-site cytopathology interpretation improves the diagnostic yield of EUS-guided FNA.METHODS:EUS-guided FNA results from two university hospital centers were reviewed and compared. At center 1, where EUS-guided FNA was performed with a cytopathologist on site, the results of 108 consecutive patients were evaluated. At center 2, where a cytopathologist is unavailable, the results of 87 consecutive patients were reviewed. One endoscopist performed all procedures at both institutions. Cytologic diagnoses were categorized as positive or negative for malignancy, suspicious for malignancy, atypical/indeterminate, or unsatisfactory. The number of repeat procedures, needle passes, medication use, target site, age, and sex were compared between the two sites.RESULTS:Patients at center 2 were older (p = 0.04) and predominantly female (p = 0.03). Pancreas was the most common target site at center 2, whereas thoraco-abdominal nodes were the most common at center 1 (p = 0.0001). Patients at center 1 had a diagnosis of positive or negative for malignancy more frequently (p = 0.001) and were less likely to have an unsatisfactory specimen (p = 0.035) or repeat procedure, although the latter was not significant (p = 0.156)CONCLUSION:On-site cytopathology interpretation improves the diagnostic yield of EUS-guided FNA. EUS centers should allocate resources to cover for on-site cytopathology evaluation.

Recent advances in cell biology, diagnosis and therapy of gastrointestinal stromal tumor (GIST)

No abstract yet available.

Endoscopic sonographically guided fine-needle aspiration yield in submucosal tumors of the gastrointestinal tract.

Objective. To study the yield of endoscopic ultrasonographically guided fine‐needle aspiration cytologic examination in the diagnosis of submucosal masses. Methods. From 1999 to 2003, 10 patients underwent ultrasonographically guided fine‐needle aspiration for the cytologic diagnosis of submucosal masses in our institution. The endoscopic ultrasonography records and the cytology database were consulted, and the reports were analyzed, as were slide material and the technical aspects related to these procedures. All procedures were performed under conscious sedation and cardiorespiratory monitoring on an outpatient basis. Ten patients (4 men and 6 women; mean age, 60.8 years) were studied. Results. Eight lesions were located in the stomach, and 2 were located in the esophagus, with a mean diameter of 3.3 cm. An experienced cytopathologist was present on‐site during all procedures for assessment of adequacy and preliminary cytologic examination. Cytologic diagnoses were obtained in 8 cases as follows: 6 gastrointestinal stromal tumors, 1 organizing submucosal hematoma, and 1 low‐grade mucosa‐associated lymphoid tissue–associated lymphoma. Two cases consisted of scant gastric epithelium only and were considered nondiagnostic. The cytologic diagnoses guided further clinical treatment. Conclusions. Ultrasonographically guided fine‐needle aspiration with cytopathologic analysis has a high accuracy rate (80%) for diagnosing submucosal lesions. These findings potentially affect clinical decision making.

Synergistic interaction of hyperthermia and gemcitabine in lung cancer

Hyperthermia increases cytotoxicity of various antineoplastic agents. We investigated the cytotoxic effects of Gemcitabine and/or hyperthermia on BZR-T33 (human non-small-cell lung cancer cells) in vitro and in immune-suppressed athymic nude mice. Isobologram analysis of monolayer cell cultures for cytotoxicity demonstrates a synergistic interaction between hyperthermia and Gemcitabine. Clonogenic results show significant reductions in surviving fractions and colony size for both therapies; greatest reduction was for the combined therapy group. Using cell cycle analysis, hyperthermia enhanced Gemcitabine-induced G2-M arrest resulting in destruction of 3.5 log cells. Apoptotic studies (Annexin-V FITC staining) showed that hyperthermia augmented Gemcitabine-induced apoptosis. Transmission electron microscopy demonstrated pathology observed in cultures exposed to either therapy present in cultures exposed to both therapies. Studies in nude mice show that the combination therapy group had both an initial decrease in tumor size, and a significantly delayed rate of growth. Additionally, using tumor material harvested from nude mice two days after end to treatment reveals a significantly greater apoptotic index and significantly smaller mitotic index for the combined therapy group. Western blots of the same tumor material, showed that heat shock protein 70 was not significantly increased, however, caspase-3 activity of was significantly increased because of the combined therapy. In conclusion, the combined therapy is synergistic in effect because of hyperthermia enhancing Gemcitabine-induced apoptosis.

