HIV-associated lymphoma: A 5-year clinicopathologic study from India.

CONTEXT: Relative risk of non-Hodgkin lymphoma (NHL) in people living with HIV is 60-200 times that of normal population. This is the largest series from India on lymphomas arising in HIV-infected individuals including workup for Epstein-Barr virus (EBV) and human herpesvirus-8 (HHV-8). AIMS: This study aims to ascertain the distribution and detailed clinicopathologic features of lymphoma arising in HIV-infected persons in India. SETTINGS AND DESIGN: The study was done during the period of 2007-2011 in the pathology department of a tertiary care center in South India. SUBJECTS AND METHODS: All cases diagnosed as lymphoma in the department of pathology during the study period were identified, and patients with HIV positive by serology were included in the study. Clinical details were obtained from electronic records, slides were reviewed and tissue blocks retrieved, and immunohistochemistry for HHV-8 and in situ hybridization for EBV-encoded RNA was done. STATISTICAL ANALYSIS USED: Descriptive statistics were done using SPSS software. Kaplan-Meier curves were used to do survival analysis. RESULTS: Of 3346 patients diagnosed with lymphoma, 73 (2%) were diagnosed to be positive for HIV. About 87.6% of the cases were NHL, of which diffuse large B-cell lymphoma was the most common and plasmablastic lymphoma was the second common subtype. Survival was uniformly poor in 36% of the cases where follow-up was available. CONCLUSIONS: The striking differences from world literature included higher frequency of plasmablastic lymphomas, lack of primary central nervous system lymphomas, and low association with HHV8.

Frequency, distribution, and immunomorphologic characteristics of peripheral T-cell lymphoma, not otherwise specified in a tertiary care center in Southern India.

AIMS: In world literature, Peripheral T-cell lymphomas (PTCLs) constituted about 12% of non-Hodgkin's lymphomas (NHL) of which PTCL not otherwise specified (NOS) was the most common subtype. This study was undertaken to ascertain the frequency and to assess the morphologic and immunophenotypic characteristics of PTCL, NOS over a period of 5 years in a tertiary care referral center in Southern India. MATERIALS AND METHODS: Slides and blocks of all PTCL, NOS were retrieved, and a detailed morphologic and immunophenotypic study using a wide panel of antibodies was done. RESULTS: During this study, NHL constitutes 77.61% of all lymphomas. PTCL formed about 12.55% (251 cases) of all NHL. PTCL NOS was the most common subtype (30.68%). The most common site of involvement was lymph nodes (75%) followed by extranodal sites such as soft tissue (8.33%), gastrointestinal tract including oral cavity (6.67%), nasal cavity (5%), central nervous system (1.67%), lung (1.67%), and spleen (1.67%). PTCL, NOS showed a broad morphologic spectrum and had varied morphologic patterns with some mimicking reactive hyperplasia and some mimicking known type of T-cell lymphomas, B-cell lymphomas, and Hodgkin's lymphoma. CONCLUSIONS: PTCL, NOS constituted about 30.68% of all PTCLs in our institution during a 5-year period and was the second most common type of PTCL. Immunophenotyping using a wide panel of T-cell antibodies is necessary to distinguish PTCL, NOS from other lymphomas which they mimic, as they are known to carry a worse prognosis.

Lymphomatoid granulomatosis: A case series from South India.

