Fatal transfer of malignant melanoma from multiorgan donor to four allograft recipients.

BACKGROUND: In this report we describe the transfer of malignant melanoma from a single donor to four solid organ transplant recipients, all of whom died from metastatic melanoma. METHODS AND CASE HISTORIES: The donor of a heart, liver, and two kidneys to four separate recipients died of intracerebral hemorrhage. The donor had no history or clinical evidence of melanoma. All four recipients, treated with standard immunosuppression protocols, developed metastatic malignant melanoma within 1 year after transplantation Three patients died within 14 months after transplantation, although the fourth, whose immunosuppressive therapy was discontinued, died of metastatic melanoma 30 months after renal transplantation. FINDINGS: Tumors from all recipients were histologically identical. Donor origin of tumor cells was confirmed by polymerase chain reaction (PCR)-based DNA analysis for polymorphic short tandem tetrameric repeats (Geneprint STR, Promega Corp., Madison, WI). DNAs from nontumorous donor tissue and tumor tissue available from three recipients tested positive for CSF1P0 alleles 10 and 12 and for TH01 alleles 6 and 7, although DNAs from nonneoplastic recipient tissues all exhibited different allelotypes. INTERPRETATION: Transmission of fatal or potentially fatal malignant tumors, notably malignant melanoma, from donor to recipient is an uncommon complication of solid organ transplantation. PCR-based genetic analysis permits definitive assignment of the source of posttransplant tumors.

Inguinal lymphadenitis caused by Entamoeba histolytica: case report and literature review.

Liver abscesses are the most common manifestation of extraintestinal infection by Entamoeba histolytica. Involvement of other sites, including the peritoneum, pericardium, brain, or genitourinary tract, is unusual. We describe a case of inguinal necrotizing lymphadenitis caused by E histolytica. Our patient responded well to surgical drainage, metronidazole, and paramomycin therapy. A literature review of genitourinary and other uncommon sites of E histolytica infection is included.

A comparison of three malaria diagnostic tests, under field conditions in North-west Thailand.

A hospital-based trial to compare the clinical diagnosis of malaria; microscopy, and a rapid diagnostic antigen capture detection dipstick (ParaSight-F) was conducted in North-west Thailand. 301 people who presented themselves at the hospital were selected. 204 (68%) were presumptively diagnosed as having malaria by the triage nurses; 64 (21.3%) were P. falciparum parasite positive, and 94 (32%) tested positive for P. falciparum with the ParaSight-F test strips. There was no association between hemoglobin levels (<10g/dl and > or = 10g/dl) and malaria, and although there was a good statistical association between temperature and malaria the specificity, sensitivity and positive predictive values were all low, indicating that temperature alone is a poor indicator of the disease. Based on the microscopy results, we found that a presumptive clinical diagnosis dramatically over-diagnosed malaria, and similarly there were a large number of false positives using the ParaSight-F test. We believe that many of the patients had received some form of malaria treatment prior to presentation at the hospital, and that the high number of false positives are explained by persistent antigenemia and the possibility of there being sequestered parasites following incomplete chemotherapy.

Unusual dural and skull-based mesenchymal neoplasms: a report of four cases.

Dural and skull-base mesenchymal neoplasms other than meningiomas are rare. We report four such tumors, some of which are uncommon even in nonintracranial sites, in three adults and one child. The adult tumors consisted of a synovial sarcoma of the third ventricle region in a 19-year-old woman, a leiomyoma of the suprasellar region in a 57-year-old woman, and an Epstein-Barr virus (EBV)-associated smooth muscle tumor of the cavernous sinus in a 35-year-old woman with acquired immunodeficiency syndrome (AIDS). The pediatric tumor was an EBV-associated leiomyosarcoma of the left dural transverse sinus in a 14-year-old girl with common variable immunodeficiency syndrome. All tumors were thought to be primary in their dural or skull-base locations. The two EBV-associated smooth muscle tumors in immunocompromised patients expand the locations for EBV-associated smooth muscle tumors to dural and skull-base sites, the synovial sarcoma is unique to the intracranial space, and the sellar leiomyoma represents the third reported sellar smooth muscle tumor.

Large cell calcifying Sertoli cell tumor of the testis: contrasting features of six malignant and six benign tumors and a review of the literature.

