Induction of oral mucosal tumors in hamsters and rats treated with methyl(acetoxymethyl)nitrosamine.

An oral tumor model has been developed in inbred Syrian golden hamsters by continuous applications every 2 weeks of methyl(acetoxymethyl)nitrosamine [(DMN-OAC) CAS: 56856-83-8; methylnitrosaminomethyl ester acetic acid] at 2 mg/kg body weight alone or by a single application of DMN-OAC followed by continuous twice weekly applications of 12-O-tetradecanoylphorbol 13-acetate (TPA) (1 microgram/animal). Similar studies were done in the W rat buccal mucosa. In the hamsters treated continuously with DMN-OAC, 100% of the tumors were observed in the cheek pouch; none were observed at other sites. In contrast, in the rats treated similarly, only a 67% tumor incidence was observed, of which only 42% were oral tumors. A promoter effect of TPA was observed in hamster cheek pouch tumors induced by DMN-OAC, whereas rat oral mucosa did not respond to TPA treatment.

Restriction fragment length polymorphism of the L-myc oncogene in non-Hodgkin's lymphoma patients from India.

We examined 89 non-Hodgkin's lymphoma (NHL) patients of Indian origin for EcoRI restriction fragment length polymorphism (RFLP) of the L-myc gene with a view to testing the hypothesis that the presence of the L-myc S-allele predisposes towards NHL. We found no significant difference either in the distribution of the LL, LS and SS genotypes or in the allelic frequencies between the patient group and the control group with the frequencies of L-myc alleles, L (10.0 kb) and S (6.6 kb), being 0.56 and 0.44, respectively, in the patient group and 0.54 and 0.46, respectively, in the control group. However, a higher proportion (70%) of the S-allele was observed in our control group of normal healthy volunteers. Thus, the presence of L-myc S-allele did not indicate increased susceptibility or predisposition to the malignancy.

Incidence of 5' bcl-2 rearrangement in patients with B cell chronic lymphocytic leukemia from India.

The incidence of B cell chronic lymphocytic leukemia (B-CLL) is lower in Asian countries, including India, when compared with Western countries. The bcl-2 gene rearrangement was restricted to the 5' region and seen in only one of the 20 Indian patients analyzed. The incidence remains similar to that reported from Western and Japanese institutions.

A study of p53 protein, proliferating cell nuclear antigen, and p21 in Hodgkin's disease at presentation and relapse.

About one fourth of patients with Hodgkin's disease relapse after therapy. The mechanisms that lead to resistance to treatment in these patients are poorly understood. The authors describe the differential protein expression of p53, proliferating cell nuclear antigen (PCNA), and p21 at initial presentation and relapse, and discuss their role in disease progression and resistance to therapy. Thirty-four patients with Hodgkin's disease who had relapsed after standard chemotherapy and radiotherapy regimens were assessed for the expression of p53 protein, PCNA, and p21 protein (waf/cip 1). In 14 of these cases, sequential biopsies performed both at presentation and at relapse were available for the study. Seventy-five percent of the cases were positive for the p53 protein. Tumors at relapse had higher p53 and PCNA scores than those at initial presentation. In the paired samples, a significant increase was noted in the number of p53 and PCNA-positive cells and in the intensity of staining with p53 antibody. Six of seven paired samples tested for p21 showed an increased p21 expression at relapse. These results suggest that, at relapse, Reed-Sternberg (RS) cells and their variants positive for p53, PCNA, and p21 are increased in number and individually have an increased expression of p53, PCNA, and p21 proteins. These findings suggest that therapy failure and relapse may, at least in part, be associated with altered p53, p21, and PCNA pathways. HUM PATHOL 28:549-555. This work was carried out during an exchange fellowship program at the National Cancer Institute, Bethesda. There are no restrictions on its use

Hodgkin's disease involving Waldeyer's ring: a study of four cases.

