Increases in levels of antibody to hepatitis B surface antigen in an immunized population

OBJECTIVE AND IMPORTANCE: Mycosis fungoides is a rare T-cell lymphoma of the skin that can, in one-half to three-quarters of patients suffering from this disease, involve the viscera in late stages of the disease. Although autopsy series performed more than 2 decades ago showed that the incidence of metastatic mycosis fungoides to the central nervous system is approximately one of seven, a total of only several dozen cases have been reported to date. As compared to meningeal involvement, intraparenchymal metastases are even rarer. We describe a biopsy-proven case of intraparenchymal central nervous system mycosis fungoides in a patient with nonprogressive skin involvement and no detectable visceral involvement, and we present a review of the relevant literature. CLINICAL PRESENTATION: A 68-year-old man, 3 years after the diagnosis of his skin disease, developed fatigue, confusion, and frontal lobe signs without the presence of cerebriform cells in the peripheral blood or any other clinical evidence of visceral involvement. Magnetic resonance imaging revealed a diffuse area of increased T2-weighted signal involving the white matter of both cerebral hemispheres as well as a focal area of T2 abnormality along the body of the corpus callosum. The radiological differential diagnosis was either leukodystrophy caused by chemotherapy, progressive multifocal leukoencephalopathy, or glioma with associated white matter changes. INTERVENTION: A stereotactic serial brain biopsy revealed diffuse perivascular infiltrates of atypical lymphocytes, as well as several large cells with cerebriform nuclei consistent with mycosis fungoides. The cells were immunoreactive for LCA, MT1, UCHL1, and CD3. CONCLUSION: We stress the importance of including mycosis fungoides as part of the differential diagnosis for a brain lesion in patients with cutaneous T-cell lymphoma, because treatments do exist, and we conclude that a serial stereotactic biopsy may be necessary to provide a definitive diagnosis.     

Primary anaplastic large-cell lymphoma in adults: clinical presentation, immunophenotype, and outcome

Anaplastic, CD30+, large-cell lymphoma is now a well-recognized pathologic entity that accounts for 2% to 8% of all lymphomas. Recent progress has been made in the understanding of certain biologic features found in anaplastic large-cell lymphoma, but information about its clinical behavior, in comparison to other large-cell lymphomas, is limited. The pathologic review of a large multicenter study of the treatment of aggressive lymphoma identified 146 cases of anaplastic large-cell lymphoma (ALCL) on the basis of morphology and CD30 expression. We compared initial presentation, immunophenotype, and clinical outcome of these cases with those of the 1,695 nonanaplastic diffuse large-cell lymphomas (non-ALCL) included in the same trial. Patients with ALCL were more likely to be male (P = .018) and were younger (P < .0001) than those with non-ALCL. B symptoms were more frequent in ALCL (P = .006). Skin (P < .0001) and lung (P < .05) involvement was also more frequent in ALCL, but frequency of bone marrow involvement was identical (P = . 5). Tumor cell phenotype was B in 56 cases (38%), T in 49 cases (34%), and null in 33 cases (22%). Response to chemotherapy (P = . 001), event-free survival (P = .006), and overall survival (P = . 0004) were better for ALCL than for non-ALCL. Multivariate analyses identified anaplastic character as an independent factor that predicted a longer survival. Tumor cell phenotype did not influence event-free survival (P = .72) or overall survival (P = .83). ALCL in adults is a clinicopathologic entity which, independent of its phenotypic characteristics, has a better outcome than other diffuse large-cell lymphomas.     

Pathology of intravascular malignant lymphomatosis

On the basis of six necropsied cases of intravascular malignant lymphomatosis (IML), we elucidated its pathological characteristics. In the brain of IML, multiple softened areas of various size were observed, dominantly in the white matter of the cerebral hemisphere, which showed bilateral distribution with no relation to the supply area of the large vessels and intermingled fresh and old lesions. The spinal cord was one of the most often involved areas in IML, particularly at the lumbosacral segmental level. The origin of the tumor cells, based upon the findings that the tumor cell of all our cases were positive for SL-26, LN1, and LN2, were considered to be B-cell. We speculated that not only the circulatory failure due to the tumor cells which filled the vascular lumen, but also circulatory disturbances due to thrombosis, thickening of the intima and angiitis were significant findings for the necrosis in IML. IML is an important disease as the fourth type of central nervous system involvement due to malignant lymphoma, in addition to primary malignant lymphoma of the brain, meningeal lymphomatosis, compression of the spinal cord caused by extradural metastasis of lymphoma.     

