Signs Of Lymphoma Research Articles

When Pruritus is Not Allergy: Appropriate Signs of Lymphoma and Other Malignancies for the Community Allergist

Pruritus is a common symptom that all individuals have experienced at some time. Although general malignancy is a rare cause of pruritus, there is an increased risk of hematologic malignancy in those with chronic itch. For the allergist assessing chronic itch, we have outlined an approach in the case of suspected hematologic malignancy and steps for an initial work-up.

Is It Possible to Omit Bone Marrow Biopsy in Diagnostic Workup in Patients with Newly Diagnosed Primary CNS Lymphoma? a Retrospective Analysis in the PET/CT Era

Background: Primary central nervous system lymphoma (PCNSL) is a rare and aggressive extra-nodal non-Hodgkin lymphoma (NHL) confined to the brain, eyes, leptomeninges, and spinal cord. More than 90% of patients belong to diffuse large B-cell lymphoma (DLBCL). The consensus around the extensive systematic staging in patients with suspected or proven PCNSL is still a matter of debate. Current diagnostic and staging guidelines recommend extensive workup to exclude systemic disease with computed tomography (CT) scan of the chest, abdomen, and pelvis, a bone marrow biopsy (BMB), and testicular ultrasonography in males. Whole-body 18F-fluorodeoxyglucose positron emission tomography (PET-CT) is currently considered optional in diagnostic workup in patients with presumed PCNSL. The utility of BMB in the era of PET-CT has been challenged in systemic lymphomas, but data are lacking for patients with PCNSL. Among patients with PCNSL, BMB is often normal or reveals low-grade lymphomas or just clonal B-cells. In rare instances, aggressive lymphoma involves both bone marrow (BM) and the central nervous system (CNS). However, the role of BMB in PCNSL patients in the PET-CT era is yet to be established. This study aimed to analyze whether BMB could be safely omitted in the diagnostic workup in patients with PCNSL of DLBCL histology without signs of systemic lymphoma on PET-CT scans. Methods: A comprehensive nationwide retrospective multicenter study with enrollment of patients from the referent medical centers in Denmark for treatment of PCNSL was performed. Patients included in the study were diagnosed between 2002 and 2020 and identified through the Danish Pathology Register. All patients with CNS involvement were potential candidates. Inclusion criteria were the following: 1) patients should be diagnosed with DLBCL in brain, eyes, leptomeninges, cerebrospinal fluid, and spinal cord; 2) have available BMB; and 3) have available PET-CT without signs of lymphoma outside of CNS. Patients with PCNSL and prior history of other lymphoma were also included in the study. Patients were excluded if they were diagnosed with systemic lymphoma or PCNSL other than DLBCL. Patients who did not have PET-CT and BMB performed or in whom this information could not be retrieved through medical records were also excluded from further analysis. Results: Of 1238 potential candidates identified through the Danish pathology register, only 300 patients fulfilled the inclusion criteria. Most patients were excluded due to a lack of information on PET-CT scans and BMB. All included patients had available BMB and no signs of systemic lymphoma on PET-CT. Of the included patients, 252 (84%) were diagnosed with PCNSL without a previous lymphoma diagnosis, while 48 (16%) had a previous history of lymphoma. The median age of patients was 68 years. There was a slight predomination of men (60%) compared to women (40%). Twenty-three (7.7%) patients were found to have discordant findings in BMB. However, none of these showed infiltration with DLBCL. The histologies included various low-grade lymphomas found in 17 patients (5.7%), monoclonal B-cells in 3 patients (1%), and smoldering multiple myeloma in one patient. Conclusion: In this retrospective study of 300 patients with PCNSL with PET-CT scans without signs of systemic lymphoma outside CNS, we found no cases with BM infiltration of DLBCL. A small proportion of patients with PCNSL have a discordant, often low-grade lymphoma in the bone marrow. With a sample size of 300, the chance of overlooking DLBCL infiltration in the BM is ≤ 1 % (95% CI). Therefore, the results of this, so far the most extensive study evaluating BMB in PCNSL in the PET-CT era, suggest that BMB can safely be omitted in patients with PCNSL of DLBCL histology and no signs of systemic lymphoma on PET-CT scans.

