The Mexican consensus on the detection and treatment of early gastric cancer. / Consenso mexicano sobre detección y tratamiento del cáncer gástrico incipiente.

Gastric cancer is one of the most frequent neoplasias in the digestive tract and is the result of premalignant lesion progression in the majority of cases. Opportune detection of those lesions is relevant, given that timely treatment offers the possibility of cure. There is no consensus in Mexico on the early detection of gastric cancer, and therefore, the Asociación Mexicana de Gastroenterología brought together a group of experts and produced the "Mexican consensus on the detection and treatment of early gastric cancer" to establish useful recommendations for the medical community. The Delphi methodology was employed, and 38 recommendations related to early gastric cancer were formulated. The consensus defines early gastric cancer as that which at diagnosis is limited to the mucosa and submucosa, irrespective of lymph node metástasis. In Mexico, as in other parts of the world, factors associated with early gastric cancer include Helicobacter pylori infection, a family history of the disease, smoking, and diet. Chromoendoscopy, magnification endoscopy, and equipment-based image-enhanced endoscopy are recommended for making the diagnosis, and accurate histopathologic diagnosis is invaluable for making therapeutic decisions. The endoscopic treatment of early gastric cancer, whether dissection or resection of the mucosa, should be preferred to surgical management, when similar oncologic cure results can be obtained. Endoscopic surveillance should be individualized.

Liver transplantation for neurologic Wilson's disease: reflections on two cases within a mexican cohort.

BACKGROUND: Liver transplantation (LT) in Wilson s disease (WD) is mostly indicated when progressing liver disease or acute liver failure occurs. In patients with neurological manifestations, this procedure has not gained wide acceptance based on previous reports of dismal prognosis. OBJECTIVE: To describe a Mexican cohort of pa- tients with WD with special focus on LT in patients with deteriorating neurological manifestations. MATERIAL AND METHODS: Patients with confirmed WD and their first-degree relatives were evaluated at the hepatology clinic of a tertiary referral hospital. Attention was placed on therapy and outcome. RESULTS: Eleven patients were followed for a period of up to 80 months (7 probands and 4 affected family members), 10 patients having hepatic manifestations and 4 having neuro psychia- tric phenomena. Pharmacologic treatment was uniform in most patients, and LT was indicated in 2 cases because of deteriorating neurological status. These patients had total remission of their neurological manifestations with marked improvement on imaging studies. CONCLUSIONS: Follow-up and pharmacologic treatment was flawed by several adverse conditions present in our population. Patients with progressing neurological disease had a favorable outcome after LT, a similar response to the one reported by several authors. In conclusion, LT should be strongly considered for the treatment of these patients.

[Concordance between pathologists in the diagnosis of gastric atrophy according with the OLGA system]. / Concordancia en el diagnóstico de atrofia gástrica entre patólogos según el sistema OLGA.

BACKGROUND: The intestinal gastric cancer is preceded by a sequence of pathological changes whose link is mucosal atrophy. The modified Sydney system for atrophy is a parameter not reproducible among pathologists. AIM: To know the interobserver variability using the OLGA system (Operative Link on Gastritis Assessment). METHODS: We selected 116 histologic slides. Sixty cases of both types of atrophy and 56 without atrophy were included. Three general pathologists, interested in gastrointestinal biopsies independently review the slides and established a diagnosis. For statistical analyses we employed singles frequencies in order to describe the individual diagnosis and the kappa test for evaluate the concordance between 2 and 4 observers with 2 and 3 categories. RESULTS: The global concordance has a kappa index of 0.48 (IC 95% 0.4-0.57). When we compared two pathologists the kappa index varies from 0.82(IC 95% 0.73-0.91) to 0.36 (IC 95% 0.22-0.5). The consensus among three pathologists was achieved in 25 out 30 slides in the metaplastic variety and 11 out 30 for the non-metaplastic type. The concordance for the atrophy scale has a kappa index between 0.2 and 0.5. CONCLUSION: The problematic atrophic evaluation with the Sydney system justify every effort to improve the interobserver evaluation. The OLGA system seems reproducible, although laborious,it requires a careful application, but with daily practice it could be applied easier. The clinician acceptation becomes crucial.

