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1.
Appl Immunohistochem Mol Morphol ; 9(1): 19-23, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11277409

ABSTRACT

The authors investigated the relations between outcome and apoptosis, immunohistochemical demonstration of bcl-2 protein, and immunohistochemical staining for p53 protein in patients with gastrointestinal stromal/smooth muscle tumors (GIST). Patients whose tumors demonstrated cellular apoptosis using the terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate-biotin nick end labeling (TUNEL) assay had an improved survival over those whose tumors did not improve. In contrast, patients whose tumors demonstrated staining for bcl-2 protein had a decreased survival compared with those whose tumors did not demonstrate bcl-2. There was no relation between p53 immunoreactivity and survival. These results suggest that inhibition of apoptosis may be associated with malignant behavior in patients with gastrointestinal stromal/smooth muscle tumors.


Subject(s)
Apoptosis , Gastrointestinal Neoplasms/metabolism , Gastrointestinal Neoplasms/pathology , Neoplasms, Muscle Tissue/metabolism , Neoplasms, Muscle Tissue/pathology , Proto-Oncogene Proteins c-bcl-2/metabolism , Tumor Suppressor Protein p53/metabolism , Humans , Immunohistochemistry , In Situ Nick-End Labeling , Leiomyoma/metabolism , Leiomyoma/pathology , Leiomyosarcoma/metabolism , Leiomyosarcoma/pathology , Mitotic Index , Neoplasms, Connective Tissue/metabolism , Neoplasms, Connective Tissue/pathology
2.
Dig Dis Sci ; 45(7): 1337-42, 2000 Jul.
Article in English | MEDLINE | ID: mdl-10961712

ABSTRACT

The purpose of the study was to quantify gastric mucosal macrophages and define their association with the histopathologic features of stomach biopsies obtained from Helicobacter pylori-infected and uninfected children. Endoscopically obtained gastric biopsies from symptomatic children were independently evaluated by two groups of pathologists. Thirty children were evaluated; 14 were H. pylori-infected. H. pylori positivity was determined by hematoxylin and eosin (H&E), Giemsa, Warthin-Starry and an H. pylori-specific immunoperoxidase stain. A macrophage-specific, KP-1, immunoperoxidase stain was used to quantify positive cells. Inflammatory cell infiltrates were graded by severity with scores of mild to severe. Increased numbers of gastric mucosal macrophages were observed in biopsies of H. pylori-infected versus uninfected children (P < 0.05) and correlated with gastritis severity. The role of this inflammatory cell the in persistence of gastric mucosal inflammation in H. pylori infection warrants further study to develop targeted immunotherapeutic strategies.


Subject(s)
Gastric Mucosa/pathology , Helicobacter Infections/pathology , Helicobacter pylori , Macrophages/pathology , Adolescent , Biopsy , Child , Child, Preschool , Female , Gastritis/microbiology , Humans , Infant , Male , Reference Values , Retrospective Studies
3.
Am J Surg Pathol ; 23(9): 1109-18, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10478672

ABSTRACT

Gastrointestinal stromal tumor or smooth muscle tumor (GIST) is the designation for a major subset of gastrointestinal mesenchymal tumors that histologically, immunohistochemically, and genetically differ from typical leiomyomas, leiomyosarcomas, and schwannomas. Because GISTs, like the interstitial cells of Cajal, the gastrointestinal pacemaker cells, express CD117 (c-kit protein), the origin of GISTs from the interstitial cells of Cajal has been recently proposed. Comparison of GISTs primary in the omentum and mesentery to GISTs primary in the tubular gastrointestinal tract is of particular diagnostic and histogenetic interest in view of the possible similarity of these tumors with the GIST group. In this study, we analyzed 14 omental and 12 mesenteric primary mesenchymal tumors representing smooth muscle tumors or GISTs. These tumors were phenotypically compared with gastric and small intestinal GISTs, leiomyomas of the esophagus, and leiomyosarcomas of the retroperitoneum. Most (13 of 14) omental and mesenteric (10 of 12) tumors showed histologic features similar to GISTs with elongated spindle cells or epithelioid cells with high cellularity; most of these tumors showed low mitotic activity. Omental and mesenteric GISTs were typically positive for CD117 and less consistently for CD34. They often showed alpha-smooth muscle actin reactivity but were virtually negative for desmin and S-100 protein. One omental and two mesenteric tumors showed features of leiomyosarcoma with ovoid, less elongated nuclei, cytoplasmic eosinophilia; all these tumors had significant mitotic activity. These tumors were positive for alpha-smooth muscle actin and two of them for desmin, but all were negative for CD34 and CD117, similar to retroperitoneal leiomyosarcomas. Tumor-related mortality occurred in the group of mesenteric GISTs, but not in the group of omental GISTs. In contrast, all three patients with a true leiomyosarcoma of the omentum or mesentery had documented liver metastases or died of tumor. In summary, we show that tumors phenotypically identical with GISTs occur as primary tumors in the omentum and mesentery. The occurrence of CD117-positive tumors outside the gastrointestinal tract militates against an origin of these tumors exclusively from the interstitial cells of Cajal.


