Gastrointestinal stromal tumors (GIST): a proposal of a "CT-based predictive model of Miettinen index" in predicting the risk of malignancy.

PURPOSE: To identify the predictors of malignancy on CT for the evaluation of gastrointestinal stromal tumors (GIST) by correlating CT findings with the mitotic index in order to propose a "CT-based predictive model of Miettinen index." METHODS: One radiologist and one resident in radiology with 14- and 4-year experience in oncological field reviewed the CT findings of 42 patients by consensus, with respect to lesion site, size, contour, tumor growth pattern, enhancing pattern, degree of enhancement of tumor, percentage of tumor necrosis, mesenteric fat infiltration, ulceration, calcification, regional lymphadenopathy, direct invasion to adjacent organs, and distant metastasis. All parameters were correlated with the mitotic index evaluated at histopathological analysis following surgery. Normality of variables was evaluated using Shapiro-Wilk test. Pearson's correlation test was used to assess the interaction between variables. The diagnostic accuracy percentage of tumor necrosis was measured by receiver operating characteristic (ROC) analysis for detecting whether the number of mitosis per 50 high-power fields was > 5. RESULTS: A significant statistical correlation was found between percentage of tumor necrosis and the mitotic index (p < 0.005), dimension, and location of the tumor. CONCLUSION: CT could be an accurate technique in the prediction of malignancy of GIST in a CT risk assessment system, based on the location of the tumor, its size, and the percentage of tumor necrosis.

Childhood infectious diseases and risk of multiple myeloma: an analysis of the Italian multicentre case-control study.

Common childhood infectious diseases have been associated with a reduced risk of following haematopoietic malignancies, but investigations on multiple myeloma (MM) are scarce. Information about 213 MM cases and 1128 healthy controls were obtained from a multicentre population-based Italian case-control study. The association between chickenpox, measles, mumps, pertussis and rubella and the MM risk was estimated by unconditional logistic regression, adjusting for age, gender and residence area. No association was found between MM risk and any considered infectious disease. The number of infections was slightly inversely associated with the risk of MM, but statistical significance was not reached (OR 0.87, 95% CI 0.55-1.4 for 1-2 diseases vs. none and OR 0.68, 95% CI 0.41-1.1 for 3-5 diseases, respectively, P = 0.131). We did not find a clear evidence that common infections during childhood are associated with the subsequent risk of developing MM.

Gastric GISTs: Analysis of c-Kit, PDGFRA and BRAF mutations in relation to prognosis and clinical pathological characteristics of patients - A GIRCG study.

BACKGROUND: Gastric gastrointestinal stromal tumors (GISTs) represent a subgroup of GISTs with a better prognosis than those located in other areas. In this retrospective study we performed a molecular characterization of a large series of patients with gastric GISTs in relation to clinical-pathological characteristics and prognosis. METHODS: DNA was extracted from paraffin-embedded sections from 221 gastric GIST patients submitted to surgery. Exons 9, 11, 13 and 17 of KIT, exons 12 and 18 of PDGFRA and exons 11 and 15 of BRAF were analyzed by direct sequencing. Cox regression analysis adjusted for clinical-pathological factors was performed to evaluate KIT and PDGFRA mutations in relation to the composite endpoint of relapse or death. RESULTS: KIT and PDGFRA mutations were observed in 119 (53.8%) and 56 (25.3%) patients, respectively, whereas 46 (20.8%) patients had wild type (wt) disease. Univariable analyses showed that a high Miettinen risk category and the presence of ulceration and KIT deletions were associated with increased risk of relapse or death (p < 0.001; p = 0.0389 and p = 0.002, respectively). After adjusting for Miettinen risk score, KIT deletions remained an independent prognostic factor (HRadj = 2.65, 95% CI [1.15-6.13], p = 0.023). Moreover, KIT deletions in exon 11 codons 557, 558 or 559 were associated with a higher risk of relapse or death than wt tumors (HRadj = 3.29 95% CI [1.64-6.64], p = 0.001). CONCLUSIONS: KIT deletions in exon 11, especially those involving codons 557, 558 or 559, were correlated with a more aggressive gastric GIST phenotype and increased risk of relapse or death.

VEGF-A clinical significance in gastric cancers: immunohistochemical analysis of a wide Italian cohort.

