Expressions of p53 and p21 in primary gastric lymphomas.

The p21 overexpression is thought to be a consequence of the p53 induced activation of the p21 gene. The immunohistochemical evaluation of p53 and p21 can be a valuable means of assessing the functional status of the p53 gene product. We examined the overexpression of p21 and p53 proteins in primary gastric lymphomas and the correlation with prognosis. A total of 32 cases of gastric lymphomas was classified into low-grade lymphomas of mucosa-associated lymphoid tissue type (n=16) and high-grade B-cell lymphomas (n=16). In low-grade lymphomas, only one case showed p53 positivity and all cases were p21-negative. In high-grade lymphomas, seven cases were p53+/p21- (44%), one case was p53+/p21+ (6%), and eight cases were p53-/p21- (50%). The p53+/p21- cases had a much lower percentage of patients sustaining a continuous complete remission state (3/7, 43%) compared with other cases (6/7, 86%). From these results, we concluded that p21 expression is rare in primary gastric lymphomas. Therefore, p53-positive lymphomas can be assumed as having p53 mutation. And combined studies of p53 and p21 may be used as a prognostic indicator in primary gastric high-grade lymphomas.

Mutational analysis of the 5' noncoding region of the bcl-6 gene in primary gastric lymphomas.

Bcl-6 mRNA and protein are frequently expressed in the transformed counterparts of the germinal center B-cells, diffuse large B-cell lymphoma and follicular lymphoma, irrespective of the gene rearrangements. Most of the primary gastric lymphomas are thought to be of mucosa-associated lymphoid tissue (MALT) origin, and neither bcl-6 gene rearrangement nor protein expression is found in low-grade gastric lymphomas of the MALT type as in normal marginal zone cells. However, bcl-6 protein expression was identified in high-grade gastric lymphomas, suggesting its role in high-grade transformation. In this study, polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis for bcl-6 primer was performed in order to ascertain the molecular mechanisms of bcl-6 protein expression in primary gastric lymphomas. A total 31 cases of gastric lymphoma were classified into low-grade gastric lymphomas of MALT type (n = 13), high-grade gastric lymphomas of MALT type (n = 6) and gastric diffuse large B-cell lymphomas (n = 12). Bcl-6 mutations were observed in 11 of 13 (84.6%) low-grade gastric lymphomas of the MALT type and in 8 of 12 (66.7%) diffuse large B-cell gastric lymphomas. In 6 cases of the high-grade gastric lymphomas of the MALT type, both the low- and high-grade components demonstrated the same frequency (3/6, 50%) of mutations. The tissue obtained from the marginal zone of Peyer's patch by microdissection technique revealed no bcl-6 mutations by the PCR-SSCP analysis. These findings suggest that the acquisition process of bcl-6 mutations by the marginal zone cells may be involved in the lymphomagenesis of the stomach, but our data does not explain the reason why bcl-6 protein is expressed only in high-grade gastric lymphomas.

Expression Pattern of p27 Protein in Primary Gastric Lymphomas.

PURPOSE: To investigate the expression pattern of p27 protein in primary gastric lymphomas. MATERIALS AND METHODS: Immunostaining for the p27 protein was performed in 16 cases of low grade mucosa-associated lymphoid tissue (MALT) lymphomas and 16 cases of high grade B-cell lymphomas of the stomach. RESULTS: All low grade MALT lymphomas were positive, however all high grade lymphomas were negative forp27 protein. Most of the monocytoid cells in the low grade lymphoma were unstained. CONCLUSION: Loss of p27 protein expression is well correlated with histologic grade and appears to be associated with the high grade transformation seen in primary gastric lymphomas.

Bcl-6 expression in reactive follicular hyperplasia, follicular lymphoma, and angioimmunoblastic T-cell lymphoma with hyperplastic germinal centers: heterogeneity of intrafollicular T-cells and their altered distribution in the pathogenesis of angioimmunoblastic T-cell lymphoma.