Characteristics of clinical, laboratory, and immunological manifestations in patients with anticentromere antibody-associated Sjögren's disease

Objective: to study clinical and laboratory features in patients with anticentromere antibody (ACA)-positive SjЪgren's disease (SD), as well as the sensitivity of different methods for determination of ACA, and to elaborate an algorithm for differential diagnosis in ACA-positive patients.Patients and methods. The V.A. Nasonova Research Institute of Rheumatology followed up 136 patients who were highly positive for ACA. The investigators used the 2001 Russian criteria for the diagnosis for SD; the 2013 ACR/European League Against Rheumatism (EULAR) criteria for that of scleroderma systematica (SDS); the guidelines of the American Association for the Study of Liver Diseases, the Russian Gastroenterological Association, and the Russian Society for the Study of the Liver for that of primary biliary cholangitis (PBC)/biliary duct epitheliitis in the presence of SD. Lymphomas were diagnosed by biopsies of affected organs according to the WHO classification. SD was diagnosed in 119 patients; SDS in 49 cases (37 with SDS concurrent with SD and 12 with isolated SDS), PBC/biliary duct epitheliitis in 23 (all cases with PBC/biliary duct epitheliitis concurrent with SD and/or SDS); 5 patients were excluded from the investigation. Further analysis included 131 ACA-positive patients. The patients were divided into three groups: SD (n=82 or 62.6%); SD+SDS (n=37 or 28.24%); SDS (n=12 or 9.16%).Results and discussion. Autoantibodies to centromere peptide (CENP) A and CENP-B in the same titers were detected in all ACA-positive patients, regardless of diagnosis. Comparative analysis of three patient groups revealed no statistically significant differences in the frequency of laboratory deviations. The signs characteristic of classical SD (rheumatoid factor (RF)), anti-Ro and anti-La antibodies, leukopenia, higher ESR values, hypergammaglobulinemia, and elevated IgG/IgA levels) were found in a small proportion of patients. The frequency and severity of glandular manifestations did not differ in SD and SD + SDS. PBC/biliary duct epitheliitis was present in 17.5% of ACA-positive patients (in most antimitochondrial antibody-positive cases); no statistically significant differences in its frequency were found between the groups. Other extraglandular manifestations in SD and SD + SDS were identified in a smaller number of patients. All sclerodermic spectrum manifestations were more common in SD and SD + SDS than in BS. Pulmonary arterial hypertension was not diagnosed in any patient from the SD group. MALT lymphomas were detected in 19 ACA-positive patients. Those were present only in BS patients and absent in the SDS group. MALT lymphomas developed in the first 10 years after the onset of SD. The transformation of MALT lymphoma into diffuse large B-cell lymphoma was observed in 2 patients. The main signs of lymphomas in SD patients were persistent parotid salivary gland enlargement, decreased levels of complement C4 and peripheral blood CD19+ cells, as well as cryoglobulinemic vasculitis, serum monoclonal secretion, lymphoid infiltration in the minor salivary glands (a focus score of >4), and severe damage to the salivary and lacrimal glands.Conclusion. ACA-associated SD is an independent disease subtype characterized by an increased risk for SDS, PBC, and MALT lymphomas and by a low frequency of the systemic manifestations and laboratory signs characteristic of classical SD. Regardless of the detected type of antibodies and the presence or absence of extraglandular manifestations, damage to the salivary and lacrimal glands progresses in SD, which often leads to lymphomas; therefore, the therapy that may prevent this complication should be initiated as soon as possible after SD diagnosis. The lymphoproliferation signs identified in this investigation should be taken into account in all ACA-positive patients with SD for the early diagnosis of lymphoid tumors before therapy is prescribed. An algorithm for differential diagnosis in seropositivity for ACA is presented. Determination of autoantibodies to CENP-A and CENP-B does not allow the differential diagnosis in ACA-positive patients.

Population-based study of patients with primary Sjögren’s syndrome and lymphoma: lymphoma subtypes, clinical characteristics, and gender differences

Objective: To examine lymphoma subtypes, clinical characteristics, and gender differences in patients with primary Sjögren’s syndrome (pSS) and lymphoma in a population-based setting.Method: Patients with Sjögren’s syndrome and lymphoma diagnoses were identified by linkage of the Swedish Patient Register 1964–2007 with the Cancer Register 1990–2007. Clinical data were collected from medical records and lymphoma tissues were re-examined. The lymphoma subtype distribution was compared with the Swedish Lymphoma Register.Results: We identified 105 pSS patients with lymphoma. Diffuse large B-cell lymphoma (DLBCL) (32%) and marginal zone lymphoma [MZL including mucosa-associated lymphoid tissue (MALT) lymphoma] (31%) were the most common lymphoma subtypes. The proportion of DLBCL was not increased compared to the general population reference (32%, p = 1), in contrast to MZL (general population 5%, p < 0.0001). Compared to DLBCL, MALT lymphoma was diagnosed at a younger age (55 vs 67 years, p = 0.0001), and earlier after patient-reported sicca onset (7 vs 18 years, p = 0.0001) and pSS diagnosis (2 vs 9 years, p = 0.0005). Sixteen of the pSS-lymphoma cases were men (15%), twice the proportion in general pSS populations. Compared to women, men had a shorter median time from pSS diagnosis to lymphoma diagnosis (1 vs 8 years, p = 0.0003) and more often had lymphoma in the salivary glands (56% vs 29%, p = 0.04).Conclusion: DLBCL and MZL are common in pSS patients, but only MZL/MALT lymphoma occurs at an increased relative frequency in pSS compared to the general population. The study supports increased awareness of signs of lymphoma in men in the first years after pSS diagnosis.

