Brian T. Collins

Positron emission tomography scanning in the evaluation of hepatocellular carcinoma

BACKGROUND/AIMS 18F-fluorodeoxyglucose uptake allows estimation of glucose metabolism by tumor cells using positron emission tomography (PET). We evaluated the role of PET imaging in the diagnosis of hepatocellular carcinoma. METHODS PET images were collected after intravenous injection of 8-12 mCi of 18F-FDG in 20 patients with hepatocellular carcinoma (HCC). PET tumor activity level was assessed on a scale of 1 to 4 compared to normal liver tissue. The PET score was compared with abdominal computerized tomography (CT) scan results and between tumors of different grades and differentiation. RESULTS Of the 20 patients studied, 11 (55%) had positive PET scans (PET score: 3 or 4) while nine (45%) were negative (PET score: 1 or 2). CT scan was positive in 18 patients (90%) and negative in two (10%). PET, however, revealed metastases in three patients that were not seen on CT. On pathological review, well-differentiated and low-grade tumors had lower PET scores. Comparison of the well-differentiated with the moderately- and poorly-differentiated tumors revealed a statistically significant difference. No statistical significance was observed between the moderately- and poorly-differentiated tumors or between different tumor grades and PET scores. CONCLUSIONS The sensitivity of PET in diagnosis of HCC was 55% compared to 90% for CT scanning, although only PET detected some tumors (including distant metastases). Well-differentiated and low tumor grades had lower activity on PET and correspondingly lower PET scores. PET imaging may help assess tumor differentiation and may be useful in the diagnosis and staging and prognostication of HCC as an adjunct to CT.

Surveillance for recurrent head and neck cancer using positron emission tomography.

PURPOSE Earlier detection of head and neck cancer recurrence may improve survival. We evaluated the ability of [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET) to detect recurrence in a prospective trial using sequential PET scans. PATIENTS AND METHODS Serial posttherapy FDG-PET was prospectively performed in 44 patients with stage III or IV head and neck cancer. PET was performed twice during the first posttreatment year (at 2 and 10 months after therapy) and thereafter as needed. After therapy, patients were grouped, based on tissue biopsies, into those who achieved a complete response (CR) and those who had residual disease (RD). Patients who achieved a CR were further grouped into those without evidence of disease and those who had recurrence by 1 year after completion of therapy. Disease status as determined by physical examination (PE), PET, and correlative imaging was compared. RESULTS Eight patients were lost to follow-up and six had RD after therapy. Of the remaining 30 patients with a CR, 16 had recurrence in the first year after therapy. Five of these 16 patients had recurrence detected by PET only, four by PET and correlative imaging only, five by PE and PET only, and two by PE, correlative imaging, and PET. Only PET detected all recurrences in the first year. PET performed better than correlative imaging (P =.013) or PE (P =.002) in the detection of recurrence. CONCLUSION PET can detect head and neck tumor recurrence when it may be undetectable by other clinical methods. FDG-PET permits highly accurate detection of head and neck cancer recurrence in the posttherapy period.

Comparison of Liver Biopsy and Noninvasive Methods for Diagnosis of Hepatocellular Carcinoma

BACKGROUND & AIMS Current management guidelines for hepatocellular carcinoma (HCC) do not require biopsy to prove the diagnosis. We evaluated our experience of patients with liver disease and hepatic lesions suspicious for HCC who underwent both fine-needle aspiration and core biopsy and correlated the results with those from commonly used noninvasive approaches. METHODS We retrospectively reviewed the outcomes of a series of patients undergoing biopsy because of a suspicion of HCC and compared sensitivity, specificity, and predictive value of biopsy with existing noninvasive methods for diagnosing HCC. RESULTS HCC was diagnosed by biopsy in 74 (63%) of 118 cases, and an additional 10 were found to have HCC on follow-up. Patients with positive biopsy results had significantly higher serum alpha-fetoprotein levels (median, 57 vs 12; P = .014) than those with negative biopsies, although these 2 groups were otherwise similar with regard to tests of liver function, lesion size on imaging, and Child-Pugh class. No patient developed evidence of tumor spread along the needle track after biopsy. We compared the diagnosis of HCC by biopsy with noninvasive diagnostic criteria advocated by the European Association for the Study of the Liver and those used by the United Network for Organ Sharing. Compared with criteria of the European Association for the Study of the Liver and the United Network for Organ Sharing, biopsy had greater sensitivity, specificity, and predictive value. CONCLUSIONS We recommend a greater role for image-guided biopsy of lesions greater than 1 cm clinically suspicious for HCC to allow adequate treatment planning because the risks of biopsy appear small and the potential benefits significant. Obtaining material for both cytologic and histologic examination at biopsy maximizes the diagnostic yield.