We report six malignant and six benign large cell calcifying Sertoli cell tumors of the testis and compare the features of malignant and benign cases based on these cases and those in the literature. All the tumors in this report consisted of sheets, nests, solid tubules, and cords of eosinophilic cells, with focal calcifications, as well as a substantial neutrophilic infiltrate in 11 of them. Analysis of our cases and those in the literature showed that the malignant tumors were unilateral and solitary and occurred at a mean age of 39 years (range 28-51 years), whereas the benign neoplasms were bilateral and multifocal in 28% of cases and occurred at a mean age of 17 years (range 2-38 years). Only one malignant tumor occurred in a patient with evidence of a genetic syndrome (Carney syndrome), whereas 36% of benign tumors had various genetic syndromes or endocrine abnormalities. Most of the tumors in the latter cases were bilateral and multifocal. There were strong associations of malignant behavior with size >4 cm, extratesticular growth, gross or microscopic necrosis, high-grade cytologic atypia, vascular space invasion, and mitotic rate greater than three mitoses per 10 high-power fields. All malignant cases exhibited at least two of these features, whereas all benign cases lacked any of them. The presence of any one of these features in a solitary large cell calcifying Sertoli cell tumor, especially in a patient >25 years of age, should be viewed as suspicious for malignant behavior, whereas the presence of two or more of these features indicates a strong probability of a malignant course. "Low" percentages (< or =35%) of tumor cells staining for proliferating cell nuclear antigen (PCNA) also may correlate with benign behavior, but some benign tumors have high PCNA values. Ki-67 values (MIB-1 antibody) did not correlate with biologic behavior, nor did immunostains for p53 protein.

Telomerase expression in normal endometrium, endometrial hyperplasia, and endometrial adenocarcinoma.

Telomerase activity has been detected in a broad range of human cancers and its expression could be an important step in tumor progression. Here, telomerase activity by the telomeric repeat amplification protocol in cases of benign endometrium, endometrial hyperplasia, and endometrial adenocarcinoma was tested. Telomerase expression was detected in 13 of 14 cases of proliferative phase endometrium, in 7 of 12 cases of secretory phase endometrium, but was not detected in any of 7 cases of atrophic endometrium. Three of three cases with evidence of luteal phase defect and one of four cases of chronic endometritis also expressed telomerase activity. Hyperplastic endometrium was positive for telomerase in 13 of 17 cases. Telomerase activity was detected in 40 of 48 cases of endometrial adenocarcinoma, which included 36 of 43 cases of endometrioid adenocarcinoma and four of five cases of papillary serous carcinoma. The detection of telomerase in endometrial adenocarcinoma was not associated with either architectural grade, myometrial invasion, or stage. There was statistically significant association, however, between telomerase activity in benign atrophic endometrium versus any endometrial abnormality in women 52 years of age or older.

Longitudinal measurement of anticardiolipin antibodies during normal pregnancy: a prospective study.

We have previously shown that elevation of anticardiolipin antibodies (aCL) at the first prenatal visit is associated with increased fetal loss in normal pregnancy. The variation in aCL levels during normal pregnancy has not been established. To examine this question we measured IgG, IgM and IgA aCL levels five times during pregnancy at weeks 5-15, 16-25, 26-35, 36-37 and at delivery. Data were analyzed to determine: (a) the within and between subject variability of aCL during pregnancy; (2) the temporal trend of aCL; and (3) the relation of serial measures of aCL with maternal complications of pregnancy. We divided our cohort of 354 subjects into two groups. Group A included those subjects with consistently normal levels of aCL and group B those subjects with at least one elevated level of aCL. In group A the within subject variability was relatively low (28-34%). In group B we found wide fluctuations in aCL levels and a within subject variability of 88-91%. Subjects in group B had no increase in maternal complications of pregnancy. The present data suggest that aCL may fluctuate significantly during normal pregnancy and there is little clinical value in measuring aCL on a serial basis during pregnancy.

Dedifferentiated chordoma. Response to aggressive chemotherapy in two cases.