Musculocutaneous nerve palsy following traumatic spinal cord injury

Whipple's disease is a multisystem bacterial disease usually characterized by malabsorption, diarrhea and polyarthritis. Ocular manifestations include uveitis, vitreitis, retinis, myositis, papilledema and optic atrophy. We report a case of a chronic bilateral vitreitis in a 63 year-old man who had been treated for a Whipple's disease with gastrointestinal involvement 30 years before. The jejunal biopsy was negative but the polymerase-chain-reaction (PCR) revealed the presence of Trophyrema Whippelii in the vitreous prelevement of both eye. This new, original strategy of PCR is specific and more sensitive than histological diagnosis.     

Bilateral non-Hodgkin''s lymphoma of the breast mimicking mastitis

We recently encountered a case of recurrent non-Hodgkin's lymphoma manifested after a long period of quiescence as bilateral involvement of the breasts. This 37-year-old woman had stage IVA nodular poorly differentiated lymphocytic lymphoma diagnosed 9 years previously and was followed up without treatment. She was lost to follow-up after 4 years but had been in good health until seen with malaise and fever and pain, swelling, and erythema involving both breasts. Biopsies of lymph node and bone marrow showed a high-grade non-Hodgkin's lymphoma (lymphoblastic lymphoma) of B cell origin with central nervous system involvement. Combination chemotherapy produced a dramatic remission, but the patient died of Pseudomonas septicemia.     

Pre-operative assessment of cardiac risk for non-cardiac surgery

We describe the cases of two patients who presented with granulocytic sarcoma with mediastinal involvement 15 and 21 months before development of acute myeloid leukemia. In both cases several bone marrow aspirates and trephine biopsy specimens, obtained at presentation and subsequently, revealed no evidence of leukemic infiltration. One case was originally misdiagnosed as large-cell non-Hodgkin's lymphoma, which resulted in inappropriate therapy. In both cases immunohistochemical staining revealed that tumor cells were positive for leucocyte common antigen but not for conventional B- or T-lymphoid-cell markers. Retrospective analysis revealed that tumor cells in both cases were positive for myeloid markers. Histopathologists should be aware that granulocytic sarcoma may occur in unusual extramedullary sites without evidence of bone marrow involvement. If inappropriate treatment is to be avoided, a diagnosis of granulocytic sarcoma should be considered when hemopoietic tumor cells do not stain with conventional antibodies against B- and T-lymphoid cells. Both histochemical and immunohistochemical staining should be performed in such cases to determine whether the cells are of myeloid lineage. A diagnosis of granulocytic sarcoma is not ruled out when bone marrow biopsy specimens show no evidence of leukemic infiltration.     

Ocular involvement in Epstein-Barr virus-associated T-cell lymphoma

PURPOSE: To determine if serous retinal detachment may occur in a case of Epstein-Barr virus-associated T-cell lymphoma. METHODS: We examined a 51-year-old man who had recent loss of vision and poor general health. RESULTS: Ocular involvement consisted of bilateral serous retinal detachment and choroidal infiltrates. The diagnosis of lymphoma was made by liver biopsy. The course of the disease was fulminant. Postmortem histologic examination disclosed a massive infiltration of the choroid and hematopoietic organs by pleomorphic large T cells. Epstein-Barr virus was detected by in situ hybridization. CONCLUSION: Ocular involvement, including choroidal infiltrates and serous retinal detachment, may occur in Epstein-Barr virus-associated T-cell lymphoma.     