We report four cases of Hodgkin's disease who presented with involvement of Waldeyer's ring. Their clinical, morphological and immunohistochemical features are discussed. The patients were immuno-competent, were between 17 and 65 years of age and presented with symptoms related to swelling in the nasopharynx or oropharynx and cervical lymphadenopathy. The nasopharyngeal biopsy and the cervical lymph node in all four cases showed features of classical Hodgkin's disease. The Reed Sternberg cells expressed CD15 and CD30, and in three cases, CD20 and Epstein-Barr virus--latent membrane protein -1 (EBV-LMP-1). Extranodal involvement by Hodgkin's disease which is not in continuity with nodal disease is rare in immunocompetent patients. Morphologically, such extranodal lesions, especially in locations like the oropharynx and nasopharynx, should be differentiated from EBV-associated lymphoproliferations.

Primary Liver Lymphoma: A Case Report with Review of Literature.

Primary non-Hodgkin's lymphoma of the liver is exceedingly rare and until now only 53 cases have been recorded. Most extranodal non-Hodgkin's lymphomas are in the head and neck region and the gastrointestinal tract. We report a patient with primary non-Hodgkin's lymphoma of the liver and also review the relevant literature.

Brain tumors following cure of acute lymphoblastic leukemia.

The majority of children with acute lymphoblastic leukemia can be cured with effective modern day therapy. However, more and more long term sequelae including carcinogenic potential of the treatment are being recognised. We report two children who developed acute lymphoblastic leukemia at the age of 4 and 5 years respectively and were successfully treated. They developed meningioma and astrocytoma at 9 and 3 years respectively after completion of therapy. Both were treated surgically and the patient with astrocytoma also received radiotherapy. Both are now free of disease 19 months after diagnosis of second neoplasm.

Expression of P53 and bcl-2 proteins in T-cell lymphoblastic lymphoma: prognostic implications.

In patients (pts) with non-Hodgkin's lymphoma (NHL) under 25 years, treatment with MCP-842 protocol, a short duration intense protocol, yields worse survival in pts with lymphoblastic lymphoma (LL) compared to other high grade lymphomas. In order to identify both favourable and unfavourable subgroups in pts with T-cell LL (T-LL) with respect to relapse free survival following treatment with MCP-842 protocol, we analysed the expression of p53 and bcl-2 proteins in 22 pts with T-LL treated at the Tata Memorial Hospital, Mumbai by immunohistochemistry. p53 protein overexpression was noted in 59% cases and bcl-2 overexpression was noted in 29.4% cases. p53 expression correlated with a higher rate of relapse (p = 0.03; RR 7.9). The 5-year relapse free survival (RFS) was better in p53 negative patients compared to positive patients (70 vs 38%) (log-rank sigma = 0.04). In conclusion, in this study, overexpression of p53 protein was common in patients with T-LL. T-LL pts negative for p53 are likely to benefit from the short intense protocol--MCL-842. Bcl-2 protein overexpression was not a prognostic factor in these patients.

Regional variation in the distribution of subtypes of lymphoid neoplasms in India.

Lymphoid malignancies (LM) are a heterogeneous group of tumours. The relative frequencies of the various types of LMs vary across geographic regions. The pattern in India shows significant differences from the rest of the world. As India is a vast country, we set out to investigate whether there are regional differences in the relative frequencies of the various LMs. A total of 562 LMs from three different regions in India--Barshi (western India, 102 cases), Pondicherry (southern India, 156 cases) and Jaipur (northern India, 304 cases) were analysed according to the WHO classification. The non-Hodgkin lymphoma (NHL) to Hodgkin disease (HD) ratio was 6.28 in Barshi, 1.26 in Pondicherry and 2.27 in Jaipur. The frequency of HD's various subtypes did not significantly differ among the three regions. While T-cell NHLs constituted only 12.5% of NHLs at Barshi, they accounted for 31 and 27.5% of all NHLs at Pondicherry and Jaipur, respectively. There were also notable differences in the specific subtypes of NHL between the three different geographic regions in India.