Laparoscopic approach to fever of unknown origin.

BACKGROUND: Fever of unknown origin (FUO) is difficult to diagnose. Laparotomy is needed to establish the etiologic diagnosis in some patients. The aim of this study was to analyze the feasibility, safety, and success rate of a protocolized laparoscopy in patients with FUO. METHODS: An extensive clinical evaluation was performed before surgery. Laparoscopy included inspection of the abdominal cavity, wedge and tru-cut liver biopsies, lymph node biopsy, splenectomy, and bone marrow biopsy. Histologic analysis, permanent section analysis, and cultures were obtained. RESULTS: The study involved 15 patients with a mean age of 43.6 +/- 14.5 years. The mean operative time was 122 +/- 60 min. Minor complications occurred in 9% of the patients. One patient bled after surgery and underwent reoperation. There was no operative mortality. An etiologic diagnosis was made in 66% of the patients, and laparoscopy helped to rule out intraabdominal pathology in four additional patients, giving a total success rate of 93%. CONCLUSION: Protocolized laparoscopy in patients with FUO is safe, feasible, and accurate.

Histologic diagnosis of primary hyperparathyroidism: a concordance analysis between three pathologists.

Primary hyperparathyroidism (HPT) is caused by a parathyroid adenoma, hyperplasia or carcinoma. Difficulties for the histologic diagnosis of abnormal parathyroid tissue are widely recognized. The aim of the study was to evaluate the reproducibility of the morphologic criteria through a concordance study among three pathologists. Representative slides of 40 patients with biochemically primary HPT stained with hematoxylin and eosin were blindly reviewed by three pathologists. Each pathologist established the diagnosis of adenoma or hyperplasia and assessed the presence of fat cells, a rim of normal tissue, a fibrous capsule, the number of cellular types, the lobular pattern, and the characteristics of the blood vessel's wall. A concordance analysis was then performed. Mean age of the group was 55 +/- 14 yr, 7 were males and 33 females. The concordance analysis among the three pathologists for the differential diagnosis between adenoma and hyperplasia, showed a Kappa index of 0.5. Kappa index for the presence of fat cells was 0.56, for the presence of a rim of normal tissue 0.47, and for the number of cellular types 0.29. The concordance for the differential diagnosis between parathyroid adenoma and hyperplasia in this study was low.

Carcinoid tumors of the extrahepatic bile ducts: a study of seven cases.

The authors report seven patients with carcinoid tumors of the extrahepatic bile ducts (EHBDs). All patients were women, with an average age at diagnosis of 49.8 years (range, 37-67 yrs). The most common presenting symptom was painless jaundice with or without pruritus. Although one patient had peptic ulcer disease before the onset of obstructive jaundice, none had systemic endocrine manifestations. These neoplasms were most often located in the common bile duct. Grossly, the carcinoid tumors were usually nodular and poorly demarcated, and ranged from 1.1 to 2.7 cm in size. Only one of the neoplasms was polypoid. Microscopically, the tumors had a trabecular or nesting pattern with occasional tubule formation, and were composed of relatively small cells with granular chromatin. All of the neoplasms expressed chromogranin and two expressed synaptophysin. Three expressed serotonin and two of the three were also immunoreactive for pancreatic polypeptide or somatostatin. Two tumors were focally positive for gastrin and one of these two tumors was also positive for serotonin and pancreatic polypeptide. All seven carcinoid tumors showed no immunoreactivity for p53, and assays for p53 loss of heterozygosity analysis were negative in two, suggesting that p53 mutations do not play a role in the pathogenesis of EHBD carcinoids. A mutation in codon 12 of K-ras was found in one carcinoid tumor whereas two of two showed immunoreactivity for Dpc4 protein. In view of the small number of carcinoids studied, the importance of these findings in the pathogenesis of these tumors is unclear. Ultrastructural examination of three of the tumors revealed numerous membrane-bound, round neurosecretory granules. Clinically, these lesions had an indolent course. Even in the presence of lymph node metastases (noted in two patients), all of the patients remained disease free 2 to 11 years (average follow up, 6.6 yrs) after segmental resection or pancreaticoduodenectomy (Whipple's procedure). Because carcinoid tumors of the EHBD are of low malignant potential, they should be separated from the more common adenocarcinomas in this location.