In situ demonstration of Epstein-Barr virus small RNAs (EBER 1) in acquired immunodeficiency syndrome-related lymphomas: correlation with tumor morphology and primary site

Some acquired immunodeficiency syndrome (AIDS)-related lymphomas (ARLs) are infected with Epstein-Barr virus (EBV), although the frequency and importance of this association is disputed. Using paraffin section RNA in situ hybridization (ISH) with digoxigenin-labeled riboprobes, we screened 16 central nervous system (CNS) non-Hodgkin's lymphomas (NHLs), 101 systemic NHLs, and 11 Hodgkin's disease cases arising in human immunodeficiency virus-seropositive individuals for EBV-encoded small RNA (EBER 1) expression, an EBV gene product transcribed in abundance during latent infection. Tumor cells contained EBV in 85 of 128 ARLs (66%), but infection rates differed with lymphoma type. EBER 1 was expressed in tumor cells in 11 of 11 Hodgkin's disease cases (100%), 15 of 16 CNS NHLs (94%), and 46 of 60 systemic immunoblast-rich/large-cell lymphomas (77%), but in only 12 of 35 Burkitt-type (small noncleaved cell) (34%) and 1 of 6 monomorphic centroblastic (diffuse large noncleaved cell) (17%) lymphomas. In most EBV-positive ARLs, all recognizable viable tumor cells expressed EBER 1. We conclude that (1) EBV infects tumor cells in all AIDS-related Hodgkin's disease cases, in virtually all primary CNS ARLs, and in most systemic immunoblast-rich/large-cell ARLs; (2) only a minority of Burkitt-type and monomorphic centroblastic lymphomas are associated with EBV; and (3) EBER-ISH is ideal for the histopathologic detection of latent EBV in routine tissue specimens.     

Central nervous system involvement in hepatitis C virus infection

Few well-documented cases of central nervous system involvement in patients with hepatitis C virus infection have been reported. We describe three patients (two men and one woman) with cerebral involvement (ischemia and/or hemorrhage). Hepatitis C virus infection was confirmed in all patients by polymerase chain reaction detection of hepatitis C virus RNA. These three cases document the occurrence of central nervous system involvement in patients with hepatitis C virus infection and mixed cryoglobulinemia. Cerebral involvement may be the initial manifestation of hepatitis C virus infection.     

Clinical heterogeneity of non-Hodgkin's lymphoma of the eye with extraocular manifestations

Primary, ocular Non-Hodgkin lymphoma is a multicentric disease. The prognosis is mostly determined by involvement of the central nervous system and/or visceral organs. Since ocular symptoms often precede accompanying manifestations and since the eye is easily accessible to diagnostic measures, the ophthalmological diagnosis is essential for early detection and treatment of this complex disease, which has a poor prognosis. To illustrate the extraordinary heterogeneity of the clinical symptoms, four case reports have been selected which demonstrate various ocular symptoms and extraocular localizations. The ophthalmological variability ranges from typical uveitis to retinitis and vasculitis with varying symptoms during the progression of the disease. Completely different extraocular features were induced by long-standing, local infiltrates within basal ganglia, a diffuse infiltration of the brain leading to an acute increase in intracranial pressure, a peripheral tumour within the spinal channel or massive infiltrates of liver, lung and kidneys. Lack of pathognomonic features, high clinical variability and the limited value of imaging techniques and histopathological measures often lead to serious delays in diagnosis.     

D-dimer levels in the cerebrospinal fluid: a marker of central nervous system involvement in neoplastic disease

D-dimer assay was performed on 145 cerebrospinal fluid (CSF) samples from patients with or without neoplastic diseases. Levels of D-dimers were significantly higher in carcinoma and lymphoid malignancies with clinical or biological evidence of central nervous system (CNS) involvement than in diseases without such complications. In one patient, serial determinations of D-dimers were well correlated with the appearance and disappearance of CNS involvement. Although this test is not specific for neoplastic affections, our data suggest that the measurement of D-dimers in CSF may be useful in the diagnosis of CNS involvement of neoplastic cells and in monitoring intrathecal therapy in patients with lymphoma, acute lymphoblastic leukaemia or carcinoma. In this study, the D-dimer assay was also positive in some non neoplastic diseases, but failed to differentiate subarachnoid haemorrhage from traumatic lumbar puncture.     