CONTEXT: Lymphomatoid granulomatosis (LYG) is a rare B-lymphoproliferative disorder characterised by an angiocentric and angiodestructive pattern along with Epstein - Barr virus (EBV) association. It is one of the diagnostic challenges in lymphoma pathology. Deregulation of EBV immune surveillance is one of the narrated hypotheses in the literature. Extrapulmonary manifestations are rare with LYG. Morphological grading is done based on the number of EBV-positive B cells, which is useful to strategize treatment protocol. AIMS: We report here a series of nine cases of LYG to discuss the clinical, histological, and immunohistochemistry findings. SETTINGS AND DESIGN: This is the first case series from India in published literature. SUBJECTS AND METHODS: We reviewed cases of LYG diagnosed at our center for the past 11 years (2006-2016). A total of nine cases were included in this study. Histomorphology was studied in conjunction with immunohistochemistry and clinical details. Cases without classical morphology and negative for EBV immunostain were excluded from the study. RESULTS: There were nine patients in our study (7 males and 2 female; M:F ratio 3.5:1). The age of these patients ranged from 4 years to 57 years (mean age: 30 years). The most common site involved was the lung (4, 44%), followed by the skin (2, 22%), central nervous system (2, 22%) and lymph node (1, 11%). One patient had primary immunodeficiency. Another patient had undergone renal transplant 11 years before the development of the lesion. Angiocentricity and angioinvasion were appreciated in all nine cases (9/9) with necrosis in four cases (44%) and ill-defined histiocytic aggregates in three cases (33%). The histological features were as follows: Grade 1(4 cases, 44%), Grade 2(2 cases, 22%), and Grade 3(3 cases, 33%). CONCLUSION: LYG is a rare EBV driven angiodestructive disease with predominantly lung involvement as well as isolated extrapulmonary sites as seen in our study. It is often progressive and ultimately fatal in the absence of appropriate treatment. Grading of the lesion helps to initiate the appropriate treatment of choice.

Follicular variant of peripheral T-cell lymphoma.

Globally, peripheral T-cell lymphomas (PTCLs) constitute about 12% of all non-Hodgkin lymphomas, of which the unspecified category is the most common subtype (30%). Mostly, the unspecified category shows a diffuse pattern of involvement in the lymph nodes. However, rarely, they may show a follicular/nodular pattern mimicking a follicular lymphoma. We report a case of a follicular variant of PTCL, not otherwise specified. This case displayed a striking nodular/follicular pattern with an admixture of small (centrocyte-like) and large (centroblast-like) cells, thus mimicking a follicular lymphoma. The neoplastic cells were strongly positive for both CD3 and CD20. In addition, they were positive for pan T-cell markers and PD-1. T-cell receptor gene rearrangement studies highlighted a monoclonal T-cell population. Even though this variant of PTCL is very rare, it is important to keep it as a differential for the lymphomas exhibiting nodular pattern.

Peripheral T-cell lymphoma of tongue: Report of a rare case and review of literature.

Primary non-Hodgkin lymphomas of the oral region are rare, accounting for 3-5% of all malignant lesions. Of these, peripheral T-cell lymphomas (PTCLs) are extremely rare with only a few cases reported in literature. We describe a case of 50-year-old female who presented with an indurated lesion on the tongue. PTCL was diagnosed after immunohistochemical and T-cell receptor gene rearrangement analysis. Although PTCL of oral cavity is extremely rare, the possibility should always be considered in the differential diagnosis of T-lymphoid proliferations affecting this area.

Type D lymphomatoid papulosis simulating aggressive epidermotropic cytotoxic lymphoma.

Three histological subtypes of lymphomatoid papulosis (LyP), type A (histiocytic), type B (mycosis fungoides like) and type C (anaplastic large cell lymphoma like) are well recognized. Two new histological variants, type D (simulating an aggressive epidermotropic cytotoxic lymphoma) and type E (angioinvasive type) has been described recently. We describe a 27-year-old man presented with a history of asymptomatic erythematous papules on both upper and lower limbs noted since 10 years of age. There were no systemic symptoms. Biopsy revealed an atypical dermal lymphoid infiltrate with epidermotropism, and the immunohistochemical markers showed a diffuse positivity for CD3, CD8, CD56, T1A and granzyme B with the focal positivity of CD30. All other relevant tests were normal. In this case report of a recently described delineated variant of LyP we emphasize the indolent course of this entity although the histology would suggest a more aggressive disease.

Extracavitary primary effusion lymphoma: A case report from India.

We present a case of extracavitary primary effusion lymphoma presenting, as jejunal polyps in a 38-year-old man. This is the first report of this entity from India. Although rare in our country, the diagnosis should be suspected in cases of CD20 negative large cell lymphoma with plasmablastic or immunoblastic differentiation in seropositive patients. Immunostaining for latency-associated nuclear antigen-1 and in situ hybridization for Epstein-Barr virus-associated RNA will confirm the diagnosis.