PURPOSE: The clinical significance of VEGF-A expression in gastric cancer (GC) has been reported with contradicting results. We analyzed the expression and clinical significance of VEGF-A in a wide Italian cohort of GC specimens. METHODS: VEGF-A expression was tested by immunohistochemistry in 507 patients with GC of all clinical stages. The impact of VEGF-A on overall survival (OS) was evaluated in conjunction with clinical and pathological parameters. RESULTS: In the Italian cohort we studied VEGF-A was not an independent prognostic factor neither at the univariate nor at multivariate analysis. CONCLUSIONS: Although frequently expressed, in our study VEGF-A was not able to discriminate between groups of patients with different risk.

Immunolocalisation of ghrelin and obestatin in human testis, seminal vesicles, prostate and spermatozoa.

The role of ghrelin and obestatin in male reproduction has not completely been clarified. We explored ghrelin and obestatin localisation in the male reproductive system. Polyclonal antibodies anti-ghrelin and anti-obestatin were used to detect the expression of these hormones in human testis, prostate and seminal vesicles by immunocytochemistry, while in ejaculated and swim up selected spermatozoa by immunofluorescence. Sertoli cells were positive for both peptides and Leydig cells for ghrelin; germ cells were negative for both hormones. Mild signals for ghrelin and obestatin were observed in rete testis; efferent ductules were the most immune reactive region for both peptides. Epididymis was moderately positive for ghrelin; vas deferens and seminal vesicles showed intense obestatin and moderate ghrelin labelling; prostate tissue expressed obestatin alone. Ejaculated and selected spermatozoa were positive for both peptides in different head and tail regions. This study confirms ghrelin localisation in Leydig and Sertoli cells; the finding that ghrelin is expressed in rete testis, epididymis, vas deferens and seminal vesicles is novel, as well as the localisation of obestatin in almost all tracts of the male reproductive system. This research could offer insights for stimulating other studies, particularly on the role of obestatin in sperm physiology, which is still obscure.

Detection of autoantibodies against actin filaments in celiac disease.

INTRODUCTION: Serum autoantibodies specifically directed toward intracellular cytoskeletal actin filaments (anti-actin antibodies, AAA) were found to be associated with intestinal villous atrophy (IVA) in celiac disease (CD). The aim of this study was to assess IgA-AAA with a commercial test that uses sections of rat intestinal epithelial cells in a well-selected cohort of patients and to evaluate the relationship between the presence of serum IgA-AAA and the severity of intestinal mucosa damage. MATERIALS AND METHODS: Serum samples from 70 CD patients and 150 controls subjects were analyzed retrospectively for the presence of IgA-AAA. RESULTS: The indirect immunofluorescence test that we used has a specificity of 100%; the sensitivity of the test is not high (25.7%). In this study we also show that serum AAA are more frequently positive in CD patients with total IVA (77.8%) and that this association is significant DISCUSSION: IgA-AAA certainly cannot take the place of much more sensitive tests such as a-tTG and EMA in the diagnosis of CD because of their low sensitivity; nonetheless, these antibodies could be determined in a-tTG and/or EMA positive patients who cannot undergo an intestinal biopsy because of a severe contraindication, or in the case of negative consensus regarding endoscopy, or when the histology interpretation is difficult. CONCLUSION: In conclusion, the IFI commercial test with intestinal epithelial cells as substrate offers a useful method for IgA-AAA determination. Serum IgA-AAA positivity is indicative of more severe intestinal histology damage and their assay could be a real help to the clinician, especially in the complicated cases.

Eosinophilic esophagitis: an Italian experience.

BACKGROUND: Eosinophilic esophagitis is an esophageal disorder characterized by esophageal and/or upper gastrointestinal tract symptoms, and by dense esophageal eosinophilia associated with a normal gastric and duodenal mucosa. Prevalently reported in children, eosinophilic esophagitis has recently been reported with increased frequency also in adults. AIMS: The purpose of this study was to report our experience with eosinophilic esophagitis in Italy, since there are only very few series of such patients in our country. PATIENTS AND METHODS: We retrospectively reviewed the histological data of consecutive patients with a diagnosis of esophagitis or reflux disease in the period September 2004-September 2008. Eosinophils were counted where they appeared most numerous in the biopsy, with a cutoff > 15 eosinophils in more than one high-power field as diagnostic of eosinophilic esophagitis. Patients were excluded if gastric or duodenal biopsies showed a prominent eosinophilic infiltrate. RESULTS: Twenty two patients (14 adults, 8 children, age range 2-59 years) were identified according to the above criteria. The average eosinophil count was 86/ high-power field (range 31-150), associated with other pathologic features (eosinophilic microabscesses eosinophil degranulation, basal zone hyperplasia, papillary elongation). The main clinical complaints were dysphagia, food impaction, and heartburn, and endoscopic findings consisted of mucosal thickening and inelasticity, longitudinal shearing, rings, and white specks, without difference between adults and children for both clinical and endoscopic variables. CONCLUSIONS: Eosinophilic esophagitis is not rare in Italy, and displays clinical, endoscopic, and pathologic features similar to those described in other countries.

