Missed diagnosis in hematological patients—an autopsy study

Autopsy findings of missed diagnoses that would probably have changed management or prognosis occur in up to 29% of cases in general hospitals. Such proportions may be higher in subsets of patients with complex diseases. We reviewed 2908 consecutive autopsies performed over a period of 29 months in a large-volume hospital, analyzing 118 autopsies of patients with hematological malignancies or severe aplastic anemia. A review of macroscopic reports as well as microscopic examination of tissue samples was performed. Medical records were reviewed for clinical diagnoses. Discordances between clinical and autopsy diagnoses were classified using Goldmans criteria. Additionally, we searched for clinical parameters correlated with occurrence of class-I discrepancy using a multivariate method. Median age was 46.5 years, and 25.4% had received a hematopoietic stem-cell transplant. Overall, 11.9% (6.6–19.1%) of patients died before conclusion of the hematological diagnosis and 33% (24.6–42.3%) died with no active hematological disease. We found class-I discrepancy in 31.3% (23.1–40.5 %) of cases. The most common among these diagnoses were hematological disease, pneumonia and gastrointestinal bleeding. In a univariate analysis, being elderly (P=0.04) was positively correlated with the finding of class-I discrepancies; while, having received previous specific hematological treatment (P=0.0005) or hematopoietic stem-cell transplants (P=0.013), or being admitted to a specialized hematology unit (P=0.0006) were negatively correlated to the occurrence of such discrepancies. Multivariate analysis showed that care in a specialized hematology unit (OR 0.34, 0.12–0.93) was independently associated with lower occurrence of discrepancies. We concluded that critical diagnoses are often missed in highly complex hematological patients especially in the absence of admission to specialized hematology units.     

Improved immunodiagnosis of human cysticercosis with scolex protein antigens

Crude antigenic extract (CAE) and a scolex protein antigen (SPA) of Taenia solium cysticerci were used in indirect haemagglutination (IH) and enzyme-linked immunosorbent assay (ELISA) to detect serum antibodies in cysticercosis patients. Complement fixation (CF) was used for comparison with antigens obtained as an alcoholic extract of CAE (ACAE) and SPA (ASPA). For each test, a dilution was chosen which showed no cross-reactivity with sera from patients with other parasitic diseases such as taeniasis, schistosomiasis, ancylostomiasis, ascaridiasis, strongyloidiasis, Chagas' disease and syphilis. For the CF, 14 was the discriminative dilution determined; for IH, 116 and for ELISA, 1256. The CF could detect serum antibodies to cysticerci in 45% of patients when ACAE antigen was used and 73% using ASPA. In the IH, serum antibody was detected in 73% of patients when CAE was used and 86% using SPA. In ELISA 63% of patients were positive when CAE was used and 91% using SPA. The use of SPA improved the serological distinction between infected and uninfected patients in all tests and the ELISA showed a significantly higher capacity to detect infected patients.     

Early vulvar squamous neoplasia: advances in classification, diagnosis, and differential diagnosis

The recognition and classification of preinvasive vulvar neoplasia are complicated by the facts that (a) their respective carcinomas have a diverse (human papillomavirus [HPV]- and non-HPV-related) pathogenesis; (b) not all vulvar squamous carcinomas are associated with precursors with strictly defined morphologic features; (c) many carcinomas have epithelial changes that are abnormal but lack sufficient nuclear atypia to warrant classification as an intraepithelial neoplasm; and (d) even lesions associated with a common etiologic agent (HPV) present a diverse morphologic spectrum. In this review, five categories of early vulvar neoplasia are defined, based on the available literature, into (a) low-grade lesions with minimal cancer risk, (b) high-grade lesions associated with HPV, (c) high-grade lesions associated with other etiologies, (d) squamous atypias defined by abnormalities in differentiation rather than abnormalities in nuclear morphology, and (d) early carcinomas that do not exhibit conspicuous stromal invasion. The first three groups are arranged into low- and high-grade intraepithelial lesions, the fourth into intraepithelial atypias that bear careful follow-up and attention to the co-existing squamous mucosa, and the fifth into a category that, depending on the degree of cell differentiation, may warrant local excision or lymph node dissection. Recognition of these five categories is germane to proper management of women with squamous lesions of the vulva.     

Clusterin, a marker for anaplastic large cell lymphoma immunohistochemical profile in hematopoietic and nonhematopoietic malignant neoplasms

We evaluated the immunohistochemical staining profile of clusterin in paraffin sections of 143 neoplasms (non-Hodgkin lymphoma, 83, including 41 anaplastic large cell lymphomas [ALCLs]; Hodgkin lymphoma, 17; primary and metastatic carcinoma, 30; and other neoplasms, 13). In 40 of 41 ALCLs (34 systemic, 7 cutaneous), neoplastic cells revealed clusterin reactivity characterized by a Golgi staining pattern. The proportion of reactive cells varied with more than 25% positive cells in the majority of cases. In 7 non-Hodgkin lymphomas of other types, fine cytoplasmic (3 cases) or strong membranous reactivity (4 cases) was observed for clusterin. In Hodgkin lymphoma, rare Reed-Sternberg cells exhibited focal cytoplasmic or membranous clusterin positivity. In the nonhematopoietic neoplasms, a Golgi staining pattern was apparent in only 2 cases, 1 lobular carcinoma of the breast and 1 poorly differentiated colonic carcinoma; however, cytoplasmic reactivity was noted in 12 of 30 carcinomas and 1 of 5 neuroendocrine neoplasms. A Golgi pattern of reactivity for clusterin seems highly characteristic of ALCL among hematopoietic neoplasms, but also might be observed in rare nonhematopoietic tumors, necessitating the use of a broad immunohistochemical panel for evaluation of poorly differentiated neoplasms of indeterminate derivation.     

