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Arch Pathol Lab Med

Protocol for the examination of specimens removed from patients with gastric carcinoma: a basis for checklists. Members of the Cancer Committee, College of American Pathologists, and the Task Force for Protocols on the Examination of Specimens From Pat

Compton C. Sobin LH.
Department of Pathology, Massachusetts General Hospital, Boston 02114, USA.
A protocol for the pathologic examination and reporting of specimens from patients with gastric carcinoma has been developed by the Cancer Committee of the College of American Pathologists and a multidisciplinary task force of specialists dealing with patients with gastric carcinoma. The protocol incorporates all basic pathology data of diagnostic and prognostic significance appropriate for the treatment of patients with gastric carcinoma. The purpose of the protocol is to serve as a basis for the development of checklists, as on outline for full narrative reporting, as a basis for research protocols, or as a guide for other types of synoptic or reporting formats. The protocol is stratified to accommodate the surgical procedures usually employed for gastric carcinomas, including acquisition of cytologic specimens, incisional endoscopic biopsy, excisional biopsy, and gastric resection (partial or complete). Explanatory notes detailing specific procedures and rationales for documentation of specific pathologic data are included in the protocol. The protocol uses the staging system for gastric carcinoma defined by the American Joint Committee on Cancer and the International Union Against Cancer.

Metastatic tumors of the thyroid gland: a study of 79 cases in Chinese patients.

Lam KY. Lo CY.
Department of Pathology, Queen Mary Hospital, Hong Kong.
OBJECTIVE: To evaluate the clinical and pathologic impact of metastases to the thyroid gland. CASE MATERIAL: We studied the clinical/autopsy records and pathologic features of 79 Chinese patients (38 men, 41 women) with secondary tumors of the thyroid over a 26-year period. RESULTS: The incidence of thyroid secondaries at autopsy was 0.5% and at thyroidectomies for malignancy was 1.2%. Eighteen (23%) of the 79 patients presented with an enlarged mass in the thyroid. The diagnosis of metastasis in the thyroid gland was suspected clinically in six cases. Fine-needle aspiration cytology detected an 80% malignancy rate, but in only half of such cases was the diagnosis specific for secondary malignancy. Many of the metastatic lesions in the thyroid gland occurred shortly after the detection of primaries (mean latency period, 9 months). The time from diagnosis of the primary tumor to metastasis to the thyroid gland was greater than or equal to 3 years in only eight patients. The majority (81%) of the secondary tumors were carcinomas. Of these, the lung was the most common primary tumor site (43%), followed by the breast (9%) and stomach (8%). Rare sources of primary tumors, such as nasopharyngeal carcinoma, choriocarcinoma, malignant phylloides, and osteosarcoma, were also found. The metastatic lesions in the thyroid gland could be identified macroscopically in 43 patients (54%). Lesions were often solitary (n = 24) rather than diffuse (n = 8) or multiple (n = 11). Microscopic examination revealed that secondary thyroid tumors were often moderate or poorly differentiated adenocarcinomas (n = 42). All the patients died shortly after the appearance of metastatic lesions in the thyroid gland. CONCLUSIONS: Metastasis in the thyroid gland is uncommon and may be a diagnostic problem. Its presence often indicates a poor prognosis.

Cell proliferative activity in intraductal papillary-mucinous neoplasms and invasive ductal adenocarcinomas of the pancreas: an immunohistochemical study.

Terada T. Ohta T. Kitamura Y. Ashida K. Matsunaga Y.
Second Department of Pathology, Tottori University Faculty of Medicine, Yonago, Japan.
OBJECTIVE: To evaluate cell proliferative activity and expression of cytokeratins (CKs) and epithelial membrane antigen (EMA) in intraductal papillary-mucinous neoplasm of the pancreas (IPNP). METHODS: We examined cell proliferative activity in normal pancreatic ducts, IPNP, and invasive ductal adenocarcinoma of the pancreas by immunohistochemistry for proliferating cell nuclear antigen (PCNA) and Ki67 antigen. Expression of CKs and EMA was also examined immunohistochemically. RESULTS: In normal pancreas (n = 5), PCNA- or Ki67-positive ductal epithelia were not found. Cytokeratins (polyclonal, CAM5.2, CK-7, CK-8, CK-18, and CK-19) were expressed in the ducts and ductules but not in the acinus, and EMA expression was noted in the acinus but rarely in the ducts. In IPNP (n = 9) and invasive ductal adenocarcinoma (n = 6) of the pancreas, the overall PCNA-labeling index (PCNA-LI) was 3.2 +/- 4.1 and 16.0 +/- 7.2, respectively, and overall Ki67-LI was 2.2 +/- 2.6 and 14.5 +/- 6.3, respectively. In IPNP, the PCNA-LI and Ki67-LI were low in adenoma areas (PCNA-LI = 0.9 +/- 0.7), intermediate in dysplastic areas (PCNA-LI = 3.7 +/- 2.4), and rather high in carcinoma in situ areas (PCNA-LI = 11.5 +/- 8.4). Both CKs and EMA were noted in tumor cells. CONCLUSIONS: The data suggest that cell proliferative activity is low in IPNP compared to invasive ductal adenocarcinoma, that cell proliferative activity increases with the grade of cell atypia in IPNP, and that CK expression is not changed during the neoplastic change, but EMA is newly expressed or overexpressed during the neoplastic change.