Eosinophilic esophagitis: an Italian experience

Background: eosinophilic esophagitis is an esophageal disorder characterized by esophageal and/or upper gastrointestinal tract symptoms, and by dense esophageal eosinophilia associated with a normal gastric and duodenal mucosa. Prevalently reported in children, eosinophilic esophagitis has recently been reported with increased frequency also in adults. Aims: the purpose of this study was to report our experience with eosinophilic esophagitis in Italy, since there are only very few series of such patients in our country. Patients and methods: we retrospectively reviewed the histological data of consecutive patients with a diagnosis of esophagitis or reflux disease in the period September 2004-September 2008. Eosinophils were counted where they appeared most numerous in the biopsy, with a cutoff > 15 eosinophils in more than one high-power field as diagnostic of eosinophilic esophagitis. Patients were excluded if gastric or duodenal biopsies showed a prominent eosinophilic infiltrate. Results: twenty two patients (14 adults, 8 children, age range 2-59 years) were identified according to the above criteria. The average eosinophil count was 86/ high-power field (range 31- 150), associated with other pathologic features (eosinophilic microabscesses eosinophil degranulation, basal zone hyperplasia, papillary elongation). The main clinical complaints were dysphagia, food impaction, and heartburn, and endoscopic findings consisted of mucosal thickening and inelasticity, longitudinal shearing, rings, and white specks, without difference between adults and children for both clinical and endoscopic variables. Conclusions: eosinophilic esophagitis is not rare in Italy, and displays clinical, endoscopic, and pathologic features similar to those described in other countries(AU)

Undifferentiated gastric carcinoma with lymphoid stroma (lymphoepithelioma-like carcinoma/medullary carcinoma).

Undifferentiated gastric carcinoma with lymphoid stroma is a histological type of gastric cancer with favourable prognosis, microscopically characterised by nests of neoplastic epithelial cells intermingled with a dense lymphoid proliferation. Various studies have shown a close relationship between undifferentiated gastric carcinoma with lymphoid stroma and Epstein-Barr virus infection; the presence of viral DNA in tumour cell nuclei has been demonstrated using polymerase chain reaction and Epstein-Barr virus-encoded small RNA in neoplastic cell nuclei have been found using in situ hybridization. We describe two cases of undifferentiated gastric carcinoma with lymphoid stroma, one infiltrating the submucosa of the gastric body and the other invading the muscularis propria of the antrum. No lymph node neoplastic invasion was documented in either case. Epstein-Barr virus was detected in the neoplastic cell nuclei in both cases with in situ hybridization.

Immunohistochemical expression of p53 and Ki67 in colorectal adenomas and prediction of malignancy and development of new polyps.

The aim of this study was to investigate the immunohistochemical expression of p53 and Ki67 in colorectal adenomas in order to clarify their significance as indicators of malignancy and development of new polyps. Seventy-eight polyps were removed from 51 patients and examined. Twenty-nine patients (56.9%) had adenomas with low-grade atypia (13 of them developed new polyps at 3-year follow-up) and 22 (43.1%) had adenomas with high-grade atypia (6 of them developed new polyps at 3-year follow-up). We tested the association between p53 and Ki67 expression and various clinicopathological variables, and regression analysis was performed to identify the risk factors for malignancy and development of new adenomas. A significant correlation between the grade of atypia and p53 immunoreactivity was observed. Ki67 expression was not related to atypia and no correlation was found between p53 and Ki67 immunoreactivity. Regression analysis showed that size (p=0.0002) and p53 staining (p=0.0111) were the selected factors related to malignant transformation, whereas the number of synchronous primary polyps emerged as the only predictive factor of development of new adenomas, although without statistical significance. The expression of biological markers may be in future added to the currently examined features of polyps; however, further studies are needed to better define their predictive value.

