Association between hepatitis C virus and non-Hodgkin's lymphoma, and effects of viral infection on histologic subtype and clinical course.

PURPOSE: Because an etiologic role for hepatitis C virus in non-Hodgkin's B-cell lymphoma has been suggested by several reports, we assessed the prevalence of hepatitis C virus infection in patients with non-Hodgkin's B lymphoma and in controls, and evaluated the influence of viral infection on histologic and clinical features of the lymphoma patients. PATIENTS AND METHODS: We prospectively investigated 175 consecutive patients with non-Hodgkin's lymphoma and 350 controls for serologic and molecular markers of hepatitis C virus infection. Controls were selected from inpatients (n = 175) and outpatients (n = 175) cared for at our hospital. Patients with lymphoma who had hepatitis C virus infection were tested for mixed cryoglobulinemia. Aminotransferase levels were measured in all lymphoma patients at baseline and during and after chemotherapy. RESULTS: Hepatitis C virus prevalence in patients with non-Hodgkin's lymphoma was significantly greater than in control subjects (37% vs 9%, P = 0.0001). Among patients with lymphoma, viral infection was associated with older mean (+/-standard deviation) age (67 +/- 14 vs 61 +/- 8 years, P = 0.001), and women (41 of 87, 47%) were more likely than men (24 of 88, 27%) to have evidence of hepatitis C infection (P = 0.006). Thirteen of the 20 cases of immunocytoma were associated with hepatitis C virus infection, which was also more common in patients with orbital and conjunctival localization of lymphoma. Patients with mucosa-associated lymphoid tissue (MALT) lymphoma of the stomach were less likely to have evidence of hepatitis C infection. Mixed cryoglobulinemia was much more common in patients with hepatitis C virus infection (14 of 65 vs 1 of 110, P = 0.0001); it was not associated with the histologic type of lymphoma. Patients with and without hepatitis C virus infection underwent similar chemotherapy regimens and had no differences in response to chemotherapy or in overall and disease-free survival. Hepatic toxicity from chemotherapy was seen only in patients with hepatitis C virus infection, although all but one of these patients were able to complete their planned treatment. CONCLUSION: These findings suggest that the hepatitis C virus may have a role as an etiologic agent in non-Hodgkin's B-cell lymphoma. Some clinical and pathologic features of the disease are associated with hepatitis C virus infection, but the virus does not seem to affect prognosis.

Confirmation of anti-HCV EIA reactivities by RIBA and neutralization assay among blood donors and patients with chronic liver disease and hepatocellular carcinoma.

The aim of our study was to confirm by Recombinant Immunoblot Assay (RIBA) and by neutralization assay the repeat positive reactions found by two commercially available EIAs (Ortho and Abbott) when testing samples from volunteer blood donors, patients with chronic liver disease and with hepatocellular carcinoma. Our data show a high confirmatory rate among patients with chronic viral NANBH and HCC, while among donors and patients with CLD other than NANBH the percentage of presumptive EIA positive reactions confirmed by RIBA and/or neutralization assay is much lower. In our experience, the neutralization assay appears to be somewhat more sensitive than RIBA, especially when samples show low EIA optical densities.

Acute myelocytic leukemia and chronic myelomonocytic leukemia simultaneously with resectable breast cancer: a report of two cases.

This report describes 2 patients who developed acute myelocytic leukemia (AML) type M2 and chronic myelomonocytic leukemia (CMML) of the FAB classification, respectively 2 months and 2 weeks after diagnosis of operable breast cancer. The patient with AML showed pancytopenia 2 months before the diagnosis of AML, had a normal karyotype, and showed a good response to chemotherapy. The patient with CMML had a normal karyotype, and she was treated with hydroxyurea and supportive therapy. The 2 patients had no previous exposure to irradiation or cytotoxic therapy. These cases show that breast cancer and either leukemia or myelodysplastic syndrome may be associated even without previous irradiation or combination chemotherapy.

Value of rapid staining and assessment of ultrasound-guided fine needle aspiration biopsies.

In a series of 160 ultrasonically guided fine needle aspiration (FNA) biopsies, immediate cytologic evaluation of each specimen's adequacy was performed using a rapid staining method. The number of passes was thus limited to what was strictly necessary in order to obtain sufficient material; the average number of passes was only 1.27 per patient. The total series of FNA biopsies had a sensitivity of 95.6%, a specificity of 100% and an overall accuracy of 97.3%. In addition, the cumulative accuracy after each pass was calculated. A significant increase in diagnostic accuracy was found only after the second pass; the third and the fourth passes gave little further improvement. The results indicate that a rapid evaluation of the aspirated material during ultrasound-guided FNA biopsy can reduce the number of punctures needed per case, resulting in less discomfort and, probably, a reduced likelihood of complications for the patient. The results also suggest that a maximum of two punctures will probably yield adequate diagnostic material in most cases.