2740 IgG₄-Related Disease: A Gastric Mass With an IgG4 Surprise

INTRODUCTION: IgG₄-related disease is a rare autoimmune syndrome that causes fibrosis of glands, most commonly of the pancreas and biliary tract1,3. The overall prevalence is unknown, with an estimated less than 1:100,000 of the general population typically found in middle-aged males2,3. Diagnosis is made with IgG₄ levels at least 2x the upper limit of normal and dense lymphoplasmacytic infiltrate, however, it may be seen with normal IgG₄ levels6. Although rare, it can present similar to GI malignancies and should be considered in the differential for patients with autoimmune disease1,3,4,5. Here we present one of those unusual cases. CASE DESCRIPTION/METHODS: A 65-year-old lady with PMH of DM2 and Sjogren's Syndrome (SS) who presented to the hospital with intractable nausea, vomiting, and failure to thrive for over 1 month. The physical exam, labs that included CMP, LFTs, and serology was unremarkable; previous EGD revealed diffuse thickening of the gastric submucosa. Biopsy via open gastrectomy revealed chronic inflammation with multiple IgG₄ plasma cells and no signs of lymphoma, suspicious for IgG₄-RD. After the partial gastrectomy, serum Na levels were 162, which improved with DDAVP and was later confirmed to be diabetes insipidus (DI). Further workup and imaging were negative and baseline IgG and IgG₄ levels were 1178 and 61, respectively. Treatment included steroid therapy and DDAVP which improved her symptoms and preceded an uneventful hospital course. DISCUSSION: IgG₄-RD is a disease with numerous presentations based on the organs involved. It presents as a GI-specific illness due to its affinity for the pancreas and biliary tract1,2,3. As seen in our patient, although rare, it may also affect the stomach, form mass lesions and cause symptomatology similar to a GI malignancy3,5. In patients with autoimmune diseases, where GI malignancy is considered, it is reasonable to include IgG₄-RD in the differential. IgG₄-RD may mimic symptoms of SS, and therefore case-patients with SS should also be considered for IgG₄-RD. This patient also experienced DI which may be a manifestation of IgG₄-RD, as the syndrome may affect the pituitary4. This case is one of the few instances reported to have pituitary involvement after the onset of multiorgan involvement4. Like other autoimmune disorders, IgG₄-RD is responsive to steroid therapy or rituximab. Therefore, a timely diagnosis can help slow down or prevent symptomatic manifestations, as seen in the case. Clinicians should be aware of this clinical presentation.

Tumor syndrome, hepatic and hematological features revealing undiagnosed early rheumatoid arthritis

Background: Extra-articular manifestations in rheumatoid arthritis (RA) are rare and generally occur in an advanced stage of the disease. We report a case of an unusual onset of early RA. Case presentation: A 21 year old male complains of polyathritis involving small and large joints, associated with fever, asthenia, anorexia and weight loss. The temperature was up to 38.8°. There was a left cervical adenopathies, hepato-splenomegaly and there were synovitis in all joints sparing distal interphalangial joints. The erythrocyte sedimentation rate was accelerated; the C-reactive protein was up to 222 mg/l. The number of white blood cells were 9000/mm3 with monocytosis, lymphocytosis and thrombocytosis at 986000/mm3 . There was cholestasis with cytolysis. Rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (ACCP) were positive. The hands X-ray didn’t show any RA specific signs. The chest X-Ray showed a left pleurisy. The CT scan showed multiple axillar and mediastinal lymphadenopathies, hepato-splenomegaly with multiple coelio-mesenteric and retroperitoneal lymph nodes. The pleural biopsy as well as the biopsy of the adenopathy and the salivary glands didn’t show any specific abnormalities or signs of lymphoma. The hepatic biopsy revealed an inflammatory lymphohistiocytic infiltrate with rare foci of necrosis and a dilatation of the hepatic sinusoids. The diagnosis of RA was suspected and confirmed by the MRI of the hands. Conclusion: RA may have an unusual onset such as hematologic, hepatic, pleuropulmonary features or tumor syndrome, but it is rarely reported. The diagnosis in this case is difficult

Clinical Scenarios in Chronic Kidney Disease: Parenchymal Chronic Renal Diseases - Part 2.