Alcohol consumption and risk of Hodgkin's lymphoma and multiple myeloma: a multicentre case-control study.

BACKGROUND: Few studies have analysed the association between alcohol intake and Hodgkin's lymphoma (HL) or multiple myeloma (MM) risks. MATERIALS AND METHODS: A multicentre population-based case-control study of 363 HL, 270 MM cases, and 1771 controls offered the opportunity to evaluate the relationship between alcohol and HL/MM risks. Unconditional logistic regression was carried out to estimate odds ratios (ORs) and 95% confidence intervals (CIs), associated with alcohol intake (servings per week, grams per day of ethanol intake) or duration of exposure (year). RESULTS: For HL, considering nonsmokers only, ever drinkers had a significantly decreased risk than never drinkers (OR=0.46). Significantly lower risks in all levels of total alcohol intake were also detected, considering servings per week (OR for one to four servings per week=0.51, 95% CI 0.32-0.82; OR for five to nine servings per week=0.39, 95% CI 0.21-0.73; OR for 10-19 servings per week=0.26, 95% CI 0.12-0.54; OR for >or=20 servings per week=0.34, 95% CI 0.15-0.79) and grams per day of ethanol intake (OR for 0.1-9.0 g/day=0.45, 95% CI 0.27-0.74; OR for 9.1-17.9 g/day=0.52, 95% CI 0.30-0.90; OR for 18.0-31.7 g/day=0.27, 95% CI 0.13-0.57; OR for >31.7 g/day=0.35, 95% CI 0.15-0.79). In the analysis for ever-smoking HL cases and controls, ever drinkers had the same risk as never drinkers. For MM, ever drinkers had a non-significantly decreased risk than non-drinkers (OR=0.74), and ORs in almost all consumption levels were not significant (OR for 0.1-9.0 g/day=0.93; OR for 9.1-17.9 g/day=0.82; OR for 18.0-31.7 g/day=0.47; 95% CI 0.28-0.81; OR for >31.7 g/day=0.68). For HL and MM, the beverage type did not affect the risk significantly, and no consistent dose-response relationships were found, considering intensity or duration of alcohol consumption. CONCLUSIONS: Our study indicates a protective effect of alcohol consumption for nonsmoking HL cases.

Hereditary diffuse gastric cancer and E-cadherin: description of the first germline mutation in an Italian family.

AIMS: Germline mutation of the E-cadherin gene (CDH1) accounts for the Hereditary Diffuse Gastric Cancer (HDGC) syndrome. Fourteen pedigrees with Diffuse Gastric Cancer that fulfilled the International Gastric Cancer Linkage Consortium (IGCLC) criteria were selected and screened for CDH1 germline mutations. METHODS: The entire coding region of the CDH1 gene and all intron-exon boundaries were analyzed by direct sequencing in the 14 families fulfilling the IGCLC criteria. E-cadherin immunohistochemical expression was evaluated on tumour as well as normal formalin-fixed paraffin embedded tissues. RESULTS: A novel germline missense mutation was found. It was a single C-->T substitution in exon 8, resulting in a transition of CCG-->CTG (C1118T; Pro373Leu) demonstrated in the proband and her brother. At immunohistochemical analysis, the staining intensity was reduced and considered weakly positive (15%). CONCLUSIONS: The first CDH1 germline mutation of an Italian family is herein reported. The present missense mutation has never been described so far.

Increased phospholipase activity in Helicobacter pylori strains isolated from patients with gastric carcinoma.