Clinical course of disseminated Kaposi sarcoma in a HIV and hepatitis B co-infected heterosexual male.

AIDS associated Kaposi sarcoma (AIDS-KS) was first reported from India in 1993. Since then only 16 cases have been reported. Three of them had proven Human Herpesvirus 8 (HHV-8) infection. We report a case of disseminated KS in a heterosexual male from India with HIV, hepatitis B and HHV-8 infection. He was given six cycles of chemotherapy with liposomal doxorubicin over three months to which he showed a good response. The case highlights the clinical course and management of a HHV-8 positive disseminated KS in a patient co-infected with Hepatitis B and HIV.

Clinicopathological correlates of primary central nervous system lymphoma: experience from a tertiary care center in South India.

BACKGROUND: Primary central nervous system lymphomas (PCNSL) constitute a rare group of extranodal non-Hodgkin's lymphomas (NHLs). AIM: To study the clinical and immunophenotypic profile of patients with a PCNSL who presented between the years 2000 and 2013 in a tertiary care center in South India. MATERIALS AND METHODS: This was a retrospective study. Demographic and clinical data were obtained from the clinical case records. INCLUSION CRITERIA: Cases of PCNSL involving brain. EXCLUSION CRITERIA: Cases of PCNSL involving the spinal cord, meninges and orbit as well as intravascular large B-cell lymphoma, lymphomas with evidence of systemic disease or secondary lymphomas. Archived slides and tissue blocks were retrieved. All cases had hematoxylin and eosin stained sections and immunohistochemistry for CD20, CD3, and MIB-1. Additional immunohistochemistry was performed for CD10, BCL6, and MUM1 on paraffin blocks with sufficient tissue. RESULTS: There were a total of 73 cases with the mean age of presentation being 45.9 years (range 8-71 years) and with a male predominance (male: female (M:F) = 2.3:1). Headache was the commonest presenting complaint. The mean duration of symptoms was 10.6 weeks. All patients were immunocompetent. Most tumors were supratentorial in location. Out of 73 cases, 70 presented with a diffuse large B-cell lymphoma (DLBCL), two with a Burkitt's lymphoma, and one with a lymphomatoid granulomatosis. Only 51 of the DLBCL cases had sufficient tissue for additional studies. Non-germinal center was the most common phenotype seen in 65.7% (33/51) of cases. Germinal center B-cell (GCB) phenotype was seen in 18/51 cases (34.3%). CONCLUSION: DLBCL constituted the majority of PCNSLs and although non-germinal center was the predominant phenotype, more than a third of the cases were of the GCB phenotype. As the germinal center phenotype is known to have a better prognosis, further studies to explore its relevance in the Asian population are indicated.

V-raf murine sarcoma viral oncogene homolog B (BRAF) mutations in hairy cell leukaemia.

INTRODUCTION: Hairy cell leukemia (HCL) is a B-cell non-Hodgkin lymphoma with distinct clinical, morphological and immunophenotypic features; however, there are many other B-cell lymphomas, which closely mimic HCL. Accurate diagnosis of HCL is important as treatment with 2-chloro-2'-deoxyadenosine (cladribine) is associated with >80% chance of complete cure. The recent description of BRAF p.V600E mutations in almost all HCL cases in various studies has not only improved the pathogenetic understanding of this entity but also increased the diagnostic accuracy of this disorder. AIM: The aim of the study was to standardize a molecular test for diagnosis of HCL and compare with standard established morphological, cytochemical and immunophenotypic parameters for HCL diagnosis. MATERIALS AND METHODS: The incidence of this mutation was sought in 20 patients with either classical HCL or HCL variant (HCLv) by Sanger sequencing and allele-specific polymerase chain reaction. BRAF p.V600E mutation was present in all HCL cases and absent in the only HCLv case. RESULTS: A high degree of correlation was noted between the presence of BRAF p.V600E and established diagnostic criteria in 20/20 patients with HCL/HCLv. Our data supports the observation that this mutation is present in all cases of HCL and is absent in HCLv. Hence, detection of the BRAF p. V600E mutation can be a useful adjunct in the diagnostic algorithm.

Hydroa vacciniforme-like lymphoma: a case report from India.