Secondary nephropathies can be associated with disreactive immunological disorders or with a non-inflammatory glomerular damage. In systemic lupus erythematosus (SLE), scleroderma and rheumatoid arthritis as in other connective tissue diseases, kidney volume and cortex echogenicity are the parameters that best correlate with clinical severity of the disease, even if the morphological aspect is generally non-specific. Doppler studies in SLE document the correlation between resistance indexes (RIs) values and renal function. Acquired immunodeficiency syndrome (HIV) causes different types of renal damage. At ultrasound (US), kidneys have almost a normal volume, while during superinfection they enlarge (coronal diameter >13 cm) and become globular, loosing their normal aspect. Cortex appears highly hyperechoic, uniform or patchy. Microcalcifications of renal cortex and medulla are a US sign that can suggest HIV. In amyloidosis, kidneys appear normal or increased in volume in the early stages of disease. Renal cortex is diffusely hyperechoic and pyramids can show normal size and morphology, but more often they appear poorly defined and hyperechoic. RIs are very high since the early stages of the disease. Nephromegaly with normal kidney shape is the first sign of lymphoma or multiple myeloma. In systemic vasculitis, renal cortex is diffusely hyperechoic, while pyramids appear hypoechoic and globular due to interstitial edema. When vasculitis determines advanced chronic kidney disease stages, kidneys show no specific signs. Microcirculation damage is highlighted by increased RIs values >0.70 in the chronic phase.

Diffuse Large B-Cell Lymphoma with Mass Lesions of Skull Vault and Ileocecum

We report a rare case of non-Hodgkin lymphoma with mass lesions of skull vault and ileocecum. The patient was an 82-year-old Japanese woman who exhibited a painless subcutaneous scalp tumor in the right parietal region associated with no neurological abnormalities. Magnetic resonance imaging of the head demonstrated a mass in the skull vault with iso- to hypointense signals on both T1- and T2-weighted imaging. Biopsy of the mass revealed that the tumor comprised large cells that were immunoreactive for CD20 (L-26) and CD79a. Diffuse large B-cell lymphoma (DLBCL) was therefore diagnosed. Further investigation could not identify any other evidence of systemic lymphoma other than ileocecal lesions. She was treated by irradiation (45 Gy) of the mass on the parietal bone and with rituximab, pirarubicin, cyclophosphamide, and vincristine. The patient achieved complete remission after 3 cycles of systemic chemotherapy. As of 30 months after presentation, no signs of lymphoma have been found.

Non Pegilated Liposomal Doxorubicin (TLC-D99; Myocet ™) Can Be Safely and Effectively Used As Part of the R-COMP Regimen in Patients with Diffuse Large B-Cell Lymphoma Who Show Contraindications to Anthracyclines Due to Concomitant Moderate/Severe Heart Disease. Results of the HEART01 Phase II trial by the Fondazione Italiana Linfomi (NCT01009970)

AbstractAbstract 3644 Background:R-CHOP is the standard treatment for Diffuse Large B-Cell Lymphoma (DLBCL) but is usually contraindicated in patients with concomitant heart disease due to the unsafe cardiac profile of doxorubicin. The encapsulation of doxorubicin into liposomes modifies its pharmacokinetic reducing its concentration in the heart. We conducted a multicenter phase II trial investigating activity and safety of R-COMP regimen where conventional doxorubicin was substituted with non-pegilated liposomal doxorubicin (TLC-D99; Myocet ™) in patients with DLBCL presenting with moderate/severe concomitant heart disease. Methods:Main inclusion criteria were: age >18 years, diagnosis of DLBCL, no previous oncological treatments. Patients were also required to have cardiac disorder defined by at least one of the following: left ventricular ejection fraction (LVEF) < 50%, left ventricular hypertrophy, uncontrolled moderate/severe arterial hypertension, history of ischemic cardiopathy, clinically significant ventricular arrhythmia, atrial fibrillation (AF), pulmonary hypertension, moderate/severe mitral valvular disorder, moderate aortic valvular disorder. Enrolled patients received 6 courses of 3-weekly R-COMP (rituximab 375 mg/m2, cyclophosphamide 750 mg/m2, vincristine 1.4 mg/m2, TLC-D99 50 mg/m2, prednisone 40 mg/m2/day day 1–5). Cardiac function was monitored with LVEF and electrocardiogram (ECG) after cycle 3, at the end of treatment, and during follow-up. It was adopted a Bayesian sequential design that required the monitoring of complete reponse (CR) and cardiac events (CE) rates defined as primary endpoints. Response was defined according to international criteria (Cheson 2007). CE were defined as a LVEF < 25%, a LVEF reduction > 20% from baseline, or occurrence of significant cardiac disorder. Initial study assumptions were a CR rate of at least 70% and a rate of CE below 20%; with a power of 80% and a level of significance of 5%, the study sample was fixed at 50 patients. The proposed strategy would be considered as active and safe if at least 26 CRs and no more than 14 CEs were recorded at the end of the study. Results:Between 2009 and 2011, 51 patients were enrolled. One patient was excluded after registration due to violation of inclusion criteria. Median age was 77 years (range 53 – 91 years), 69% were male and 33% had stage IV disease. IPI score at study entry was 0–1 in 25%, 2 in 25%, and 3–5 in 50%. Sixty-three cardiac disorders were identified at baseline; the most frequent was ischemic cardiopathy (40%), followed by AF (17%), baseline LVEF <50% (16%), left ventricular hypertrophy (16%); 2 and 3 concomitant cardiac disorders were described in 4 patients; altered profiles at baseline ECG were detected in 38% patients. Median baseline LVEF was 58%. Treatment was completed in 76% of patients with a median dose intensity for TLC-D99 of 98%. R-COMP was interrupted prematurely due to lack of response (n=1), CEs (n=5), severe infection (n=2), deep venous thrombosis (n=1), renal failure (n=1), other toxicity (n=1), and patient’s decision (n=1). As requested by the sequential Bayesian model, the CR rate and the rate of CE never fell outside activity and safety boundaries. In fact, 27 patients achieved a CR (55%; 95%CI=42–72%) and 6 CE were observed, which included significant LVEF reduction (2 patients), clinically significant s-troponine increase (2), hearth failure (1), and cardiac arrest (1). Median LVEF after cycle 3 and at the end of treatment was 59% (range 25–72%) and 56% (30–69%), without significant modifications from baseline values. Grade 3–4 hematological toxicity included neutropenia in 67% of pcases, anemia and thrombocytopenia in 10% each, and infections in 4%.With a median follow-up of 13 months (range 1–28) 6 patients had lymphoma progression, 6 experienced relapse and 6 died without signs of lymphoma relapse/progression. Overall, 10 patients died due to lymphoma (2), severe infection (2), second cancer (1), hemorrhage (1), myocardial infarction (1), renal insufficiency (1), respiratory insufficiency (1), and unknown cause (1). The 1-year OS and PFS were 76% (95%CI: 58–87%) and 60% (95%CI: 42–74%), respectively. Conclusions:The substitution of conventional doxorubicin with non pegilated liposomal doxorubicin (TLCD99-Myocet™) in the R-CHOP regimen is a safe and active option for patients with DLBCL presenting with concomitant moderate/severe cardiac disorders. Disclosures:No relevant conflicts of interest to declare.