MALT lymphoma of nasal mucosa treated with antibiotics.

Mucosa associated lymphoid tissue (MALT) lymphomas occur in sites other than the gastrointestinal tract and in the early stages respond to treatment with antibiotics. We report a rare case of nasal mucosal MALT lymphoma which responded to treatment with antibiotics and has since then remained in remission.

Expression of Fas and Fas ligand in Hodgkin's disease.

Fas and Fas ligand expression were investigated in twenty two cases of classical Hodgkin's disease (HD) by immunohistochemistry. While Reed-Sternberg (RS) cells in 7/22 (32%) cases expressed Fas ligand, reactive lymphoid cells expressed Fas ligand in only 2 (9%) cases. In 20/22 (91%) cases, the RS cells expressed Fas. A higher proportion of RS cells in the nodular sclerosis subtype expressed Fas as compared to the mixed cellularity subtype. In 18/22 (82%) cases, Fas expression was also noted in the reactive lymphoid cells. In eight cases, the reactive lymphoid cells were also analyzed by flow cytometry and a majority of them were CD4+CD45RO+. Most of these activated T-cells expressed Fas but were negative for Fas Ligand. To investigate the co-expression of Fas and Fas Ligand in the RS cells, six cases were subjected to Fas and Fas ligand immunostaining on consecutive sections. The co-expression was documented in the RS cells in four of six cases. These six cases with expression of both Fas and Fas ligand were investigated for the incidence of apoptosis. There was no statistically significant relationship between expression of Fas on reactive cells, expression of FasL on RS cells and the proportion of apoptotic reactive cells. In all these cases apoptosis was not observed in the RS cells. Thus Fas - FasL interactions may not lead to apoptosis of the RS cells.

Characterization of lymphokine-activated killer cells from peripheral blood and lymph nodes of non-Hodgkin's lymphoma patients.

Peripheral blood lymphocytes (PBL) and lymph node lymphocytes (LNL) from non-Hodgkin's lymphoma patients were tested for LAK cell cytotoxicity using appropriate targets in a short-term 51chromium-release assay. The results showed a significant depression in LNL-LAK activity suggesting the reduced capacity of LNL to generate LAK cells. LNL-LAK cells demonstrated significantly low percentages of cells expressing CD16, CD56 and CD25 as compared to PBL-LAK of patients and healthy donors. The reduced capacity to generate LAK cells in lymph nodes could be due to the presence of low numbers of NK cells which are thought to be the main precursors of LAK cells. The IL-2 producing ability of lymph node mononuclear cells was found to be significantly higher than that of peripheral blood mononuclear cells from both healthy donors and NHL patients.

Natural killer activity and NK cytotoxic factors in peripheral blood and lymph node cells from non-Hodgkin's lymphoma patients.

Natural killer (NK) activity and natural killer cytotoxic factors (NKCF) were found to be depressed in large granular lymphocytes (LGL) from the peripheral blood and lymph node lymphocytes (LNL) from untreated non-Hodgkin's lymphoma (NHL) patients. The LGL number was also reduced in NHL patients as compared to the normal subjects. The depression in all the activities mentioned above showed a correlation with the clinical status of the patients. Exogenous interferon-alpha (IFN-alpha) treatment of the effector cells could augment the NK activity to a comparable extent in normal as well as patient's LNL. The results indicate that the production of interferon may be affected in cases of NHL and therefore it would be worthwhile to test the tolerance and efficacy of IFN-alpha in these patients.

Hexachlorocyclohexane-induced tumorigenicity in mice under different experimental conditions.

Continuous administration of 500 ppm hexachlorocyclohexane (HCH) in the diet induced 100% liver tumors in mice, but none were observed in rats and hamsters treated with the same dose of HCH. In Swiss male mice, tumor incidence at earlier ages was greater than that observed in corresponding age groups of Swiss female mice. It was further observed that in Swiss females, sex hormones retarded the tumorigenic effect of HCH; in BALB/c mice a similar phenomenon was not observed.

