Characteristics of chronic hepatitis B patients who underwent liver biopsies.

Significant liver disease has been reported in chronic hepatitis B patients with normal alanine aminotransferase (ALT) but most studies performed biopsies on selected patients only. The aims of this study were to determine the rate of liver biopsy, characteristics of patients who underwent a biopsy and factors associated with significant liver disease in a cohort of such patients. Records of patients with chronic hepatitis B during a 10-year period were reviewed. Significant liver disease was defined as Knodell HAI ≥ 7 and/or Ishak fibrosis ≥ 3. Of 743 patients, 55.7% were Asian, 56.4% were men, and the mean age was 43.1 years. One hundred and ninety-three (26%) had undergone a biopsy. Biopsied patients were more likely to be men, HBeAg positive, and had lower platelet and higher alkaline phosphatase, bilirubin, ALT and hepatitis B virus (HBV) DNA. Significant liver disease was observed in 20% of patients who had normal ALT at presentation, 14% of those with normal ALT at the time of biopsy and in none of the patients with persistently normal ALT. Patients with normal ALT who were biopsied had higher HBV DNA and higher ALT than those not biopsied. Multivariate analysis showed that low albumin at the time of biopsy and HBV DNA >5 log(10) copies/mL were predictors of significant liver disease. Significant liver disease is rare in patients with chronic HBV and persistently normal ALT and liver histology of chronic HBV infected patients with normal ALT cannot be generalized to other patients with normal ALT that were not biopsied.

HER-2/neu gene amplification by FISH predicts poor survival in Barrett's esophagus-associated adenocarcinoma.

The HER-2/neu oncogene is localized to chromosome 17q and shares significant homology with the epidermal growth factor receptor. HER-2/neu protein overexpression has been associated with poor prognosis in a variety of tumors, but its significance in Barrett's esophagus-associated adenocarcinoma (BEAd) is unknown. Therefore, the aim of this study was to evaluate the prevalence and prognostic value of HER-2/neu gene amplification by fluorescence in situ hybridization (FISH) in 63 cases of BEAd. Routinely processed tissue sections from resection specimens of 63 patients with BEAd (M/F ratio, 10:1; mean age, 63 years) were assayed for HER-2/neu gene amplification by FISH using the Ventana unique sequence probe (Ventana Medical Systems, Inc, Tuscon, AZ). FISH results were correlated with the pathological features of the tumors and with patient survival. Clinical follow-up data were available for 54 patients (mean follow-up, 31 months [range, 1 to 152 months]). The HER-2/ neu gene was amplified in 12 of 63 (19%) cases. The presence of HER-2/neu gene amplification showed a trend toward a correlation with depth of tumor invasion (P = .07), lymph node metastasis (P = .13), and pathological stage (P = .14), but did not correlate with any of the other pathological features, such as degree of differentiation or tumor size. On both univariate and multivariate analysis, HER-2/neu gene amplification was associated with shortened survival (P = .03). HER-2/neu oncogene amplification, as determined by FISH, correlates with shortened patient survival and independently predicts poor outcome in patients with BEAd.

Bronchioloalveolar carcinoma in a child with congenital cystic adenomatoid malformation.

An 11-year-old girl was evaluated for chest pain, and chest radiographic findings of multiple nodules throughout both lungs. She underwent resection of several of the lesions from her left lung, which were found at pathologic examination to be bronchioloalveolar carcinoma. Her previous medical history included incomplete resection of a type I congenital cystic adenomatoid malformation in the neonatal period. To our knowledge, this girl is the youngest reported case of bronchioloalveolar carcinoma in a nonimmunocompromised patient, and one of several in which the association of congenital cystic adenomatoid malformation and bronchioloalveolar carcinoma has been observed.

Ectopic creatine kinase MB production in metastatic cancer.

This case concerns the presence of high serum levels of creatine kinase MB isoenzyme in a patient with metastatic cancer. This patient did not have a myocardial infarction, so the source of the CK-MB was investigated. Because of the observation of macro-creatine kinase in patients with cancer, it was necessary to rule out the presence of this form of the enzyme. Extensive laboratory analysis demonstrated that the isoenzyme was true CK-MB, not an atypical or macro CK. Results of the study showed that ectopic production of the isoenzyme was the apparent source of the high serum activity. Homogenization of the cancer tissue demonstrated the presence of a high percentage of CK-MB activity. The implications of CK-MB production in cancer are discussed, including the use of various technics to rule out interfering activities when situations such as this occur.

