Early-stage gastric MALT lymphoma: is it a truly localized disease?

Early-stage gastric mucosa-associated lymphoid tissue lymphoma (GML) is considered a localized disease with an indolent course. Circulating malignant cells have been detected in other early-stage indolent lymphomas by molecular methods. We investigated the incidence of occult blood disease in early-stage GML patients, its impact on clinical outcome, and the similarity between blood and gastric lymphocytic clones. Sixty-two patients with localized GML were included in the study; 51 of them had Helicobacter pylori infection. Monoclonality was investigated by leader polymerase chain reaction. Sequencing was performed for the immunoglobulin variable gene (VH) analysis. Blood involvement was absent in all patients by conventional staging methods. In the whole group of 62 patients, the incidence of blood IgH rearrangement was 45%, and this did not correlate with baseline patient characteristics. The monoclonal blood and gastric products of five patients were sequenced and compared with each other. Clonal identity was evident in four of five patients. The VH3 gene was the most frequently used, both in the blood and in the stomach. Early-stage GML is not a truly localized disease because half the patients had a circulating clone, probably identical to the gastric one. The clinical significance of occult blood disease and the potential appropriate intervention need to be further investigated.

Topoisomerase IIalpha expression as an independent prognostic factor in Hodgkin's lymphoma.

PURPOSE: To correlate the immunohistochemical expression of topoisomerase IIalpha (topoIIalpha) in Hodgkin's lymphoma (HL) with clinicopathological parameters, the expression of Ki-67 and the outcome of patients, who had been homogenously treated with ABVD or equivalent regimens. EXPERIMENTAL DESIGN: Immunohistochemistry using the monoclonal antibody Ki-S1 (topoIIalpha) was performed in 238 HL patients. MiB1 (Ki-67) expression was evaluated in 211/238. RESULTS: The mean +/- SD percentage of topoIIalpha- and Ki-67-positive Hodgkin-Reed-Sternberg (HRS) cells was 63 +/- 19% (5%-98%) and 73 +/- 19% (8%-99%), respectively. The median percentage of topoIIalpha-positive HRS cells was 64% (interquartile range, 51-78%). There was no correlation between topoIIalpha expression and patient characteristics. TopoIIalpha and Ki-67 expression were correlated (Spearman's Rho 0.255, P < 0.001). TopoIlalpha expression within the highest quartile of this patient population was predictive of failure free survival (FFS) (10-year rates 82 +/- 3% vs 68 +/- 7%, P = 0.02 for patients falling into the quartiles 1-3 and 4 respectively). In multivariate analysis topoIIalpha expression was independently predictive of FFS. CONCLUSION: TopoIIalpha was expressed in all cases of HL showing a correlation with Ki-67 expression. Under current standard therapy including drugs inhibiting its activity, topoIIalpha was an independent adverse predictor of FFS with no statistically significant correlation with other established prognostic factors.

Spiradenoma reminiscent of thymoma: report of a case and review of the literature.

BACKGROUND: Spiradenoma (Sp) is a rare adnexal cutaneous tumor with a prominent vasculature. There are few reports in the literature suggesting that the majority of the cases contain perivascular spaces with numerous lymphocytes, a feature that is characteristic in thymus neoplasms. However, there is little information available about the nature and maturity of the lymphocytes comprising these spaces. METHODS: We report a case of a Sp that presented as a palpable painless mass in a 45-year-old woman and had histological similarities with thymomas. Furthermore, we compare these two entities in detail, discussing the differences and possible similarities between them. RESULTS: On histological grounds, the lesion consisted of epithelial lobules with prominent ductal differentiation admixed with conspicuous perivascular spaces containing numerous lymphocytes. Immunohistochemical analysis showed that perivascular spaces contained mostly T lymphocytes (CD3 positive), which in contrast with those seen in most thymomas were mature (CD99, CD1a and Terminal deoxynucleotidyl transferase (Tdt) negative). A detailed comparison between Sps and thymomas shows that there exist several important clinicopathological and cytological differences between these two tumors. CONCLUSIONS: We suggest that the resemblance between Sps and thymomas is strictly architectural, and we raise some questions regarding the role of these perivascular spaces in tumor development.

Incidental pathologic extracardiac uptake of 99mTc-tetrofosmin in myocardial perfusion imaging.

