Michael A. Varello

The Fibrolamellar Variant of Hepatocellular Carcinoma Its Association With Focal Nodular Hyperplasia

A case of fibrolamellar hepatocellular carcinoma (FL‐HCC) associated with adjacent focal nodular hyperplasia (FNH) is described. These two regions were adjacent but distinct, both on gross and microscopic examination. Currently, it is unclear whether FL‐HCC rarely arises in preexisting FNH, or whether FNH is a typical response to this vascular variant of hepatocellular carcinoma (HCC). The FNH region, which is peripheral, may be biopsied to exclude the underlying carcinoma, and thus lead to inadequate therapy. Previous reports of this association are reviewed.

Flow cytometric DNA analysis as a diagnostic aid for cervical condyloma and cancer

Flow cytometric DNA analysis data (FCDA) were obtained from 324 samples provided through the Gynecology‐Oncology Clinic. These samples consisted of 294 combined endoectocervical and vaginal smears and 30 peritoneal washings. Using a conventional scheme for G0/G1, S + G2/M and the coefficient of variation with computer correction for the cell‐cycle kinetics, it was possible to assign a diagnostic Class, I, II, III or V similar to that used by the Cytology Laboratory. These data were then compared with the histopathologic and colposcopic diagnoses. The correlation between FCDA and cytologic results were essentially similar to the previous data obtained from only endocervical sampling.14 The most interesting finding in this study was the recognition of an FCDA pattern showing a higher DNA content in the G0/G1 and the early S regions in 70 of 94 (74.5%) of samples from patients with condyloma acuminata. All condyloma samples were diagnosed either by cytologic, histopathologic, or colposcopic examination, or a combination of two or three. All biopsy specimens were then reviewed by one pathologist to verify any discrepancies. The relationship of this pattern to the viral etiology of this disease is discussed with the three methods of diagnosis and electron microscopic observations. It is suggested that, based on this study, FCDA analysis of pap smears may also be useful in determining the presence of condyloma in a gynecology clinic. The potential value of FCDA analysis from peritoneal washings for the diagnosis of gynecologic cancer can not be ascertained in this preliminary investigation because of insufficient samples.

Measurement of Platelet Collagen Receptor Density in Human Subjects

To the Editor: We are writing to provide data on a novel approach for measuring platelet collagen receptors in human subjects. Immediately after vascular injury, circulating platelets are exposed to collagen, a matrix protein that both supports platelet adhesion and activates platelets through platelet collagen receptors.1 Collagen signals generated at a site of arterial vessel injury are therefore likely to be among the first platelet activating signals that generate the coronary thrombi responsible for myocardial infarction. The molecular basis of platelet collagen responses has recently been elucidated by the identification and characterization of two platelet collagen receptors: the immune receptor homologue glycoprotein VI (GPVI)2 and the integrin α2β1.3 GPVI is required for platelet activation in response to collagen,4,5 whereas α2β1 plays an accessory role to support platelet responses to immobilized collagen in the setting of high shear forces.6 Preliminary findings from both laboratory and clinical studies suggest that the surface density of the platelet collagen receptors GPVI and α2β1 may regulate the degree of platelet activation by collagen and its clinical outcome.7–11 Despite these preliminary findings, the precise role of platelet collagen receptor density as a risk factor for MI remains poorly understood, with the few reported studies yielding apparently contradictory results. A study examining the correlation of platelet GPVI receptor polymorphisms with surface receptor density in normal individuals found one common allele (associated with the coding region polymorphism T683C) that correlated with lower GPVI receptor density and reduced collagen-mediated platelet aggregation.8 In contrast, …

Simultaneous Flow Cytometric Deoxyribonucleic Acid and Acid Phosphatase Analysis of Benign and Malignant Lesions of the Prostate

Flow cytometry can differentiate benign from malignant lesions of the prostate through deoxyribonucleic acid distribution analysis. A method has been developed that permits simultaneous cytometric determination of deoxyribonucleic acid and acid phosphatase activity in the cell cycle compartments of prostatic biopsy specimens. Histograms of prostatic carcinoma reveal higher acid phosphatase activity and greater deoxyribonucleic acid content in the S and S + G2/M populations than the histograms representing benign lesions. This compartmental difference may have prognostic usefulness.

Flow cytometric DNA and 5′‐nucleotide phosphodiesterase in endometrium

One hundred endometrium specimens have been studied with flow cytometry for DNA analysis (FCDA) and a proliferative enzyme marker, 5′‐nucleotide phosphodiesterase (5′‐NPD). FCDA data showed that aneuploidy was present in only 5 of 40 cancer specimens. However, with corrected histograms, a higher DNA value was observed in the G2/M (6%) of all cancer compared with noncancer specimens (4%). Thus, FCDA can be a useful diagnostic aid for endometrial cancer. The determination of 5′‐NPD was done with a quenching method based on the use of 5′‐(5‐iodo‐3‐indoxyl)‐thymidine phosphodiester as a substrate and 4′,6‐diamidino‐2‐phenylindole for DNA. This method could qualitatively define which population of the cell cycle had a higher enzyme level and also quantitatively gave the enzyme units per cell. It was found that 12.5% of all cancer specimens had 5′‐NPD activity in the G0/G1 cells and 87.5% in the S and/ or G2/M cells, whereas in the noncancer specimens 5′‐NPD was found in 28.5% of the G0/C1 cells and 71.5% of the specimens had 5′‐NPD in the S and/or G2/M cells. Furthermore, the concentration of 5′‐NPD was found to be five times higher in the G2/M cells of the cancer specimens than that in the noncancer specimens. However, in the hyperplasia specimens, the activity was only two times higher in the same cell cycle fraction than in the normal specimens. The results of this investigation provided for the first time evidence that this exonuclease activity alters in the cell cycle fractions and that a decrease in the enzyme activity in G0/G1 cells and an increase in G2/M cells may be a useful marker for neoplastic development in human endometrial cancer.