Effect of a nutritional reconditioning program for thin dairy cattle on body weight, carcass quality, and fecal pathogen shedding

To assess changes in body weight, carcass quality, and fecal pathogen shedding in cull dairy cows fed a high-energy ration for 28 or 56 days prior to slaughter. Randomized clinical trial. 31 adult Holstein dairy cows. Cows were randomly assigned to a control (immediate slaughter) group or a 28-day or 56-day feeding group. Cows in the feeding groups received a high-energy feed and were weighed every 7 days. Carcasses were evaluated by USDA employees. Fecal and blood samples were collected at the start and end of the feeding periods. Body condition score and adjusted preliminary yield grade were significantly increased in both feeding groups, compared with values for the control group; body weight, hot carcass weight, dressing percentage, and ribeye area were significantly increased after 56 days, but not after 28 days, compared with values for the control group. Average daily gain and marbling score were significantly lower after feeding for 28 days versus after 56 days. Prevalence of Escherichia coli O157:H7 shedding in feces decreased from 14% to 5.6%, but this difference was not significant. Cows seropositive for antibodies against bovine leukemia virus that had signs of lymphoma and lame cows had a low average daily gain. Net loss was $71.32/cow and $112.80/cow for the 28-day and 56-day feeding groups, respectively. Feeding market dairy cows improved body condition and carcass quality. Cows seropositive for antibodies against bovine leukemia virus that have signs of lymphoma and lame cows might be poor candidates for reconditioning.

Multifocal colonic mucosa-associated lymphoid tissue lymphoma with synchronous tubular adenoma: a coincidental association?

Dear Editor: Primary colorectal lymphoma is a rare condition, accounting for 10% to 20% of all gastrointestinal lymphomas and 0.2% to 0.6% of all large bowel malignancies. Most colonic lymphomas are non-Hodgkin's lymphomas and include diffuse large B-cell lymphoma, follicular lymphoma, small lymphocytic lymphoma, Burkitt's lymphoma, and mantle cell lymphoma. Mucosa-associated lymphoid tissue (MALT) lymphoma is one of the less common histological types and is mostly restricted to one segment of colon. We herein present a case of multifocal colonic MALT lymphoma, with concomitant tubular adenoma, with undistinguishable endoscopic features. A 52-year-old man was referred to our department after colonic polyps were diagnosed in a screening colonoscopy. He was asymptomatic, and his past medical history was irrelevant. His mother died at the age of 72 due to colorectal cancer, and his 54-year-old brother had already been treated for the same condition. Physical examination was unremarkable. Total colonoscopy was performed, revealing three polypoid lesions: two sessile polyps, measuring 15 mm, located in the transverse and descending colon; and a pedunculated polyp, measuring 12 mm in the sigmoid colon. En bloc snare polypectomy of all polyps was performed without complications. Histological study of both sessile polyps revealed colonic mucosa with marked expansion of the lamina propria by atypical lymphoid cells, of small to intermediate size and irregular nucleus with dense chromatin. Sparse lymphoepithelial lesions were also observed. On immunohistochemistry, tumor cells were positive for CD20, CD79a, and BCL2, but negative for CD5, CyclinD1, CD10, and CD23 markers. A diagnosis of MALT lymphoma was made. The pedunculated polyp was a tubular adenoma with low-grade dysplasia. Based on this unexpected information, staging work-up was performed. β2-microglobulin titer was within normal range. Whole-body computed tomography (CT) scan showed neither lymphadenopathy, nor involvement of the liver or spleen. Bone marrow biopsy and aspirate were normal. Upper endoscopy revealed no remarkable findings. Gastric biopsy specimens from antrum and corpus showed no signs of lymphoma and were positive for Helicobacter pylori (H. pylori) infection. Based on these findings, a final diagnosis of primary extranodal MALT lymphoma stage IE-A from modified Ann Arbor staging system was made. The patient was treated with H. pylori eradication therapy (esomeprazole–amoxicillin–clarithromycin) and 6 cycles of chemotherapy (cyclophosphamide, vincristine, adriamicine, prednisolone, and rituximab). Three months later, a urea breath test was negative, and a follow-up colonoscopy showed no signs of disease. R. Ferreira (*) : J. Torres :M. J. Pereira : J. Carvalheiro : S. Mendes :M. Ferreira : C. Agostinho :M. J. Campos Gastroenterology Service of the Hospitalar Center of Coimbra, Coimbra, Portugal e-mail: rosa.l.ferreira@gmail.com