Diffuse hyperplasia of the peribiliary glands.

Dumas A. Thung SN. Lin CS.
Lillian and Henry M. Stratton-Hans Popper Department of Pathology, Mount Sinai School of Medicine of the City University of New York, NY 10029, USA.
Diffuse, severe, macroscopically recognizable dilatation and hyperplasia of the peribiliary glands of intrahepatic and extrahepatic bile ducts is an extremely rare condition. To our knowledge, this is the first such case reported in the literature. We encountered this condition in a patient with massive hepatic necrosis. The pathogenesis of the condition is discussed. Unfamiliarity with this pathology could lead to an erroneous diagnosis of a well-differentiated cholangiocarcinoma.

Giant heterotopic gastric polyp in the jejunum.

Nowak M. Deppisch L.
Department of Pathology, Western Reserve Care System, Youngstown, Ohio 44501, USA.
Polypoid lesions composed of gastric mucosa in the jejunum are rare. The vast majority of cases of ectopic gastric tissue occur in the duodenum. In this article, we present a case of heterotopic gastric mucosa forming a giant polyp in the mid jejunum. A review of the literature is presented, and the clinical and pathologic features of this unusual lesion are discussed.

Allogeneic blood transfusion, hospital charges, and length of hospitalization: a study of 487 consecutive patients undergoing colorectal cancer resection.

Year 1998
Vamvakas EC. Carven JH.
Massachusetts General Hospital, and Department of Pathology, Harvard Medical School, Boston, USA.
OBJECTIVE: To investigate the independent association of allogeneic blood transfusion with longer hospital stays and higher hospital charges, after adjustment for the effects of confounding factors that are related to both these outcomes and the receipt of a perioperative transfusion. DESIGN AND METHODS: The records of 487 consecutive patients undergoing colorectal cancer resection and assigned a diagnosis-related group code between 146 and 149 were reviewed. The influence of allogeneic transfusion in explaining the variation in the observed length of stay and total hospital charges was calculated after adjustment for the effects of 20 confounding factors that related to severity of illness, difficulty of operation, and risk of postoperative infection. RESULTS: Length of stay (mean +/- SE) was 16.7 +/- 0.81 days in the transfused group, compared with 10.3 +/- 0.26 days in the untransfused group (P < .0001); hospital charges were $28101 +/- 1121 and $15978 +/- 265, respectively (P < .0001). After adjustment for the effects of 20 confounding factors, length of stay increased by 1.3% (95% confidence interval 0.5% to 2.1%) per unit of red blood cells and/or platelets transfused (P < .001), and hospital charges increased by 2.0% (95% confidence interval, 1.4% to 2.6%) per unit (P < .001). CONCLUSION: Allogeneic transfusion was independently associated with longer hospital stays and higher hospital charges. This association may be due to a relationship between allogeneic transfusion and a higher incidence of septic complications of surgery or may reflect the function of blood transfusion as a surrogate marker for severity of illness.

Cathepsin B expression and its correlation with tumor-associated laminin and tumor progression in gastric cancer.

Year 1998
Khan A. Krishna M. Baker SP. Malhothra R. Banner BF.
Department of Pathology and Academic Computing, University of Massachusetts Medical Center, Worcester 01655, USA.
OBJECTIVE: Cathepsin B, a lysosomal cysteine proteinase, is associated with degradation of laminin. Its activity has been shown to be increased in gastric carcinomas. Laminin is one of the major components of basement membrane involved in cell-matrix interactions and tumor progression. The objectives of this study were to correlate cathepsin B expression in tumor cells with tumor-associated laminin and to further correlate the two with tumor progression. DESIGN AND SETTING: Resected gastric carcinomas (n = 29) taken from the surgical pathology files of the University of Massachusetts Medical Center, Worcester, were immunostained with cathepsin B and laminin using the avidin-biotin complex technique. Statistical analysis was performed using the exact linear by linear association test and exact Kruskal-Wallis test. Kaplan-Meier curves were plotted, and survival analysis was performed using a nonparametric log-rank test. RESULTS: Cathepsin B was expressed in 27 (93%) of 29 tumors (11 weak and 16 strong). Staining of tumor-associated laminin showed patterns ranging from almost continuous (n = 4) to moderately discontinuous (n = 11) and highly fragmented (n = 14). The degree of cathepsin B staining in tumor cells significantly correlated with the laminin distribution pattern (P = .0001). The association between increased cathepsin B, decreased laminin, and higher tumor stage was also significant. CONCLUSIONS: Increased cathepsin B expression by tumor cells associated with decreased tumor-associated laminin may suggest a mechanism for local tumor progression and metastasis. Staining for cathepsin B and laminin may be of prognostic value in gastric carcinomas.