[Comparison of the usefulness of intraoperative examination and fine needle aspiration biopsy in thyroid lesions. Analysis of discordant cases in aspiration biopsy]. / Comparación de la utilidad del estudio transoperatorio y la biopsia por aspiración con aguja delgada en lesiones de tiroides. Análisis de casos discordantes en biopsias por aspiración.

INTRODUCTION: Fine-needle aspiration biopsy (FNAB) is currently considered the most reliable and cost effective examination for diagnosis of solitary thyroid nodules prior to surgery. Because of its great utility the indication of intraoperative examination (IOE) (macroscopic examination, cytology and frozen section), has recently been questioned. OBJECTIVE: To compare the accuracy of the FNAB and IOE, in those patients with nodular thyroid disease who undergo thyroidectomy. As well as to analyse the, discrepant cases by FNAB. MATERIAL AND METHODS: The results of IOE and FNAB were compared in a period of two years (1997-98) at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ). In all cases the diagnosis established from paraffin embedded tissue sections was considered to be the gold standard. The cytologyc smears and the histologic sections of the discrepant cases were reviewed. RESULTS: One thousand and fourteen IOE were done during two consecutive years; from these cases, 136 (13.4%) were thyroid lesions. Half of the thyroid lesions (69 cases) corresponded to carcinomas, the others were follicular adenomas (13 cases) and non-neoplasic lesions (54 cases). The analysis of the copacity to discriminate between malignant and benign diseases with IOE and FNAB demonstrated sensitivity of 89% (CI: 78.2-95.1) and 97.7% (CI: 86.8-99.9), specificity of 100% (CI: 93.1-100) and 90% (CI: 90.4-96.7). The positive predictive value of 100% and 91.6%, negative predictive value of 90.4% and 97.3%, and equal accuracy (94.6% and 94.1% respectively). When the analysis of capacity to stratify diseases was performed, IOE and FNAB showed similar percentages in all the cases, including the follicular adenomas and carcinomas. The causes of false positive and false negative cases by FNAB, reproduce what has been written in the literature. CONCLUSIONS: FNAB preoperative examination is adequate for the selection of patients that undergo thyroidectomy. Nevertheless, IOE should be done in most of the cases, and routinely in those cases with inconclusive FNAB results and in cases of follicular tumor.

Primary Sjögren's Syndrome and Celiac Disease: Causal Association or Serendipity?

Primary Sjögren's syndrome (pSS) is an autoimmune disease associated with other autoimmune diseases like thymoma, hypothyroidism or mucosa-associated lymphoid tissue lymphomas. Celiac disease (CD) is a gluten sensitive enteropathy that causes small bowel mucosal damage in genetically susceptible individuals. Several immunologic alterations and immune-associated diseases, for example, insulin dependent diabetes mellitus, autoimmune thyroid disease, and connective tissue disorders, have been described in CD. We report 3 of 141 pSS patients who also had CD and review literature that suggests that CD is increased in patients with pSS. Successful treatment of CD did not relieve sicca symptoms or signs; thus, the two diseases must be treated independently. Although intestinal inflammation can occur in patients with pSS, diarrhea should be evaluated for CD and other causes. Because of the occasional severity of CD, clinicians must be aware of the possible association with pSS.

Obstructive jaundice as the first clinical manifestation of a metastatic malignant melanoma in the ampulla of vater.

The authors report a patient with obstructive jaundice as the first clinical manifestation of a primary malignant melanoma metastatic in the ampulla of Vater. After the histologic diagnosis of the metastases was made, the primary tumor was located in the skin of the back. Obstruction jaundice secondary to ampullary obstruction due to metastatic melanoma has only been reported twice, and in neither case was jaundice the first symptom of the disease.

High prevalence of a 30-base pair deletion in the Epstein-Barr virus (EBV) latent membrane protein 1 gene and of strain type B EBV in Mexican classical Hodgkin's disease and reactive lymphoid tissue.