Just Another Case of Sjögren’s Syndrome?

To the Editor: A 60-year-old woman was seen at the outpatient clinic of the Department of Rheumatology because of increased complaints of xerophthalmia. In 1997, she had already been diagnosed with Sjogren’s syndrome (SS) based on xerophthalmia, xerostomia, bilateral salivary gland swelling, and positive sialography showing chronic inflammation without local obstruction. Antinuclear antibodies (ANA) and anti-SSA/SSB were negative. Because of persistent progressive salivary gland swelling at that time, a total bilateral submandibular gland excision was performed as development of non-Hodgkin lymphoma as a complication of SS was suspected. Histology showed sialoadenitis as seen in SS without signs of lymphoma. In 2002, a renal biopsy performed because of increased creatinine level without proteinuria revealed focal global glomerulosclerosis with interstitial nephritis due to SS or chronic ischemia. In an attempt to treat possible active interstitial nephritis due to SS, she was treated with 30 mg of prednisone and azathioprine. Prednisone was stopped after 6 months and azathioprine after one year, however, there was no …

Hepatic Failure and Death due to New Onset T Cell Lymphoma

Liver involvement is commonly seen in disseminated T cell lymphoma; however, it is rarely the presenting organ. Here, we describe a case of T cell lymphoma presenting as acute hepatobiliary disease leading to hepatic failure and death. Forty-seven-year-old male with history of cirrhosis (etiology undetermined), diabetes mellitus, and pancytopenia was admitted to ICU for hypotension and failure to thrive. He had icterus, minimal ascitis, and hepatosplenomegaly on physical examination. No lymphadenopathy was noted. Laboratory workup on admission showed elevated total bilirubin (10.1mg/dl) and liver enzymes. Serology for acute viral hepatitis, human immunodeficiency virus, Epstein-Barr virus, and autoimmune hepatitis was negative. CT abdomen showed cirrhotic liver with heterogeneous arterial enhancement of the liver without definite mass lesions. Hospital course was complicated by progressively worsening hypotension, respiratory failure, profound acidosis, disseminated intravascular coagulation, and multi-organ system failure leading to death on hospital day12. Autopsy of the liver showed cirrhotic changes with infiltration with atypical small lymphocytes confined to septa which were CD3 and CD5 positive (CD4 weakly positive, CD8, CD20, CD57, CD56, CD30, Alk-1, granzyme B, TIA1, and S100 negative). Unusual clinical/histological features include (1) initial clinical presentation of hepatic dysfunction without obvious physical signs of lymphoma, (2) negative workup for viral, toxic, autoimmune, and metabolic liver disease, (3) involvement of the entire liver, observed as heterogeneous enhancement of liver without any focal mass lesion as seen on CT scan, (4) an aggressive nature of disease, and (5) autopsy of liver with T cell infiltration confined to septa. Initial diagnosis was challenging due to unusual clinical presentation suggesting inflammatory hepatobiliary disease and the absence of enlarged lymph nodes. In conclusion, early suspicion of this aggressive lymphoma is important and should be considered in the evaluation of a patient whose course is atypical for hepatitis. Even in the absence of a mass lesion or lymphadenopathy, hepatosplenic T cell lymphoma should be included in the differential diagnosis of acute hepatic dysfunction in a patient who has no evidence of viral, toxic, autoimmune, or metabolic liver disease.

