Sistemas expertos en Anatomía Patológica: un futuro común para la Medicina / Expert system in pathological anatomy: A common future for medicine

Objetivos: Crear un sistema experto que sea abierto y cuya base de conocimiento esté representada por imágenes y pueda ser utilizada como vehículo de información relevante. Material y métodos: Uno de los autores actuó como ingeniero del conocimiento. Con un ordenador Pentium 133 MHz y en Visual Basic se ha creado SARA (Sistema Abierto de Razonamiento Artificial). Para su elaboración se ha construido la aplicación SEADLINH (Sistema Experto de Ayuda al Diagnóstico de Linfomas No Hodgkin). Resultados: El sistema ofrece imágenes con las que comparar la arquitectura microscópica y el aspecto citológico del caso problema. La selección de distintas imágenes (patrones) lleva a un diagnóstico indicando la probabilidad de certeza. El sistema permite acceder a su base de conocimiento y modificarla. Admite información complementaria en forma de imágenes o texto. Conclusiones: Se ha creado un sistema experto (SARA) de tipo abierto, que está disponible para llenar de contenidos su base de datos y su base de conocimientos. Su calidad ulterior dependerá de los recursos que se empleen en su confección, abriendo el campo de acción de los patólogos (AU)

Sistemas de información en anatomía patológica: análisis de las soluciones existentes / Information System in anatomical pathology: Analysis of the existing solutions

Antecedentes: En los últimos dos años se está procediendo a la renovación de los sistemas informáticos en anatomía patológica de numerosos hospitales. Por ello consideramos interesante revisar los sistemas informáticos más habituales y conocer los principales aspectos que debemos exigir en estos programas. Material y métodos: Cuatro sistemas informáticos (Master-Pat NovoPath, PatWin e InfoPAT) han sido evaluados por los usuarios de siete hospitales distribuyendo entre los usuarios y los fabricantes una encuesta con 105 variables. Resultados: Los sistemas más modernos ofrecen un número muy alto de funcionalidades, destacando los más modernos por su integración en el resto del sistema de información hospitalario, si bien los sistemas de ayuda, la codificación y la gestión de imágenes son algunos aspectos que la mayoría de programas necesitan mejorar. Conclusión: Los nuevos programas informáticos son de gran calidad y las prestaciones muy parecidas, por lo que es aconsejable evaluar las necesidades de cada servicio para poder escogerla solución óptima (AU)

High frequency of altered HLA class I phenotypes in laryngeal carcinomas.

The exact frequency of HLA class I losses in human tumors is unknown. We have previously shown that primary breast and colorectal carcinomas frequently lose HLA class I molecules (88% and 73%, respectively). Now we report that this phenomenon is also a frequent event in laryngeal carcinomas. Of a total of 76 laryngeal carcinomas analyzed, 66% of the tumors showed an alteration in HLA class I phenotype. These altered HLA phenotypes were classified as total HLA loss (10.52%) (phenotype I); HLA-A locus-specific loss (13.15%) (phenotype IIIa); HLA-B locus-specific loss (10.52%) (phenotype IIIb); HLA allelic loss (27.63%) (phenotype IV); and HLA-A and B locus loss (3.9%). Comparison of histopathological parameters with HLA expression showed that poorly differentiated tumors had the lowest levels of HLA class I expression (p < 0.05).

Automated segmentation of cell nuclei in fine needle aspirates of the breast.

OBJECTIVE: To achieve a classifier of breast lesions to discriminate between benign and malignant cases of cytologic smears with automated segmentation image analysis techniques. STUDY DESIGN: The techniques were applied to images of epithelial cell nuclei from cytologic smears obtained by fine needle aspiration. The images of the nuclei were taken from 95 cases of malignant lesions and 47 benign (approximately 25 nuclei per case), and 28 nuclear variables were measured. The data were analyzed by a double methodology, discriminant analysis and classification and regression trees (CART), to determine which provided the best results. RESULTS: CART selected the SD of the nuclear area with correct classification of 85.1% of benign and 94.7% malignant aspirates. Discriminant analysis selected the group of variables formed by axis lengths, SD of the longest axis, sphericity and variance of gray levels, with results similar to those of CART. CONCLUSION: Automated segmentation image analysis techniques were effective, and the classifier was quick, simple and efficacious in malignant-benign discrimination.

Coexistence of tetrasomy 8 and trisomy 8 in a case with myeloid metaplasia with myelofibrosis.

We present a case of myeloid metaplasia with myelofibrosis (MM/MF), with tetrasomy 8 as the sole cytogenetic abnormality detected by conventional cytogenetic studies. Tetrasomy 8 was also detected by in situ interphase studies and confirmed by chromosome painting in metaphase. To our knowledge, this is the first case of MM/MF with tetrasomy 8. Noteworthy is the association with neurofibromatosis.

Buschke-Löwenstein tumor and immunity.