Technetium-99m-tetrofosmin ((99m)Tc-TF) myocardial perfusion studies have incidentally detected various extracardiac abnormalities. The interpretation of these findings may be essential for early diagnosis and treatment of important diseases. We present a rare case of a mediastinal thymoma incidently detected during myocardial perfusion imaging. A 60 year-old woman, with precardiac symptoms of possible myocardial ischemia, underwent a (99m)Tc-TF stress-rest single photon emission tomography test. Intense uptake of the radiotracer in the left paracardiac area, was observed. The computerized tomography and the magnetic resonance imaging tests revealed a mass in the left lower anterior mediastinal area. Biopsy and subsequent histology showed that this mass was a thymoma.

Primary Hepatic Burkitt Lymphoma in a Kidney Transplant Recipient.

This is a case of a renal transplant recipient who developed a primary hepatic Burkitt lymphoma a few years after kidney transplantation. The past medical history of the patient was significant for anti-HCV positivity with liver histopathology showing minimal changes of grades 0 and 1, stage 0. She received a graft from a deceased donor, with rabbit antithymocyte globulin and methyl-prednisolone, as induction therapy, and was maintained on azathioprine, cyclosporine, and low dose methyl-prednisolone with normal renal function. Four years after KTx she presented with fatigue, hepatomegaly, and impaired liver function and the workup revealed multiple, variable-sized, low density nodules in the liver, due to diffuse monotonous infiltration of highly malignant non-Hodgkin lymphoma of B-cells, which turned out to be a Burkitt lymphoma. Bone marrow biopsy and spinal fluid exam were free of lymphoma cells. At time of lymphoma diagnosis she was shown to be positive for Epstein-Barr virus polymerase chain reaction. She received aggressive chemotherapy but died due to sepsis, as a result of toxicity of therapy.

Maltoma of the thyroid and Sjögren's syndrome in a woman with Hashimoto's thyroiditis.

We report the case of a 70-yr-old woman with maltoma of the thyroid, Sjögren's syndrome, and a history of Hashimoto's thyroiditis. The patient underwent a total thyroidectomy for a recently growing mass of the thyroid, while being treated with L-thyroxine for Hashimoto's thyroiditis. Postoperatively, routine histologic examination was consistent with the diagnosis of chronic lymphocytic thyroiditis of autoimmune etiology. Three years later, the patient presented with high temperature, anorexia, and coughing. This time, a microscopic examination of deeper thyroid tissue sections and an immunohistochemical study revealed a low-grade, non-Hodgkin lymphoma, MALT type. Simultaneously, the diagnosis of Sjögren's syndrome was established and the patient is currently under investigation for generalized lymphoma. This case clearly demonstrates the difficulty in differentially diagnosing Hashimoto's thyroiditis from low-grade MALT lymphoma by the use of routine histologic examination.

Increased angiogenesis in the bone marrow of HIV-positive patients with myelodysplasia.

AIM: Little is known about the significance of angiogenesis in the bone marrow of HIV-positive patients with myelodysplastic features (MDF). However, this process has been associated with the pathogenesis of primary myelodysplastic syndromes (MDS). The aim of the study was to investigate angiogenesis in the bone marrow of HIV-positive patients. METHODS: Bone marrow biopsies from 28 HIV-positive patients were immunostained for factor VIII and the microvessel density (MVD) was quantitatively evaluated and compared with that of 32 biopsies from patients with primary MDS and to 18 control bone marrows from patients with no evidence of bone marrow disease. RESULTS: Bone marrow MVD in HIV-positive patients was similar to that of MDS. However, both groups revealed significantly higher MVD counts compared to those of control bone marrows (MDF vs controls P=0.022, MDS vs controls P=0.001). CONCLUSIONS: Bone marrow from HIV-positive patients with MDF reveals similar microvessel counts compared to those with primary MDS, although both differ significantly from that of control bone marrow. Elucidation of the mechanisms underlying bone marrow angiogenesis in HIV-positive patients, may provide further insights into the pathobiology of AIDS and might be of value for the development of new therapeutic strategies for this disease.

T cell lymphoblastic lymphoma in parotidectomy for Warthin's tumor: case report and review of the literature.

Lymphomas associated with Warthin's tumor (WT) are extremely uncommon and the majorities are of B cell type. We report the simultaneous occurrence of T-cell lymphoblastic lymphoma (T-LBL) and WT in an 81-year-old patient, who presented with fever, night sweats and enlargement of the right parotid gland. The parotidectomy specimen showed a WT with extensive replacement of the lymphoid stroma by T-LBL, but preservation of the oncocytic epithelium. Staging investigations revealed mediastinal and abdominal lymphadenopathy, bilateral pleural effusions and bone marrow infiltration, in keeping with stage IVB disease. The patient received combination chemotherapy treatment but responded poorly, and died three months after diagnosis. To our knowledge, this is the first case report of T-LBL involving WT. The present study indicates that the lymphoid stroma in WT belongs to the systemic lymphoid tissue and can be involved in disseminated lymphoma. It highlights the importance of careful examination of WT's lymphoid stroma for the possible presence of any coexistent malignancy.