Depending on geographic location and patient age Hodgkin's disease (HD) is associated with Epstein-Barr virus (EBV), mostly type A EBV, in 20% to 100%. The highest prevalence occurs in children of developing countries. Molecular analysis of the oncogene coding for the latent membrane protein 1 (LMP-1) revealed a 30-base pair (bp) deletion in up to 46% of EBV-positive HD. We investigated the presence of EBV in a series of Mexican classical HD (n = 57) and reactive lymphoid tissues (n = 20) from a private and a public hospital with special emphasis on the prevalence of the 30-bp deletion and the type of EBV. EBV infection was analyzed at the cellular level by Epstein-Barr encoded early RNA transcripts (EBER) in situ hybridization (ISH) and by LMP-1 protein immunohistochemistry (IHC). Molecular analysis of the LMP-1 gene configuration was performed by polymerase chain reaction (PCR) with primers spanning the site of the deletion and subsequent Southern and/or dot blot hybridization using wild-type and deletion-specific probes. The prevalence of type A and type B EBV was investigated by PCR-analysis for divergence in the coding region of Epstein-Barr nuclear antigen (EBNA)-2. EBV was detected in Hodgkin- and Reed-Sternberg cells (H-RS) by LMP-1 IHC and/or EBER ISH in 35/57 (61%) Mexican HD including 18/32 (56%) with nodular sclerosis, 15/20 (75%) with mixed cellularity and 2/4 (50%) with lymphocyte depletion. In addition, LMP-1 gene sequences were detected by PCR in 9 cases of HD without LMP/EBER expression by H-RS cells and in 17/20 (85%) reactive lymph nodes, supposedly originating from rare latently infected B cells. Surprisingly, the 30-bp LMP-1 deletion was found in 28/35 (80%) EBV-positive HD. This deletion, however, was also found in all 9 (100%) HD with H-RS cells negative for EBV and in 10/17 (59%) reactive lymph nodes. Thus, the overall LMP-1 del prevalence in reactive tissue is 73% (19/26). Typing of EBV was successful in 26 cases of EBV-positive HD, 10 of these were infected by type B EBV (38%). Of the reactive lymphoid tissue, 9 (47%) were infected by type A, and 10 (53%) by type B; All 20 cases (100%) associated with type B, whether neoplastic or reactive, displayed the LMP-1 del variant compared with 18/25 (72%) infected by type A EBV. To our knowledge, this is the highest incidence for both the LMP-1 deletion variant and the infection by type B EBV in HD reported so far worldwide. Our data suggest that EBV infection contributes to the pathogenesis of the majority of Hodgkin's disease cases in Mexico. The specific tumorigenic role of the LMP-1 deletion variant, however, is doubtful with regard to its high frequency in nonneoplastic lesions. Moreover, type B infection frequently occurs in Mexican HD and reactive lymphoid tissue and is consistently associated with the deletion variant pointing to a pathogenetic role of this combined genotype.

Oral manifestations as a hallmark of malignant acanthosis nigricans.

We present a case of malignant acanthosis nigricans (AN) that initially manifested in the oral cavity. In the present report, the patient had typical clinical and histological findings of oral and esophageal AN, with subtle skin changes, associated with a gallbladder adenocarcinoma. The importance of the clinical oral examination is emphasized because the recognition of oral lesions led to the diagnosis of AN and to the following detection of the internal malignancy. Since the tumours associated with AN are highly malignant, it is of the utmost importance to recognize the skin and mucous membrane changes in adults.

A clinicopathologic variant of intramucosal early gastric cancer with widespread dissemination: report of three cases.