Simultaneous relapse of liver cell carcinoma and non-Hodgkin's lymphoma in the liver. Report of a case with diagnosis by ultrasonically guided fine needle aspiration biopsy.

A 50-year-old man was diagnosed with non-Hodgkin's lymphoma (NHL) in 1980; he was treated with chemotherapy and achieved complete remission. Six years later he reported upper abdominal pain. Ultrasound (US) showed a 3-cm mass in the right lobe of the liver. Needle aspiration showed hepatocellular carcinoma (HCC). The patient was treated with radical resection of the tumor. Three years later (June 1989), abdominal US showed two lesions in the right lobe of the liver. Needle aspiration and tissue core biopsy showed NHL in one lesion and HCC in the other. The lymphomatous lesion resolved after chemotherapy. The patient died 30 months later (January 1992) from a gastrointestinal hemorrhage; the NHL was in complete remission. This case of the simultaneous presence of HCC and hepatic lymphoma is, to our knowledge, the first diagnosed in vivo.

Predictive value of time-intensity curves obtained with contrast-enhanced ultrasonography (CEUS) in the follow-up of 30 patients with Crohn's disease.

OBJECTIVES: CEUS can provide accurate quantitative estimates of intestinal wall microvascularization in Crohn's disease. We hypothesized that inflammation of the intestinal wall is correlated not with the amount of wall vascularization (study of vascularization patterns, SVP) but with the degree of wall flow during a period of time (time-intensity study, TIS). Our objective was to discover whether CEUS SPV and/or CEUS-TIS reflect(s) vascular inflammation of the intestinal wall and display(s) correlation with clinical activity of the disease at the time of the examination (T0) or at the 3- and 6-month follow-up (T3, T6). MATERIALS AND METHODS: 30 patients with Crohn's disease (12 men, 18 women, mean age: 41.96 years; treatment: 5-ASA (n = 8), steroids (n = 13), anti-TNF (n = 7), azathioprine (n = 2) were studied with CEUS SPV and CEUS-TIS and followed for at least 6 months. The sonographic examinations were performed with SonoVue (BR1, Bracco) and a dedicated scanner (TECHNOS MPX, Esaote) equipped with software for calculation of time-intensity curves. Four vascular patterns (1: vascularization of the entire wall; 2: vascularization of >50% of the wall; 3: flow exclusively within the submucosal layer; 4: no signal). The semiquantitative analysis consisted in measurement of the area under the curve (AUC) (cut-off between active and inactive disease, 15), mean intesnity (IMA) (cut-off = 10). Each examination (180 s) was digitally recorded and analyzed. RESULTS: T0: cDAI <150 in 22 pts; cDAI > 150 in 8; T3: 22 pts. with cDAI<150, 8 with cDAI >150. At T0 CEUS SPV and CEUS-TIS both displayed low specificity, diagnostic accuracy, and negative predictive values (p = ns). At T0, CEUS SPV produced 8 true positives (TP), 15 true negatives (TN), 8 false positives (FP), 0 false negative (FN) (sensitivity: 100%; specificity: 68.2%; diagnostic accuracy: 69.5%; Positive predictive value (PPV): 100%; negative predictive value (NPV: 53.3%), and CEUS-TIS produced 6 TP, 18 TN, 4 FP, 2 FN (sensitivity 75%; specificity: 81.8%; diagnostic accuracy: 75%; PPV: 60%; NPV: 90%). At T3, CEUS SPV produced 8 TP, 12 TN, 7 FP, 3 FN (sensitivity: 72.7%; specificity: 63.2%; diagnostic accuracy: 50%; PPV: 53.3%; NPV: 80%), and CEUS SIT produced the following results: 10 TP, 19 TN, 0 FP, 1 FN (sensitivity: 90,9%; specificity: 100%; diagnostic accuracy: 96,5%; PPV: 100%; NPV: 95%). At T3 CEUS-SVP displayed low sensitivity and low diagnostic accuracy, whereas SIT was able to predict clinical activity during follow-up in all but one case (which showed reactivation after 6 months) (p = 0.001) CONCLUSION: CEUS-TIS alone was found to reflect vascular inflammation of the intestinal wall in Crohn's disease and predicted clinical activity during follow-up.