BACKGROUND: Dedifferentiated chordoma is an unusual and aggressive variant of chordoma which is likely to metastasize. Few reports exist of treatment of these tumors with chemotherapy. METHODS: In 1988, two patients with dedifferentiated sacral chordomas were seen at the University of Chicago Hospitals. Both developed metastatic disease less than a year after sacral resection and radiation therapy. These patients' diagnoses, courses, and treatments were reviewed along with the literature on chemotherapy in both conventional and dedifferentiated chordomas. RESULTS: Both patients obtained complete remissions, one to a six-drug regimen and the other to ifosfamide. CONCLUSIONS: A trial of reasonably aggressive chemotherapy is warranted in patients with metastatic dedifferentiated chordoma. The optimum regimen is unclear, but agents active in high-grade sarcomas are logical choices.

Chronic hyperplastic sinusitis: association of tissue eosinophilia with mRNA expression of granulocyte-macrophage colony-stimulating factor and interleukin-3.

BACKGROUND: We investigated the association among tissue eosinophilia, cellular infiltration, and cytokine mRNA expression in chronic hyperplastic sinusitis (CHS). METHODS: Percutaneous biopsies of the maxillary sinuses and nasal polyps were performed in 12 adult patients (six men and six women) of whom seven were nonallergic and 11 were asthmatic. Tissues were compared with biopsy specimens from the inferior and middle turbinates of normal control subjects. RESULTS: Histologically, an eosinophil-predominant inflammatory infiltrate was seen in 10 of 12 patients, whereas a mild to moderate neutrophilic infiltrate was seen in 4 of 12 patients. As determined by immunocytochemistry, diseased tissues and normal control tissues differed significantly in terms of the number of activated (EG2+) eosinophils (p = 0.005) but not in terms of CD3+ or CD4+ T lymphocytes, elastase-positive neutrophils or CD68+ macrophages. The number of eosinophils did not correlate with that of any other cell type. By in situ hybridization, CHS tissues showed significantly higher numbers of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-3 mRNA-positive cells than normal control tissues (p = 0.002 and 0.0005, respectively) per high-powered field. There was a significant correlation between the number of infiltrating EG2+ eosinophils and cells that expressed mRNA for GM-CSF (r = 0.60, p = 0.041) or IL-3 (r = 0.69, p = 0.013). Furthermore, epithelial cells did not show detectable mRNA expression for GM-CSF or IL-3. No significant correlation was found between IL-5 mRNA expression and infiltrating EG2+ eosinophils in diseased tissues. However, the IL-5 density was significantly higher in the five patients with CHS who had positive allergy skin test results than in the seven patients with negative skin test results (p = 0.017) or in normal control subjects. CONCLUSIONS: Our data support a role for GM-CSF and IL-3 in the eosinophilia characteristic of CHS and show that IL-5 mRNA expression is not a prominent feature of nonallergic inflammation. The cellular sources of GM-CSF and IL-3 in CHS remain to be definitely determined.

Differential gene expression in the amnion, chorion, and trophoblast of the human placenta.

Human chorionic gonadotrophin (hCG), placental alkaline phosphatase (PLAP), and pregnancy-specific glycoprotein (PSG) are three major proteins produced by the trophoblast of the human placenta. Immunocytochemical studies suggest that PSG and hCG are also present in the human amnion. In this study, we examined whether amniotic and chorionic membranes were capable of expressing trophoblastic-specific genes. As previously reported, trophoblasts express high levels of hCG beta, hCG alpha, PLAP, and PSG. Both amnion and chorion were found to express PLAP and hCG beta mRNA. However, the hCG alpha transcript was expressed only by the amnion, but not by the chorion in the term placenta. Recent molecular cloning studies indicate that human PSGs are a group of closely related placental proteins that, together with the carcinoembryonic antigen family members, comprise a subfamily within the immunoglobulin superfamily. To demonstrate that amnion and chorion also express PSG transcripts, we employed ribonuclease protection analysis using probes specific to the 5' and 3' region of PSG mRNAs. Our data indicate that while amniotic as well as chorionic membrane expressed low levels of the PSG genes, only a certain subpopulation of PSG transcripts were expressed. Furthermore, the amnion and chorion demonstrated differences in PSG species expression from each other and from trophoblastic tissue. Thus, human amnion, chorion and trophoblast selectively express several placental genes.