Gender-related cytokine patterns in sera of schistosomiasis patients with Symmers' fibrosis

Cytokine levels were compared between schistosomiasis patients affected by intense fibrosis defined by ultrasound examination and graded from F-0 to F-3. The concentrations of interleukin-1beta (IL-1beta), IL-4, IL-5, IL-10, IL-13, gamma interferon, and tumor necrosis factor alpha (TNF-alpha) were determined by enzyme-linked immunosorbent assay of serum samples. Levels of IL-4, IL-5, and TNF-alpha in the sera of F-3 patients were significantly higher than those found in F-0 individuals, while levels of IL-13 were lower. Levels of IL-4, IL-5, and TNF-alpha in serum were significantly higher in F-3 males than in F-0 males or F-3 females. Conversely, levels of IL-13 were significantly lower in F-3 females than in F-0 females and males.     

Genomic fingerprinting of bacteriocin-producer strains of Staphylococcus aureus

Among 363 strains of Staphylococcus aureus, 21 were shown to produce bacteriocins (Bac), antimicrobial peptides with potential biotechnological applications. This collection includes strains which are either isolated from food, patients and healthy cattle, or are involved in subclinical bovine mastitis. From these 21 strains, 17 were shown to carry closely-related 8.0-kb Bac plasmids encoding bacteriocins either identical to or similar to aureocin A70, a bacteriocin able to inhibit strains of Listeria monocytogenes, a food-borne pathogen. Such findings prompted us to investigate the genetic relationships among these Bac+ strains. To obtain more discriminatory results, a combined analysis of AP-PCR, rep-PCR, and a modified PCR technique that we designated SD-PCR was employed. The 17 Bac+ strains harboring 8.0-kb Bac plasmids exhibited seven fingerprint patterns. One such genotype was composed of 8 out of the 11 strains associated with bovine mastitis, which suggests the prevalence of a clone of Bac+ strains involved in this animal infection carrying 8.0-kb Bac plasmids. Our data support the assumption that Bac+ strains of S. aureus carrying genetically related 8.0-kb Bac plasmids do not belong to a single clone. It seems, therefore, that 8.0-kb Bac plasmids have spread horizontally among different S. aureus strains. There also seems to be genetic diversity among the remaining Bac+ strains analyzed.     

Molecular characterization of Kaposi's sarcoma associated herpesvirus (KSHV) from patients with AIDS-associated Kaposi's sarcoma in Sao Paulo, Brazil.

BACKGROUND: Kaposi's sarcoma (KS) is caused by Kaposi's sarcoma associated herpesvirus (KSHV/HHV-8), the eighth Herpesvirus found to infect humans. The molecular epidemiology of KSHV is related closely to ethnicity and geographical location of studied populations. There is little epidemiological and molecular information about KSHV strains circulating in Brazil. OBJECTIVES: To characterize KSHV strains isolated from AIDS patients with Kaposi's sarcoma (AIDS-KS) in Sao Paulo, Brazil, and to examine associations between KSHV subtypes, ethnicity and HIV risk categories. METHODS: AIDS-KS patients were recruited consecutively at the largest AIDS reference hospital in Sao Paulo. Fragments (420 bp) of the VR1 and VR2 regions of KSHV open reading frame (ORF) K1 were amplified by nested PCR and sequenced directly. RESULTS: We analysed 37 samples from 33 patients, and found subtypes A-C in 48%, 21% and 30% of patients respectively, including two patients infected with subtype A5, a first report from Brazil. Sexual orientation was associated with subtype: 12/14 (86%) patients with subtype A were male homo/bisexual, compared with 3/8 (38%) among patients infected with subtype C (P = 0.05). A higher proportion of male patients with subtype C were of Caucasian origin (7/8 (87%)), compared with 7/16 (44%) among male patients with subtype A (P = 0.08). CONCLUSIONS: This first detailed report of KSHV subtypes among AIDS-KS patients in Brazil reports the first isolation of KSHV subtype A5 in this country, and suggests KSHV strain transmission between different ethnic groups, and association of specific strains with sexual orientation.     

Extraskeletal myxoid chondrosarcoma: a clinicopathologic, immunohistochemical, and ploidy analysis of 23 cases.

Twenty-three cases of extraskeletal myxoid chondrosarcoma, evaluated at the Mayo Clinic between 1968 and 1996, were studied for clinicopathologic features, immunohistochemical profile, Ki-67 activity, and ploidy status to identify adverse prognostic factors. Females and males were equally affected, and the median age at diagnosis was 50 years. The tumors were located mainly in the lower extremities (83%), and the median tumor size was 9.5 cm. Sixteen tumors showed low cellularity (70%), and eight tumors had high mitotic activity (more than two per 10 high-power fields). The tumors were immunoreactive for vimentin (89%), synaptophysin (72%), epithelial membrane antigen (28%), and S-100 protein (17%). Nine tumors were diploid, three aneuploid, and one tetraploid. Mean Ki-67 activity was 11% (range, 1 to 45%). The 10-year overall survival rate was 78%. On univariate analysis, tumor size > or = 10 cm, high cellularity, presence of anaplasia or rhabdoid features, mitotic activity more than two per 10 high-power fields, Ki-67 > or = 10%, and Ki-67 "hot spot" > or = 25% were associated with decreased metastasis-free or overall survival. Ploidy status was not associated with any adverse outcome. The presence of any of these adverse prognostic factors can indicate the possibility of a more aggressive behavior in extraskeletal myxoid chondrosarcoma, and a closer follow-up is suggested.