Imaging detection of new HCCs in cirrhotic patients treated with different techniques: Comparison of conventional US, spiral CT, and 3-dimensional contrast-enhanced US with the Navigator technique (Nav 3D CEUS)().

INTRODUCTION: The commercially available Navigator system(©) (Esaote, Italy) allows easy 3D reconstruction of a single 2D acquisition of contrast-enhanced US (CEUS) imaging of the whole liver (with volumetric correction provided by the electromagnetic device of the Navigator(©)). The aim of our study was to compare the efficacy of this panoramic technique (Nav 3D CEUS) with that of conventional US and spiral CT in the detection of new hepatic lesions in patients treated for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: From November 2006 to May 2007, we performed conventional US, Nav 3D CEUS, and spiral CT on 72 cirrhotic patients previously treated for 1 or more HCCs (M/F: 38/34; all HCV-positive; Child: A/B 58/14) (1 examination: 48 patients; 2 examinations: 20 patients; 3 examinations: 4 patients). Nav 3D CEUS was performed with SonoVue(©) (Bracco, Milan, Italy) as a contrast agent and Technos MPX(©) scanner (Esaote, Genoa, Italy). Sensitivity, specificity, diagnostic accuracy, and positive and negative predictive values (PPV and NPV, respectively) were evaluated. Differences between the techniques were assessed with the chi-square test (SPSS release-15). RESULTS: Definitive diagnoses (based on spiral CT and additional follow-up) were: 6 cases of local recurrence (LocRecs) in 4 patients, 49 new nodules >2 cm from a treated nodule (NewNods) in 34 patients, and 10 cases of multinodular recurrence consisting of 4 or more nodules (NewMulti). The remaining 24 patients (22 treated for 1-3 nodules, 2 treated for >3 nodules) remained recurrence-free. Conventional US correctly detected 29/49 NewNods, 9/10 NewMultis, and 3/6 LocRecs (sensitivity: 59.2%; specificity: 100%; diagnostic accuracy: 73.6%; PPV: 100%; NPV: 70.1%). Spiral CT detected 42/49 NewNods plus 1 that was a false positive, 9/10 NewMultis, and all 6 LocRecs (sensitivity: 85.7%; specificity: 95.7%; diagnostic accuracy: 90.9%; PPV: 97.7%; NPV: 75.9%). 3D NAV results were: 46N (+9 multinodularN and 6 LR), 3 false-negatives, and one false-positive (sensitivity: 93.9; specificity: 97.9%; diagnostic accuracy: 95.6; PPV: 97.9; NPV: 93.9). CONCLUSIONS: 3D Nav CEUS is significantly better than US and very similar to spiral CT for detection of new HCCs. This technique revealed the presence of lesions that could not be visualized with spiral CT.

Ultrasonically guided percutaneous drainage of abdominal fluid collections: a long-term study of its therapeutic efficacy.

Fifty patients underwent ultrasonically guided percutaneous drainage (US-GPD) either with needle aspiration or catheter drainage. The procedures resulted in 70% complete recovery, 20% partial success and 10% of failures. The same patients were followed with clinical examination and sonography for a mean time of 36.3 months (minimum follow-up: 12 months). During the follow up period, 10 relapses occurred and one patient, considered for surgery after partial percutaneous treatment of a pyogenic liver abscess, recovered completely under conservative treatment. An analysis of the factors potentially related to the recurrence was made. It was found that one-step needle aspiration of abdominal abscesses and percutaneous treatment of chronic pancreatic pseudocysts are more prone to relapses. We conclude that US-GPD is an efficacious therapy for abdominal fluid collections, but an adequate drainage technique and a careful selection of the patients is crucial to avoid the possibility of relapse.

Hepatocellular carcinoma in liver cirrhosis. A prospective study.

From January 1984 to December 1991 we carried out a prospective surveillance of the development of hepatocellular carcinoma (HCC) in 200 cirrhotic patients, monitored from the first histologic diagnosis of cirrhosis. Real-time ultrasonography (US) and serum alpha-fetoprotein (AFP) assays were performed every 3-6 months. During this period we detected HCC in 38 patients. The overall cumulative incidence of HCC in the 8 years was 41%, with a yearly incidence of 5.1%. Eighteen of 38 patients (48%) had a tumor < 5 cm in diameter. AFP reached diagnostic levels (> 500 ng/ml) in eight cases only (21%). Patients with initial AFP values > 20 ng/ml developed HCC more frequently than patients with values < or = 20 ng/ml; the percentage of HCC was statistically higher (p < 0.01) in patients in Child's B and C than in Child's A class. A periodic follow-up, using US and AFP, is suggested for the early diagnosis of HCC in cirrhotic patients.