Fine-needle aspiration of secondary neoplasms involving the salivary glands. A report of 36 cases.

Metastases or secondary deposits account for 16% of the malignant neoplasms involving the major salivary glands. A correct diagnosis of a secondary neoplasm is important to avoid unnecessary radical surgery and to guide further therapy. Fine-needle aspiration biopsy (FNAB) is an excellent noninvasive diagnostic tool for evaluating salivary gland lesions. We reviewed 36 secondary malignant salivary gland neoplasms evaluated by FNAB. Ancillary studies were performed in selected cases. Follow-up included clinical correlation and review of histologic material. For 4 adenocarcinomas, 4 squamous cell carcinomas, 1 undifferentiated carcinoma, 1 cutaneous basal cell carcinoma, 10 cutaneous melanomas including 1 desmoplastic variant, 3 osteosarcomas, 11 non-Hodgkin lymphomas, and 2 multiple myelomas, there was 1 false-negative FNAB result. The desmoplastic melanoma was interpreted as reactive lymphoid hyperplasia. A malignant diagnosis was given in all remaining cases except the secondary basal cell carcinoma, which was diagnosed as a neoplasm with basal cell features. FNAB is a reliable tool to differentiate hematologic malignant neoplasms and melanomas from other salivary gland neoplasms. A complete knowledge of the clinical history, review of previous pathologic materials, and, in some instances, the use of ancillary studies are crucial for recognizing solid malignant neoplasms secondarily involving the salivary glands.

Second primary Barrett's adenocarcinoma after 19 years.

Because long survival after resection of esophageal carcinoma is uncommon, second esophageal cancers are rare. We report the case of a patient in whom adenocarcinoma developed within residual Barrett's esophagus 19 years after esophagectomy for stage IIb Barrett's adenocarcinoma. Implications relative to the type of operation and adequacy of resection are discussed. Long-term survival after Barrett's adenocarcinoma may occur more often if surveillance protocols achieve their aim. Questions concerning the management of such patients are identified.

Utility of fine-needle aspiration in the diagnosis of salivary gland lesions in patients infected with human immunodeficiency virus.

Fine-needle aspiration (FNA) has been increasingly utilized as a diagnostic tool in evaluating salivary gland masses, primarily to differentiate nonneoplastic from neoplastic lesions. Patients infected with human immunodeficiency virus (HIV) frequently present with salivary gland lesions. In this study, we reviewed the cytology of salivary gland lesions in HIV-infected patients and assessed the value of FNA in the diagnosis of salivary gland lesions in HIV-infected patients. One hundred and three FNAs of salivary gland lesions from 78 HIV-infected patients (63 males and 15 females) were included in our study. The patients' ages ranged from 7-65 yr, with a mean age of 40.9 yr. FNAs were classified into three categories: benign lymphoepithelial lesions (BLL) (77 cases or 74.8%), inflammatory processes (14 cases or 13.6%), including 3 reactive lymphoid hyperplasia, and neoplastic lesions (6 cases or 5.8%). The latter included three malignant lymphomas, a multiple myeloma, a metastatic adenocarcinoma from a lung primary, and a direct extension of basal-cell carcinoma. Six (5.8%) aspirates were nondiagnostic. No false-positive or false-negative cases were noted during follow-up of these patients. In conclusion, FNA is a simple and cost-effective procedure for the diagnosis of HIV-related salivary gland lesions. The majority of these lesions are cystic BLL and can be managed conservatively. Malignant lesions are rarely encountered and are readily recognized by FNA. Diagn. Cytopathol. 1999;21:260-264.

Pigmented villonodular synovitis. Report of a case with diagnostic synovial fluid cytologic features.

BACKGROUND: The identification of neoplastic cells in synovial fluid is an uncommon occurrence and most often is related to extension of extraarticular tumor into the joint space than to primary neoplasm arising in the joint. CASE: In this report the cytologic features of synovial fluid obtained from the right knee of an 18-year-old male with biopsy-proven pigmented villonodular synovitis are described and compared with the features of the concurrent surgical specimen. CONCLUSION: The cytologic features of pigmented villonodular synovitis in synovial fluid include abundant mononuclear histiocytic cells occurring singly and in papillary clusters, hemosiderin within histiocytes and few multinucleated giant cells.