Solid and papillary epithelial neoplasm of the pancreas. Diagnosis by fine needle aspiration cytology in four cases.

The cytologic features of four cases of solid and papillary epithelial neoplasm of the pancreas that were diagnosed on fine needle aspiration cytology are described. Papillary structures with delicate vascular cores covered with several layers of bland tumor cells were a distinctive feature. The papillae in two of the cases showed mucoid material in their cores. The cytologic features of solid and papillary epithelial neoplasm of the pancreas are distinct from those of other cystic pancreatic tumors.

Reactive oxygen species involvement in ricin-induced thyroid toxicity in rat.

Ricin is known to have diverse effects on the cells of different organs like liver, kidney, pancreas, intestines and parathyroid. Acute decrease in serum thyroid hormone level 24 h after ricin administration (1.5 micrograms/100 g) led us to suspect the toxic action of ricin on the thyroid. We monitored the lipid peroxidation (LP) and anti-oxidant status of the thyroid tissue to determine the role, if any, played by reactive oxygen species (ROS) in this pathology. An increase of 39% in LP and 47% in superoxide dismutase, along with a 8.5% decrease in catalase points to the imbalance in the antioxidant defence involving hydrogen peroxide and its univalent reduction product, the hydroxyl radical. Thyroid histopathology shows destruction of thyroid follicles and necrosis, which may be due to ROS and may partly explain the 50% reduction in circulating thyroid hormones seen after ricin administration.

Psammomatous carcinoid tumor of the duodenum.

We report a case of psammomatous calcification in a carcinoid tumor of the ampulla of Vater. Although the tumor was glandular, its neuroendocrine nature was proved using chromogranin immunostain.

Small cell carcinoma of gall bladder.

Small cell carcinoma of the gall bladder is very rare. We report a 25-year-old woman with this tumor. These tumors typically occur in elderly women with cholelithiasis; chemotherapy is not known to improve survival.

Animal model for liver dysfunction using lomustine in Wistar rats.

AIM: To induce intrahepatic cholestasis in rats using lomustine 1(2-chloroethyl)-3-cyclohexyl-l-nitrosourea (CCNU). METHODS: Doses of 10 mg, 20 mg and 30 mg/Kg body weight of CCNU were injected intraperitoneally in separate groups of animals. RESULTS: With 10 mg/Kg body weight of CCNU, serum bilirubin levels increased for up to 72 hours and then slowly returned to normal. With a dose of 20 mg/Kg body weight of CCNU, serum bilirubin, AST, ALT and alkaline phosphatase levels increased for 72 hours and then returned to normal over 4-5 weeks. With a dose of 30 mg/Kg body weight peak levels of serum bilirubin were reached on day 17. Pathological studies were carried out after injection of 30 mg/Kg body weight of CCNU. After 72 hours hepatocytes were normal, with minimal nonspecific inflammation and bile duct proliferation. After 16 days, triaditis was observed with deposition of collagen. Focal fibrosis was also noticed. There was no significant abnormality of hepatocytes. After 75 days, hepatocytes showed focal ballooning. Bile duct proliferation was seen invading the parenchyma. Nodules of hepatocytes separated by irregular fibrous bands indicated cirrhosis. CONCLUSIONS: An animal model of intrahepatic cholestasis has been developed using CCNU; this model may be used to assess the utility of hepatobiliary radiopharmaceuticals.

Extragonadal malignant teratoma of the foot.

This report documents the occurrence of an extragonadal malignant teratoma on the sole of the foot, in a young male. The patient also developed a groin nodule showing the same histology. The testes, retroperitoneum and mediastinum, which are usual sites of germ cell tumours were all normal, and no other primary could be detected. A teratoma growing in the tip of an extremity is a unique occurrence, biologically difficult to explain, and, which to the best of our knowledge has never been reported in literature.