BACKGROUND: The Bcl-6 gene product, a nuclear phosphoprotein, is expressed independently of Bcl-6 gene rearrangement. In lymph nodes, expression of Bcl-6 protein is restricted to germinal center (GC) B-cells and 10% to 15% of CD3/CD4+ intrafollicular T cells. Interfollicular cells are negative for Bcl-6 protein, except for rare CD3+/CD4+ T cells. Recently, we reported cases of angioimmunoblastic T-cell lymphoma (AITL) with hyperplastic GCs (AITL/GC), and observed that borders of enlarged GCs were ill defined, with features suggestive of an outward migration of GC cells to surrounding interfollicular zones. This prompted a study of follicular borders with Bcl-6 staining in reactive follicular hyperplasias and follicular lymphomas to compare with AITL/GC. MATERIALS AND METHODS: Formalin-fixed paraffin sections were used for immunostaining of Bcl-6. Six cases of AITL/GC, 12 nonspecific reactive follicular hyperplasia (FH), 7 HIV adenopathy, 10 follicular lymphoma (FL), and 8 typical AITL (ie, AITL without GC) were studied. Double staining for Bcl-6/CD20, Bcl-6/CD3, and Bcl-6/CD57 was performed in selected cases. RESULTS: In FH and HIV adenopathy, staining for Bcl-6 revealed densely populated GCs with well-defined and regular GC borders, whereas Bcl-6+ cells were rare in the interfollicular areas. An occasional GC with an ill-defined border was invariably surrounded by a broad mantle zone; those with indistinct mantle zones had well-defined, regular borders. In FL, follicles were densely populated, and their borders were irregular, with some Bcl-6+ cells in the interfollicular zones. In AITL/GC, GCs were less dense, GC borders were ill defined and irregular, and the number of interfollicular Bcl-6+ cells was markedly increased. Double staining revealed that these interfollicular Bcl-6+ cells in AITL/GC were Bcl6+/CD3+/CD20-/CD57- T cells. Moreover, CD3+ intrafollicular T cells were depleted in AITL/GC, whereas they were abundant in FH. Intrafollicular CD57+ cells did not stain for Bcl-6, and were also depleted in AITL/GC. In typical AITL, some neoplastic cells were positive for Bcl-6, showing variable degrees of staining. CONCLUSIONS: (1) GCs of AITL/GC differed from those of other reactive follicular hyperplasias and follicular lymphomas, and staining for Bcl-6 was useful to discern them. (2) Intrafollicular CD3+ T cells, many of which were also positive for Bcl-6, were markedly depleted in AITL/GC, with increased interfollicular Bcl-6+/CD3+ cells, suggesting an outward migration of intrafollicular T cells in this condition. (3) Interfollicular Bcl-6+/CD3+ cells in AITL/GC were too numerous to be accounted for by migration alone, suggesting local proliferation. (4) Intrafollicular CD57+ cells were negative for Bcl-6, indicating heterogeneity of the intrafollicular T-cell population. (5) Some neoplastic cells in AITL stained for Bcl-6, suggesting up-regulation of Bcl-6 expression in this tumor.

Angioimmunoblastic lymphoma (AILD-type T-cell lymphoma) with hyperplastic germinal centers.

Angioimmunoblastic T-cell lymphoma (or angioimmunoblastic lymphadenopathy with dysgammaglobulinemia [AILD]) was originally considered to be an abnormal immune reaction in which reactive follicles with germinal centers (GCs) are usually absent. When hyperplastic GCs are present along with an angioimmunoblastic reaction, the lesion has been interpreted as a benign hyperimmune reaction. We report seven patients with angioimmunoblastic T-cell lymphoma (AITL) who initially had hyperplastic GCs, shown to be malignant lymphoma by further studies and clinical follow-up. Clonal T-cell populations were observed in all specimens evaluated, and sequential biopsies showed histologic progression to typical AITL in two patients. Clinical presentation was characterized by generalized lymphadenopathy of acute onset, constitutional symptoms, hepatosplenomegaly, skin rash, and polyclonal hypergammaglobulinemia in five patients; regional adenopathy preceded generalized adenopathy in two patients. Five patients had rapid progression of disease, and three patients whose treatment was delayed due to inadequate evidence to diagnose lymphoma died of infection. The initial biopsy findings of each patient were similar and showed angioimmunoblastic proliferation, hyperplastic GCs with ill-defined borders, and interfollicular tingible-body macrophages. These GCs differed from occasional residual follicles of typical AITL in that the GCs were enlarged and hyperplasia of follicular dendritic cells was not seen. Diagnostic clear cells were not observed. Apoptotic bodies were markedly increased and bcl-2+ lymphocytes were sparse compared with typical AITL. Results of in situ hybridization for Epstein-Barr virus were positive in each case. We conclude that hyperplastic germinal centers with ill-defined borders and frequent interfollicular tingible-body macrophages occur in a histologic variant of AITL that is necessary to recognize for early diagnosis and treatment.

Hybrid verrucous squamous cell carcinoma of sinonasal tract: a case report.

Verrucous carcinoma is a variant of squamous cell carcinoma and should be distinguished from benign papilloma and well-differentiated nonverrucous squamous cell carcinoma. It is rare tumor of the sinonasal tract. Occasionally, conventional squamous cell carcinomatous components may be seen in verrucous carcinoma. This entity is called a hybrid verrucous squamous cell carcinoma. We report a case of hybrid verrucous squamous cell carcinoma occurring in the nasal cavity and paranasal sinus of a 67-year-old male. The removed mass shows the typical feature of verrucous carcinoma, but focally conventional squamous cell carcinomatous area is also noted. The treatment of this case follows verrucous carcinoma, but close follow up is mandatory because it may potentially spread to regional lymph nodes in contrast to pure form of verrucous carcinoma.

Cleaved variant of plasmacytoma with myelomonocytic differentiation--immunohistochemical and ultrastructural studies.