Pulmonary fibrosis after high cumulative dose nitrosourea chemotherapy in a cat

Small to intermediate cell alimentary lymphoma was diagnosed in a cat after abdominal exploratory surgery with no prior history of pulmonary disease. Initial response to several chemotherapy regimens was poor, but a long-term remission was achieved with CCNU (lomustine) and corticosteroid therapy. After receiving a total cumulative CCNU dose of 552 mg m(-2) over 12 months, an acute episode of respiratory distress occurred and the cat died. Necropsy identified severe diffuse pulmonary fibrosis and no signs of lymphoma. This is the first report of pulmonary fibrosis following high cumulative dose nitrosourea chemotherapy in a cat.

A Single-Centre Experience of Clinico-Pathological Features, Risk Factors and Treatment Outcome of Posttransplant Lymphoproliferative Disorders (PTLD) after Renal Transplantation.

Background: PTLD is a lymphoid proliferation that develops as a consequence of immunosuppression and represents monoclonal B-cell, or rarely T-cell proliferations, occurring in a setting of decreased T-cell immune surveillance. PTLD is a major complication after solid organ transplantation. The disease is often unpredictable and devastating of nature resulting in a high rate of morbidity and patient mortality.Methods: Between 1990 and 2005 872 renal transplantations in 793 patients were performed at Skejby University Hospital in Aarhus and 11 cases of PTLD were identified retrospectively. PTLD Patients were investigated according to transplantation procedure, patient characteristics, type of lymphoma, treatment and outcome.Results: 11 of 793 renal transplant recipients (1,4%) developed PTLD. Patients (7 male, 4 female) ranged from 19 to 73 years of age at the time of diagnosis (mean age: 42 years). 8 had a cadaveric renal transplant while 3 received a transplant from related donor. Lymphomas were classified as diffuse large B-cell lymphoma in 10 cases and as Burkitt lymphoma in 1 case. No cases were of T-cell origin or Hodgkins lymphomas. Six cases were EBV positive (54%). Out of 11 cases, 5 were diagnosed within 1 year after transplantation, among which 4 were EBV positive, whereas 6 had a latency period of more than 1 year, among which only 2 were EBV positive. The mean latency time between grafting and diagnosis of PTLD among the early lesions was 7 months and among late lesions 6 years and 2 months (ranging from 1 month to 10 years and 8 months). Sites involved in PTLD were renal graft in 2 cases (both early lesions), lungs in 1 case, bowel system in 4 cases, CNS in 1 case, isolated lymph nodes in 1 case, widespread disease in 1 case and uncertain location in 1 case. All patients were treated by tapering of the immunosuppressive regimen. Two were treated with additional surgery and 3 with chemotherapy - all 5 of them are alive and in complete remission. Among those 5 patients 3 have preserved graft function (60%) and 2 returned to dialysis. One patient was treated with anti-CD20 monoclonal antibody, 3 had both conventional chemotherapy and anti-CD20 immunotherapy and 2 did not receive additional treatment. All 6 were dead at the end of the study period. With a median follow-up period of 5 years and 2 months (ranging from 6 months to 11½ years) 5 patients of 11 PTLD cases (45%) were alive with no sign of lymphoma relapse.Conclusions: PTLD is a severe complication, usually running an aggressive course and the outcome remains poor. The incidence in our population-based regional study material is 1,4%. Overall survival after a median follow-up of 62 months was 45%, with 60% of survivors maintaining graft function.

Downregulation of p56(lck) tyrosine kinase activity in T cells of squirrel monkeys (Saimiri sciureus) correlates with the nontransforming and apathogenic properties of herpesvirus saimiri in its natural host.

Herpesvirus saimiri is capable of transforming T lymphocytes of various primate species to stable growth in culture. The interaction of the T-cellular tyrosine kinase p56(lck) with the transformation-associated viral protein Tip has been shown before to activate the kinase and provides one model for the T-cell-specific transformation by herpesvirus saimiri subgroup C strains. In contrast to other primate species, squirrel monkeys (Saimiri sciureus) are naturally infected with the virus without signs of lymphoma or other disease. Although the endogenous virus was regularly recovered from peripheral blood cells from squirrel monkeys, we observed that the T cells lost the virus genomes in culture. Superinfection with virus strain C488 did not induce growth transformation, in contrast to parallel experiments with T cells of other primate species. Surprisingly, p56(lck) was enzymatically inactive in primary T-cell lines derived from different squirrel monkeys, although the T cells reacted appropriately to stimulatory signals. The cDNA sequence revealed minor point mutations only, and transfections in COS-7 cells demonstrated that the S. sciureus lck gene codes for a functional enzyme. In S. sciureus, the tyrosine kinase p56(lck) was not activated after T-cell stimulation and enzymatic activity could not be induced by Tip of herpesvirus saimiri C488. However, the suppression of p56(lck) was partially released after administration of the phosphatase inhibitor pervanadate. This argues for unique species-specific conditions in T cells of S. sciureus which may interfere with the transforming activity and pathogenicity of herpesvirus saimiri subgroup C strains in their natural host.