Fine-needle aspiration of Merkel cell carcinoma of the skin with cytomorphology and immunocytochemical correlation

Merkel cell carcinoma (MCC) of the skin is a rare, primary malignant skin neoplasm which can present as a cutaneous nodule. These neoplasms are seen primarily in the elderly and located in the head and neck area or extremities. Twenty‐nine aspirates from primary and metastatic lesions obtained by percutaneous fine‐needle aspiration in 19 patients have been studied. The cytomorphologic features, clinical information, and immunocytochemical (ICC) findings are detailed. Aspirate smears demonstrated small‐to‐intermediate‐sized cells with a loosely cohesive pattern. Nuclei were round with finely granular chromatin and multiple, small nucleoli. Cells possessed a thin rim of cytoplasm, and infrequent pseudorosette formations were noted in cell groups. ICC results were universally positive for cytokeratin, which showed a paranuclear “dot‐like” pattern. Neuron‐specific enolase, epithelial membrane antigen, and S‐100 protein were positive in varying degrees. Leukocyte common antigen was universally negative. The diagnosis of MCC of the skin by FNA can be made by applying cytologic features in addition to ancillary studies and clinical information. Diagn. Cytopathol. 1998;18:251–257.

Malignant mediastinal lymphadenopathy detected by staging EUS in patients with pancreaticobiliary cancer

BACKGROUND In patients with pancreatic cancer, the presence of malignant mediastinal lymphadenopathy (MML) would preclude definitive resection. A recent study suggested routine evaluation for mediastinal lymph-node metastases in all patients being evaluated for pancreaticobiliary masses. In our practice, we routinely assess for mediastinal lymph-node metastases in all patients undergoing EUS for pancreaticobiliary cancer. METHODS We retrospectively evaluated the presence of MML by EUS-guided FNA (EUS-FNA) in 160 consecutive patients with a definite diagnosis of pancreaticobiliary cancer (pancreatic and periampullary cancers) who underwent EUS-FNA by a single operator from 2000 to 2004. Lymph nodes that were round and hypoechoic with sharp margins were considered suspicious and were sampled by FNA. RESULTS Of the 160 patients included in this study, 78 had peripancreatic lymph nodes (49%: 95% CI[41%, 58%]), 25 had celiac lymph nodes (16%: 95% CI[10%, 22%]), and 14 patients had mediastinal lymph nodes (9%: 95% CI[4%, 13%]) that were suspicious for malignancy by morphologic criteria. In 8 of 14 patients with suspicious mediastinal lymph nodes, FNA documented MML in 5%: 95% CI[2%, 8%]. Only one of these 8 patients with MML had other sites of documented distant metastases by CT and/or positron emission tomography scans. However, 7 of 8 patients had locally advanced cancers. CONCLUSIONS MML is detected by staging EUS-FNA in 5% of patients with pancreaticobiliary cancer. Because of its important implications, endosonographers should routinely assess for MML in patients who undergo staging EUS for pancreaticobiliary malignancy.

Telepathology in Cytopathology: Challenges and Opportunities

Objective: Telepathology in cytopathology is becoming more commonly utilized, and newer technologic infrastructures afford the laboratory a variety of options. The options and design of a telepathology system are driven by the clinical needs. This is primarily focused on providing rapid on-site evaluation service for fine needle aspiration. Study Design: The clinical requirements and needs of a system are described. Available tools to design and implement a telepathology system are covered, including methods of image capture, network connectivity and remote viewing options. Results: The primary telepathology method currently used and described involves the delivery via a network connection of a live video image to a remote site which is passively viewed by an internet web-based browser. By utilizing live video information and a voice connection to the on-site location, the remote viewer can collect clinical information and direct their view of the slides. Conclusions: Telepathology systems for use in cytopathology can be designed and implemented with commercially available infrastructure. It is necessary for the laboratory to validate the designed system and adhere to the required regulatory requirements. Telepathology for cytopathology can be reliably utilized by adapting existing technology, and newer advances hold great promise for further applications in the cytopathology laboratory.

Immunostaining as an Adjunct to Cytology for Diagnosis of Pancreatic Adenocarcinoma

BACKGROUND & AIMS Serial analysis of gene expression has helped identify several proteins that are expressed differentially in pancreatic cancer and are highly sensitive and specific for pancreatic adenocarcinoma. We evaluated if the diagnostic accuracy of pancreatic cancer from endoscopic ultrasound (EUS)-fine-needle aspiration (FNA) can be improved by combined evaluation of cytology and immunostaining with these markers. METHODS This study involved the use of archived specimens from patients treated at Saint Louis University Hospital from 2002 to 2006. We identified 5 protein markers that appeared most promising from published literature. We sequentially evaluated immunostaining with these markers in (1) surgical resection specimens, (2) cell blocks from EUS-FNA, and (3) direct smears of EUS-FN aspirates. Finally, we performed a combined evaluation of cytology and immunostaining in direct smears that were difficult to interpret and required a second consultative cytologic opinion. RESULTS In resection specimens, the majority of pancreatic adenocarcinomas expressed all 5 markers but fascin, maspin, and carcinoembryonic antigen-related cell adhesion molecule 6 also were expressed abnormally in normal pancreata and in chronic pancreatitis. Further evaluation therefore was limited to the other 2 markers: mesothelin and 14-3-3sigma. It was feasible and useful to perform immunostaining in cell blocks and direct smear for diagnosing pancreatic cancer. In cases requiring a second cytologic consultation, a combined evaluation of cytologic morphology and immunostaining had 90% accuracy for a pancreatic adenocarcinoma diagnosis. CONCLUSIONS In conclusion, immunostaining with newer protein markers is feasible in EUS-FNA specimens and can assist cytopathologists in diagnosing pancreatic cancer. Among the currently available protein immunomarkers, a combination of mesothelin and 14-3-3sigma seems most promising, but needs to be validated in prospective studies before routine clinical use.