Errors enacted during endoscopic surgery--a human reliability analysis

PURPOSE: Current knowledge on central nervous system sarcoidosis. CURRENT KNOWLEDGE AND KEY POINTS: Sarcoidosis is localized in the central nervous system in 5 to 16% of the cases. Various neurological manifestations are observed, including: seizures, cognitive or psychic manifestations, hypothalamic and pituitary involvement, local pseudotumors, and hydrocephalus very frequently associated with asymptomatic lymphocytic meningitis and with cranial nerve palsy, particularly palsy of the seventh nerve, occurring less regularly. CNS localization is most often an early manifestation of the disease, unmasking sarcoidosis. It is often part of primary or secondary systemic polyvisceral sarcoidosis. The diagnosis is mainly based on two arguments: confirmation of the existence of systemic sarcoidosis and clinical and paraclinical compatibility of neurological abnormalities (particularly at magnetic resonance imaging [MRI]). Neurological histopathology is rarely necessary to confirm the diagnosis. Corticotherapy is indicated in all symptomatic cases and most often leads to a more or less complete clinical response evidenced by regression of active lesions identified on MRI. The treatment must often be prolonged for several years, and clinical and MRI evolution help guide therapeutical choices for dosages and threshold doses. CNS involvement is potentially severe with mortality and morbidity rates that are not insignificant. Limiting of iatrogenic risks requires adequate follow-up. PERSPECTIVES AND PROJECTS: Multicenter studies are necessary to determine factors influencing the incidence and long-term prognosis of CNS sarcoidosis treated with corticotherapy. The efficacy of treatments other than corticotherapy must be evaluated.     

Enteropathy-associated T-cell lymphoma in the West of Ireland: low-frequency of Epstein-Barr virus in these tumors

The Epstein-Barr virus has been implicated in the etiology of endemic Burkitt's lymphoma, post-transplant lymphoma, large-cell anaplastic CD30 (Ki-1)-positive lymphoma, and in many T-cell lymphomas. A recent report has found Epstein-Barr virus genome in association with 4 of 11 cases (36%) of enteropathy-associated T-cell lymphoma. In a retrospective study, we have characterized 22 consecutive cases of enteropathy-associated T-cell lymphoma from the West of Ireland where celiac disease is endemic. All cases were immunophenotyped with T- and B-cell markers including the anaplastic large-cell lymphoma marker CD30 or Ki-1. Nineteen cases were studied for latent membrane protein expression and 16 for Epstein-Barr virus small RNAs by in situ hybridization using EBER oligonucleotides on routinely processed sections. Only 1 of 16 cases (6%) showed Epstein-Barr virus in tumor cells and no cases stained with latent membrane protein. Eight of 22 cases (36%) including the EBER-positive case were positive for CD30. These results suggest that the Epstein-Barr virus does not commonly play a role in the pathogenesis of enteropathy-associated T-cell lymphoma from this area.     

Cholesteryl ester transfer protein mutations, protein activity and HDL-cholesterol concentration

Three diffuse centroblastic lymphomas developed at the site of previous surgery. Two were preceded by atypical lymphoid infiltrates. Clinical data, microscopic features, and immunophenotypic studies were reviewed. All three patients presented with soft tissue masses at the site of previous surgery and metallic implants, with no evidence of lymphadenopathy, hepatosplenomegaly, or bone marrow involvement. There was no history of immunosuppression or risk factors. In two cases the initial diagnosis was of atypical lymphoid infiltrate progressing to lymphoma. Pathological examination showed a diffuse centroblastic lymphoma with an angiocentric pattern in one case. Phenotypic studies confirmed B cell origin. Soft tissue malignant lymphoma, though uncommon, can occur at the site of previous orthopaedic surgery, in particular joint replacement. Atypical lymphoid infiltrate may signal such an event.     

Studies on the method of the analysis of sapogenin. III. Coulometric titration of diosgenin (author''s transl)

Fifteen of 146 (10%) adult patients with non-Hodgkin's lymphoma showed clinical and pathologic evidence of involvement of the central nervous system (CNS): in 6 patients, the CNS lymphoma was present at the onset of disease, in 3 of them it was the only sign detected. In the remaining 9 cases, CNS involvement appeared during the course of systemic disease. In all cases symptoms related to infiltration of the CNS were associated with advanced disease (stage IV); bone marrow or bone involvement was found in 9 patients (60%). The histologic subtypes were mostly of high-grade malignancy according to the Kiel classification: immunoblastic (3), centroblastic (3), Burkitt type (2), lymphoblastic (1), LP immunocytoma in polymorphic variant (3), unclassifiable (3). The prominent signs and symptoms of CNS lymphoma are listed: the cranial nerve palsies are the most common finding. The principal means of detecting CNS involvement are discussed: cerebrospinal fluid cytology, brain scan and CAT scan were the most useful diagnostic procedures. The reported data allow identification of patients at high risk of CNS lymphoma: this includes histologies of high-grade malignancy, advanced stage of disease, and bone marrow or bone infiltration. Therefore, either intensive systemic chemotherapy or CNS prophylaxis are recommended for patients with high risk of CNS disease.     