Isolated oculomotor nerve palsy in lymphoma

We report a patient with non-Hodgkin’s lymphoma who developed a unilateral left oculomotor nerve palsy. Only eyelid lifting and vertical gaze were involved. Lateral gaze or sizes and light reactions of pupils were not involved. Magnetic resonance imaging revealed an enhancement of an upper part of left cavernous sinus and the posterior clinoid process. It was conceivable that lymphoma invaded the upper branch of oculomotor nerve. Such neurological symptoms in cases of oculomotor nerve palsy by lymphoma have not been reported previously. Because cranial neuropathy could occur as the first sign of lymphoma, lymphoma is an important differential diagnosis for the partial oculomotor palsy such as our present case. [Neurol Res 2000; 22: 347-348]

INHIBITION OF LYMPHOMA USING RIBONUCLEOTIDE REDUCTASE INHIBITORS DIDOX OR TRIMIDOX IN THE MURINE IMMUNODEFICIENCY MAIDS MODEL

Background: To obtain additional in vivo experimental evidence to determine whether a new series of ribonucleotide reductase inhibitors (RRI), 3,4-dihydroxybenzohydroxamic acid (Didox) and 3,4,5-trihydroxybenzamidoxime(Trimidox) can inhibit retrovirus replication by depriving virus of its source of the deoxynucleotides obligatory for the synthesis of the proviral DNA intermediate of retrovirus replication in the murine model of AIDS (MAIDS). C57BL6 female mice were inoculated i.p. with LP-BM5 MuLV. Non-infected and infected mice were treated (M-F) with either Didox or Trimidox i.p., alone or in combination with didanosine (ddI, s.c.) beginning 1-day or 1-week post-viral infection. Controls consisted of virally infected mice not receiving RRIs or ddI. Mice were monitored for disease progression via: survival, presence of splenomegaly, lymphadenopathy, hypergammaglobulinemia, blood and bone marrow toxicity, reverse transcriptase activity, and flow cytometric analysis of infected PBMCs exhibiting viralgag 12 envelope glycoprotein expression. Results: Infected mice receiving either Didox (300, 460 mg/kg/bw) or Trimidox(150, 220 mg/kg/bw) either alone or in combination with ddI (600 mg/kg/bw) demonstrated increased survival compared to viral controls with reduced splenomegaly, lymphadenopathy, hypergammaglobulinemia, reverse transcriptase activitiy from lymph tissue and viral infected PBMCs. This antiviral effect was enhanced with ddI; however, ddI alone had only marginal antiviral activity. No sign of lymphoma or blood or marrow toxicity was observed following >50 weeks post-viral infection compared to infected control animals not receiving drugs. Conclusions: These results demonstrate RRIs are potent antiviral agents capable of increasing survival and reducing several markers of immunodeficiency disease, in particular, the inductiona and presence of lymphoma using the MAIDS model. Further studies are justified in order to elucidate the role of RRIs as antiviral agents in animal models and warrant initiation of clinical trials to examine their antiviral potential in patients infected with HIV.

Long-term follow-up of pathologic stage I large cell non-Hodgkin's lymphoma patients after primary radiotherapy.

The purpose of this study was to examine the long-term outcome of Stage I large-cell non-Hodgkin's lymphoma patients treated with primary radiotherapy and to assess the potential influence of these results on the development of future treatment protocols for non-Hodgkin's lymphoma. Between April 1970 and July 1983, 15 pathological Stage I and four pathological Stage II large cell lymphoma patients were treated with primary radiotherapy at the University of Minnesota Hospital and Clinics. This paper focuses on the long-term outcome of the 15 Stage I patients. As of March 1995, with a median survival of 171 months, five of the 15 Stage I patients are alive: four with no sign of lymphoma and one with recurrence and a secondary malignant neoplasm (SMN). Estimated 5- and 10- year recurrence-free survival rates are 86% and 78%, respectively. Overall survival at 5 years is 80% and at 10 years, 67%. Six patients developed SMNs, all of which were solid tumors. Ten of the 15 patients died: four from SMNs, three from non-Hodgkin's lymphoma, and three from other causes without recurrence (two died of cardiovascular disease and one of a pulmonary embolism). Deaths due to lymphoma in pathologic Stage I patients treated by radiotherapy alone have not changed significantly since our last report in 1985; however, deaths due to SMNs have increased. To provide optimal treatment for early non-Hodgkin's large-cell lymphoma, examination of the long-term treatment risks provides useful information for newer treatment regimens that do not yet have long-term treatment outcomes available.

Ofuji Papuloerythroderma: A New European Case

We report a new case of Ofuji papuloerythroderma. There was no obvious sign of lymphoma or underlying malignancy. This is the 7th European case of papuloerythroderma. This recently described clinical entity is characterized by a pruritic eruption of widespread red-brown flat papules sparing the skin folds, with eosinophilia. The recognition, report and follow-up of further cases are necessary to clarify its relationship with paraneoplastic syndromes, hypereosinophilic syndrome, or prelymphoma skin eruptions.