We report a 14-year-old Indian boy who presented with a history of weight loss, fever, facial edema, and a relapsing papulovesicular eruption on the face and limbs for 1 year. Histopathology of the skin showed dense lymphoid infiltrate from dermis to subcutaneous fat. Immunohistochemistry of this lymphoid infiltrate was CD3, CD8, CD56, CD57, Granzyme B, TIA, and Epstein Barr virus LMP1. The histopathology and immunohistochemistry were consistent with the diagnosis of hydroa vacciniforme-like T-cell lymphoma. The child responded remarkably to oral steroids but relapsed on tapering doses. CHOP (Cyclophosphamide, Adriamycin, Vincristine, and Prednisolone) chemotherapy was initiated in view of systemic involvement to which he showed some response, however, the disease relapsed again. He then had a rapidly progressive disease and ultimately succumbed to his illness. This is the first case of hydroa vacciniforme-like T-cell lymphoma being reported from this subcontinent.

Kikuchi-fujimoto disease: clinical and laboratory characteristics and outcome.

INTRODUCTION: Kikuchi-Fujimoto disease is an uncommon disorder with worldwide distribution, characterized by fever and benign enlargement of the lymph nodes, primarily affecting young adults. Awareness about this disorder may help prevent misdiagnosis and inappropriate investigations and treatment. The objective of the study was to evaluate the clinical and laboratory characteristics of histopathologically confirmed cases of Kikuchi's disease from a tertiary care center in southern India. MATERIALS AND METHODS: Retrospective analysis of all adult patients with histopathologically confirmed Kikuchi's disease from January 2007 to December 2011 in a 2700-bed teaching hospital in South India was done. The clinical and laboratory characteristics and outcome were analyzed. RESULTS: There were 22 histopathologically confirmed cases of Kikuchi's disease over the 5-year period of this study. The mean age of the subjects' was 29.7 years (SD 8.11) and majority were women (Male: female- 1:3.4). Apart from enlarged cervical lymph nodes, prolonged fever was the most common presenting complaint (77.3%). The major laboratory features included anemia (54.5%), increased erythrocyte sedimentation rate (31.8%), elevated alanine aminotransferase (27.2%) and elevated lactate dehydrogenase (LDH) (31.8%). CONCLUSION: Even though rare, Kikuchi's disease should be considered in the differential diagnosis of young individuals, especially women, presenting with lymphadenopathy and prolonged fever. Establishing the diagnosis histopathologically is essential to avoid inappropriate investigations and therapy.

Diffuse large B cell lymphoma in wiskott-Aldrich syndrome: a case report and review of literature.

Wiskott-Aldrich syndrome (WAS) is an X linked rare primary immunodeficiency syndrome with an increased propensity for infection, autoimmunity and malignancy. Here we report a male child, who was diagnosed with WAS at 1 year of age following evaluation for symptomatic thrombocytopenia and eczematous skin lesions. He presented later with lymphadenopathy, which was consistent with diffuse large B cell lymphoma on histopathology. He received 6 cycles of R-CHOP chemotherapy for the same and is presently in remission after 6 months. We review the major publications of lymphoma in WAS and discuss the pathological findings, treatment and prognosis of lymphoma in WAS.

Our experience with papillary thyroid microcancer.