Autocrine and paracrine functions of cytokines in malignant lymphomas

Cytokines play important roles in the pathogenesis of lymphomas via an autocrine or a paracrine mechanism, or both. The characteristic clinical and histopathological features of malignant lymphomas may be due in part to elevated serum or tissue levels of cytokines. Determination of the effects of cytokines on the growth or differentiation of lymphoma cells is often complicated by the fact that more than one cytokine is responsible, and by the failure of anti-cytokine antibodies or antisense oligonucleotides to block the proliferation in vitro of lymphoma cells. However, it appears that IL-6 and/or IL-9 may play a prominent role in the tumor cell proliferation of Hodgkin's disease (HD), anaplastic large-cell lymphoma, or immunoblastic lymphoma. IL-6 may also be responsible for the plasmacytoid differentiation of lymphoma cells in polymorphic immunocytoma. The histopathological changes as a result of paracrine effects are most noticeable in HD. The malignant (H-RS) cells of HD have been shown to express IL-1, IL-5, IL-6, IL-9, TNF-alpha, M-CSF, TGF-beta, and CD80, and, less frequently, IL-4 and G-CSF. These cytokines may be responsible for the increased cellular reaction and fibrosis observed in tissues involved by HD and for the immunosuppression found in patients with HD. In contrast to H-RS cells, most non-HD lymphoma cells do not produce cytokines in excess amounts and reveal only a minimal cellular reaction. Exceptions include T-cell-rich B-cell lymphoma, angiocentric T-cell lymphoma, and angio-immunoblastic lymphadenopathy (AILD-like T-cell lymphoma. IL-4 is responsible for the T-cell reaction in T-cell-rich B-cell lymphoma, whereas IL-6 accounts for the plasma cell reaction in AILD-type T-cell lymphoma. The authors extensively review the role of cytokines in lymphomas because this may lead to major advances in the understanding of the molecular processes involved in the histopathogenesis of lymphomas.     

Primary (granulomatous) angiitis of the central nervous system with multiple aneurysms of spinal arteries. Case report

A 55-year-old woman with primary (granulomatous) angiitis of the central nervous system in association with non-Hodgkin's lymphoma (mucosa-associated lymphoid tissue type) presented with an acute spinal subdural hemorrhage secondary to rupture of one of several fusiform inflammatory aneurysms of the spinal cord radicular arteries. The literature on hemorrhagic complications, aneurysms, and spinal cord involvement in granulomatous angiitis is reviewed. Recognition of granulomatous angiitis is important, as the condition may be responsive to immunosuppressive therapy.     

Treatment and prognosis in a series of primary extranodal lymphomas of the ocular adnexa

BACKGROUND: The aim of this study was to assess clinicopathological characteristics and outcome in a series of primary ocular adnexal lymphomas (POALs). PATIENTS AND METHODS: Nineteen patients with localised (stage IE) POAL were followed for a median of 96 months (24-156). The diagnosis was based on surgical biopsies followed by immunohistochemistry in 16 cases or fine-needle aspiration followed by immunocytophenotypic analysis in three cases. Twelve patients were treated with local radiotherapy (RT), five with chemotherapy (CT), and two refused further therapy after apparently radical tumour removal achieved by the diagnostic excisional biopsy. RESULTS: The histological and immunological pattern was consistent with a diagnosis of MALT-type lymphoma (11 cases), follicular center non-Hodgkin's lymphoma (three cases). a large-cell variant of Burkitt's lymphoma (one case), and large-cell transformed MALT lymphoma (one case). Low-grade lymphoma was diagnosed in the three cases which underwent fine-needle aspiration biopsy. All of the patients achieved and maintained complete remission except for those treated with surgical excision alone (two MALT conjunctival lymphoma cases): one of these relapsed locally, the other experienced the systemic spread of a transformed diffuse large-cell lymphoma and died 72 months after diagnosis. The side effects consisted of two cases of RT-related cataract after 52 and 72 months. CONCLUSIONS: Regardless of histology, prognosis was excellent when surgery plus RT was adopted, and CT seems to be a valid alternative to RT. Surgery alone may be sub-optimal.