Inflammatory pseudotumor associated with Mycobacterium tuberculosis infection.

BACKGROUND: Inflammatory pseudotumor is a relatively rare entity; originally identified in the lung, it has been described in multiple extrapulmonary anatomic locations. CASE REPORT: We report on the unusual case of an inflammatory pseudotumor associated with Mycobacterium tuberculosis infection, which was initially mistaken for a renal malignancy both in clinical and radiological settings. We additionally present three brief reviews concerning: (1) infectious agents postulated to induce morphological changes of an inflammatory pseudotumor; (2) mycobacterial pseudotumors; and (3) distinction from inflammatory myofibroblastic tumors of the renal pelvis. CONCLUSIONS: The present case highlights the diagnostic importance of PCR-based detection of mycobacterial DNA in granulomatous tissue responses. It is of crucial importance that clinicians are aware of this unusual manifestation of mycobacterial infection to ensure that pertinent laboratory evaluation is employed and appropriate treatment is administered in order to avoid potential clinical implications.

Development and validation of a clinical prediction rule for bone marrow involvement in patients with Hodgkin lymphoma.

We developed a clinical prediction rule for bone marrow involvement (BMI) in Hodgkin lymphoma based on 826 patients and validated it in 654 additional patients. Independent prognostic factors for BMI were x1, B symptoms; x2, stage III/IV prior to bone marrow biopsy; x3, anemia; x4, leukocytes fewer than 6 x 10(9)/L; x5, age 35 years or older; and x6, iliac/inguinal involvement. Each factor was graded as x(i)=1, if present, or x(i)=0, if absent. A simplified score Zs=8x1+6x2+5x3+5x4+3x5+3x6-8 was assigned to each patient. The sensitivity, specificity, and positive and negative predictive value of this prediction rule was 97.8%, 51.5%, 10.6%, and 99.8%, respectively. In the validation group, they were 98.1%, 40.3%, 12.7%, and 99.6%. According to Zs value, 3 risk groups for BMI were defined: low risk (Zs<0, 44% of patients, 0.3% risk), standard risk (Zs, 0-9; 37% of patients; 4.2% risk), and high risk (Zs>or=10, 20% of patients, 25.5% risk). Patients with low risk (stage IA/IIA without anemia and leukopenia; stage IA/IIA, younger than 35 years, with either anemia or leukopenia but no inguinal/iliac involvement; and stage IIIA/IVA without any of these 4 risk factors) do not need bone marrow (BM) biopsy. Patients with standard risk should be staged with unilateral biopsy, but patients with high risk may benefit from bilateral biopsy.

A morphometric study of bone marrow angiogenesis in hairy cell leukaemia with clinicopathological correlations.

Bone marrow angiogenesis has recently been implicated in the pathophysiology and course of various haematological malignancies. Little is known, however, about the significance of this phenomenon in hairy cell leukaemia (HCL). We evaluated various morphometric characteristics of microvessels, highlighted by means of anti-CD34 immunohistochemistry, in the bone marrow of 44 patients with typical HCL, before and after treatment with interferon-alpha (IFN-alpha). Overall, bone marrow from 103 HCL patients and 20 controls was examined. Microvessel density (MVD) and several size- and shape-related parameters were quantified in the region of most intense vascularization using image analysis. MVD, size-related parameters and the percentage of branching microvessels were higher in HCL than in controls. Likewise, perimeter counts were higher in partial/non-responders than in complete responders. Achievement of complete response was accompanied by smaller calibre microvessels. IFN-alpha induced a decrease in MVD and branching values in cases with diffuse marrow involvement. In univariate analysis, progression-free survival was adversely affected by MVD, branching and major axis length. Multivariate analysis indicated that MVD/branching independently affected progression-free survival and the likelihood of complete response. Our data suggest that the generation of bone marrow microvessels indicated an increased risk of progression and IFN-alpha treatment failure in HCL. Furthermore, the prognostic significance of angiogenesis requires the concomitant assessment of MVD and the complexity of the microvascular network.