We report the case of an alcoholic patient, 41 years old, with negative results of serologic tests for human immunodeficiency virus (HIV) with a perianal Buschke-Löwenstein tumor present for eight years and exceptionally large. The patient's cell-mediated immunity was evaluated by two functional tests: the Multitest IMC (Institut Mérieux, Lyon) and the dinitrochlorobenzene (DNCB) test. The patient neither responded to any Multitest antigens nor was sensitized by DNCB. We consider that the immune short-age in this patient could influence the appearance of the Buschke-Löwenstein tumor.

[Histo-morphometry of bone mass and cellularity using image analysis: characterization of infiltration patterns in CLL]. / Histomorfometría de masa ósea y celularidad mediante análisis de imagen: caracterización de los patrones de infiltración en LLC.

PURPOSE: The aim of this study was to investigate a possible influence of lymphocytic infiltration in Chronic Lymphocytic Leukemia (CLL) on bone mass, according to the infiltration patterns. MATERIAL AND METHODS: We have studied histological preparations from decalcified and paraffin included bone biopsies and used a histomorphometric study through a mixed (interactive-automatic) image analysis, in order to quantify bone trabecular (BT/TV) and cellular volume (CV). Preparations were visualized via a 2.5 objective; a video camera was adapted and connected to a computer with analogical-digital converter incorporated. After the image was captured, a binarization was made by trabecular and medullary spaces segmentation; automatically, we calculated trabecular area (TA) and cellular area (CA). Expressions indicated above were used to calculate BV/TV and CV, expressed in percentage: BV/TV (%) = [TA/(TA + CA)] x 100, and CV (%) = [CA/(TA + CA)] x 100. RESULTS: 92 normal biopsies and 79 CLL biopsies were studied (Nodular 12, Diffuse 22, Interstitial 23, Mixed 22). BT/TV in normal subjects age over 45, was 18.40%; it was lower in CLL subjects, 17.25%. CV was 33.62% in normal cases and significantly higher in CLL with 42.95%. According to the infiltration patterns, Nodular pattern showed similar value to normal biopsies, versus Diffuse pattern with BT/TV of 16.19% and CV of 51.49%. Significantly, a high CV value was accompanied of a low B/TV value, in normal and CLL subjects. CONCLUSIONS: We analyzed histomorphometrically trabecular volume as expression of bone mass in undecalcified biopsies. CLL infiltration tended to show a lower trabecular volume. Diffuse pattern presented the higher cellular infiltration and bone mass destruction.

Purely cutaneous Rosai-Dorfman disease.

Sinus histiocytosis with massive lymphadenopathy is an entity that exceptionally appears as a purely cutaneous disease. We described 2 cases of this form with spontaneous involution. Histology showed a polymorphic infiltrate in the dermis and hypodermis composed of large histiocytes with lymphophagocytosis, neutrophils and plasma cells. Immunohistochemical stains demonstrated the positivity of histiocytes for protein S-100 and MAC 387.

[A CT cytomorphodensitometric study of the proliferating epithelial activity in middle ear cholesteatoma]. / Estudio citomorfodensitométrico por análisis de imagen de la actividad proliferativa epitelial en el colesteatoma de oído medio.

A cytomorphodensitometric study was made by analysis of the computerised image of the germinative and intermediate epithelial layers in a sample of five specimens of cholesteatoma and the corresponding skin from the external auditory canal. A morphometric variable corresponding to the nuclear area was determined and densitometric variables equivalent to the relative quantity of nuclear DNA were determined. Within the germinative layers of the cholesteatoma epithelium, we observed larger nuclei and more relative DNA per nucleus. The average densitometric values were in the range of 2C-4C, which is indicative of a greater cellular population in S phase in the cholesteatoma than in the skin.

[The study of proliferative epithelial activity in cholesteatoma of the middle ear during cytomorphophotometry]. / Estudio de la actividad proliferativa epitelial en el colesteatoma de oído medio mediante citomorfofotometría.

Epithelial proliferation in colesteatoma and its influence on the subepithelial inflammatory reaction was studied using morphometry and nuclear photometry of specimens. Twenty specimens of colesteatoma and 15 specimens of skin from the external auditory canal were examined. Nuclear content was greater in the basal cells of colesteatoma epithelium than in the basal cells of external auditory canal epithelium, suggesting increased proliferative activity. This activity was found to be reted to the inflammatory infiltrate of the conjunctive tissue and varied in different specimens.

HLA molecules in basal cell carcinoma of the skin.