Subject(s)
Mesentery/pathology , Peritoneal Neoplasms/pathology , Smooth Muscle Tumor/pathology , Adult , Aged , Aged, 80 and over , Antigens, CD34/analysis , Desmin/analysis , Female , Humans , Immunohistochemistry , Male , Middle Aged , Peritoneal Neoplasms/metabolism , Peritoneal Neoplasms/physiopathology , Proto-Oncogene Proteins c-kit/analysis , S100 Proteins/analysis , Smooth Muscle Tumor/metabolism , Smooth Muscle Tumor/physiopathology
4.
Am J Surg Pathol ; 23(1): 82-7, 1999 Jan.
Article in English | MEDLINE | ID: mdl-9888707

ABSTRACT

Although the significance of various prognostic factors, such as tumor size and mitotic index (MI), has been well established for smooth-muscle tumors of the stomach, the significance of these factors in other sites is less well defined. We studied 1004 patients with gastrointestinal smooth-muscle tumors for whom vital status could be determined. The average MI and tumor size varied significantly among the five major sites examined: esophagus (53 cases), stomach (524 cases), small bowel 252 cases), colon/rectum (108 cases), and omentum/mesentery/peritoneum (67 cases). There was a significant difference in site-specific survival (p = 0.001), with 10-year survival varying between 50% and 70%. Multivariate analysis demonstrated tumor location (p = 0.0320), size (p = 0.0003), MI (p < 0.0001), and patient age (p < 0.0001) to each carry independent prognostic value. The significance of MI was highly site dependent. Separation of survival curves for the stomach, using a threshold for analysis of either 5 or 10 mitotic figures/50 high-power fields, was very good. In contrast, small-bowel tumors showed little separation between survival curves, regardless of whether a threshold of 1, 5, or 10 mitotic figures MF/50 high-power fields was used to distinguish groups. In no site were tumor size and MI alone sufficient to provide an accurate long-term prediction of prognosis. Although tumor location, size, MI, and age have independent value in predicting the prognosis of patients with gastrointestinal smooth-muscle tumors, better methods are still required to accurately predict clinical course.


Subject(s)
Gastrointestinal Neoplasms/pathology , Smooth Muscle Tumor/pathology , Stromal Cells/pathology , Adolescent , Aged , Aged, 80 and over , Child , Female , Gastrointestinal Neoplasms/mortality , Humans , Male , Middle Aged , Mitotic Index , Prognosis , Proportional Hazards Models , Retrospective Studies , Smooth Muscle Tumor/mortality , Survival Analysis , Survival Rate
5.
Lab Invest ; 78(12): 1633-6, 1998 Dec.
Article in English | MEDLINE | ID: mdl-9881963

ABSTRACT

Gastrointestinal stromal/smooth muscle tumors (GISTs) are uncommon neoplasms for which current criteria for the diagnosis of malignancy (location, size, and mitotic index) do not always reliably predict patient outcome. Recently, mutation of KIT oncogene exon 11 has been observed in some of these tumors, but the relationship between mutation and clinical outcome has not yet been determined. DNA was obtained from the formalin-fixed, paraffin-embedded tissue of 35 gastric GISTs. A segment of exon 11 was amplified by PCR and sequenced on an ABI 377 sequencer. The relationship between the presence or absence of mutation, tumor size, and mitotic index was investigated using correlation analysis, and the relationship between mutation and outcome was investigated using Kaplan-Meier plots, the Cox-Mantel statistic, and the Cox regression model. Exon 11 deletion mutations were identified in 10 cases, and point mutations were identified in an additional 3 cases; 22 cases demonstrated no KIT mutations. KIT mutation was associated with decreased survival (p = 0.001), with fewer than 30% of patients surviving more than 3 years, compared with over 65% survival for patients whose tumors did not bear the mutation. KIT mutation did not correlate with either the mitotic index or the tumor size. In conclusion, KIT mutation is associated with poor prognosis in patients with gastrointestinal stromal tumors. Whether the KIT mutation will prove to be an independent prognostic factor awaits the completion of larger studies.