BACKGROUND: Papillary thyroid microcarcinoma (PTMC) describes a focus of papillary thyroid cancer that is less than 1 cm in size. These tumors are frequently found on histopathological examination of thyroid specimens, operated upon for an indication other than suspected malignancy. MATERIALS AND METHODS: From 2005 to 2012, 94 of 1300 thyroidectomy specimens in our institution were found to have PTMC. Of these, 77 were isolated PTMC while the others were associated with other differentiated cancers. We studied their clinicopathologic features, treatment and long-term outcome. RESULTS: There were 18 men and 59 women (the male: female ratio was 1:3), their mean age was 44 ± 10.5 years (range: 18-72 years). Multinodular goiter was the most common indication for surgery. Malignancy was suspected in only 31.4% cases. The mean tumor size was 4.1 ± 2.3 mm. Nearly 17% cases had slightly larger tumors measuring >6 but <10 mm. Multifocal tumor was found in 44.1% of cases and among these, multifocal disease restricted to a single lobe was found in 19.5%. Eleven patients (14.2%) had cervical lymph node metastasis, 3 (3.9%) had extra thyroid tumor extension and 2 (2.6%) had evidence of vascular invasion. One patient (1.3%) presented with bone metastasis. Majority of the patients (79.2%) underwent total thyroidectomy with or without lymph node dissection. Sixteen patients (20.7%) who had initially undergone hemithyroidectomy went on to have completion thyroidectomy. Twenty nine patients (36.8%) also received radioactive iodine. The mean duration of follow-up was 20.2 ± 13.5 months. On follow-up one patient developed cervical lymph node recurrence and one died due to a second malignancy. CONCLUSIONS: PTMC is often found as an incidental finding on the thyroidectomy specimen. Sometimes they present with regional lymph node metastasis and very rarely with distant metastasis. They have a good prognosis similar to papillary thyroid carcinoma.

Lennert's lymphoma: clinicopathological profile of five cases.

BACKGROUND AND AIM: Lennert's lymphoma is a rare variant of peripheral T-cell lymphoma (PTCL) not otherwise specified (NOS) rich in epithelioid histiocytes. This study aims to analyze the clinical, morphologic, and immunophenotypic profile of cases of Lennert's lymphoma from our country and determines the utility of T-cell receptor (TCR) gene rearrangement in the diagnosis. MATERIALS AND METHODS: All cases diagnosed as Lennert's lymphoma during the period of January 2001 to August 2011 were included in this study. Hematoxylin and eosin (H and E) stained slides and immunohistochemistry results were analyzed and TCR gene rearrangement was performed. RESULTS: There were five cases of Lennert's lymphoma diagnosed in our institution during this period, which included two males and three females. All cases showed effacement of lymph node architecture by diffuse infiltration of small lymphoid T cells [CD3+, CD4+, CD8+, T-cell intracellular antigen 1 (TIA-1+), Granzyme B-] and clusters of epithelioid histiocytes throughout the lymph node and scattered large transformed cells (CD20-, CD30+, CD15-/+). TCR rearrangement was done in three cases by polymerase chain reaction (PCR) and showed the presence of a clonal T-cell population. CONCLUSIONS: Lennert's lymphoma constituted 0.11% of all non-Hodgkin lymphomas (NHLs) in our institution. Differentiation from classical Hodgkin's lymphoma is sometimes difficult by morphology and immunohistochemistry alone and TCR gene rearrangement was extremely useful in diagnosis.

Role of imatinib in the treatment of pediatric onset indolent systemic mastocytosis: a case report.

BACKGROUND: Mastocytosis is a sporadic disease characterized by an abnormal accumulation of mast cells (MCs) in single or multiple organs. It has a heterogeneous clinical picture which is a reflection of underlying tissue MC burden, mediators released and the organs involved. Here, the authors report significant symptomatic, cutaneous and systemic response to imatinib in a case of childhood onset indolent D816V KIT unmutated systemic mastocytosis (SM). CASE REPORT: A 19-year-old female presented with a history of itchy skin lesions over the face, trunk and extremities since 6 months of age associated with recurrent bouts of angioedema. The skin and bone marrow examination were consistent with mastocytosis. No pathogenic mutations were detected in exons 8 and 17. In view of the severity of cutaneous symptoms and evidence of bone marrow involvement, she was treated with imatinib which resulted in marked improvement. CONCLUSION: Imatinib has a therapeutic role in the presence of an imatinib-sensitive KIT mutation or in KIT816-unmutated patients with aggressive SM. Its role in the treatment of indolent and cutaneous mastocytosis is less well established. However, the authors have demonstrated the usefulness of imatinib in the treatment of c-KIT-negative indolent SM with extensive cutaneous involvement.

Frequency and distribution of lymphoma types in a tertiary care hospital in South India: analysis of 5115 cases using the World Health Organization 2008 classification and comparison with world literature.