PURPOSE: Phospholipase activity, one of Helicobacter pylori pathogenicity factors, has not been investigated enough, so far, although it may induce a remarkable damage to the gastric mucosa. In the present work, we have compared the whole phospholipase activity of H. pylori strains isolated from patients with gastric carcinoma with that of strains isolated from dyspeptic patients without gastric carcinoma. METHODS: We measured the phospholipase activity of one distinct H. pylori colony isolated from each of 10 patients with gastric carcinoma and 10 controls, dyspeptic patients without endoscopic and histological signs of gastric carcinoma. We also determined the phospholipase activity of 20 additional strains isolated from different areas of neoplastic and non-neoplastic tissue of two patients with gastric carcinoma, the cagA and vacA positive G27 and 328 wild strains and their respective vacA and cagA negative isogenic mutants. The whole phospholipase activity of strains was determined by measuring the release of (14)C-labeled palmitic acid from the radioactive l-3-phosphatidylcholine, 1,2-di[1-(14)C]palmiloyl substrate; results were expressed in pmol of palmitic acid per mg of protein. RESULTS: H. pylori strains isolated from patients with gastric carcinoma had levels of phospholipase activity significantly higher than those of strains isolated from controls (99.37 [S.D. 40.45] versus 34.46 [S.D. 16.46], P<0.001). In patients with gastric carcinoma, the mean phospholipase activity of strains isolated from neoplastic tissue was similar to that of strains isolated from non-neoplastic tissues (123.02 [S.D. 44.36] and 115.77 [S.D. 81.48], respectively. Interruption of cagA gene caused a ca. 20% reduction of phospholipase activity (36.38 versus 45.22 of the wild strain); that of vacA caused no reduction of phospholipase activity (26.53 and 25.37 of the wild strain). CONCLUSIONS: The infection by H. pylori strains that produce high levels of phospholipase may increase the risk of developing gastric carcinoma. We hypothesise that indirect products of phospholipase activity, such as prostaglandins, leukotrienes and lysophospholipids, may mediate carcinogenesis.

Acute abdomen due to small bowel anisakiasis.

The popularity in Western countries of dishes based on raw fish has led to an increased incidence of anisakiasis, a human parasitic disease caused by the ingestion of live anisakid larvae. The entire digestive tract may be involved, but the stomach and the small intestine are the most frequently affected sites. We report a case of acute abdomen due to Anisakis simplex infection that caused small bowel obstruction.

Experimental internal anal sphincter replacement with demucosated colonic plication.

BACKGROUND: Selective re-creation of a new internal anal sphincter could be indicated when the natural one is irreversibly damaged or excised. METHODS: In this preliminary experimental work, surgical techniques of internal anal sphincter replacement in pigs were investigated. After preoperative anorectal manometry, surgical procedure was done in two phases: abdominal, mobilization of the colon-rectum to the pelvic floor; and perianal, dissection of the anal canal from the external anal sphincter through the intersphincteric space. The fully mobilized anorectal segment, including the internal anal sphincter, was pulled down through the anus and resected. The distal colonic stump was then demucosated and two types of plications of the demucosated segment were accomplished, each type in three animals. The plicated segment was then returned into the anal canal, inside the external sphincter. Short-term follow-up with clinical and manometric evaluations was performed and, subsequently, histological analysis of the plicated segment, after the animals were sacrificed. RESULTS: None of the animals became incontinent. Anal manometry identified a high-pressure zone and relaxation reflex in the new anal canal. Histologic studies showed hypertrophy of smooth muscle layers without degenerative changes. CONCLUSION: This study indicates that a plication of colonic smooth muscle wall can re-create a high-pressure zone in the anal canal after the internal anal sphincter has been excised.

[Expression of p27 and proliferative (MIB-1), mitotic (MI) and apoptotic indices in early-phase (EGF) gastric carcinoma. Results of a study by the Italian Gastric Cancer Research Group (IRGGC)]. / Espressione di p27, indici proliferativo (MIB-1), mitotico (MI) e apoptotico (AI) nel carcinoma gastrico in fase iniziale (EGC). Risultati di uno studio del Gruppo Italiano di Ricerca del Cancro Gastrico (IRGGC).

AIMS: Since the Japanese Society for Gastroenterology and Endoscopy (JSGE) introduced the definition of Early Gastric Cancer (EGC), much more and deeper studies were done, which demonstrated that EGC was a more complex phase of the neoplastic disease with different morphologic characteristics, tightly linked to the prognosis. We evaluated the clinical impact of some prognostic factors, known being important in the advanced lesions, in a series of EGC patients with special reference to the clinicomorphological features. METHODS AND RESULTS: We analysed the mitotic (MI) and apoptotic (AI) indices and the immunohistochemical expression of p27 and MIB-1 in 83 EGC cases consecutively recruited in the hospitals of Forlì, Verona, Siena and Milan (IRGGC) in the period 1994-95. The classifications of JSGE, Lauren and Kodama were used to define the macroscopic, microscopic and growth pattern types, respectively. Decreased p27 expression correlated with the macroscopic escavated lesions and diffused mixed histotypes; the increase of MIB-1 detection with tumour size larger than 2 cm, but lesser than 4 cm; MI with intestinal histologic types and AI with mucosal and penetrating lesions, according to Kodama. Statistical analysis showed significative correlations among MIB-1, MI and AI, but not with p27 and the other variables. All these factors did not influence the prognosis of our patients. CONCLUSIONS: In our series, p27, MIB-1, MI, and AI did not add any useful clinical. So, in EGC patients the morphological features have still the most important role in influencing the prognosis and treatment of patients.