Lipoblastomatosis combined with intestinal neuronal dysplasia.

Year 1998
Huang CC. Ko SF. Chuang JH. Chen WJ.
Department of Pathology, Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
We report the case of a male infant with multifocal lipoblastomatosis and intestinal pseudo-obstruction for whom the pathologic findings of rectal biopsy were consistent with intestinal neuronal dysplasia. Lipoblastomatosis is a benign neoplasm of human fetal white adipose tissue that mainly occurs in infants and children. Intestinal neuronal dysplasia is a disorder that clinically mimics Hirschsprung's disease and that is pathologically characterized by parasympathetic hyperganglionosis of the enteric nervous system. To our knowledge, the combination of lipoblastomatosis and intestinal neuronal dysplasia has never been documented, and the gene mutations involved are completely different. In this case, therefore, we postulate that intestinal neuronal dysplasia may be secondary to either compression of the nerve tract or inhibition of bowel movement due to lipoblastomatosis.

Nodular neuronal hyperplasia: a distinct morphologic type of pseudopolyp in inflammatory bowel disease.

Year 1998
Popiolek DA. Kahn E. Procaccino JA. Markowitz J.
Department of Laboratories, North Shore University Hospital-New York University School of Medicine, Manhasset 11030, USA.
Pseudopolyps constitute a relatively common finding in inflammatory bowel disease and have well-defined microscopic appearances. We report a new, unusual morphologic feature of colonic pseudopolyps in a patient with Crohn's disease, nodular neuronal hyperplasia.

A rare common hepatic duct diverticulum causing fatal biliary obstruction and sepsis.

Year 1998
Flowers MB. Ho KJ.
Department of Pathology, University of Alabama at Birmingham Medical Center, 35233, USA.
The case of a 59-year-old woman who presented with signs and symptoms of biliary obstruction and cholangitis is reported. The patient's clinical course was punctuated by recurring sepsis and acute hemorrhagic pancreatitis. Computed tomography revealed extrinsic compression of the common hepatic duct, which was nonfilling on cholangiography, thus raising the suspicion of a solid tumor; the common hepatic duct diverticulum was not revealed until autopsy. Diverticula in this region of the biliary tract are extremely rare and may, as in this case, present a diagnostic challenge and result in a fatal outcome.

Relationship between the effector T-cell response and viremia in symptomatic chronic hepatitis C.

Year 1998
Mosnier JF. Pham BN. Scoazec JY. Dubois S. Marcellin P. Martinot-Peignoux M. Degos F. Erlinger S. Degott C.
Service d'Anatomie et de Cytologie Pathologiques, Hopital Beaujon, Clichy, France.
OBJECTIVE: The purpose of this study was to assess the relationship between hepatitis C virus (HCV) viremia, HCV genotype, histologic activity index, and intrahepatic densities of immunocompetent lymphoid cells in chronic hepatitis C. METHOD: Liver biopsy specimens from patients with chronic hepatitis and anti-HCV antibodies, 5 with low-level HCV viremia and 26 with high-level HCV viremia, were studied. Sections of snap-frozen specimens were immunostained with monoclonal antibodies directed against different subsets of B cells, follicular reticulum cells, and T cells, including CD45RA-naive cells and CD45RO-primed cells. The densities of each subset of lymphoid cells were calculated with a computerized image analyzer. Hepatitis C virus RNA was measured with a quantitative branched DNA signal amplification assay, and HCV genotypes were determined with the line probe assay. RESULTS: A statistical correlation was found between the level of HCV viremia and the histologic activity index (P = .002). There were also significant correlations between the densities of CD3+ T cells and CD45RO+-primed cells in the liver and the histologic activity index and (P = .024 and P = .005, respectively), and significant correlations were found between the densities of CD3+ T cells, CD4+ T cells, CD8+ T cells, and CD45RO+-primed cells and HCV viremia (P = .005, P = .03, P = .03, and P = .02, respectively). Whatever the viremia status, CD45RO-primed cells were more numerous than CD45RA-naive cells in lobules and portal tracts. The CD45RO/CD45RA ratio was significantly higher when intraportal lymphoid aggregates were present. Eight patients were infected with genotype 1b, and 11 were infected with genotype 3b. There were no statistical differences in the histologic activity index, viremia, and density of immunocompetent cells in the liver between these two HCV genotypes. CONCLUSIONS: The results of this study suggest that the density of antigen-primed effector T cells in the liver of symptomatic patients with chronic hepatitis C is adapted to HCV viremia but is independent of the occurrence of genotypes 1b or 3a, the most frequent genotypes found in France.