We describe the clinicopathological characteristics and postmortem findings of three cases of intramucosal early gastric cancer (EGC) selected from nine cases of our series to characterize its unusual clinical behavior. All patients were treated at the Instituto Nacional de la Nutricion in Mexico City between January 1986 and December 1995. The following features were the most salient of the three cases: (1) The tumors were constituted by only few nests of intramucosal cells; two of them were signet-ring cell carcinomas and the other one was of the intestinal type. (2) Grossly, all tumors were inconspicuous. (3) All the patients had a short clinical course and in none of them the clinical diagnosis was suspected. (4) A wide dissemination was found at autopsy; additionally, in two of the cases, extensive lymphatic and venous thrombi and multiple secondary hemorrhages were found. (5) In all patients, the symptoms and deaths were caused by the metastases. No cases as early as those reported here were found either in the Japanese or in Western literature. Although larger series of EGC should be studied in our country, these findings suggest that at least in Mexico there is a group of EGC with unusual aggressive behavior.

[Quality control of 135 histopathological reports of colo-rectal carcinoma]. / Control de calidad de 135 informes histopatológicos de carcinoma colo-rectal.

OBJECTIVE: To evaluate the information content in our surgical pathology reports of colon and rectum carcinoma. SETTING: A third level hospital. DESIGN: Consecutive surgical reports from 1988 to 1994 were retrieved. The gross and histological variables with prognostic relevance according to the TNM system were registered using a checklist with standardized variables as proposed by two groups of pathologists. The adequacy of our reports was surveyed counting the number of histopathological variables in relation to the 11 prognostic parameters that must be included in routine surgical reports of large colon carcinomas. RESULTS: The surgical reports were 135. The histologic type, tumor grade and histological tumor invasion were provided in most of the reports. In 90% the lymph node characteristics were described and 85% had gross and histologic margin assessment. But other variables were poorly informed, i.e. vascular invasion was informed in one case (0.7%). CONCLUSIONS: Our surgical reports were considered adequate as 113/135 (84%) recorded more than eight prognostic variables. Insufficient data were: 1) a poor gross description; 2) lack of tumor grading in 12%; and 3) omission of anatomic site in 29%.

[Giant acinic cell parotid gland adenocarcinoma of the papillary- cystic type]. / Adenocarcinoma gigante de células acinares de tipo quístico papilar en parótida.

A case of a 38-year-old male having an acinic cell adenocarcinoma of the parotid gland is reported. The tumor measured 22 cm and histologically it was of the papillary-cystic type. The following features were of interest: 1) the tumor size surpassed the size of previous reported acinic cell adenocarcinomas by 9 cm; and 2) the rarity of its histological variety (cystic papillary) demanded immunohistochemical and electron microscopic studies to confirm the diagnosis.

[Leiomyosarcoma associated with Epstein-Barr virus in an adult with renal transplant]. / Leiomiosarcoma asociado con el virus de Epstein-Barr en un adulto con trasplante renal.

Recently the association between the Epstein-Barr virus (EBV) and smooth muscle lesions has been described in immunosuppressed children but it is infrequent in adults. The role of EBV in the pathogenesis of these lesions is obscure. We presents a 28 year old man with end stage renal disease transplanted in 1994. Two years later he developed several nodular lesions that affected both lungs, liver, spleen, retroperitoneal ganglia and the left thigh; one year later he died. The surgical specimen from the thigh and a liver biopsy were diagnosed as leiomyosarcoma. Immunohistochemical reactions against vimentin and smooth muscle actin were positive. In situ hybridization disclosed positivity against EBV nuclear antigens (EBNA-2) in neoplasic cells. This is the first case of sarcoma in transplanted patients of our institution and represents a rare case of leiomyosarcoma associated with EBV in adults.

Primary intestinal non-Hodgkin's lymphoma and Epstein-Barr virus: high frequency of EBV-infection in T-cell lymphomas of Mexican origin.