Subject(s)
Neoplasms, Connective Tissue/genetics , Point Mutation , Proto-Oncogene Proteins c-kit/genetics , Sequence Deletion , Smooth Muscle Tumor/genetics , Stomach Neoplasms/genetics , Amino Acid Sequence , Heterozygote , Homozygote , Humans , Mitotic Index , Molecular Sequence Data , Neoplasms, Connective Tissue/mortality , Neoplasms, Connective Tissue/pathology , Prognosis , Proto-Oncogene Proteins c-kit/chemistry , Smooth Muscle Tumor/mortality , Smooth Muscle Tumor/pathology , Stomach Neoplasms/mortality , Stomach Neoplasms/pathology , Stromal Cells , Survival Rate
7.
Radiology ; 204(3): 745-7, 1997 Sep.
Article in English | MEDLINE | ID: mdl-9280253

ABSTRACT

PURPOSE: To determine the imaging features of duodenal gangliocytic paraganglioma that can be used to differentiate this mass from other lesions. MATERIALS AND METHODS: Imaging, histopathologic, and surgical findings in five patients with proved gangliocytic paraganglioma were reviewed. The most common symptom at presentation was abdominal pain (n = 3). All patients underwent computed tomography (CT), two underwent ultrasonography (US), and one underwent magnetic resonance (MR) imaging. Imaging findings were correlated with findings from surgical resection specimens in all cases. RESULTS: All lesions were located around the second portion of the duodenum and were 3-13 cm in diameter (mean, 6.5 cm). Two extended laterally to the duodenum, two extended medially, and one was intraluminal. All appeared solid and homogeneous on US, CT, and MR images and had homogeneous contrast material enhancement on CT and MR images. All were solid, with a prominent vascular network, but no cystic hemorrhage or necrosis was noted at pathologic examination. CONCLUSION: The imaging features of gangliocytic paraganglioma are suggestive enough for the prospective diagnosis and differentiation of this benign mass from other lesions.


Subject(s)
Duodenal Neoplasms/diagnosis , Magnetic Resonance Imaging , Paraganglioma/diagnosis , Tomography, X-Ray Computed , Aged , Aged, 80 and over , Diagnosis, Differential , Duodenal Neoplasms/diagnostic imaging , Duodenal Neoplasms/pathology , Duodenum/diagnostic imaging , Duodenum/pathology , Female , Humans , Male , Middle Aged , Paraganglioma/diagnostic imaging , Paraganglioma/pathology , Retrospective Studies , Ultrasonography
8.
Am J Surg Pathol ; 21(4): 392-8, 1997 Apr.
Article in English | MEDLINE | ID: mdl-9130985

ABSTRACT

We reviewed 84 cases coded as mesenteric lipodystrophy (ML), mesenteric panniculitis (MP), or retractile mesenteritis and sclerosing mesenteritis (SM), grading fibrosis, inflammation, and fat necrosis, and evaluating clinical subgroups. There was no gender or racial predominance. Patient age range was 23-87 years (average 60). Patients most often presented with abdominal pain or a palpable mass. A history of trauma or surgery was present in four of 84 patients. The most common site of involvement was the small bowel mesentery as a single mass (58 of 84) with an average size of 10 cm, multiple masses (15 of 84), or diffuse mesenteric thickening (11 of 84). All patients had some degree of fibrosis, chronic inflammation, and fat necrosis. Although a few patients showed a sufficient prominence of fibrosis, inflammation, or fat necrosis to permit a separation into SM, MP, or ML, respectively, in most patients these three components were too mixed for a clear separation. The clinical, demographic, and gross features did not help in defining these three entities. Contributors diagnosed 12 as sarcoma. Of 39 patients followed beyond the postoperative period, none died of these lesions. We conclude that SM, MP, and ML appear to represent histologic variants of one clinical entity, and in most cases "sclerosing mesenteritis" is the most appropriate diagnostic term.


Subject(s)
Lipodystrophy/pathology , Mesentery/pathology , Panniculitis, Peritoneal/pathology , Adult , Aged , Aged, 80 and over , Diagnosis, Differential , Female , Follow-Up Studies , Humans , Lipodystrophy/diagnosis , Male , Middle Aged , Panniculitis, Peritoneal/diagnosis , Peritonitis/diagnosis , Peritonitis/pathology , Sclerosis
9.
Am J Clin Pathol ; 103(6): 696-704, 1995 Jun.
Article in English | MEDLINE | ID: mdl-7785653