This study aimed to analyze the distribution of lymphoid neoplasms in a single tertiary care center in India using the World Health Organization (WHO) 2008 classification. Histological material of 5115 patients with histopathological diagnosis of lymphoma, diagnosed over a period of 10 years (2001-2010), was analyzed retrospectively. Hodgkin lymphoma (HL) constituted 21.3% (n = 1089) and non-Hodgkin lymphomas (NHLs) constituted 78.7% (n = 4026). Of these, B-cell neoplasms accounted for 78.6% (n = 3166) and T-cell/natural killer (NK)-cell neoplasms 20.2% (n = 815) of the NHLs. The commonest subtype of NHL was diffuse large B-cell lymphoma (n = 1886, 46.9%). The frequency of peripheral T-cell/NK-cell lymphomas in this study was higher than in the Western literature but less than the frequency documented in some Asian countries. Similar to the Western literature but in contrast to previous Indian studies, peripheral T-cell lymphoma, not otherwise specified (PTCL NOS) (n = 238) was the commonest histological subtype of T-cell/NK-cell NHL in this study and constituted 5.9% of the total NHLs. Mixed cellularity (MC-CHL) (n = 488, 45%) was the major subtype of HL. Primary extranodal lymphoma (ENL) accounted for 32.8% (n = 1321) of all NHLs and most frequently involved the gastrointestinal tract. This study also documents the frequency of many rare types of lymphoma in South India.

Immunomorphologic profile and Epstein-Barr virus status of a cohort of 35 cases of extranodal natural killer/T-cell lymphoma, nasal type of upper aerodigestive tract from a tertiary care center in South India.

Extranodal natural killer (NK)/T-cell lymphoma, nasal type (EN-NK/T-NT) is a lymphoma of NK-cell or cytotoxic T-cell origin, which occurs most commonly in the upper aerodigestive tract. We have studied the immunomorphologic profile and Epstein-Barr virus (EBV) status of a cohort of 35 cases of EN-NK/T-NT of the upper aerodigestive tract (UADT) diagnosed in our institution during the period May 2002 to April 2012. At our institution these lymphomas constitute 0.7% of total non-Hodgkin lymphomas (NHLs) and 5.1% of total peripheral T-cell lymphomas (PTCLs). The median age at diagnosis was 40 years with a male-to-female ratio of 4:1, and the most common site of involvement was the nasal cavity. Morphologically, the neoplastic cells were predominantly medium sized in most cases. Necrosis and angiocentricity were common histologic features. Thirty cases (85.7%) showed NK-cell immunophenotype, CD3+ (29/30, 96.7%), CD56+ (30/30, 100%) and TIA1/Granzyme B+ (30/30, 100%). Five cases (14.3%) showed cytotoxic T-cell immunophenotype, CD3+ (5/5, 100%), CD56- (5/5, 100%) and TIA1/Granzyme B+ (5/5, 100%). EBV-encoded RNA-in situ hybridization (EBER-ISH) was positive in all 35 cases, whereas EBV latent membrane protein-1 (EBVLMP1) was positive in only 19/35 (54.3%) of cases. In conclusion, this is the first large study from India to report the immunomorphologic profile and EBV association of EN-NK/T-NT, which is known to have geographic variation. The frequency of these lymphomas in our study is comparable to that of Western and European countries and much less than that of Far Eastern countries.

Peripheral T-cell lymphoma: frequency and distribution in a tertiary referral center in South India.