Although plasma cells are terminally differentiated B cells, neoplastic plasma cells frequently express not only pre-B cell antigen, but also megakaryocytic, myelomonocytic, or erythroid markers. Since morphologic diagnosis of plasmacytoma is based on the recognition of neoplastic cells closely resembling normal plasma cells, unusual morphologic variants of neoplastic cells associated with these aberrant immunohistochemical features frequently cause diagnostic difficulty. The authors report a case of plasmacytoma with cleaved nuclei and myelomonocytic features occurring in the clavicle. The tumor was composed of immature plasma cells showing irregular, cleaved, and multilobated nuclei and abundant cytoplasm with prominent eosinophilic granules. A few tumor cells showing recognizable plasmacytic differentiation were admixed within the tumor. Immunohistochemically, the tumor cells expressed CD45RB, CD68, lysozyme, myeloperoxidase and kappa light chain with focal positivity for lambda chain. Ultrastructurally, the tumor cells contained numerous membrane bound electron dense lysosomal granules, some of them resembling Auer rods, as well as rough endoplasmic reticula arranged in lamellated stacks. Small biopsied nasal mucosal tissue in same patient revealed well differentiated plasmacytoma composed of tumor cells showing round, eccentric nuclei devoid of marked nuclear cleavage and cytoplasmic granularity. Immunohistochemically, these cells were kappa(+), lambda(-), myeloperoxidase(-), lysozyme(-) and CD68(-).

Intravascular lymphomatosis: a clinicopathological study of two cases presenting as an interstitial lung disease.

AIMS: Intravascular lymphomatosis is an uncommon type of non-Hodgkin's lymphoma characterized by intravascular proliferation of neoplastic lymphoid cells. Although the tumour is basically a systemic disease, eventually involving multiple organs, primary presentation in the lung is rare. METHODS AND RESULTS: We describe the clinicopathological features of two patients with intravascular lymphomatosis presenting in the lung. One patient complained of fever, headache and chest pain; the other, of dyspnoea on exertion and headache. Both patients showed reticulonodular density on chest radiography and decreased diffusion capacity. Lung biopsy showed features characteristic of intravascular lymphomatosis. Malignant lymphoid cells were CD30 positive T-cells of anaplastic large cell type in one patient and B-cells of large cell type in the other. There was a poor response to chemotherapy and both patients died of the disease within 3 months of diagnosis. CONCLUSIONS: These cases and 10 previous reports illustrate the need to include intravascular lymphomatosis in the differential diagnosis of interstitial lung disease.

Intracranial immature teratoma with syncytiotrophoblasts and tumor marker positive intestinal lining cells.

Intracranial teratomas are rare entities that can present as a pure type or as mixed germ cell tumor. Cases of mixed germ cell tumor composed of immature teratoma and choriocarcinoma have been reported. Also, immature teratoma can be mixed with only syncytiotrophoblasts. We report a case of immature teratoma with syncytiotrophoblasts of the brain discovered in a 3-year-old male baby. Serum human chorionic gonadotrophin (hCG) was normal and serum alpha-fetoprotein (AFP) was elevated. The tumor was mainly composed of intestinal glands, and neither endodermal sinus tumor nor embryonal carcinomatous elements were found. The cells lining the intestinal glands were positive for hCG and AFP. These findings suggest that the syncytiotrophoblasts are differentiated from the endoderm and AFP is not necessarily a marker exclusive to endodermal sinus tumor or embryonal carcinoma.

Correlation between proliferating index and prognostic factors in papillary cystic tumors of the pancreas.

Fifteen cases of papillary cystic tumor of the pancreas (PCTP) were studied (14 female patients, one male patient; mean age: 23.5 years). Most tumors developed in the head of the pancreas as a well circumscribed large mass. The tumor had a mean diameter of 6.7 cm(range; 2 to 15 cm). Histopathologically abundant delicate papillary fragments, monomorphic tumor cells and degenerative changes of the solid area of the tumor were characteristic. All but two cases had completely circumscribed capsules. Two cases had duodenal invasion; one of all cases had cul de sac metastasis. Compared with 12 non-aggressive tumors, the aggressive cases had larger tumor size (more than 9 cm) with a thicker capsule (more than 2 mm). In studies to investigate the prognostic index using nucleolar organizing region (NOR), proliferating cell nuclear antigen (PCNA) and flow cytometry as well as nuclear grade and mitotic index, we could not find the useful parameter to detect the malignant potential of PCTP. In the flow cytometric analysis of cellular DNA contents, two invasive cases and the only one case of the male patient among the non-aggressive group were aneuploid. In conclusion, although it is hard to predict the prognosis by microscopic findings only, those with a thick capsule and aneuploidy tend to be related to malignant potential.

Massive congenital intracranial teratoma--an autopsy case.

Massive congenital intracranial teratoma (MCIT) is a very rare tumor and only one case has been reported in Korea. We report a case of MCIT discovered in a male infant of 25 weeks of gestational age. Prenatal ultrasound revealed a large heterogenous echoic mass which almost replaced the intracranial content. The infant was severely macrocephalic with a small but normal appearing body. The cranial vault was almost entirely occupied by an 18cm sized, multilobulated, partially cystic mass that displaced the severely distorted and attenuated cerebral cortex. Microscopically, the bulk of the tumor was composed of embryonal neuroepithelium with mature glial tissue and choroid plexus. Cartilage, liver, mature squamous epithelium and differentiated mesenchymal elements such as muscle and adipose tissue were found within the tumor.