The HER-2/neu oncogene in tumors of the gastrointestinal tract.

The HER-2/neu oncogene is localized to chromosome 17q and shares significant homology with the epidermal growth factor receptor. As a result of its potential role in the selection of therapy, HER-2/neu testing has reached near-standard-of-practice status in breast cancer. There is considerable interest in HER-2/neu as a prognostic factor and target of therapy in tumors of the gastrointestinal tract. In this review of HER-2/neu expression in esophageal squamous cell carcinoma and adenocarcinomas of the esophagus, stomach, and colon, a wide range of expression of HER-2/neu from 0 to 83% likely reflects both differences in methods and reagents, as well as study bias associated with patient selection (i.e., early versus advanced disease). For esophageal squamous cell carcinoma, little information exists as to the prognostic significance of HER-2/neu expression. In adenocarcinoma associated with Barrett's esophagus there is contradictory data. However, most of the information available indicates that this marker has significant prognostic value. In gastric adenocarcinoma, the wide expression range may truly reflect patient selection because HER-2/neu positivity appears linked to advanced rather than early disease with limited invasion. The majority of studies favor a significant prognostic value of HER-2/neu status for this tumor. Finally, in colorectal cancer HER-2/neu overexpression also appears to be a significant adverse outcome indicator as judged by the current published literature. In conclusion, given that either HER-2/neu protein overexpression or gene amplification is associated with approximately one-fourth of all gastrointestinal tract malignancies, strategies designed to employ the marker in therapy selection appear warranted. During the next several years it will not be surprising to see these tumors treated with antiHER-2/neu modalities such as Herceptin, likely in combination with other agents initially for patients with advanced disease, and possibly for individuals with high-risk lesions in an adjuvant setting.

CD44 immunostaining of thyroid fine-needle aspirates differentiates thyroid papillary carcinoma from other lesions with nuclear grooves and inclusions.

BACKGROUND: Although nuclear grooves and inclusions are considered to be characteristic cytologic features of thyroid papillary carcinoma, a variety of other thyroid lesions may on occasion display these features in fine-needle aspiration specimens. METHODS: The authors evaluated the immunocytochemical staining of 16 fine-needle aspirations of thyroid papillary carcinoma and 14 aspirations of thyroid lesions confirmed to be other than papillary carcinoma but that included cells with nuclear grooving and/or inclusions, comprised of multinodular goiter (four cases), follicular adenoma (two cases), Hurthle cell adenoma (two cases), pure thyroiditis (three cases), and thyroiditis with nodular hyperplasia (three cases). CD44 previously has been shown to be selectively expressed in thyroid papillary carcinoma. RESULTS: Of 16 surgically confirmed cases of thyroid papillary carcinoma featuring nuclear grooves and inclusions on fine-needle aspiration, 14 (88%) stained intensely for CD44 in a membranous pattern. Of the 14 nonpapillary thyroid carcinoma cases, only 1 (7%), a Hürthle cell adenoma, featured membranous CD44 staining. The difference in the proportion of cases with CD44 staining between the two groups was statistically significant (chi-square test, P < 0.001). CONCLUSIONS: The authors conclude that immunostaining for CD44 can readily be performed on thyroid fine-needle aspiration specimens and that, for specimens featuring nuclear grooves and inclusions, the presence or absence of staining for CD44 may be of value in the distinction between thyroid papillary carcinoma and other lesions that may share some of the cytologic features of papillary carcinoma.

Giant cell angiofibroma of the nasolacrimal duct.

PURPOSE: To describe clinical and histologic features of the first case, to our knowledge, of giant cell angiofibroma located in the nasolacrimal duct region in a 28-year-old woman. METHODS: Interventional case report. A left nasolacrimal duct tumor was excised en bloc by lateral rhinotomy. Histopathologic examination was performed with the use of light microscopy. Immunohistochemical staining included S-100 protein, muscle-specific actin, desmin, myoglobin, vimentin, and CD34. RESULTS: The lesion was characterized by haphazardly arranged oval to spindled cells, a myxoid and collagenous stroma, multinucleated giant cells, prominent blood vessels, and pseudovascular spaces. Tumor cells were strongly positive for vimentin and CD34 and were negative for other antigens. After excision, there has been no recurrence over 4 years of follow-up. CONCLUSIONS: Originally described as an orbital tumor, giant cell angiofibroma also may occur in the nasolacrimal duct and lacrimal sac region. This mesenchymal neoplasm should be included in the differential diagnosis of lacrimal drainage system tumors.