ABSTRACT

The nature of perineurioma, variably termed "localized hypertrophic neuropathy," "intraneural neurofibroma," and "hypertrophic interstitial neuritis" has long been an issue of contention. Most authors consider it a neoplasm, but some a reactive process. Eight clinically and morphologically typical perineuriomas were studied by histologic, immunohistochemical and ultrastructural methods. One perineurioma was subject to tissue culture and cytogenetic study and another to fluorescence in situ hybridization (FISH) analysis. The patients, 3 males and 5 females, ranged in age from 11 to 38 years. All tumors were intraneural, and involved extremities (2 sciatic, 1 median, 1 femoral, 1 peroneal, 1 brachial plexus, 1 ulnar, and 1 radial). Neurologic symptoms, motor in all cases and sensory in 4, were present from 1 month to 7 years (mean 1.2 years). Fusiform, segmental nerve enlargement was clinically apparent in only two patients, but was evident on MRI in five of eight patients. Lesion length ranged from 3.5 to 30 cm, the largest involving the sciatic nerve from the obturator foramen to the knee. One lesion involved two nerve roots, but no association with a phakomatosis was noted. Treatment consisted of biopsy in six cases and resection in two cases. Histologically, pseudo-onion bulbs composed of epithelial membrane antigen-reactive, S-100 protein-negative perineurial cells surrounded myelinated or nonmyelinated nerve fibers. Many were accompanied by their S-100 protein-positive Schwann sheaths. Some whorls lacked a central axon. A single mitosis was noted in one case. The MIB-1 antigen labelling index ranged from 4% to 17%. Staining for p53 antigen in six cases showed no (2 of 6), rare (2 of 6), or scattered (2 of 6) immunoreactive nuclei. Cytogenetic analysis in one case demonstrated a chromosomally abnormal clone. Each of 16 metaphases was abnormal; the tumor cells appeared to be homozygously deficient for the region 22q11.2qter. In another case, 53% of interphase nuclei showed three FISH signals with a chromosome 14/22 probe, thus suggesting either monosomy for the centromere of chromosome 14 or that of chromosome 22.(ABSTRACT TRUNCATED AT 400 WORDS)


Subject(s)
Chromosome Aberrations , Chromosome Disorders , Chromosomes, Human, Pair 22 , Nervous System Neoplasms/genetics , Neuroma/genetics , Adolescent , Adult , Base Sequence , Cell Cycle , Child , Female , Histocytochemistry , Humans , Immunohistochemistry , In Situ Hybridization, Fluorescence , Male , Microscopy, Electron , Molecular Probes/genetics , Molecular Sequence Data , Nervous System Neoplasms/metabolism , Nervous System Neoplasms/pathology , Neuroma/metabolism , Neuroma/pathology
10.
Surgery ; 115(6): 762-6, 1994 Jun.
Article in English | MEDLINE | ID: mdl-8197570

ABSTRACT

Primary neuroendocrine tumors of the ampulla of Vater are rare. These tumors, like those of the respiratory tract and remainder of the gastrointestinal tract, appear along a histologic spectrum of increasing malignancy from low-grade carcinoid tumors to high-grade small cell undifferentiated cancers. We herein describe the characteristics of these ampullary neoplasms and report the first case of a neuroendocrine carcinoma of non-small cell type, which represents the middle of this histologic continuum. This tumor seems to follow a more aggressive course than the carcinoid tumor but less aggressive than its small cell counterpart.


Subject(s)
Ampulla of Vater , Carcinoid Tumor/pathology , Carcinoma, Neuroendocrine/pathology , Common Bile Duct Neoplasms/pathology , Aged , Humans , Immunohistochemistry , Male
11.
Mod Pathol ; 3(3): 277-81, 1990 May.
Article in English | MEDLINE | ID: mdl-2194211

ABSTRACT

We describe two cases of renal oncocytoma which showed an unusual light microscopic appearance characterized by nests of cells containing collections of eosinophilic hyaline material around and within oncocytic epithelial cell nests. Electron microscopy of the hyaline material showed a partly amorphous and partly lamellated structure, and immunohistochemistry for type IV collagen was positive. These cylindromatous changes are similar to the "glashelle Zylinder" of Billroth (Billroth T: Beobachtungen über geschwülste der speicheldrüsen. Virchous Arch [Pathol Anat] 17:357, 1859) described in adenoid cystic carcinoma and are most likely the result of an accumulation of basement membrane material in invaginations projecting into the surface of the basal plasmalemma. Since such invaginations occur in the normal distal tubule, our cases support origin of renal oncocytoma from distal tubular epithelial cells.


Subject(s)
Adenoma/pathology , Kidney Neoplasms/pathology , Adenoma/genetics , Adenoma/ultrastructure , Aged , Female , Humans , Immunoenzyme Techniques , Kidney Neoplasms/genetics , Kidney Neoplasms/ultrastructure , Microscopy, Electron , Middle Aged
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