Sweet's syndrome associated with monosomy 7 myelodysplastic syndrome.

Acute febrile neutrophilic dermatosis (Sweet's syndrome) is a reactive skin process frequently associated with inflammatory and neoplastic diseases, but particularly with hematologic malignancies. It usually precedes the underlying disorders for months or even years. Much of the evidence for this is based on a small series of case reports and reviews of the literature. Recently, immunological theories have suggested that helper T cell type 1 is involved in the pathogenesis of Sweet's syndrome. This process causes stimulation of the cytokine cascade, which may be responsible for the local and systemic activation of neutrophils and histiocytes. Clinically, Sweet's syndrome is characterized by an acute eruption of painful erythematous or violaceous plaques or nodules with fever, malaise, neutrophilic leukocytosis, and an elevated erythrocyte sedimentation rate. Peripheral blood neutrophilia is frequent and is one of the diagnostic criteria. However, 53% of patients with Sweet's syndrome linked to hematologic malignancies do not present any neutrophilia but rather granulocytopenia. Abnormal functioning of neutrophils is possible in many diseases. We report a case of a middle-aged male patient presenting Sweet's syndrome and granulocytopenia due to myelodysplasia and an anomalous chromosome seven (7-) with poor prognosis.

Extramedullary plasmacytoma of the testicle. Sonographic appearance and ultrasonically guided biopsy.

Extramedullary plasmacytomas of the testis are extremely rare. This is a report of a patient with plasmacytoma of the testicle who also had an extramedullary plasmacytoma of the epipharynx 12 months earlier. Sonography (US) scans showed a heterogeneous mass of the right testicle with hypoechoic echo pattern; ultrasonically guided fine-needle aspiration biopsy (UGFNAB) allowed confirmation of the diagnosis. Immunoperoxidase studies, performed on histologic specimen after a radical right orchiectomy showed a monoclonal staining pattern of intracellular immunoglobulin for IgA-K type. Bone marrow biopsy, skeletal X-ray and immunoelectrophoresis were all within normal limits. The patient was successfully treated by surgery and is still alive with no evidence of disease.

Role of ultrasound guided fine needle aspiration biopsy in the diagnosis of hepatocellular carcinoma.

In 170 cases of hepatocellular carcinoma, ultrasound showed a high sensitivity in identifying focal liver lesions. Fine needle aspiration biopsy guided by ultrasound yielded a pathological diagnosis in the majority of cases. The advantages of this technique, its high diagnostic yield and low cost, render the older technique of blind percutaneous biopsy using a coarse needle obsolete. Laparoscopy retains its essential role in selected cases. Complementary use of fine needle aspiration biopsy under ultrasound guidance and laparoscopy assures the highest rate of diagnostic accuracy in hepatocellular carcinoma. We confirm the poor sensitivity of alpha fetoprotein.

Serum antibodies to hepatitis C virus in Italian patients with hepatocellular carcinoma.

Antibodies against hepatitis C virus (anti-HCV) were detected in 60.8% of 78 patients with hepatocellular carcinoma (HCC). Cirrhosis, present in most of the patients, as well as alcohol abuse, age, sex, and alpha-fetoprotein were equally distributed in the anti-HCV-positive and -negative groups. HBsAg positivity was significatively higher in negative anti-HCV group. By contrast, hepatitis B virus (HBV) antibodies were detected more frequently in positive anti-HCV patients than in the negative anti-HCV group. These data must be considered with caution because of the small number of HBsAg-positive patients. It is concluded that the high prevalence of anti-HCV in patients with HCC may suggest an etiological role of the hepatitis C virus, although in relationship to age, alcohol abuse and cirrhosis, the similarity in the two groups questions this hypothesis.

Ultrasonically guided fine-needle aspiration biopsy: a highly diagnostic procedure for hepatic tumors.