NADPH diaphorase-containing nerve fibers and neurons in the myenteric plexus are resistant to postmortem changes: studies in Hirschsprungs disease and normal autopsy material.

Year 1998
Wester T. O'Briain S. Puri P.
Children's Research Centre, Our Lady's Hospital for Sick Children, Dublin, Ireland.
OBJECTIVE: Nitric oxide is considered to be the most important messenger of inhibitory nonadrenergic, noncholinergic nerves in the enteric nervous system. Histochemical studies have shown that nitric oxide synthase is identical to reduced nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase. Histochemical staining with NADPH diaphorase has been widely used to study nitrergic innervation of the gastrointestinal tract, but fresh tissue is considered a prerequisite for satisfactory results. The purposes of this study were to evaluate whether whole-mount specimens of human bowel obtained after death are suitable for histochemical staining with NADPH diaphorase and to compare the staining properties with those of specimens of resected bowel from patients with Hirschsprung's disease METHODS: Whole-mount preparations of the myenteric plexus were examined using NADPH diaphorase histochemical staining of bowel specimens obtained at autopsy from 18 pediatric subjects (31 specimens). Fresh tissue was also obtained from the colon of four patients with Hirschsprung's disease. The staining properties of postmortem specimens were assessed in relation to the postmortem time before fixation (

Expression spectrum of melanoma antigen-encoding gene family members in colorectal carcinoma.

Year 1998
Hasegawa H. Mori M. Haraguchi M. Ueo H. Sugimachi K. Akiyoshi T.
Department of Surgery, Medical Institute of Bioregulation, Kyushu University, Beppu, Japan.
OBJECTIVE: The 12 members of the human melanoma antigen-encoding (MAGE) gene family encode tumor-specific peptide antigens. Some antigens coded by the MAGE genes are potentially useful for cancer-specific immunotherapy. However, little information on the expression of these genes in human colon carcinomas is available. We investigated the expression of 10 of the 12 genes in human colon tissue. DESIGN: Eighty pairs of tumor and normal tissue samples from the human colon were studied by means of reverse transcription-polymerase chain reaction. RESULTS: None of the genes was expressed in the 80 control samples of normal tissue. On the other hand, expression was recognized in tumor samples, ranging from 5% of samples for MAGE-6 to 44% for MAGE-8. Seventy of the 80 tumor samples (88%) expressed at least 1 of the 10 MAGE genes. The frequency of liver metastasis was significantly higher in cases with tumor samples that expressed MAGE-3 than in those that did not express this gene. This tendency was not observed for other members of the MAGE gene family. No significant differences were observed in the other clinicopathologic factors between any MAGE-positive and -negative tumor cases. CONCLUSIONS: The MAGE genes were exclusively expressed in carcinoma tissues and not in normal tissues of the colon. The finding that nearly 90% of tumors expressed at least one MAGE gene indicates the possible clinical use of this gene for both immunotherapy and molecular diagnosis.

An unusual case associating ileal Crohns disease and diffuse large B-cell lymphoma of an adjacent mesenteric lymph node.

Year 1998
Charlotte F. Sriha B. Mansour G. Gabarre J.
Department of Pathology, Pitie-Salpetriere Hospital, Paris, France.
Intestinal non-Hodgkin's lymphomas are a rare complication of long-standing Crohn's disease and generally arise in sites of active inflammatory disease. To our knowledge, we report the first case of an unusual association between ileal Crohn's disease and a diffuse large B-cell non-Hodgkin's lymphoma involving an adjacent mesenteric lymph node but not the intestinal tract. A 22-year-old man was seen for intermittent abdominal pain, vomiting, and severe weight loss that were suggestive of intestinal obstruction. A segmental ileocolonic resection was performed. Gross examination revealed a terminal ileal inflammatory stenosis and enlarged mesenteric lymph nodes. Histologically, terminal ileal Crohn's disease was associated with a diffuse large cell lymphoma localized within one mesenteric lymph node without intestinal involvement. Immunophenotyping performed on deparaffinized sections demonstrated the B phenotype of this lymphoma.

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