Prognostic factors in gastric cancer.

Molecular assays related to cell proliferation correlate with stage and/or survival in a variety of tumors. We immunostained formalin-fixed, paraffin-embedded tissue sections from 61 patients with gastric adenocarcinoma (21 biopsy and 40 gastrectomy specimens) for cyclin A, cyclin B1, p34cdc2, p120, MIB1, and proliferating cell nuclear antigen (PCNA) by automated methods. HER-2/neu gene amplification was analyzed by automated fluorescence in situ hybridization (FISH). Immununostains, FISH results, and pathologic stage were compared with length of survival. Forty-three percent of the cases showed amplification of HER-2/neu. Sixty-two percent of cases showed positive immunostaining for cyclin A, 38% for cyclin B1, 31% for p34cdc2, 49% for p120, 69% for MIB1, and 33% for PCNA. On univariate analysis, pathologic stage (P = .003) and HER-2/neu gene amplification (P < .001) correlated with length of survival. Cyclin A, cyclin B1, p34cdc2, p120, MIB1, and PCNA did not correlate with survival. On multivariate analysis, pathologic stage (P = .015) and HER-2/neu gene amplification (P = .002) independently predicted survival. These correlations were unrelated to tubular or signet ring cell histologic characteristics or to location within the cardia or more distally. Pathologic stage and HER-2/neu gene amplification by FISH were independent prognostic factors in gastric cancer, but the various proliferation markers that we studied did not correlate with survival.

Telomerase activity in benign and malignant cytologic fluids.

BACKGROUND: Telomerase is a ribonucleoprotein that maintains telomeric base pair repeats at the ends of mammalian chromosomes during DNA replication. Telomerase is expressed in various human tumors, some normal tissues, and immortalized cell lines. The assay of telomerase activity has potential as an adjunct for cancer detection in cytologic fluids. METHODS: Twenty-four unfixed cytologic fluids, including 13 ascitic fluids, 7 pleural fluids, 3 pelvic washings, and 1 bronchial washing, were prepared for polymerase chain reaction (PCR)-based telomeric repeat amplification protocol (Oncor, Inc., Gaithersburg, MD). Telomerase activity was determined by PCR. The presence of a ladder of products with 6 base pair increments, separated by polyacrylamide gel electrophoresis and detected by phosphoimaging, was considered a positive result. Results were compared with cytologic evaluation of alcohol fixed, Papanicolaou stained smears. RESULTS: Of the 14 cytologically malignant specimens, 11 (79%) contained detectable telomerase activity. Two cytologically malignant samples could not be evaluated for telomerase activity due to the presence of inhibitory substances of PCR reaction. Of the 10 cytologically negative specimens, 1 (10%) was positive for telomerase activity; this specimen was from a patient with history of both endometrial and lung carcinomas. CONCLUSIONS: Telomerase activity can be detected in malignant cytologic specimens and thus has potential as a diagnostic adjunct in cytopathology.

Acute eosinophilic pneumonia associated with shock.

OBJECTIVE: To describe an unusual case of acute eosinophilic pneumonia (AEP) associated with hemodynamic instability. DESIGN: Case report, clinical. SETTINGS: Tertiary care intensive care unit (ICU). PATIENT: A single patient admitted to the ICU. INTERVENTIONS: Intravenous corticosteroids. MEASUREMENTS AND MAIN RESULTS: Resolution of distributive shock and respiratory failure. CONCLUSIONS: AEP with respiratory failure was first reported in 1989 as a distinct clinical entity. Patients with this variant of eosinophilic lung disease develop acute hypoxemic respiratory failure with a rapid response to treatment with corticosteroids, The characteristic feature of this syndrome is a predominance of eosinophils found in bronchoalveolar lavage fluid and lung biopsy. Despite the increasing number of reported cases, to our knowledge, distributive shock has not been reported as a feature of AEP. We report a unique case of AEP associated with shock and review the pertinent literature.