Delayed infection, late tonsillectomy or adenoidectomy and adult leukaemia: a case-control study.

In a population-based case-control study among adults in Italy, of 261 lymphoid and 313 myeloid leukaemias and 1718 controls, a later age at adenoidectomy and tonsillectomy (after age 10 years) increased considerably the risk of lymphocytic (but not myeloid) leukaemia (odds ratio 4.2, 95% confidence interval 1.1-16.2). We propose that late infection is a proliferative stimulus for B-cells.

Inactivation of the E-cadherin gene in sporadic diffuse-type gastric cancer.

Loss of the cell adhesion molecule E-cadherin has been observed in a variety of human carcinomas, and germline E-cadherin mutations have been found in several familial cases of diffuse gastric cancer. We sought to determine the prevalence and nature of E-cadherin alterations in "sporadic" gastric carcinomas. We performed comprehensive sequencing of the coding region, loss of heterozygosity (LOH) analysis, and immunohistochemical protein expression determination on 40 sporadic gastric adenocarcinomas. In total, 7 of 25 diffuse-type cancers harbored genetic alterations in the E-cadherin gene. Novel mutations predicted to significantly compromise protein function were found within 4 of these cancers, 2 of which harbored alterations resulting in biallelic inactivation of the gene product. Three diffuse cancers failed to amplify Exon 8 of E-cadherin, suggesting the presence of a homozygous abnormality. Notably, one germline E-cadherin mutation was also identified within these "sporadic" diffuse cancers. Significant gene mutations were not found in the 14 intestinal-type or histologically mixed cancer. Immunohistochemistry revealed aberrant or negative protein expression in seven diffuse-type tumors, four of which correlated with the genetic alterations. Both diffuse and intestinal-type tumors exhibited low rates of LOH, suggesting that allelic loss at the locus is not a common mechanism for E-cadherin inactivation during gastric tumorigenesis. Our observations suggest that inactivation of the E-cadherin gene occurs only in a subset of diffuse-type gastric cancers, as the majority of cases did not contain genetic alterations or identifiable protein abnormalities. Germline E-cadherin alterations, although rare, may underlie some diffuse gastric cancer cases that have important biologic and practical implications

Smoking and hematolymphopoietic malignancies.

OBJECTIVE: Tobacco use is the most prominent cause of respiratory cancers. Little is known, however, about the influence of smoking on hematolymphopoietic malignancies. To evaluate this relation, a population-based case-control study was carried out in 12 areas of Italy. METHODS: Detailed interviews on tobacco smoking habits were administered to 1450 non-Hodgkin's lymphoma (NHL), 365 Hodgkin's disease (HD), 270 multiple myeloma (MM), and 649 leukemia (LEU) patients occurring from 1990 to 1993, and 1779 population controls. RESULTS: We found a slightly increased risk for NHL in smokers (odds ratio 1.2, 95% confidence interval 1.0-1.4 for ever smokers), but a consistent positive association was shown only for follicular NHL. In this subtype, a significant excess risk was observed for ever versus never smokers, after adjustment for gender, age, geographic residence, education, and respondent (OR = 1.8, 95%, CI 1.3-2.7), with a positive exposure-response gradient for smoking duration (p < 0.01). The risk for follicular NHL was significantly elevated only among women, with ever smokers showing OR = 2.3 (CI 1.4-3.8), while for men we found OR = 1.3 (CI 0.69-2.3). No major differences were shown according to age. Female subjects also showed significant positive exposure-response trends for duration. CONCLUSION: Cigarette smoking could be a risk factor for follicular NHL among women. For HD, MM, or LEU, no clear association was observed.