Epstein-Barr virus is universally associated with endemic Burkitt's lymphoma (BL) and undifferentiated nasopharyngeal carcinoma and can be detected in a significant proportion of cases of Hodgkin's disease (HD) and peripheral T-cell lymphoma, but only rarely in sporadic B-NHL. The frequency of EBV-positivity in certain neoplasms shows important geographic variations. Both HD and sporadic BL from Latin America have shown higher rates of EBV-association than cases from Western countries. In T-NHL, the frequency of EBV-positivity is influenced by the site of the primary tumor and the phenotype of the neoplastic cells. Nasal and nasal-type T-NHL, which show a T/NK-cell phenotype with expression of CD56 are virtually always EBV-associated, whereas only a proportion of nodal, gastrointestinal and pulmonary T-NHL are EBV-infected. A recent investigation of primary intestinal lymphomas of Mexican origin demonstrated EBV-positivity in all examined cases of T-NHL and BL and a proportion of other B-NHLs. The presence of EBV was independent of the presence or absence of enteropathy. Two of 6 cases studied showed CD56 expression. The high rate of EBV-positivity independent of histologic subtype is in contrast to the low to intermediate rates of EBV-positivity found in cases of intestinal T-NHL from Western countries and indicates that geographic differences in the frequency of EBV-association of lymphoid neoplasms might also extend to a fraction of peripheral T-cell lymphomas.

Post-transplantation lymphoproliferative disorders in Mexico: an aggressive clonal disease associated with Epstein-Barr virus type A.

Post-transplantation lymphoproliferative disorders (PT-LPDs) are a complication of immunosuppression with variable clinical behavior and frequent Epstein-Barr virus (EBV) association. There is geographic variation in the association of EBV with certain tumors and a lack of studies of PT-LPDs from developing countries, so we decided to study in detail a series of PT-LPDs from Mexico to identify similarities and differences between populations in Mexico and those in Europe and the United States. We used paraffin-embedded tissue from eight PT-LPDs (six from men, two from women) that arose after renal transplantation. Clinical data, morphologic features, and clonality on the basis of immunoglobulin (Ig) light chain restriction, as well as polymerase chain reaction (PCR) for Ig heavy chain genes, were studied. The presence of EBV was investigated with PCR, immunohistochemical analysis for latent membrane protein (LMP)-1, and in situ hybridization for EBV early RNA transcripts. In addition, the subtype of EBV based on the EBNA 2A and 2B genes and the presence of a 30-bp deletion in the LMP-1 gene were investigated by PCR. Seven (87.5%) of eight cases presented with gastrointestinal involvement; five patients died. Three cases were polymorphic PT-LPDs, four were monomorphic large cell lymphomas (one diffuse large cell, three immunoblastic), and one was unclassifiable. All showed a B-cell phenotype, with a clonal population demonstrated in seven of the eight cases. Tumor cells expressed EBERs in all of the cases and LMP-1 in six of seven evaluable cases. Seven of seven cases showed EBV subtype A. Two (25%) of eight cases had the 30-bp LMP-1 deletion. This study shows that PT-LPDs in Mexico are clonal disorders associated with EBV subtype A. In contrast to series from Europe and the United States, our cases showed a significantly higher incidence of gastrointestinal tract involvement (P < .001), and a lower incidence of the 30-bp LMP-1 deletion, although this was not statistically significant (P < .28).

Tall cell variant of papillary thyroid carcinoma. A cytohistologic correlation.

OBJECTIVE: To identify the cytologic characteristics of the tall cell variant of papillary thyroid carcinoma in fine needle aspiration biopsies and make a cytohistologic correlation. STUDY DESIGN: The study group consisted of six patients subjected to fine needle aspiration biopsy of the thyroid prior to surgical resection of the tumor. RESULTS: Nineteen cases of the tall cell variant were identified in 229 cases of papillary thyroid carcinoma (8.5%) from 1957 to 1993. Six cases had aspirates with tall cells. The patients were females with a median age of 43 years, and all had aggressive neoplastic diseases. The tumors had > 30% tall cells. The fine needle aspiration biopsy findings included nuclear grooves and abundant oxyphilic cytoplasm (100%), pseudonuclear inclusions (83.3%) and ground glass chromatin (67%). The majority of neoplastic cells had a nuclear/cytoplasmic ratio of 1:2. A tadpole shape was observed in noncohesive cells, and a respiratory epithelium-like arrangement was seen in cohesive cells. CONCLUSION: Fine needle aspiration biopsy is the best method of identifying tall cells preoperatively. Nuclear and cytoplasmic changes should be added to make a firm diagnosis of the tall cell variant and to rule out columnar cell carcinoma or squamous metaplasia in goiter or usual thyroid papillary carcinoma.