Regulation of lung cancer cell growth and invasiveness by β-TRCP†

Beta‐transducin‐repeat‐containing protein (β‐TRCP) serves as a substrate‐recognition subunit of Skp1/Cullin/F‐box (SCF)β‐TRCP E3 ligases, involved in regulation of several important signaling molecules. SCFβ‐TRCP E3 ligases play a critical role in cell mitosis as well as in various signaling pathways. Here, we provide evidence to support that β‐TRCP negatively regulates cell growth and motility of lung cancer cells. With specific antibodies, we detect loss of β‐TRCP1 protein in several lung cancer cell lines. One cell line contains an inactivated mutation of the β‐TRCP1 gene. Loss of β‐TRCP1 protein is also found in subsets of lung cancer specimens. We observe that retrovirus‐mediated stable expression of β‐TRCP1 in β‐TRCP1 negative cells inhibits cell growth in soft‐agar and tumor formation in nude mice. Furthermore, expression of β‐TRCP1 alters cell motility, as indicated by morphological changes and a reduced level of active matrix metalloproteinase (MMP)11. Conversely, inactivation of β‐TRCP1 by specific siRNA accelerates cell invasion. Of the 10 known substrates of SCFβ‐TRCP E3 ligases, the protein level of cell division cycle 25 (CDC25)A is clearly affected in these lung cancer cells. Cells treated with CDC25A inhibitors become less invasive. Thus, loss of β‐TRCP1 may promote both growth and cell motility of lung cancer cells, possibly through regulation of CDC25A and the MMP11 level.

Serous cystadenoma of the pancreas with papillary features: A diagnostic pitfall on fine-needle aspiration biopsy

Serous cystadenoma of the pancreas is an uncommon neoplasm that occasionally exhibits papillary differentiation. The cytomorphologic structure of pancreatic serous cystadenoma has been rarely described, and, to our knowledge, such papillary morphologic structure has never been reported on fine-needle aspiration cytologic examination. We present a case of serous cystadenoma of the pancreas in a 77-year-old woman. Endoscopic ultrasonography showed a well-demarcated solid/cystic mass in the midbody of the pancreas, suggestive of solid pseudopapillary tumor. Aspiration cytologic examination, performed under endoscopic ultrasound guidance, showed a predominantly papillary epithelial neoplasm consistent with the radiologic impression. Gross and histologic examination of the excised specimen revealed a pancreatic serous cystadenoma with multifocal papillae. This case illustrates the cytomorphologic structure of serous cystadenoma that presents with prominent papillary differentiation on aspiration cytologic examination. The unusual cytologic appearance of this tumor introduces significant diagnostic challenges to the pathologist. Serous cystadenoma must be included in the differential diagnosis of pancreatic neoplasms with papillary morphologic structure as evaluated by fine-needle aspiration cytologic examination.

Fine needle aspiration cytology of hepatobiliary cystadenoma with mesenchymal stroma

Hepatobiliary cystadenomas (HBCs) with mesenchymal stroma (MS) are rare cystic neoplasms occurring exclusively in women. Hepatobiliary cystadenoma consists of a mucin‐producing cyst lining epithelium underlined by a dense MS cell layer. In the current study, the authors review the fine needle aspiration cytology of HBC with MS and identify characteristic cytologic features that suggest such an uncommon neoplasm on aspirates.

Fine-needle aspiration cytology of hemangiopericytoma: report of two cases.

The fine‐needle aspiration biopsy (FNAB) findings in two cases of hemangiopericytoma (HP), arising in the parotid gland and on the inner chest wall, respectively, are reported. Smear preparations in each case showed cytologic features of an undifferentiated spindle‐cell neoplasm, whereas a core needle biopsy specimen of the chest wall mass showed a spindle‐cell tumor with a “staghorn‐like” arrangement of endothelium‐lined vascular channels. Immunostains performed on this core biopsy, and on the surgical resection specimens in both cases, showed positive staining of tumor cells for vimentin and CD34, with negative staining for a variety of smooth muscle, epithelial, neural, and neuroendocrine markers. Electron microscopy performed in one case further supported the diagnosis of HP. With adequate sampling and appropriate use of ancillary studies, a diagnosis of HP can be reliably suggested on the basis of FNAB and core biopsy of a soft‐tissue mass. Diagn. Cytopathol. 2000;23:187–191.

Microcystic adenoma of the pancreas: Cytologic appearance on percutaneous and endoscopic ultrasound-guided fine-needle aspiration: Report of a case

Microcystic adenoma is an uncommon neoplasm of the pancreas usually affecting older people. Its histologic features have been well characterized. The cytologic appearance of this tumor has been described only rarely, however. Microcystic adenomas may enlarge considerably and often produce symptoms related to their compression to adjacent anatomic structures. The fact that this neoplasm is almost always benign indicates the need for accurate preoperative diagnosis to differentiate it from other, more common, malignant or potentially malignant tumors of the pancreas. We present a case of pancreatic microcystic adenoma initially diagnosed by percutaneous image‐guided fine‐needle aspiration cytologic examination and core biopsy and further evaluated by endoscopic ultrasound‐guided fine‐needle aspiration on follow‐up. This case report illustrates that microcystic adenoma of the pancreas can be accurately diagnosed by aspiration cytology. Fine‐needle aspiration—percutaneous, guided by computerized tomography, or endoscopically guided by ultrasonography—constitutes a reliable and cost‐efficient diagnostic tool associated with minimal trauma to the patient. Diagn. Cytopathol. 1998;20:298–301.