BACKGROUND AND AIM: Peripheral T/NK-cell lymphomas are uncommon types of non-Hodgkin's lymphoma (NHL) with a higher frequency in Far East countries as compared to the West. This study was undertaken to ascertain the frequency and distribution pattern of peripheral T-cell lymphomas (PTCLs) diagnosed in a tertiary care center in South India. MATERIALS AND METHODS: This retrospective study was carried out in Department of General Pathology, Christian Medical College, Vellore. The time period was for 2 years from 1 st January 2008 till 31st December 2009. All PTCLs were reviewed and classified according to the World Health Organization (WHO) 2008 classification. RESULTS: Of a total of 1032 cases of NHL, 180 cases were PTCL, which accounted for 17.4% cases of all the NHLs. Of these, PTCL, not otherwise specified (PTCL, NOS) was the most common subtype (48 cases, 26.1%), followed by anaplastic large cell lymphoma (41 cases, 22.8%), mycosis fungoides (21 cases, 11.7%), angioimmunoblastic T-cell lymphoma (16 cases, 8.9%), subcutaneous panniculitis like T-cell lymphoma (15 cases, 8.4%), extranodal NK/T-cell lymphoma, nasal type (12 cases, 6.7%), and hepatosplenic T-cell lymphoma (10 cases, 5.6%). The most common primary site of presentation was nodal accounting for 42% followed by cutaneous (34%), upper aerodigestive sites (8.9%), spleen (6.7%), and gastrointestinal tract (GIT; 3.3%). CONCLUSIONS: This is the largest single study on PTCLs in India and we document that its frequency is higher than that reported in Western literature and previous Indian studies and almost similar to that reported in some Far East studies. The frequency of mycosis fungoides, subcutaneous panniculitis like T-cell lymphoma, and hepatosplenic T-cell lymphoma was higher than that reported in the World literature and previous Indian studies. The frequency of extranodal NK/T-cell lymphoma and angioimmunoblastic T-cell lymphoma was much lower than that reported in the Far East literature.

Low dose aspirin prevents duodenoesophageal reflux induced mucosal changes in wistar rat esophagus by MAP kinase mediated pathways.

BACKGROUND: Investigations of molecular mechanisms behind the progression of neoplastic changes in the esophagus have uncovered the role of the COX & 5-Lox pathways. Human squamous esophageal mucosa produces relatively large amounts of eicosanoids in the presence of inflammation. Laboratory and epidemiological data suggest that aspirin and non-steroidal anti-inflammatory drugs may be chemo preventive through their inhibitory effect on COX25, 10. Cell culture studies have shown that the members of the mitogen activated protein (MAP) kinase family plays an important role in the development of bile acid-induced carcinogenesis. Differences in MAPK pathways activated by bile exposure were also noted in esophageal squamous cell lines and biopsies from patients with GERD. The protective role of aspirin and its molecular mechanism is not well understood. AIMS: 1. The effect of duodenal reflux on esophageal mucosa. 2. The role of aspirin in preventing duodenal reflux induced esophageal mucosa changes. 3. If it is proven to be preventive, the mechanism of its action. A duodenal reflux rat animal model was used by an end- to-side esophago duodenostomy. METHODS: Total of 56 rats was included. 3 were "Naive control" animals which did not undergo the surgical procedure. The remaining animals were divided into two groups: Surgery alone (experimental) and Surgery + aspirin [therapy group], esophagoduodenostomy. At 40 weeks, the rats were euthanized and appropriate esophageal samples were analysed for histopathology and p38 & ERK MAP kinases, VEGF, protease activity and caspase 3 activities. RESULTS: The presence of gross mucosal nodularity was seen in 21 and 10 rats of the experimental and therapy group respectively (p = 0.03; Table 1). Reflux-associated changes such as basal cell hyperplasia were more common in the experimental group, however this association did not reach statistical significance (p = 0.15; Table 1). Epithelial hyperplasia was seen more in the experimental group, which was prevented by aspirin [p < 0.01]. Papillomatosis, as shown in Fig. 4 was more common in the experimental group (p = 0.02). Activation of p38 & ERK MAP kinases was prevented in aspirin group (p < 0.05, CI -1.796--0.014). Examination of protease activity by zymographic analysis of the esophageal samples revealed a number of gelatinolytic bands in 50% rats of the experimental group, not observed in the therapy group. No significant changes were seen in Caspase 3 [Normal areas -99.74 & nodular areas - 100.34 percent of controls] or VEGF [mean 0.64, sd ± 0.76 Vs 0.69 ± 0.96] activity. CONCLUSIONS: Our data demonstrated that low dose aspirin reduced the incidence of duodenoesophageal reflux induced histological changes in the esophagus by preventing activation of proliferative & anti-apoptotic MAP kinases such as p38 & ER as well as protease activity. Though Barretts' changes and adenocarcinoma have not developed, it could explain the role of duodenoesophageal reflux in the development of different histological but potential premalignant lesions and molecular level changes which are prevented by low dose aspirin.