DNA polymerase chain reaction using fine needle aspiration biopsy smears to evaluate non-Hodgkin's lymphoma.

OBJECTIVE To apply polymerase chain reaction (PCR) analysis to the fine needle aspiration biopsy (FNAB) evaluation of lymphoid proliferations. STUDY DESIGN We analyzed 37 consecutive archived FNAB malignant lymphoma specimens. Immunophenotypic data from the fine needle aspiration biopsy and excisional biopsy material was available for all specimens. PCR to identify monoclonal rearrangements of the immunoglobulin heavy chain gene, T-cell receptor and translocations involving the bcl-1 and bcl-2 genes was performed. RESULTS Seventy-eight percent of cases were detected by at least one of these assays. Where DNA analysis was performed on excisional biopsy material, 70% of the cases had identical results; no discordant results for the immunoglobulin heavy chain gene or T-cell receptor were found. In 23% of cases, after review of all available data, a discordant result was thought to be a consequence of a false negative result in DNA analysis of excisional biopsy material. CONCLUSION These findings indicate that PCR analysis of archived FNAB material, when necessary, provides useful information for diagnosis and staging of malignant non-Hodgkins lymphomas.

Fine Needle Aspiration Biopsy of Gastric Duplication Cysts with Endoscopic Ultrasound Guidance

OBJECTIVE To evaluate the ability of endoscopic ultrasound (EUS)-guided fine needle aspiration biopsy (FNAB) to diagnose gastric duplication cysts. STUDY DESIGN FNAB reports from the Department of Pathology, Saint Louis University Hospital, were retrospectively searched for reports of EUS-guided FNABs of the stomach. These reports were then reviewed to find instances in which gastric duplication cysts were diagnosed. The charts of patients diagnosed with gastric duplication cysts were reviewed. RESULTS Two patients were identified. The first was a 35-year-old, Caucasian male with an asymptomatic submucosal (versus extrinsic) gastric mass discovered during computed tomography of the abdomen. The second was a 44-year-old, Caucasian male with a history of treated low grade B cell lymphoma of mucosa-associated lymphoid tissue (MALToma) who was found to have an asymptomatic gastric wall abnormality by EUS when undergoing follow-up for the MALToma. Respiratory-type epithelial cells were present in each of these gastric duplication cysts. At this writing, both patients were being followed clinically and with imaging. CONCLUSION Gastric duplication cysts, particularly those that have respiratory-type epithelium, can be diagnosed by EUS-guided FNAB. The diagnosis of gastric duplication cysts by EUS-guided FNAB can preclude surgery, with its associated morbidity.

Pulmonary epithelioid hemangioendothelioma: report of a case with fine needle aspiration biopsy.

BACKGROUND Pulmonary epithelioid hemangioendothelioma (PEH) is a rare, low grade, malignant vascular tumor that typically presents with multiple pulmonary nodules in young women. This report details the cytopathologic and pathologic findings in an unusual case presenting in an older male with a pleural effusion, dominant nodule and multiple bilateral infiltrates. CASE A 62-year-old, male nonsmoker was referred due to increasing dyspnea. Chest radiography revealed a pleural effusion and nodular infiltrate in the right upper lobe of the bronchus. Thoracocentesis and thoracoscopy were performed, with a pleural drain inserted. Bronchoscopy revealed a right upper lobe bronchus occluded by a greyish, necrotic mass. Various cytopathologic sampling techniques, including fine needle aspiration biopsy, as well as traditional histopathologic biopsies were performed. Cytologic specimens showed loosely cohesive, epithelioid cells that were binucleated and multinucleated. Chromatin was granular, with scattered, small, multiple nucleoli with occasional, variably sized cytoplasmic vacuoles. The patients condition deteriorated, and he died 3 weeks after admission. CONCLUSION Pulmonary epithelioid hemangioendotheliomas are unusual neoplasms with a epithelioid, discohesive cellular appearance. It can mimic other, more commonly seen pulmonary neoplasms. Careful attention to cytomorphologic features and application of ancillary studies assist in making the diagnosis.