In 481 patients, with sonographically suspected neoplastic involvement of the liver, we performed an ultrasonically guided fine-needle aspiration biopsy with 22-gauge Chiba needle. In the 441 controlled cases, we obtained 68.5% true positive, 26.5% true negative, and 5% false negative, with a sensitivity of 93.2%, specificity of 100%, and overall accuracy of 95%. The true positive include 42.1% hepatocellular carcinomas, 28.1% metastases from known extrahepatic malignancy, 24.5% metastases from unknown primary site, 5% hepatic involvement by non-Hodgkin lymphomas, and 0.3% undetermined malignancy. Also, in a larger series, ultrasonically guided fine-needle biopsy confirms its high specificity and overall accuracy. The cytologic assessment of the obtained material is almost always adequate. The use of immediate cytologic staining reduces the number of passes in each lesion with absence of insufficient sampling. Biopsy with fine cutting needles should be reserved only for cases not diagnosed by cytology.

Angioimmunoblastic lymphadenopathy with disproteinemia associated with carcinoma. Case report and review of the literature.

Angioimmunoblastic lymphadenopathy with disproteinemia (AILD) is a rare lymphoproliferative disorder. The clinical course varies and about 15-20% of the patients develop a malignant lymphoma. The association of AILD and carcinoma is very rare: only 4 cases have been reported in the literature. They are reviewed here and 1 case is described. This case is of special interest for the following reasons: (1) the exceptional length of time which elapsed between the diagnosis of AILD and the onset of an adenocarcinoma of the colon (118 months); (2) the long survival (the patient is still alive and well 140 months after the diagnosis of AILD); (3) unlike the cases reviewed, in our patient the carcinoma was diagnosed when AILD was in clinical remission, so a radical treatment was possible. In the cases previously reported, carcinomas arose in the lung (2 patients), pancreas (1 case), and stomach (1 case). The rare association of AILD and carcinoma is probably coincidental; however, the growth of solid tumors of nonlymphoid nature may be related to the impaired T cell function, and should be kept in mind in the management of patients with AILD.

Vascular signals from pleura-based lung lesions studied with pulsed Doppler ultrasonography.

Vascular signals arising from pleura-based lung lesions were studied in 50 patients using pulsed Doppler ultrasonography. Twenty-seven had malignant lesions and 23 benign lesions. In 24/27 of the malignant masses, we observed no Doppler signals: in 2 cases, a low-velocity, turbulent, pulsatile flow was demonstrated; in 1 case pulsed Doppler ultrasonography showed only a low-velocity, continuous flow. In 20/23 of the benign lesions, we found 2 types of Doppler signal waveforms: an irregularly pulsatile, venous-like signal, and a regularly pulsatile, arterial-like waveform. The last 8 patients of our series underwent color Doppler ultrasound examination, which demonstrated the presence of arterial and venous vessels in 4 benign lesions and the absence of blood flow in 4 malignant masses. To our knowledge, we report for the first time the ability of obtaining Doppler signals from a variety of lung lesions. The actual clinical relevance of this application requires further studies.

Complications of ultrasonically guided fine-needle abdominal biopsy. Results of a multicenter Italian study and review of the literature. The Cooperative Italian Study Group.

This report describes the complications following 10,766 ultrasonically guided fine-needle biopsies performed from 1979 to 1987 in 33 Italian echographic units. The mortality was 0.018%: the two reported deaths were due to hemoperitoneum and occurred in patients with hepatocellular carcinoma arising in a cirrhotic liver. Twenty patients (0.18%) had major complications. This series confirms that abdominal biopsy with fine needles is safe, even though our death rate was higher than in previous reports. Among the other nine fatalities following fine-needle abdominal biopsy reported in the literature, seven were secondary to hemorrhage. The biopsy of pancreatic carcinoma was more dangerous for needle-tract seeding (five of eight reported cases, including one in our series).

Diagnostic aspects and follow-up of 174 cases of hepatocellular carcinoma. Second report.

From June 1981 to June 1989 we diagnosed 174 cases of hepatocellular carcinoma (HCC) at our institution (Piacenza, Northern Italy). Average age was 65.6 years; male to female ratio 3.4. 149 patients were cirrhotic (85.6%); alcohol abuse was present in 88/169 (52.1%); in 53/145 patients all hepatitis B virus markers were negative. Alpha-fetoprotein showed a low diagnostic sensitivity (values above 500 ng only in 49/169 or 29.0%). We used ultrasound (US) examination with a very high identification rate in all cases; pathological diagnosis was achieved by US guided fine-needle aspiration biopsy in 135 patients; in 13, by laparoscopy-histology. Metastases were found in 24/169 cases (14.2%); a second malignancy was diagnosed in 13/169 (7.7%): the most common association was HCC-non-Hodgkin lymphoma. Only 14 patients could be referred to surgery, which significantly improved prognosis.