Fifty basal cell carcinomas (BCC) and 8 samples of healthy skin were studied for HLA class I and class II antigen expression and for the presence of mutations in codon 12 of the K-ras and H-ras genes. All samples of healthy skin and of epithelium near the tumor showed high levels of class I molecules, whereas 38% of the tumors showed complete absence. Sixty-two percent of the tumors presented positive class I expression with heterogeneous staining. These losses were due to the simultaneous lack of heavy chain and beta 2-microglobulin. Selective losses of HLA-A or HLA-B antigens were not detected. Class II antigens were absent in most of the tumors, only two tumors showing a few weakly positive cells with anti-HLA-DR mAb. The loss of class I expression correlated significantly with the degree of histological differentiation and aggressiveness. We were unable to correlate class I expression with clinical size, depth of invasion or the extent of leukocytic infiltrate surrounding the tumor. Analysis by PCR amplification of codon 12 of the K-ras and H-ras oncogenes detected H-ras mutations in 1 out of 50 cases, and no K-ras mutations in any of the tumors studied. Thus, a positive relationship between K-ras and H-ras mutations and BCC tumorigenesis or MHC alterations seems unlikely in this neoplasia.

Primary non-Hodgkin lymphoma of the vulva.

We report a rare case of non-Hodgkin lymphoma located in the vulva. The diagnosis was supported by the cytological anomalies in material obtained by fine needle aspiration. The tumor was removed with wide excision, and the patient was alive and in good health ten months after surgery.

[Evaluation of IgG and IgA type antibodies to capsid and early antigens of the Epstein-Barr virus in the diagnosis of nasopharyngeal carcinoma]. / Valoración de anticuerpos tipo IgG e IgA frente a antígenos de cápside y tempranos del virus de Epstein-Barr en el diagnóstico del carcinoma de nasofaringe.

BACKGROUND: The Epstein-Barr virus (EBV) is related with nasopharyngeal carcinoma (NPC) in that, in this neoplasm, high levels of antibodies are found vs different EBV antigens. METHODS: The determinations of IgG and IgA type antibodies were evaluated vs capsid antigens (VCA) and early antigen (EA) of the EBV by indirect immunofluorescence in 14 patients diagnosed with NPC, in 12 patients with other tumors of the head and neck and in 61 blood donors. RESULTS: The detection of IgA type antibodies with a sensitivity and specificity of 100% and 92% for the VCA antigen and of 86% and 100% for the EA antigen are the most useful tests in the early diagnosis of nasopharyngeal carcinoma. The determination of IgG type antibodies were of a more limited usefulness with sensitivities and specificities of 86% and 67% for IgG anti-VCA and 100% and 83% of IgG anti-EA. CONCLUSIONS: The detection of antibodies vs VCA and EA antigens is useful in the differential diagnosis of NPC with other tumors of the head and neck.

K-ras mutations (codon 12) are not involved in down-regulation of MHC class-I genes in colon carcinomas.

Fifty-eight colorectal carcinomas were studied for HLA class-I antigen expression and for the presence of point mutations in codons 12 and 61 of the K-ras gene. Eight carcinomas were completely negative for class I by the APAAP technique. Analyses using the polymerase chain reaction (PCR) method, together with selective hybridization using mutation-specific synthetic oligonucleotides, demonstrated K-ras mutations in 14 cases (24.1%), all of them in codon 12. None of the mutations corresponded to the negative cases for class-I HLA antigen expression. We did not observe any correlation between K-ras mutations and the extent of tumor differentiation.

Class II HLA antigen expression in familial polyposis coli is related to the degree of dysplasia.

Class II HLA antigen expression was studied in 30 polyps from 3 patients who were diagnosed with familial polyposis coli. The highest levels of this expression were associated with the most severe grades of dysplasia (p less than 0.00001), the sequence of positivity being HLA-DR greater than DQ greater than DP. No association was observed between the expression of these antigens and the presence of a specific inflammatory leukocytic infiltrate. Our results imply that HLA class II molecule expression is somehow related to malignant transformation in familial polyposis coli in accordance with the adenoma-dysplastic adenoma-adenocarcinoma sequence. Thus these antigens may be useful markers to tumoral progression.

Class I and II HLA antigen distribution in normal mucosa, adenoma and colon carcinoma: relation with malignancy and invasiveness.

HLA class I and II antigen expression was studied in normal mucosa, adenoma and colon carcinoma. Alkaline phosphatase anti-alkaline phosphatase (APAAP) staining techniques were used in cryostatic sections with anti-HLA-ABC and DR,DP,DQ monoclonal antibodies. All normal mucosa were intensely positive for HLA class I antigen expression, while failing to express class II molecules, except in mucosa adjacent to tumors (15/19 cases). All adenomatous polyps expressed HLA class I antigen, while the intensity of class II expression (DR greater than DQ greater than DP) was paralleled by the degree of dysplasia. In colon carcinoma, the loss of class I expression was seen in 4 out of 32 cases, and class II expression was found to be heterogeneous in 16 of these 32 cases (DR greater than DP greater than DQ). No relationship was noted between class II expression and degree of differentiation. However a correlation was seen between HLA-DR antigen expression and degree of invasiveness, mononuclear infiltrate and prognosis, according to Jass's criteria.